FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gantz, S Tomaszewski, JG DeLaPena, L Molenda, J Bernato, DL Kryk, J AF Gantz, S Tomaszewski, JG DeLaPena, L Molenda, J Bernato, DL Kryk, J TI Programmed instruction: Biotherapy module .3. Interferons SO CANCER NURSING LA English DT Article RP Gantz, S (reprint author), NIH,CTR CLIN,DEPT NURSING,BETHESDA,MD 20892, USA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD DEC PY 1995 VL 18 IS 6 BP 479 EP 493 PG 15 WC Oncology; Nursing SC Oncology; Nursing GA TM660 UT WOS:A1995TM66000009 PM 8564945 ER PT J AU MYEROFF, LL PARSONS, R KIM, SJ HEDRICK, L CHO, KR ORTH, K MATHIS, M KINZLER, KW LUTTERBAUGH, J PARK, K BANG, YJ LEE, HY PARK, JG LYNCH, HT ROBERTS, AB VOGELSTEIN, B MARKOWITZ, SD AF MYEROFF, LL PARSONS, R KIM, SJ HEDRICK, L CHO, KR ORTH, K MATHIS, M KINZLER, KW LUTTERBAUGH, J PARK, K BANG, YJ LEE, HY PARK, JG LYNCH, HT ROBERTS, AB VOGELSTEIN, B MARKOWITZ, SD TI A TRANSFORMING GROWTH-FACTOR-BETA RECEPTOR-TYPE-II GENE MUTATION COMMON IN COLON AND GASTRIC BUT RARE IN ENDOMETRIAL CANCERS WITH MICROSATELLITE INSTABILITY SO CANCER RESEARCH LA English DT Note ID CELL-PROLIFERATION; FACTOR-BETA-1; STIMULATION; EXPRESSION AB We have recently demonstrated that mutation of the transforming growth factor-beta (TGF-beta) receptor type II (RII) gene is characteristic of colon cancers exhibiting microsatellite instability or replication errors (RER+), Moreover, we have shown that RII mutations in these RER+ colon cancers are characteristically frameshift mutations within a 10-bp polyadenine repeat present in the RII-coding region, We now show that RII gene mutations in this polyadenine repeat are also commonly present in RER+ gastric cancers (71%). In contrast, we find these same RII gene mutations are distinctly uncommon in RER+ endometrial cancers (17%, P < 0.02), These results suggest that RII gene mutations confer a growth advantage and are selected for in RER+ cancers of both the upper and lower gastrointestinal tract, The genesis of RER+ endometrial tumors must, however, be by a different route. C1 UNIV HOSP CLEVELAND,IRELAND CANC CTR,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,DEPT MED,CLEVELAND,OH 44106. JOHNS HOPKINS UNIV,DEPT PATHOL,BALTIMORE,MD 21231. JOHNS HOPKINS UNIV,CTR ONCOL,BALTIMORE,MD 21231. HOWARD HUGHES MED INST,CHEVY CHASE,MD 20815. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. UNIV MICHIGAN,DIV MED & MOLEC GENET,ANN ARBOR,MI 48109. UNIV TEXAS,SW MED SCH,SIMMONS CANC CTR,DALLAS,TX 75235. SEOUL NATL UNIV,COLL MED,CANC RES CTR,SEOUL,SOUTH KOREA. CREIGHTON UNIV,SCH MED,DEPT PREVENT MED & PUBL HLTH,OMAHA,NE 68178. RI Park, Jae-Gahb/J-5494-2012; Bang, Yung Jue/J-2759-2012 FU NCI NIH HHS [P01 CA51183, CA57208, P30 CA4370301] NR 25 TC 434 Z9 448 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1995 VL 55 IS 23 BP 5545 EP 5547 PG 3 WC Oncology SC Oncology GA TG211 UT WOS:A1995TG21100014 PM 7585631 ER PT J AU LUCIA, MS ANZANO, MA SLAYTER, MV ANVER, MR GREEN, DM SHRADER, MW LOGSDON, DL DRIVER, CL BROWN, CC PEER, CW ROBERTS, AB SPORN, MB AF LUCIA, MS ANZANO, MA SLAYTER, MV ANVER, MR GREEN, DM SHRADER, MW LOGSDON, DL DRIVER, CL BROWN, CC PEER, CW ROBERTS, AB SPORN, MB TI CHEMOPREVENTIVE ACTIVITY OF TAMOXIFEN, N-(4-HYDROXYPHENL)RETINAMIDE, AND THE VITAMIN-D ANALOG RO24-5531 FOR ANDROGEN-PROMOTED CARCINOMAS OF THE RAT SEMINAL-VESICLE AND PROSTATE SO CANCER RESEARCH LA English DT Article ID ENDOCRINE THERAPY; BREAST-CANCER; ORGAN-CULTURE; ESTROGEN; PREVENTION; RECEPTORS; GROWTH; N-(4-HYDROXYPHENYL)RETINAMIDE; CARCINOGENESIS; INDUCTION AB We evaluated the ability of dietary N-(4-hydroxyphenyl)retinamide; 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531); and tamoxifen to inhibit the development of androgen-promoted carcinomas of the accessory sex organs of male Lobund-Wistar rats. Invasive carcinomas of the seminal vesicle (SV) and anterior prostate (AP) were induced in Lobund-Wistar rats with three different combinations of initiator [N-nitroso-N-methylurea (NMU)] and promoter [testosterone propionate (TP)]: (a) high-dose NMU (30 mg/kg) + high-dose TP (20 mg via implant every 2 months); (b) high-dose NMU + low-dose TP (10 mg implanted every 2 months); or (c) low-dose NMU (15 mg/kg) + low-dose TP. During the period of TP administration, rats were fed a diet supplemented with either N-(4-hydroxyphenyl)retinamide (1 or 2 mmol/kg diet), Ro24-5531 (1.25 or 2.5 nmol/kg diet), tamoxifen (0.5 or 5 mg/kg diet), or vehicle alone. After sacrifice at 8.5 or 11 months, the prostate-seminal vesicle complex from each rat was processed in tote and histologically staged as to the extent of tumor involvement. In animals given low-dose TP, an three agents were significantly effective at reducing the incidence of invasive carcinomas of the SV and, to a lesser degree, the AP. Of the three agents, tamoxifen given in high dose (5 mg/kg) had the strongest activity, reducing the occurrence of invasive SV carcinomas from 72-83% in controls to 6% (P = 0.0001) and the occurrence of invasive AP carcinomas from 50-72% to 18-22% (P < 0.05). C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NCI,BIOMETRY BRANCH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT VET PATHOL,WASHINGTON,DC 20306. SCI APPLICAT INT CORP,FREDERICK,MD 21702. NR 48 TC 89 Z9 89 U1 1 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 DEC 1 PY 1995 VL 55 IS 23 BP 5621 EP 5627 PG 7 WC Oncology SC Oncology GA TG211 UT WOS:A1995TG21100027 PM 7585644 ER PT J AU RISINGER, JI UMAR, A BOYER, JC EVANS, AC BERCHUCK, A KUNKEL, TA BARRETT, JC AF RISINGER, JI UMAR, A BOYER, JC EVANS, AC BERCHUCK, A KUNKEL, TA BARRETT, JC TI MICROSATELLITE INSTABILITY IN GYNECOLOGICAL SARCOMAS AND IN HMSH2 MUTANT UTERINE SARCOMA CELL-LINES DEFECTIVE IN MISMATCH REPAIR ACTIVITY SO CANCER RESEARCH LA English DT Article ID GENETIC INSTABILITY; COLORECTAL-CANCER; CARCINOMA; MUTATIONS; HOMOLOG; TUMORS; COLON AB We have examined a panel of gynecological sarcomas for microsatellite instability. The genomic DNA from 11 of 44 sarcomas contained somatic alterations in the lengths of one or more di-, tri-, tetra-, or pentanucleotide microsatellite sequence markers, and 6 of these cases had alterations in two or more markers. In addition, di-, tri-, and tetranucleotide microsatellites were found to be highly unstable in single cell clones of two cell lines derived from a uterine mixed mesodermal tumor. Since such instability is characteristic of cells defective in postreplication mismatch repair, we examined mismatch repair activity in extracts made from these lines. Both extracts were repair deficient, while an extract of another gynecological sarcoma cell line not exhibiting microsatellite instability was repair proficient. The repair deficiency was complemented by a colon tumor cell extract that was defective in the hMLH1 protein but not by an extract defective in hMSH2 protein. This suggested that the defect in the uterine sarcoma line could be in hMSH2. Subsequent analysis of the gene revealed a 2-bp deletion in exon 14, leading to premature truncation of the hMSH2 protein at codon 796 and no detectable wild-type gene present. These data suggest that the microsatellite instability observed in these cell lines, and possibly in a significant number of gynecological sarcomas, is due to defective postreplication mismatch repair. There was no apparent correlation with microsatellite instability and clinical outcome. C1 NIEHS,MOLEC CARCINOGENESIS LAB,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. NIEHS,GENET MOLEC LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM GENET & MOLEC BIOL,CHAPEL HILL,NC 27599. DUKE UNIV,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,DURHAM,NC 27710. NR 34 TC 49 Z9 49 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1995 VL 55 IS 23 BP 5664 EP 5669 PG 6 WC Oncology SC Oncology GA TG211 UT WOS:A1995TG21100034 PM 7585651 ER PT J AU JURCIC, JG CARON, PC NIKULA, TK PAPADOPOULOS, EB FINN, RD GANSOW, OA MILLER, WH GEERLINGS, MW WARRELL, RP LARSON, SM SCHEINBERG, DA AF JURCIC, JG CARON, PC NIKULA, TK PAPADOPOULOS, EB FINN, RD GANSOW, OA MILLER, WH GEERLINGS, MW WARRELL, RP LARSON, SM SCHEINBERG, DA TI RADIOLABELED ANTI-CD33 MONOCLONAL-ANTIBODY M195 FOR MYELOID LEUKEMIAS SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT 5th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer CY OCT 06-08, 1994 CL PRINCETON, NJ SP Ctr Molec Med & Immunol, Garden State Canc Ctr ID ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; POLYMERASE CHAIN-REACTION; MINIMAL RESIDUAL DISEASE; TRANS RETINOIC ACID; DOSIMETRY; TRIAL; EXPRESSION AB M195, a mouse monoclonal antibody reactive with the early myeloid antigen CD33, has been shown to target leukemia cells in patients and to reduce large leukemic burdens when labeled with I-131, A complementarity-determining region-grafted, humanized version (HuM195) has demonstrated similar targeting of leukemia cells without immunogenicity, We have studied two applications of therapy with I-131-M195. First, to intensify therapy prior to bone marrow transplantation (BMT), we combined I-131-M195 with busulfan and cyclophosphamide, Fifteen patients received first BMT for relapsed or refractory acute myelogenous leukemia or accelerated or blastic chronic myelogenous leukemia; four received second BMT for relapsed chronic or accelerated chronic myelogenous leukemia. Doses of I-131-M195 ranged from 120 to 230 mCi/m(2). Few toxicities could be attributed to I-131-M195 therapy, and all patients engrafted, Eighteen patients achieved complete remission, Among those patients receiving first BMT, three have remained in unmaintained remission for 18+ to 29+ months, Six patients relapsed, including one with isolated central nervous system disease 32 months after BMT, Ten patients died in complete remission of transplant-related complications, Second, we studied whether I-131-M195 could reduce minimal residual disease and prolong remission and survival durations safely in patients with relapsed acute promyelocytic leukemia after they attained remission with all-trans-retinoic acid. Seven patients were treated with either 50 or 70 mCi/m(2) I-131-M195, Toxicity was limited to myelosuppression, As a measure of minimal residual disease, we monitored PML/RAR-alpha mRNA by reverse transcription PCR, Six patients had positive reverse transcription PCR assays prior to receiving I-131-M195; two converted transiently to negative, Median disease-free survival and overall survival of the seven patients were 8 (range, 3-14.5) months and 28 (range, 5.5-43+) months, respectively. This regimen compares favorably with others for relapsed acute promyelocytic leukemia, In an effort to avoid nonspecific cytotoxicity associated with I-131 in future trials for minimal residual disease, we have conjugated short-range, alpha particle-emitting radioisotopes to HuM195 using a bifunctional chelate, 2-(p-isothiocyanatobenzyl)-cyclohexyldiethyl- enetriaminepentaacetic acid, with high efficiency and specific activities, Bi-212-HuM195 has demonstrated dose- and specific activity-dependent killing of HL60 cells in vitro, Injection of Bi-213-HuM195 into healthy BALB/c mice produced no effects on weight or viability. C1 MEM SLOAN KETTERING CANC CTR,DEV CHEMOTHERAPY SERV,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,BONE MARROW TRANSPLANT SERV,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT MED,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT RADIOL,NUCL MED SERV,NEW YORK,NY 10021. NCI,RADIAT ONCOL BRANCH,CHEM SECT,BETHESDA,MD 20892. PHARMACTINIUM INC,WILMINGTON,DE. RP JURCIC, JG (reprint author), MEM SLOAN KETTERING CANC CTR,LEUKEMIA SERV,1275 YORK AVE,NEW YORK,NY 10021, USA. NR 20 TC 81 Z9 84 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1995 VL 55 IS 23 SU S BP S5908 EP S5910 PG 3 WC Oncology SC Oncology GA TH916 UT WOS:A1995TH91600038 ER PT J AU MURRAY, JL MACEY, DJ GRANT, EJ ROSENBLUM, MG KASI, LP ZHANG, HZ GATZ, RL RIEGER, PT LEBHERZ, D BHADKAMKAR, V GREINER, JW SCHLOM, J PODOLOFF, DA AF MURRAY, JL MACEY, DJ GRANT, EJ ROSENBLUM, MG KASI, LP ZHANG, HZ GATZ, RL RIEGER, PT LEBHERZ, D BHADKAMKAR, V GREINER, JW SCHLOM, J PODOLOFF, DA TI ENHANCED TAG-72 EXPRESSION AND TURNER UPTAKE OF RADIOLABELED MONOCLONAL-ANTIBODY CC49 IN METASTATIC BREAST-CANCER PATIENTS FOLLOWING ALPHA-INTERFERON TREATMENT SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT 5th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer CY OCT 06-08, 1994 CL PRINCETON, NJ SP Ctr Molec Med & Immunol, Garden State Canc Ctr ID TUMOR-ASSOCIATED ANTIGENS; CARCINOEMBRYONIC ANTIGEN; GAMMA-INTERFERON; LEUKOCYTE ALPHA; CELLS; MELANOMA; PHARMACOKINETICS; GLYCOPROTEIN-72; COMBINATION AB The IFNs, alpha and gamma, have been shown to enhance the tumor-associated glycoprotein (TAG-72) on adenocarcinoma cells is vitro and in mice with human breast cancer xenografts, resulting in improved targeting of monoclonal antibody CC49, To determine the effect of IFN-alpha on biodistribution and tumor uptake of I-131-labeled CC49, patients with metastatic breast cancer were randomized to either receive or not receive IFN-alpha (3 million units daily for 14 days) by s.c. injection, Three days after beginning IFN-alpha, all patients received 10-20 mCi of I-131-CC49 (specific activity, 16.7 mCi/mg) i.v. Total-body Anger camera scans, along with total-body blood and plasma pharmacokinetics, were performed, Tumor biopsies were taken in all patients before and 48 h after IFN-alpha treatment, There were no significant differences in number of metastases imaged or whole-body, blood and plasma pharmacokinetics between IFN-alpha-treated and untreated patients, Quantitative immunohistochemistry on biopsy specimens from IFN-alpha-treated patients demonstrated a significant increase in mean +/- SEM TAG-72 expression (45.7 +/- 19.4%) compared to patients that were not given IFN-alpha (1.3 +/- 0.95%; P < 0.05), Although slight increases in the percent injected dose of I-131-CC49 in tumor occurred after IFN-alpha-treatment, the changes were not significant at the P < 0.05 level. These data suggest that IFN-alpha may be useful in enhancing TAG-72 antigen expression in vivo in humans, despite modest improvement in tumor uptake of CC49, possibly because of limited tumor access or other unknown factors. C1 NCI,BETHESDA,MD 20892. RP MURRAY, JL (reprint author), UNIV TEXAS,MD ANDERSON CANCER CTR,1515 HOLCOMBE BLVD,BOX 041,HOUSTON,TX 77030, USA. FU NCI NIH HHS [CM97610] NR 20 TC 42 Z9 42 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1995 VL 55 IS 23 SU S BP S5925 EP S5928 PG 4 WC Oncology SC Oncology GA TH916 UT WOS:A1995TH91600042 PM 7493372 ER PT J AU SLAVINCHIORINI, DC KASHMIRI, SVS SCHLOM, J CALVO, B SHU, LM SCHOTT, ME MILENIC, DE SNOY, P CARRASQUILLO, J ANDERSON, K HAND, PH AF SLAVINCHIORINI, DC KASHMIRI, SVS SCHLOM, J CALVO, B SHU, LM SCHOTT, ME MILENIC, DE SNOY, P CARRASQUILLO, J ANDERSON, K HAND, PH TI BIOLOGICAL PROPERTIES OF CHIMERIC DOMAIN-DELETED ANTICARCINOMA IMMUNOGLOBULINS SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT 5th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer CY OCT 06-08, 1994 CL PRINCETON, NJ SP Ctr Molec Med & Immunol, Garden State Canc Ctr ID 2ND-GENERATION MONOCLONAL-ANTIBODIES; TUMOR-LOCALIZATION; CH2 DOMAIN; HALF-LIFE; THERAPY; B72.3; GENERATION; CARCINOMA; FRAGMENTS; RADIOIMMUNOTHERAPY AB CC49 is a second-generation monoclonal antibody (MAb) that has high affinity for the tumor-associated pancarcinoma antigen tumor-associated glycoprotein-72, In clinical trials using gamma scanning, radiolabeled CC49 has facilitated the detection of more than 90% of carcinomas, We report here the development of a constant heavy-chain 2 (C(H)2) domain-deleted chimeric (c) CC49 MAb by transfecting an expression construct consisting of the CC49 murine variable region and a C(H)2 domain-deleted human IgG1 constant region into cCC49 kappa producing SP2/0 murine myeloma cells, As determined by SDS-PAGE, the intact cCC49 Delta C(H)2 has a molecular weight of 153,000 and, under reducing conditions, molecular weights of 43,000 and 27,000, The plasma clearance and tumor-targeting properties of cCC49 Delta C(H)2 were evaluated and compared with those of mouse/human chimeric forms cCC49 Delta C(H)1 and intact cCC49. Previous studies have shown that the in vitro antigen-binding properties of cCC49 Delta C(H)1 are similar to those of cCC49. Biodistribution studies reported here, using I-131-labeled cCC49 Delta C(H)1 and I-125-labeled cCC49 in athymic mice bearing human colon carcinoma xenografts, demonstrated that both cMAbs localized to the tumor and cleared from the normal tissues similarly, However, in comparison with I-125-labeled cCC49, I-131-labeled cCC49 Delta C(H)2 localized to tumors earlier and had a significantly lower percentage of the injected dose of cMAb/g (%ID/g) in normal tissues than cCC49, Immunoscintigraphy of I-131-labeled cCC49 Delta C(H)2 and I-125-labeled cCC49 in athymic mice bearing human tumor xenografts demonstrated a clear image of the tumor by 24 h after i,v, administration of the Delta C(H)2 cMAb versus the 72 h required for cCC49, Biodistribution studies using Lu-177-conjugated cCC49 Delta C(H)1 and cCC49 showed no significant difference between the radiolocalization indices (% ID/g in tumor divided by %ID/g in normal tissue), Lu-177-conjugated cCC49 Delta C(H)2, however, had lower %ID/g values in tumor xenografts and lower radiolocalization indices than either Lu-177-conjugated cCC49 Delta C(H)1 or Lu-177-conjugated cCC49, Pharmacokinetic studies in non-tumor-bearing athymic mice using cCC49 Delta C(H)1 and cCC49 revealed no significant difference between these cMAbs, However, the plasma clearance of cCC49 Delta C(H)2 in non-tumor-bearing mice was significantly faster than that of cCC49, These results were similar when the cMAbs were labeled with either iodine or lutetium, In nonhuman primates, I-131-labeled cCC49 Delta C(H)2 cleared significantly faster than I-125-labeled cCC49, The similar plasma clearance and tumor localization of cCC49 and cCC49 Delta C(H)1 suggest that these two cMAbs may be used in similar clinical settings, However, because of the unique pharmacokinetics and tumor targeting of cCC49 Delta C(H)2 versus cCC49 or ECC49 Delta C(H)1, this chimeric immunoglobulin form may be useful in clinical settings that require efficient tumor targeting and rapid serum and whole-body clearance. C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NCI,BUR BIOL,BETHESDA,MD 20892. CTR CLIN,BETHESDA,MD 20892. DOW CHEM CO USA,MIDLAND,MI 48674. RP SLAVINCHIORINI, DC (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B07,BETHESDA,MD 20892, USA. RI Carrasquillo, Jorge/E-7120-2010 NR 45 TC 50 Z9 50 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1995 VL 55 IS 23 SU S BP S5957 EP S5967 PG 11 WC Oncology SC Oncology GA TH916 UT WOS:A1995TH91600047 ER PT J AU Bohr, VA AF Bohr, VA TI DNA repair fine structure and its relations to genomic instability SO CARCINOGENESIS LA English DT Article ID HAMSTER OVARY CELLS; DIHYDROFOLATE-REDUCTASE GENE; NUCLEOTIDE EXCISION REPAIR; COMPLEMENTATION GROUP-C; MITOCHONDRIAL-DNA; TRANSCRIBED STRAND; PYRIMIDINE DIMERS; HUMAN FIBROBLASTS; DHFR GENE; P53 GENE RP Bohr, VA (reprint author), NIA,MOLEC GENET LAB,NIH 4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 85 TC 81 Z9 82 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1995 VL 16 IS 12 BP 2885 EP 2892 DI 10.1093/carcin/16.12.2885 PG 8 WC Oncology SC Oncology GA TL668 UT WOS:A1995TL66800001 PM 8603460 ER PT J AU Orner, GA Mathews, C Hendricks, JD Carpenter, HM Bailey, GS Williams, DE AF Orner, GA Mathews, C Hendricks, JD Carpenter, HM Bailey, GS Williams, DE TI Dehydroepiandrosterone is a complete hepatocarcinogen and potent tumor promoter in the absence of peroxisome proliferation in rainbow trout SO CARCINOGENESIS LA English DT Article ID RAT-LIVER; LAURIC ACID; SHORT-TERM; F344 RATS; INDUCTION; SERUM; CARCINOGENESIS; IDENTIFICATION; CIPROFIBRATE; MODULATION AB Dehydroepiandrosterone (DHEA), fed for 30 weeks to rainbow trout after initiation with the hepatocarcinogen aflatoxin B-1 (AFB(1)), produced a dose-dependent enhancement of carcinogenesis as measured by increased tumor incidence, multiplicity and size, Significant enhancement was observed at 222 p,p,m,, which corresponds to a daily dosage one-half that previously administered to humans in clinical trials, DHEA was also capable of acting as a complete carcinogen in this model, producing liver tumors at doses as low as 222-444 p,p,m, Tumors isolated from trout treated with DHEA alone contained mutations in Ki-ras, primarily codon 12[1] G-->A transitions, providing the first suggestive evidence that DHEA could be a genotoxic carcinogen, The carcinogenicity of DHEA in trout is independent of peroxisome proliferation, as measurements of peroxisomal beta-oxidation and catalase activity support previous observations that trout, like humans, are weak responders to peroxisome proliferators. C1 OREGON STATE UNIV,TOXICOL PROGRAM,CORVALLIS,OR 97331. OREGON STATE UNIV,NIEHS,MARINE FRESHWATER BIOMED SCI CTR,CORVALLIS,OR 97331. OREGON STATE UNIV,DEPT FOOD SCI & TECHNOL,CORVALLIS,OR 97331. RI Orner, Gayle/F-6876-2013 OI Orner, Gayle/0000-0002-4812-5297 FU NIEHS NIH HHS [ES07612, ES04766, ES03850] NR 48 TC 24 Z9 25 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1995 VL 16 IS 12 BP 2893 EP 2898 DI 10.1093/carcin/16.12.2893 PG 6 WC Oncology SC Oncology GA TL668 UT WOS:A1995TL66800002 PM 8603461 ER PT J AU Poirier, MC Fullerton, NF Smith, BA Beland, FA AF Poirier, MC Fullerton, NF Smith, BA Beland, FA TI DNA adduct formation and tumorigenesis in mice during the chronic administration of 4-aminobiphenyl at multiple dose levels SO CARCINOGENESIS LA English DT Article ID RESPONSE RELATIONSHIP; MOLECULAR DOSIMETRY; RAS PROTOONCOGENE; ETHYLENE-OXIDE; 1ST BASE; RATS; 2-ACETYLAMINOFLUORENE; CARCINOGENESIS; CHROMATOGRAPHY; AFLATOXIN-B1 AB Recent studies have demonstrated the presence of DNA adducts from 4-aminobiphenyl (4-ABP) in the bladder cells of humans; however, the correlation between the concentration of these adducts and the tumorigenic response is not clear, To help elucidate this relationship, we have investigated DNA adduct formation in experimental animals continuously administered 4-ABP, Male and female BALB/c mice were treated for 28 days with 4-ABP hydrochloride in their drinking water, DNA adducts in target tissues (liver of females and bladder of males) were identified and quantified by P-32-postlabeling analyses and radioimmunoassays, These results were compared to previously reported tumor incidences obtained from the lifetime administration of 4-ABP hydrochloride, The major adduct observed in both tissues was N-(deoxyguanosin-8-yl)-4-ABP, In the bladders of both sexes and the livers of female mice, adduct levels increased with dose at low doses, but saturation was observed at high doses. In the livers of males, the adduct levels were linearly correlated with dose throughout the entire dose range, A comparison between DNA adducts and tumorigenesis indicated a linear correlation between adduct levels and the incidence of liver tumors in female mice, In the bladders of male mice, however, the relationship was markedly nonlinear, These data suggest that adduct formation alone is insufficient for tumorigenesis in the bladder and that other factors such as cell proliferation are necessary for tumor production. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP Poirier, MC (reprint author), NCI,BLDG 37,RM 3B25,37 CONVENT DR,BETHESDA,MD 20892, USA. NR 31 TC 38 Z9 38 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1995 VL 16 IS 12 BP 2917 EP 2921 DI 10.1093/carcin/16.12.2917 PG 5 WC Oncology SC Oncology GA TL668 UT WOS:A1995TL66800005 PM 8603464 ER PT J AU Herman, DG Schut, HAJ Davis, CD Snyderwine, EG Bailey, GS Dashwood, RH AF Herman, DG Schut, HAJ Davis, CD Snyderwine, EG Bailey, GS Dashwood, RH TI Protection by chlorophyllin and indole-3-carbinol against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced DNA adducts and colonic aberrant crypts in the F344 rat SO CARCINOGENESIS LA English DT Article ID 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE IQ; METABOLIC-ACTIVATION; FISCHER-344 RATS; CARCINOGENESIS; FOCI; BINDING; PHIP; AZOXYMETHANE; INHIBITION; MUTAGEN AB The most abundant heterocyclic amine in fried ground beef, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces colon carcinomas in the male F344 rat, The potential chemopreventive effects of two compounds, namely, the 'interceptor molecule' chlorophyllin (CHL) and a modulator of carcinogen activation, indole-3-carbinol (I3C), were examined in a PhIP colon carcinogenesis model, During weeks 3 and 4 of a 16-week study, F344 rats were given PhIP by oral gavage (50 mg/kg body weight, alternating days), Inhibitors were given either before and during PhIP exposure, after PhIP treatment, or continuously for 16 weeks, Treatment of rats with 0.1% CHL in the drinking water inhibited the formation of aberrant crypt foci (ACF) with greater than or equal to 4 crypts/focus, from 1.4 +/- 0.9 in controls to 0.7 +/- 0.3 following post-initiation CHL treatment, and to 0.3 +/- 0.5 in rats given CHL continuously for 16 weeks (mean +/- SD; P < 0.05), Potent inhibition of PhIP-induced ACF occurred following initiation, postinitiation and continuous exposure to 0.1% I3C in the diet, Using the initiation protocol, I3C completely inhibited the induction of ACF with greater than or equal to 4 crypts/focus, In a separate experiment, rats were given 0.1% CHL in the drinking water or 0.1% I3C in the diet for 4 weeks, At the end of week 3, animals received 50 mg PhIP/kg body weight by single oral gavage and PhIP-DNA adducts were quantified in the colon and several other tissues by P-32-postlabeling analysis, In addition, the urine and feces were collected to study the effects of inhibitor treatment on PhIP metabolism and excretion, No significant protection against PhIP-DNA adduct formation was detected in the colon after CHL dosing, nor was a consistent pattern of CHL inhibition observed in several other tissues, In contrast, I3C shifted the time-course of adducts in all tissue; compared with controls, adducts were increased by I3C at 6 h but decreased at 24 h and 7 days following PhIP treatment, Analysis of urine metabolites revealed that I3C and CHL decreased the excretion of unmetabolized PhIP and 4'-hydroxy-much less than PhIP but increased the phase II detoxification products PhIP-4'-O-glucuronide and PhIP-4'-sulfate, In the feces, the elimination of unmetabolized PhIP was increased from 54,5% in controls to similar to 67% in CHL-treated rats and decreased to 28% in rats given I3C (P < 0.05), These results support a protective role for CHL and I3C against PhIP-induced colon carcinogenesis through mechanisms which alter the uptake or metabolism of the carcinogen, and by suppression in the post-initiation phase. C1 UNIV HAWAII,DEPT ENVIRONM BIOCHEM,HONOLULU,HI 96822. MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43614. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. OREGON STATE UNIV,DEPT FOOD SCI & TECHNOL,CORVALLIS,OR 97331. RI Dashwood, Roderick/E-9090-2011 NR 55 TC 0 Z9 0 U1 0 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 DEC PY 1995 VL 16 IS 12 BP 2931 EP 2937 PG 7 WC Oncology SC Oncology GA TL668 UT WOS:A1995TL66800007 ER PT J AU Shinmura, K Sugimura, H Naito, Y Shields, PG Kino, I AF Shinmura, K Sugimura, H Naito, Y Shields, PG Kino, I TI Frequent co-occurrence of mutator phenotype in synchronous, independent multiple cancers of the stomach SO CARCINOGENESIS LA English DT Article ID COLORECTAL-CANCER; HETEROZYGOSITY; HOMOLOG; TISSUE; GENE AB The prevalence of multiple independent primary cancer of the stomach is high in Japanese, We hypothesized that individuals with multiple, independent gastric cancers might have a greater genetic susceptibility than persons with solitary gastric cancer at the time of diagnosis, We therefore determined the frequency of mutator phenotypes in 20 persons with independent multiple gastric cancers and 42 persons with solitary primary lesions, The mutator phenotype was determined by examining dinucleotide CA repeats at the microsatellite loci D2S136 (chromosome 2), MSX2 (chromosome 5q34), D5S82 (chromosome 5q14-q21) and TP53 (chromosome 17p13,1), Although there were no significant differences between the clinical and pathological features (stage or histopathological subtype) of the two groups, the prevalence of any one microsatellite instability in patients with multiple gastric cancer was greater (65% versus 24%; P = 0.003) than in those with solitary gastric cancer, The prevalence of co-occurrence of mutator phenotype in synchronous lesions was greater than expected based on their frequency in solitary gastric cancer (12% versus 9%x9%), Persons with advanced-stage multiple primary lesions were more likely to exhibit the mutator phenotype (P = 0.10), These findings indicate that individual predisposition for qualitative or quantitative defects in DNA repair systems significantly contribute to the simultaneous occurrence of gastric cancer in Japanese. C1 HAMAMATSU UNIV SCH MED, DEPT PATHOL 1, HAMAMATSU, SHIZUOKA 43131, JAPAN. NCI, HUMAN CARCINOGENESIS LAB, MOLEC EPIDEMIOL SECT, BETHESDA, MD 20892 USA. RI Shields, Peter/I-1644-2012; Shinmura, Kazuya /K-8940-2012 OI Shinmura, Kazuya /0000-0003-4963-746X NR 29 TC 31 Z9 31 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1995 VL 16 IS 12 BP 2989 EP 2993 DI 10.1093/carcin/16.12.2989 PG 5 WC Oncology SC Oncology GA TL668 UT WOS:A1995TL66800015 PM 8603474 ER PT J AU Petersen, LN Stevnsner, T Bohr, VA AF Petersen, LN Stevnsner, T Bohr, VA TI DNA repair in a UV resistant Chinese hamster ovary cell line SO CARCINOGENESIS LA English DT Article ID DIHYDROFOLATE-REDUCTASE GENE; DAMAGE-RECOGNITION PROTEINS; NUCLEOTIDE EXCISION REPAIR; 6-4 PHOTOPRODUCTS; ESCHERICHIA-COLI; DHFR GENE; CISPLATIN; OVEREXPRESSION; ULTRAVIOLET; EXPRESSION AB We have established an ultraviolet (UV) resistant Chinese hamster ovary (CHO) cell line B11(UVres) by repetitive UV exposure of the CHO cell line B11, We have characterized the resistant cell line with respect to growth, sensitivity to various DNA damaging agents, and the repair of UV induced DNA lesions. When examining sensitivity to UV in clonogenic survival studies, we find that the ID50 is increased 2.3-fold in the resistant cell line B11(UVres) compared to the parental cell line B11, Although the doubling time of the resistant cell line is greater than that of the parental cell line, there is no difference in the rate of replication after UV irradiation, When measuring repair of UV induced DNA lesions in the overall genome we find no significant difference between the two cell lines, However, at early times after UV, there is a significant increase in the rate of repair of cyclobutane pyramidine dimers (CPDs) in the transcribed strand of the dihydrofolate reductase (DHFR) gene in the B11(UVres) cells compared to the B11 cells, There is a small increase of steady state transcription of the DHFR gene in the UV resistant cells, but hardly enough to account for the repair increase, The UV resistant cell line B11(UVres) is not cross-resistant to the cross-linking agents mitomycin C or cisplatin, but shows increased sensitivity to these compounds. C1 UNIV COPENHAGEN HOSP,DEPT ONCOL,DK-2100 COPENHAGEN,DENMARK. RP Petersen, LN (reprint author), NIA,MOLEC GENET LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 42 TC 7 Z9 7 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1995 VL 16 IS 12 BP 3075 EP 3081 DI 10.1093/carcin/16.12.3075 PG 7 WC Oncology SC Oncology GA TL668 UT WOS:A1995TL66800029 PM 8603488 ER PT J AU Lapis, K Zalatnai, A Timar, F Thorgeirsson, UP AF Lapis, K Zalatnai, A Timar, F Thorgeirsson, UP TI Quantitative evaluation of lysozyme- and CD68-positive Kupffer cells in diethylnitrosamine-induced hepatocellular carcinomas in monkeys SO CARCINOGENESIS LA English DT Article ID RAT-LIVER; LOCALIZATION; MONOCYTES; SINUSOIDS; LESIONS AB Quantitative analysis of lysozyme- and CD68-positive Kupffer cells was carried out in connection with diethylnitrosamine-induced hepatocarcinogenesis in non-human primates, The number of Kupffer cells/mm(2) was determined in 28 cases of hepatocellular carcinoma (HCC) and seven age-matched controls, The Kupffer cell counts (mean +/- SEM) gradually decreased in the following order, irrespective of the histochemical markers (lysozyme or CD 68) used: healthy control liver (101.7 +/- 13.5 and 103.2 +/- 11.9 respectively), non-cirrhotic and non-neoplastic host liver (54.3 +/- 13.6 and 50.5 +/- 15.4), cirrhotic host liver (26.2 +/- 8.2 and 27.2 +/- 3.3), HCC tissue (20.7 +/- 4.4 and 19.3 +/- 4.1) and metastatic foci in the lung (9.8 +/- 1.8 and 9.7 +/- 2.8), The difference between the normal liver and the non-neoplastic, non-cirrhotic portions of the HCC-bearing liver was significant (P < 0.05), A highly significant difference was found between the number of Kupffer cells found in healthy control or non-neoplastic liver and those found in HCC nodules (P < 0.0001 and P < 0.0005 respectively), The results obtained by hematoxylin and eosin staining and lysozyme/CD68 immunohistochemistry were highly similar, indicating that this decrease was attributable primarily to numeric loss of Kupffer cells, The results suggest that the reduction in the number of Kupffer cells in HCC is a constant feature of hepatocarcinogenesis not only in rodent models, but also in non-human primates. C1 NCI,DIV CANC ETIOL,BETHESDA,MD 20892. RP Lapis, K (reprint author), SEMMELWEIS UNIV MED,INST PATHOL & EXPTL CANC RES 1,H-1085 BUDAPEST,HUNGARY. NR 22 TC 8 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1995 VL 16 IS 12 BP 3083 EP 3085 DI 10.1093/carcin/16.12.3083 PG 3 WC Oncology SC Oncology GA TL668 UT WOS:A1995TL66800030 PM 8603489 ER PT J AU Davis, CD Snyderwine, EG AF Davis, CD Snyderwine, EG TI Analysis of EGFR, TGF-alpha, neu and c-myc in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mammary tumors using RT-PCR SO CARCINOGENESIS LA English DT Article ID TRANSFORMING GROWTH-FACTOR; HUMAN-BREAST CARCINOMAS; SHORT-TERM PROGNOSIS; RIBONUCLEIC-ACID; CANCER-PATIENTS; PROTO-ONCOGENE; P53 MUTATIONS; EXPRESSION; RECEPTOR; AMPLIFICATION AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a mutagen found in cooked meat, has been shown to induce mammary gland tumors in rats, Our laboratory recently observed that a high fat diet enhances the incidence and severity of PhIP-induced mammary gland cancer in rats. In the current study, reverse transcription followed by polymerase chain reaction amplification was used to determine whether EGFR, TGF-alpha, neu and c-myc are differentially expressed in PhIP-induced mammary gland tumors classified histologically as benign or malignant and to evaluate whether dietary fat intake influences the expression of these genes, Of 23 total PhIP-induced mammary tumors examined, 43%, 57% and 74% had increased expression of EGFR, TGP-alpha and neu mRNA respectively, Increased expression of these genes appeared to be consistently present in tumors displaying papillomatosis. In contrast to the other three genes, c-myc mRNA levels were infrequently elevated. The percentage of dietary fat did not appear to influence the expression of EGFR, TGF-alpha or neu in either tumors or mammary gland from control rats, However, the levels of c-myc mRNA were 1.8- and 2.9-fold higher in the control mammary gland and benign PhIP-induced tumors respectively in rats fed the high-fat diet than in rats fed the low-fat diet, suggesting a slight effect of dietary fat (P < 0.08) on c-myc expression. These results suggest that increased expression of EGFR, TGF-alpha and especially neu is associated with PhIP-induced mammary gland cancer in rats. RP Davis, CD (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 36 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1995 VL 16 IS 12 BP 3087 EP 3092 DI 10.1093/carcin/16.12.3087 PG 6 WC Oncology SC Oncology GA TL668 UT WOS:A1995TL66800031 PM 8603490 ER PT J AU WERNER, MH CLORE, GM FISHER, CL FISHER, RJ TRINH, L SHILOACH, J GRONENBORN, AM AF WERNER, MH CLORE, GM FISHER, CL FISHER, RJ TRINH, L SHILOACH, J GRONENBORN, AM TI THE SOLUTION STRUCTURE OF THE HUMAN ETS1-DNA COMPLEX REVEALS A NOVEL MODE OF BINDING AND TRUE SIDE-CHAIN INTERCALATION SO CELL LA English DT Article ID SERUM RESPONSE ELEMENT; CO-CRYSTAL STRUCTURE; TATA-BOX COMPLEX; TRANSCRIPTION FACTORS; DNA COMPLEX; PROTEIN; MOTIF; RESOLUTION; SUGGESTS; PROGRAM AB The solution structure of a 24.4 kDa specific complex of the DNA-binding domain (DBD) of the human ETS1 (hETS1) oncoprotein with a 17-mer DNA has been solved by NMR. The interaction of the hETS1 DBD with DNA reveals a surprising twist on the general features of helix-turn-helix (HTH)-DNA interactions, Major groove recognition involves the C-terminal two thirds of the HTH recognition helix, while minor groove recognition occurs via true intercalation of the side chain of Trp-28, which extends from the minor to the major groove. This results in a sharp kink of similar to 60 degrees and a widening of the minor groove over one-half turn of the DNA. The orientation of the HTH element of the hETS1 DBD with respect to the major groove is significantly rotated relative to other HTH proteins. These observations establish the ETS family of DNA-binding proteins as a distinct family of HTH proteins. C1 NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21701. NIDDKD,CELLULAR & DEV BIOL LAB,BIOTECHNOL UNIT,BETHESDA,MD 20892. RP WERNER, MH (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008; Fisher, Robert/B-1431-2009 OI Clore, G. Marius/0000-0003-3809-1027; NR 45 TC 111 Z9 113 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 1 PY 1995 VL 83 IS 5 BP 761 EP 771 DI 10.1016/0092-8674(95)90189-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TH948 UT WOS:A1995TH94800013 PM 8521493 ER PT J AU ENOMOTO, KI FURUYA, K YAMAGISHI, S OKA, T MAENO, T AF ENOMOTO, KI FURUYA, K YAMAGISHI, S OKA, T MAENO, T TI RELEASE OF ARACHIDONIC-ACID VIA CA2+ INCREASE STIMULATED BY PYROPHOSPHONUCLEOTIDES AND BRADYKININ IN MAMMARY-TUMOR CELLS SO CELL BIOCHEMISTRY AND FUNCTION LA English DT Article DE ATP; UTP; BRADYKININ; CALCIUM; ARACHIDONIC ACID; MAMMARY CELL ID EXTRACELLULAR ATP; EPITHELIAL-CELLS; NUCLEOTIDE RECEPTOR; CALCIUM RESPONSES; ENDOTHELIAL-CELLS; PHOSPHOLIPASE-A2; PATHWAYS; PHOSPHATIDYLINOSITOL; OSCILLATIONS; NEUTROPHILS AB The relationship between the increase of intracellular Ca2+ and the release of arachidonic acid by bradykinin and pyrophosphonucleotides was studied in cultured mammary tumour cells, MMT060562. Bradykinin, ATP, UTP and UDP induced an increase of intracellular Ca2+ and the release of arachidonic acid from phospholipids into the extracellular fluid. Release of arachidonic acid was also induced by the application of the Ca2+ ionophore, A23187. Liberation of arachidonic acid by bradykinin and ATP was reduced by mepacrine, a blocker of phospholipase A(2) and W-7, a calmodulin antagonist. It is suggested that the increase in cytosolic Ca2+-induced release of arachidonic acid occurs through activation of calmodulin-dependent phospholipase A(2). C1 NATL INST PHYSIOL SCI,DEPT CELL PHYSIOL,OKAZAKI,AICHI 444,JAPAN. NATL INST HLTH,MOLEC & CELL BIOL LAB,BETHESDA,MD 20892. RP ENOMOTO, KI (reprint author), SHIMANE MED UNIV,DEPT PHYSIOL,IZUMO,SHIMANE 693,JAPAN. NR 30 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0263-6484 J9 CELL BIOCHEM FUNCT JI Cell Biochem. Funct. PD DEC PY 1995 VL 13 IS 4 BP 279 EP 286 DI 10.1002/cbf.290130409 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TG195 UT WOS:A1995TG19500007 PM 8565149 ER PT J AU DENNING, MF KAZANIETZ, MG BLUMBERG, PM YUSPA, SH AF DENNING, MF KAZANIETZ, MG BLUMBERG, PM YUSPA, SH TI CHOLESTEROL SULFATE ACTIVATES MULTIPLE PROTEIN-KINASE-C ISOENZYMES AND INDUCES GRANULAR-CELL DIFFERENTIATION IN CULTURED MURINE KERATINOCYTES SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; CROSS-LINKED PROTEIN; MOUSE KERATINOCYTES; STEROID-SULFATASE; MAMMALIAN EPIDERMIS; LIPID-METABOLISM; GENE-EXPRESSION; NPKC-ETA; ICHTHYOSIS; ISOZYMES AB The accumulation of cholesterol sulfate (CS) in differentiating keratinocytes coincides with the expression of protein kinase C (PKC)-regulated granular layer differentiation markers both in vitro and in vivo. In this study, we examined the ability of CS to induce differentiation marker expression in primary mouse keratinocytes and to modulate keratinocyte PKC isozymes (alpha, delta, epsilon, eta, and zeta). Treatment of basal keratinocytes with CS induced the expression of the granular layer proteins filaggrin and loricrin and decreased the level of the spinous keratin K1. CS stimulated cornification and blocked the induction of K10 in keratinocytes induced to differentiate by calcium. The induction of filaggrin and loricrin by CS corresponds to a granular layer differentiation program, where PKC activation occurs and was blocked by the PKC inhibitor GF 109203X. Treatment of keratinocytes with CS caused PKC epsilon, eta, and zeta to be selectively lost from the cytosol fraction and increased in the cytoskeletal fraction. The loss of soluble PKC epsilon, eta, and zeta was rapid (1 h) and sustained (44 h). PKC alpha and delta were not redistributed. In vitro, CS induced kinase activity of PKC epsilon, eta, and zeta to a greater extent than did the phorbol ester 12-O-tetradecanoylphorbol-13-acetate for these isoforms. PKC ru and delta were activated to a lesser extent by CS than by 12-O-tetradecanoylphorbol-13-acetate. The translocation of PKC epsilon, eta, and zeta in intact cells treated with CS, together with the in vitro activation of recombinant PKC epsilon, eta, and zeta preferentially by CS, suggests a role for these isoforms in the induction of keratinocyte differentiation by CS. C1 NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 50 TC 80 Z9 81 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD DEC PY 1995 VL 6 IS 12 BP 1619 EP 1626 PG 8 WC Cell Biology SC Cell Biology GA TJ112 UT WOS:A1995TJ11200014 PM 9019167 ER PT J AU Gozes, I Fridkin, M Brenneman, DE AF Gozes, I Fridkin, M Brenneman, DE TI A VIP hybrid antagonist: From developmental neurobiology to clinical applications SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE vasoactive intestinal peptide; VIP, hybrid antagonist; hybrid peptides; neurotrophism ID VASOACTIVE-INTESTINAL-PEPTIDE; CELL LUNG-CANCER; CYCLASE-ACTIVATING POLYPEPTIDE; PRECURSOR MESSENGER-RNA; STRUCTURAL REQUIREMENTS; FUNCTIONAL EXPRESSION; NEURONAL SURVIVAL; BINDING-SITES; RAT-BRAIN; RECEPTOR AB 1. The 28 amino acid vasoactive intestinal peptide, VIP, was originally isolated from the intestine, following a bioassay measuring vasodilating properties, Immunocytochemistry, receptor binding assays and in situ hybridizations have demonstrated VIP abundance in the nervous system, suggesting multiple bioactivities. 2. A pharmacological approach was chosen to dissect VIP activities and a prototype VIP antagonist (Met-Hybrid) consisting of a carboxyl fragment of VIP7-28 and a six amino acid fragment of neurotensin, neurotensin(6-11)-VIP7-28 was synthesized. 3. This hybrid peptide was designed to maintain the binding capacity of one parent molecule (VIP), while loosing the agonistic properties, representing a classical competitive receptor antagonist, Furthermore, the new molecule exhibited increased specificity to central nervous system VIP receptors. 4. The Met-Hybrid was originally discovered as a potent inhibitor of VIP function in vivo. In the adult rodent, acute administration of the antagonist resulted in blockade of VIP-mediated potentiation of sexual behavior and chronic intracerebroventricular application impaired VIP-associated learning abilities. During ontogeny, chronic injections of the molecule resulted in neuronal damage, disruption of the diurnal rhythmicity of motor behavior, and retardation in the acquisition of neonatal reflexes in the rat. 5. During gestation, severe microcephaly was induced by acute administration of the Met-Hybrid to pregnant mice. The hybrid antagonist inhibited VIP-stimulated mitosis in whole embryo cultures and in a variety of cancer cell lines in vitro and in vivo, suggesting therapeutical potential. C1 WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-76100 REHOVOT,ISRAEL. NICHHD,DEV NEUROBIOL LAB,SECT DEV & MOLEC PHARMACOL,BETHESDA,MD 20892. RP Gozes, I (reprint author), TEL AVIV UNIV,SACKLER SCH MED,DEPT CLIN BIOCHEM,IL-69978 TEL AVIV,ISRAEL. NR 74 TC 21 Z9 21 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD DEC PY 1995 VL 15 IS 6 BP 675 EP 687 DI 10.1007/BF02071131 PG 13 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA TP926 UT WOS:A1995TP92600005 PM 8719036 ER PT J AU HARGUS, SJ MARTIN, BM GEORGE, JW POHL, LR AF HARGUS, SJ MARTIN, BM GEORGE, JW POHL, LR TI COVALENT MODIFICATION OF RAT-LIVER DIPEPTIDYL PEPTIDASE-IV (CD26) BY THE NONSTEROIDAL ANTIINFLAMMATORY DRUG DICLOFENAC SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Note ID HEPATITIS; IDENTIFICATION; HEPATOTOXICITY; GLYCOPROTEIN; HEPATOCYTES; SEQUENCE; DOMAIN; CDNA AB Diclofenac is a nonsteroidal anti-inflammatory drug that has been implicated in several cases of severe hepatotoxicity. Our previous study showed that diclofenac metabolites bound covalently and selectively to rat liver plasma membrane proteins with estimated monomeric masses of 110, 140, and 200 kDa. We report here that we have identified the 110 kDa diclofenac-labeled protein in rat liver as dipeptidyl peptidase IV, also known as CD26. In addition, we found that the activity of dipeptidyl peptidase IV in liver plasma membrane fractions was lowered after diclofenac treatment of rats. These results suggest that the hepatotoxicity associated with diclofenac might be due, in part, to the covalent modification of dipeptidyl peptidase IV. C1 GEORGETOWN UNIV,DEPT ANESTHESIA,WASHINGTON,DC. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP HARGUS, SJ (reprint author), NHLBI,MOLEC IMMUNOL LAB,MOLEC & CELLULAR TOXICOL SECT,BLDG 10,ROOM 8N104,BETHESDA,MD 20892, USA. NR 33 TC 74 Z9 76 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 1995 VL 8 IS 8 BP 993 EP 996 DI 10.1021/tx00050a001 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA TH883 UT WOS:A1995TH88300001 PM 8605291 ER PT J AU SZELIGA, J PAGE, JE HILTON, BD KISELYOV, AS HARVEY, RG DUNAYEVSKIY, YM VOUROS, P DIPPLE, A AF SZELIGA, J PAGE, JE HILTON, BD KISELYOV, AS HARVEY, RG DUNAYEVSKIY, YM VOUROS, P DIPPLE, A TI CHARACTERIZATION OF DNA-ADDUCTS FORMED BY ANTI-BENZO[G]CHRYSENE 11,12-DIHYDRODIOL 13,14-EPOXIDE SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; REGION DIOL-EPOXIDES; FJORD-REGION; MAMMALIAN-CELLS; MOUSE SKIN; BINDING; ADENINE; 7,12-DIMETHYLBENZ(A)ANTHRACENE; 1,2-EPOXIDES; MUTAGENICITY AB The anti-11,12-dihydrodiol 13,14-epoxide of benzo[g]chrysene, a fjord-region-containing hydrocarbon, was found to react with DNA in vitro to yield, as the major product, an adduct in which the epoxide of the 11R,12S,13S,14R enantiomer was opened trans by the amino group of deoxyadenosine. The structures of this adduct and other deoxyadenosine and deoxyguanosine adducts were established by spectroscopic methods. In reactions with deoxyguanylic acid, a product tentatively identified as a 7-substituted guanine was also detected. The mutagenic properties of this dihydrodiol epoxide in shuttle vector pSP189 showed that mutation at AT pairs accounted for 39% of base change mutations whereas chemical findings indicated that about 60% of adducts formed in calf thymus DNA involved adenines. Since calf thymus DNA is 56% AT and the target supF gene is 41% AT, the findings represent a fairly close relationship between adduct formation and mutagenic response. Overall, the chemical and mutagenic selectivities for the two purine bases in DNA were similar, though not identical, to these for the only other fjord-region-containing hydrocarbon studied in depth, i.e., benzo[c]phenanthrene. A major difference for these two hydrocarbon derivatives, however, is that benzo[c]phenanthrene dihydrodiol epoxides react to much higher extents (approximate to 4-fold) with DNA than did the benzo[g]chrysene derivative. C1 NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, CHEM SYNTH & ANAL LAB, FREDERICK, MD 21702 USA. UNIV CHICAGO, BEN MAY INST, CHICAGO, IL 60637 USA. NORTHEASTERN UNIV, DEPT CHEM, BOSTON, MA 02115 USA. NORTHEASTERN UNIV, BARNETT INST, BOSTON, MA 02115 USA. RP SZELIGA, J (reprint author), NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, ABL BASIC RES PROGRAM, CHEM CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. FU NIEHS NIH HHS [ES 04732] NR 27 TC 43 Z9 44 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 1995 VL 8 IS 8 BP 1014 EP 1019 DI 10.1021/tx00050a004 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA TH883 UT WOS:A1995TH88300004 PM 8605283 ER PT J AU Li, X Yang, WQ Yano, J Braun, C Plattner, H Bell, WE vanHouten, J AF Li, X Yang, WQ Yano, J Braun, C Plattner, H Bell, WE vanHouten, J TI Glutamate chemoresponse in paramecium SO CHEMICAL SENSES LA English DT Meeting Abstract C1 UNIV VERMONT,DEPT BIOL,BURLINGTON,VT 05405. NHLBI,BETHESDA,MD 20892. UNIV KONSTANZ,W-7750 CONSTANCE,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD DEC PY 1995 VL 20 IS 6 BP 166 EP 166 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA TM989 UT WOS:A1995TM98900172 ER PT J AU Weiffenbach, JM Yeh, CK Chamberlain, CK Cornell, JE Saunders, MJ McAnear, JT AF Weiffenbach, JM Yeh, CK Chamberlain, CK Cornell, JE Saunders, MJ McAnear, JT TI Taste intensity performance of edentulous persons: Effects of dentures and dental implants SO CHEMICAL SENSES LA English DT Meeting Abstract C1 NATL INST HLTH,BETHESDA,MD. ALMM VET HOSP,DENT SERV,SAN ANTONIO,TX. ALMM VET HOSP,GRECC,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD DEC PY 1995 VL 20 IS 6 BP 322 EP 322 PG 2 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA TM989 UT WOS:A1995TM98900328 ER PT J AU Caughey, B Kocisko, DA Raymond, GJ Lansbury, PT AF Caughey, B Kocisko, DA Raymond, GJ Lansbury, PT TI Aggregates of scrapie-associated prion protein induce the cell-free conversion of protease-sensitive prion protein to the protease-resistant state SO CHEMISTRY & BIOLOGY LA English DT Article DE scrapie; prion protein; aggregation; in vitro formation; sedimentation ID RADIATION INACTIVATION; PRP 27-30; FORM; LIPOSOMES; AGENT; IDENTIFICATION; INFECTIVITY; PRECURSOR; ANTIBODY; FIBRILS AB Introduction: Scrapie infection instigates the in vivo conversion of normal, protease-sensitive prion protein (PrPC) into a protease-resistant form (PrPSc) by an unknown mechanism. In vitro studies have indicated that PrPSc can induce this conversion, consistent with proposals that PrPSc itself might be the infectious scrapie agent. Using this cell-free model of the PrPC to PrPSc conversion, we have studied the dependence of conversion on reactant concentration, and the properties of the PrPSc-derived species that has converting activity. Results: The cell-free conversion of S-35 PrPC to the proteinase K-resistant form was dependent on the reaction time and initial concentrations of PrPSc (above an apparent minimum threshold concentration) and S-35 PrPC. Analysis of the physical size of the converting activity indicated that detectable converting activity was associated only with aggregates. Under mildly chaotropic conditions, which partially disaggregated PrPSc and enhanced the converting activity the active species were heterogeneous in size, hut larger than either effectively solubilized PrP or molecular weight: standards of similar to 2000 kDa. Conclusions: The entity responsible for the converting activity was many times larger than a soluble PrP monomer and required a threshold concentration of PrPSc. These results are consistent with a nucleated polymerization mechanism of PrPSc formation and inconsistent with a heterodimer mechanism. C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. RP Caughey, B (reprint author), NIAID,ROCKY MT LAB,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 47 TC 158 Z9 161 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD DEC PY 1995 VL 2 IS 12 BP 807 EP 817 DI 10.1016/1074-5521(95)90087-X PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TP782 UT WOS:A1995TP78200005 PM 8807814 ER PT J AU TROISI, RJ SPEISER, FE ROSNER, B TRICHOPOULOS, D WILLETT, WC AF TROISI, RJ SPEISER, FE ROSNER, B TRICHOPOULOS, D WILLETT, WC TI CIGARETTE-SMOKING AND INCIDENCE OF CHRONIC-BRONCHITIS AND ASTHMA IN WOMEN SO CHEST LA English DT Article DE ASTHMA; CHRONIC BRONCHITIS; CIGARETTE SMOKING ID GENERAL-POPULATION SAMPLE; SYMPTOMS; ADULTS; EMPHYSEMA; DISEASE AB Study objective: To examine the relation of smoking habits and development of asthma in a large cohort of US women. Design: Prospective cohort study. Participants: Among 74,072 women, 34 to 68 years of age, who were free of major diseases, we documented 671 incident asthma cases and 798 incident cases of chronic bronchitis during 10 years of follow-up. Methods: Age-adjusted relative risk estimates for smoking categories were calculated separately for chronic bronchitis and asthma. Results: Risk of chronic bronchitis was significantly higher in current smokers than in never smokers (relative risk [RR] =2.85; 95% confidence interval [CI] =2.45 to 3.32) and increased with the number of cigarettes smoked per day (p for trend <0.0001), Approximately 5 years after quitting, chronic bronchitis risk in past smokers approached that in never smokers, In contrast, current smokers were at significantly lower risk for asthma than women who never smoked (RR=0.57; 95% CI=0.46 to 0.71) and women who quit (RR=0.50; 95% CI=0.40 to 0.62), possible because individuals with sensitive airways are less likely to become regular smokers, and smokers who develop respiratory symptoms of any etiology tend to quit. Asthma risk in past smokers initially increased compared with that in never smokers, possibly because of quitting prior to diagnosis in response to symptoms of any etiology, but decreased with time since quitting (p for trend=0.007); within approximately 5 years, the risk did not differ between past and never smokers. Conclusion: These data suggest that smoking in adults may not be an independent cause of asthma but could exacerbate or be perceived as exacerbating asthma symptoms in susceptible individuals. C1 HARVARD UNIV, SCH MED, DEPT MED, CHANNING LAB, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT EPIDEMIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT NUTR, BOSTON, MA 02115 USA. NCI, ENVIRONM EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA 40356]; NHLBI NIH HHS [HL07427] NR 15 TC 118 Z9 121 U1 2 U2 5 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1995 VL 108 IS 6 BP 1557 EP 1561 DI 10.1378/chest.108.6.1557 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA TJ741 UT WOS:A1995TJ74100022 PM 7497760 ER PT J AU WALTER, MF JANG, C KASRAVI, B DONATH, J MECHLER, BM MASON, JM BIESSMANN, H AF WALTER, MF JANG, C KASRAVI, B DONATH, J MECHLER, BM MASON, JM BIESSMANN, H TI DNA ORGANIZATION AND POLYMORPHISM OF A WILD-TYPE DROSOPHILA TELOMERE REGION SO CHROMOSOMA LA English DT Article ID HUMAN SEX-CHROMOSOMES; PSEUDOAUTOSOMAL REGION; PLASMODIUM-FALCIPARUM; HET-A; SUBTELOMERIC REGIONS; CHIRONOMUS TELOMERES; REPEATED SEQUENCE; TANDEM REPEATS; MELANOGASTER; ENDS AB Telomeres at the ends of linear chromosomes of eukaryotes protect the chromosome termini from degradation and fusion. While telomeric replication/elongation mechanisms have been studied extensively, the functions of subterminal sequences are less well understood. In general, subterminal regions can be quite poly morphic, varying in size from organism to organism, and differing among chromosomes within an organism. The subterminal regions of Drosophila melanogaster are not well characterized today, and it is not known which and how many different components they contain. Here we present the molecular characterization of DNA components and their organization in the subterminal region of the left arm of chromosome 2 of the Oregon RC wildtype strain of D. melanogaster; including a minisatellite with a 457 bp repeat length. Two distinct polymorphic arrangements at 2L were found and analyzed, supporting the Drosophila telomere elongation model by retrotransposition. The high incidence of terminal chromosome deficiencies occurring in natural Drosophila populations is discussed in view of the telomere structure at 2L. C1 UNIV CALIF IRVINE,CTR DEV BIOL,IRVINE,CA 92717. GERMAN CANC RES CTR,DEPT DEV GENET,D-69121 HEIDELBERG,GERMANY. NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. FU NIGMS NIH HHS [GM46211] NR 73 TC 64 Z9 65 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD DEC PY 1995 VL 104 IS 4 BP 229 EP 241 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA TJ924 UT WOS:A1995TJ92400001 PM 8565699 ER PT J AU MUHLHAUSER, J MERRILL, MJ PILI, R MAEDA, H BACIC, M BEWIG, B PASSANITI, A EDWARDS, NA CRYSTAL, RG CAPOGROSSI, MC AF MUHLHAUSER, J MERRILL, MJ PILI, R MAEDA, H BACIC, M BEWIG, B PASSANITI, A EDWARDS, NA CRYSTAL, RG CAPOGROSSI, MC TI VEGF(165) EXPRESSED BY A REPLICATION-DEFICIENT RECOMBINANT ADENOVIRUS VECTOR INDUCES ANGIOGENESIS IN-VIVO SO CIRCULATION RESEARCH LA English DT Article DE ANGIOGENESIS; ENDOTHELIUM; GENE THERAPY; VEGF; VASCULAR PERMEABILITY FACTOR ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; GENE-TRANSFER; BASEMENT-MEMBRANE; FACTOR FAMILY; IN-VIVO; INVIVO; RNA; DIFFERENTIATION; EPITHELIUM AB To evaluate the concept that localized delivery of angiogenic factors via virus-mediated gene transfer may be useful in the treatment of ischemic disorders, the replication-deficient adenovirus (Ad) vector AdCMV.VEGF(165) (where CMV is cytomegalovirus and VEGF is vascular endothelial growth factor) containing the cDNA for human VEGF(165) secreted endothelial cell-specific angiogenic growth factor, was constructed. Human umbilical vein endothelial cells (HUVECs) and rat aorta smooth muscle cells (RASMCs) infected with AdCMV.VEGF(165) (5 and 20 plaque-forming units [pfu] per cell) demonstrated VEGF mRNA expression and protein secretion into the supernatant. Furthermore, the conditioned medium from these cells enhanced vascular permeability in vivo. In contrast, neither VEGF mRNA nor secreted protein was found in uninfected HUVECs or RASMCs or in cells infected with the control vector AdCMV.beta gal (where beta gal is beta-galactosidase). Assessment of starved HUVECs at 14 days demonstrated sixfold more cells for AdCMV. VEGF(165)-infected HUVECs (20 pfu per cell) than for either infected or uninfected control cells. RASMC proliferation was unaffected by infection with AdCMV.VEGF(165). When plated in 2% serum on dishes precoated with reconstituted basement membrane (Matrigel), HUVECs infected with AdCMV.VEGF(165) (20 pfu per cell) differentiated into capillary-like structures. Under similar conditions, both uninfected HUVECs and HUVECs infected with AdCMV.beta gal did not differentiate. To evaluate the ability of AdCMV.VEGF(165) to function in vivo, either AdCMV. VEGF(165) or AdCMV.beta gal (2x10(10) pfu) was resuspended in 0.5 mt Matrigel and injected subcutaneously into mice. Immunohistochemical staining demonstrated VEGF in the tissues surrounding the Matrigel plugs containing AdCMV.VEGF, up to 3 weeks after injection, whereas no VEGF was found in the control plugs with AdCMV.beta gal. Two weeks after injection, there was histological evidence of neovascularization in the tissues surrounding the Matrigel containing AdCMV.VEGF(165) whereas no significant angiogenesis was observed in response to AdCMV.beta gal. Furthermore, the Matrigel plugs with AdCMV.VEGF(165) demonstrated hemoglobin content fourfold higher than the plugs with AdCMV.beta gal. Together, these in vitro and in vivo studies are consistent with the concept that Ad vectors may provide a useful strategy for efficient local delivery of VEGF(165) in the treatment of ischemic diseases. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,GENE THERAPY UNIT,BALTIMORE,MD 21224. NHLBI,PULM BRANCH,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NIA,BIOL CHEM LAB,BALTIMORE,MD 21224. CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV PULM & CRIT CARE,NEW YORK,NY 10021. IST DERMOPAT IMMACOLATA,PATOL VASC LAB,ROME,ITALY. NR 42 TC 124 Z9 129 U1 1 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC PY 1995 VL 77 IS 6 BP 1077 EP 1086 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA TH103 UT WOS:A1995TH10300005 PM 7586219 ER PT J AU Mulligan, T Carrasquillo, JA Chung, Y Milenic, DE Schlom, J Feuerstein, I Paik, C Perentesis, P Reynolds, J Curt, G Goeckeler, W Fordyce, W Cheng, R Riseberg, D Cowan, K OShaughnessy, J AF Mulligan, T Carrasquillo, JA Chung, Y Milenic, DE Schlom, J Feuerstein, I Paik, C Perentesis, P Reynolds, J Curt, G Goeckeler, W Fordyce, W Cheng, R Riseberg, D Cowan, K OShaughnessy, J TI Phase I study of intravenous Lu-177-labeled CC49 murine monoclonal antibody in patients with advanced adenocarcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID GLYCOPROTEIN TAG-72; COLORECTAL-CANCER; SOLID TUMORS; B72.3; ANTIGEN; CARCINOMAS; GENERATION; DIAGNOSIS; MOLECULES; PATTERNS AB CC49, a murine monoclonal antibody that recognizes the tumor-associated glycoprotein 72, was conjugated to the chemical chelate 1,4,7,10-tetraaza-1-(1-carboxy-3-(4-amino-phenyl)propyl)-tris-4,7,10-((carboxy)methyl)cyclododecane that had been labeled with a beta emitter, Lu-177. Preclinical studies had shown that Lu-177-labeled CC49 caused regression of human colon adenocarcinoma xenografts in nude mice. Patients with advanced adenocarcinoma who had failed standard treatment and whose tumors expressed the tumor-associated glycoprotein 72 antigen were eligible for treatment to determine the maximum tolerated dose of Lu-177-labeled CC49. The starting dose of Lu-177 was 10 mCi/m(2) given i.v. with the dose of CC49 held constant at 20 mg, Pharmacokinetic sampling and immunoscintigraphy were performed over the ensuing 3 weeks, The dose of radioactive Lu-177 was escalated by 15 mCi/m(2) for each successive dose level. Unexpected bone marrow toxicity developed in patients treated at the second dose level with 25 mCi/m(2) Lu-177; two patients developed grade 4 thrombocytopenia, while the third patient developed grade 3 thrombocytopenia. Pharmacokinetic studies showed that the plasma half-life of the immunoconjugate was 67 h; whole-body retention, however, was prolonged with a biological half-life of 258 h, Serial gamma camera imaging localized known tumor in all patients, and also demonstrated prolonged Lu-177 retention in the reticuloendothelial system (RES), Bone marrow dosimetry estimates ranged from 4 to 5 REMS/mCi Lu-177 based on imaging and biopsy data, Analysis of bone marrow biopsies demonstrated that most of the Lu-177 was localized in the cellular compartment and not in the bone, No antitumor responses were observed. Intravenous administration of 15 mCi/m(2) Lu-177-labeled CC49 to previously treated advanced cancer patients was associated with acceptable hematological toxicity and was the maximum tolerated dose, However, prolonged retention of Lu-177 in the RES, including the bone marrow, was observed and limited the dose of Lu-177 that could be given, Additional studies are indicated to reduce RES uptake and retention of this immunoconjugate. C1 NCI,DIV CANC BIOL & DIAG,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. DOW CHEM CO USA,MIDLAND,MI 48667. RI Carrasquillo, Jorge/E-7120-2010 NR 35 TC 72 Z9 74 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 1995 VL 1 IS 12 BP 1447 EP 1454 PG 8 WC Oncology SC Oncology GA TL020 UT WOS:A1995TL02000002 PM 9815943 ER PT J AU Divgi, CR Scott, AM Gulec, S Broussard, EK Levy, N Young, C Capitelli, P Daghighian, F Williams, JM Finn, RD Kemeny, N Hilton, S Kelsen, D Milenic, DE Lora, ME Schlom, J Larson, SM AF Divgi, CR Scott, AM Gulec, S Broussard, EK Levy, N Young, C Capitelli, P Daghighian, F Williams, JM Finn, RD Kemeny, N Hilton, S Kelsen, D Milenic, DE Lora, ME Schlom, J Larson, SM TI Pilot radioimmunotherapy trial with I-131-labeled murine monoclonal antibody CC49 and deoxyspergualin in metastatic colon carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID GRAFT-REJECTION; 15-DEOXYSPERGUALIN; CANCER; B72.3; MICE AB An antimouse immune response is invariable following administration of murine monoclonal antibody (mAb), precluding effective multidose therapy, In advanced colorectal cancer patients, we carried out a pilot study with multiple doses of I-131-labeled CC49 administered with deoxyspergualin (DSG), an immunomodulator, to determine its effect on immune response, Cumulative toxicity and efficacy were also evaluated. Six patients with tumor-associated glycoprotein 72-expressing colorectal cancer were treated i.v. with 15 mCi/m(2) I-131-labeled to 20 mg mAb CC49 biweekly, along with concurrent DSG 200 mg/m(2) daily for 5 days, for a maximum of four courses, None had received prior murine mAbs. All patients had targeting of radioactivity to known tumor sites following initial infusion, Four of six patients received all four courses of therapy, three, without any acute side effects, In these patients, there was no change in serum clearance with variable tumor targeting following repeat infusions, Two patients had less than or equal to grade II anaphylactoid reactions, which were treated without sequelae. One of these had faster serum clearance of radioactivity following repeat infusions of I-131-labeled CC49, Human antimouse antibody titers in all patients were significantly less compared to concurrent times in patients receiving CC49 without DSG (P < 0.05), There was no correlation between the human antimouse antibody titer and serum clearance or tumor targeting of I-131-labeled CC49, There were no clinical responses. We concluded that multiple doses of murine antibody I-131-labeled CC49 can be safely administered with no change in serum or whole-body kinetics in 50% of patients treated biweekly, DSG may reduce the human immune response to the murine mAb. C1 NCI,BETHESDA,MD 20892. RP Divgi, CR (reprint author), MEM SLOAN KETTERING CANC CTR,NUCL MED SERV,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [N01-CA-97609] NR 24 TC 18 Z9 18 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 1995 VL 1 IS 12 BP 1503 EP 1510 PG 8 WC Oncology SC Oncology GA TL020 UT WOS:A1995TL02000009 PM 9815950 ER PT J AU Bigner, DD Archer, GE McLendon, RE Friedman, HS Fuchs, HE Pai, LH Herndon, JE Pastan, IH AF Bigner, DD Archer, GE McLendon, RE Friedman, HS Fuchs, HE Pai, LH Herndon, JE Pastan, IH TI Efficacy of compartmental administration of immunotoxin LMB-1 (B3-LysPE38) in a rat model of carcinomatous meningitis SO CLINICAL CANCER RESEARCH LA English DT Article ID LEPTOMENINGEAL NEOPLASIA; METHOTREXATE; CHEMOTHERAPY; METASTASES; THERAPY; CANCER; TUMORS; SYSTEM; B3 AB LMB-1 (B3-LysPE38) is an immunotoxin composed of the tumor-reactive monoclonal antibody B3 and a genetically engineered form of Pseudomonas exotoxin, Monoclonal antibody B3 reacts with a carbohydrate epitope that is found on a number of solid tumors (e.g., breast, ovarian, and lung carcinomas) that frequently invade the intrathecal space, causing neoplastic meningitis, The Pseudomonas exotoxin has been engineered to remove the binding domain to eliminate nonspecific binding, A model of human neoplastic meningitis using rats bearing the human epidermoid carcinoma A431 was used for therapeutic studies of immunotoxin LMB-1, Therapy was initiated 3 days after injection of the tumor cells, which was one third of the median survival time of untreated rats, A single intrathecal injection of 40 mu g increased median survival from 9 days with saline injection to 16 days (78%, P < 0.001), and a single dose of 200 mu g increased median survival to 25 days (188%, P < 0.001), Three doses of 40 or 200 mu g given on days 3, 6, and 8 significantly increased the median survival of 9.5 days associated with saline injection to 40.5 days (326% increase) and 33.0 days (247% increase), respectively, with two long-term survivors (191-day survival) in each treatment group, LMB-1 had no therapeutic effect on the treatment of two B3 antigen-negative neoplastic meningitis models, Treatment of the antigen-positive A431 neoplastic meningitis with B3 alone or a nonspecific monoclonal, MOPC, coupled to the engineered Pseudomonas exotoxin produced no survival effects, Nontumor-bearing athymic rats showed no toxicity with a single dose of either 40 mu g or 200 mu g, or 3 doses of 40 mu g. However, when they were given three doses of 200 mu g, these rats showed weight loss and loss of neurological function, and two of eight animals died, These studies indicate that, in the range of the most therapeutically effective dosage, the immunotoxin LMB-1 is tolerated in the intrathecal space and should be considered for human intrathecal trials. C1 DUKE UNIV,MED CTR,PREUSS LAB BRAIN TUMOR RES,DURHAM,NC 27710. DUKE UNIV,MED CTR,DIV BIOMETRY,DURHAM,NC 27710. NCI,DIV CANC BIOL,MOLEC BIOL LAB,BETHESDA,MD 20892. RP Bigner, DD (reprint author), DUKE UNIV,MED CTR,DEPT PATHOL,BOX 3156,DURHAM,NC 27710, USA. FU NCI NIH HHS [CA 11898, CA 56115]; NINDS NIH HHS [NS 20023] NR 32 TC 9 Z9 9 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 1995 VL 1 IS 12 BP 1545 EP 1555 PG 11 WC Oncology SC Oncology GA TL020 UT WOS:A1995TL02000014 PM 9815955 ER PT J AU Scala, S Dickstein, B Regis, J Szallasi, Z Blumberg, PM Bates, SE AF Scala, S Dickstein, B Regis, J Szallasi, Z Blumberg, PM Bates, SE TI Bryostatin 1 affects P-glycoprotein phosphorylation but not function in multidrug-resistant human breast cancer cells SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; PLASMA-MEMBRANE GLYCOPROTEIN; REDUCED DRUG ACCUMULATION; HUMAN-KB CELLS; PHORBOL ESTER; CARCINOMA-CELLS; LEUKEMIA-CELLS; MCF-7 CELLS; HL60 CELLS; ADRIAMYCIN AB The function of P-glycoprotein (Pgp), which confers multidrug resistance by active efflux of drug, is thought to be dependent on phosphorylation, Previous studies have suggested that protein kinase C (PKC) plays an important role in Pgp phosphorylation, We report here the effects of bryostatin 1, a unique PKC activator and inhibitor, on Pgp function in a multidrug-resistant MCF-7 human breast cancer subline which overexpresses PKC-alpha. Bryostatin 1 (100 nM) decreased Pgp phosphorylation after 24 h of treatment, In contrast, it did not affect Pgp function as demonstrated by the accumulation of [H-3]vinblastine and rhodamine 123, We compared the effect of bryostatin 1 treatment on PKC-alpha with that of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (200 nM). 12-O-tetradecanoylphorbol-13-acetate caused translocation of PKC-alpha from the cytosol to the cell membrane after a 10-min treatment and its down-regulation after 24 h of treatment, Likewise, bryostatin 1 (100 nM) caused translocation, but only after longer treatment (1 h), and it caused down-regulation of PKC-alpha at 24 h of treatment, Thus, while the MCF-7TH cells overexpress the PKC-alpha isoform, and its down-regulation by bryostatin 1 is associated with decreased Pgp phosphorylation, these alterations do not modulate drug transport, We conclude that, while bryostatin 1 may be useful clinically because of its ability to inhibit PKC, it is not able to reverse Pgp-mediated multidrug resistance. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RI Scala, Stefania/K-1380-2016 OI Scala, Stefania/0000-0001-9524-2616 NR 49 TC 20 Z9 20 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 1995 VL 1 IS 12 BP 1581 EP 1587 PG 7 WC Oncology SC Oncology GA TL020 UT WOS:A1995TL02000018 PM 9815959 ER PT J AU Kuan, CT Pai, LH Pastan, I AF Kuan, CT Pai, LH Pastan, I TI Immunotoxins containing Pseudomonas exotoxin that target Le(Y) damage human endothelial cells in an antibody-specific mode: Relevance to vascular leak syndrome SO CLINICAL CANCER RESEARCH LA English DT Article ID RICIN-A-CHAIN; PHASE-I; CANCER; CARCINOMA; LYMPHOMA; THERAPY; TRIAL; MICE; B3 AB Vascular leak syndrome (VLS) was originally found to be a major dose-limiting toxicity in humans with cancer treated with several immunotoxins (ITs) containing ricin A chain or blocked ricin, Recently, VLS has also been observed in patients treated with an IT containing the murine monoclonal antibody (MAb) B3 coupled to LysPE38, a recombinant truncated form of Pseudomonas exotoxin (PE) A, Antibody B3 (IgG1k) recognizes Lewis(Y) and related carbohydrate epitopes present on many human solid tumors, and B3-LysPE38 showed excellent antitumor activity in nude mice bearing tumors that express the B3 antigen, In the clinical trial, the development of VLS has prevented the administration of the amount of IT necessary to achieve blood levels required for good therapeutic responses, We have now investigated the effects of several PE-based ITs on different human endothelial cell lines to elucidate the mechanism of VLS induced by ITs containing PE, To assess the cytotoxic effect of IT on endothelial cells, various ITs were incubated with cells for 2 or 20 h, and the incorporation of [H-3]leucine into protein was measured, The endothelial cells studied were human umbilical vein endothelial cells, human lung-derived microvascular endothelial cells (HUVECs), human adult dermal microvascular endothelial cells, human pulmonary artery endothelial cells, and human aortic endothelial cells, We found that both B3-LysPE38 (LMB-1), a chemical conjugate of MAb B3 with PE38, as welt as B3(Fv)-PE38 (LMB-7), a recombinant single chain immunotoxin, inhibited protein synthesis, with 50% inhibitory concentrations between 600 and 1000 ng/ml for 20-h incubation in HUVECs, human lung-derived microvascular endothelial cells, and human adult dermal microvascular endothelial cells but not on human pulmonary artery endothelial cells, The cytotoxic effect was specific since PE38 itself or PE coupled to several other antibodies did not inhibit protein synthesis in these cells even at 10,000 ng/ml, Further evidence that the cytotoxicity of B3-containing ITs is due to specific B3 binding to endothelial cells comes from the fact that the cytotoxicity can be blocked by excess free MAb B3. HUVECs undergo overt morphological changes after treatment with B3-LysPE38 or B3(Fv)PE38, Gaps between the cells are formed after a 20-h exposure but not after 2 h, These studies suggest that VLS in patients is due to capillary damage caused by prolonged exposure to high concentrations of LMB-1. C1 NCI,DIV BASIC SCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 25 TC 49 Z9 51 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 1995 VL 1 IS 12 BP 1589 EP 1594 PG 6 WC Oncology SC Oncology GA TL020 UT WOS:A1995TL02000019 PM 9815960 ER PT J AU UENO, T MITSUYA, H AF UENO, T MITSUYA, H TI CURRENT STATUS OF THE DEVELOPMENT OF HIV PROTEASE INHIBITORS AND THEIR CLINICAL POTENTIAL SO CLINICAL IMMUNOTHERAPEUTICS LA English DT Article ID C2 SYMMETRICAL INHIBITORS; REVERSE-TRANSCRIPTASE; INVITRO; ZIDOVUDINE; ALLOPHENYLNORSTATINE; FIDELITY; DESIGN; AGENTS AB HIV type 1 (HIV-1) codes a virus-specific aspartic protease that mediates crucial proteolytic processing of viral protein precursors at a late stage(s) in the replication of the virus. Thus, HIV protease represents a virus-specific target for the therapy of HIV infection. Several protease inhibitors have already shown favourable antiviral activity in patients with HIV-1 infection. The critical questions now to be answered are how long the observed antiviral activity is sustained, and whether significant clinical benefit is gained in individuals receiving protease inhibitors. C1 NCI,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. RI Ueno, Takamasa/F-5788-2013 OI Ueno, Takamasa/0000-0003-4852-4236 NR 69 TC 9 Z9 9 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7039 J9 CLIN IMMUNOTHER JI Clin. Immunother. PD DEC PY 1995 VL 4 IS 6 BP 451 EP 461 PG 11 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA TH574 UT WOS:A1995TH57400004 ER PT J AU MCCRAE, RR AF MCCRAE, RR TI PERSONALITY, SOCIAL SKILLS, AND PSYCHOPATHOLOGY - AN INDIVIDUAL-DIFFERENCES APPROACH - GILBERT,DG, CONNOLLY,JJ SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP MCCRAE, RR (reprint author), NIA,GERONTOL RES CTR,PERSONAL STRESS & COPING SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD DEC PY 1995 VL 40 IS 12 BP 1170 EP 1171 PG 2 WC Psychology, Multidisciplinary SC Psychology GA TH101 UT WOS:A1995TH10100025 ER PT J AU Shih, JH AF Shih, JH TI Sample size calculation for complex clinical trials with survival endpoints SO CONTROLLED CLINICAL TRIALS LA English DT Article DE Markov model; time-dependent rates; nonproportional hazards; lag time; unconditional power AB Sample size estimation is important in planning clinical trials. The purpose of this paper is to describe features and use of SIZE, a comprehensive computer program for calculating sample size, power, and duration of study in clinical trials with time-dependent rates of event, crossover, and loss to follow-up. SIZE covers a wide range of complexities commonly occurring in clinical trials, such as nonproportional hazards, lag in treatment effect, and uncertainties in treatment benefit. The use of SIZE is illustrated by several hypothetical examples as well as applications to real study designs, each featuring a statistical issue. RP Shih, JH (reprint author), NHLBI,OFF BIOSTAT RES,2 ROCKLEDGE CTR,ROOM 8217,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [N01-AI-05073] NR 8 TC 54 Z9 55 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 1995 VL 16 IS 6 BP 395 EP 407 DI 10.1016/S0197-2456(95)00132-8 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA TN586 UT WOS:A1995TN58600003 PM 8720017 ER PT J AU DeMets, DL Fleming, TR Whitley, RJ Childress, JF Ellenberg, SS Foulkes, M Mayer, KH OFallon, J Pollard, RB Rahal, JJ Sande, M Straus, S Walters, L WhitleyWilliams, P AF DeMets, DL Fleming, TR Whitley, RJ Childress, JF Ellenberg, SS Foulkes, M Mayer, KH OFallon, J Pollard, RB Rahal, JJ Sande, M Straus, S Walters, L WhitleyWilliams, P TI The Data and Safety Monitoring Board and Acquired immune deficiency syndrome (AIDS) clinical trials SO CONTROLLED CLINICAL TRIALS LA English DT Article DE DSMBs; AIDS clinical trials ID PLACEBO-CONTROLLED TRIAL; SEQUENTIAL BOUNDARIES; DOUBLE-BLIND; COMMITTEES; ZIDOVUDINE; INFECTION; EFFICACY; ISSUES; AZT AB The urgency of the Acquired immune deficiency syndrome (AIDS) epidemic has mandated that multiple therapeutic approaches be developed and that these approaches be evaluated through clinical trials. To oversee these trials, the National Institute of Allergy and Infectious Diseases (NIAID) has created three large clinical trial programs monitored by a Data and Safety Monitoring Board (DSMB). For each clinical trial, this Board uses a standardized approach employing contemporary biostatistical, medical, and ethical principles. The DSMB is responsible for reviewing interim data on clinical trial performance, treatment safety and efficacy, and overall study progress. If interim results provide convincing evidence of either excessive adverse effects or significant treatment benefit, the DSMB may recommend early termination of the trial to the NIAID and the study investigators. The responsibility, organization, and operating procedures of this DSMB are presented and illustrated through three clinical trials sponsored by NIAID and monitored by the Board. The rationale and operational model for the DSMB may be a useful example for the development of similar review processes in other HIV clinical trial settings. C1 UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. UNIV ALABAMA,DEPT PEDIAT MICROBIOL & MED,BIRMINGHAM,AL. UNIV VIRGINIA,DEPT RELIGIOUS STUDIES,CHARLOTTESVILLE,VA. NIAID,BIOSTAT RES BRANCH,BETHESDA,MD 20892. MEM HOSP RHODE ISL,DEPT MED,PAWTUCKET,RI. MAYO CLIN,DIV BIOSTAT,ROCHESTER,MN. UNIV TEXAS,MED BRANCH,DEPT INTERNAL MED,GALVESTON,TX 77550. NEW YORK HOSP,QUEENS MED CTR,DEPT MED,NEW YORK,NY 10021. ALBERT EINSTEIN COLL MED,NEW YORK,NY. SAN FRANCISCO GEN HOSP,DEPT MED,SAN FRANCISCO,CA 94110. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,KENNEDY INST ETH,WASHINGTON,DC 20057. UNIV MED & DENT NEW JERSEY,DEPT PEDIAT,NEW BRUNSWICK,NJ. RP DeMets, DL (reprint author), UNIV WISCONSIN,SCH MED,DEPT BIOSTAT,K6-446 CLIN SCI CTR,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 31 TC 27 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 1995 VL 16 IS 6 BP 408 EP 421 DI 10.1016/S0197-2456(95)00073-9 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA TN586 UT WOS:A1995TN58600004 PM 8720018 ER PT J AU Charache, S Terrin, ML Moore, RD Dover, GJ McMahon, RP Barton, FB Waclawiw, M Eckert, SV AF Charache, S Terrin, ML Moore, RD Dover, GJ McMahon, RP Barton, FB Waclawiw, M Eckert, SV TI Design of the multicenter study of hydroxyurea in sickle cell anemia SO CONTROLLED CLINICAL TRIALS LA English DT Article DE sickle cell anemia; fetal hemoglobin; hydroxyurea; sickle cell crises prevention ID CHRONIC MYELOID-LEUKEMIA; GLOBIN GENE-CLUSTER; FETAL-HEMOGLOBIN; ALPHA-THALASSEMIA; CONTROL REGION; DISEASE; ERYTHROPOIETIN; AUGMENTATION; PREGNANCY; KINETICS AB The Multicenter Study of Hydroxyurea in Sickle Cell Anemia is a randomized double-blind placebo-controlled trial to test whether hydroxyurea can reduce the rate of painful crises in adult patients who have at least three painful crises per year. The sample size of 299 patients yields at least 90% power to detect a 50% or greater reduction in crisis rate. Dosage starts at 15 mg/kg/day and is titrated to the patient's maximum tolerated dose up to 35 mg/kg/day. Placebo dosage is titrated in similar fashion to maintain blinding. Attempts are made to ascertain medical contacts for at least 2 years after study entry. The Core Laboratory, Treatment Distribution Center, and Data Coordinating Center collaborate to provide standardized monitoring for toxicity and dose adjustments. The Core Laboratory also reduces the possibility of inadvertent unmasking of treatment assignment during review of hematologic data in clinical centers. An independent Crisis Review Committee classifies clinical events to assure that outcome evaluations are standardized and unbiased by knowledge of treatment assignments. The Data and Safety Monitoring Board assures scientific integrity of the study, as well as the safety and ethical treatment of study patients. We expect the study to determine whether or not treatment with hydroxyurea can offer significant clinical benefit to patients with the most common hereditary disorder among African-Americans in the United States. C1 MARYLAND MED RES INST,BALTIMORE,MD. NHLBI,BETHESDA,MD 20892. RP Charache, S (reprint author), JOHNS HOPKINS UNIV,SCH MED,720 RUTLAND AVE,ROSS BLDG,ROOM 1018,BALTIMORE,MD 21205, USA. RI McMahon, Robert/C-5462-2009 FU NHLBI NIH HHS [5-U02-HL45692, 5-U01-HL45696] NR 50 TC 45 Z9 46 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 1995 VL 16 IS 6 BP 432 EP 446 DI 10.1016/S0197-2456(95)00098-4 PG 15 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA TN586 UT WOS:A1995TN58600006 PM 8925656 ER PT J AU Winter, DB Gearhart, PJ AF Winter, DB Gearhart, PJ TI Somatic hypermutation: Another piece in the hypermutation puzzle SO CURRENT BIOLOGY LA English DT Note ID TRANSGENES; MUTATIONS; GENES; KAPPA AB Studies with transgenic mice are beginning to define the minimal requirements for the somatic hypermutation of immunoglobulin genes that is critical in the production of high-affinity antibodies. RP Winter, DB (reprint author), NIA,GENET MOLEC LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 14 TC 7 Z9 7 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 1 PY 1995 VL 5 IS 12 BP 1345 EP 1346 DI 10.1016/S0960-9822(95)00265-X PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TL102 UT WOS:A1995TL10200005 PM 8749380 ER PT J AU HARTL, DL KAFATOS, FC OBRIEN, S AF HARTL, DL KAFATOS, FC OBRIEN, S TI EDITORIAL OVERVIEW - GENOME EVOLUTION COMES OF AGE SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article C1 EUROPEAN MOLEC BIOL LAB,D-69117 HEIDELBERG,GERMANY. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP HARTL, DL (reprint author), HARVARD UNIV,DEPT ORGANISM & EVOLUTIONARY BIOL,16 DIVIN AVE,CAMBRIDGE,MA 02138, USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 1995 VL 5 IS 6 BP 705 EP 708 DI 10.1016/0959-437X(95)80001-L PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA TJ927 UT WOS:A1995TJ92700001 ER PT J AU CARPENTER, MA OBRIEN, SJ AF CARPENTER, MA OBRIEN, SJ TI COADAPTATION AND IMMUNODEFICIENCY VIRUS - LESSONS FROM THE FELIDAE SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID NUCLEOTIDE-SEQUENCE; NEF GENE; CATS; LENTIVIRUS; INFECTION; WILD; FIV; ORGANIZATION; PREVALENCE; EXPOSURE AB The emergence of pathogenic viruses in new species offers an unusual opportunity to monitor the coadaptation of viruses and their hosts in a dynamic ongoing process of intense biological selection. Tracking lentivirus epidemics in man, monkeys and cats reveals genomic struggles at three levels: quasispecies divergence within an individual; coadaptation of virus and host genomes subsequent to disease outbreaks; and transmission, spread and pathogenesis in related host species. Aspects of each level are revealed by examining the genetic diversity of feline immunodeficiency virus in domestic and wild cat species. This approach has been facilitated by the recent genetic characterization of a novel lentivirus in lions. RP CARPENTER, MA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,POB B,FREDERICK,MD 21702, USA. OI Carpenter, Margaret/0000-0003-1606-1986 NR 53 TC 54 Z9 54 U1 3 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 1995 VL 5 IS 6 BP 739 EP 745 DI 10.1016/0959-437X(95)80006-Q PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA TJ927 UT WOS:A1995TJ92700006 PM 8745072 ER PT J AU DEAN, M ALLIKMETS, R AF DEAN, M ALLIKMETS, R TI EVOLUTION OF ATP-BINDING CASSETTE TRANSPORTER GENES SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID P-GLYCOPROTEIN GENE; MULTIDRUG-RESISTANCE; CYSTIC-FIBROSIS; MDR-1 GENE; LEISHMANIA; PEROXISOME; SUBUNITS; HOMOLOG; DNA AB The transport of molecules across lipid membranes is an essential function of all living organisms. One of the families of genes that have evolved to carry out this function is that which encodes the ATP-binding cassette proteins. These molecules use active transport to pump specific molecules across membranes, and the genes that encode them are found in abundance in the genomes of both prokaryotes and eukaryotes. By using gene disruption techniques and by studying homologous genes in model organisms, significant progress has been made during the last few years in evaluating the physiological functions of ABC proteins in higher eukaryotes. RP DEAN, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BLDG 560,ROOM 21-18,FREDERICK,MD 21702, USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 42 TC 168 Z9 171 U1 1 U2 12 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 1995 VL 5 IS 6 BP 779 EP 785 DI 10.1016/0959-437X(95)80011-S PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA TJ927 UT WOS:A1995TJ92700011 PM 8745077 ER PT J AU HIRSCH, V DAPOLITO, G GOEKEN, R CAMPBELL, BJ AF HIRSCH, V DAPOLITO, G GOEKEN, R CAMPBELL, BJ TI PHYLOGENY AND NATURAL-HISTORY OF THE PRIMATE LENTIVIRUSES, SIV AND HIV SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; INFECTION; MONKEYS; AFRICA; PCR; VPR AB Studies of primate lentivirus phylogeny over the past decade have established a minimum of five related, but genetically distinct, groups of simian immunodeficiency virus (SIV), each originating from a different African primate species. The hypothesis that HIV-2 (and SIVmac) arose by cross-species transmission from sooty mangabeys (Cercocebus atys has been strengthened by a more detailed characterization of the SIVsm/SIVmac/HIV-2 group of viruses. SIV from all four subspecies of African green monkeys (SIVagm) have been characterized with an apparent chimeric genome structure of SIVagm from West African green monkeys. Although these naturally infected primates remain healthy, cross-species transmission to other primate species may result in immunodeficiency, as caused by SIVsm infection of macaque monkeys (Macaca sp.) and recently, SIVagm infection of pig-tailed macaques (M. nemestrina). Studies of variation within infected individuals have been facilitated by adaptation of the techniques of heteroduplex analysis and single-stranded conformational polymorphism of PCR generated fragments. RP HIRSCH, V (reprint author), NIAID,INFECT DIS LAB,TWINBROOK FACIL,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 28 TC 46 Z9 48 U1 1 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 1995 VL 5 IS 6 BP 798 EP 806 DI 10.1016/0959-437X(95)80014-V PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA TJ927 UT WOS:A1995TJ92700014 PM 8745080 ER PT J AU DEKABAN, CA DIGILIO, L FRANCHINI, G AF DEKABAN, CA DIGILIO, L FRANCHINI, G TI THE NATURAL-HISTORY AND EVOLUTION OF HUMAN AND SIMIAN T-CELL LEUKEMIA/LYMPHOTROPIC VIRUSES SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID LEUKEMIA-LYMPHOMA VIRUS; HTLV-II INFECTION; COMPLETE NUCLEOTIDE-SEQUENCE; INTRAVENOUS-DRUG-USERS; PAPUA-NEW-GUINEA; VARIANT; IDENTIFICATION; POPULATIONS; PREVALENCE; PYGMIES AB The past live years have seen significant advances in understanding the origin and evolution of human T-cell leukemia/lymphotropic virus types I and II. The highlights include the identification of human T-cell leukemia/lymphotropic virus types I and II genotypic variants in remote human populations and the discovery of widely divergent simian T-cell leukemia virus in African and Asian non-human primates. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP DEKABAN, CA (reprint author), JOHN P ROBARTS RES INST,GENE THERAPY & MOLEC VIROL GRP,POB 5015,100 PERTH DR,LONDON,ON N6A 5K8,CANADA. NR 42 TC 8 Z9 8 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 1995 VL 5 IS 6 BP 807 EP 813 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA TJ927 UT WOS:A1995TJ92700015 ER PT J AU Oliver, G Mailhos, A Wehr, R Copeland, NG Jenkins, NA Gruss, P AF Oliver, G Mailhos, A Wehr, R Copeland, NG Jenkins, NA Gruss, P TI Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development SO DEVELOPMENT LA English DT Article DE homeobox; eye development; anterior neural plate; sine oculis; optic recess; forebrain; mouse ID MOUSE; HOMEOBOX; ORGANIZATION; DROSOPHILA; DELETION; EMBRYO; HEART; RNA AB The Drosophila sine oculis homeobox-containing gene is known to play an essential role in controlling the initial events of pattern formation in the eye disc and is also required for the development of other parts of the fly visual system including the optic lobes. In this paper, we report the isolation of a sequence-related gene referred to as Six3. Based on its amino acid sequence, this gene can be included in the new Six/sine oculis subclass of homeobox genes. Early on, Six3 expression is restricted to the anterior neural plate including areas that later will give rise to ectodermal and neural derivatives. Later, once the longitudinal axis of the brain bends, Six3 mRNA is also found in structures derived from the anterior neural plate: ectoderm of nasal cavity, olfactory placode and Rathke's pouch, and also the ventral forebrain including the region of the optic recess, hypothalamus and optic vesicles. Based on this expression pattern, we conclude that Six3 is one of the most anterior homeobox gene reported to date. The high sequence similarity of Six3 with the Drosophila sine oculis, and its expression during eye development, suggests that this gene is the likely murine homologue. This finding supports the idea that mammals and insects share control genes such as eyeless/Pax6 (Halder, G., Callaerts, P. and Gehring, W. J. (1995) Science 267, 1788-1792), and also possibly other members of the regulatory cascade required for eye morphogenesis. In Small eye (Pax6) mouse mutants Six3 expression is not affected. Finally, based on the chromosomal localization and the expression pattern of the mouse Six3 gene, the human Six3 cognate could be a good candidate to be at least one of the genes affected in patients with holoprosencephaly type 2 due to an interstitial deletion of 2p21-p22. This region shares a homology with the distal region of mouse chromosome 17 where Six3 has been mapped. C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. RP Oliver, G (reprint author), MAX PLANCK INST BIOPHYS CHEM,DEPT MOLEC CELL BIOL,AM FASSBERG,D-37077 GOTTINGEN,GERMANY. NR 34 TC 522 Z9 525 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC PY 1995 VL 121 IS 12 BP 4045 EP 4055 PG 11 WC Developmental Biology SC Developmental Biology GA TM478 UT WOS:A1995TM47800013 PM 8575305 ER PT J AU Appel, B Korzh, V Glasgow, E Thor, S Edlund, T Dawid, IB Eisen, JS AF Appel, B Korzh, V Glasgow, E Thor, S Edlund, T Dawid, IB Eisen, JS TI Motoneuron fate specification revealed by patterned LIM homeobox gene expression in embryonic zebrafish SO DEVELOPMENT LA English DT Article DE primary motoneuron; commitment; islet1; islet2; lim3; zebrafish; LIM; homeobox gene; gene expression; motoneuron ID PROTEIN ISL-1; IDENTIFIED MOTONEURONS; LARVAL ZEBRAFISH; CELL PATTERN; FLOOR PLATE; NEURONS; HOMEODOMAIN; DIFFERENTIATION; NOTOCHORD; ELEGANS AB In zebrafish, individual primary motoneurons can be uniquely identified by their characteristic cell body positions and axonal projection patterns, The fate of individual primary motoneurons remains plastic until just prior to axogenesis when they become committed to particular identities, We find that distinct primary motoneurons express particular combinations of LIM homeobox genes. Expression precedes axogenesis as well as commitment, suggesting that LIM homeobox genes may contribute to the specification of motoneuronal fates. By transplanting them to new spinal cord positions, we demonstrate that primary motoneurons can initiate a new program of LIM homeobox gene expression, as well as the morphological features appropriate for the new position. We conclude that the patterned distribution of different primary motoneuronal types within the zebrafish spinal cord follows the patterned expression of LIM homeobox genes, and that this reflects a highly resolved system of positional information controlling gene transcription. C1 UNIV OREGON,INST NEUROSCI,EUGENE,OR 97403. UMEA UNIV,DEPT MICROBIOL,S-90187 UMEA,SWEDEN. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. RI Korzh, Vladimir/H-1596-2011; OI Korzh, Vladimir/0000-0002-6580-7986; Glasgow, Eric/0000-0001-7729-3954 FU NICHD NIH HHS [F32HD07658]; NINDS NIH HHS [NS01476, NS23915] NR 35 TC 221 Z9 224 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 0950-1991 J9 DEVELOPMENT JI Development PD DEC PY 1995 VL 121 IS 12 BP 4117 EP 4125 PG 9 WC Developmental Biology SC Developmental Biology GA TM478 UT WOS:A1995TM47800020 PM 8575312 ER PT J AU ZAHNWAXLER, C COLE, PM WELSH, JD FOX, NA AF ZAHNWAXLER, C COLE, PM WELSH, JD FOX, NA TI PSYCHOPHYSIOLOGICAL CORRELATES OF EMPATHY AND PROSOCIAL BEHAVIORS IN PRESCHOOL-CHILDREN WITH BEHAVIOR PROBLEMS SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID PRO-SOCIAL BEHAVIOR; CONDUCT DISORDER; ANTISOCIAL-BEHAVIOR; PERSONAL DISTRESS; RATING-SCALE; PREDICTORS; GENDER; DIFFERENTIATION; PSYCHOPATHOLOGY; PERSPECTIVE AB This study focused on empathic and prosocial orientations in preschool children who vary in externalizing problems. Children were categorized as low, moderate, or high risk for developing disruptive behavior disorders, depending on severity of current behavior problems. Hypothetical and real encounters with others in distress were used to examine children's affect, behavior, autonomic activity, and social cognitions. When children witnessed someone in distress, empathic concern and prosocial behaviors were present at similar levels for all risk groups. However, moderate and high-risk children were less able than low-risk children to remain positively engaged with distress victims. Girls showed more prosocial behavior than boys, and boys showed more anger than girls. During sadness mood inductions to assess autonomic activity, risk groups did not differ on heart rate or vagal tone. Girls showed higher skin conductance than boys, with high-risk girls showing the highest levels. Higher heart rate (and heart rate deceleration) predicted empathic concern and prosocial behavior, whereas lower heart rate was associated with aggression and avoidance, Irrespective of risk. Although biological correlates of emotions and behaviors that reflect caring versus indifference to others' distress are identified, they do not support an early direct link to externalizing psychopathologies. C1 NIMH, BETHESDA, MD 20892 USA. UNIV MARYLAND, COLLEGE PK, MD 20742 USA. NR 68 TC 113 Z9 114 U1 4 U2 32 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN PY 1995 VL 7 IS 1 BP 27 EP 48 PG 22 WC Psychology, Developmental SC Psychology GA QW179 UT WOS:A1995QW17900003 ER PT J AU Gibney, G Buonanno, A AF Gibney, G Buonanno, A TI Analysis of neural-responsive myogenin upstream sequences by myoblast implantation SO DEVELOPMENTAL BIOLOGY LA English DT Article ID RECEPTOR ALPHA-SUBUNIT; PROTEIN-KINASE-C; MUSCLE-SPECIFIC ENHANCER; MESSENGER-RNA LEVELS; LOOP-HELIX PROTEINS; GENE-EXPRESSION; ELECTRICAL-ACTIVITY; SKELETAL-MUSCLE; GAMMA-SUBUNIT; MYOD FAMILY AB The expression of myogenin is suppressed during innervation and has been implicated in determining properties of skeletal muscle which are regulated by electrical activity. We previously reported that transcription driven by 3700 bp of the mouse myogenin upstream sequence (MYG3700) is activated by denervation in transgenic mice (Nucleic Acids Res. 21, 5684-5693, 1993). To extend our investigation of the activity dependence of the myogenin promoter, we have utilized myoblast implantation as a novel approach to in vivo reporter analysis. Myoblasts for hindlimb injections were generated by stable transfection of chloramphenicol acetyltransferase (CAT) reporters into a beta-galactosidase-expressing line of C2 cells. In vitro characterization of stable myoblast clones carrying myogenin-CAT deletion constructs revealed that while the proximal myogenin 5'-flanking sequence confers myotube specificity, high-level expression requires a region upstream (-335 to -1102) which depends on chromosomal integration for its function. for analysis by implantation, incorporation of injected myoblasts into existing myofibers was confirmed by histochemical staining. Using clonal myoblasts harboring nicotinic receptor alpha-subunit (alpha 800) and myosin light chain reporters as positive and negative controls, respectively, for denervation responsiveness, we determined that the nuclei of injected myoblasts are susceptible to regulatory signals imposed by nerve-induced electrical activity of the myofiber into which they incorporate. In in vivo analysis of myogenin upstream sequence by implantation, CAT activities of MYG3700 and MYG1565 reporters in injected limbs increased up to fourfold within 4 days after denervation, whereas the activities of MYG1102 and MYG335 were unchanged. By 10 days after denervation, all myogenin reporters displayed denervation responsiveness. These implantation data suggest an early phase of denervation activation, one that is mediated by control elements residing within -1102 to -1565 of the myogenin upstream sequence. Thus, the combined analyses of stable reporter myoblast Lines in vitro and in vivo by implantation provide an efficient means of evaluating regulatory regions for high-level expression and neural modulation of muscle gene transcription. (C) 1995 Academic Press, Inc. C1 NIH,DEV NEUROBIOL LAB,MOLEC NEUROBIOL UNIT,BETHESDA,MD 20892. NR 66 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC PY 1995 VL 172 IS 2 BP 614 EP 624 DI 10.1006/dbio.1995.8057 PG 11 WC Developmental Biology SC Developmental Biology GA TK478 UT WOS:A1995TK47800022 PM 8612976 ER PT J AU BORNSTEIN, MH TAMISLEMONDA, CS AF BORNSTEIN, MH TAMISLEMONDA, CS TI PARENT-CHILD SYMBOLIC PLAY - 3 THEORIES IN SEARCH OF AN EFFECT SO DEVELOPMENTAL REVIEW LA English DT Review ID PRETEND PLAY; INFANT; MOTHER; COMPETENCE; ATTACHMENT; LANGUAGE; TODDLERS; PERIOD; PERFORMANCE; ENVIRONMENT AB In symbolic play, children construct increasingly sophisticated representations of the world as well as relations between symbols and their external referents as they advance upon their developing cognitions about people, actions, and objects. Presumably, more sophisticated partners. like parents, promote children's development in this domain. Yet, the empirical literature to date shows little support for the notion that child solitary symbolic play grows through adult-child symbolic play interactions. This paper first reviews empirical studies that address the role and effects of a moro sophisticated partner on children's early symbolic play. Next, the paper presents three theoretical perspectives that support a view that symbolic interactions with adults ought to promote childrens symbolic play and advance children's representational competencies more broadly; they include attachment, scaffolding, and ethological theory. Finally, the paper revisits the literature on interactive influences on children's play reconsidering the nature and role of specific independent and dependent variables in studies of the growth of children's symbolic play. (C) Academic Press, Inc. C1 NYU,NEW YORK,NY 10012. RP BORNSTEIN, MH (reprint author), NICHHD,BLDG 31,ROOM B2B15,9000 ROCKILLE PIKE,BETHESDA,MD 20892, USA. NR 111 TC 20 Z9 20 U1 2 U2 11 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2297 J9 DEV REV JI Dev. Rev. PD DEC PY 1995 VL 15 IS 4 BP 382 EP 400 DI 10.1006/drev.1995.1015 PG 19 WC Psychology, Developmental SC Psychology GA TJ421 UT WOS:A1995TJ42100002 ER PT J AU HAYEK, A BEATTIE, GM CIRULLI, V LOPEZ, AD RICORDI, C RUBIN, JS AF HAYEK, A BEATTIE, GM CIRULLI, V LOPEZ, AD RICORDI, C RUBIN, JS TI GROWTH FACTOR/MATRIX-INDUCED PROLIFERATION OF HUMAN ADULT BETA-CELLS SO DIABETES LA English DT Note ID HUMAN PANCREATIC-ISLETS AB Proliferation of human beta-cells in vitro is desirable for both transplantation and biological studies. In this study, human pancreatic islets obtained from cadavers were kept in tissue culture plates that favored cell attachment, When the cells attached to the matrix produced by the rat-bladder carcinoma cell line 804G, 5'-bromo-2'-deoxyuridine (BrdU) labeling increased from 4,7 +/- 2.5 to 13.2 +/- 2.2%,while cells simultaneously labeled for insulin and BrdU increased from 0 to 32%, Addition of the growth factor hepatocyte growth factor/scatter factor (HGF/SF) increased BrdU labeling to 17.5 +/- 1.8 and the percentage of double positive (BrdU + insulin) cells to 69%. This is the first in vitro demonstration that human beta-cells grown in monolayer culture are able to replicate when exposed to selected matrices and growth factors, These experiments add further evidence that HGF/SF is an important mitogenic agent for human beta-cells. C1 UNIV MIAMI,DIABET RES INST,MIAMI,FL 33152. NATL CANC INST,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD. RP HAYEK, A (reprint author), UNIV CALIF SAN DIEGO,SCH MED,WHITTIER INST,DEPT PEDIAT,9894 GENESEE AVE,LA JOLLA,CA 92037, USA. OI Ricordi, Camillo/0000-0001-8092-7153 FU NIDDK NIH HHS [R01-DK-39087] NR 14 TC 131 Z9 132 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1995 VL 44 IS 12 BP 1458 EP 1460 DI 10.2337/diabetes.44.12.1458 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TG225 UT WOS:A1995TG22500018 PM 7589854 ER PT J AU Abati, A Sanford, JS Fetsch, P Marincola, FM Wolman, SR AF Abati, A Sanford, JS Fetsch, P Marincola, FM Wolman, SR TI Fluorescence in situ hybridization (FISH): A user's guide to optimal preparation of cytologic specimens SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE fluorescence in situ hybridization; specimen preparation; cytology ID NUMERICAL CHROMOSOMAL-ABNORMALITIES; INTERPHASE CELL-NUCLEI; INSITU HYBRIDIZATION; MALIGNANT-CELLS; PROBES; CANCER AB Fluorescence in situ hybridization (FISH) is a reliable method for tagging centromeric regions of specific chromosomes in interphase nuclei. Not only is FISH useful for chromosome enumeration, but as region-specific chromosome probes are developed, the clinical applications and potentials for use by pathologists are extensive. This technique lends itself particularly to use in cytology preparations because the cells are disaggregated and monolayer preparations yield excellent technical hybridization results. Over a 7-mo period we processed cytologic samples in an attempt to define and outline a method for optimal specimen processing for FISH use in cell suspensions, techniques applicable to all fresh cytology specimens which can also be used for the processing of surgical pathology aspirates and other material. All samples should be promptly processed to ensure specimen viability, and triaged on an individual basis to ensure preparation of moderately cellular monolayered cytospins. Equivalent nuclear probe signals have been obtained with several sample fixation methods: air-drying, 95% ethanol, methanol (Diff-Quik fixative), and Carnoy's solution No difference was noted in the nuclear probe signals or specimen adhesion on positively charged or noncharged slides. After initial fixation our slides remained at room temperature until FISH was performed, without any adverse effects. A short digestion with proteinase K and subsequent rehybridization yielded positive results on samples that originally yielded poor nuclear probe signals. (C) 1995 Wiley-Liss, Inc.* RP Abati, A (reprint author), NIH,CYTOPATHOL SECT,PATHOL LAB,BLDG 10,ROOM 2A19,BETHESDA,MD 20892, USA. NR 12 TC 27 Z9 28 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD DEC PY 1995 VL 13 IS 5 BP 486 EP 492 DI 10.1002/dc.2840130518 PG 7 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA TT501 UT WOS:A1995TT50100017 PM 8834324 ER PT J AU Bustin, M Alfonso, PJ Pash, JM Ward, JM Gearhart, JD Reeves, RH AF Bustin, M Alfonso, PJ Pash, JM Ward, JM Gearhart, JD Reeves, RH TI Characterization of transgenic mice with an increased content of chromosomal protein HMG-14 in their chromatin SO DNA AND CELL BIOLOGY LA English DT Article ID MOBILITY GROUP PROTEIN-14; DOWN-SYNDROME; CELL-CYCLE; LOCALIZATION; THYMUS; GENE; DIFFERENTIATION; TRANSCRIPTION; NUCLEOSOMES; EXPRESSION AB Chromosomal protein HMG-14 is a ubiquitous nuclear protein that may modulate the chromatin structure of transcriptionally active genes, To gain insights into the cellular function of the HMG-14 protein, we generated two transgenic mouse lines carrying either two or six copies of the human HMG-14 gene, The transgenic mice express human HMG-14 mRNA and protein in all tissues examined at a level reflecting the increased gene dosage, suggesting that the HMG14 transgene contains all the control regions necessary for regulated gene expression, Expression of the human HMG-14 protein does not alter the expression of the endogenous mouse HMG-14 protein or its close homolog, protein HMG-17. The intracellular distribution of the exogenous human protein is indistinguishable from that of the endogenous mouse protein, resulting in a three-fold increase in the level of the chromatin-bound HMG-14, The transgenic mice had a higher incidence of epithelial cysts in their thymus than did control animals, We conclude that the cellular levels of HMG-14/-17 are determined by gene copy number, that the DNA fragment containing the gene and about 1,000 bp flanking its 5' and 3' ends contain most of the elements necessary for gene expression, that the upper limits of HMG-14 in chromatin are not stringently regulated, and that a three-fold increase in chromatin-bound protein cause only mild phenotypic changes in the transgenic mice. C1 NCI,OFF LAB ANIM SCI,VET & TUMOR PAHTOL SECT,FREDERICK,MD 21702. JOHNS HOPKINS UNIV,SCH MED,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. RP Bustin, M (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3D-12,BETHESDA,MD 20892, USA. RI Bustin, Michael/G-6155-2015 FU NICHD NIH HHS [HD24605] NR 34 TC 13 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD DEC PY 1995 VL 14 IS 12 BP 997 EP 1005 DI 10.1089/dna.1995.14.997 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA TM783 UT WOS:A1995TM78300003 PM 8534374 ER PT J AU Margolin, A Kosten, TR Avants, SK Wilkins, J Ling, W Beckson, M Arndt, IO Cornish, J Ascher, JA Li, SH Bridge, P AF Margolin, A Kosten, TR Avants, SK Wilkins, J Ling, W Beckson, M Arndt, IO Cornish, J Ascher, JA Li, SH Bridge, P TI A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; methadone; pharmacotherapy; addiction; bupropion ID LONGITUDINAL DATA-ANALYSIS; SUBSTANCE-ABUSE TREATMENT; OPIOID ADDICTS; DESIPRAMINE; ABSTINENCE; DISORDER; DRUGS AB We conducted a multi-site, placebo-controlled, randomized double-blind clinical trial comparing bupropion HCL (300 mg/day) to placebo for the treatment of cocaine dependence in methadone-maintained subjects. A total of 149 subjects at three sites participated in a 12-week study, Outcome measures included cocaine use, level of depression, and psychosocial functioning, Results showed no significant differences between placebo and bupropion. Exploratory analyses suggested a medication effect for the subset of subjects depressed at study entry, The need to target subgroups of cocaine abusers in future pharmacotherapy trials and the possible role of treatment readiness are discussed. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. VET ADM MED CTR,PHILADELPHIA,PA 19104. BURROUGHS WELLCOME CO,DEPT NEUROL PYSCHIAT,RES TRIANGLE PK,NC 27709. NIDA,ROCKVILLE,MD 20857. RP Margolin, A (reprint author), YALE UNIV,SCH MED,DEPT PSYCHIAT,CONNECTICUT MENTAL HLTH CTR,SAC,34 PK ST,NEW HAVEN,CT 06519, USA. FU NIDA NIH HHS [P50-DA04060, R18-DA06190] NR 47 TC 111 Z9 111 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC PY 1995 VL 40 IS 2 BP 125 EP 131 DI 10.1016/0376-8716(95)01198-6 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA TN450 UT WOS:A1995TN45000004 PM 8745134 ER PT J AU Johnson, EO Schutz, CG Anthony, JC Ensminger, ME AF Johnson, EO Schutz, CG Anthony, JC Ensminger, ME TI Inhalants to heroin: A prospective analysis from adolescence to adulthood SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE inhalants; heroin; longitudinal; epidemiology; adolescent ID DRUG-USE; ABUSE; ADDICTS; HISTORY AB Recent cross-sectional studies have indicated that inhalant use might be a vulnerability marker for the development of heroin use. This study is the first prospective investigation of the hypothesized association between early inhalant use and later heroin use. Analyses were conducted using longitudinal data from a community sample of Woodlawn (an all African American community on the South side of Chicago). Six-hundred subjects participated in both the adolescent and the adult assessments (approximately ages 16 and 32, respectively). Youths with a history of inhalant use by age 16 were over nine times more likely to begin heroin use by age 32, even when other plausible risk factors for the development of heroin use were held constant (RR = 9.3; 95% C.I. = 1.3-51.3). These findings add to and are consistent with prior cross-sectional evidence from data based on treatment samples and national survey data. The results from this longitudinal assessment support the idea that youthful inhalant use should be regarded as a vulnerability marker for the development of more serious drug use involvement in the form of heroin use. C1 NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. RP Johnson, EO (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,615 N WOLFE ST,BALTIMORE,MD 21218, USA. FU NIDA NIH HHS [DA0663, R01 DA006630, DA07292, DA04392] NR 27 TC 45 Z9 46 U1 2 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC PY 1995 VL 40 IS 2 BP 159 EP 164 DI 10.1016/0376-8716(95)01201-X PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA TN450 UT WOS:A1995TN45000008 PM 8745138 ER PT J AU Ollo, C Lindquist, T Alim, TN Deutsch, SI AF Ollo, C Lindquist, T Alim, TN Deutsch, SI TI Predicting premorbid functioning in crack cocaine abusers SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE crack; cocaine; IQ; neuropsychology; cognition ID NEUROPSYCHOLOGICAL DEFICITS; WAIS-R; INTELLIGENCE; VALIDATION AB The Wide Range Achievement Test (Revised) (WRAT-R) reading test, demographic variables and drug use severity were used to develop prediction equations to estimate premorbid ability in 92 cocaine abusers. WRAT-R reading was correlated significantly with full scale, verbal and performance IQ. Stepwise regression indicated that only WRAT-R reading score and age accounted for 23% of the variance in Full Scale IQ (FSIQ) and 28% in Verbal IQ (VIQ). Abstinence and severity of use variables did not correlate with nor predict IQ. Actual and predicted IQ scores were correlated significantly and did not differ based on within group I-tests. Thus, these formulas accurately estimate premorbid functioning in cocaine-dependent research patients with FSIQs in the average to low average range, replicating the results in normal adults with average IQs. C1 DEPT VET AFFAIRS MED CTR,NIDA,RES UNIT,WASHINGTON,DC 20422. DEPT VET AFFAIRS MED CTR,PSYCHIAT SERV 116A,WASHINGTON,DC 20422. GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC 20007. HOWARD UNIV,MED CTR,DEPT PSYCHIAT,WASHINGTON,DC 20006. NR 15 TC 5 Z9 5 U1 1 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC PY 1995 VL 40 IS 2 BP 173 EP 175 DI 10.1016/0376-8716(95)01191-9 PG 3 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA TN450 UT WOS:A1995TN45000010 PM 8745140 ER PT J AU Fisher, MB Lawton, MP AttaAsafoAdjei, E Philpot, RM Rettie, AE AF Fisher, MB Lawton, MP AttaAsafoAdjei, E Philpot, RM Rettie, AE TI Selectivity of flavin-containing monooxygenase 5 for the (S)-sulfoxidation of short-chain aralkyl sulfides SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID STEREOSELECTIVE SULFOXIDATION C1 UNIV WASHINGTON,DEPT MED CHEM,SEATTLE,WA 98195. NIEHS,MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC. FU NIGMS NIH HHS [GM43511] NR 9 TC 11 Z9 11 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD DEC PY 1995 VL 23 IS 12 BP 1431 EP 1433 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL485 UT WOS:A1995TL48500020 PM 8689956 ER PT J AU Gosiewska, A Peterkofsky, B AF Gosiewska, A Peterkofsky, B TI Insulin-like growth factor (IGF) binding proteins and their mRNAs in connective tissues of fasted guinea-pigs SO ENDOCRINE LA English DT Article DE autocrine paracrine regulation; collagen; growth factors; bone; cartilage; skin ID HUMAN-SKIN FIBROBLASTS; FETAL-RAT CALVARIAE; FACTOR-I; COLLAGEN-SYNTHESIS; MOLECULAR-CLONING; SOMATOMEDIN-C; EXPRESSION; CULTURES; CHONDROCYTES; CELLS AB Lasting (with vitamin C-supplementation) and vitamin C-deficiency in guinea-pigs are associated with decreased collagen gene expression in connective tissues. Recently we presented evidence that circulating insulin-like growth factor binding protein (IGFBP)-1 and -2 that are induced during both nutritional deficiencies may be responsible for this inhibition by interfering with ICF-I action. The present objective was to determine whether circulating IGFBPs are accumulated in bone, skin and cartilage during fasting, which would support an endocrine role for them. IGFBP-1 mRNA was not detected in any of the connective tissues. The protein, as measured by ligand blotting was not present in tissues of normal animals but accumulated early during fasting in all of the tissues. Bone and cartilage from normal animals contained IGFBP-2 and its mRNA, but only in bone did their levels increase during fasting. IGFBP-3 mRNA was not detected in connective tissues from normal or fasted guineapigs. Little or no IGFBP-3 was detected in normal tissue extracts, but protein accumulated during fasting and presumably was derived from the circulation. IGF-I and -II mRNAs were expressed in bone and cartilage but in skin, only IGF-II mRNA was detected. Affinity cross-linking revealed that in skin, IGFBP-3 contained relatively few unoccupied IGF-I binding sites compared to IGFBP-1 while in bone and cartilage, only IGFBP-1 contained unoccupied binding sites. IGFBP-1, acting by endocrine action, is probably the major factor responsible for inhibition of IGF-I-dependent collagen gene expression during fasting. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 40 TC 4 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0969-711X J9 ENDOCRINE JI Endocrine PD DEC PY 1995 VL 3 IS 12 BP 889 EP 897 DI 10.1007/BF02738894 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TP099 UT WOS:A1995TP09900005 PM 21153217 ER PT J AU THEOHARIDES, TC SPANOS, C PANG, XZ ALFERES, L LIGRIS, K LETOURNEAU, R ROZNIECKI, JJ WEBSTER, E CHROUSOS, GP AF THEOHARIDES, TC SPANOS, C PANG, XZ ALFERES, L LIGRIS, K LETOURNEAU, R ROZNIECKI, JJ WEBSTER, E CHROUSOS, GP TI STRESS-INDUCED INTRACRANIAL MAST-CELL DEGRANULATION - A CORTICOTROPIN-RELEASING HORMONE-MEDIATED EFFECT SO ENDOCRINOLOGY LA English DT Article ID RAT DURA-MATER; SUBSTANCE-P; ULTRASTRUCTURAL CHARACTERISTICS; TRIGEMINAL STIMULATION; INFLAMMATORY DISEASE; DIFFERENTIAL RELEASE; SUGGESTIVE EVIDENCE; DIRECT INNERVATION; HISTAMINE-RELEASE; BLOOD-VESSELS AB Stress is known to precipitate or worsen a number of disorders, such as migraines, in which mast cells are suspected of being involved by releasing vasoactive, nociceptive, and proinflammatory mediators. However, no functional association has been demonstrated yet between a migraine trigger and brain mast cell activation. Nontraumatic immobilization (restrain) stress has been shown to stimulate the hypothalamic-pituitary-adrenal axis and to cause redistribution of immune cells. Here,restrain stress caused degranulation in 70% of rat dura mast cells within 30 min, as shown both by light and electron microscopy. These morphologic findings were accompanied by cerebrospinal fluid elevation of rat mast cell protease I, but not II, indicating secretion from connective tissue type mast cells. Mast cell activation due to stress was abolished in animals that had been treated neonatally with capsaicin, indicating that neuropeptides in sensory nerve endings are involved in this response. Complete inhibition was also achieved by pretreating the animals ip with polyclonal antiserum to CRH. Mast cells in the dura were localized close to nerve processes containing substance P, but no CRH-positive fibers were identified even though these were found close to mast cells in the median eminence. This is the first time that stress is shown to activate intracranial mast cells, apparently through the sequential action of CRH and sensory neuropeptides. These findings may have implications for the pathophysiology and possible therapy of neuroinflammatory disorders such as migraines, which are induced or exacerbated by stress. C1 NIH, PEDIAT ENDOCRINOL SECT, BETHESDA, MD 20892 USA. RP THEOHARIDES, TC (reprint author), TUFTS UNIV, SCH MED, DEPT PHARMACOL & EXPTL THERAPEUT, 136 HARRISON AVE, BOSTON, MA 02111 USA. RI Theoharides, Theoharis/E-5596-2010 NR 71 TC 194 Z9 198 U1 1 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 DEC PY 1995 VL 136 IS 12 BP 5745 EP 5750 DI 10.1210/en.136.12.5745 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TH008 UT WOS:A1995TH00800066 PM 7588332 ER PT J AU Olden, K AF Olden, K TI Education: A first step in solving the planet's pollution problems SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material RP Olden, K (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 3 TC 2 Z9 2 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1995 VL 103 IS 12 BP 1078 EP 1078 DI 10.2307/3432594 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TL532 UT WOS:A1995TL53200001 PM 8747003 ER PT J AU Boluyt, MO Bing, OHL Lakatta, EG AF Boluyt, MO Bing, OHL Lakatta, EG TI The ageing spontaneously hypertensive rat as a model of the transition from stable compensated hypertrophy to heart failure SO EUROPEAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Heart Failure 95 Meeting - Neurohormonal Modulation of Heart Failure: ACE Inhibition and Beyond CY APR 01-04, 1995 CL AMSTERDAM, NETHERLANDS SP European Soc Cardiol DE compensated cardiac hypertrophy; heart failure; cardiac remodelling; extracellular matrix; ventricular stiffness; spontaneously hypertensive rat ID MYOCYTE CELL LOSS; CARDIOMYOPATHY; FIBRONECTIN; ALDOSTERONE; COLLAGENASE; MYOCARDIUM; ACTIVATION; EXPRESSION; CAPTOPRIL; FIBROSIS AB Spontaneously hypertensive rats (SHR) of advanced age exhibit depressed myocardial contractile function and ventricular fibrosis, as stable compensated hypertrophy progresses to heart failure. Transition to heart failure in SHR aged 18-24 months was characterized by impaired left ventricular (LV) function, ventricular dilatation, and reduced ejection fraction without an increase in LV mass. Studies of papillary muscles from SHR with failing heal fs (SHR-F), SHR without failure (SHR-NF), and age-matched Wistar Kyoto (WKY) rats allowed examination of changes in the mechanical properties of myocardium during the transition to heart failure. Papillary muscles of SHR-F exhibited increased fibrosis, impair ed contraction, and decreased myocyte fractional area. These findings in papillary muscles were correlated with a higher concentration of hydroxyproline and increased histological evidence of fibrosis in the LV free wall. While a depression in active tension accompanied these structural alterations in papillary muscles, if was not evident when active tension was normalized to myocyte fractional area. Together, these data suggest that individual myocyte function may be preserved but that myocyte loss and replacement by extracellular matrix contribute substantially to the decrement in active tension. An absent or negative inotropic response to isoproterenol is observed in SHR-F and SHR-NF papillary muscles and may result in part fr om age-related alterations in beta-adrenergic receptor dynamics and a shift from alpha- to beta-myosin heavy chain (MHC) protein. During the transition to failure, ventricles of SHR exhibit a mm lied increase in collagen and fibronectin mRNA levels, suggesting that an increase in the expression of specific extracellular matrix genes may contribute to fibrosis, tissue stiffness, and impaired function. Transforming growth factor-beta(1), (TGF-beta(1)) mRNA levels also increase in SHR-F, consistent with the concept that TGF-beta(1) plays a key regulatory role in remodelling of the extracellular matrix gene during the transition to failure. The renin-angiotensin-aldosterone system is also implicated in the transition to failure: SHR treated with the angiotensin converting enzyme inhibitor captopril starting at IZ months of age din not develop heart failure during the 18-24 month observation period Captopril treatment that was initiated after rats were identified with evidence of failure led to a reappearance of alpha-MHC mRNA but did not improve papillary muscle function. Research opportunities include investigation of apoptosis as a mechanism of cell loss, delineation of the regulatory roles of TGF-beta(1) and the renin-angiotensin-aldosterone system in matrix accumulation, and studies of proteinase cascades that regulate matrix remodelling. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224. VET AFFAIRS MED CTR,DEPT MED,BOSTON,MA. NR 49 TC 66 Z9 71 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD DEC PY 1995 VL 16 SU N BP 19 EP 30 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TZ649 UT WOS:A1995TZ64900005 PM 8682057 ER PT J AU Cannon, RO AF Cannon, RO TI Chest pain and the sensitive heart SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE angina pectoris; syndrome X; oesophageal motility; chronic pain ID NORMAL CORONARY ANGIOGRAMS; LEFT-VENTRICULAR HYPERTROPHY; SYNDROME-X; ANGINA-PECTORIS; ENDOTHELIAL DYSFUNCTION; FLOW RESERVE; VASODILATOR RESERVE; RESISTANCE VESSELS; ARTERY DISEASE; EXERCISE AB The origin of symptoms and appropriate management of patients who have chest pain despite normal coronary angiograms remain controversial. In the past, research has focused on the possibility that abnormal coronary flow reserve caused by microvascular dysfunction may cause myocardial ischaemia during stress in a subset of patients, particularly those with abnormal exercise electrocardiograms. However, recent evidence suggests that the majority of patients with chest pain and normal coronary angiograms, including those with ischaemic-appearing exercise electrocardiograms, may have exaggerated or abnormal cardiac pain perception. A shift in therapy from anti-ischaemic medications to drugs that are useful in managing chronic pain syndromes may be more efficacious in managing chest pain symptoms. RP Cannon, RO (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7815,10 CTR DR,MSC 1650,BETHESDA,MD 20892, USA. NR 44 TC 4 Z9 4 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD DEC PY 1995 VL 7 IS 12 BP 1166 EP 1171 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TQ713 UT WOS:A1995TQ71300007 ER PT J AU HIROSE, T AUSTIN, SJ JETTEN, AM AF HIROSE, T AUSTIN, SJ JETTEN, AM TI IDENTIFICATION OF A TRANSPOSON-RELATED RNA DOWN-REGULATED BY RETINOIC ACID IN EMBRYONAL CARCINOMA AND EMBRYONIC STEM-CELLS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; DIFFERENTIAL DISPLAY; NUCLEOTIDE-SEQUENCE; MESSENGER-RNAS; MOUSE EMBRYOS; EXPRESSION; CLONING; GENE; TRANSCRIPTS; RETROVIRUS AB The differential display polymerase chain reaction was employed to identify changes in mRNA expression during retinoic acid-induced differentiation in embryonal carcinoma PCC4.aza1R cells, In this study, we report on one cDNA, EC1, that was identified by this method, EC-1 encodes a 0.6-kb mRNA that is present in PCC4.aza1R cells and down-regulated by retinoic acid, Sequence analysis revealed that EC-1 exhibits a 47% identity with the early transposon RNA ETn and does not contain a long open reading frame, EC-1 mRNA expression was reduced by 50% after 24 h of treatment with 10 nM retinoic acid and was undetectable after 48 h, Down-regulation of EC-1 mRNA was observed at retinoic acid concentrations as low as 0.1 nM. EC-1 was found to be expressed in several other embryonal carcinoma cell lines as well as in embryonic stem cells but was undetectable in differentiated cell types obtained after RA treatment, Northern blot analysis using RNA from multiple mouse tissues demonstrated that the expression of EC-1 is restricted to the testis, Treatment of PCC4.aza1R cells with an RAR-selective agonist also repressed the expression of EC-1 mRNA while treatment with an RXR-selective agonist reduced EC-1 expression slightly. The RAR alpha-specific antagonist Ro 41-5253 had little effect on the downregulation of EC-1 by retinoic acid, Our observations indicate that the repression of EC-1 is associated with the induction of differentiation in embryonal carcinoma and embryonic stem cells and involves an RAR-activated signaling pathway. (C) 1995 Academic Press, Inc. C1 NIEHS,CELL BIOL SECT,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. RI Hirose, Takahisa /E-6117-2011; OI Jetten, Anton/0000-0003-0954-4445 NR 41 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD DEC PY 1995 VL 221 IS 2 BP 294 EP 300 DI 10.1006/excr.1995.1378 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA TH623 UT WOS:A1995TH62300005 PM 7493627 ER PT J AU Vernick, KD Barreau, C Seeley, DC AF Vernick, KD Barreau, C Seeley, DC TI Plasmodium: A quantitative molecular assay for detection of sporogonic-stage malaria parasites SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Plasmodium; mosquito; vector; parasite; ribosomal RNA ID RIBOSOMAL-RNA; FALCIPARUM; SPOROZOITES; MOSQUITOS AB We present a molecular assay to detect malaria parasites during sporogonic development in the mosquito host. Specific primers for Plasmodium-specific small-subunit ribosomal RNA sequences nor present in mosquito RNA were used in a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. A synthetic RNA quantitative competitor was made which included targets for two primers and a target sequence for a hybridization probe which is also present in the natural parasite ribosome. The heterobifunctional Tth polymerase was used to carry out both reverse transcription and DNA-dependent polymerase chain reaction in a single reaction tube. Ookinetes and sporozoites, the stages from the beginning and end of sporogonic development, respectively, were both recognized in the assay. The assay was calibrated for quantitation of sporozoites by making a standard curve with counted sporozoites. The linear range of the calibrated assay allowed accurate quantitation of parasite number over at least two orders of magnitude, from 10 to 1000 sporozoites, in each RT-PCR reaction. (C) 1995 Academic Press, Inc. RP Vernick, KD (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 12 TC 10 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD DEC PY 1995 VL 81 IS 4 BP 436 EP 444 DI 10.1006/expr.1995.1136 PG 9 WC Parasitology SC Parasitology GA TN324 UT WOS:A1995TN32400003 PM 8542984 ER PT J AU Alleman, MM Mann, VH Bacchi, CJ Yarlett, N Gottlieb, M Dwyer, DM AF Alleman, MM Mann, VH Bacchi, CJ Yarlett, N Gottlieb, M Dwyer, DM TI Crithidia luciliae: Effect of purine starvation on S-adenosyl-L-methionine uptake and protein methylation SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Crithidia luciliae; purine starvation; trypanosomatid; nuclease; nucleotide monophosphoesterase; nutrient starvation; purine salvage; protein methyltransferases; Leishmania spp; Trypanosoma brucei brucei ID TRYPANOSOMA-BRUCEI-BRUCEI; 3'-NUCLEOTIDASE NUCLEASE ACTIVITY; DL-ALPHA-DIFLUOROMETHYLORNITHINE; NUTRIENT-DEPENDENT METHYLATION; MEMBRANE-ASSOCIATED PROTEIN; LEISHMANIA-DONOVANI; ESCHERICHIA-COLI; PROMASTIGOTES; SINEFUNGIN; METABOLISM AB The utilization of S-adenosyl-L-[methyl-H-3]methionine ([H-3-methyl]AdoMet) by Crithidia luciliae was assessed under nutrient-replete and purine-starvation conditions. Uptake experiments with intact cells demonstrated that the radiolabel from this molecule was accumulated by purine-starved organisms at a rate similar to 10-fold greater than that observed in those cultivated in nutrient-replete medium. Purine-starved cells also incorporated the radiolabel into trichloroacetic acid insoluble material at an similar to 10-fold faster rate than nutrient-replete cells. No differences, however, were observed in the intracellular levels of AdoMet and its metabolites between organisms cultivated under the two conditions. Results of comparative labeling studies with [H-3-methyl]AdoMet, S-adenosyl-L-[carboxyl-C-14]methionine, L-[methyl-H-3] methionine and L-[S-35]methionine in the presence and absence of cycloheximide demonstrated that the incorporation of label from [H-3-methyl]AdoMet was due to transmethylation and was independent of protein synthesis. Further, similar to 15 methylated protein bands were identified by SDS-PAGE analysis. Lysates from both purine-starved and nutrient-replete organisms demonstrated similar levels of activity of three protein methyltransferases (PMI, II, III). The differences observed in [H-3-methyl]AdoMet utilization between purine-starved and nutrient-replete C. luciliae may reflect the enhanced purine transport capacity which results from purine starvation. (C) 1995 Academic Press, Inc. C1 NIAID,PARASIT DIS LAB,CELL BIOL SECT,DIV INTRAMURAL RES,BETHESDA,MD 20892. NIAID,DIV MICROBIOL & INFECT DIS,PARASITOL & INT PROGRAMS BRANCH,BETHESDA,MD 20892. QUEENSLAND INST MED RES,BRISBANE,QLD 4029,AUSTRALIA. PACE UNIV,DEPT BIOL,NEW YORK,NY 10038. PACE UNIV,HASKINS LABS,NEW YORK,NY 10038. FU NIAID NIH HHS [AI-17340] NR 37 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD DEC PY 1995 VL 81 IS 4 BP 519 EP 528 DI 10.1006/expr.1995.1145 PG 10 WC Parasitology SC Parasitology GA TN324 UT WOS:A1995TN32400012 PM 8542993 ER PT J AU HADDAD, D LILJEQVIST, S KUMAR, S HANSSON, M STAHL, S PERLMANN, H PERLMANN, P BERZINS, K AF HADDAD, D LILJEQVIST, S KUMAR, S HANSSON, M STAHL, S PERLMANN, H PERLMANN, P BERZINS, K TI SURFACE DISPLAY COMPARED TO PERIPLASMIC EXPRESSION OF A MALARIAL ANTIGEN IN SALMONELLA-TYPHIMURIUM AND ITS IMPLICATIONS FOR IMMUNOGENICITY SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE SALMONELLA TYPHIMURIUM; STAPHYLOCOCCAL PROTEIN A; OUTER MEMBRANE PROTEIN A; PLASMODIUM FALCIPARUM; PFL 55/RESA ID PLASMODIUM-FALCIPARUM ANTIGEN; STAPHYLOCOCCAL PROTEIN-A; ESCHERICHIA-COLI; ORAL SALMONELLA; ATTENUATED SALMONELLA; RECOMBINANT BACTERIA; ANTIBODY-RESPONSE; IMMUNE-SYSTEM; T-CELL; EPITOPE AB Two different expression systems were investigated for the production of an 80 amino acid polypeptide, M3, from the C-terminus of the Plasmodium falciparum blood stage antigen Pf155/RESA in an attenuated Salmonella typhimurium vaccine strain, Upon expression, the malarial polypeptide was targeted either to the periplasm as a soluble fusion protein containing two IgG-binding domains (ZZ) from the staphylococcal protein A or, to the bacterial surface as an insert within a chimeric outer membrane protein A (OmpA) derived from Escherichia coli and Shigella dysenteriae. Both the ZZM3 and the OmpAM3 proteins were stably expressed in the periplasm or on the surface of Salmonella, respectively. The ZZ expression system yielded 10-100 times more malarial immunogen than did the OmpA system. Live recombinant Salmonella expressing ZZM3 or OmpAM3 were used to immunize mice intraperitoneally. Both the ZZM3 and OmpAM3 genes persisted for up to three weeks in bacteria isolated from different lymphoid organs. Bacteria expressing ZZM3 induced antibodies to M3, ZZ and to the Pf155/RESA antigen whereas, bacteria producing OmpAM3 induced similar levels of antibodies reactive with M3 but not with Pf155/RESA, Both recombinants induced a memory response of antibodies reactive with both M3 and Pf155/RESA, The high levels of M3 produced by the ZZ expression system make it suitable for the expression of heterologous antigens in Salmonella. Nevertheless, in spite of the quantitative difference in M3 expression, the ZZ and OmpA constructs elicited comparable immune responses to M3. C1 ROYAL INST TECHNOL,DEPT BIOCHEM,S-10044 STOCKHOLM,SWEDEN. NATL INST HLTH,MALARIA RES LAB,BETHESDA,MD. RP HADDAD, D (reprint author), UNIV STOCKHOLM,DEPT IMMUNOL,S-10691 STOCKHOLM,SWEDEN. NR 37 TC 41 Z9 41 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD DEC PY 1995 VL 12 IS 3-4 BP 175 EP 185 DI 10.1111/j.1574-695X.1995.tb00190.x PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TK182 UT WOS:A1995TK18200002 PM 8745001 ER PT J AU ELLIS, GB AF ELLIS, GB TI NO NEWS HERE SO FERTILITY AND STERILITY LA English DT Editorial Material DE HUMAN SUBJECT; INFORMED CONSENT; INSTITUTIONAL REVIEW BOARD; IN VITRO FERTILIZATION; 45 CFR PART 46 C1 NIH,OFF PROTECT RES RISKS,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD DEC PY 1995 VL 64 IS 6 BP 1062 EP 1063 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA TF354 UT WOS:A1995TF35400002 PM 7589652 ER PT J AU Siegel, KL Kepple, TM OConnell, PG Gerber, LH Stanhope, SJ AF Siegel, KL Kepple, TM OConnell, PG Gerber, LH Stanhope, SJ TI A technique to evaluate foot function during the stance phase of gait SO FOOT & ANKLE INTERNATIONAL LA English DT Article AB A technique to measure foot function during the stance phase of gait is described. Advantages of the method include its three-dimensional approach with anatomically based segment coordinate systems. This allows variables such as ground reaction forces and center of pressure location to be expressed in a local foot coordinate system, which gives more anatomical meaning to the interpretation of results. Application of the measurement technique to case examples of patients with rheumatoid arthritis demonstrated its ability to discriminate normal from various levels of pathological function. Future studies will utilize this technique to study the impact of pathology and treatment on foot function. RP Siegel, KL (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT REHABIL MED,BLDG 10,RM 6S235,BETHESDA,MD 20892, USA. RI Siegel, Karen Lohmann/B-5898-2008; OI Siegel, Karen Lohmann/0000-0002-0788-6612 NR 0 TC 40 Z9 40 U1 0 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD DEC PY 1995 VL 16 IS 12 BP 764 EP 770 PG 7 WC Orthopedics SC Orthopedics GA TK537 UT WOS:A1995TK53700005 PM 8749347 ER PT J AU Bull, RJ Birnbaum, LS Cantor, KP Rose, JB Butterworth, BE Pegram, R Tuomisto, J AF Bull, RJ Birnbaum, LS Cantor, KP Rose, JB Butterworth, BE Pegram, R Tuomisto, J TI Water chlorination: Essential process or cancer hazard? SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Editorial Material ID MALE B6C3F1 MOUSE; DRINKING-WATER; DICHLOROACETIC ACID; WASHINGTON COUNTY; RISK ASSESSMENT; BLADDER-CANCER; UNITED-STATES; BY-PRODUCTS; CARCINOGENICITY; MARYLAND AB Chlorine has been successfully used for the control of waterborne infectious disease for nearly a century. In the 1970s it was found that chlorine reacted with natural organic matter present in surface waters to produce disinfection by-products (DBP). Concern focused initially on the trihalomethanes (THM), but a wide variety of DBPs are now known to result from chlorination. Chlorination of drinking water has been one of the most effective public health measures ever undertaken. There are a number of alternatives to chlorination that are in active use in many parts of the world, but the risks associated with their by-products are even less well established than for chlorination. Moreover, the use of these alternatives vary in their effectiveness and some require greater sophistication in their application. This can mean less protection to public health as a result of inappropriate application and control. Therefore, hazards associated with the use of such a clearly beneficial process as chlorination must be carefully considered not only in an absolute sense, but also in the context of alternative approaches for producing a safe drinking water. The key question is whether the hazards associated with by-products have been sufficiently well established to warrant regulations that will undoubtedly have both positive and negative impacts on the public health. This symposium examined the toxicological and epidemiological data on chemical hazards associated with chlorination and attempted to measure this hazard against competing microbial risks, The first presentation discussed the available analytical epidemiological studies, A second presentation dealt with the importance of chlorination to the prevention of waterborne infectious disease, Pharmacokinetic, mechanistic, and modeling information on the prototypical DBP, chloroform, were discussed and contrasted with data on brominated THMs to determine if it was scientifically appropriate to regulate THMs as a single toxicological class. The fifth presentation dealt with the carcinogenic properties of a potent mutagen that is produced by chlorination. The final presentation discussed the haloacetates, carcinogenic DBPs whose concentrations approach and occasionally exceed those of the THMs. Clearly, there is a need to carefully weigh these different types and sometimes competing risks when considering the delivery of drinking water to ever-increasing populations for which there are finite sources of fresh water. (C) 1995 Society of Toxicology C1 US EPA, HLTH EFFECTS RES LAB, RES TRIANGLE PK, NC 27711 USA. NCI, BETHESDA, MD 20892 USA. UNIV S FLORIDA, DEPT MARINE SCI, ST PETERSBURG, FL 33701 USA. CHEM IND INST TOXICOL, RES TRIANGLE PK, NC 27709 USA. NATL PUBL HLTH INST, DIV ENVIRONM HLTH, KUOPIO, FINLAND. RP Bull, RJ (reprint author), PACIFIC NW LAB, DEPT HLTH RISK ASSESSMENT, RICHLAND, WA 99352 USA. NR 63 TC 133 Z9 136 U1 2 U2 42 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 DEC PY 1995 VL 28 IS 2 BP 155 EP 166 DI 10.1006/faat.1995.1156 PG 12 WC Toxicology SC Toxicology GA TL885 UT WOS:A1995TL88500001 PM 8835225 ER PT J AU Hunter, ES Kotch, LE Cefalo, RC Sadler, TW AF Hunter, ES Kotch, LE Cefalo, RC Sadler, TW TI Effects of cocaine administration during early organogenesis on prenatal development and postnatal growth in mice SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID EARLY-PREGNANCY; FETAL; ABUSE; EXPOSURE; TERATOGENICITY; RAT; MALFORMATIONS; ABNORMALITIES; INFANTS; DAMAGE AB Cocaine use has been associated with adverse developmental effects in humans. However, clinical reports both confirm and deny an association between cocaine use and malformations. Similarly, differences in species and strain, as well as route and timing of cocaine administration, have added to the difficulties in determining the teratogenicity of cocaine in animal models. This study was undertaken to compare the effects of dose, route, and timing of cocaine administration in ICR mice during early organogenesis, A single intraperitoneal (ip) administration of cocaine (greater than or equal to 60 mg/kg) on Day 9 of gestation (plug day = 1) produced maternal lethality. The predominant developmental effect of cocaine administration was an increase in the percentage of litters exhibiting an enlarged renal pelvis. Despite a high incidence of affected pups at these doses, the enlargement was not severe, These results, in agreement with previous reports, provide further evidence that the developing urogenital system is sensitive to cocaine administration, When cocaine was administered using a subcutaneous route, pup weights were greater and the incidence of enlarged renal pelvis was lower than when an ip route was used. To better mimic human binge cocaine abuse, the toxicity of a ''split dose'' was determined. A 60 mg/kg dose was administered using one administration of 60 mg/kg, two treatments of 30 mg/kg, or three administrations of 20 mg/kg with 1 hr separating the treatments. The incidence of enlarged renal pelvis was similar when cocaine was administered as one or two but was decreased when cocaine was administered as three treatments. Both the route and split-dose studies suggest that high-peak serum concentrations are required to perturb development. There were no differences in the incidence or severity of enlarged renal pelvis when cocaine was administered on Day 8, 9, or 10 or on all 3 days of gestation. This suggested that the increase in enlarged renal pelvis may not be a specific teratogenic effect of cocaine administration but may be a delay of normal development induced by cocaine exposure during this early period of organogenesis. To address this hypothesis, cocaine was administered on Day 9 using an ip route and the pups were allowed to be naturally born. In pups whose mothers received cocaine there was an increase in postnatal deaths and a trend toward a reduction in pup body weight/litter at Postnatal Day 21, However, when renal morphology was assessed on Postnatal Day 21 no abnormal kidneys were seen. This supports the hypothesis that enlarged renal pelvis produced by cocaine administration during early organogenesis represents a developmental delay and not a persistent teratogenic defect. These studies suggest that high peak cocaine concentrations are required to delay normal kidney morphogenesis in mice. (C) 1995 Society of Toxicology C1 NIEHS,SYST TOXICOL BRANCH,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,DEV BIOL & TOXICOL LABS,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CTR BIRTH DEFECTS,CHAPEL HILL,NC 27599. NR 38 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD DEC PY 1995 VL 28 IS 2 BP 177 EP 186 DI 10.1006/faat.1995.1158 PG 10 WC Toxicology SC Toxicology GA TL885 UT WOS:A1995TL88500003 PM 8835227 ER PT J AU Jakubiak, CH Callahan, JJ AF Jakubiak, CH Callahan, JJ TI Treatment of mental disorders among nursing home residents: Will the market provide? SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article C1 BRANDEIS UNIV,POLICY CTR AGING,WALTHAM,MA 02254. RP Jakubiak, CH (reprint author), BRANDEIS UNIV,NATL INST MENTAL HLTH TRAINING PROGRAM MENTAL HLT,HELLER SCH,WALTHAM,MA 02254, USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST STE 511, SAN FRANCISCO, CA 94103-1824 SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD WIN PY 1995 VL 19 IS 4 BP 39 EP 42 PG 4 WC Gerontology SC Geriatrics & Gerontology GA TW375 UT WOS:A1995TW37500009 ER PT J AU HUDSON, RR KAPLAN, NL AF HUDSON, RR KAPLAN, NL TI DELETERIOUS BACKGROUND SELECTION WITH RECOMBINATION SO GENETICS LA English DT Article ID DROSOPHILA-MELANOGASTER; DNA POLYMORPHISM; GENETIC HITCHHIKING; CENTROMERIC REGION; X-CHROMOSOME; POPULATIONS; MUTATIONS; EVOLUTION; ANANASSAE; SIMULANS AB An analytic expression for the expected nucleotide diversity is obtained for a neutral locus in a region with deleterious mutation and recombination. Our analytic results are used to predict levels of variation for the entire third chromosome of Drosophila melanogaster. The predictions are consistent with the low levels of variation that have been observed at loci near the centromeres of the third chromosome of D. melanogaster. However, the low levels of variation observed near the tips of this chromosome are not predicted using currently available estimates of the deleterious mutation rate and of selection coefficients. If considerably smaller selection coefficients are assumed, the low observed levels of variation at the tips of the third chromosome are consistent with the background selection model. C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. RP HUDSON, RR (reprint author), UNIV CALIF IRVINE,DEPT ECOL & EVOLUTIONARY BIOL,IRVINE,CA 92717, USA. FU NIGMS NIH HHS [GM-42397] NR 32 TC 227 Z9 229 U1 1 U2 15 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 1995 VL 141 IS 4 BP 1605 EP 1617 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA TH419 UT WOS:A1995TH41900031 PM 8601498 ER PT J AU ARKING, R BAKER, GT AF ARKING, R BAKER, GT TI HUMAN AGING - BIOLOGICAL PERSPECTIVES - DIGIOVANNA,AG SO GERONTOLOGIST LA English DT Book Review C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP ARKING, R (reprint author), WAYNE STATE UNIV,DEPT BIOL SCI,DETROIT,MI 48202, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD DEC PY 1995 VL 35 IS 6 BP 845 EP 845 PG 1 WC Gerontology SC Geriatrics & Gerontology GA TJ547 UT WOS:A1995TJ54700020 ER PT J AU Blithe, D AF Blithe, D TI Expertise in glycobiology - The invisible category SO GLYCOBIOLOGY LA English DT Editorial Material RP Blithe, D (reprint author), NICHHD,UNIT GLYCOBIOL,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD DEC PY 1995 VL 5 IS 8 BP 731 EP 731 DI 10.1093/glycob/5.8.731 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TQ843 UT WOS:A1995TQ84300001 ER PT J AU BOEGGEMAN, EE BALAJI, PV QASBA, PK AF BOEGGEMAN, EE BALAJI, PV QASBA, PK TI FUNCTIONAL DOMAINS OF BOVINE BETA-1,4 GALACTOSYLTRANSFERASE SO GLYCOCONJUGATE JOURNAL LA English DT Article DE BETA-1,4 GALACTOSYLTRANSFERASE; CATALYTIC DOMAINS; SITE DIRECTED MUTAGENESIS; BINDING STUDIES; DELETION MUTANS ID HUMAN BETA-1,4-GALACTOSYLTRANSFERASE; ESCHERICHIA-COLI; GOLGI RETENTION; GENOMIC STRUCTURE; DISULFIDE BOND; UDP-GALACTOSE; PROTEIN; EXPRESSION; BINDING; CLONING AB A number of N- and C-terminal deletion and point mutants of bovine beta-1,4 galactosyltransferase (beta-1,4GT) were expressed in E. coli to determine the binding regions of the enzyme that interact with N-acetylglucosamine (NAG) and UDP-galactose. The N-terminal truncated forms of the enzyme between residues 1-129, do not show any significant difference in the apparent K(m)s towards NAG or linear oligosaccharide accepters e.g. for chitobiose and chitotriose, or for the nucleotide donor UDP-galactose. Deletion or mutation of Cys 134 results in the loss of enzymatic activity, but does not affect the binding properties of the protein either to NAG- or UDP-agarose. From these columns the protein can be eluted with 15 mM NAG and 50 mM EDTA, like the enzymatically active protein, TL-GT129, that contains residues 130-402 of bovine beta-1,4GT. Also the N-terminus fragment, TL-GT129NAG, that contains residues 130-257 of the beta-1,4GT, binds to, and elutes with 15 mM NAG and 50 mM EDTA from the NAG-agarose column as efficiently as the enzymatically active TL-GT129. Unlike TL-GT129, the TL-GT129NAG binds to UDP-columns less efficiently and can be eluted from the column with only 15 mM NAG. The C-terminus fragment GT-257UDP, containing residues 258-402 of beta-1,4GT, binds tightly to both NAG- and UDP-agarose columns. A small fraction, 5-10% of the bound protein, can be eluted from the UDP-agarose column with 50 mM EDTA alone. The results show that the binding behaviour of N- and C-terminal fragments of beta-1,4GT towards the NAG- and UDP-agarose columns differ, the former binds preferentially to NAG-columns, while the latter binds to UDP-agarose columns via Mn2+. C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. NR 35 TC 20 Z9 23 U1 0 U2 2 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 DEC PY 1995 VL 12 IS 6 BP 865 EP 878 DI 10.1007/BF00731249 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ618 UT WOS:A1995TJ61800020 PM 8748165 ER PT J AU Johnson, KW Anderson, NB Bastida, E Kramer, BJ Williams, D Wong, M AF Johnson, KW Anderson, NB Bastida, E Kramer, BJ Williams, D Wong, M TI Panel II: Macrosocial and environmental influences on minority health SO HEALTH PSYCHOLOGY LA English DT Article; Proceedings Paper CT National Conference on Behavioral and Sociocultural Perspectives on Ethnicity and Health CY SEP 17-20, 1992 CL WASHINGTON, DC SP Amer Psychol Assoc, Duke Univ Med Ctr, Howard Univ Sch Med, NHLBI, NIMH, Dept Hlth & Human Serv, Off Minority Hlth, Upjohn Corp DE minority; socioeconomic; Asian; Hispanic; African American; Native American; health status environment; ethnic ID AMERICAN-INDIANS; NATIVE-AMERICANS; CARE; BLACK; SERVICES; CHINESE; CANCER; EPIDEMIOLOGY; MORTALITY; DISEASE C1 DUKE UNIV,DEPT PSYCHIAT,DURHAM,NC 27706. DUKE UNIV,DEPT PSYCHOL SOCIAL & HLTH SCI,DURHAM,NC 27706. VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,DURHAM,NC 27705. UNIV TEXAS,DEPT SOCIOL,HOUSTON,TX. VET ADM MED CTR,GERIATR EDUC CTR,SEPULVEDA,CA. UNIV MICHIGAN,SURVEY RES CTR,ANN ARBOR,MI 48109. TEXAS CHRISTIAN UNIV,DEPT SOCIOL,FT WORTH,TX. RP Johnson, KW (reprint author), NIA,BEHAV & SOCIAL RES PROGRAM,GATEWAY BLDG,SUITE 533,BETHESDA,MD 20892, USA. NR 108 TC 61 Z9 62 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD DEC PY 1995 VL 14 IS 7 BP 601 EP 612 DI 10.1037//0278-6133.14.7.601 PG 12 WC Psychology, Clinical; Psychology SC Psychology GA TT685 UT WOS:A1995TT68500003 PM 8654338 ER PT J AU Bagley, SP Angel, R DilworthAnderson, P Liu, W Schinke, S AF Bagley, SP Angel, R DilworthAnderson, P Liu, W Schinke, S TI Panel V: Adaptive health behaviors among ethnic minorities SO HEALTH PSYCHOLOGY LA English DT Article; Proceedings Paper CT National Conference on Behavioral and Sociocultural Perspectives on Ethnicity and Health CY SEP 17-20, 1992 CL WASHINGTON, DC SP Amer Psychol Assoc, Duke Univ Med Ctr, Howard Univ Sch Med, NHLBI, NIMH, Dept Hlth & Human Serv, Off Minority Hlth, Upjohn Corp DE aging; behavior; coping; ethnicity; health ID MEXICAN-AMERICAN POPULATION; HHANES 1982-84; UNITED-STATES; BICULTURAL COMPETENCE; SPANISH SURNAME; MORTALITY; DISEASE; ACCULTURATION; DIFFERENTIALS; ADOLESCENTS C1 UNIV TEXAS,DEPT SOCIOL,AUSTIN,TX 78712. UNIV N CAROLINA,DEPT HUMAN DEV & FAMILY STUDIES,GREENSBORO,NC 27412. UNIV ILLINOIS,DEPT SOCIOL,CHICAGO,IL 60680. COLUMBIA UNIV,SCH SOCIAL WORK,NEW YORK,NY 10027. RP Bagley, SP (reprint author), NIA,BLDG 31C,ROOM 5C35,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAAA NIH HHS [R01 AA011924] NR 59 TC 44 Z9 44 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD DEC PY 1995 VL 14 IS 7 BP 632 EP 640 DI 10.1037//0278-6133.14.7.632 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA TT685 UT WOS:A1995TT68500006 PM 8654341 ER PT J AU Jeong, LS Marquez, VE Yuan, CS Borchardt, RT AF Jeong, LS Marquez, VE Yuan, CS Borchardt, RT TI 4',1'a-methanocarbocyclic adenosine analogues as potential inhibitors of S-adenosylhomocysteine hydrolase SO HETEROCYCLES LA English DT Article ID L-HOMOCYSTEINE HYDROLASE; NUCLEOSIDES AB Cyclopropane-fused carbocyclic adenosine (4) and its 5'-carboxaldehyde analogue (5) were synthesized as potential inhibitors of S-adenosylhomocysteine hydrolase. The key bicyclo[3.1.0]hexane alcohol(8) was obtained from the optically pure cyclopentenone synthon (6), and attachment of the purine base was performed in a single step from the methylsulfonate ester of 8 (compound(9)). Both target compounds behaved as weak inhibitors of the hydrolase. C1 UNIV KANSAS,DEPT BIOCHEM,LAWRENCE,KS 66045. RP Jeong, LS (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892, USA. NR 13 TC 24 Z9 24 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 DEC 1 PY 1995 VL 41 IS 12 BP 2651 EP 2656 PG 6 WC Chemistry, Organic SC Chemistry GA TL640 UT WOS:A1995TL64000002 ER PT J AU Pei, XF Brossi, A AF Pei, XF Brossi, A TI Facile preparation of (3S)-1,3-dimethyl-3-cyanomethyl-5-ethoxyoxindole from Julian's nitrile enriched in the (3S)enantiomer SO HETEROCYCLES LA English DT Article ID ANALOGS; (-)-PHYSOSTIGMINE; (-)-PHYSOVENOL; PHYSOSTIGMINE; OXINDOLES AB (3S)-1,3-Dimethyl-3-cyanomethyl-5-ethoxyoxindole (4a) was prepared in high optical purity from a 4a enriched enantiomeric mixture obtained by asymmetric 3-cyanomethylation of oxindole (11) by removal of the racemate with a single recrystallization. C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT CHEM,WASHINGTON,DC 20057. NR 19 TC 8 Z9 8 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD DEC 1 PY 1995 VL 41 IS 12 BP 2823 EP 2826 PG 4 WC Chemistry, Organic SC Chemistry GA TL640 UT WOS:A1995TL64000020 ER PT J AU Jaffe, ES AF Jaffe, ES TI Nasal and nasal-type T/NK cell lymphoma: A unique form of lymphoma associated with the Epstein-Barr virus SO HISTOPATHOLOGY LA English DT Note ID LETHAL MIDLINE GRANULOMA; T-CELL; POLYMORPHIC RETICULOSIS; MOLECULAR ANALYSIS; DNA RP Jaffe, ES (reprint author), NCI,PATHOL LAB,HEMATOPATHOL SECT,BLDG 10,ROOM 2N202,10 CTR DR,MSC-1500,BETHESDA,MD 20892, USA. NR 26 TC 55 Z9 57 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD DEC PY 1995 VL 27 IS 6 BP 581 EP 583 DI 10.1111/j.1365-2559.1995.tb00333.x PG 3 WC Cell Biology; Pathology SC Cell Biology; Pathology GA TK985 UT WOS:A1995TK98500015 PM 8838342 ER PT J AU Chiorini, JA Wendtner, CM Urcelay, E Safer, B Hallek, M Kotin, RM AF Chiorini, JA Wendtner, CM Urcelay, E Safer, B Hallek, M Kotin, RM TI High-efficiency transfer of the T cell co-stimulatory molecule B7-2 to lymphoid cells using high-titer recombinant adeno-associated virus vectors SO HUMAN GENE THERAPY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; ADENOASSOCIATED VIRUS; COSTIMULATORY SIGNAL; GENE-EXPRESSION; B-CELLS; CD28; INTEGRATION; ANTIGEN; CTLA-4; DNA AB Adeno-associated virus (AAV) is a single-stranded DNA virus that can either integrate or replicate in host cells, Production of recombinant viral particles (rAAV) requires expression of the viral structural genes and the viral inverted terminal repeats in cis. By using an SV40 replicon to amplify the structural genes, the yield of recombinant viral particles was increased 60-fold over a nonreplicating helper plasmid. The rAAV particles produced by this system have similar physical properties to wild-type particles, including buoyant density, size, and morphology. This novel rAAV packaging system was used to produce rAAV particles that contain the gene for the T cell co-stimulatory protein B7-2. Transduction of the human nonadherent lymphoid cell line LP-1 with these particles significantly increased the percentage of cells expressing B7-2 from 6.8% to 78.0%. Expression of B7-2 in the human lymphoid cell line RPMI-8226 was also substantially increased. Targeting of tumor cells grown in suspension was hampered by low-efficiency transduction using other viral or nonviral vector systems, Our new packaging system for recombinant AAV should allow generation of sufficient quantities of B7-2 containing particles to develop tumor vaccines for non-Hodgkin's lymphoma. C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. UNIV MUNICH,LAB MOLEC BIOL,GENE CTR,D-81377 MUNICH,GERMANY. UNIV MUNICH,KLINIKUM INNENSTADT,MED KLIN,W-8000 MUNICH,GERMANY. RI kotin, robert/B-8954-2008 NR 47 TC 95 Z9 97 U1 0 U2 3 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 DEC PY 1995 VL 6 IS 12 BP 1531 EP 1541 DI 10.1089/hum.1995.6.12-1531 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA TN847 UT WOS:A1995TN84700005 PM 8664378 ER PT J AU SUCHY, SF OLIVOSGLANDER, IM NUSSBAUM, RL AF SUCHY, SF OLIVOSGLANDER, IM NUSSBAUM, RL TI LOWE-SYNDROME, A DEFICIENCY OF A PHOSPHATIDYL-INOSITOL 4,5-BISPHOSPHATE 5-PHOSPHATASE IN THE GOLGI-APPARATUS SO HUMAN MOLECULAR GENETICS LA English DT Article ID PHOSPHOLIPID TRANSFER PROTEIN; OCULOCEREBRORENAL SYNDROME; YEAST GOLGI; GENE; POLYPHOSPHATE-5-PHOSPHATASE; MUTATIONS; IDENTIFICATION; BINDING; KINASE; ARF AB The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by congenital cataracts, renal tubular dysfunction and neurological deficits, The gene responsible for this disorder, OCRL-1, has been cloned and mutations identified in patients. The gene product (ocrl-1) has extensive sequence homology to a 75 kDa inositol polyphosphate 5-phosphatase. We report here that OCRL patients' fibroblasts show no abnormality in inositol polyphosphate 5-phosphatase activity, but are deficient in a phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P-2] 5-phosphatase activity localized to the Golgi apparatus, Direct biochemical diagnosis of this human disease should now be possible. PtdIns(4,5)P-2 has been implicated in Golgi vesicular transport through its role in the regulation of ADP-ribosylation factor, phospholipase D and actin assembly in the cytoskeleton, The regulation of PtdIns(4,5)P-2 levels by PtdIns(4,5)P-2 5-phosphatase may, therefore, be important in the modulation of Golgi vesicular transport, Given that the primary defect in OCRL is a deficiency of a Golgi PtdIns(4,5)P-2 phosphatase, we hypothesize that the disorder results from dysregulation of Golgi function and in this way causes developmental defects in the lens and abnormal renal and neurological function. C1 NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892. NR 38 TC 105 Z9 108 U1 0 U2 3 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 DEC PY 1995 VL 4 IS 12 BP 2245 EP 2250 DI 10.1093/hmg/4.12.2245 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA TK363 UT WOS:A1995TK36300008 PM 8634694 ER PT J AU JAIN, PK FUKUSHIMA, K DESHMUKH, D RAMESH, A THOMAS, E LALWANI, AK KUMAR, S PLOPLIS, B SKARKA, H SRISAILAPATHY, CRS WAYNE, S ZBAR, RIS VERMAN, EC SMITH, RJH WILCOX, ER AF JAIN, PK FUKUSHIMA, K DESHMUKH, D RAMESH, A THOMAS, E LALWANI, AK KUMAR, S PLOPLIS, B SKARKA, H SRISAILAPATHY, CRS WAYNE, S ZBAR, RIS VERMAN, EC SMITH, RJH WILCOX, ER TI A HUMAN RECESSIVE NEUROSENSORY NONSYNDROMIC HEARING IMPAIRMENT LOCUS IS A POTENTIAL HOMOLOG OF THE MURINE DEAFNESS (DN) LOCUS SO HUMAN MOLECULAR GENETICS LA English DT Article ID AUDITORY EVOKED-POTENTIALS; FRIEDREICHS ATAXIA; ABNORMALITIES AB A locus for recessive neurosensory nonsyndromic hearing impairment maps to chromosome 9q13-q21 in two regionally separate consanguineous families from India. Each family demonstrates a LOD score greater than 4.5 to this region, D9S15, tightly linked to the Friedreich's ataxia locus, a region that has been defined with over 1 Mb of YAC contig information and several expressed sequences, is one of the flanking markers, In mice, the deafness (dn) locus maps to mouse chromosome 19 and flanking loci are syntenic to human chromosome 9q11-q21. The dn mouse is a potential model for the hearing impairment found in both these families. C1 NIDOCD,GENET MOLEC LAB,ROCKVILLE,MD 20850. UNIV IOWA,DEPT OTOLARYNGOL,MOLEC OTOLARYNGOL RES LABS,IOWA CITY,IA 52242. ROTARY DEF SCH,KOLHAPUR 416115,MAHARASHTRA,INDIA. UNIV MADRAS,DEPT GENET,MADRAS,TAMIL NADU,INDIA. ALL INDIA INST MED SCI,NEW DELHI 110029,INDIA. EPSTEIN LABS,MOLEC ONCOL LAB,SAN FRANCISCO,CA 94143. NR 32 TC 46 Z9 46 U1 0 U2 3 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 DEC PY 1995 VL 4 IS 12 BP 2391 EP 2394 DI 10.1093/hmg/4.12.2391 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA TK363 UT WOS:A1995TK36300029 PM 8634715 ER PT J AU GILCREASE, MZ SCHMIDT, L ZBAR, B TRUONG, L RUTLEDGE, M WHEELER, TM AF GILCREASE, MZ SCHMIDT, L ZBAR, B TRUONG, L RUTLEDGE, M WHEELER, TM TI SOMATIC VON HIPPEL-LINDAU MUTATION IN CLEAR-CELL PAPILLARY CYSTADENOMA OF THE EPIDIDYMIS SO HUMAN PATHOLOGY LA English DT Article DE PAPILLARY CYSTADENOMA; CLEAR CELL; EPIDIDYMIS; VON HIPPEL-LINDAU DISEASE; VON HIPPEL-LINDAU GENE ID DISEASE; CARCINOMA AB Papillary cystadenoma of the epididymis is an uncommon benign lesion that may occur sporadically or as a manifestation of von Hip pel-lindau (VHL) disease. Neither immunohistochemical studies nor molecular genetic analyses of the VHL gene have been reported previously for this lesion. The authors describe two cases of clear cell papillary cystadenoma of the epididymis, both of which were initially confused with metastatic renal cell carcinoma. Both lesions showed positive immunohistochemical staining for low and intermediate molecular weight keratins (Cam 5.2 and AE1/AE3), EMA, vimentin, alpha(1)-antitrypsin, and alpha(1)-antichymotrypsin. Each was negative for CEA. Because clear cell papillary cystadenoma is similar to renal cell carcinoma histologically, and because both occur as components of the von Hippel-Lindau disease complex, the authors analyzed both cases for the presence of mutations in the VHL gene. A somatic VHL gene mutation was detected in one of the two tumors by polymerase chain reaction followed by single-strand conformation polymorphism analysis. Direct sequencing revealed a cytosine to thymine transition at nucleotide 694, resulting in the replacement of an arginine with a stop codon after the sixth amino acid of exon 3. As the VHL gene is believed to function as a tumor suppressor gene, VHL gene mutations may play a role in the initiation of tumorigenesis in sporadic cystadenomas of the epididymis. Copyright (C) 1995 by W.B. Saunders Company C1 METHODIST HOSP,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PATHOL,HOUSTON,TX 77030. FREDERICK CANC RES & DEV CTR,NCI,INC DYNCORP,PROGRAM RESOURCES,BIOL CARCINOGENESIS & DEV PROGR,FREDERICK,MD. FREDERICK CANC RES & DEV CTR,NCI,IMMUNOBIOL LAB,FREDERICK,MD. NR 23 TC 32 Z9 38 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 1995 VL 26 IS 12 BP 1341 EP 1346 DI 10.1016/0046-8177(95)90299-6 PG 6 WC Pathology SC Pathology GA TK356 UT WOS:A1995TK35600009 PM 8522307 ER PT J AU Zhang, XK Papas, TS Bhat, NK Watson, DK AF Zhang, XK Papas, TS Bhat, NK Watson, DK TI Generation and characterization of monoclonal antibodies against the ERGB/FLI-1 transcription factor SO HYBRIDOMA LA English DT Article ID ETS GENE FAMILY; DNA-BINDING DOMAIN; ACTIVATION DOMAINS; TRANSFORMING GENE; FLI-1; PROTEIN; TRANSLOCATION; C-ETS-1; MEMBER; FUSION AB Five monoclonal antibodies were produced from mice immunized with recombinant full length human ERGB protein, Among these monoclonal antibodies, four clones did not cross react with other ets family proteins and thus are specific for the ERGB protein; however, one clone did react with the ERG protein, which has high amino acid identity with the ERGB protein, The epitope location of these antibodies was studied using bacterially expressed fragments of the human ERGB protein, These monoclonal antibodies recognized 51 kDa (p51) and 48 kDa (p48), two ERGB gene-encoded proteins, from human, mouse, and rat cell lines, These results suggest that the monoclonal antibodies can be used in human, mouse, or rat cell lines and will be useful for the biochemical and functional analysis of the ERGB protein. C1 NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702. RP Zhang, XK (reprint author), MED UNIV S CAROLINA,HOLLINGS CANC CTR,CTR MOLEC & STRUCT BIOL,ROOM 321,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 28 TC 15 Z9 15 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD DEC PY 1995 VL 14 IS 6 BP 563 EP 569 DI 10.1089/hyb.1995.14.563 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA TP893 UT WOS:A1995TP89300007 PM 8770644 ER PT J AU GARCIA, CE KILCOYNE, CM CARDILLO, C CANNON, RO QUYYUMI, AA PANZA, JA AF GARCIA, CE KILCOYNE, CM CARDILLO, C CANNON, RO QUYYUMI, AA PANZA, JA TI EFFECT OF COPPER-ZINC SUPEROXIDE-DISMUTASE ON ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH ESSENTIAL-HYPERTENSION SO HYPERTENSION LA English DT Article DE HYPERTENSION, ESSENTIAL; ENDOTHELIUM; ENDOTHELIUM-DERIVED FACTORS; ACETYLCHOLINE; BLOOD VESSELS; FREE RADICALS ID NITRIC-OXIDE SYNTHESIS; OXYGEN FREE-RADICALS; RELAXING FACTOR; VASCULAR RELAXATION; SMOOTH-MUSCLE; RESISTANCE ARTERIES; L-ARGININE; ACETYLCHOLINE; RAT; CONTRACTIONS AB Patients with essential hypertension have abnormal endothelium-dependent vasodilation related to decreased nitric oxide activity. The specific mechanism responsible for this abnormality is unknown. Recent studies in hypertensive animals have suggested an augmented destruction of nitric oxide by superoxide anions. Therefore, in the present study we aimed to investigate whether this mechanism is responsible for the abnormal vasodilator function of hypertensive patients. To this end, we studied the vascular responses to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct smooth muscle dilator) before and after combined administration of copper-zinc superoxide dismutase (a scavenger of superoxide anions with poor intracellular penetrance; 6000 U/min) in 20 healthy control subjects (11 men and 9 women; aged 50+/-6 years) and 20 hypertensive patients (13 men and 7 women; aged 51+/-9 years). Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by plethysmography. The vasodilator response to acetylcholine was significantly blunted in hypertensive patients compared with control subjects (maximal flow: 8.2+/-4 versus 12.7+/-3 mL/min per 100 mL; P<.02); however, no difference was observed in the response to sodium nitroprusside (8.1+/-4 versus 9.5+/-3 mL/min per 100 mL). In healthy control subjects superoxide dismutase infusion did not modify the vasodilator response to acetylcholine (maximal flow: 12.7+/-3 before versus 12.1+/-3 after superoxide dismutase). Similarly, in hypertensive patients superoxide dismutase infusion did not alter the response to acetylcholine (maximal flow: 8.2+/-4 versus 7.7+/-4). Prolonged (up to 60 minutes) infusion of higher doses (24 000 U/min) of copper-zinc superoxide dismustase did not modify the response to acetylcholine in either healthy control subjects or hypertensive patients. The administration of this form of superoxide dismutase did not modify the response to sodium nitroprusside in either group. These findings confirm previous observations of impaired endothelium-dependent vasodilation in patients with essential hypertension and demonstrate that copper-zinc superoxide dismutase does not alter these responses. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 53 TC 43 Z9 47 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 1995 VL 26 IS 6 BP 863 EP 868 PN 1 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TJ551 UT WOS:A1995TJ55100004 PM 7490141 ER PT J AU IBRAHIM, MM RIZK, H APPEL, LJ ELAROUSSY, W HELMY, S SHARAF, Y ASHOUR, Z KANDIL, H ROCCELLA, E WHELTON, PK AF IBRAHIM, MM RIZK, H APPEL, LJ ELAROUSSY, W HELMY, S SHARAF, Y ASHOUR, Z KANDIL, H ROCCELLA, E WHELTON, PK TI HYPERTENSION PREVALENCE, AWARENESS, TREATMENT, AND CONTROL IN EGYPT - RESULTS FROM THE EGYPTIAN NATIONAL HYPERTENSION PROJECT (NHP) SO HYPERTENSION LA English DT Article DE EGYPT; BLOOD PRESSURE; HEALTH SERVICES RESEARCH; PREVALENCE; DATA COLLECTION AB This report from the Egyptian National Hypertension Project presents national estimates of the prevalence of hypertension and the extent to which high blood pressure is being detected, treated with medications, and controlled in the Egyptian population. The results are based on findings from a national probability survey of adults greater than or equal to 25 years of age conducted in six Egyptian governorates. With the use of a stratified multistage probability design, 6733 people (85% response rate) were examined. Hypertension was defined as systolic pressure greater than or equal to 140 mm Hg, and/or diastolic pressure greater than or equal to 90 mm Hg, and/or reported treatment with one or more antihypertensive medications. Overall, the estimated prevalence of hypertension in Egypt was 26.3%. Hypertension prevalence increased progressively with age, from 7.8% in 25- to 34-year-olds to 56.6% in those 75 years or older. Hypertension was slightly more common in women than in men (26.9% versus 25.7%, respectively). Overall, 37.5% of hypertensive individuals were aware that they had high blood pressure, 23.9% were being treated with antihypertensive medications, and 8.0% were under control (systolic pressure <140 mm Hg and diastolic pressure <90 mm Hg). Hypertension prevalence as well as awareness, treatment, and control rates varied by region, with Cairo having the highest prevalence (31.0%) and the Coastal Region having the highest control rate (15.9%). Rates of awareness, treatment, and control tended to be lowest in areas of lower socioeconomic status. Our results indicate that hypertension is highly prevalent in Egypt and that the rates of hypertension awareness, treatment, and control are relatively low. These findings argue for a nationwide effort to prevent and control high blood pressure in Egypt in order to avert an epidemic of cardiovascular disease. C1 JOHNS HOPKINS UNIV,WELCH CTR PREVENT EPIDEMIOL & CLIN RES,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. NHLBI,BETHESDA,MD 20892. RP IBRAHIM, MM (reprint author), CAIRO UNIV,DEPT CARDIOL,1 EL SHERIFEIN ST,CAIRO 11111,EGYPT. NR 18 TC 114 Z9 118 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD DEC PY 1995 VL 26 IS 6 BP 886 EP 890 PN 1 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA TJ551 UT WOS:A1995TJ55100007 PM 7490144 ER PT J AU ROTH, BJ AF ROTH, BJ TI A MATHEMATICAL-MODEL OF MAKE AND BREAK ELECTRICAL-STIMULATION OF CARDIAC TISSUE BY A UNIPOLAR ANODE OR CATHODE SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article ID ACTION-POTENTIAL PROPAGATION; SODIUM CURRENT; MUSCLE; CELLS; THRESHOLDS; ELECTRODES; BIDOMAIN; FIBERS AB Numerical simulations of electrical stimulation of cardiac tissue using a unipolar extracellular electrode were performed. The bidomain model with unequal anisotropy ratios represented the tissue, and the Beeter-Reuter model represented the active membrane properties. Four types of excitation were considered: cathode make (CM), anode make (AM), cathode break (CB), and anode break (AB). The mechanisms of excitation were: for CM, tissue under the cathode was depolarized to threshold; for AM, tissue at a virtual cathode was depolarized to threshold; for CB, a long cathodal pulse produced a steady-state depolarization under the cathode and hyperpolarization at a virtual anode. At the end (break) of the pulse, the depolarization diffused into the hyperpolarized tissue, resulting in excitation. For AB, a long anodal pulse produced a steady-state hyperpolarization under the anode and depolarization at a virtual cathode. At the end (break) of the pulse, the depolarization diffused into the hyperpolarized tissue, resulting in excitation. For AB stimulation, decay of the hyperpolarization faster than that of the depolarization was necessary. The thresholds for rheobase and diastolic CM, AM, CB, and AB stimulation were 0.038, 0.41, 0.49, and 5.3 mA, respectively, for an electrode length of 1 mm and a surface area of 1.5 mm(2). Threshold increased as the size of the electrode increased. The strength-duration curves for CM and AM were similar except when the duration was shorter than 0.2 ms, in which case the AM threshold rose more quickly with decreasing duration than did the CM threshold. CM and AM resulted in similar strength-frequency curves. The model agrees qualitatively, but (in some cases) not quantitatively, with experiments. C1 NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RI Roth, Bradley/A-4920-2008 NR 43 TC 125 Z9 126 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. biomed. Eng. PD DEC PY 1995 VL 42 IS 12 BP 1174 EP 1184 DI 10.1109/10.476124 PG 11 WC Engineering, Biomedical SC Engineering GA TJ292 UT WOS:A1995TJ29200004 PM 8550059 ER PT J AU Wagtmann, N Rajagopalan, S Winter, CC Peruzzi, M Long, EO AF Wagtmann, N Rajagopalan, S Winter, CC Peruzzi, M Long, EO TI Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer SO IMMUNITY LA English DT Article ID NK CLONES; T-CELL; I ALLELES; RECOGNITION; EXPRESSION; LYSIS; MOLECULES; SUSCEPTIBILITY; PROTECTION; RESISTANCE AB An inhibitory signal is delivered to natural killer (NK) cells and a subset of cytotoxic T cells upon recognition of HLA class I molecules on target cells. We demonstrate that soluble forms of killer cell inhibitory receptors (KIR) bind directly and specifically to HLA-C alleles on transfected cells. Furthermore, transfer of individual KIR into NK clones reconstituted recognition of HLA-C on target cells, leading to inhibition of lysis. Using such functional reconstitution, a related KIR that confers specificity for some HLA-B alleles was also identified. These KIR share conserved tyrosine phosphorylation motifs in their cytoplasmic tails. Thus, a single receptor in NK cells provides both specificity for HLA class I on target cells and the inhibitory signal that prevents lysis. RP Wagtmann, N (reprint author), NIAID,IMMUNOGENET LAB,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 54 TC 263 Z9 270 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 1995 VL 3 IS 6 BP 801 EP 809 DI 10.1016/1074-7613(95)90069-1 PG 9 WC Immunology SC Immunology GA TM023 UT WOS:A1995TM02300014 PM 8777725 ER PT J AU Yao, ZB Fanslow, WC Seldin, MF Rousseau, AM Painter, SL Comeau, MR Cohen, JI Spriggs, MK AF Yao, ZB Fanslow, WC Seldin, MF Rousseau, AM Painter, SL Comeau, MR Cohen, JI Spriggs, MK TI Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor SO IMMUNITY LA English DT Article ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL; BIOLOGICAL CHARACTERIZATION; INTERSPECIFIC CROSS; CYTOPLASMIC REGION; MOLECULAR-CLONING; SIGNAL TRANSDUCER; LINKAGE MAP AB Herpesvirus Saimiri gene 13 (HVS13) exhibits 57% identity with the predicted sequence of a T cell-derived molecule termed CTLA8. Recombinant HVS13 and CTLA8 stimulate transcriptional factor NF-kappa B activity and interleukin-6 (IL-6) secretion in fibroblasts, and costimulate T cell proliferation. An HVS13.Fc fusion protein was used to isolate a cDNA encoding a novel receptor that also binds CTLA8. This receptor is unrelated to previously identified cytokine receptor families. A recombinant soluble receptor inhibited T cell proliferation and IL-2 production induced by PHA, concanavalin A (conA), and anti-TCR MAb. These results define CTLA8 and HVS13 as novel cytokines that bind to a novel cytokine receptor. We propose to call these molecules IL-17, vlL-17, and IL-17R, respectively. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MICROBIOL,DURHAM,NC 27710. NIH,CLIN INVEST LAB,BETHESDA,MD 20892. RP Yao, ZB (reprint author), IMMUNEX RES & DEV CORP,51 UNIV ST,SEATTLE,WA 98101, USA. FU NHGRI NIH HHS [HG00734]; NIAMS NIH HHS [AR41053] NR 69 TC 591 Z9 649 U1 0 U2 17 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 1995 VL 3 IS 6 BP 811 EP 821 DI 10.1016/1074-7613(95)90070-5 PG 11 WC Immunology SC Immunology GA TM023 UT WOS:A1995TM02300015 PM 8777726 ER PT J AU Leonard, WJ Shores, EW Love, PE AF Leonard, WJ Shores, EW Love, PE TI Role of the common cytokine receptor gamma chain in cytokine signaling and lymphoid development SO IMMUNOLOGICAL REVIEWS LA English DT Review ID SEVERE COMBINED IMMUNODEFICIENCY; HUMAN INTERLEUKIN-2 RECEPTOR; FUNCTIONAL COMPONENT; MOLECULAR-CLONING; IL-2 RECEPTOR; MUTANT MICE; EXPRESSION; GENE; DISEASE; CDNAS C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD. NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. RP Leonard, WJ (reprint author), NHLBI,LAB MOLEC IMMUNOL,BLDG 10,RM 7N244,BETHESDA,MD 20892, USA. NR 77 TC 112 Z9 113 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 1995 VL 148 BP 97 EP 114 DI 10.1111/j.1600-065X.1995.tb00095.x PG 18 WC Immunology SC Immunology GA TP903 UT WOS:A1995TP90300006 PM 8825284 ER PT J AU NEURATH, MF STUBER, ER STROBER, W AF NEURATH, MF STUBER, ER STROBER, W TI BSAP - A KEY REGULATOR OF B-CELL DEVELOPMENT AND DIFFERENTIATION SO IMMUNOLOGY TODAY LA English DT Editorial Material ID TRANSCRIPTION FACTOR BSAP; DNA-BINDING PROTEIN; SWITCH REGIONS; PAX GENES; PROMOTER; ENHANCER; SITES AB B-cell-specific activator protein (BSAP) is a recently identified member of the Pax-gene family of transcription factors; in the lymphoid system, BSAP is produced only in B cells. Here, Markus Neurath, Eckhard Stuber and Warren Strober describe the molecular structure of BSAP and focus on the ability of this protein to regulate the expression of B-cell-specific genes. They propose that BSAP is a key protein of B cells and that it not only influences B-cell development, but also influences the balance between B-cell proliferation and immunoglobulin secretion at later stages of B-cell differentiation. RP NEURATH, MF (reprint author), NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,10 CTR DR,BETHESDA,MD 20892, USA. NR 34 TC 54 Z9 58 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD DEC PY 1995 VL 16 IS 12 BP 564 EP 569 DI 10.1016/0167-5699(95)80078-6 PG 6 WC Immunology SC Immunology GA TJ252 UT WOS:A1995TJ25200005 PM 8579748 ER PT J AU Shu, LM Qi, CF Hand, PH Schlom, J Kashmiri, SVS AF Shu, LM Qi, CF Hand, PH Schlom, J Kashmiri, SVS TI Generation and characterization of a single-gene encoded single-chain immunoglobulin-interleukin-2 fusion protein SO IMMUNOTECHNOLOGY LA English DT Article DE single-chain immunoglobulin; single gene; fusion protein; monoclonal antibody CC49; interleukin-2; carcinoma ID MONOCLONAL-ANTIBODY; TUMOR-CELLS; DOSE INTERLEUKIN-2; GROWTH-FACTOR; CANCER; EXPRESSION; INVIVO; B72.3; CONSTRUCTION; SPECIFICITY AB Background: Interleukin-2 (IL-2), a potent inducer of cellular immune responses, has been used for biological therapy of human cancer; however, the high doses of IL-2 required to mediate patients' immune responses can cause considerable systemic toxicity. The murine monoclonal antibody (MAb) CC49, which reacts with tumor-associated glycoprotein (TAG)-72, expressed on a variety of human carcinomas, has shown excellent tumor localization in recent clinical trials. Objectives: Development and characterization of a single-chain immunoglobulin-IL-2 (SCIg-IL-2) fusion protein which, by delivering IL-2 selectively to the tumor site, can serve as an effective reagent for CC49/IL-2 combination therapy. Study design: A single-gene encoding the SCIg-IL-2 fusion protein derived from the chimeric (c) CC49 was designed, generated and inserted in an expression vector. The monomeric single-chain protein consisted of the CC49 heavy and light chain variable domains covalently joined through a (GGGGS)3 linker peptide. The carboxyl end of the variable domain of the light chain was linked to the amino terminus of the human yl Fc through the hinge region, and the carboxyl end of the CH3 domain was linked to the amino terminus of the human IL-2 through a GGGSGGG linker peptide. The SCIg-IL-2, expressed from the murine myeloma cells transfected with the expression construct, was characterized for its antigen-binding specifity, antibody effector functions and IL-2 biological activity. Results and conclusion: Transfection of murine myeloma cells with the single-gene expression construct SCIg-IL-2 expressed a single-chain protein of approximately 70 kD, which was secreted into tissue culture fluid as a homodimer of approximately 140 kD. SCIg-IL-2 competed completely with cCC49 for binding to the TAG-72 antigen, but approximately three- to four-fold more of the SCIg-IL-2 was required to achieve levels of competition similar to those observed with the murine or chimeric CC49. With human effector cells, the fusion protein mediated lysis of TAG-72-positive human carcinoma cells. Prior treatment of human effector cells with 100 U/ml of human IL-2 enhanced the fusion protein-mediated cytolysis from 32 to 65%. At doses of greater than or equal to 1 ng/ml, the stimulatory effect of SCIg-IL-2 on IL-2 dependent murine HT-2 cell proliferation was comparable to that of the recombinant human IL-2. The single-gene construct may also facilitate inoculation of the gene in animal tissue for in vivo expression of the fusion protein. C1 NCI,NIH,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 42 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1380-2933 J9 IMMUNOTECHNOLOGY JI Immunotechnology PD DEC PY 1995 VL 1 IS 3-4 BP 231 EP 241 PG 11 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA TU273 UT WOS:A1995TU27300008 PM 9373351 ER PT J AU WEST, M HOOVER, T KUNG, HF RAZIUDDIN AF WEST, M HOOVER, T KUNG, HF RAZIUDDIN TI TAT MEDIATES TRANSCRIPTIONAL ACTIVATION OF HIV-1 GENE IN-VITRO SO INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; TRANS-ACTIVATION; HTLV-III; BINDING DOMAINS; T-CELLS; EXPRESSION; PROTEIN; RNA; REGION AB Gene expression of human immunodeficiency virus (HIV-1) is greatly enhanced by a viral transactivator, the Tat protein, which interacts with R region sequences' of the HIV-1 long terminal repeat (LTR). There is no direct evidence to indicate transcriptional activation of HIV-1 by Tat. Using an in vitro transcription system, we demonstrate that an established mouse cell line, which constitutively expresses Tat protein, selectively stimulates the steady state levels of the transcripts directed from the Long terminal repeat (LTR) sequences of HIV-1. The gel binding retardation assays further demonstrate a stable activated complex, formed due to direct binding of Tat to DNA elements of the HIV-1 LTR. These data implicate transcription as the site of Tat action in trans-activation and could play an essential role in human immunodeficiency virus replication, similar to the nuclear trans-activators of other viruses. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NR 28 TC 0 Z9 0 U1 0 U2 0 PU COUNCIL SCIENTIFIC INDUSTRIAL RESEARCH PI NEW DELHI PA PUBL & INFO DIRECTORATE, NEW DELHI 110012, INDIA SN 0301-1208 J9 INDIAN J BIOCHEM BIO JI Indian J. Biochem. Biophys. PD DEC PY 1995 VL 32 IS 6 BP 351 EP 355 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TJ563 UT WOS:A1995TJ56300006 PM 8714203 ER PT J AU KOLENBRANDER, PE PARRISH, KD ANDERSEN, RN GREENBERG, EP AF KOLENBRANDER, PE PARRISH, KD ANDERSEN, RN GREENBERG, EP TI INTERGENERIC COAGGREGATION OF ORAL TREPONEMA SPP WITH FUSOBACTERIUM SPP AND INTRAGENERIC COAGGREGATION AMONG FUSOBACTERIUM SPP SO INFECTION AND IMMUNITY LA English DT Article ID ACTINOMYCES-NAESLUNDII; EPITHELIAL-CELLS; NUCLEATUM; ADHERENCE; BACTERIA; STRAINS; GINGIVALIS; DENTICOLA AB A total of 22 strains of Treponema spp, including members of all four named human oral species were tested for coaggregation with 7 strains of oral fusobacteria, 2 strains of nonoral fusobacteria, and 45 strains of other oral bacteria, which included actinobacilli, actinomyces, capnocytophagae, eubacteria, porphyromonads, prevotellae, selenomonads, streptococci, and veillonellae. None of the treponemes coaggregated with any of the latter 45 oral strains or with the two nonoral fusobacteria, All treponemes, eight Treponema denticola strains, eight T. socranskii strains, four oral pectinolytic treponemes, one T. pectinovorum strain, and one T. vincentii strain coaggregated with at least one strain of the fusobacteria tested as partners, The partners consisted of one strain of Fusobacterium periodonticum, five F. nucleatum strains including all four subspecies of F. nucleatum, and a strain of F. simiae obtained from the dental plaque of a monkey, In the more than 100 coaggregations observed, the fusobacterial partner was heat inactivated (85 degrees C for 30 min), while the treponemes were unaffected by the heat treatment, Furthermore, the fusobacteria were usually inactivated by proteinase K treatment, and the treponemes were not affected, Only the T. denticola coaggregations were inhibited by lactose and D-galactosamine, None were inhibited by any of 23 other different sugars or L-arginine. Intrageneric coaggregations were seen among the subspecies of F. nucleatum and with F. periodonticum, and none were inhibited by any of the sugars tested or by L-arginine, No intrageneric coaggregations were observed among the treponemes. These data indicate that the human oral treponemes show a specificity for oral fusobacteria as coaggregation partners, Such cell-to-cell contact may facilitate efficient metabolic communication and enhance the proliferation of each cell in the progressively more severe stages of periodontal disease, C1 NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. UNIV IOWA,DEPT MICROBIOL,IOWA CITY,IA 52242. FU NIDCR NIH HHS [DE00175, R01-DE10730] NR 34 TC 74 Z9 77 U1 0 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 DEC PY 1995 VL 63 IS 12 BP 4584 EP 4588 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TF967 UT WOS:A1995TF96700005 PM 7591109 ER PT J AU MORRISON, RP FEILZER, K TUMAS, DB AF MORRISON, RP FEILZER, K TUMAS, DB TI GENE KNOCKOUT MICE ESTABLISH A PRIMARY PROTECTIVE ROLE FOR MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-RESTRICTED RESPONSES IN CHLAMYDIA-TRACHOMATIS GENITAL-TRACT INFECTION SO INFECTION AND IMMUNITY LA English DT Article ID HUMORAL IMMUNE-RESPONSE; OUTER-MEMBRANE PROTEIN; BETA-2-MICROGLOBULIN DEFICIENT MICE; MEDIATED CYTO-TOXICITY; FEMALE GUINEA-PIGS; CYTOTOXIC T-CELLS; MOUSE PNEUMONITIS; ANTIBODY; EPITOPES; HELPER AB Mice with disrupted beta(2)-microglobulin (beta(2)m(-/-)), I-A (class II-/-), or CD4 (CD4(-/-)) genes were examined for their capacity to resolve Chlamydia trachomatis genital tract infection, C57BL/6 and beta(2)m(-/-) mice resolved infection similarly and were culture negative by 4 to 5 weeks following infection, Conversely, major histocompatibility complex (MHC) class II-/- mice failed to resolve infection, and CD4(-/-) mice showed a significant delay (2 weeks), Secondary challenge of C57BL/6, beta(2)m(-/-), and CD4(-/-) mice established that acquired protective immunity, which was characterized by an infection of shortened duration and reduced shedding of infectious organisms, developed. Serological analysis of C57BL/6 and beta(2)m(-/-) mice by enzyme-linked immunosorbent assays revealed no striking differences in the immunoglobulin subclass specificity of the anti-Chlamydia response, although some differences were observed in the magnitude of the immunoglobulin G2a (IgG2a) and IgG2b responses, Class II-/- mice produced lower-titered serum anti Chlamydia antibodies of all isotypes. The serum antibody responses of CD4(-/-) mice were similar to those of C57BL/6 mice, except that the anti-Chlamydia IgA response was delayed by approximately 3 weeks, Analysis of vaginal washes for Chlamydia-reactive antibodies revealed the presence of IgG2a, IgG2b, and IgA in C57BL/6 and beta(2)m(-/-) mice and primarily of IgA in CD4(-/-) mice, Vaginal washes from class II-/- mice were consistently antibody negative, Interestingly, the Chlamydia-specific IgA response in the vaginal washes of CD4(-/-) mice was delayed, but its appearance coincided with decreased shedding of infectious organisms and resolution of infection, Our results demonstrate that MHC class II-restricted T-cell responses are necessary for the development of protective immunity to Chlamydia genital tract infection and that local (vaginal) anti-Chlamydia IgA antibody coincides with the resolution of infection, A substantive role for MHC class I-restricted T-cell responses in protective immunity to Chlamydia genital tract infection was not confirmed. C1 UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. RP MORRISON, RP (reprint author), UNIV ALABAMA,DEPT MED,DIV INFECT DIS,TINSLEY HARRISON TOWER 229,1900 UNIV BLVD,BIRMINGHAM,AL 35294, USA. NR 48 TC 219 Z9 222 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1995 VL 63 IS 12 BP 4661 EP 4668 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TF967 UT WOS:A1995TF96700016 PM 7591120 ER PT J AU COTTER, TW MENG, Q SHEN, ZL ZHANG, YX SU, H CALDWELL, HD AF COTTER, TW MENG, Q SHEN, ZL ZHANG, YX SU, H CALDWELL, HD TI PROTECTIVE EFFICACY OF MAJOR OUTER-MEMBRANE PROTEIN-SPECIFIC IMMUNOGLOBULIN-A (IGA) AND IGG MONOCLONAL-ANTIBODIES IN A MURINE MODEL OF CHLAMYDIA-TRACHOMATIS GENITAL-TRACT INFECTION SO INFECTION AND IMMUNITY LA English DT Article ID PIG INCLUSION CONJUNCTIVITIS; CELL-DEFICIENT MICE; FEMALE GUINEA-PIGS; SECRETORY IMMUNOGLOBULIN; IMMUNE-RESPONSE; RESISTANCE; NEUTRALIZATION; REINFECTION; RESOLUTION; TRANSPORT AB The protective efficacy of immunoglobulin A (IgA) and IgG monoclonal antibodies (MAbs) specific for the major outer membrane protein of Chlamydia trachomatis MoPn was evaluated in a murine genital tract infection model, MAbs were delivered into serum and vaginal secretions of naive mice by using the backpack hybridoma tumor system, and protective efficacy was assessed over the first 8 days following challenge by quantitative determination of chlamydial recovery from cervicovaginal swabs, histopathological evaluation of genital tract tissue, and immunohistochemical detection of chlamydial inclusions, IgA and Ige significantly reduced the incidence of infection following vaginal challenge with 5 50% infectious doses, but such protection was overwhelmed by 10- and 100-fold higher challenge doses. Both MAbs also consistently reduced vaginal shedding from infected animals with all three challenge doses compared with the negative control MAb, although the magnitude of this effect was marginal, Blinded pathological evaluation of genital tract tissues at 8 days postinfection showed a significant reduction in the severity of the inflammatory infiltrate in oviduct tissue of infected IgA- and IgG-treated animals. Immunohistochemical detection of chlamydial inclusions revealed a marked reduction in the chlamydial burden of the oviduct epithelium; this finding is consistent with the reduced pathological changes observed in this tissue. These studies indicate that the presence of IgA or IgG MAbs specific to major outer membrane proteins has a marginal effect in preventing chlamydial colonization and shedding from the genital tract but has a more pronounced effect on ascending chlamydial infection and accompanying upper genital tract pathology. C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,IMMUNOL SECT,HAMILTON,MT 59840. BOSTON UNIV,BOSTON CITY HOSP,SCH MED,MAXWELL FINLAND LAB INFECT DIS,BOSTON,MA 02118. UNIV WISCONSIN,SCH MED,DEPT MED MICROBIOL & IMMUNOL,MADISON,WI 53706. NR 27 TC 131 Z9 134 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1995 VL 63 IS 12 BP 4704 EP 4714 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TF967 UT WOS:A1995TF96700022 PM 7591126 ER PT J AU CLEMANS, DL KOLENBRANDER, PE AF CLEMANS, DL KOLENBRANDER, PE TI IDENTIFICATION OF A 100-KILODALTON PUTATIVE COAGGREGATION-MEDIATING ADHESIN OF STREPTOCOCCUS-GORDONII DL1 (CHALLIS) SO INFECTION AND IMMUNITY LA English DT Article ID BACTEROIDES-LOESCHEI; EUKARYOTIC CELLS; ORAL BACTERIA; SURFACE; HYDROPHOBICITY; COLONIZATION; ACTINOMYCES AB Streptococcus gordonii DL1 (Challis) bears coaggregation-relevant surface proteins which mediate lactose-inhibitable coaggregations with other streptococci. Six spontaneously occurring coaggregation defective (Cog(-)) mutants of wild-type strain S. gordonii DL1 unable to coaggregate with wild-type streptococcal partners were characterized, Antiserum raised against wild-type cells and absorbed with Cog(-) cells specifically blocked lactose inhibitable coaggregations between S. gordonii DL1 and its streptococcal partner strains; it did not block lactose-noninhibitable coaggregations with actinomyces partners. Surface proteins were released from the cells by mild sonication treatment and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, A 100-kDa surface protein from S. gordonii DL1 was identified by immunoblot analysis with the mutant-absorbed antiserum. Each of the six Cog(-) mutants lacked the 100-kDa protein, Several other oral viridans streptococci that exhibit intrageneric lactose-inhibitable coaggregations expressed an immunoreactive protein with about the same size as the 100-kDa putative adhesin, It is proposed that the 100-kDa protein is the adhesin which mediates coaggregation between S. gordonii DL1 and its streptococcal partners, The role of this putative adhesin in accretion of streptococci in early colonization of the tooth surface is discussed. C1 NIDR, MICROBIAL ECOL LAB, BETHESDA, MD 20892 USA. NR 21 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1995 VL 63 IS 12 BP 4890 EP 4893 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TF967 UT WOS:A1995TF96700047 PM 7591151 ER PT J AU JOHNSTON, MI AF JOHNSTON, MI TI PROGRESS IN AIDS VACCINE DEVELOPMENT SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE AIDS; HUMAN IMMUNODEFICIENCY VIRUS; SIMIAN IMMUNODEFICIENCY VIRUS; VACCINE; IMMUNE RESPONSES; ANTIBODIES; CYTOTOXIC T CELLS; ENVELOPE ID HIV-1; GLYCOPROTEIN; CHIMPANZEES; PROTECTION; INFECTION; CHALLENGE AB Because of a unique combination of challenges facing human immunodeficiency virus vaccine developers, a number of traditional and novel vaccine designs are being evaluated essentially in parallel. Monomeric proteins, poxvirus vectors, peptides, and particle-based candidate vaccines have entered or will soon enter human trials. Other designs are at earlier stages of development. All candidates evaluated to date in phase I/II human trials have proven safe and immunogenic. One or more of the most promising designs will soon progress to 'test of concept' clinical trials to determine efficacy. RP JOHNSTON, MI (reprint author), NIAID,DIV AIDS,BETHESDA,MD 20892, USA. NR 29 TC 8 Z9 8 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD DEC PY 1995 VL 108 IS 4 BP 313 EP 317 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA TH744 UT WOS:A1995TH74400004 PM 7580300 ER PT J AU Trembleau, S Giacomini, P Guery, JC Setini, A Hammer, J Sette, A Appella, E Adorini, L AF Trembleau, S Giacomini, P Guery, JC Setini, A Hammer, J Sette, A Appella, E Adorini, L TI DR alpha:EP heterodimers in DRA transgenic mice hinder expression of E alpha:EP molecules and are more efficient in antigen presentation SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE antigen presentation; hemixenogenic MHC class II; HLA-DRA transgenic mice ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL RECOGNITION; CLASS-II MOLECULES; MONOCLONAL-ANTIBODIES; HLA-DR; SURFACE EXPRESSION; IA MOLECULE; AMINO-ACIDS; GENE; PEPTIDES AB HLA-DRA transgenic (tg) mice on H-2(d) background were constructed to study assembly, expression and function of DR alpha:E beta class II heterodimers when an alternate E alpha chain is available. Cytofluorimetric analysis and immunoprecipitation studies demonstrate that the majority (90%) of E beta(d) molecules on class II-positive splenocytes from DRA-tg mice are associated with DR alpha rather than E alpha chains. To characterize the functional role of the interspecies as compared with the wild-type I-E molecules, MHC restriction and T cell epitope immunodominance of synthetic peptides spanning the entire sequence of 65 kDa heat shock protein (hsp) from Mycobacterium tuberculosis were determined in hsp-primed DRA-tg and DBA/2 mice. A similar pattern of responsiveness was observed in both strains, but hsp epitopes recalled a higher response in DRA-tg as compared with DBA/2 mice. A panel of T cell hybridomas specific for two hsp peptides or a hen egg white lysozyme peptide presented by both DR alpha:E beta(d) and E alpha(d):E beta(d) was studied in detail. Surprisingly, DR alpha:E beta(d) dimers present these peptides more efficiently than E alpha:E beta(d), even when the TCR was selected in mice expressing only E alpha(d):E beta d molecules. The higher efficiency of antigen presentation by DR alpha:E beta(d) dimers does not appear to depend on increased binding affinity for peptides, as demonstrated by competition for antigen presentation, nor on increased efficiency in the interaction with CD4 molecules. Rather, the higher efficiency of antigen presentation could be explained by a more effective ligand-TCR interaction. This is consistent with molecular modeling based on the class II structure, indicating that 16 out of 17 substitutions between the first domain of E alpha(d) and DR alpha chains lie outside the peptide binding groove and are potentially available for interaction with the TCR. C1 ROCHE MILANO RIC,I-20132 MILAN,ITALY. IST REGINA ELENA,IMMUNOL LAB,I-00158 ROME,ITALY. NCI,BETHESDA,MD 20892. RI GUERY, Jean-Charles/G-1452-2013; Giacomini, Patrizio/K-5217-2016 OI GUERY, Jean-Charles/0000-0003-4499-3270; Giacomini, Patrizio/0000-0001-6109-1709 NR 38 TC 8 Z9 8 U1 0 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 DEC PY 1995 VL 7 IS 12 BP 1927 EP 1938 DI 10.1093/intimm/7.12.1927 PG 12 WC Immunology SC Immunology GA TL633 UT WOS:A1995TL63300005 PM 8746562 ER PT J AU Lash, JW Yamada, KM Bellairs, R AF Lash, JW Yamada, KM Bellairs, R TI Cell surface alterations in embryonic tissues exposed to RGD-peptides: Selective expression SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE cell surface; RGD-peptides; embryonic tissues ID ADHESION MOLECULES; CHICK-EMBRYO; FIBRONECTIN; MIGRATION; INTEGRINS; IDENTIFICATION; MEMBRANE; RECEPTOR; REGION AB Whole animal studies have implicated cell adhesion molecules in a diverse array of developmental processes. The present study reports on the morphological effects of RGD-related peptides on the cell surface of various living chick embryonic tissues. We report a novel and characteristic plasma membrane reaction that is caused by treatment with different RGD-peptides. Not only does each peptide evoke a response in certain tissues and not in others, but each brings about a specific type of plasma membrane reaction (bleb). Although the mechanisms are unknown, the specificity of this phenomenon suggests that it could provide a window into new surface interactions in morphogenetic systems. C1 UNIV PENN, SCH MED, DEPT CELL & DEV BIOL, PHILADELPHIA, PA 19104 USA. NIDR, DEV BIOL LAB, NIH, BETHESDA, MD 20892 USA. UCL, DEPT ANAT & DEV BIOL, LONDON, ENGLAND. FU NICHD NIH HHS [HD-21048]; Wellcome Trust NR 34 TC 1 Z9 1 U1 0 U2 0 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD DEC PY 1995 VL 39 IS 6 BP 933 EP 938 PG 6 WC Developmental Biology SC Developmental Biology GA TY884 UT WOS:A1995TY88400005 PM 8901195 ER PT J AU Hu, JCC Zhang, CH Slavkin, HC AF Hu, JCC Zhang, CH Slavkin, HC TI The role of platelet-derived growth factor in the development of mouse molars SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE PDGF; PDGF receptor; immunolocalization; RT-PCR; pulp cell culture; tooth development ID HUMAN-FIBROBLASTS; RECEPTOR; PDGF; GENE; EXPRESSION; MORPHOGENESIS; SEPARATE; MUTATION; INVITRO; BINDING AB Platelet-derived growth factor (PDGF) is a potent mitogen that functions in cytodifferentiation and wound healing. PDGF receptor-alpha (PDGFR-alpha) is required for the normal development of the dental ectomesenchyme (Stephenson at al., Proc. Natl. Acad. Sci. USA 88:6-10, 1991). To investigate the regulatory potential of PDGF on tooth development, the expression of PDGF-AA was determined by reverse transcription-polymerase chain reaction (RT-PCR), the PDGF ligands and receptors were localized by immunohistochemistry. The growth-promoting effects of exogenous PDGF-AA on molar explants were determined by assaying for tritiated thymidine incorporation, the presence of type I collagen and amelogenin messenger RNA transcripts, and total DNA, RNA and protein accumulation. Based upon the temporal and spatial localization, PDGFs and their receptors are present in the enamel epithelia and pulpal mesenchyme of developing mouse molars. Exogenous PDGF-AA administration increased the total protein accumulation of mouse molar explants but produces no discernible effect on amelogenin and type I collagen expression. C1 NIH,BETHESDA,MD 20892. RP Hu, JCC (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PEDIAT DENT,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDCR NIH HHS [DE-06425] NR 36 TC 11 Z9 11 U1 0 U2 0 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD DEC PY 1995 VL 39 IS 6 BP 939 EP 945 PG 7 WC Developmental Biology SC Developmental Biology GA TY884 UT WOS:A1995TY88400006 PM 8901196 ER PT J AU Goedert, JJ Pizza, G Gritti, FM Costigiola, P Boschini, A Bini, A Lazzari, C Palareti, A AF Goedert, JJ Pizza, G Gritti, FM Costigiola, P Boschini, A Bini, A Lazzari, C Palareti, A TI Mortality among drug users in the AIDS era SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE drug abuse; mortality; AIDS; human immunodeficiency virus (HIV); liver disease; Italy ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; ACQUIRED-IMMUNODEFICIENCY; HIV-INFECTION; RISK; DEATH; TUBERCULOSIS; DISEASE; HEMOPHILIA; SPECTRUM AB Background. Infection with human immunodeficiency virus type 1 (HIV-1) causes progressive immune deficiency, the acquired immunodeficiency syndrome (AIDS), and death. Mortality, however, particularly with causes other than AIDS, deserves further study. A retrospective cohort study among drug users in Italy was performed to estimated absolute and proportional mortality rates due to AIDS and other causes, with or without HIV-1 infection. Methods. All subjects who enrolled between January 1980 and July 1990 in the drug treatment programme in the Province of Bologna, Italy, were included in the cohort. Each subject was categorized for HIV-1 antibody status (positive, negative, untested), vital status (in 1990 by national surveillance), and causes of death (by death certificate). Data were analysed with actuarial and time-dependent covariate methods. Results. There were 332 deaths among 4962 drug users who were followed for 21 130 person-years. This mortality rate (1.57 per 100 person-years) was increased 18-fold compared to the general population. Actuarial 10-year mortality estimates were 28.2% for the 2040 HIV-1 positive subjects, 12.1% for the 1859 HIV-1 untested subjects, and 2.5% for the 1063 HIV-1 negative subjects. AIDS contributed to 150 deaths, followed by drug overdose (64 deaths) and trauma (39 deaths). Compared to others in the cohort, mortality with AIDS and non-AIDS causes was reduced for HIV-1 negative subjects. In contrast, mortality for HIV-1 positive subjects was increased with AIDS, trauma, overdose, various bacterial infections, hepatitis, and cirrhosis. Conclusions. Mortality with HIV-1 infection was associated not only with opportunistic infections and malignancies but also with competing causes of death, particularly hepatic disease. Further investigation is needed to clarify whether alcohol, analgesics, hepatitis viruses, or other agents have enhanced hepatotoxicity for HIV-1 infected patients. C1 MAGGIORE HOSP,DEPT INFECT DIS,BOLOGNA,ITALY. MALPIGHI BOLOGNA HOSP,EXPTL UROL SERV,BOLOGNA,ITALY. UNIV BOLOGNA,INST INFECT DIS,BOLOGNA,ITALY. SAN PATRIGNANO COMMUNITY MED CTR,SAN PATRIGNANO,ITALY. UNIV BOLOGNA,DEPT STAT,BOLOGNA,ITALY. RP Goedert, JJ (reprint author), NCI,AIDS & CANC SECT,VIRAL EPIDEMIOL BRANCH,6130 EXECUT BLVD,SUITE 434,ROCKVILLE,MD 20852, USA. NR 34 TC 27 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1995 VL 24 IS 6 BP 1204 EP 1210 DI 10.1093/ije/24.6.1204 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TR611 UT WOS:A1995TR61100019 PM 8824864 ER PT J AU RAVUSSIN, E AF RAVUSSIN, E TI LOW RESTING METABOLIC-RATE AS A RISK FACTOR FOR WEIGHT-GAIN - ROLE OF THE SYMPATHETIC NERVOUS-SYSTEM SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article; Proceedings Paper CT Satellite Symposium on Obesity and the Sympathetic Nervous System, of the 6th European Congress of Obesity CY JUN, 1995 CL COPENHAGEN, DENMARK SP Knoll Pharm DE OBESITY; SYMPATHETIC NERVOUS SYSTEM; RESTING METABOLIC RATE; PIMA INDIANS ID ENERGY-EXPENDITURE; OBESITY; MEN AB Resting metabolic rate (RMR) comprises 50-80% of daily energy expenditure. and is highly variable between subjects even after adjusting for body weight and body composition. RMR is believed to be genetically determined. Individuals with a low RMR for a given body size are at higher risk of significant weight gain, relative to those with a high RMR. Studies in Caucasians indicate that sympathetic nervous system (SNS) activity is related to the three major components of energy expenditure: RMR, the thermic effect of food and spontaneous physical activity. Pima Indians have low SNS activity and, unlike Caucasians, their RMR does not correlate with SNS activity. A variant of the beta(3)-adrenoceptor gene has been found to be weakly associated with metabolic rate. Low resting SNS activity and its apparent dissociation from metabolic rate could be a causative factor in the development of obesity. RP RAVUSSIN, E (reprint author), NATL INST HLTH,CLIN DIABET & NUTR SECT,ROOM 541-A,4212 N 16 ST,PHOENIX,AZ 85016, USA. NR 16 TC 46 Z9 46 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 1995 VL 19 SU 7 BP S8 EP S9 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA TK020 UT WOS:A1995TK02000003 PM 8963370 ER PT J AU WEINTRAUB, M KHALED, HM ZEKRI, AR BAHNASI, A EISSA, S VENZON, DJ MAGRATH, IT BHATIA, KG AF WEINTRAUB, M KHALED, HM ZEKRI, AR BAHNASI, A EISSA, S VENZON, DJ MAGRATH, IT BHATIA, KG TI P53 MUTATIONS IN EGYPTIAN BLADDER-CANCER SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE P53; BLADDER CANCER; SCHISTOSOMIASIS ID SCHISTOSOMIASIS; GENE; DNA AB Cancer of the bladder is a frequent malignancy in Egypt and other developing countries in which bladder infection with the parasite Schistosoma haematobium is common. Several epidemiological, histopathological and clinical characteristics of cancer of the Bilharzial bladder suggest that it is distinct from bladder cancer seen in industrialized countries. Little is known, however, about molecular aberrations in Egyptian bladder cancer. We studied the status of p53 in a series of 25 cases of Egyptian bladder cancer using immunohistochemistry to detect the p53 protein and SSCP/sequencing to identify mutations in the p53 gene. Ten of 25 (40%) tumor samples showed a mutation by SSCP/sequencing. Mutations were seen in both the squamous and transitional cell variants. The presence of mutations was associated with advanced stage of disease. Immunohistochemistry had a sensitivity of 70%, and a Specificity of 85% for detecting p53 mutations. Our data show that p53 mutations are a common event in Egyptian bladder cancer, and may be an indicator of advanced disease. Immunohistochemistry is both sensitive and specific for detecting p53 mutations in this tumor, and may be used to assess the prognostic value of p53 mutations in this disease. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. NATL CANC INST,DEPT MED ONCOL,CAIRO,EGYPT. NATL CANC INST,DEPT BIOL,CAIRO,EGYPT. NATL CANC INST,DEPT PATHOL,CAIRO,EGYPT. RI Venzon, David/B-3078-2008; OI Zekri, Abdel-Rahman/0000-0003-3939-0416 NR 26 TC 3 Z9 3 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 DEC PY 1995 VL 7 IS 6 BP 1269 EP 1274 PG 6 WC Oncology SC Oncology GA TG988 UT WOS:A1995TG98800004 PM 21552959 ER PT J AU Westergaard, GC Suomi, SJ AF Westergaard, GC Suomi, SJ TI The stone tools of capuchins (Cebus apella) SO INTERNATIONAL JOURNAL OF PRIMATOLOGY LA English DT Article DE tools; artifacts; capuchins; Cebus apella; Oldowan; archaeology ID MONKEYS; OLDOWAN; APES AB We examined the production of stone tools by capuchins (Cebus apella). Eleven subjects used five reduction techniques to produce 346 stone tools (48 cores and 298 flakes). They produced a sharp edge on 83% of the cores and largest flakes. Three monkeys later used a sample of these objects as cutting tools. These results demonstrate that monkeys produce lithic tools analogous to those produced by Oldowan hominids. C1 NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. RI Davidson, Iain/A-9216-2011 NR 28 TC 10 Z9 11 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0164-0291 J9 INT J PRIMATOL JI Int. J. Primatol. PD DEC PY 1995 VL 16 IS 6 BP 1017 EP 1024 DI 10.1007/BF02696114 PG 8 WC Zoology SC Zoology GA TM704 UT WOS:A1995TM70400006 ER PT J AU Merril, CR Zullo, S AF Merril, CR Zullo, S TI Mitochondrial genome deletions in the brain and their role in neurodegenerative diseases SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Article ID KEARNS-SAYRE SYNDROME; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; OBSTRUCTIVE PULMONARY-DISEASE; APOLIPOPROTEIN-E POLYMORPHISM; NUCLEOTIDE PRIMER EXTENSION; LARGE-SCALE DELETIONS; DNA DELETION; RAT-LIVER; ALZHEIMERS-DISEASE; MULTIPLE DELETIONS AB Many of the acute and chronic diseases affecting the central nervous system (CNS) are still of unknown etiology. Given that brain cells are the most aerobic and metabolically active cells in the body, deficits in aerobic energy metabolism may play an important role in many of these diseases. Over the past decade numerous diseases affecting highly active metabolic tissues including the brain and skeletal musculature have been shown to be associated with alterations in the mitochondria, the subcellular organelle responsible for aerobic energy metabolism. In addition, a number of maternally inherited diseases have been linked to mutations in the circular, 16,569 nucleotide pair mitochondrial genome. Mendelian inherited genetic variations and diseases have also been found to affect the mitochondrial function, structure, and genome in certain tissues. Specific regions of the brain appear to be more prone to the occurrence of mitochondrial DNA (mtDNA) deletion mutations. For example, mtDNA extracted from the putamen from individuals with conditions associated with chronic hypoxia often contain relatively high levels of mtDNA deletions while such mtDNA deletions are rarely found in the cerebellum. These observations raise the question as to why these mutations are region specific and whether they ave primary or secondary to pathophysiological processes. The regional specificity of the mtDNA deletions may be due in part to variations in regional blood flow, metabolic rates and the presence of known mutagens, such as nitric oxide. If mtDNA mutation events are primary they may serve as trigger mechanisms for disease processes. The loss of critical mitochondrial functions is particularly detrimental to neurons, which require considerable amounts of energy to restore the transmembrane potentials following each depolarization. In addition, mitochondrial dysfunction can lead to a metabolic catastrophe in which overproduction of free radicals results in ever increasing damage to the cell's aerobic capacities. If such processes are involved in neurodegenerative diseases, such as Alzheimer's disease, there should be evidence of a genetic association between variations in the mitochondrial genome and the occurrence of this disease. In this regard, deletion and point mutations in the mitochondrial genome have been associated with Alzheimer's disease and these mutations may in part be responsible for some of the genetic complexity displayed by this disease. C1 NIMH,LAB BIOCHEM GENET,NIH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032. NR 95 TC 2 Z9 2 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD DEC PY 1995 VL 7 IS 3-4 BP 385 EP 398 DI 10.3109/09540269509022989 PG 14 WC Psychiatry SC Psychiatry GA UF144 UT WOS:A1995UF14400006 ER PT J AU SCHOEN, TJ BONDY, CA ZHOU, J DHAWAN, R MAZURUK, K ARNOLD, DR RODRIGUEZ, IR WALDBILLIG, RJ BEEBE, DC CHADER, GJ AF SCHOEN, TJ BONDY, CA ZHOU, J DHAWAN, R MAZURUK, K ARNOLD, DR RODRIGUEZ, IR WALDBILLIG, RJ BEEBE, DC CHADER, GJ TI DIFFERENTIAL TEMPORAL AND SPATIAL EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-2 IN DEVELOPING CHICK OCULAR-TISSUES SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE DEVELOPMENT; EYE; GROWTH; INSULIN-LIKE GROWTH FACTOR; INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN ID HUMAN-EMBRYONIC CORNEA; IGF-I GENE; DEVELOPMENTAL REGULATION; PIGMENT-EPITHELIUM; CELL-PROLIFERATION; DNA-SYNTHESIS; RECEPTORS; SEQUENCE; NEURONS; RETINA AB Purpose, To determine the developmental expression and localization of mRNA for insulinlike growth factor binding protein-2 (IGFBP-2), a major binding protein of IGF-I and IGF-II, in ocular tissues of the embryonic and early posthatched chick. Methods, In situ hybridization and northern blot analysis were used to analyze the cellular origin and relative expression of IGFBP-2 mRNA in ocular tissues. Results, Wholemount in situ hybridization reveals that, as early as 3.5 days of embryonic development (E3.5), IGFBP-2 mRNA is already expressed in many areas of the embryo, including surface ectoderm, certain regions of the brain, pharyngeal clefts, somites, and limb buds. In the eye, IGFBP-2 mRNA is expressed only in the presumptive corneal epithelium at this time. By E6, IGFBP-2 mRNA expression is present in both the corneal epithelium and endothelium. By E12, IGFBP-2 mRNA is detected clearly in the corneal stroma as well as in several other ocular structures, such as the sclera, eyelid, and ciliary body. In the neural retina, a low, diffuse expression of IGFBP-2 mRNA is found at E6, which becomes more localized to the nuclear layers by E12. Northern blot analysis confirms that a high level of IGFBP-2 expression is present in the cornea and sclera by E8 to E12. A high level of IGFBP-2 mRNA expression, however, is not observed in the retina until E18. At posthatch day 2 (P2), northern blot analyses of ocular tissues reveal that the cornea contains the highest ocular level of IGFBP-2 mRNA expression, a value equal to that of brain and liver. Conclusions. The early appearance, along with differential temporal and spatial expression of IGFBP-2 mRNA in developing ocular tissues, suggests a role for IGFBP-2 in the regulation of growth and differentiation of several ocular tissues, including the cornea, sclera, and retina. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. UNIFORMED SERV UNIV HLTH SCI,DEPT ANAT & CELL BIOL,BETHESDA,MD 20814. RP SCHOEN, TJ (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BLDG 6,ROOM 304,BETHESDA,MD 20892, USA. NR 38 TC 17 Z9 18 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 1995 VL 36 IS 13 BP 2652 EP 2662 PG 11 WC Ophthalmology SC Ophthalmology GA TJ299 UT WOS:A1995TJ29900010 PM 7499087 ER PT J AU Lee, JKT Warshauer, DM Bush, WH McClennan, BL Choyke, PL AF Lee, JKT Warshauer, DM Bush, WH McClennan, BL Choyke, PL TI Determination of serum creatinine level before intravenous administration of iodinated contrast medium - A survey SO INVESTIGATIVE RADIOLOGY LA English DT Article DE iodinated contrast medium; computed tomography; excretory urography; serum creatinine ID HIGH-OSMOLALITY; RENAL-INSUFFICIENCY; NEPHROTOXICITY; DYSFUNCTION; AGENTS; TRIAL AB RATIONALE AND OBJECTIVES. To study the practice of obtaining serum creatinine before administering intravenous iodinated contrast medium and the costs associated with this practice. MATERIALS AND METHODS. In June 1993, a questionnaire was sent to 217 physicians who are members of the Society of Uroradiology or the Society of Computed Body Tomography/Magnetic Resonance. There were 149 respondents who completed a total of 70 questionnaires, providing a response rate of 69% (149/217). RESULTS. The percentage of institutions that always require a serum creatinine before administering intravenous contrast medium for excretory urography, body computed tomography, and head computed tomography was 13%, 20%, and 14%, respectively, In institutions where routine serum creatinine is not required, approximately 60% request a serum creatinine in either insulin-dependent or juvenile type 1 diabetes. The mean maximal acceptable time between the serum creatinine value and contrast administration is 29 days. It takes a mean of 69 minutes to get the results of a stat serum creatinine and costs a mean of 15 dollars for the test, In patients with no risk factors, the mean for the highest serum creatinine value at which respondents still gave contrast was 2.1 mg/dL; in patients with risk factors, the mean was 1.9 mg/dL. There was no correlation between the use of serum creatinine and the number of studies performed in the institution or the type of contrast used. CONCLUSIONS. The practice of requiring a pretest serum creatinine and its interpretation regarding the use of contrast media are quite variable. In view of this disparity in opinion, development and acceptance of a list of patients who are at increased risk for contrast-induced nephropathy may be desirable. C1 UNIV WASHINGTON,SCH MED,DEPT RADIOL,SEATTLE,WA 98195. WASHINGTON UNIV,MED CTR,MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110. NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP Lee, JKT (reprint author), UNIV N CAROLINA,SCH MED,DEPT RADIOL,CAMPUS BOX 7510,2006 OLD CLIN BLDG,CHAPEL HILL,NC 27599, USA. NR 10 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD DEC PY 1995 VL 30 IS 12 BP 700 EP 705 DI 10.1097/00004424-199512000-00002 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TK451 UT WOS:A1995TK45100002 PM 8748182 ER PT J AU JASON, J SLEEPER, LA DONFIELD, SM MURPHY, J WARRIER, I ARKIN, S EVATT, B WILLOUGHBY, A WASSERMAN, J PEQUEGNAT, W GOMPERTS, E KAUFMAN, F NELSON, M SCHULTZE, ME PEARSON, S HILGARTNER, M GERTNER, J SCIACCA, J HOOTS, WK LOVELAND, K CANTINI, M CURRY, C MCKINLAY, S DONFIELD, S MAEDER, MA CONTANT, C KISKER, CT STEHBENS, J BALE, J COOL, V ANDES, WA SIROIS, P SEXAUER, C OLSON, R BOWMAN, M HAWK, S ALEDORT, L ARROYO, M HAIRE, W ERICKSON, J PARMLEY, R MANGOS, J SCOTT, A HONECK, L LUSHER, J BAIRDCOX, K HERSHEY, MS EYSTER, E PATTISHALL, E SCHAFER, J NEAGLEY, CS SHAPIRO, A HATCHER, S DAVIGNON, G MOLLEN, P WICKLUND, B SPOOR, M AF JASON, J SLEEPER, LA DONFIELD, SM MURPHY, J WARRIER, I ARKIN, S EVATT, B WILLOUGHBY, A WASSERMAN, J PEQUEGNAT, W GOMPERTS, E KAUFMAN, F NELSON, M SCHULTZE, ME PEARSON, S HILGARTNER, M GERTNER, J SCIACCA, J HOOTS, WK LOVELAND, K CANTINI, M CURRY, C MCKINLAY, S DONFIELD, S MAEDER, MA CONTANT, C KISKER, CT STEHBENS, J BALE, J COOL, V ANDES, WA SIROIS, P SEXAUER, C OLSON, R BOWMAN, M HAWK, S ALEDORT, L ARROYO, M HAIRE, W ERICKSON, J PARMLEY, R MANGOS, J SCOTT, A HONECK, L LUSHER, J BAIRDCOX, K HERSHEY, MS EYSTER, E PATTISHALL, E SCHAFER, J NEAGLEY, CS SHAPIRO, A HATCHER, S DAVIGNON, G MOLLEN, P WICKLUND, B SPOOR, M TI EVIDENCE FOR A SHIFT FROM A TYPE-I LYMPHOCYTE PATTERN WITH HIV DISEASE PROGRESSION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV; T CELLS; LYMPHOCYTE SUBSETS ID INFECTION; ELEVATION; IGE AB Whether a shift from a type I (cell mediated) immune profile occurs with progressive HIV-related immune dysfunction is a matter of heated debate. We analyzed data for 333 HIV antibody-positive (HIV+) and -negative (HIV-) homophilic children/adolescents, to examine whether the relationships among immunologic parameters and vaccine-related serology supported a shift with advancing HIV infection. In stepwise logistic regression analysis of HIV+ children's data, anergy to a panel of delayed hypersensitivity skin test antigens was positively associated with serum immunoglobulin A (IgA) levels (p = 0.012) and CD8(+) cell counts (p = 0.021) and negatively associated with CD4(+) cell counts (p = 0.002). Modeling supported anergy as a positive correlate of log IgA level (p = 0.046) and CD4(+) lymphocyte count as a negative correlate, for HIV+ participants only (p < 0.0001). For mumps, the proportion of vaccinated HIV+ participants with protective IgG antibody titers was higher among those with CD4(+) lymphocyte counts <200 cells/mm(3) (p = 0.058). For HIV+ participants <14 years of age, this same trend was seen for measles and rubella, but was not seen in any age group for bacterial vaccine antigens. The intercorrelations among skin test anergy, CD4(+) lymphocyte counts, serum IgA levels, and viral vaccine antigen-related serologic titers for HIV+ participants are consistent with an association between progressive HIV-related immune dysfunction and a predominance of type II (humoral immunity) or Type 0 (mixed immunity), relative to type I, lymphocyte profiles. C1 EMORY UNIV, ATLANTA, GA 30322 USA. NEW ENGLAND RES INST, WATERTOWN, MA 02172 USA. CHILDRENS HOSP MICHIGAN, DETROIT, MI 48201 USA. MT SINAI MED CTR, NEW YORK, NY 10029 USA. NICHHD, BETHESDA, MD 20892 USA. NATL HEMOPHILIA FDN, NEW YORK, NY USA. NIMH, BETHESDA, MD 20892 USA. CHILDRENS HOSP LOS ANGELES, LOS ANGELES, CA USA. CORNELL UNIV, NEW YORK HOSP, MED CTR, ITHACA, NY 14853 USA. UNIV TEXAS, SCH MED, HOUSTON, TX USA. NEW ENGLAND RES INST INC, WATERTOWN, MA USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. UNIV IOWA HOSP & CLIN, IOWA CITY, IA 52242 USA. TULANE UNIV, NEW ORLEANS, LA 70118 USA. CHILDRENS HOSP OKLAHOMA, OKLAHOMA CITY, OK USA. MT SINAI MED CTR, NEW YORK, NY USA. UNIV NEBRASKA, MED CTR, LINCOLN, NE 68583 USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. MILTON S HERSHEY MED CTR, HERSHEY, PA USA. INDIANA UNIV, JAMES WHITCOMB RILEY HOSP CHILDREN, BLOOMINGTON, IN 47405 USA. UNIV CALIF SAN DIEGO, MED CTR, SAN DIEGO, CA 92103 USA. CHILDRENS MERCY HOSP, KANSAS CITY SCH MED, KANSAS CITY, MO 64108 USA. RP JASON, J (reprint author), US PHS, CTR DIS CONTROL & PREVENT, NATL CTR INFECT DIS, DIV HIV AIDS, 1600 CLIFTON RD NE, ATLANTA, GA 30333 USA. FU NCRR NIH HHS [M1-RR00071]; NICHD NIH HHS [N01-HD-8-2908]; PHS HHS [MCJ-060570] NR 22 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD DEC 1 PY 1995 VL 10 IS 4 BP 471 EP 476 DI 10.1097/00042560-199512000-00011 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TF607 UT WOS:A1995TF60700011 PM 7583444 ER PT J AU Ryschon, TW Fowler, MD Arai, AA Wysong, RE Leighton, SB Clem, TR Balaban, RS AF Ryschon, TW Fowler, MD Arai, AA Wysong, RE Leighton, SB Clem, TR Balaban, RS TI A multimode dynamometer for in vivo MRS studies of human skeletal muscle SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE exercise; magnetic resonance spectroscopy; eccentric contractions; magnetic resonance imaging; exercise testing ID NUCLEAR MAGNETIC-RESONANCE; P-31 NMR; EXERCISE; SPECTROSCOPY; FOREARM; INVIVO AB The implementation of muscle ergometry during magnetic resonance spectroscopy and imaging is complicated by the restrictive dimensions of the magnet bore and the presence of a strong static magnetic field. We have developed a dynamometer that is compatible with these constraints. This device can provide resistance to voluntary muscle contraction during isometric, isokinetic concentric, and isokinetic eccentric muscle contractions. While controlling muscle contraction speed, the dynamometer simultaneously records muscle torque production at a 10-Hz sampling frequency to allow assessment of compliance and retrospective normalization of power output for the mass of active muscle. All parameters relevant to muscle contraction are selectable, including percentage of maximal voluntary contraction, velocity of muscle contraction, duty cycle, and range of motion for the contraction. This paper provides examples of P-31-magnetic resonance spectroscopic measurements during isokinetic concentric contractions of the ankle dorsiflexors, isokinetic eccentric contractions of the soleus, and isometric contractions of the soleus. Operation of the dynamometer has no adverse effects on the integrity of the P-31-magnetic resonance spectra at 4 T, permitting temporal resolution of the phosphocreatine resynthesis rate of similar to 1 spectrum/s. The unique capabilities of this dynamometer will facilitate studies into the metabolic response of working muscle in healthy and diseased populations. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP Ryschon, TW (reprint author), NHLBI,CARDIAC ENERGET LAB,BLDG 1,RM B3-07,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 18 TC 14 Z9 14 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 DEC PY 1995 VL 79 IS 6 BP 2139 EP 2147 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA TM779 UT WOS:A1995TM77900043 PM 8847284 ER PT J AU ULLRICH, J VANPUTTEN, JPM AF ULLRICH, J VANPUTTEN, JPM TI IDENTIFICATION OF THE GONOCOCCAL GLMU GENE ENCODING THE ENZYME N-ACETYLGLUCOSAMINE 1-PHOSPHATE URIDYLTRANSFERASE INVOLVED IN THE SYNTHESIS OF UDP-GLCNAC SO JOURNAL OF BACTERIOLOGY LA English DT Article ID NEISSERIA-GONORRHOEAE; ESCHERICHIA-COLI; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; NEURAMINIC ACID; DNA-SEQUENCE; EXPRESSION; LIPOOLIGOSACCHARIDE; PROTEINS; LIPOPOLYSACCHARIDE AB In searching for the gonococcal sialyltransferase gene(s), we cloned a 3.8-kb DNA fragment from gonococcus strain MS11 that hybridized with the oligonucleotide JU07, which was derived from the conserved C terminus of the sialyl motif present in mammalian sialyltransferases. Sequencing of the fragment revealed four putative open reading frames (ORFs), one of which (ORF-1) contained a partial sialyl motif including the amino acid sequence VGSKT, which is highly conserved among sialyltransferases. The gene was flanked by two inverted repeats containing the neisserial DNA uptake sequence and was preceded by a putative sigma 54 promoter, Database searches, however, revealed a high degree of homology between ORF-1 and the N-acetylglucosamine 1-phosphate uridyltransferase (GlmU) of Escherichia coli and Bacillus subtilis and not with any known sialyltransferase. This homology was further established by the successful complementation of an orf-1 mutation by the E, coli glmU gene, Enzyme assays demonstrated that ORF-1 did not possess sialyltransferase activity but mimicked GlmU function catalyzing the conversion of N-acetylglucosamine 1-phosphate into UDP-N-acetylglucosamine, which is a key metabolite in the syntheses of lipopolysaccharide, peptidoglycan, and sialic acids. C1 NIAID, ROCKY MT LABS, LMSF, HAMILTON, MT 59840 USA. MAX PLANCK INST BIOL, INFEKT BIOL ABT, D-72076 TUBINGEN, GERMANY. OI van Putten, Jos/0000-0002-4126-8172 NR 49 TC 12 Z9 13 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1995 VL 177 IS 23 BP 6902 EP 6909 PG 8 WC Microbiology SC Microbiology GA TG224 UT WOS:A1995TG22400029 PM 7592484 ER PT J AU JAIR, KW MARTIN, RG ROSNER, JL FUJITA, N ISHIHAMA, A WOLF, RE AF JAIR, KW MARTIN, RG ROSNER, JL FUJITA, N ISHIHAMA, A WOLF, RE TI PURIFICATION AND REGULATORY PROPERTIES OF MARA PROTEIN, A TRANSCRIPTIONAL ACTIVATOR OF ESCHERICHIA-COLI MULTIPLE ANTIBIOTIC AND SUPEROXIDE RESISTANCE PROMOTERS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RESPONSE REGULON; LOCUS; SOXR; EXPRESSION; INDUCTION; GENES AB Expression of the marA or soxS genes is induced by exposure of Escherichia coli to salicylate or superoxides, respectively, This, in turn, enhances the expression of a common set of promoters (the mar/soxRS regulons), resulting in both multiple antibiotic and superoxide resistance, Since MarA protein is highly homologous to SoxS, and since a MalE-SoxS fusion protein has recently been shown to activate soxRS regulon transcription, the ability of MarA to activate transcription of these genes was tested, MarA was overexpressed as a histidine-tagged fusion protein, purified, cleaved with thrombin (leaving one N-terminal histidine residue), and renatured, Like MalE-SoxS, MarA (i) activated the transcription of zwf,fpr,fumC, micF, nfo, and sodA; (ii) required a 21-bp ''soxbox'' sequence to activate zwf transcription; and (iii) was ''ambidextrous,'' i.e., required the C-terminal domain of the alpha subunit of RNA polymerase for activation of zwf but not fumC or micF, Thus, the mar and soxRS systems use activators with very similar specificities and mechanisms of action to respond to different environmental signals. C1 UNIV MARYLAND,DEPT BIOL SCI,CATONSVILLE,MD 21228. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NATL INST GENET,DEPT MOLEC GENET,MISHIMA,SHIZUOKA 411,JAPAN. FU NIGMS NIH HHS [GM27113] NR 39 TC 105 Z9 106 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1995 VL 177 IS 24 BP 7100 EP 7104 PG 5 WC Microbiology SC Microbiology GA TJ644 UT WOS:A1995TJ64400012 PM 8522515 ER PT J AU JOHNSTON, JA WANG, LM HANSON, EP SUN, XJ WHITE, MF OAKES, SA PIERCE, JH OSHEA, JJ AF JOHNSTON, JA WANG, LM HANSON, EP SUN, XJ WHITE, MF OAKES, SA PIERCE, JH OSHEA, JJ TI INTERLEUKIN-2, INTERLEUKIN-4, INTERLEUKIN-7, AND INTERLEUKIN-15 STIMULATE TYROSINE PHOSPHORYLATION OF INSULIN-RECEPTOR SUBSTRATE-1 AND SUBSTRATE-2 IN T-CELLS - POTENTIAL ROLE OF JAK KINASES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID IL-2 RECEPTOR; GAMMA-CHAIN AB The signaling molecules insulin receptor substrate (IRS)-1 and the newly described IRS-2 (4PS) molecule are major insulin and interleukin 4 (IL-4)-dependent phosphoproteins. We report here that IL-2, IL-7, and IL-15, as well as IL-4, rapidly stimulate the tyrosine phosphorylation of IRS-1 and IRS-2 in human peripheral blood T cells, NK cells, and in lymphoid cell lines. In addition, we show that the Janus kinases, JAK1 and JAK3, associate with IRS-1 and IRS-2 in T cells. Coexpression studies demonstrate that these kinases can tyrosine-phosphorylate IRS-2, suggesting a possible mechanism by which cytokine receptors may induce the tyrosine phosphorylation of IRS-1 and IRS-2. We further demonstrate that the p85 subunit of phosphoinositol 3-kinase associates with IRS-1 in response to IL-2 and IL-4 in T cells. Therefore, these data indicate that IRS-1 and IRS-2 may have important roles in T lymphocyte activation not only in response to IL-4, but also in response to IL-2, IL-7, and IL-15. C1 NCI,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20814. RP JOHNSTON, JA (reprint author), NIAMS,ARTHRIT & RHEUMATISM BRANCH,LYMPHOCYTE CELL BIOL SECT,BLDG 10,ROOM 9N262,BETHESDA,MD 20892, USA. NR 37 TC 120 Z9 121 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 1 PY 1995 VL 270 IS 48 BP 28527 EP 28530 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TH056 UT WOS:A1995TH05600009 PM 7499365 ER PT J AU MIMNAUGH, EG WORLAND, PJ WHITESELL, L NECKERS, LM AF MIMNAUGH, EG WORLAND, PJ WHITESELL, L NECKERS, LM TI POSSIBLE ROLE FOR SERINE/THREONINE PHOSPHORYLATION IN THE REGULATION OF THE HETEROPROTEIN COMPLEX BETWEEN THE HSP90 STRESS PROTEIN AND THE PP60(V-SRC) TYROSINE KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROUS-SARCOMA VIRUS; HEAT-SHOCK PROTEIN; RSV-TRANSFORMED CELLS; 2 CELLULAR PROTEINS; OKADAIC ACID; RETINOBLASTOMA PROTEIN; STEROID-RECEPTORS; TUMOR PROMOTER; CASEIN KINASE; PP60SRC AB The abundant, cytoplasmic 90-kDa heat-shock protein associates transiently with the Rous sarcoma virus oncogenic protein tyrosine kinase, pp60(v-src), directs its cellular trafficking and negatively regulates its kinase activity, Here we report that the serine/threonine phosphatase inhibitor, okadaic acid, destabilized the heat-shock protein 90-pp60(v-src) chaperone complex in v-src-transfected cells. Concomitant with complex destabilization by okadaic acid, phosphoserine was doubled and phosphothreonine was increased 20-fold in the heat-shock protein 90. Although phosphorylation of the total pool of immunoprecipitable pp60(v-src) was unchanged, okadaic acid slightly increased phosphoserine and phosphothreonine levels specifically in pp60(v-src) bound to heat-shock protein 90. The low level of tyrosine phosphorylation in the pp60(v-src) complexed with heat-shock protein 90 was further decreased by okadaic acid. Interestingly, okadaic acid-stabilized hyperphosphorylation of the heat-shock protein 90-pp60(v-src) complex lowered the level of pp60(v-src) in cell membranes, the functional location for pp60(v-src). We suggest that serine/threonine phosphorylation of heat-shock protein 90 and/or pp60(v-src) functions as a regulatory molecular trigger to release pp60(v-src) from the chaperone complex at the inner surface of cell membranes. C1 NCI,BIOL CHEM LAB,BETHESDA,MD 20892. UNIV ARIZONA,HLTH SCI CTR,STEELE MEM CHILDRENS RES CTR,TUCSON,AZ 85724. RP MIMNAUGH, EG (reprint author), NCI,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 43 TC 72 Z9 72 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 1 PY 1995 VL 270 IS 48 BP 28654 EP 28659 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TH056 UT WOS:A1995TH05600028 PM 7499384 ER PT J AU EVANS, GA GOLDSMITH, MA JOHNSTON, JA XU, WD WEILER, SR ERWIN, R HOWARD, OMZ ABRAHAM, RT OSHEA, JJ GREENE, WC FARRAR, WL AF EVANS, GA GOLDSMITH, MA JOHNSTON, JA XU, WD WEILER, SR ERWIN, R HOWARD, OMZ ABRAHAM, RT OSHEA, JJ GREENE, WC FARRAR, WL TI ANALYSIS OF INTERLEUKIN-2 DEPENDENT SIGNAL-TRANSDUCTION THROUGH THE SHC/GRB2 ADAPTER PATHWAY - INTERLEUKIN-2-DEPENDENT MITOGENESIS DOES NOT REQUIRE SHC PHOSPHORYLATION OR RECEPTOR ASSOCIATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE PHOSPHORYLATION; KINASE-ACTIVITY; IL-2 RECEPTOR; CELL LINE; PROTEIN; ACTIVATION; GROWTH; RAF-1; GRB2; DOMAIN AB The interleukin (IL)-2 receptor system has previously been shown to signal through the association and tyrosine phosphorylation of Shc. This study demonstrates that the IL-2 receptor beta (IL-2R beta) chain is the critical receptor component required to mediate this effect. The use of IL-2R beta chain deletion mutants transfected into a Ba/F3 murine cell model describes a requirement for the IL-2R beta ''acid-rich'' domain between amino acids 315 and 384 for Shc tyrosine phosphorylation and receptor association. COS cell co-transfection studies of IL-BR beta chain constructs containing point mutations of tyrosine to phenylalanine along with the tyrosine kinase Jak-1 and a hemagglutinin-tagged Shc revealed that the motif surrounding phosphorylated tyrosine 338 within the acid-rich domain of the IL-2R beta is a binding site for Shc. Deletion of this domain has previously been shown to abrogate the ability of IL-2 to activate Ras but does not affect IL-2-dependent mitogenesis in the presence of serum. Proliferation assays of Ba/F3 cells containing IL-2R beta chain deletion mutants in serum-free medium with or without insulin shows that deletion of the acid-rich domain does not affect IL-2-driven mitogenesis regardless of the culture conditions. This study thus defines the critical domain within the IL-2R beta chain required to mediate Shc binding and Shc tyrosine phosphorylation and further shows that Shc binding and phosphorylation are not required for IL-2-dependent mitogenesis. Neither serum nor insulin is required to supplement the loss of induction of the Shc adapter or Ras pathways, which therefore suggests a novel mechanism for mitogenic signal transduction mediated by this hematopoietin receptor. C1 SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,CYTOKINE MECH SECT,FREDERICK,MD 21702. UNIV CALIF SAN FRANCISCO,SCH MED,GLADSTONE INST VIROL & IMMUNOL,SAN FRANCISCO,CA 94141. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT MED,SAN FRANCISCO,CA 94141. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT IMMUNOL & MICROBIOL,SAN FRANCISCO,CA 94141. NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,LYMPHOCYTE CELL BIOL SECT,BETHESDA,MD 20892. MAYO CLIN & MAYO FDN,DEPT IMMUNOL,ROCHESTER,MN 55905. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 50 TC 67 Z9 67 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 1 PY 1995 VL 270 IS 48 BP 28858 EP 28863 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TH056 UT WOS:A1995TH05600055 PM 7499411 ER PT J AU HE, YF CHEN, H QUON, MJ REITMAN, M AF HE, YF CHEN, H QUON, MJ REITMAN, M TI THE MOUSE OBESE GENE - GENOMIC ORGANIZATION, PROMOTER ACTIVITY, AND ACTIVATION BY CCAAT/ENHANCER-BINDING PROTEIN-ALPHA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXPRESSION; DIFFERENTIATION; TRANSCRIPTION; DNA; TRANSFECTION; INSULIN; CELLS; C/EBP; RATS; SITE AB The obese gene product, leptin, regulates adiposity. Mice homozygous for a nonfunctional obese gene become massively obese and develop diabetes mellitus due to overeating and increased metabolic efficiency. The cDNA sequence of obese was recently reported (Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., and Friedman, J. L. (1994) Nature 372, 425-432; Correction: (1995 Nature 374, 479). We have determined the genomic organization of the 5' end of the mouse obese gene. The coding sequence is in exons 2 and 3, A single TATA-containing promoter was found upstream of exon 1. A minority (probably similar to 5%) of the obese mRNA contained an extra, untranslated exon between exons 1 and 2. Transcription of the obese gene was detected only in adipose cells. A 762 base pair obese gene promoter driving a luciferase gene yielded abundant activity in transiently transfected rat adipose cells in primary culture. The obese promoter was inactive in erythroid K562 cells. Deletion of bases from -762 downstream to -161 did not affect promoter activity in transfected adipose cells. The -161 minimal promoter contained consensus Spl and CCAAT/enhancer-binding protein (C/EBP) motifs. Cotransfection with C/EBP alpha (a transcription factor important in adipose cell differentiation) caused 23-fold activation. These data suggest that the obese promoter is a natural target of C/EBP alpha. C1 NIDDK, DIABET BRANCH, BETHESDA, MD 20892 USA. RI Quon, Michael/B-1970-2008; Reitman, Marc/B-4448-2013; OI Reitman, Marc/0000-0002-0426-9475; Quon, Michael/0000-0002-9601-9915 NR 41 TC 140 Z9 149 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 1 PY 1995 VL 270 IS 48 BP 28887 EP 28891 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TH056 UT WOS:A1995TH05600060 PM 7499416 ER PT J AU MARVIN, KW FUJIMOTO, W JETTEN, AM AF MARVIN, KW FUJIMOTO, W JETTEN, AM TI IDENTIFICATION AND CHARACTERIZATION OF A NOVEL SQUAMOUS CELL-ASSOCIATED GENE-RELATED TO PMP22 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRACHEAL EPITHELIAL-CELLS; HUMAN EPIDERMAL KERATINOCYTE; RETINOIC ACID; GROWTH ARREST; L2/HNK-1 CARBOHYDRATE; MYELIN PROTEIN; DIFFERENTIATION; ADHESION; EXPRESSION; TRANSGLUTAMINASE AB In this study, we identify and characterize a novel gene, CL-20, that encodes a 17.8-kDa protein with sequence and structural similarity to the growth arrest specific gene gas3/peripheral myelin protein gene PMP22. The CL-20 protein exhibits a 43% identity with PMP22. The positions of the four lipophilic domains and the N-glycosylation site of PMP22 are conserved in CL-20, suggesting that it also is an integral membrane glycoprotein. The CL-20 gene is located on human chromosome 12 rather than 17 and encodes a 2.8-kilobase mRNA instead of 1.7-kilobase mRNA. These observations indicate that the CL-20 gene is related to but distinct from PMP22. In contrast to PMP22, CL-20 mRNA and protein are induced during squamous differentiation of rabbit tracheal epithelial cells in vitro, and Northern blot analysis and in situ hybridization demonstrated that CL-20 mRNA is most abundant in squamous epithelia. These results indicate that the high expression of CL-20 is closely correlated with squamous differentiation. The differences in tissue-specific expression and regulation between CL-20 and PMP22 suggest different roles for these two proteins. Retinoids, which inhibit squamous differentiation, repress the induction of CL-20. The retinoic acid receptor selective retinoid SRI-6751-84 is the most effective in suppressing CL-20, suggesting that the activation of the retinoic acid receptor signaling pathway is important in this suppression. RP MARVIN, KW (reprint author), NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Jetten, Anton/0000-0003-0954-4445 NR 56 TC 48 Z9 52 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 1 PY 1995 VL 270 IS 48 BP 28910 EP 28916 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TH056 UT WOS:A1995TH05600064 PM 7499420 ER PT J AU BALOW, JP WEISSMAN, JD KEARSE, KP AF BALOW, JP WEISSMAN, JD KEARSE, KP TI UNIQUE EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I PROTEINS IN THE ABSENCE OF GLUCOSE TRIMMING AND CALNEXIN ASSOCIATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL; INHIBITORS; MOLECULES; DEFICIENT; ANTIGENS; ER AB Recent evidence indicates that efficient expression of major histocompatibility complex (MHC) complexes requires their interaction with the resident endoplasmic reticulum (ER) chaperone calnexin, which for certain proteins functions as a lectin specific for monoglucosylated glycans, In the current report, we studied the expression of MHC class I proteins in BW wild type thymoma cells (BW WT) and glucosidase II-deficient BW PHAR2.7 cells, Consistent with a requirement for glucose (Glc) trimming for interaction of class I proteins with calnexin, we found that nascent H-2K(k) proteins associated with calnexin in untreated BW WT cells, but not in BW WT cells treated with the glucosidase inhibitor castanospermine (cas), or in untreated glucosidase II-deficient BW PHAR2.7 cells, Suprisingly, we found that H-2K(k) expression occurred with similar efficiency in EW PHAR2.7 cells as in BW WT cells and that formation of nascent H-2K(k) complexes was perturbed by cas treatment in BW WT cells but not in BW PHAR2.7 cells, Finally, it was noted that expression of the molecular chaperone Rip was markedly increased in BW PHAR2.7 cells relative to EW WT cells, which is suggested to play a role in regulating the expression of H-2K(k) complexes in BW PHAR2.7 cells, The current study demonstrates that Glc trimming is required for efficient interaction of nascent H-2K(k) proteins with calnexin; that expression of MHC class I proteins can, under certain conditions, proceed effectively in the absence of Glc trimming and calnexin association; and that Bip expression is markedly increased under conditions where diglucosylated glycans persist on nascent glycoproteins within the ER, These data are consistent with the hypothesis that alternative oligomerization pathways exist for class I proteins within the quality control system of the ER that have differential requirements for removal of Glc residues from nascent glycan chains. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 29 TC 51 Z9 51 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 1 PY 1995 VL 270 IS 48 BP 29025 EP 29029 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TH056 UT WOS:A1995TH05600080 PM 7499436 ER PT J AU Pritchard, WF Davies, PF Derafshi, Z Polacek, DC Tsao, RC Dull, RO Jones, SA Giddens, DP AF Pritchard, WF Davies, PF Derafshi, Z Polacek, DC Tsao, RC Dull, RO Jones, SA Giddens, DP TI Effects of wall shear stress and fluid recirculation on the localization of circulating monocytes in a three-dimensional flow model SO JOURNAL OF BIOMECHANICS LA English DT Article DE atherosclerosis; hemodynamics; monocyte adhesion; cardiovascular model; chemotactic factors ID CAROTID BIFURCATION; ATHEROSCLEROTIC LESIONS; NUMERICAL-SOLUTIONS; PULSATILE FLOW; U937 CELLS; ADHESION; VELOCITY; BLOOD; MECHANISMS; ARTERIES AB There is a correlation between the location of early atherosclerotic lesions and the hemodynamic characteristics at those sites. Circulating monocytes are key cells in the pathogenesis of atherosclerotic plaques and localize at sites of atherogenesis. The hypothesis that the distribution of monocyte adhesion to the vascular wall is determined in part by hemodynamic factors was addressed by studying monocyte adhesion in an in vitro how model in the absence of any biological activity in the model wall. Suspensions of U937 cells were perfused (Re = 200) through an axisymmetric silicone flow model with a stenosis followed by a reverse step. The model provided spatially varying wall shear stress, flow separation and reattachment, and a three-dimensional flow pattern. The cell rolling velocity and adhesion rates were determined by analysis of videomicrographs. Wall shear stress was obtained by numerical solution of the equations of fluid motion. Cell adhesion patterns were also studied in the presence of chemotactic peptide gradients. The cell rolling velocity varied linearly with wall shear stress. The adhesion rate tended to decrease with increasing local wall shear stress, but was also affected by the radial component of velocity and the dynamics of the recirculation region and flow reattachment. Adhesion was increased in the vicinity of chemotactic peptide sources downstream of the expansion site. Results with human monocytes were qualitatively similar to the U937 experiments. Differences in the adhesion rates of U937 cells occurring solely as a function of the fluid dynamic properties of the how field were clearly demonstrated in the absence of any biological activity in the model wall. C1 NIH,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892. UNIV CHICAGO,DEPT PATHOL,CHICAGO,IL 60637. GEORGIA INST TECHNOL,SCH MECH ENGN,ATLANTA,GA 30332. JOHNS HOPKINS UNIV,DEPT MECH ENGN,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT BIOMED ENGN,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH ENGN,BALTIMORE,MD 21218. FU NHLBI NIH HHS [HL 15062, HL 36049, HL 36028] NR 31 TC 61 Z9 63 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD DEC PY 1995 VL 28 IS 12 BP 1459 EP 1469 DI 10.1016/0021-9290(95)00094-1 PG 11 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA TL564 UT WOS:A1995TL56400006 PM 8666586 ER PT J AU ANDERSON, JM CIMA, LG ESKIN, SG GRAHAM, LM GREISLER, H HUBBELL, J LEVY, RJ NAUGHTON, G NORTHUP, SJ RATNER, BD SCOTTBURDEN, T TERMIN, P DIDISHEIM, P AF ANDERSON, JM CIMA, LG ESKIN, SG GRAHAM, LM GREISLER, H HUBBELL, J LEVY, RJ NAUGHTON, G NORTHUP, SJ RATNER, BD SCOTTBURDEN, T TERMIN, P DIDISHEIM, P TI TISSUE ENGINEERING IN CARDIOVASCULAR-DISEASE - A REPORT SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Editorial Material C1 MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. TEXAS BIOTECHNOL CORP,HOUSTON,TX. VET AFFAIRS MED CTR,CLEVELAND,OH. LOYOLA UNIV,STRITCH SCH MED,DEPT SURG,MAYWOOD,IL. CALTECH,DIV CHEM & CHEM ENGN,PASADENA,CA 91125. UNIV MICHIGAN,SCH MED,PEDIAT CARDIOL RES LABS,ANN ARBOR,MI. ADV TISSUE SCI INC,LA JOLLA,CA. BAXTER HLTHCARE CORP,TOXICOL & MAT TESTING,ROUND LAKE,IL. UNIV WASHINGTON,CTR BIOENGN,CTR NESAC BIO,SEATTLE,WA 98195. TEXAS HEART INST,HOUSTON,TX 77025. ORGANOGENESIS INC,CANTON,MA. NHLBI,DIV HEART & VASC DIS,BIOENGN RES GRP,BIOMAT PROGRAM,BETHESDA,MD. RP ANDERSON, JM (reprint author), CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106, USA. RI Hubbell, Jeffrey/A-9266-2008 OI Hubbell, Jeffrey/0000-0003-0276-5456 NR 0 TC 4 Z9 4 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD DEC PY 1995 VL 29 IS 12 BP 1473 EP 1475 PG 3 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA TG459 UT WOS:A1995TG45900002 ER PT J AU FOX, KM KIMURA, S POWELLTHREETS, K PLATO, CC AF FOX, KM KIMURA, S POWELLTHREETS, K PLATO, CC TI RADIAL AND ULNAR CORTICAL THICKNESS OF THE 2ND METACARPAL SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID MENOPAUSAL BONE LOSS; 2ND METACARPAL; BODY-COMPOSITION; ESTROGEN; MASS; PREVENTION; MUSCLE; AGE AB Differential bone mass at various skeletal sites, which may be due to mechanical stress exerted by the muscles attached to the bone, has been demonstrated for athletes who exert one limb more than the other, The question arises as to whether this bilateral asymmetry extends to the two sides of the same bone,vith different muscular attachments, The objectives of this study were to ascertain whether the radial and ulnar sides of the second metacarpal have similar cortical thicknesses and determine if bone mass decreases equally with age on the radial and ulnar sides. Hand-wrist radiographs were obtained from 201 male and 191 female Caucasian participants of the Baltimore Longitudinal Study of Aging, Differences between radial and ulnar cortical thickness within age groups,were tested with Student's t-test and between age groups using analysis of variance, Radial cortical thickness of the second metacarpal was found to be 11-12% greater in men and 10-12% greater in women than ulnar cortical thickness in both the left and right hands, Age-related changes in radial cortical thickness were evident in both sexes, In men, radial cortex decreased linearly from age 40 to 89, For women, there was a sharp decline in radial thickness from age 50 to age 60. Ulnar cortical thickness declined from age 50 to 60 for women only, Muscle attachment along the radial length of the second metacarpal may influence the accumulation of bone mass on the radial side at younger ages while muscle disuse may precipitate the loss of bone preferentially from the radial side. C1 UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. KYOTO UNIV,DEPT ANAT,KYOTO,JAPAN. NIA,GERONTOL RES CTR,APPL PHYSIOL SECT,BALTIMORE,MD 21224. NR 28 TC 19 Z9 20 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 1995 VL 10 IS 12 BP 1930 EP 1934 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TJ130 UT WOS:A1995TJ13000011 PM 8619373 ER PT J AU WHALLEY, T TERASAKI, M CHO, MS VOGEL, SS AF WHALLEY, T TERASAKI, M CHO, MS VOGEL, SS TI DIRECT MEMBRANE RETRIEVAL INTO LARGE VESICLES AFTER EXOCYTOSIS IN SEA-URCHIN EGGS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CORTICAL GRANULE EXOCYTOSIS; FROG NEUROMUSCULAR-JUNCTION; EXTRACELLULAR-MATRIX; FUSION PORE; MAST-CELLS; FERTILIZATION ENVELOPE; ENDOCYTOSIS; PROTEINS; CAPACITANCE; PROPAGATION AB At fertilization in sea urchin eggs, elevated cytosolic Ca2+ leads to the exocytosis of 15,000-18,000 1.3-mu m-diam cortical secretory granules to form the fertilization envelope. Cortical granule exocytosis more than doubles the surface area of the egg. It is thought that much of the added membrane is retrieved by subsequent endocytosis. We have investigated how this is achieved by activating eggs in the presence of aqueous- and lipid-phase fluorescent dyes. We find rapid endocytosis of membrane into 1.5-mu m-diam vesicles starting immediately after cortical granule exocytosis and persisting over the following 15 min. The magnitude of this membrane retrieval can compensate for the changes in the plasma membrane of the egg caused by exocytosis. This membrane retrieval is not stimulated by PMA treatment which activates the endocytosis of clathrin-coated vesicles. When eggs are treated with short wavelength ultraviolet light, cortical granule exocytosis still occurs. but granule cores fail to disperse. After egg activation, large vesicles containing semi-intact cortical granule protein cores are observed. These data together with experiments using sequential pulses of fluid-phase markers support the hypothesis that the bulk of membrane retrieval immediately after cortical granule exocytosis is achieved through direct retrieval into large endocytotic structures. C1 NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. NINCDS,NEUROBIOL LAB,BETHESDA,MD 20892. RI Vogel, Steven/A-3585-2012; OI Whalley, Tim/0000-0003-3362-0006; Vogel, Steven/0000-0002-3005-2667 NR 59 TC 77 Z9 77 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1995 VL 131 IS 5 BP 1183 EP 1192 DI 10.1083/jcb.131.5.1183 PG 10 WC Cell Biology SC Cell Biology GA TJ295 UT WOS:A1995TJ29500006 PM 8522582 ER PT J AU ROCHLIN, MW ITOH, K ADELSTEIN, RS BRIDGMAN, PC AF ROCHLIN, MW ITOH, K ADELSTEIN, RS BRIDGMAN, PC TI LOCALIZATION OF MYOSIN-II A-ISOFORMS AND B-ISOFORMS IN CULTURED NEURONS SO JOURNAL OF CELL SCIENCE LA English DT Article DE MYOSIN II; NEURON; GROWTH CONE; CYTOSKELETON ID HEAVY-CHAIN GENE; ACTIN-FILAMENTS; CELLULAR MYOSIN; GROWTH CONE; DIFFERENTIAL EXPRESSION; UNCONVENTIONAL MYOSIN; BRAIN; ORGANIZATION; ANTIBODIES; VESICLES AB Tension generated by growth cones regulates both the rate and the direction of neurite growth, The most likely effecters of tension generation are actin and myosins, We are investigating the role of conventional myosin in growth cone advance, In this paper we report the localization of the two most prominent isoforms of brain myosin II in growth cones, neurites and cell bodies of rat superior cervical ganglion neurons, Affinity purified polyclonal antibodies were prepared against unique peptide sequences from human and rat A and B isoforms of myosin heavy chain. Although each of these antibodies brightly stained nonneuronal cells, antibodies to myosin heavy chain B stained neurons with greater intensity than antibodies to myosin heavy chain A, In growth cones, myosin heavy chain B was most concentrated in the margin bordering the thickened, organelle-rich central region and the thin, actin-rich peripheral region, The staining colocalized with actin bundles proximal and distal to the marginal zone, though the staining was more prominent proximally. The trailing edge of growth cones and the distal portion of the neurite often had a rimmed appearance, but more proximal regions of neurites had cytoplasmic labelling. Localizing MHC-B in growth cones previously monitored during advance (using differential interference contrast microscopy) revealed a positive correlation with edges at which retraction had just occurred and a negative correlation with lamellipodia that had recently undergone protrusion, Cell bodies were brightly labelled for myosin heavy chain B, Myosin heavy chain A staining was dimmer and its colocalization with filamentous actin bundles in growth cones was less striking than that of myosin heavy chain B, Growth cones stained for both myosin heavy chain A and B revealed that the two antigens overlapped frequently, but not exclusively, and that myosin heavy chain A lacked the elevation in the marginal zone that was characteristic of myosin heavy chain B, The pattern of staining we observed is consistent with a prominent role for myosin heavy chain B in either generating tension between widely separated areas of the growth cone, or bundling of actin filaments, which would enable other motors to effect this tension, These data support the notion that conventional myosin is important in growth cone advance and turning. C1 WASHINGTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,ST LOUIS,MO 63110. NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. NR 37 TC 151 Z9 153 U1 0 U2 1 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 DEC PY 1995 VL 108 BP 3661 EP 3670 PN 12 PG 10 WC Cell Biology SC Cell Biology GA TJ656 UT WOS:A1995TJ65600003 PM 8719872 ER PT J AU GRANT, DS KINSELLA, JL KIBBEY, MC LAFLAMME, S BURBELO, PD GOLDSTEIN, AL KLEINMAN, HK AF GRANT, DS KINSELLA, JL KIBBEY, MC LAFLAMME, S BURBELO, PD GOLDSTEIN, AL KLEINMAN, HK TI MATRIGEL INDUCES THYMOSIN BETA-4 GENE IN DIFFERENTIATING ENDOTHELIAL-CELLS SO JOURNAL OF CELL SCIENCE LA English DT Article DE NEOVASCULARIZATION; ENDOTHELIUM; MATRIX; DIFFERENTIATION; MATRIGEL; SUBTRACTION LIBRARY; THYMOSIN BETA 4; BASEMENT MEMBRANE ID ACTIN-SEQUESTERING PEPTIDE; BASEMENT-MEMBRANE; MESSENGER-RNAS; TUMOR-GROWTH; EXPRESSION; ANGIOGENESIS; LAMININ; INVITRO; INVIVO; MODULATION AB We performed differential cDNA hybridization using RNA from endothelial cells cultured for 4 hours on either plastic or basement membrane matrix (Matrigel), and identified early genes induced during the morphological differentiation into capillary-like tubes, The mRNA for one clone, thymosin beta 4, was increased 5-fold. Immunostaining localized thymosin beta 4 in vivo in both growing and mature vessels as well as in other tissues. Endothelial cells transfected with thymosin beta 4 showed an increased rate of attachment and spreading on matrix components, and an accelerated rate of tube formation on Matrigel. An antisense oligo to thymosin beta 4 inhibited tube formation on Matrigel, The results suggest that thymosin beta 4 is induced and likely involved in differentiating endothelial cells. Thymosin beta 4 may play a role in vessel formation in vivo. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. GEORGE WASHINGTON UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20052. RP GRANT, DS (reprint author), NIDR,DEV BIOL LAB,BLDG 30,RM 430,BETHESDA,MD 20892, USA. RI Burbelo, Peter/B-1027-2009 NR 53 TC 120 Z9 126 U1 1 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD DEC PY 1995 VL 108 BP 3685 EP 3694 PN 12 PG 10 WC Cell Biology SC Cell Biology GA TJ656 UT WOS:A1995TJ65600006 PM 8719875 ER PT J AU Hennighausen, L Wall, RJ Tillmann, U Li, ML Furth, PA AF Hennighausen, L Wall, RJ Tillmann, U Li, ML Furth, PA TI Conditional gene expression in secretory tissues and skin of transgenic mice using the MMTV-LTR and the tetracycline responsive system SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE tetracycline; MMTV-LTR; tTA; MMTV-tTA; beta-galactosidase ID ONCOGENE EXPRESSION; MAMMARY-TUMORS; HA-RAS; INDUCTION; PROMOTER; PREGNANCY; LACTATION; CELLS; GLAND AB Molecular mechanisms of development and disease can be studied in transgenic animals. Controlling the spatial and temporal expression patterns of transgenes, however, is a prerequisite for the elucidation of gene function in the whole organism. Previously we reported that mice carrying a tetR/VP16 hybrid gene (tTA), under the control of the human cytomegalovirus immediate early 1 (HCMV-IE1) gene promoter, can be used to temporally activate the expression of transgenes under the control of a promoter containing tetop sequences. We now show that the MMTV-LTR can be used to target expression of tTA to the epithelial cells of secretory organs and skin in transgenic mice. Notably, nearly uniform expression of a tetop-lacZ transgene was found in seminal vesicle, salivary gland, and Leydig cells of mice carrying also the MMTV-tTA transgene. More heterogeneous patterns of gene expression were observed in mammary epithelial cells and basal cells of the epidermis. Different MMTV-tTA lines had comparable tissue expression patterns. Transcriptional activation mediated by tTA was up to several hundredfold, and it was abrogated after the administration of tetracycline. The MMTV-tTA mice established in this work will be useful for experiments examining the roles of biological factors at defined developmental stages in the epithelial cells of salivary gland, seminal vesicle, mammary gland, and skin and the Leydig cells of testes. In addition, in combination with the CRE/lox recombination system, these mice will be useful to achieve gene deletions at defined time points in these organs. (C) 1995 Wiley-Liss, Inc.* C1 USDA ARS,BELTSVILLE,MD 20725. UNIV MARYLAND,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21201. VET AFFAIRS MED CTR,BALTIMORE,MD 21201. RP Hennighausen, L (reprint author), NIDDKD,BIOCHEM & METAB LAB,BLDG 10,ROOM 9N113,BETHESDA,MD 20892, USA. NR 27 TC 87 Z9 87 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD DEC PY 1995 VL 59 IS 4 BP 463 EP 472 DI 10.1002/jcb.240590407 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TL559 UT WOS:A1995TL55900006 PM 8749716 ER PT J AU LI, XS SHAO, ZM SHEIKH, MS EISEMAN, JL SENTZ, D JETTEN, AM CHEN, JC DAWSON, MI AISNER, S RISHI, AK GUTIERREZ, P SCHNAPPER, L FONTANA, JA AF LI, XS SHAO, ZM SHEIKH, MS EISEMAN, JL SENTZ, D JETTEN, AM CHEN, JC DAWSON, MI AISNER, S RISHI, AK GUTIERREZ, P SCHNAPPER, L FONTANA, JA TI RETINOIC ACID NUCLEAR RECEPTOR-BETA INHIBITS BREAST-CARCINOMA ANCHORAGE-INDEPENDENT GROWTH SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; CANCER CELLS; LUNG-CANCER; TERATOCARCINOMA CELLS; EXPRESSION; GENE; DIFFERENTIATION; ALPHA; PROLIFERATION; GAMMA AB Retinoids modulate cellular proliferation and mediate gene function through a series of nuclear receptors. The retinoic acid nuclear receptor beta (RAR beta) plays an important role in the differentiation of a number of cell types. We now demonstrate that RAR beta expression is confined to normal mammary tissue and is not expressed in either immortalized normal or malignant cell lines. Treatment of RAR beta-transfected MDA-MB-231 cells with 1 mu M all-trans-retinoic acid (RA) significantly inhibited monolayer growth of the cells which express recombinant RAR beta. RAR beta-expressing MDA-MB-231 cells formed significantly smaller and fewer colonies in soft agar than the mock-transfected cells. Addition of 1 mu M RA stimulated colony size and number in the RAR beta-transfected MDA-MB-231 cells. In contrast to the RAR beta-expressing cells, colony formation by the RAR alpha-expressing cells was similar to the mock-transfected controls and the addition of 1 mu M RA to the RAR alpha-transfected cells inhibited colony formation. While demonstrating decreased colony formation in agar, RAR beta-expressing MDA-MB-231 cells failed to exhibit decreased growth in SCID mice. Our results show that RAR beta functions as a negative regulator of growth in breast epithelial cells. In addition, the growth of these cells is differentially regulated by RAR alpha and RAR beta which is most likely the result of the modulation of different genes. (C) 1995 Wiley-Liss, Inc. C1 UNIV MARYLAND,SCH MED,CTR CANC,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT MED,DIV ONCOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT BIOCHEM,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT SURG,BALTIMORE,MD 21201. VET ADM MED CTR,BALTIMORE,MD 21201. NATL INST ENVIRONM HLTH SCI,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. SRI INT,DIV LIFE SCI,MENLO PK,CA 94025. OI Jetten, Anton/0000-0003-0954-4445; Fontana, Joseph/0000-0003-3829-3358 FU NCI NIH HHS [CA51993, CA63335] NR 57 TC 55 Z9 56 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1995 VL 165 IS 3 BP 449 EP 458 DI 10.1002/jcp.1041650302 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TG931 UT WOS:A1995TG93100001 PM 7593223 ER PT J AU SELLERI, C SATO, T ANDERSON, S YOUNG, NS MACIEJEWSKI, JP AF SELLERI, C SATO, T ANDERSON, S YOUNG, NS MACIEJEWSKI, JP TI INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA SUPPRESS BOTH EARLY AND LATE STAGES OF HEMATOPOIESIS AND INDUCE PROGRAMMED CELL-DEATH SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; SEVERE APLASTIC-ANEMIA; PROGENITOR CELLS; MYELODYSPLASTIC SYNDROMES; INTERLEUKIN-3; INVITRO; PROLIFERATION; EXPRESSION; GROWTH; LINES AB Increased expression of interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in bone marrow failure disorders suggests a possible pathophysiologic role of these cytokines in disease. In this study, we tested the action of TNF-alpha and IFN-gamma on phenotypically and functionally defined stages of hematopoietic development using highly purified progenitor cell populations assayed in standardized culture systems. We hypothesized that the inhibitory effects of IFN-gamma and TNF-alpha might be related to the induction of programmed cell death. In methylcellulose colony assays, IFN-gamma and TNF-alpha inhibited the growth of early hematopoietic cells, including committed CD34(+)CD38(+) progenitor cells and phenotypically less mature CD34(+)CD38(-) cells, with 50% decreased colony formation occurring in the range of 750-1,000 U/ml of lFN-gamma and 10-15 ng/ml of TNF-alpha. More potent suppressive effects were observed in cultures supplemented with the combination of both cytokines than in cultures treated with IFN-gamma or TNF-alpha alone. When used at these concentrations, IFN-gamma and TNF-alpha inhibited growth of CD34(+) -enriched long-term culture-initiating cells by 88% and 68%, respectively. IFN-gamma and TNF-alpha triggered apoptosis of total bane marrow and CD34(+) cells, recognized by the presence of a characteristic pattern of DNA degradation after low molecular weight DNA extraction, and by detection of apoptotic cells by the in situ terminal deoxynucleotidyl transferase assay. We speculate that chronic exposure of hematopoietic tissue to TNF-alpha and IFN-gamma in vivo may result in broad depletion of the stem and progenitor cell pools. Death of these cells due to apoptosis rather than transient inhibition of proliferation maybe responsible for long-lasting hematologic consequences. (C) 1995 Wiley-Liss, Inc. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 46 TC 147 Z9 155 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1995 VL 165 IS 3 BP 538 EP 546 DI 10.1002/jcp.1041650312 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TG931 UT WOS:A1995TG93100011 PM 7593233 ER PT J AU XING, MZ MIELE, L MUKHERJEE, AB AF XING, MZ MIELE, L MUKHERJEE, AB TI ARACHIDONIC-ACID RELEASE FROM NIH 3T3 CELLS BY GROUP-I PHOSPHOLIPASE A(2) - INVOLVEMENT OF A RECEPTOR-MEDIATED MECHANISM SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PANCREATIC-TYPE PHOSPHOLIPASE-A(2); PROTEIN-KINASE-C; CYTOSOLIC PHOSPHOLIPASE-A2; BINDING-SITE; EXTRACELLULAR PHOSPHOLIPASE-A2; OVER-EXPRESSION; MUSCLE-CELLS; INHIBITION; ACTIVATION; ALPHA AB Group I pancreatic phospholipase A(2) (PLA(2) I) is primarily a digestive enzyme. Recently, however, in addition to its catalytic activity a receptor-mediated function has been described for this enzyme. PLAL(2) I binding to its receptor induces cellular chemokinesis, proliferation, and smooth muscle contraction. This enzyme also induces the production of prostaglandin E(2) in certain cells and may have a proinflammatory role. However, despite its ability to hydrolyze phospholipids in in vitro assays, PLA(2)-I does not efficiently catalyze release of AA from intact cells. Here, we demonstrate that while short-term exposure of NIH 3T3 cells to PLA(2) is ineffective, exposure of 6 h or longer significantly increases the basal release of AA. Dose-response curve of PLA(2)-l-induced AA release was saturable with an EC(50) of 14.01 +/- 1.36 nM (n = 3). [H-3]-AA was preferentially released over [H-3]oleic acid by PLA(2)-I. PLA(2)-I, inactivated with 4-bromophenacyl bromide, was fully capable of mediating AA release. These data suggest that a non-catalytic, receptor-mediated mechanism is involved in PLA(2)-l-induced AA release in NIH-3T3 cells. This release of AA is not dependent on protein kinase C or Ca2+ concentration. Comparison of the effect of PLA(2)-I with those of ATP and platelet-derived growth factor indicates that each of these agonists regulates AA release via independent pathways. Neither the basal enzymatic activity of the 85-kDa cytosolic PLA(2) nor the protein level of this enzyme was affected by treatment of cells with PLA(2)-I. However, the increase in basal enzymatic activity of 85 kDa PLA(2) due to protein kinase C activation was further enhanced by pretreatment of cells with PLA(2)-I. We conclude that: (1) short-term exposure oi cells to PLA(2) I does not cause measurable AA release; (2) release of AA from intact cells by this enzyme requires long-term exposure; (3) AA release is not mediated by a direct catalytic effect of PLA(2) I; and (4) AA release by PLA(2) I is accomplished via a receptor-mediated process. Taken together, these results raise the possibility that PLA(2) I, in addition to its digestive function, may also contribute to aggravate preexisting inflammatory processes and/or to initiate new ones when chronic exposure of cells to this enzyme occurs. (C) 1995 Wiley-Liss, Inc. C1 NICHHD, HUMAN GENET BRANCH, DEV GENET SECT, BETHESDA, MD 20892 USA. NR 54 TC 16 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1995 VL 165 IS 3 BP 566 EP 575 DI 10.1002/jcp.1041650315 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TG931 UT WOS:A1995TG93100014 PM 7593236 ER PT J AU ZWANZIG, R AF ZWANZIG, R TI A HIGHLY CONNECTED RANDOM MASTER EQUATION SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID RANDOM ENERGY-MODEL; RELAXATION AB In a highly connected master equation, each state is connected to a substantial fraction of all other states. A special case, in which the connections are made at random, is investigated here by means of an effective medium approximation. The eigenvalue spectrum of the resulting effective medium agrees well with the spectrum of the original master equation. (C) 1995 American Institute of Physics. RP ZWANZIG, R (reprint author), NIDDK,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892, USA. NR 11 TC 10 Z9 10 U1 0 U2 5 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 1 PY 1995 VL 103 IS 21 BP 9397 EP 9400 DI 10.1063/1.469999 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA TF808 UT WOS:A1995TF80800029 ER PT J AU Chan, KC Muschik, GM Issaq, HJ AF Chan, KC Muschik, GM Issaq, HJ TI Separation of tryptophan and related indoles by micellar electrokinetic chromatography with KrF laser-induced fluorescence detection SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; 5-HYDROXYINDOLEACETIC ACID; ELECTROCHEMICAL DETECTION; HUMAN PLASMA; CAPILLARY CHROMATOGRAPHY; HUMAN SERUM; METABOLITES; SEROTONIN; DERIVATIZATION; PHENYLGLYOXAL AB Micellar electrokinetic chromatography (MEKC) was applied for the separation of tryptophan and related indoles. Using a 5 mM sodium berate buffer (pH 9.2) containing 50 mM sodium dodecyl sulfate and 5% acetonitrile, eleven indoles were baseline separated in under 17 min. Most of the indoles were detected at the nM level by native fluorescence using KrF laser-induced fluorescence (LIF),which was approximately 100 times more sensitive than UV absorption detection at 200 nm. Preliminary results show that the MEKC-LIF with direct sample injection is a feasible method for assessing indole profiles in diluted urine and serum. RP Chan, KC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,POB B,FREDERICK,MD 21702, USA. NR 35 TC 33 Z9 33 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD DEC 1 PY 1995 VL 718 IS 1 BP 203 EP 210 DI 10.1016/0021-9673(95)00675-3 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA TK909 UT WOS:A1995TK90900022 PM 8556162 ER PT J AU Parker, ES Eaton, EM Whipple, SC Heseltine, PNR Bridge, TP AF Parker, ES Eaton, EM Whipple, SC Heseltine, PNR Bridge, TP TI University of Southern California Repeatable Episodic Memory Test SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID INFECTION; BRAIN; AIDS AB The University of Southern California Repeatable Episodic Memory Test (USC-REMT) was developed to provide a brief assay of memory in clinical drug trials where the same subject is tested multiple times over days or weeks. Therefore, it had to be minimally affected by repeated testing. The test also provides a measure of subjective organization, a cognitive strategy that might be sensitive to frontal lobe dysfunction and HIV-related memory deficits. The USC-REMT has seven different lists, each composed of 15 semantically unrelated, high-frequency nouns. The words are presented in a different order on three study-test trials. After each study trial the subject recalls the words in any order. The test takes about 10 min to administer and score. The recall protocol can be scored for (a) global mnemonic efficiency, (b) primary and secondary memory, (c) subjective organization, (d) recall consistency and (e) recall as a function of serial position. We report initial data showing that the test is sensitive to memory decrements. Thirty-six HIV-1 seropositive men, at various stages of illness, recalled significantly fewer words and exhibited less subjective organization than 14 matched controls. The test had no significant practice effects over the first three administrations when separated by several days. The seven alternate lists are essentially equivalent. The USC-REMT appears to complement currently published verbal memory tasks. C1 UNIV SO CALIF,LOS ANGELES CTY MED CTR,DEPT PSYCHIAT,UNIT 1,LOS ANGELES,CA 90033. CTR NEUROPSYCHOL,IRVINE,CA. NIDA,ROCKVILLE,MD. FU NCRR NIH HHS [M01 RR-43] NR 30 TC 24 Z9 24 U1 0 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD DEC PY 1995 VL 17 IS 6 BP 926 EP 936 DI 10.1080/01688639508402441 PG 11 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA TM776 UT WOS:A1995TM77600012 PM 8847398 ER PT J AU ROBBINS, J AF ROBBINS, J TI GENE AMPLIFICATION AS A CAUSE FOR INHERITED THYROXINE-BINDING GLOBULIN EXCESS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID X-CHROMOSOME; ABNORMALITIES; DEFICIENCY RP ROBBINS, J (reprint author), NIDDK, BLDG 10, RM-8N315, 10 CTR DR MSC 1766, BETHESDA, MD 20892 USA. NR 23 TC 0 Z9 0 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1995 VL 80 IS 12 BP 3425 EP 3426 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TJ049 UT WOS:A1995TJ04900007 PM 8530577 ER PT J AU SIEBLER, T LOPACZYNSKI, W TERRY, CL CASELLA, SJ MUNSON, P DELEON, DD PHANG, L BLAKEMORE, KJ MCEVOY, RC KELLEY, RI NISSLEY, P AF SIEBLER, T LOPACZYNSKI, W TERRY, CL CASELLA, SJ MUNSON, P DELEON, DD PHANG, L BLAKEMORE, KJ MCEVOY, RC KELLEY, RI NISSLEY, P TI INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR EXPRESSION AND FUNCTION IN FIBROBLASTS FROM 2 PATIENTS WITH DELETION OF THE DISTAL LONG ARM OF CHROMOSOME-15 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SOMATOMEDIN-C; RING CHROMOSOME-15; BINDING; GENE; ACID; HORMONE; CELLS; STIMULATION; DEFICIENCY; MUTATIONS AB Most patients with deletion of the distal long arm of chromosome 15 have intrauterine growth retardation and postnatal growth deficiency in addition to developmental abnormalities. It has been proposed that the absence of one copy of the insulin-like growth factor I (IGF-I) receptor gene may play a role in the growth deficiency seen in this syndrome. To address this question we examined IGF-I receptor expression and function in fibroblasts from two patients with deletion of the distal long arm of chromosome 15 (15q26.1-->qter). Quantitative Southern blot analysis of the IGF-I receptor gene was performed on HindIII digests of fibroblast DNA. Radioactivity in the 1.7-kilobase receptor fragment in the two patients was 55% and 51% of the values in controls, consistent with the absence of one copy of the IGF-I receptor gene. IGF-I receptor messenger ribonucleic acid levels were quantitated by a solution hybridization/nuclease protection assay. Receptor messenger ribonucleic acid levels in the two patients were 45% and 52% of the values in controls. Northern blotting demonstrated normal size IGF-I receptor transcripts and affinity crosslinking of [I-125]]IGF-I to Triton X-100-solubilized fibroblasts demonstrated a normal size receptor in the patients. Analysis of placental membranes prepared from one patient revealed no difference in [I-125]IGF-I binding. In the patients' fibroblasts, however, binding of [I-125]long [R(3)]-IGF-I to the IGF-I receptor was significantly reduced, as assessed by the amount of radioactivity competed by the monoclonal antibody alpha IR-3 or insulin and Scatchard analysis of binding data. To assess IGF-I receptor function, stimulation of [alpha-1-C-14]methylaminoisobutyric acid transport and stimulation of [methyl-H-3]thymidine incorporation into DNA by a full range of IGF-I concentrations was examined in patient and control fibroblasts. There was a significant decrease in the maximal response to IGF-I in both assays for one of the two patients when data were expressed as fold response over the basal value. However, there was no evidence for impairment of response to IGF-I in either patient's fibroblasts when data were expressed as net stimulation (maximal response minus basal). In conclusion, although IGF-I receptor expression was decreased in fibroblasts from two patients with deletion of the distal long arm of chromosome 15, we were unable to provide conclusive evidence for impairment of the biological response to IGF-I. C1 NCI, METAB BRANCH, BETHESDA, MD 20892 USA. NIH, DIV COMP RES & TECHNOL, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PEDIAT, BALTIMORE, MD 21287 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT OBSTET & GYNECOL, BALTIMORE, MD 21287 USA. JOHNS HOPKINS UNIV, SCH MED, KENNEDY INST, BALTIMORE, MD 21287 USA. UNIV WASHINGTON, SCH MED, DEPT PEDIAT, SEATTLE, WA 98105 USA. FU NICHD NIH HHS [HD-24061] NR 47 TC 46 Z9 47 U1 0 U2 1 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 DEC PY 1995 VL 80 IS 12 BP 3447 EP 3457 DI 10.1210/jc.80.12.3447 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TJ049 UT WOS:A1995TJ04900012 PM 8530582 ER PT J AU MAHESHWARI, H LILLIOJA, S CASTILLO, CE MERCADO, M BAUMANN, G AF MAHESHWARI, H LILLIOJA, S CASTILLO, CE MERCADO, M BAUMANN, G TI GROWTH HORMONE-BINDING PROTEIN IN HUMAN LYMPH SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GH-BINDING; RECEPTOR; PLASMA; SERUM; RAT AB The high affinity GH-binding protein (GHBP) is a soluble circulating ectodomain of the GH receptor (GHR). In humans, it is thought to be released from the plasma membrane-bound GHR by proteolysis at or near the transmembrane domain. GHBP modulates GH action by 1) intravascular complex formation, and 2) competing with the GHR for ligand in tissues (interstitial complex formation). Little is known about the tissue source(s) of GHBP, the local regulation of GHBP generation, or its concentration in the interstitium. To begin addressing these questions, we studied GHBP levels in peripheral lymph, whose composition approximates that of interstitial fluid. Lymph was collected in 13 healthy adult men from cannulated lymphatic vessels in the calf. Venous and arterial blood samples were collected from the femoral vein and radial artery contemporaneously with lymph collection. Potential GHBP production by endothelial or blood cells was assessed by examining conditioned medium from in vitro cell cultures. GHBP activity was measured by standardized GH binding/column chromatography assay. GHBP was consistently and significantly lower in lymph (mean +/- SD, 4.6 +/- 1.2% GH bound/200 mu L) than in venous (14.1 +/- 3.0%) or arterial (14.9 +/- 3.6%) plasma. Conditioned medium from endothelial or blood cell cultures did not contain detectable GHBP. We conclude that the level of GHBP in peripheral lymph is substantially lower than that in the peripheral circulation, and that components of the vasculature are not important sources of GHBP. These findings suggests that 1) the main tissue sources of GHBP in man are the central organs (especially liver); and 2) transcapillary diffusion of GHBP into the interstitial space is restricted. C1 NORTHWESTERN UNIV, SCH MED, CTR ENDOCRINOL METAB & MOLEC MED, DEPT MED, CHICAGO, IL 60611 USA. NIDDKD, CLIN DIABET & NUTR SECT, PHOENIX, AZ 85016 USA. RI Lillioja, Stephen/A-8185-2012; OI Lillioja, Stephen/0000-0001-5333-5240 NR 25 TC 3 Z9 3 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1995 VL 80 IS 12 BP 3582 EP 3584 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TJ049 UT WOS:A1995TJ04900032 PM 8530602 ER PT J AU Fiebiger, E Maurer, D Holub, H Reininger, B Hartmann, G Woisetschlager, M Kinet, JP Stingl, G AF Fiebiger, E Maurer, D Holub, H Reininger, B Hartmann, G Woisetschlager, M Kinet, JP Stingl, G TI Serum IgG autoantibodies directed against the a chain of Fc epsilon RI: A selective marker and pathogenetic factor for a distinct subset of chronic UrtiCaria patients? SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE autoimmunity; IgE receptors; histamine release; mast cell degranulation; pseudoallergic reaction ID ANTI-IGE; HISTAMINE-RELEASE; MAST-CELLS; ATOPIC-DERMATITIS; IMMUNOGLOBULIN-E; HUMAN BASOPHILS; RECEPTORS; ANTIBODIES AB While it is well established that acute allergic urticaria is caused by degranulation of skin mast cells occurring after allergen/IgE-dependent cross-linking of high affinity IgE receptors (Fc epsilon RI), the pathophysiologic mechanisms operative in chronic urticaria (CU) are less well understood, Some evidence points to the existence of histamine-releasing activity in the serum of CU patients which possibly acts via triggering of Fc epsilon RI. In this study, we aimed to better characterize this anti-Fc epsilon RI alpha reactivity of CU patients using affinity-purified, IgE-depleted IgG fractions of such individuals (CU-IgG), Using immobilized, recombinant soluble Fc epsilon RI alpha as a reaction target for Western blot studies, we found that 12/32 (37%) CU-IgG serum samples exhibited IgG autoreactivity against Fc epsilon RI alpha. These findings were confirmed by experiments demonstrating that immunoblot-reactive, but not immunoblot-nonreactive, CU-IgG preparations precipitated the Fc epsilon RI alpha from Fc epsilon RI alpha gamma-transfected cells, No anti-Fc epsilon RI alpha reactivity was observed in IgG fractions from atopic dermatitis (AD) patients (0/15) or healthy control individuals (CO: 0/15), As opposed to the selective occurrence of IgG anti-Fc epsilon RI alpha autoantibodies in CU patients, IgG anti-IgE antibodies were detected in all groups investigated (CU: 69%; AD: 73%; CO: 26%), While both types of autoantibodies can exhibit histamine-releasing properties, not all of the autoantibodies proved to be functional in vitro, Our results indicate that the occurrence of IgG anti-Fc epsilon RI alpha reactivity defines an autoimmune-mediated subentity of CU and provide a basis for the development of new diagnostic procedures and, perhaps, therapeutic strategies for this disease. C1 SANDOZ GMBH,A-1230 VIENNA,AUSTRIA. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20892. RP Fiebiger, E (reprint author), UNIV VIENNA,SCH MED,DEPT DERMATOL,DIV IMMUNOL ALLERGY & INFECT DIS,WAHRINGER GURTEL 18-20,A-1090 VIENNA,AUSTRIA. NR 28 TC 193 Z9 194 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1995 VL 96 IS 6 BP 2606 EP 2612 DI 10.1172/JCI118325 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TK257 UT WOS:A1995TK25700010 PM 8675625 ER PT J AU Schwartz, LB Sakai, K Bradford, TR Ren, SL Zweiman, B Worobec, AS Metcalfe, DD AF Schwartz, LB Sakai, K Bradford, TR Ren, SL Zweiman, B Worobec, AS Metcalfe, DD TI The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE tryptase; mast cell; mastocytosis; anaphylaxis ID MAST-CELL TRYPTASE; MONOCLONAL-ANTIBODIES; COMPLEMENTARY-DNA; MONO MAC-6; ANAPHYLAXIS; ACTIVATION; CHYMASE; CLONING AB Tryptase, a protease produced by all mast cells, was evaluated as a clinical marker of systemic mastocytosis, Two sandwich immunoassays were evaluated, one which used the mAb G5 for capture, the other which used B12 for capture, The B12 capture assay measured both recombinant alpha- and beta-tryptase, whereas the G5 capture assay measured primarily recombinant beta-tryptase. G5 binds with low affinity to both recombinant alpha-tryptase and tryptase in blood from normal and nonacute mastocytosis subjects, and binds with high affinity to recombinant beta-tryptase, tryptase in serum during anaphylaxis, and tryptase stored in mast cell secretory granules, B12 recognizes all of these forms of tryptase with high affinity, As reported previously, during systemic anaphylaxis in patients without known mastocytosis, the ratio of B12- to G5-measured tryptase was always < 5 and approached unity (Schwartz L. B., T. R. Bradford, C. Rouse, A.-M. Irani, G. Rasp, J. K. Van der Zwan and P.-W. G. Van Der Linden J. Clin. Immunol. 14:190-204), In this report, most mastocytosis patients with systemic disease have B12-measured tryptase levels that are elevated(> 20 ng/ml) and are at least 10-fold greater than the corresponding G5-measured tryptase level, Most of those subjects with B12-measured tryptase levels of < 20 ng/ml had only cutaneous manifestations. The B12 assay for alpha-tryptase and beta-tryptase, particularly when performed in conjunction with the G5 assay for beta-tryptase, provides a more precise measure of mast cell involvement than currently available assessments, a promising potential screening test for systemic mastocytosis and may provide an improved means to follow disease progression and response to therapy. C1 UNIV PENN,SCH MED,DEPT MED,DIV ALLERGY & IMMUNOL,PHILADELPHIA,PA 19104. NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. RP Schwartz, LB (reprint author), VIRGINIA COMMONWEALTH UNIV,DEPT MED,DIV RHEUMATOL ALLERGY & IMMUNOL,POB 980236,RICHMOND,VA 23298, USA. FU NIAID NIH HHS [AI14332, AI20487, AI27517] NR 25 TC 251 Z9 253 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1995 VL 96 IS 6 BP 2702 EP 2710 DI 10.1172/JCI118337 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TK257 UT WOS:A1995TK25700022 PM 8675637 ER PT J AU Pandey, JP Elson, LH Sutherland, SE Guderian, RH Araujo, E Nutman, TB AF Pandey, JP Elson, LH Sutherland, SE Guderian, RH Araujo, E Nutman, TB TI Immunoglobulin kappa chain allotypes (KM) in onchocerciasis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GM; immunity; phenotype; haplotype; gene frequency ID IMMUNE-RESPONSE; DISEASE; INFLUENZAE; ASSOCIATION; GM; SUSCEPTIBILITY; CHILDREN; ANTIGENS; VACCINE; ECUADOR AB GM and KM allotypes, powerful tools for genetic characterization of human populations, have been shown to play an important role in genetic predisposition to some infectious diseases. Two diverse racial groups-Afro-Ecuadorians and Amerindians-living in a single restricted geographical area of Ecuador, appear to have different risk factors for acquisition and clinical expression of onchocerciasis, a disease caused by the filarial parasite Onchocerca volvulus, In this study, GM and KIM allotypes were determined in 25 Afro-Ecuadorians and 24 Amerindians infected with Onchocerca volvulus (INF) and in putative immune individuals (PI), In Afro-Ecuadorians, the frequency of the homozygous KM 3 phenotype was significantly decreased in INF as compared with the PI group (20 vs, 68%; P = 0.0012), while the frequency of the heterozygous KM 1,3 phenotype was increased in INF as compared with the PI subjects (48 vs 9%; P = 0.0044). These results suggest that in Afro-Ecuadorians KM 3 is associated with a lower relative risk (resistance), whereas KM 1,3 is associated with an increased risk (susceptibility) of onchocerciasis. C1 MED UNIV S CAROLINA,DEPT BIOMETRY & EPIDEMIOL,CHARLESTON,SC 29425. NATL INST HLTH,NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. HOSP VOZANDES,DEPT CLIN INVEST,QUITO,ECUADOR. RP Pandey, JP (reprint author), MED UNIV S CAROLINA,DEPT MICROBIOL & IMMUNOL,CHARLESTON,SC 29425, USA. FU NIDCR NIH HHS [DE-10703] NR 32 TC 23 Z9 23 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1995 VL 96 IS 6 BP 2732 EP 2734 DI 10.1172/JCI118341 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TK257 UT WOS:A1995TK25700026 PM 8675641 ER PT J AU Abdallah, JM Lombardi, DP Kirsch, IR AF Abdallah, JM Lombardi, DP Kirsch, IR TI Genetic instability in patients with Hodgkin's disease undergoing chemotherapy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE T cell; gene rearrangement; malignancy ID GENOMIC INSTABILITY; LYMPHOCYTES; RISK; RECOMBINATION AB We have studied the effect of chemotherapy on the level of a particular kind of genetic instability in patients with Hodgkin's disease. The particular type of genetic instability assayed is exemplified by trans-rearrangements between two (rather than within one) T cell antigen receptor. 16 patients were studied during their course of treatment. Presentation samples were available for 13 of these patients; 9 of them showed an increase in the level of trans-rearrangements during their exposure to chemotherapeutic agents (P < 0.043). All patients for whom posttherapy samples were available (10 out of 16) showed a return to baseline levels of trans-rearrangements 1-5 mo after completion of therapy (P < 0.03). Thus, this assay appears to be a marker for the ''destabilizing'' effects of certain chemotherapeutic agents. C1 NATL NAVAL MED CTR, NCI, MED ONCOL BRANCH, BETHESDA, MD 20889 USA. NR 18 TC 24 Z9 24 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1995 VL 96 IS 6 BP 2744 EP 2747 DI 10.1172/JCI118343 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TK257 UT WOS:A1995TK25700028 PM 8675643 ER PT J AU Pan, DA Lillioja, S Milner, MR Kriketos, AD Baur, LA Bogardus, C Storlien, LH AF Pan, DA Lillioja, S Milner, MR Kriketos, AD Baur, LA Bogardus, C Storlien, LH TI Skeletal muscle membrane lipid composition is related to adiposity and insulin action SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE dietary fats; euglycemic clamp; body composition; elongase activity; desaturase activity ID FATTY-ACID COMPOSITION; PIMA-INDIANS; WEIGHT-GAIN; DIABETES-MELLITUS; HUMAN-DISEASE; RESISTANCE; METABOLISM; GLUCOSE; GENE; LIVER AB The cellular basis of insulin resistance is still unknown, however, relationships have been demonstrated between insulin action in muscle and the fatty acid profile of the major membrane structural lipid (phospholipid). The present study aimed to further investigate the hypothesis that insulin action and adiposity are associated with changes in the structural lipid composition of the cell, In 52 adult male Pima Indians, insulin action (euglycemic clamp), percentage body fat (pFAT; underwater weighing), and muscle phospholipid fatty acid composition (percutaneous biopsy of vastus lateralis) were determined, Insulin action (high-dose clamp; MZ) correlated with composite measures of membrane unsaturation (% C20-22 polyunsaturated fatty acids [r = 0.463, P < 0.001], unsaturation index [r = -0.369, P < 0.01]), a number of individual fatty acids and with Delta 5 desaturase activity (r = 0.451, P < 0.001), pFAT (range 14-53%) correlated with a number of individual fatty acids and Delta 5 desaturase activity (r = -0.610, P < 0.0001), Indices of elongase activity (r = -0.467, P < 0.001), and Delta 9 desaturase activity (r = 0.332, P < 0.05) were also related to pFAT but not insulin action, The results demonstrate that Delta 5 desaturase activity is independently related to both insulin resistance and obesity, While determining the mechanisms underlying this relationship is important for future investigations, strategies aimed at restoring ''normal'' enzyme activities, and membrane unsaturation, may have therapeutic importance in the ''syndromes of insulin resistance.'' C1 ROYAL PRINCE ALFRED HOSP, DEPT ENDOCRINOL, SYDNEY, NSW 2050, AUSTRALIA. NIDDKD, CLIN DIABET & NUTR SECT, PHOENIX, AZ 85016 USA. UNIV WOLLONGONG, DEPT BIOMED SCI, WOLLONGONG, NSW 2522, AUSTRALIA. RP Pan, DA (reprint author), UNIV WOLLONGONG, DEPT BIOMED SCI, WOLLONGONG, NSW 2170, AUSTRALIA. RI Lillioja, Stephen/A-8185-2012; OI Lillioja, Stephen/0000-0001-5333-5240 NR 50 TC 216 Z9 226 U1 0 U2 10 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1995 VL 96 IS 6 BP 2802 EP 2808 DI 10.1172/JCI118350 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TK257 UT WOS:A1995TK25700035 PM 8675650 ER PT J AU Newman, KD Dunn, PF Owens, JW Schulick, AH Virmani, R Sukhova, G Libby, P Dichek, DA AF Newman, KD Dunn, PF Owens, JW Schulick, AH Virmani, R Sukhova, G Libby, P Dichek, DA TI Adenovirus-mediated gene transfer into normal rabbit arteries results in prolonged vascular cell activation, inflammation, and neointimal hyperplasia SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE adenoviruses; arteries; gene transfer; inflammation; rabbits ID ADHESION MOLECULE-1; ATHEROSCLEROTIC PLAQUES; IN-VIVO; EXPRESSION; VECTORS; THERAPY AB Adenovirus vectors are capable of high efficiency in vivo arterial gene transfer, and are currently in use as therapeutic agents in animal models of vascular disease, However, despite substantial data on the ability of viruses to cause vascular inflammation and proliferation, and the presence in current adenovirus vectors of viral open reading frames that are translated in vivo, no study has examined the effect of adenovirus vectors alone on the arterial phenotype, In a rabbit model of gene transfer into a normal artery, we examined potential vascular cell activation, inflammation, and neointimal proliferation resulting from exposure to replication-defective adenovirus, Exposure of normal arteries to adenovirus vectors resulted in: (a) pronounced infiltration of T cells throughout the artery wall; (b) upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in arterial smooth muscle cells; (c) neointimal hyperplasia, These findings were present both 10 and 30 d after gene transfer, with no evidence of a decline in severity over time. Adenovirus vectors have pleiotropic effects on the arterial wall and cause significant pathology, Interpretation of experimental protocols that use adenovirus vectors to address either biological or therapeutic issues should take these observations into account. These observations should also prompt the design of more inert gene transfer vectors. C1 GLADSTONE INST CARDIOVASC DIS,SAN FRANCISCO,CA 94141. NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,WASHINGTON,DC 20307. CHILDRENS HOSP,DEPT SURG,WASHINGTON,DC 20010. BRIGHAM & WOMENS HOSP,DEPT MED,DIV CARDIOVASC,VASC MED & ATHEROSCLEROSIS UNIT,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,SAN FRANCISCO,CA 94141. UNIV CALIF SAN FRANCISCO,DAIICHI RES CTR,SAN FRANCISCO,CA 94141. NR 49 TC 250 Z9 256 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1995 VL 96 IS 6 BP 2955 EP 2965 DI 10.1172/JCI118367 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TK257 UT WOS:A1995TK25700052 PM 8675667 ER PT J AU WALSH, TJ FRANCESCONI, A KASAI, M CHANOCK, SJ AF WALSH, TJ FRANCESCONI, A KASAI, M CHANOCK, SJ TI PCR AND SINGLE-STRAND CONFORMATIONAL POLYMORPHISM FOR RECOGNITION OF MEDICALLY IMPORTANT OPPORTUNISTIC FUNGI SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; INVASIVE CANDIDIASIS; DNA; DIAGNOSIS; AMPLIFICATION; MUTATIONS; SSCP AB The application of PCR technology to molecular diagnostics holds great promise for the early identification of medically important pathogens, PCR has been shown to be useful for the detection of the presence of fungal DNA in both laboratory and clinical samples, Considerable interest has been focused on the utility of selecting universal primers, those that recognize constant regions among most, if not all, medically important fungi, Once an amplicon, or piece of amplified DNA determined by the unique pair of oligonucleotide primers, has been generated, several different methods may be used to distinguish between genera and between species, The two major approaches have utilized differences in restriction enzyme digestion patterns or hybridization with specific probe, We report the application of single-strand conformational polymorphism (SSCP) as a technique to delineate the differences between fungal species and/or genera, Minor sequence variations in small single-stranded DNA cause subtle changes in conformation, allowing these strands to be separated on polyacrylamide gels by SSCP, We used a 197-bp fragment amplified from the 18S rRNA gene, common to all medically important fungi, After amplification, the fragments were denatured and run on an acrylamide-glycerol gel at room temperature or 4 degrees C for 4.5 or 4 h, respectively, Under room temperature conditions, the SSCP patterns for Candida albicans, Candida tropicalis, and Candida parapsilosis were identical and all strains within each species demonstrated the same pattern, These patterns differed markedly from those of the genus Aspergillus, The SSCP patterns of major and minor bands at room temperature permitted distinction between strains of Aspergillus fumigatus and Aspergillus flavus. There also was consistency of the SSCP banding pattern among different strains of the same Aspergillus species, The SSCP patterns for other medically important opportunistic fungi, such as Cryptococcus neoformans, Pseudallescheria boydii, and Rhizopus arrhizus, were sufficiently unique to permit distinction from those of C. albicans and A. fumigatus. We conclude that the technique of PCR-SSCP provides a novel method by which to recognize and distinguish medically important opportunistic fungi and which has potential applications to molecular diagnosis, taxonomic classification, molecular epidemiology, and elucidation of mechanisms of antifungal drug resistance. RP WALSH, TJ (reprint author), NCI,INFECT DIS SECT,BLDG 10,RM 13N-240,BETHESDA,MD 20892, USA. NR 25 TC 115 Z9 121 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1995 VL 33 IS 12 BP 3216 EP 3220 PG 5 WC Microbiology SC Microbiology GA TF015 UT WOS:A1995TF01500029 PM 8586705 ER PT J AU WEST, BC OBERLE, AD KWONCHUNG, KJ AF WEST, BC OBERLE, AD KWONCHUNG, KJ TI MUCORMYCOSIS CAUSED BY RHIZOPUS-MICROSPORUS VAR MICROSPORUS - CELLULITIS IN THE LEG OF A DIABETIC PATIENT CURED BY AMPUTATION SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID RHIZOPODIFORMIS; CUNNINGHAMELLA; ZYGOMYCOSIS; DIALYSIS AB Mucormycosis accompanied the development of bacterial infection in the leg of a diabetic African-American man. Local injury, diabetic ketoacidosis, renal insufficiency, and antimicrobial therapy were factors that contributed to the pathogenesis of the mucormycosis. The cellulitis was caused in part by Rhizopus microsporus var, microsporus and was cured by amputation. We report this unusual case of mucormycosis to emphasize the value of fungal identification, to illustrate a dramatic and successful clinical result, and to draw attention to an apparent role for bacterial infection and its treatment in the pathogenesis of mucormycosis. It is the third case report of mucormycosis in a human in which R. microsporus var. microsporus was definitively identified as the etiologic agent. C1 LOUISIANA STATE UNIV,MED CTR,DEPT MED,SHREVEPORT,LA 71130. LOUISIANA STATE UNIV,MED CTR,CLIN MICROBIOL LAB,SHREVEPORT,LA 71130. NIAID,CLIN MYCOL SECT,CLIN INVEST LAB,BETHESDA,MD 20892. NR 24 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1995 VL 33 IS 12 BP 3341 EP 3344 PG 4 WC Microbiology SC Microbiology GA TF015 UT WOS:A1995TF01500058 PM 8586734 ER PT J AU KETTER, TA FLOCKHART, DA POST, RM DENICOFF, K PAZZAGLIA, PJ MARANGELL, LB GEORGE, MS CALLAHAN, AM AF KETTER, TA FLOCKHART, DA POST, RM DENICOFF, K PAZZAGLIA, PJ MARANGELL, LB GEORGE, MS CALLAHAN, AM TI THE EMERGING ROLE OF CYTOCHROME-P450 3A IN PSYCHOPHARMACOLOGY SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Review ID HUMAN-LIVER-MICROSOMES; PHARMACOKINETIC DRUG-INTERACTIONS; SEROTONIN REUPTAKE INHIBITORS; CALCIUM-CHANNEL BLOCKERS; HUMAN CELL-LINE; N-DEMETHYLATION; EPILEPTIC PATIENTS; HUMAN HEPATOCYTES; OXIDATION POLYMORPHISM; NIFEDIPINE OXIDASE AB Recent advances in molecular pharmacology, have allowed the characterization of the specific isoforms that mediate the metabolism of various medications. This information can be integrated with older clinical observations to begin to develop specific mechanistic and predictive models of psychotropic drug interactions. The polymorphic cytochrome P450 2D6 has gained much attention, because competition for this isoform is responsible for serotonin reuptake inhibitor-induced increases in tricyclic antidepressant concentrations in plasma. However, the cytochrome P450 3A subfamily and the 3A3 and 3A4 isoforms (CYP3A3/4) in particular are becoming increasingly important in psychopharmacology as a result of their central involvement in the metabolism of a wide range of steroids and medications, including antidepressants, benzodiazepines, calcium channel blockers, and carbamazepine. The inhibition of CYP3A3/4 by medications such as certain newer antidepressants, calcium channel blockers, and antibiotics can increase the concentrations of CYP3A3/4 substrates, yielding toxicity. The induction of CYP3A3/4 by medications such as carbamazepine can decrease the concentrations of CYP3A3/4 substrates, yielding inefficiency. Thus, knowledge of the substrates, inhibitors, and inducers of CYP3A3/4 and other cytochrome P450 isoforms may help clinicians to anticipate and avoid pharmacokinetic drug interactions and improve rational prescribing practices. C1 GEORGETOWN UNIV,MED CTR,DEPT MED,DIV CLIN PHARMACOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,WASHINGTON,DC 20007. RP KETTER, TA (reprint author), NIMH,BIOL PSYCHIAT BRANCH,3 W CLIN RES UNIT,BLDG 10,ROOM 3N212,9000 ROCKVIL,BETHESDA,MD 20892, USA. NR 172 TC 154 Z9 154 U1 1 U2 2 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 DEC PY 1995 VL 15 IS 6 BP 387 EP 398 DI 10.1097/00004714-199512000-00002 PG 12 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA TK567 UT WOS:A1995TK56700002 PM 8748427 ER PT J AU BROOKS, BR JANEZIC, D KARPLUS, M AF BROOKS, BR JANEZIC, D KARPLUS, M TI HARMONIC-ANALYSIS OF LARGE SYSTEMS .1. METHODOLOGY SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article ID PANCREATIC TRYPSIN-INHIBITOR; NEUTRON-SCATTERING ANALYSIS; NORMAL-MODES; MOLECULAR-DYNAMICS; CONFIGURATIONAL ENTROPY; VIBRATIONAL ANALYSIS; LANGEVIN MODES; PROTEINS; MACROMOLECULES; FLUCTUATIONS AB Methods have been developed for the determination of vibrational frequencies and normal modes of large systems in the full conformational space (including all degrees of freedom) and in a reduced conformational space (reducing the number of degrees of freedom). The computational method, which includes Hessian generation and storage, full and iterative diagonalization techniques, and the refinement of the results, is presented. A method is given for the quasiharmonic analysis and the reduced basis quasiharmonic analysis. The underlying principle is that from the atomic fluctuations, an effective harmonic force field can be determined relative to the dynamic average structure. Normal mode analysis tools can be used to characterize quasiharmonic modes of vibration. These correspond to conventional normal modes except that anharmonic effects are included. Numerous techniques for the analyses of vibrational frequencies and normal modes are described. Criteria for the analysis of the similarity of low-frequency normal modes is presented. The approach to determining the natural frequencies and normal modes of vibration described here is general and applicable to any large system. (C) 1995 by John Wiley & Sons, Inc.double dagger C1 NATL INST CHEM,LJUBLJANA 61115,SLOVENIA. HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138. RP BROOKS, BR (reprint author), NIH,DCRT,STRUCT BIOL LAB,BETHESDA,MD 20892, USA. NR 44 TC 348 Z9 358 U1 1 U2 35 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD DEC PY 1995 VL 16 IS 12 BP 1522 EP 1542 DI 10.1002/jcc.540161209 PG 21 WC Chemistry, Multidisciplinary SC Chemistry GA TE611 UT WOS:A1995TE61100008 ER PT J AU JANEZIC, D BROOKS, BR AF JANEZIC, D BROOKS, BR TI HARMONIC-ANALYSIS OF LARGE SYSTEMS .2. COMPARISON OF DIFFERENT PROTEIN MODELS SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article ID DYNAMICS; FLUCTUATIONS AB A series of normal mode analyses of bovine pancreatic trypsin inhibitor (BPTI) has been performed. The results of modifying the long-range truncation of electrostatics, reducing the conformational spate of the system (reduced basis normal mode analysis), and using different parameter sets and models for the potential function are reported. Both explicit (904 atoms) and polar hydrogen (580 atoms) representations of BPTI were examined and produced nearly identical normal mode vectors but slightly modified vibrational frequencies. The truncation methods-no cutoff, shift, and switch-were examined, and the use of a short switching function was found to alter harmonic motion greatly. A table relating the different cutoff methods to several previously published frequencies for BPTI indicates that the diversity of published lowest frequencies is due to the use of different electrostatic models rather than to inherent differences in the models or energy parameters. Examining reduced basis results demonstrates that a dihedral basis yields similar normal mode vectors, though the vibrational frequencies are shifted to higher values. The analysis of BPTI harmonic dynamics using a spherical harmonic reduced basis set yields significantly altered dynamics, indicating that BPTI is not well represented as a homogeneous object at low temperatures. (C) 1995 by John Wiley & Sons, Inc.double dagger C1 NIH,DCRT,STRUCT BIOL LAB,BETHESDA,MD 20892. NATL INST CHEM,LJUBLJANA 61115,SLOVENIA. NR 17 TC 76 Z9 78 U1 0 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD DEC PY 1995 VL 16 IS 12 BP 1543 EP 1553 DI 10.1002/jcc.540161210 PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA TE611 UT WOS:A1995TE61100009 ER PT J AU JANEZIC, D VENABLE, RM BROOKS, BR AF JANEZIC, D VENABLE, RM BROOKS, BR TI HARMONIC-ANALYSIS OF LARGE SYSTEMS .3. COMPARISON WITH MOLECULAR-DYNAMICS SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article ID CONFIGURATIONAL ENTROPY; PROTEIN DYNAMICS; SIMULATION; MACROMOLECULES; INTEGRATION; ENERGY; MODES AB Atomic motions in bovine pancreatic trypsin inhibitor (BPTI), derived from molecular dynamics, harmonic analysis, and quasiharmonic analysis, are compared when a single protein model, energy parameters, and environment are employed. Molecular dynamics (MD) was carried out for 2 nanoseconds. An average structure was determined from the last nanosecond of the MD simulation, when no major structural changes were observed. This structure was used for several harmonic analysis calculations as well as for a reference structure for the quasiharmonic analysis, for both full basis and reduced basis sets. In contrast to the harmonic analysis results, the quasiharmonic reduced basis calculation using a spherical harmonics reduced basis provided good agreement with the full basis calculation, suggesting that when anharmonic effects are considered, BPTI can behave as a homogeneous object. An extensive analysis of the normal modes from a diverse set of 201 minimized MD simulation frames was performed. On only the sub-picosecond time scale were energy minima revisited after a transition to another state. This analysis shows that the dynamics average structure is not representative of the simulation frames in terms of energy and vibrational frequencies. For this model of BPTI, 42% of the motion (mean-squared fluctuation) can be attributed to harmonic limit behavior. A spectral analysis of the correlation function of deformation for a particular normal mode or quasiharmonic mode can be used to determine the time scales of motions which correspond to harmonic vibration, large-scale drift, or sharp transitions between local substrates. (C) 1995 by John Wiley & Sons, Inc. C1 NIH,DCRT,STRUCT BIOL LAB,BETHESDA,MD 20892. NATL INST CHEM,LJUBLJANA 61115,SLOVENIA. US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,BETHESDA,MD 20892. NR 25 TC 90 Z9 94 U1 0 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD DEC PY 1995 VL 16 IS 12 BP 1554 EP 1566 DI 10.1002/jcc.540161211 PG 13 WC Chemistry, Multidisciplinary SC Chemistry GA TE611 UT WOS:A1995TE61100010 ER PT J AU Booth, V Rinzel, J AF Booth, V Rinzel, J TI A minimal, compartmental model for a dendritic origin of bistability of motoneuron firing patterns SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE motoneurons; dendrites; bistability; plateau potentials; compartmental modeling ID PLATEAU POTENTIALS; ALPHA-MOTONEURONES; PYRAMIDAL CELLS; MOTOR UNITS; SPINAL CAT; TURTLE; CONDUCTANCES; THRESHOLD; CHANNELS; INVITRO AB Various nonlinear regenerative responses, including plateau potentials and bistable repetitive firing modes, have been observed in motoneurons under certain conditions. Our simulation results support the hypothesis that these responses are due to plateau-generating currents in the dendrites, consistent with a major role for a noninactivating calcium L-type current as suggested by experiments. Bistability as observed in the soma of low- and higher-frequency spiking or, under TTX, of near resting and depolarized plateau potentials, occurs because the dendrites can be in a near resting or depolarized stable steady state. We formulate and study a two-compartment minimal model of a motoneuron that segregates currents for fast spiking into a soma-like compartment and currents responsible for plateau potentials into a dendrite-like compartment. Current flows between compartments through a coupling conductance, mimicking electrotonic spread. We use bifurcation techniques to illuminate how the coupling strength affects somatic behavior. We look closely at the case of weak coupling strength to gain insight into the development of bistable patterns. Robust somatic bistability depends on the electrical separation since it occurs only for weak to moderate coupling conductance. We also illustrate that hysteresis of the two spiking states is a natural consequence of the plateau behavior in the dendrite compartment. RP Booth, V (reprint author), NIDDK,MATH RES BRANCH,9190 WISCONSIN AVE,SUITE 350,BETHESDA,MD 20814, USA. NR 29 TC 43 Z9 43 U1 1 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD DEC PY 1995 VL 2 IS 4 BP 299 EP 312 DI 10.1007/BF00961442 PG 14 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA TN053 UT WOS:A1995TN05300003 PM 8746404 ER PT J AU HARRISON, LD AF HARRISON, LD TI THE VALIDITY OF SELF-REPORTED DATA ON DRUG-USE SO JOURNAL OF DRUG ISSUES LA English DT Article ID TESTING HUMAN-HAIR; ABUSE; URINE AB Surveys of drug use are continually criticized on the premise that respondents underreport the extent of their drug use. Validation studies conducted prior to the mid-1980s involving known samples of drug users or urinalysis techniques showed that drug use was fairly accurately reported in self-report surveys. However, more recent validation studies conducted with criminal justice clients using improved urinalysis techniques suggest less concordance between urinalysis and self-report. This paper reviews these studies and their implications for the validity of self-report in epidemiological drug surveys. Some general conclusions can be drawn from various validation studies. Valid self-reporting of drug use is a function of: 1) the recency of the event, 2) the social desirability of the drug, and 3) nuances of data collection methodology. The paper discusses methods used to improve the validity and quality of self-report data on drug use. C1 NIDA,BALTIMORE,MD 21224. RP HARRISON, LD (reprint author), UNIV DELAWARE,CTR DRUG & ALCOHOL STUDIES,77 E MAIN ST,NEWARK,DE 19716, USA. NR 31 TC 138 Z9 138 U1 0 U2 8 PU J DRUG ISSUES INC PI TALLAHASSEE PA PO BOX 4021, TALLAHASSEE, FL 32315 SN 0022-0426 J9 J DRUG ISSUES JI J. Drug Issues PD WIN PY 1995 VL 25 IS 1 BP 91 EP 111 PG 21 WC Substance Abuse SC Substance Abuse GA QM278 UT WOS:A1995QM27800007 ER PT J AU MELILLO, G MUSSO, T SICA, A TAYLOR, LS COX, GW VARESIO, L AF MELILLO, G MUSSO, T SICA, A TAYLOR, LS COX, GW VARESIO, L TI A HYPOXIA-RESPONSIVE ELEMENT MEDIATES A NOVEL PATHWAY OF ACTIVATION OF THE INDUCIBLE NITRIC-OXIDE SYNTHASE PROMOTER SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MACROPHAGE CELL-LINE; PICOLINIC-ACID; INDOLEAMINE 2,3-DIOXYGENASE; INTERFERON-GAMMA; IFN-GAMMA; BACTERIAL LIPOPOLYSACCHARIDE; ERYTHROPOIETIN GENE; MURINE MACROPHAGES; MOUSE MACROPHAGES; MAMMALIAN-CELLS AB Picolinic acid, a catabolite of L-tryptophan, activates the transcription of the inducible nitric oxide synthase gene (iNOS) in IFN-gamma-treated murine macrophages. We performed functional studies on the 5' flanking region of the iNOS gene linked to a CAT reporter gene to identify the cis-acting element(s) responsible for the activation of iNOS transcription by picolinic acid. Transient transfection assays showed that the full-length iNOS promoter in the murine macrophage cell line ANA-1 was activated by the synergistic interaction between IFN-gamma and picolinic acid. Deletion or mutation of the iNOS promoter region from -227 to -209, containing a sequence homology to a hypoxia-responsive enhancer (iNOS-HRE), decreased picolinic acid- but not LPS-induced CAT activity by more than 70%. Functional studies using a tk promoter-CAT reporter gene plasmid demonstrated that the iNOS-HRE was sufficient to confer inducibility by picolinic acid but not by IFN-gamma or LPS. Electrophoretic mobility shift assays confirmed that picolinic acid alone induced a specific binding activity to the iNOS-HRE. Furthermore, we found that the INOS-HRE activity was inducible by hypoxia and that hypoxia in combination with IFN-gamma activated the iNOS promoter in transient transfection assays and induced iNOS transcription and mRNA expression. These data establish that the iNOS-HRE is a novel regulatory element of the iNOS promoter activity in murine macrophages and provide the first evidence that iNOS is a hypoxia-inducible gene. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP MELILLO, G (reprint author), NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,DIV CANC TREATMENT,FREDERICK,MD 21702, USA. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 NR 56 TC 475 Z9 480 U1 2 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1995 VL 182 IS 6 BP 1683 EP 1693 DI 10.1084/jem.182.6.1683 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TJ870 UT WOS:A1995TJ87000007 PM 7500013 ER PT J AU BRUTKIEWICZ, RR BENNINK, JR YEWDELL, JW BENDELAC, A AF BRUTKIEWICZ, RR BENNINK, JR YEWDELL, JW BENDELAC, A TI TAP-INDEPENDENT, BETA(2)-MICROGLOBULIN-DEPENDENT SURFACE EXPRESSION OF FUNCTIONAL-MOUSE CD1.1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CLASS-I MOLECULES; CYTOTOXIC LYMPHOCYTES-T; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; HISTOCOMPATIBILITY ANTIGENS; SPECIALIZED FUNCTIONS; MUTANT-CELLS; MHC; RECOGNITION; PEPTIDE AB CD1 molecules consist of beta(2)-microglobulin (beta(2)m) noncovalently complexed to a non-major histocompatibility complex (MHC)-encoded monomorphic integral membrane protein homologous to MHC class I alpha chains. Little is known about the requirements for cell surface expression and T cell recognition of CD1. We inserted the mouse CD1.1 gene into vaccinia virus to create a recombinant virus expressing CD1.1 under the control of a viral promoter. Using this recombinant virus to infect normal or mutant cell lines, we found that the expression of molecules reactive with the CD1.1-specific monoclonal antibody 3C11 requires the expression of beta(2)m but was not affected by the absence of the MHC-encoded peptide transporter (TAP). Consistent with these results, IL-2 production by the mCD1.1-specific T cell hybridoma DN32.D3 was induced by thymocytes from normal mice or mice with a homozygous deletion of the TAP1 gene, but not by thymocytes from mice with a homozygous deletion of the beta(2)m gene. These results indicate that expression of functional mCD1.1 occurs in a beta(2)m-dependent, TAP-independent manner. C1 PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08540. RP BRUTKIEWICZ, RR (reprint author), NIAID,VIRAL DIS LAB,ROOM 213,BLDG 4,BETHESDA,MD 20892, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 58 TC 143 Z9 143 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1995 VL 182 IS 6 BP 1913 EP 1919 DI 10.1084/jem.182.6.1913 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TJ870 UT WOS:A1995TJ87000031 PM 7500037 ER PT J AU ROMAGNOLI, P GERMAIN, RN AF ROMAGNOLI, P GERMAIN, RN TI INHIBITION OF INVARIANT CHAIN-(II)-CALNEXIN INTERACTION RESULTS IN ENHANCED DEGRADATION OF II BUT DOES NOT PREVENT THE ASSEMBLY OF ALPHA-BETA-II COMPLEXES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MHC CLASS-II; CELL-SURFACE EXPRESSION; HLA-DR MOLECULES; ENDOPLASMIC-RETICULUM; HISTOCOMPATIBILITY ANTIGENS; MICE LACKING; PEPTIDE; TRANSPORT; PROTEIN; CHAPERONE AB Calnexin is a resident protein of the endoplasmic reticulum (ER) that associates with nascent protein chains. Among the newly synthesized integral membrane proteins known to bind to calnexin is invariant chain (Ii), and Ii release from calnexin coincides with proper assembly with major histocompatibility complex (MHC) class II heterodimers. Although calnexin association with several membrane glycoproteins depends on interactions involving N-linked glycans, we previously reported that a truncation mutant oi mouse Ii (mIi1-107) lacking both N-glycosylation sites was highly effective in associating with MHC class II heterodimers and escorting these dimers through the secretory pathway. This could indicate that calnexin, despite binding to both Ii and class II, is not necessary for the proper interaction of these proteins, or that in contrast to most membrane glycoproteins, the N-linked glycans of Ii are not critical to its interaction with this chaperone. To examine this issue, we have directly explored the binding of calnexin to both Ii truncation mutants lacking the typical sites of N-glycosylation or Ii produced in cells treated with tunicamycin to prevent glycan addition. These experiments revealed that either method of eliminating N-linked carbohydrates on Ii also inhibited association with calnexin. A lumenally truncated form of Ii (mIi1-131) that still has N-linked carbohydrates showed a decreased affinity for calnexin compared with intact Ii, however, indicating that calnexin-Ii binding is not determined solely by the sugar moieties. All forms of Ii lacking N-linked sugars and showing defective association with calnexin also had enhanced rates of preendosomal degradation. Despite this effect on degradation rate, tunicamycin treatment did not inhibit the association of class II with glycan-free Ii. These data support the view that calnexin is not an absolute requirement for the proper assembly of class II-Ii nonamers, but rather acts primarily to retain Ii in the ER and to inhibit its degradation. These two properties of calnexin-Ii interaction may help ensure that sufficient intact Ii is available for efficient inactivation of the binding sites of newly synthesized class II molecules, while limiting the ability of excess free Ii to alter the transport properties of the early endocytic pathway. C1 NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892. RI Romagnoli, Paola/K-2237-2014 NR 64 TC 24 Z9 24 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1995 VL 182 IS 6 BP 2027 EP 2036 DI 10.1084/jem.182.6.2027 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TJ870 UT WOS:A1995TJ87000042 PM 7500048 ER PT J AU BOCK, TA ORLIC, D DUNBAR, CE BROXMEYER, HE BODINE, DM AF BOCK, TA ORLIC, D DUNBAR, CE BROXMEYER, HE BODINE, DM TI IMPROVED ENGRAFTMENT OF HUMAN HEMATOPOIETIC-CELLS IN SEVERE COMBINED IMMUNODEFICIENT (SCID) MICE CARRYING HUMAN CYTOKINE TRANSGENES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID UMBILICAL-CORD BLOOD; IMMUNE-DEFICIENT MICE; HUMAN BONE-MARROW; STEM-CELLS; PROGENITOR CELLS; HU MOUSE; TRANSPLANTATION; DEFINITION; CHIMERAS; MUTATION AB We have generated immunodeficient scid(-)/scid(-) (SCID)-transgenic mice expressing the genes for human interleukin 3, granulocyte/macrophage-colony stimulating factor, and stem cell factor. We have compared engraftment and differentiation of human hematopoietic cells in transgenic SCID mice with two strains of nontransgenic SCID mice. Human bone marrow cells carrying the CD34 antigen or human umbilical cord blood were injected into sublethally irradiated recipients. Human DNA was detected by polymerase chain reaction in peripheral blood and bone marrow of 14 of 28 transgenic SCID mice after transplantation, but in only 2 of 15 nontransgenic SCID littermates at a 10-fold lower level. Bone marrow cultures 8 wk after transplantation of cord blood gave rise to human burst-forming unit erythroid, colony-forming unit granulocyte/macrophage, or granulocyte/erythroid/macrophage/megakaryocyte colonies. Engraftment was observed for up to 6 mo in transgenic SCID mice, twice as long as nontransgenic littermates or previous studies in which transplanted SCID mice were given daily injections of growth factors. We conclude that the level and duration of engraftment of human cells in SCID mice can be improved by expression of human cytokine transgenes and that transgenic SCID mice are an efficient model system for the study of human hematopoiesis. C1 NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,HEMATOPOIESIS SECT,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. FU NCI NIH HHS [R37 CA36464]; NHLBI NIH HHS [R0I HL 46549, R0I HL 54037] NR 42 TC 63 Z9 64 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1995 VL 182 IS 6 BP 2037 EP 2043 DI 10.1084/jem.182.6.2037 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TJ870 UT WOS:A1995TJ87000043 PM 7500049 ER PT J AU BENDELAC, A AF BENDELAC, A TI POSITIVE SELECTION OF MOUSE NK1(+) T-CELLS BY CD1-EXPRESSING CORTICAL THYMOCYTES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID LYMPHOKINE SECRETION; HEMATOPOIETIC-CELLS; DEFICIENT MICE; GENE FAMILY; EXPRESSION; CD4+; CD1; CHAIN; SUBSET; THYMUS AB Mouse NK1(+) T cells constitute a subset of alpha/beta TCR(+) T cells that specialize in the rapid production of cytokines, in particular IL-4, and may promote the differentiation of Th2-type CD4 T cells. Their TCRs, like those of a homologous subset of human T cells, use an invariant TCR alpha chain and were recently shown to be specific for the beta 2-microglobulin-associated, MHC class I-like CD1 molecules, which are encoded outside the MHC. In contrast to mainstream thymocytes, which recognize their positively selecting MHC ligand on thymic epithelial cells, positive selection of NK1(+) T cells requires their CD1 ligand to be expressed on bone marrow-derived cells. To investigate the nature of the bone marrow-derived cell involved, chimeric mice were constructed with tissues from normal, SCID, and MHC-deficient mice, so that CD1 could be selectively expressed by different subsets of bone marrow-derived cells in the thymus. CD1 expression was also directly assessed using an anti-CD1 mAb, and a CD1-specific T cell hybridoma. The results suggest that immature (CD4(+)8(+) double-positive) cortical thymocytes are the source of CD1 presentation for positive selection of NK1(+) T cells. C1 NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. RP BENDELAC, A (reprint author), PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544, USA. NR 38 TC 363 Z9 368 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1995 VL 182 IS 6 BP 2091 EP 2096 DI 10.1084/jem.182.6.2091 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TJ870 UT WOS:A1995TJ87000048 PM 7500054 ER PT J AU JOHNSON, DN YANTIS, S AF JOHNSON, DN YANTIS, S TI ALLOCATING VISUAL-ATTENTION - TESTS OF A 2-PROCESS MODEL SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-HUMAN PERCEPTION AND PERFORMANCE LA English DT Article ID MINDS EYES MOVEMENT; SELECTIVE ATTENTION; SIGNALS AB Observers require less time to identify a visual target when its location is cued in advance than when it is not cued, and the magnitude of the improvement depends on the validity of the cue. According to J. Jonides's (1983) 2-process model, there exist 2 possible modes of attentional readiness: a focused-attention mode and a diffuse-attention mode. Observers are assumed to enter the focused-attention mode on a proportion of trials that matches the validity of the cue and to enter the diffuse-attention mode on the remaining trials. The present experiment tested and rejected the response time mixture prediction of the 2-process model. An instance of the class of 1-process models in which perceptual objects are sampled in parallel according to, the validity of the cue was evaluated. A stochastic simulation of the model yielded results that paralleled those of the experiment. C1 JOHNS HOPKINS UNIV,DEPT PSYCHOL,BALTIMORE,MD 21218. NIAAA,CLIN STUDIES LAB,COGNIT NEUROSCI SECT,BETHESDA,MD. RI Yantis, Steven/A-7488-2009 NR 20 TC 29 Z9 29 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0096-1523 J9 J EXP PSYCHOL HUMAN JI J. Exp. Psychol.-Hum. Percept. Perform. PD DEC PY 1995 VL 21 IS 6 BP 1376 EP 1390 DI 10.1037//0096-1523.21.6.1376 PG 15 WC Psychology; Psychology, Experimental SC Psychology GA TG918 UT WOS:A1995TG91800010 PM 7490586 ER PT J AU Bustamante, JO Prendergast, R Hanover, JA Oberleithner, H Liepins, A AF Bustamante, JO Prendergast, R Hanover, JA Oberleithner, H Liepins, A TI Macromolecular translocation reduces ion flow along nuclear pores: Relevance to measuring transcriptional control mechanism SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 MEM UNIV NEWFOUNDLAND,SCH MED,DIV BASIC MED SCI,ST JOHNS,NF,CANADA. JOHNS HOPKINS UNIV,SCH MED,WILMER EYE INST,BALTIMORE,MD 21205. NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD. UNIV WURZBURG,DEPT PHYSIOL,W-8700 WURZBURG,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1995 VL 106 IS 6 BP 51 EP 51 PG 2 WC Physiology SC Physiology GA TM544 UT WOS:A1995TM54400061 ER PT J AU Clay, JR Kuzirian, A AF Clay, JR Kuzirian, A TI Potassium ion channels on the move: A characterization of squid axoplasmic vesicles which contain K+ channels SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 MARINE BIOL LAB,WOODS HOLE,MA 02543. NIH,NEUROPHYSIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1995 VL 106 IS 6 BP 77 EP 77 PG 1 WC Physiology SC Physiology GA TM544 UT WOS:A1995TM54400087 ER PT J AU MAN, YG BALL, WD CULP, DJ HAND, AR MOREIRA, JE AF MAN, YG BALL, WD CULP, DJ HAND, AR MOREIRA, JE TI PERSISTENCE OF A PERINATAL CELLULAR PHENOTYPE IN SUBMANDIBULAR GLANDS OF ADULT-RAT SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article ID CYSTEINE PROTEINASE-INHIBITOR; SUB-MANDIBULAR GLAND; ISOPROTERENOL-TREATED RATS; ACID-RICH PROTEINS; SECRETORY PROTEINS; NEONATAL RAT; MULTIGENE FAMILY; MUCIN-GLYCOPROTEIN; MOLECULAR-CLONING; SALIVARY-GLANDS AB In the perinatal submandibular gland (SMG) of the rat, Type I cells secrete protein C (89 KD) and Type III cells secrete B1-immunoreactive proteins (20-30 KD); both cell types secrete protein D (175 KD). After the disappearance of both perinatal cell types from the maturing acini, only cells of the intercalated ducts (ID) show strong reactivity for the perinatal antigens. In adult ID, light and electron microscopic immunocytochemical analysis showed that most cells had either C or B1 reactivity, a few had either C and D or B1 and D reactivities, and some cells were unreactive for all of the perinatal proteins. Occasional dusters of ''adult'' acini, however, were strongly positive for B1 and for D, and these dusters were negative for a typical adult acinar marker, the glutamine/glutamic acid-rich proteins (GRP). Also seen in some preparations were a few anomalous acini with the histological appearance of sublingual (SLG) acini. These were negative for the perinatal and adult submandibular gland marker proteins but reactive with an antibody against SLG mucin. We suggest that the B1-positive acini in the adult SMG consist of newly differentiated replacement cells that have arisen from the ID, and that the anomalous mucous acini are, phenotypically, SLG acini that have differentiated within the SMG parenchyma. C1 HOWARD UNIV,COLL MED,DEPT ANAT,WASHINGTON,DC 20059. HOWARD UNIV,COLL MED,CTR CANC,WASHINGTON,DC 20059. UNIV ROCHESTER,MED CTR,DEPT DENT RES,ROCHESTER,NY 14642. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. FU NIDCR NIH HHS [DE-07003, DE-06635, DE-10480] NR 53 TC 52 Z9 53 U1 0 U2 2 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 1995 VL 43 IS 12 BP 1203 EP 1215 PG 13 WC Cell Biology SC Cell Biology GA TE947 UT WOS:A1995TE94700003 PM 8537636 ER PT J AU DING, L GREEN, JM THOMPSON, CB SHEVACH, EM AF DING, L GREEN, JM THOMPSON, CB SHEVACH, EM TI B7/CD28-DEPENDENT AND B7/CD28-INDEPENDENT INDUCTION OF CD40 LIGAND EXPRESSION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HELPER T-CELLS; VIVO CD40-GP39 INTERACTIONS; DEPENDENT HUMORAL IMMUNITY; X-LINKED IMMUNODEFICIENCY; HYPER-IGM SYNDROME; B-CELLS; MONOCLONAL-ANTIBODIES; COSTIMULATORY ACTIVITY; DEFECTIVE EXPRESSION; COGNATE INTERACTIONS AB The induction of a T cell-dependent Ab response is mediated by the interaction of the T cell activation Ag, CD40 ligand (CD40L), with CD40. Since this interaction is independent of Ag, coreceptors such as CD4, and MHC molecules, the expression of the CD40L must be strictly regulated or B cell-mediated autoimmunity may be produced. In this study, we examined the requirements for costimulatory signals for induction of CD40L expression in vitro and in vivo on CD4(+) T cells from normal and CD28-deficient mice following stimulation with anti-CD3, Con A, or specific peptide Ag. Expression of B7-1 was both necessary and sufficient for induction of the CD40L on normal CD4(+) T cells when L cell transfectants were used as APCs. When normal accessory cell populations were used, only partial inhibition of induction of the CD40L was observed with reagents that inhibit B7/CD28 interactions. Furthermore, the CD40L could be induced on CD4(+) T cells from CD28-deficient mice, Thus, non-B7/CD28 cellular interactions can also mediate the costimulatory signals needed for induction of CD40L expression. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. UNIV CHICAGO,DEPT MED,GWEN KNAPP CTR LUPUS & IMMUNOL RES,CHICAGO,IL 60637. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 67 TC 84 Z9 84 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1995 VL 155 IS 11 BP 5124 EP 5132 PG 9 WC Immunology SC Immunology GA TF686 UT WOS:A1995TF68600006 PM 7594521 ER PT J AU TORTOLANI, PJ LAL, BK RIVA, A JOHNSTON, JA CHEN, YQ REAMAN, GH BECKWITH, M LONGO, D ORTALDO, JR BHATIA, K MCGRATH, I KEHRL, J TUSCANO, J MCVICAR, DW OSHEA, JJ AF TORTOLANI, PJ LAL, BK RIVA, A JOHNSTON, JA CHEN, YQ REAMAN, GH BECKWITH, M LONGO, D ORTALDO, JR BHATIA, K MCGRATH, I KEHRL, J TUSCANO, J MCVICAR, DW OSHEA, JJ TI REGULATION OF JAK3 EXPRESSION AND ACTIVATION IN HUMAN B-CELLS AND B-CELL MALIGNANCIES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; GAMMA SIGNAL-TRANSDUCTION; INTERLEUKIN-2 RECEPTOR; INTERFERON-GAMMA; IL-2 RECEPTOR; LYMPHOMA; GROWTH; LINES; ASSOCIATION; CHAIN AB Members of the Janus family (JAK) of protein tyrosine kinases are critical enzymes in signaling pathways via hematopoietin receptors. We have cloned JAK3, which unlike other known family members (JAK1, JAK2, and TYK2) is preferentially expressed in hematopoietic cells but not in a variety of other cells. Functionally, JAK3 and JAK1 are coupled to the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15 in T cells and NK cells. Because of the importance of IL-2, IL-4, and IL-7 in B cell physiology, we sought to determine whether JAK3 was also present in B lymphocytes and whether it was involved in signaling via cytokines that are important for B cell development and function. In this report, we demonstrate that JAK3 is expressed in normal human peripheral blood B cells at levels that are comparable to those in T cells. In addition, the levels were found to be markedly up-regulated following stimulation with staphylococcal protein A Cowan and anti-CD40 Abs. In addition, IL-4 and IL-7 induced the rapid tyrosine phosphorylation of JAK3 and JAK1, and IL-4 activated both JAK3 and JAK1 phosphotransferase activity. JAK3 protein was also detected in immature B cell lines, but not in more well differentiated cell lines. Additionally, JAK3 was detected in lysates from bone marrow lymphoblasts of patients with B cell precursor acute lymphocytic leukemia and cell lines derived from human B cell lymphomas. Together, these data suggest that the regulation of JAK3 expression and activity is likely to be important in B cell development and function. C1 NIAMSD,LYMPHOCYTE CELL BIOL SECT,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT HEMATOL & ONCOL,WASHINGTON,DC 20010. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,OFF ASSOCIATE DIRECTOR,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. RI McVicar, Daniel/G-1970-2015; OI Kehrl, John/0000-0002-6526-159X NR 51 TC 66 Z9 66 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1995 VL 155 IS 11 BP 5220 EP 5226 PG 7 WC Immunology SC Immunology GA TF686 UT WOS:A1995TF68600018 PM 7594533 ER PT J AU FORCE, WR WALTER, BN HESSION, C TIZARD, R KOZAK, CA BROWNING, JL WARE, CF AF FORCE, WR WALTER, BN HESSION, C TIZARD, R KOZAK, CA BROWNING, JL WARE, CF TI MOUSE LYMPHOTOXIN-BETA RECEPTOR - MOLECULAR-GENETICS, LIGAND-BINDING, AND EXPRESSION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; HETEROMERIC COMPLEX; CELL-SURFACE; T-CELL; TNF; PROMOTER; PROTEIN; MURINE; MONOCYTOGENES; LOCALIZATION AB Lymphotoxin (LT)-alpha beta heterotrimer is a membrane-anchored ligand expressed by activated T cells which binds specifically to the LT beta receptor (LT beta R), a member of the TN beta R family. The LT beta R is implicated as a critical element in controlling lymph node development and cellular immune reactions. To address this hypothesis we have isolated a mouse cDNA encoding a single transmembrane protein of 415 amino acids with 76% identity to human LT beta R. The receptor function of this molecule was demonstrated by the ability of the extracellular domain, constructed as a chimera with the Fc region of IgG1, to bind to LT alpha beta complexes expressed on the surface of activated T cells or insect cells infected with baculoviruses containing LT alpha and LT beta cDNAs. The gene encoding mouse LT beta R, Ltbr, contains 10 exons spanning 6.9 kb and maps to mouse chromosome 6, which is closely linked to Tnfr1, consistent with the tight linkage of the human homologue of these genes on chromosome 12p13. Mouse LT beta R mRNA is expressed by cell lines of monocytic and epithelial origin but not by a CTL line, and in vivo it is constitutively expressed in visceral and lymphoid tissues. The delineation of the structure of the mouse LT beta R will aid investigations into the role of this cytokine-receptor system in immune function and development. C1 UNIV CALIF RIVERSIDE,DIV BIOMED SCI,RIVERSIDE,CA 92521. BIOGEN INC,CAMBRIDGE,MA 02142. NIAID,BETHESDA,MD 20892. OI Browning, Jeffrey/0000-0001-9168-5233 FU NIAID NIH HHS [AI33068] NR 44 TC 111 Z9 112 U1 3 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1995 VL 155 IS 11 BP 5280 EP 5288 PG 9 WC Immunology SC Immunology GA TF686 UT WOS:A1995TF68600026 PM 7594541 ER PT J AU SWIETER, M BERENSTEIN, EH SIRAGANIAN, RP AF SWIETER, M BERENSTEIN, EH SIRAGANIAN, RP TI PROTEIN-TYROSINE-PHOSPHATASE ACTIVITY ASSOCIATES WITH THE HIGH-AFFINITY IGE RECEPTOR AND DEPHOSPHORYLATES THE RECEPTOR SUBUNITS, BUT NOT LYN OR SYK SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEMATOPOIETIC-CELL PHOSPHATASE; IMMUNOGLOBULIN-E RECEPTORS; LEUKOCYTE-COMMON ANTIGEN; HISTAMINE-RELEASE; PHOSPHOTYROSINE PHOSPHATASE; MONOCLONAL-ANTIBODIES; RBL-2H3 CELLS; PHOSPHORYLATION; STIMULATION; AGGREGATION AB Protein tyrosine phosphorylation is an early event in the high affinity IgE receptor (Fc epsilon RI)-mediated signaling cascade leading to secretion in mast cells. Numerous proteins, including the beta- and gamma-subunits of Fc epsilon RI, become tyrosine phosphorylated after receptor aggregation, Dephosphorylation of these proteins may be important to reverse and limit transmembrane signaling. RBL-2H3 mast cell lysates were found to contain protein tyrosine phosphatase activity that dephosphorylated the tyrosine-phosphorylated beta- and gamma-subunits of Fc epsilon RI. The protein tyrosine phosphatase activity associated with Fc epsilon RI and was equally present with receptors from nonactivated and stimulated cells. Moreover, the phosphatase eluted from the immunoprecipitates and, when added back, dephosphorylated both tyrosine-phosphorylated beta- and gamma-subunits, but not tyrosine-phosphorylated Lyn or Syk. These results strongly suggest that the IgE receptor-associated protein tyrosine phosphatase may regulate the steady state level of tyrosylphosphate of the beta- and gamma-subunits and, therefore, may modulate the interaction of these subunits with other downstream molecules, such as Syk. RP SWIETER, M (reprint author), NIDR,IMMUNOL LAB,BLDG 10,ROOM 1N106,BETHESDA,MD 20892, USA. NR 45 TC 25 Z9 25 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1995 VL 155 IS 11 BP 5330 EP 5336 PG 7 WC Immunology SC Immunology GA TF686 UT WOS:A1995TF68600032 PM 7594547 ER PT J AU HARA, T BACON, KB CHO, LC YOSHIMURA, A MORIKAWA, Y COPELAND, NG GILBERT, DJ JENKINS, NA SCHALL, TJ MIYAJIMA, A AF HARA, T BACON, KB CHO, LC YOSHIMURA, A MORIKAWA, Y COPELAND, NG GILBERT, DJ JENKINS, NA SCHALL, TJ MIYAJIMA, A TI MOLECULAR-CLONING AND FUNCTIONAL-CHARACTERIZATION OF A NOVEL MEMBER OF THE C-C CHEMOKINE FAMILY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MOUSE CHROMOSOME-11; CYTOKINE FAMILY; EXPRESSION; GENE; LINKAGE; ALPHA; INTERLEUKIN-6; CONSERVATION; BIOLOGY; MAP AB Chemokines play an important role in immune and inflammatory responses by inducing migration and adhesion of leukocytes. We have isolated a novel chemokine cDNA, designated CCF18, from a cDNA library of an IL-3-dependent murine pro-B cell line, Ba/F3. The cDNA encodes a protein structurally related to the C-C chemokine members. Among this family, C10 shows the highest homology to CCF18, and MIP-1 alpha also has a significant homology but to a lesser extent, CCF18 produced from COS cells induced chemotaxis and Ca2+ flux in CD4(+) T cell clones, Moreover, prior administration of MIP-1 alpha desensitized the cells to CCF18. The CCF18 gene (Scya10) was mapped to a middle region of murine chromosome 11, where other genes for several C-C chemokine members are localized. These results clearly indicate that CCF18 is a new member of the C-C chemokine family, Since a high level of CCF18 mRNA is constitutively expressed in macrophage and myeloid cell lines, CCF18 may play a role in inflammatory processes. C1 DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. UNIV TOKYO,INST MOLEC & CELLULAR BIOSCI,TOKYO,JAPAN. KURUME UNIV,INST LIFE SCI,FUKUOKA,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LAB,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Yoshimura, Akihiko/K-5515-2013 FU NCI NIH HHS [N01-CO-46000] NR 39 TC 40 Z9 41 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1995 VL 155 IS 11 BP 5352 EP 5358 PG 7 WC Immunology SC Immunology GA TF686 UT WOS:A1995TF68600035 PM 7594550 ER PT J AU WIDEROFF, L SCHIFFMAN, MH NONNENMACHER, B HUBBERT, N KIRNBAUER, R GREER, CE LOWY, D LORINCZ, AT MANOS, MM GLASS, AG SCOTT, DR SHERMAN, ME KURMAN, RJ BUCKLAND, J TARONE, RE SCHILLER, J AF WIDEROFF, L SCHIFFMAN, MH NONNENMACHER, B HUBBERT, N KIRNBAUER, R GREER, CE LOWY, D LORINCZ, AT MANOS, MM GLASS, AG SCOTT, DR SHERMAN, ME KURMAN, RJ BUCKLAND, J TARONE, RE SCHILLER, J TI EVALUATION OF SEROREACTIVITY TO HUMAN PAPILLOMAVIRUS TYPE-16 VIRUS-LIKE PARTICLES IN AN INCIDENT CASE-CONTROL STUDY OF CERVICAL NEOPLASIA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID L1 PROTEIN; INFECTION; EXPRESSION; CELLS AB An ELISA to detect serum IgG antibody response to human papillomavirus (HPV) type 16 virus-like particles (VLPs) was evaluated in a case-control study of cervical neoplasia, nested within a prospective cohort study. Subjects included 688 controls with continued normal cytology and 152 cases with confirmed incident squamous intraepithelial lesions who were tested for DNA of a broad spectrum of HPV types at cohort enrollment and follow-up. Of controls, 16.6% were seropositive compared with 30.8% and 52.4% of cases with low- and high-grade lesions, respectively. Of HPV-16 DNA-negative subjects, 16.5% were seropositive. Seropositivity increased from 22.2% in subjects who were HPV-16 DNA-positive by polymerase chain reaction once only (enrollment or follow-up) to 83.3% in those who were HPV-16 DNA-positive at both time points. These data imply that serum antibody to HPV-16 VLPs is a relatively sensitive indicator of persisting cervical HPV-16 infection. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. DIGENE DIAGNOST & INFORMAT MANAGEMENT SERV,SILVER SPRING,MD. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR. CETUS CORP,EMERYVILLE,CA 94608. RP WIDEROFF, L (reprint author), NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,EPN 443,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Hernandez, Jessica/G-6527-2011 NR 21 TC 121 Z9 123 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1995 VL 172 IS 6 BP 1425 EP 1430 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TF776 UT WOS:A1995TF77600001 PM 7594698 ER PT J AU KARRON, RA WRIGHT, PF NEWMAN, FK MAKHENE, M THOMPSON, J SAMORODIN, R WILSON, MH ANDERSON, EL CLEMENTS, ML MURPHY, BR BELSHE, RB AF KARRON, RA WRIGHT, PF NEWMAN, FK MAKHENE, M THOMPSON, J SAMORODIN, R WILSON, MH ANDERSON, EL CLEMENTS, ML MURPHY, BR BELSHE, RB TI A LIVE HUMAN PARAINFLUENZA TYPE-3 VIRUS-VACCINE IS ATTENUATED AND IMMUNOGENIC IN HEALTHY INFANTS AND CHILDREN SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID YOUNG-CHILDREN; WEANLING HAMSTERS; AVIAN-HUMAN; COLD; CHIMPANZEES; INFECTION; MUTANT; EPIDEMIOLOGY; VOLUNTEERS; H1N1 AB The safety, infectivity, immunogenicity, and phenotypic stability of the cold-passaged (cp) candidate vaccine cp-45, a cold-adapted (ca), temperature-sensitive (ts) mutant of the JS strain of human parainfluenza virus type 3 (HPIV-3), was evaluated in 114 children 6 months to 10 years old in a randomized, placebo-controlled, double-blind trial. The cp-45 vaccine was well tolerated when given intranasally to parainfluenza virus type 3 (PIV-3)-seropositive and -seronegative children. With 10(4) or 10(5) TCID50 of cp-45 vaccine, 86% of seronegative vaccinees were infected, 83% of whom shed virus at a mean peak titer of 10(2.2) pfu/ml. Virus present in respiratory specimens retained the ts phenotype, and each of 86 PIV-3 isolates tested retained both the ca and ts phenotypes. One dose of 10(5) TCID50 of vaccine induced a serum hemagglutination-inhibiting antibody response in 81% of vaccinees; the geometric mean titer was 1:32. These studies indicate that the cp-45 HPIV-3 vaccine is satisfactorily attenuated, infectious, immunogenic, and phenotypically stable and merits further evaluation in infants and young children. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,VACCINE EVALUAT UNIT,NASHVILLE,TN 37212. ST LOUIS UNIV,CTR VACCINE DEV,DEPT INTERNAL MED,DIV INFECT DIS,ST LOUIS,MO 63103. ST LOUIS UNIV,CTR VACCINE DEV,DEPT PEDIAT,DIV INFECT DIS,ST LOUIS,MO 63103. VET ADM MED CTR,ST LOUIS,MO. RP KARRON, RA (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR IMMUNIZAT RES,DEPT INT HLTH,HAMPTON HOUSE 125,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [AI-05050, AI-05051, AI-15095] NR 35 TC 82 Z9 82 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1995 VL 172 IS 6 BP 1445 EP 1450 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TF776 UT WOS:A1995TF77600004 PM 7594701 ER PT J AU MEHENDALE, SM RODRIGUES, JJ BROOKMEYER, RS GANGAKHEDKAR, RR DIVEKAR, AD GOKHALE, MR RISBUD, AR PARANJAPE, RS SHEPHERD, ME ROMPALO, AE SULE, RR TOLAT, SN JADHAV, VD QUINN, TC BOLLINGER, RC AF MEHENDALE, SM RODRIGUES, JJ BROOKMEYER, RS GANGAKHEDKAR, RR DIVEKAR, AD GOKHALE, MR RISBUD, AR PARANJAPE, RS SHEPHERD, ME ROMPALO, AE SULE, RR TOLAT, SN JADHAV, VD QUINN, TC BOLLINGER, RC TI INCIDENCE AND PREDICTORS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SEROCONVERSION IN PATIENTS ATTENDING SEXUALLY-TRANSMITTED DISEASE CLINICS IN INDIA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RISK-FACTORS; TRANSMISSION; PROSTITUTES; INFECTION; NAIROBI; FEMALE AB The first estimates of the seroincidence of human immunodeficiency virus type 1 (HIV-1) and of the risk factors for seroconversion in a cohort of high-risk patients attending sexually transmitted disease (STD) clinics in India are reported. Between 1993 and 1995, 851 HIV-1-seronegative persons were evaluated prospectively every 3 months for HIV infection and biologic and behavioral characteristics. The overall incidence of HIV-1 was 10.2/100 person-years (95% confidence interval, 7.9-13.1). The incidence among commercial sex workers (CSWs) was 26.1/100 person-years, compared with 8.4 among non-CSWs. Recurrent genital ulcer disease and urethritis or cervicitis during the follow-up period were independently associated with a 7- (P < .001) and 3-fold (P = .06) increased risk of HIV-1 seroconversion, respectively. Because of the association of recurrent ulcerative and nonulcerative STDs with HIV-1 seroconversion in this setting, behavioral and biologic measures directed at the prevention and control of STDs would be expected to greatly reduce the transmission of HIV-1 infection in similar high-risk groups. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. BJ MED COLL,NATL AIDS RES INST,POONA,MAHARASHTRA,INDIA. DR KOTNIS MUNICIPAL DISPENSARY,POONA,MAHARASHTRA,INDIA. NIAID,BETHESDA,MD 20892. RI Quinn, Thomas/A-2494-2010 FU FIC NIH HHS [D43-TW0000]; NCRR NIH HHS [RR-00722]; NIAID NIH HHS [AI-33879] NR 21 TC 103 Z9 104 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1995 VL 172 IS 6 BP 1486 EP 1491 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TF776 UT WOS:A1995TF77600010 PM 7594707 ER PT J AU CHENG, G ICENOGLE, JP KIRNBAUER, R HUBBERT, NL STLOUIS, ME HAN, CL SVARE, EI KJAER, SK LOWY, DR SCHILLER, JT AF CHENG, G ICENOGLE, JP KIRNBAUER, R HUBBERT, NL STLOUIS, ME HAN, CL SVARE, EI KJAER, SK LOWY, DR SCHILLER, JT TI DIVERGENT HUMAN PAPILLOMAVIRUS TYPE-16 VARIANTS ARE SEROLOGICALLY CROSS-REACTIVE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID SEXUALLY-TRANSMITTED DISEASES; VIRUS; DNA; SEQUENCE; SPREAD; WOMEN AB It is not known whether DNA sequence variants of human papillomavirus type 16 (HPV-16) are distinct serotypes. To examine this question, the reactivities of women's sera from Zaire (n = 97) and Denmark (n = 123) were compared in IgG-specific ELISAs based on virus-like particles (VLPs) composed of the L1 major capsid protein derived from an HPV-16 variant common in central Africa (Z-1194) or one common in northern Europe (114K), These L1s differ in seven amino acids, There was a strong correlation between reactivity in the two assays for both sets of sera (correlation coefficients, 0.73 and 0.85 for Zairian and Danish sera, respectively), In only 1 serum was there evidence for a specific reaction to one but not the other VLP variant, The results support the conclusion that the virions of strains Z-1194 and 114K are serologically cross-reactive. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,ATLANTA,GA 30341. DANISH CANC SOC,DIV CANC EPIDEMIOL,COPENHAGEN,DENMARK. NR 16 TC 52 Z9 54 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1995 VL 172 IS 6 BP 1584 EP 1587 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TF776 UT WOS:A1995TF77600024 PM 7594721 ER PT J AU CARTWRIGHT, CP AF CARTWRIGHT, CP TI POLYMERASE CHAIN-REACTION RIBOTYPING - A UNIVERSAL APPROACH SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter RP CARTWRIGHT, CP (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BLDG 10,ROOM 2C-385,BETHESDA,MD 20892, USA. NR 3 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1995 VL 172 IS 6 BP 1638 EP 1638 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TF776 UT WOS:A1995TF77600042 PM 7594737 ER PT J AU Drew, PD Franzoso, G Becker, KG Bours, V Carlson, LM Siebenlist, U Ozato, K AF Drew, PD Franzoso, G Becker, KG Bours, V Carlson, LM Siebenlist, U Ozato, K TI NF kappa B and interferon regulatory factor 1 physically interact and synergistically induce major histocompatibility class I gene expression SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID ENHANCER-BINDING-PROTEIN; MHC CLASS-I; TRANSCRIPTION FACTOR; ONCOPROTEIN BCL-3; BETA; ALPHA; CELLS; DNA; SEQUENCE; ELEMENTS AB Major histocompatibility (MHC) class I gene expression is synergistically induced by the cytokines TNF-alpha and IFN-gamma. However, the mechanism that results in synergistic activation of these genes has remained unclear. We demonstrated here that TNF-alpha induced binding of NF kappa B p50 and p65 to the NF kappa B-like element of the MHC class I promoter termed region I and IFN-gamma induced binding of IRF-1 to the adjacent interferon consensus sequence (ICS), We further demonstrated that NF kappa B and IRF-1 physically interacted with each other and cooperatively induced MHC class I gene expression when cotransfected into CHP-126 neuroblastomas. These results provide a molecular mechanism by which TNF-alpha and IFN-gamma synergistically induce the expression of a variety of genes involved in immune responses, including MHC class I. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 37 TC 100 Z9 100 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD DEC PY 1995 VL 15 IS 12 BP 1037 EP 1045 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA TM414 UT WOS:A1995TM41400004 PM 8746784 ER PT J AU MAURER, D EBNER, C REININGER, B FIEBIGER, E KRAFT, D KINET, JP STINGL, G AF MAURER, D EBNER, C REININGER, B FIEBIGER, E KRAFT, D KINET, JP STINGL, G TI PERIPHERAL-BLOOD DENDRITIC CELLS EXPRESS FUNCTIONAL FC-EPSILON-RI SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAID,ROCKVILLE,MD. UNIV VIENNA,SCH MED,DEPT DERMATOL GEN & EXP PATHOL,DIAID,VIENNA,AUSTRIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1995 VL 105 IS 6 BP 10 EP 10 PG 1 WC Dermatology SC Dermatology GA TH090 UT WOS:A1995TH09000036 ER PT J AU LAZAROVA, Z YEE, C YANCEY, KB AF LAZAROVA, Z YEE, C YANCEY, KB TI ANTI-LAMININ-5 IGG INDUCES SUBEPIDERMAL BLISTERS IN ADULT BALB/C MICE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1995 VL 105 IS 6 BP 873 EP 873 PG 1 WC Dermatology SC Dermatology GA TH090 UT WOS:A1995TH09000109 ER PT J AU Komschlies, KL Grzegorzewski, KJ Wiltrout, RH AF Komschlies, KL Grzegorzewski, KJ Wiltrout, RH TI Diverse immunological and hematological effects of interleukin 7: Implications for clinical application SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE lymphopoiesis; myeloid progenitors; T cell function; cancer; AIDS; vaccine ID CYTOTOXIC LYMPHOCYTES-T; HUMAN PERIPHERAL-BLOOD; TUMOR-INFILTRATING LYMPHOCYTES; ACTIVATED KILLER-CELLS; BONE-MARROW; MURINE INTERLEUKIN-7; GROWTH-FACTOR; INTERFERON-GAMMA; PROGENITOR CELLS; B-LYMPHOPOIESIS AB Interleukin-7 (IL-7) was originally discovered to be a pre-B cell growth factor. Soon thereafter, a broader role for IL-7 in leukocyte development and function began to be identified, IL-7 now has been shown to be a critical cytokine for normal T and B lymphopoiesis and a mobilizer of pluripotent stem cells and myeloid progenitors, IL-7 has been demonstrated to enhance T cell function and induce cytokine expression in monocytes. Preclinical studies have already found that IL-7 could accelerate murine lymphocyte regeneration following chemotherapy and bone marrow transplantation, induce antitumor effects in mice, and expand anti-HIV-specific human T cells. Thus it is essential that further preclinical and clinical research be performed to evaluate IL-7 as a potential therapy for leukopenia, bone marrow/stem cell transplantation, cancer, and HIV/AIDS. C1 NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. RP Komschlies, KL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,BLDG 560,FREDERICK,MD 21702, USA. NR 138 TC 42 Z9 44 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 1995 VL 58 IS 6 BP 623 EP 633 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA TK772 UT WOS:A1995TK77200001 PM 7499959 ER PT J AU Dhawan, S Wahl, LM Heredia, A Zhang, YH Epstein, JS Meltzer, MS Hewlett, IK AF Dhawan, S Wahl, LM Heredia, A Zhang, YH Epstein, JS Meltzer, MS Hewlett, IK TI Interferon-gamma inhibits HIV-induced invasiveness of monocytes SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE interferon-gamma; human immunodeficiency virus monocytes; metalloproteinase; extracellular matrix ID AIDS; COLLAGENASE AB HIV-infected monocytes form highly invasive network on basement membrane matrix and secrete high levels of 92-kd metalloproteinase (MMP-9), an enzyme that degrades basement membrane proteins. In the present study, using matrigel as a model basement membrane system, we demonstrate that treatment of human immunodeficiency virus (HIV)-infected monocytes with interferon-gamma at 50 U/ml inhibited the ability of infected monocytes to form an invasive network on matrigel and their invasion through the matrigel matrix. These effects were associated with a significant reduction in the levels of MMP-9 produced by HIV-infected monocytes treated with interferon-gamma 1 day prior to infection with HIV as compared with that of untreated HIV-infected monocytes. Monocytes treated with interferon-gamma 1 day after HIV infection showed the presence of integrated HIV sequences; however, the levels of MMP-9 were substantially lower than those produced by monocytes inoculated with live HIV, heat-inactivated HIV, or even the control uninfected monocytes. Exposure of monocytes to heat-inactivated HIV did not result in increased invasiveness or high MMP-9 production, suggesting that regulation of metalloproteinase by monocytes was independent of CD4-gp120 interactions and required active virus infection. Furthermore, addition of interferon-gamma to monocytes on day 10 after infection inhibited MMP-9 production by more than threefold with no significant reduction of virus replication. These results indicate that the mechanism of interferon-gamma-induced down-regulation of MMP-9 levels and reduced monocyte invasiveness may be mediated by a mechanism independent of antiviral activity of IFN-gamma in monocytes. Down-regulation of MMP-9 in HIV-infected monocytes by interferon-gamma may play an important role in the control of HIV pathogenesis. C1 NIDR,IMMUNOL LAB,BETHESDA,MD 20892. WALTER REED ARMY INST RES,DEPT CELLULAR IMMUNOL,WASHINGTON,DC. RP Dhawan, S (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,MOLEC VIROL LAB,ROCKVILLE,MD 20852, USA. NR 11 TC 22 Z9 22 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 1995 VL 58 IS 6 BP 713 EP 716 PG 4 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA TK772 UT WOS:A1995TK77200012 PM 7499970 ER PT J AU OConnell, TM London, RE AF OConnell, TM London, RE TI Identification of 2-fluoro-2-deoxy-D-glucose metabolites by F-19{H-1} hetero-RELAY SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; CEREBRAL GLUCOSE-UTILIZATION; TRANSFER NMR-SPECTROSCOPY; F-19 NMR; COHERENCE-TRANSFER; HARTMANN-HAHN; RAT-BRAIN; PROTON; 2-DEOXY-2-FLUORO-D-GLUCOSE; ASSIGNMENTS AB It has been proposed that in mammalian systems the glucose analog 2-fluoro-2-deoxy-D-glucose (FDG) is phosphoryated and subsequently converted to the corresponding mannose derivative via the action of phosphoglucose isomerase. As is generally true in metabolic studies of fluorinated molecules, the fluorine spectrum alone is suggestive, without providing definitive structural evidence, while the use of H-1 NMR techniques generally suffers from a lack of adequate selectivity. A H-1-F-19 version of the hetero-RELAY experiment has been applied to this problem, Formation of the corresponding C-6 phosphorylated 2-FDG analog with hexokinase, followed by treatment of the resulting phosphorylated products with phosphoglucose isomerase, resulted in the observation of additional F-19 resonances consistent with the corresponding 2-fluoro-2-deoxy-D-mannose-6-phosphate metabolite. A more definitive product identification was obtained using the hetero-RELAY experiment, which provides a complete F-19-decoupled proton spectrum for each of the fluorinated species, (C) 1995 Academic Press, Inc. RP NIEHS, MOLEC BIOPHYS LAB, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 48 TC 5 Z9 5 U1 3 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD DEC PY 1995 VL 109 IS 3 BP 264 EP 269 DI 10.1006/jmrb.1995.9996 PG 6 WC Physics, Atomic, Molecular & Chemical SC Physics GA TN774 UT WOS:A1995TN77400004 PM 8542195 ER PT J AU MCNELLIS, D AF MCNELLIS, D TI A VIEW FROM BETHESDA - LESSONS LEARNED IN THE MATERNAL-FETAL MEDICINE UNITS NETWORK SO JOURNAL OF MATERNAL-FETAL INVESTIGATION LA English DT Editorial Material RP MCNELLIS, D (reprint author), NICHHD,PREGNANCY & PERINATOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-6322 J9 J MATERN-FETAL INVES JI J. Matern.-Fetal Invest. PD WIN PY 1995 VL 5 IS 1 BP 2 EP 3 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RD050 UT WOS:A1995RD05000001 ER PT J AU KISHIDA, T CHEN, F LERMAN, MI ZBAR, B AF KISHIDA, T CHEN, F LERMAN, MI ZBAR, B TI DETECTION OF GERMLINE MUTATIONS IN THE VON HIPPEL-LINDAU DISEASE GENE BY THE PRIMER SPECIFIED RESTRICTION MAP MODIFICATION METHOD SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; SMALL REGION; VHL LOCUS; DNA; LOCALIZATION; DIAGNOSIS; LINKAGE; MARKERS AB Von Hippel-Lindau disease (VHL) is an inherited disorder characterised by a predisposition to develop tumours in the eyes, central nervous system, kidneys, and adrenal glands. Recently the VHL gene was cloned and shown to be mutated in 75% of US and Canadian VHL families. To develop simple, rapid methods for the detection of mutations found in large numbers of affected people, we designed tests based on the primer specified restriction site modification method. These tests have proved useful in identifying asymptomatic mutated VHL gene carriers who have the nt 505 T to C mutation or the nt 686 T to C mutation. Together with an MspI digestion test which can detect a mutation hot spot in codon 238, polymerase chain reaction/restriction endonuclease based tests can now detect VHL mutations in more than 50% of VHL type 2 families. C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NR 24 TC 3 Z9 3 U1 0 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD DEC PY 1995 VL 32 IS 12 BP 938 EP 941 DI 10.1136/jmg.32.12.938 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA TJ588 UT WOS:A1995TJ58800005 PM 8825919 ER PT J AU Kovbasnjuk, O Chatton, JY Friauf, WS Spring, KR AF Kovbasnjuk, O Chatton, JY Friauf, WS Spring, KR TI Determination of the Na permeability of the tight junctions of MDCK cells by fluorescence microscopy SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE Na; cAMP; SBFO; protein kinase A; transference number ID CANINE KIDNEY-CELLS; ION SELECTIVITY; CYCLIC-AMP; EPITHELIUM; OUABAIN; SHAPE; CAMP; SIZE AB The kinetics of Na movement across the tight junctions of MDCK cells, grown on coverslips and perfused with HEPES or bicarbonate Ringer at 37 degrees C, were investigated after filling the lateral intercellular spaces (LIS) of the epithelium with SBFO, an Na-sensitive fluorescent dye. Dilution and bi-ionic potential measurements showed that MDCK cell tight junctions, although cation-selective, were poorly permeable to N-methyl-D-glucamine Cl (NMDG) but freely permeable to Li. In previous experiments in which Na was replaced by NMDG, a very slow decrease in LIS Na concentration (time constant = 4.8 min) resulted. In the present study, reduction of perfusate Na from 142 to 14 or 24 mM with Na replaced by Li caused LIS Na concentration to decrease with a time constant of 0.43 min. The time constant for Na increase of the LIS was 0.28 min, significantly shorter than that for Na decrease because of the additional component of transcellular Na influx. Ouabain eliminated the transcellular component and equalized the time constants for Na influx and efflux. These results were incorporated into a mathematical model which enabled calculation of the transcellular and paracellular Na fluxes during fluid reabsorption. Regulation of the Na permeability of individual tight junctions by protein kinase A (PKA) was evaluated by treating the monolayers with the Sp-cAMPS, a cAMP substitute, or Rp-cAMPS, a specific inhibitor of PKA. Stimulation of PKA strikingly increased tight junctional permeability while PKA inhibition diminished junctional Na permeability. C1 NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP Kovbasnjuk, O (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892, USA. NR 21 TC 18 Z9 18 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD DEC PY 1995 VL 148 IS 3 BP 223 EP 232 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA TM173 UT WOS:A1995TM17300002 PM 8747554 ER PT J AU Lockwich, T Chauthaiwale, J Ambudkar, SV Ambudkar, IS AF Lockwich, T Chauthaiwale, J Ambudkar, SV Ambudkar, IS TI Reconstitution of a passive Ca2+-transport pathway from the basolateral plasma membrane of rat parotid gland acinar cells SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE reconstitution; Calcium influx; basolateral membrane vesicles; proteoliposomes; parotid gland; octyl glucoside ID DEPENDENT CA-2+ TRANSPORT; SARCOPLASMIC-RETICULUM; CALCIUM CHANNELS; MAST-CELLS; INOSITOL PHOSPHATE; ATP HYDROLYSIS; ACTIVATION; VESICLES; RELEASE; ENTRY AB We have previously reported that rat parotid gland basolateral plasma membrane vesicles (BLMV) have a relatively high affinity Ca2+ transport pathway and an unsaturable Ca2+ flux component (Lockwich et al., 1994. J. Membrane Biol. 141:289-296). In this study, we have solubilized BLMV with octylglucoside (1.5%) and have reconstituted the solubilized proteins into proteoliposomes (PrL) composed of E. coli bulk phospholipids, by using a detergent dilution method. PrL exhibited 3-5-fold higher Ca-45(2+) influx than control liposomes (without protein). Ca2+ uptake into PrL was dependent on the [protein] in PrL and steady state [Ca2+] in PrL was in equilibrium with external [Ca2+]. These data demonstrate that a passive, protein-mediated Ca2+ transport has been reconstituted from BLMV into PrL. Ca-45(2+) influx into liposomes did not saturate with increasing [Ca2+] in the assay medium. In contrast, PrL displayed saturable Ca-45(2+) influx and exhibited a single Ca2+ flux component with an apparent K-Ca = 242 +/- 50.9 mu M and V-max = 13.5 +/- 1.14 nmoles Ca2+/mg protein/ minute. The K,, of Ca2+-transport in PrL was similar to that of the high affinity Ca2+ influx component in BLMV while the V-max was about 4-fold higher. The unsaturable Ca2+ flux component was not detected in PrL. Ca-45(2+) influx in PrL was inhibited by divalent cations in the order of efficacy, Zn2+ > Mn2+ > Co2+ = Ni2+, and appeared to be more sensitive to lower concentrations of Zn2+ than in BLMV. Consistent with our observations with BLMV, the carboxyl group reagent N,N'-dicyclohexylcarbodiimide (DCCD) inhibited the reconstituted Ca2+ transport in PrL. importantly, in both BLMV and PrL, DCCD induced a 40-50% decrease in V-max of Ca2+ transport without an alteration in K-Ca. These data strongly suggest that the high affinity, passive Ca2+ transport pathway present in BLMV has been functionally reconstituted into PrL. We suggest that this approach provides a useful experimental system towards isolation of the protein(s) involved in mediating Ca2+ influx in the rat parotid gland basolateral plasma membrane. C1 NATL INST HLTH,CLIN INVEST & PATIENT CARE BRANCH,SECRETORY PHYSIOL SECT,NIDR,BETHESDA,MD 20292. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV NEPHROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. RI Ambudkar, Suresh/B-5964-2008 NR 36 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD DEC PY 1995 VL 148 IS 3 BP 277 EP 285 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA TM173 UT WOS:A1995TM17300007 PM 8747559 ER PT J AU BOGDANOV, KY ZIMAN, BD SPURGEON, HA LAKATTA, EG AF BOGDANOV, KY ZIMAN, BD SPURGEON, HA LAKATTA, EG TI L-TYPE AND T-TYPE CALCIUM CURRENTS DIFFER IN FINCH AND RAT VENTRICULAR CARDIOMYOCYTES SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE CALCIUM CURRENTS; FINCH VENTRICULAR MYOCYTES; T TUBULES ID PHYSIOLOGICAL ION FLUX; PIG HEART-CELLS; CARDIAC MYOCYTES; CA-2+ CURRENTS; UNITARY PROPERTIES; MEMBRANE CURRENTS; ATRIAL MYOCYTES; PURKINJE-CELLS; CA2+ CHANNELS; MUSCLE-CELLS AB We compared L-type Ca current (I-CaL) and T-type Ca current (I-CaT) in finch and rat myocytes, using whole-cell patch clamp techniques. Cell capacitance averaged 50 +/- pF in finch (n = 25) v 145 +/- 8 pF in rat (n = 38) cells, P < 0.001. In cells bathed in 1 mM Ca-o at 22 degrees C, peak I-CaL amplitude, during a voltage clamp step (10 mM EGTA in pipette) from -45 mV to -5 mV, averaged 10.5 +/- 0.3 pA/pF in finch v 6.9 +/- 0.6 pA/pF, P < 0.001 in rat cells. I-CaL inactivation kinetics were faster in finch (4.6 +/- 0.3 ms) than in rat (13.4 +/- 1.3 ms) cells, P < 0.001. I-CaL was not detectable in rat cells (2 mM bathing [Ca]); but in finch cells, a large I-CaT which averaged 6.8 +/- 1.4 pA/pF was activated at -30 mV and was relatively insensitive to nitrendipine (0.1 mu M) The distinctive features of I-CaL and I-CaT in finch cells may have a role in the ability of the finch to achieve a very rapid heart rate. They may also facilitate excitation-Ca2+ release coupling in finch ventricular cells which are devoid of T tubules and have relatively few junctions between the sarcolemma and the sarcoplasmic reticulum. (C) 1995 Academic Press Limited C1 NATL INST HLTH, NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. NR 45 TC 27 Z9 27 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD DEC PY 1995 VL 27 IS 12 BP 2581 EP 2593 DI 10.1006/jmcc.1995.0045 PG 13 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA TK247 UT WOS:A1995TK24700006 PM 8825879 ER PT J AU Jiang, P Stone, S Wagner, R Wang, S Dayananth, P Kozak, CA Wold, B Kamb, A AF Jiang, P Stone, S Wagner, R Wang, S Dayananth, P Kozak, CA Wold, B Kamb, A TI Comparative analysis of Homo sapiens and Mus musculus cyclin-dependent kinase (CDK) inhibitor genes P16 (MTS1) and P15 (MTS2) SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE P16; P15; MTS1; MTS2; CDK inhibitor; gene conversion; mouse; human ID TYROSINE KINASE; IDENTIFICATION; CONVERSION; MOUSE; P21; DNA AB Cyclin-dependent kinase inhibitors are a growing family of molecules that regulate important transitions in the cell cycle. At least one of these molecules, p16, has been implicated in human tumorigenesis while its close homolog, p15, is induced by cell contact and transforming growth factor-beta (TGF-beta). To investigate the evolutionary and functional features of p15 and p16, we have isolated mouse (Mus musculus) homologs of each gene. Comparative analysis of these sequences provides evidence that the genes have similar functions in mouse and human. In addition, the comparison suggests that a gene conversion event is part of the evolution of the human p15 and p16 genes. C1 MYRIAD GENET INC,SALT LAKE CITY,UT 84108. CALTECH,DEPT BIOL,PASADENA,CA 91125. NIAID,BETHESDA,MD 20892. NR 36 TC 17 Z9 17 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD DEC PY 1995 VL 41 IS 6 BP 795 EP 802 PG 8 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA TM930 UT WOS:A1995TM93000016 PM 8587124 ER PT J AU Hoffman, SMG FernandezSalguero, P Gonzalez, FJ Mohrenweiser, HW AF Hoffman, SMG FernandezSalguero, P Gonzalez, FJ Mohrenweiser, HW TI Organization and evolution of the cytochrome P450 CYP2A-2B-2F subfamily gene cluster on human chromosome 19 SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE cytochrome P450; CYP2A; CYP2B; CYP2F; gene family; tandem duplication ID FLUORESCENCE INSITU HYBRIDIZATION; CDNA-DIRECTED EXPRESSION; INVERTED DUPLICATION; HIGH-RESOLUTION; HUMAN-LIVER; IDENTIFICATION; SUPERFAMILY; SEQUENCES; COUMARIN; FAMILY AB Cytochrome P450 genes from the CYP2A, CYP2B, and CYP2F subfamilies form a tight cluster which we have localized on the detailed physical map of human chromosome 19. The corresponding three gene subfamilies are also clustered in the mouse genome, on the region of chromosome 7 known to be syntenic to human chromosome 19. One hundred eight cosmid clones from the human P450 region were assembled into a single contig of 350 kb, restriction mapped, and probed with cDNAs from the three gene subfamilies. A total of 11 genes were identified in humans, including five from the 2A subfamily, three from the 2B subfamily, and three from the 2F subfamily; at least six of the 11 are pseudogenes. The organization of the genes, with members of the three subfamilies intermixed, indicates that the evolution of this gene cluster has been complex. The modern gene arrangement in humans is probably the result of a series of tandem duplications, plus at least one inverted duplication. The identification of all genes and pseudogenes in this cluster also makes it possible to determine the origins of some previously known variant P450 transcripts. C1 LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,BIOL & BIOL RES PROGRAM,LIVERMORE,CA 94551. NCI,BETHESDA,MD 20892. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 34 TC 68 Z9 72 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD DEC PY 1995 VL 41 IS 6 BP 894 EP 900 PG 7 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA TM930 UT WOS:A1995TM93000026 PM 8587134 ER PT J AU Jaworski, CJ AF Jaworski, CJ TI A reassessment of mammalian alpha A-crystallin sequences using DNA sequencing: Implications for anthropoid affinities of tarsier SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE alpha A-crystallin; Tarser; DNA sequencing; anthropoid ID MITOCHONDRIAL-DNA; MOLECULAR PHYLOGENY; NUCLEOTIDE-SEQUENCE; GENE; LENS; PRIMATES; EVOLUTION; MEGABATS; CHICKEN; POLYMERASE AB alpha A-crystallin, a major structural protein in the ocular lenses of all vertebrates, has been a valuable tool for molecular phylogenetic studies. This paper presents the complete sequence for human alpha A-crystallin derived from cDNA and genomic clones. The deduced amino acid sequence differs at two phylogenetically informative positions from that previously inferred from peptide composition. This led us to examine the same region of the alpha A-crystallin gene in 12 other mammalian species using direct sequencing of PCR-amplified genomic DNA. New sequences were added to the database, and corrections were made to all anthropoid sequences, defining clear synapomorphies for anthropoids as a clade distinct from prosimians. Within the anthropoids there are further synapomorphies delineating hominoids, Old World monkeys, and New World monkeys. Significantly, sequence revisions and the addition of new sequence for a prosimian, the sifaka, eliminate the previous support for the proposed anthropoid affinities of the tarsier inferred from alpha A-crystallin protein sequences. In addition, DNA sequences provide greater resolution of certain relationships. For example, although they are identical in protein sequence, comparison of DNA sequences clearly separates mouse and the common tree shrew, grouping the tree shrew closer to prosimians. These results show that adding DNA sequences to the to the existing alpha A-crystallin database can enhance its value in resolving phylogenetic relationships. RP Jaworski, CJ (reprint author), NEI,MOLEC & DEV BIOL LAB,MOLEC STRUCT & FUNCT SECT,ROOM 222,BLDG 6,BETHESDA,MD 20892, USA. NR 54 TC 18 Z9 22 U1 1 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD DEC PY 1995 VL 41 IS 6 BP 901 EP 908 DI 10.1007/BF00173170 PG 8 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA TM930 UT WOS:A1995TM93000027 PM 8587135 ER PT J AU Tomarev, SI Chung, S Piatigorsky, J AF Tomarev, SI Chung, S Piatigorsky, J TI Glutathione S-transferase and S-crystallins of cephalopods: Evolution from active enzyme to lens-refractive proteins SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE lens; squid; crystallin; glutathione; S-transferase; parallel evolution ID SITE-DIRECTED MUTAGENESIS; POLYMERASE CHAIN-REACTION; HOMEOBOX-CONTAINING GENE; PHYSICOCHEMICAL CHARACTERIZATION; 3-DIMENSIONAL STRUCTURE; CATALYTIC MECHANISM; SQUID; RECRUITMENT; RESOLUTION; SEQUENCE AB Our previous studies have shown that the S-crystallins of cephalopod (Ommastrephes sloani pacificus) eye lenses comprise a family of at least ten members which are evolutionarily related to glutathione S-transferase (GST, EC 2.5.1.18), Here we show by cDNA cloning that there are at least 24 different S-crystallins that are 46-99% identical to each other by amino acid sequence in the squid Loligo opalescens. In each species, all but one S-crystallin (SL11 in O. pacificus and Lops4 in L. opalescens) examined has an inserted central peptide of variable length and sequence. cDNA expression studies conducted in Escherichia coli showed that squid GST (which is expressed little in the lens) has very high enzymatic activity using 1-chloro-2, 4-dinitrobenzene (CDNB) as a substrate; by contrast, SL20-1 of O. pacificus and Lops12 of L. opalescens (which are encoded by abundant lens mRNAs) have no GST activity. Interestingly, SL11 and Lops4 have some enzymatic activity with the CDNB substrate. Site-specific mutations at Y7 or W38, both residues essential for activity of vertebrate GSTs, or insertion of the central peptide present in the inactive SL20-1, reduced the specific activity of squid GST by 30- to 100-fold. These data indicate that the S-crystallins consist of a family of enzymatically inactive proteins (when using CDNB as a substrate) which is considerably larger than previously believed and that GST activity was lost by gradual drift in sequence as well as by insertion of an extra peptide by exon shuffling. The results are also consistent with the idea that SL11 and Lops4 are orthologous crystallins representing the first descendants of the ancestral GST gene in the pathway which gave rise to the extensive S-crystallin family of lens proteins. RP Tomarev, SI (reprint author), NEI,MOLEC & DEV BIOL LAB,BLDG 6,ROOM 203,6 CTR DR MSC,BETHESDA,MD 20892, USA. NR 58 TC 29 Z9 29 U1 0 U2 10 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD DEC PY 1995 VL 41 IS 6 BP 1048 EP 1056 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA TM930 UT WOS:A1995TM93000043 PM 8587103 ER PT J AU Rappaport, J Arya, SK Richardson, MW BaierBitterlich, G Klotman, PE AF Rappaport, J Arya, SK Richardson, MW BaierBitterlich, G Klotman, PE TI Inhibition of HIV-1 expression by HIV-2 SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE HIV-1; HIV-2; molecular interference; gene therapy; gene expression ID IMMUNODEFICIENCY-VIRUS TYPE-2; LONG TERMINAL REPEAT; MOLECULAR CHARACTERIZATION; TRANSACTIVATOR TAT; TRANS-ACTIVATOR; GENE; RETROVIRUSES; INFECTION; REQUIRES; BINDING AB HIV-1 and HIV-2 are co-endemic in certain geographic areas. HIV-2 is more weakly pathogenic than HIV-1, and progression to AIDS occurs less frequently and over a longer period of time. Recent epidemiologic studies suggest that individuals infected with HIV-2 have a lower risk of HIV-1 infection. Both immune mechanisms and various modes of viral interference have been proposed to account for these results. Our findings, de scribed in this paper, suggest that HIV-2 inhibits HIV-1 replication. To study the molecular interactions between HIV-1 and HIV-2, proviral clones were transfected alone or in combination into the human T cell line GEM. LTR-CAT indicator constructs were included for the purpose of monitoring viral promoter activity. Viral replication in transfected cells was monitored by p24 antigen capture assay of cell culture supernatants and Western blot analysis of cell extracts. HIV-2 inhibited HIV-I replication as determined by intracellular and extracellular p24 antigen levels. Similar results were obtained with simultaneous virus infection using HIV-1 and HIV-2, rather than transfections of proviral DNA. Using cotransfection of HIV-1 and HIV-2 LTR indicator gene constructs, the mechanism of inhibition was found to be suppression of the HIV-1 LTR by HIV-2. The inhibitory effect of HIV-2 is not due to Tar-2, but appears to discriminate between the HIV-1 and HIV-2 LTRs based on differences in the Tar activation response element, TAR. These results suggest both a molecular mechanism for HIV-2 interference with HIV-1 replication and a potential molecular approach to therapy. C1 NCI, TUMOR CELL BIOL LAB, BETHESDA, MD 20892 USA. UNIV INNSBRUCK, INST MED CHEM & BIOCHEM, A-6020 INNSBRUCK, AUSTRIA. RP Rappaport, J (reprint author), MT SINAI SCH MED, DIV NEPHROL, BOX 1243, 1 GUSTAVE L LEVY PL, NEW YORK, NY 10029 USA. NR 29 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED JI J. Mol. Med. PD DEC PY 1995 VL 73 IS 12 BP 583 EP 589 PG 7 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA TK546 UT WOS:A1995TK54600002 PM 8825754 ER PT J AU Hallock, YF Cardellina, JH Blaschak, MS Alexander, MR Prather, TR Shoemaker, RH Boyd, MR AF Hallock, YF Cardellina, JH Blaschak, MS Alexander, MR Prather, TR Shoemaker, RH Boyd, MR TI Antitumor activity and stereochemistry of acetylenic alcohols from the sponge Cribrochalina vasculum SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID MOLECULAR-WEIGHT POLYACETYLENES; BIOACTIVE MARINE METABOLITES; ABSOLUTE-CONFIGURATION; PETROSIA-FICIFORMIS; NMR APPLICATION; MOSHER METHOD AB Antitumor bioassay-guided fractionation of the organic extract of the marine sponge Cribrochalina vasculum resulted in the isolation of several closely related cytotoxic acetylenic alcohols [1-8], the structures of which were assigned on the basis of chemical and spectral studies. 3-Hydroxyeicos-(4E)-en-1-yne[1], 3-hydroxydocosa-(4E,15Z)-dien-1-yne[2], 3-hydroxy-16-methyleicos-(4E)-en-1-yne[3], 3-hydroxy-19-methyleicos-(4E)-en-1-yne[4], 3-hydroxy-21-methyldocosa-(4E,15Z)-dien-1-yne[5], and 3-hydroxy-14-methyldocosa-(4E)-en-1-yne[6] are enantiomers of known compounds, while 3-hydroxyheneeicos-(4E)-en-1-yne[7] and 5-hydroxy-16-methyleicos-(3Z)-en-1-yne[8] are new metabolites isolated as minor components. The absolute configuration of C-3 in 1-7 and C-5 in 8 has been assigned as S using the modified Mosher's method. Compounds selected from this series showed selective in vitro antitumor activity against the H-522 non-small cell lung line and the IGROV-1 ovarian line. Synthetic racemic 1 demonstrated a modest dose-related therapeutic activity in a preliminary in vivo xenograft assay based on the latter cell line. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,LAB DRUG DISCOVERY RES & DEV,FREDERICK,MD 21702. NR 24 TC 56 Z9 56 U1 0 U2 8 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 DEC PY 1995 VL 58 IS 12 BP 1801 EP 1807 DI 10.1021/np50126a001 PG 7 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA TW336 UT WOS:A1995TW33600001 PM 8691203 ER PT J AU Erickson, KL Beutler, JA Gray, GN Cardellina, JH Boyd, MR AF Erickson, KL Beutler, JA Gray, GN Cardellina, JH Boyd, MR TI Majapolene A, a cytotoxic peroxide, and related sesquiterpenes from the red alga Laurencia majuscula SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID VACUUM LIQUID-CHROMATOGRAPHY; TUMOR-CELL-LINES; SEPARATION; MIXTURES AB Seven new sesquiterpenes, majapolenes A [1] and B [2], majapolone [3], and majapols A [4], B [5], C [6], and D [7], were isolated from a Philippine collection of Laurencia majuscula. With the exception of majapolene B [2], all compounds mere isolated as inseparable diastereomeric mixtures. Structure elucidation was achieved by spectroscopic methods. Majapolene A [1], a dioxabicyclo[2.2.2]-alkene, displayed modest activity in the NCI 60-cell line cytotoxicity screen. Majapolene A was also found as a major component of a Philippine collection of Laurencia caraibica. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,LAB DRUG DISCOVERY RES & DEV,FREDERICK,MD 21702. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 20 TC 27 Z9 30 U1 1 U2 7 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 DEC PY 1995 VL 58 IS 12 BP 1848 EP 1860 DI 10.1021/np50126a007 PG 13 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA TW336 UT WOS:A1995TW33600007 PM 8691206 ER PT J AU NILLNI, EA FRIEDMAN, TC TODD, RB BIRCH, NP LOH, YP JACKSON, IMD AF NILLNI, EA FRIEDMAN, TC TODD, RB BIRCH, NP LOH, YP JACKSON, IMD TI PRO-THYROTROPIN-RELEASING HORMONE PROCESSING BY RECOMBINANT PC1 SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE POSTTRANSLATIONAL PROCESSING; PEPTIDE BIOSYNTHESIS; PROHORMONE CONVERTASES; CRYPTIC PEPTIDES ID RAT-BRAIN; PROPROTEIN CONVERTASE; FUNCTIONAL EXPRESSION; ENDOPROTEASE FAMILY; SECRETORY GRANULES; SEQUENCE-ANALYSIS; DEGRADING ENZYME; MAMMALIAN-CELLS; NERVOUS-SYSTEM; GENE-PRODUCT AB Pro-thyrotropin-releasing hormone (proTRH) is the precursor to thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2), the hypothalamic releasing factor that stimulates synthesis and release of thyrotropin from the pituitary gland. Five copies of the TRH progenitor sequence (Gln-His-Pro-Gly) and seven cryptic peptides are formed following posttranslational proteolytic cleavage of the 26-kDa rat proTRH precursor. The endopeptidase(s) responsible for the physiological conversion of proTRH to the TRH progenitor form is currently unknown. We examined the in vitro processing of [H-3]leucine-labeled or unlabeled proTRH by partially purified recombinant PC1. Recombinant PC1 processed the 26-kDa TRH precursor by initially cleaving the prohormone after the basic amino acid at either position 153 or 159, Based on the use of our well-established antibodies, we propose that the initial cleavage gave rise to the formation of a 15-kDa N-terminal peptide (preproTRH(25-152) or preproTRH(25-158)) and a 10-kDa C-terminal peptide (pre-proTRH(154-255) or preproTRH(160-255)) Some initial cleavage occurred after amino acid 108 to generate a 16,5-kDa C-terminal peptide. The 15-kDa N-terminal intermediate was further processed to a 6-kDa peptide (preproTRH(25-78) or preproTRH(25-82)) and a 3.8-kDa peptide (preproTRH(83-108)), whereas the 10-kDa C-terminal intermediate was processed to a 5.4-kDa peptide (preproTRH(206-255)). The optimal pH for these cleavages was 5.5. ZnCl2, EDTA, EGTA, and the omission of Ca2+ inhibited the formation of pYE(27) (preproTRH(25-50)), one of the proTRH N-terminal products, by 48, 82, 72, acid 45%, respectively. This study provides evidence, for the first time, that recombinant PC1 enzyme can process proTRH to its predicted peptide intermediates. C1 NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. UNIV AUCKLAND,SCH BIOL SCI,AUCKLAND,NEW ZEALAND. RP NILLNI, EA (reprint author), BROWN UNIV,RHODE ISL HOSP,DEPT MED,DIV ENDCORINOL,593 EDDY ST,PROVIDENCE,RI 02903, USA. RI Birch, Nigel/H-2498-2011 OI Birch, Nigel/0000-0002-8417-3587 NR 57 TC 53 Z9 53 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 DEC PY 1995 VL 65 IS 6 BP 2462 EP 2472 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TF554 UT WOS:A1995TF55400010 PM 7595540 ER PT J AU Gallant, PE Hammar, K Reese, TS AF Gallant, PE Hammar, K Reese, TS TI Cytoplasmic constriction and vesiculation after axotomy in the squid giant axon SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID ULTRASTRUCTURAL-CHANGES; CUT END; MEMBRANE; TRANSECTION; TRANSPORT; FIBERS; MECHANISMS; MYELIN; INJURY; FUSION AB The squid giant axon responded to a transection injury by producing a gradient of cytoplasmic and vesicular changes at the cut end. At the immediate opening of the cut axon the cytoplasm was fragmented and dispersed and the vesicles in this region were in rapid Brownian movement. Approximately 0.1 mm further in, at the site of maximal axonal constriction, the axoplasm was condensed into a compact, constricted mass containing many large vesicles. The axoplasm was normal a few millimetres beyond this constricted, vesiculated end. It appears that transection triggered the transformation of normal axoplasm into a tightly constricted, highly vesiculated structure. This modified axoplasm at the cut end may slow the spread of damage and degeneration by preventing the bulk outflow of axoplasm, by slowing down the loss of intracellular molecules and by slowing down the influx of destructive extracellular ions (like calcium and chloride). C1 MARINE BIOL LAB,WOODS HOLE,MA 02543. RP Gallant, PE (reprint author), NIH,NEUROBIOL LAB,BLDG 36,ROOM 2A-21,BETHESDA,MD 20892, USA. NR 26 TC 10 Z9 10 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD DEC PY 1995 VL 24 IS 12 BP 943 EP 954 DI 10.1007/BF01215644 PG 12 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA TL879 UT WOS:A1995TL87900005 PM 8719821 ER PT J AU RabadanDiehl, C Lolait, SJ Aguilera, G AF RabadanDiehl, C Lolait, SJ Aguilera, G TI Regulation of pituitary vasopressin V1b receptor mRNA during stress in the rat SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE vasopressin receptor; V1b receptor; pituitary corticotroph; mRNA levels; stress ID CORTICOTROPIN-RELEASING-FACTOR; STIMULATED ADRENOCORTICOTROPIN; ADRENAL AXIS; ARGININE VASOPRESSIN; MESSENGER-RNA; SECRETION; RESPONSES; CRF; GLUCOCORTICOIDS; RESPONSIVENESS AB Previous studies have shown a parallel relationship between pituitary vasopressin (VP) receptor content and responsiveness of the corticotroph during chronic stress. The regulation of pituitary VP receptors was further studied by analysis of V1b VP receptor mRNA levels in pituitaries of rats subjected to chronic immobilization, i.p. hypertonic saline injection (physical stress paradigms associated with increased pituitary responsiveness), and water deprivation, or to 2% saline in the drinking water (osmotic stress paradigms associated with decreased pituitary responsiveness). Northern blot hybridization with a 363 bp P-32-labelled fragment of the rV1b receptor cDNA coding sequence revealed two bands of about 3.7 and 3.2 Kb, whereas a probe directed to the 5' untranslated region recognized only the 3.7 Kb band, Repeated i.p. hypertonic saline injection: 3 times in 24 h at 8 h intervals, or daily for 8 days, increased the intensity of the 3.7 Kb band by 155+/-17.5% (P<0.01) and 118+/-14.6% (P<0.01), respectively, while the 3.2 Kb band increased by 122+/-39.3% (P<0.01) only after 3 times injection. Smaller increases of 39+/-11 and 33+/-9% (P<0.05) in the 3.7 Kb band were found after repeated immobilization 3 times in 24 h and 2 h for for 8 days respectively, In situ hybridization studies confirmed significant increases (P<0.05) in V1b receptor mRNA levels after 8 and 14 days repeated immobilization (63+/-19% and 83+/-10%) or i.p. hypertonic saline injection (110+/-13% and 73+/-20%). In response to acute stress, V1b receptor mRNA increased by 77+/-5% (3.7 Kb band) after 4 h immobilization for 1 h, whereas both bands were reduced by 49+/-5% and 45+/-5%, 4 h after a single i.p. hypertonic saline injection, The decrease in V1b receptor mRNA following a single i.p. hypertonic saline injection was prevented by pretreatment with a V1 receptor antagonist, suggesting that increased VP secretion may account for this effect. In spite of the decrease in V1b receptor mRNA following i.p. hypertonic saline injection, VP binding in pituitary membrane rich fractions, and VP-stimulated inositol phosphate formation in quartered hemipituitaries were increased by 24 and 39%, respectively, V1b receptor mRNA levels were unchanged or decreased following prolonged osmotic stimulation. These studies suggest that increased V1b receptor mRNA levels contribute to the VP receptor upregulation observed during repeated immobilization and i.p. hypertonic saline injection, whereas the lack of parallelism between V1b receptor mRNA and VP binding indicates that regulation of steady-state levels of V1b receptor mRNA is not a primary determinant in the control of pituitary VP receptor concentration during stress. C1 NICHHD,DEV ENDOCRINOL BRANCH,SECT ENDOCRINE PHYSIOL,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 45 TC 64 Z9 64 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD DEC PY 1995 VL 7 IS 12 BP 903 EP 910 DI 10.1111/j.1365-2826.1995.tb00734.x PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA TQ785 UT WOS:A1995TQ78500002 PM 8745267 ER PT J AU Mamounas, LA Blue, ME Siuciak, JA Altar, CA AF Mamounas, LA Blue, ME Siuciak, JA Altar, CA TI Brain-derived neurotrophic factor promotes the survival and sprouting of serotonergic axons in rat brain SO JOURNAL OF NEUROSCIENCE LA English DT Article DE brain-derived neurotrophic factor; neurotrophin-3; NGF; neurotrophic; 5-HT; p-chloroamphetamine; neurodegeneration; regeneration ID NERVE GROWTH-FACTOR; SEPTAL CHOLINERGIC NEURONS; PARA-CHLOROAMPHETAMINE; PREVENTS DEGENERATION; DOPAMINE NEURONS; MESSENGER-RNA; FACTOR FAMILY; TRK FAMILY; FOREBRAIN; TERMINALS AB A pathology of brain serotonergic (5-HT) systems has been found in psychiatric disturbances, normal aging and in neurodegenerative disorders including Alzheimer's and Parkinson's disease. Despite the clinical importance of 5-HT, little is known about the endogenous factors that have neurotrophic influences upon 5-HT neurons. The present study examined whether chronic brain parenchymal administration of the neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) or NGF could prevent the severe degenerative loss of serotonergic axons normally caused by the selective 5-HT neurotoxin p- chloroamphetamine (PCA). The neurotrophins (5-12 mu g/d) or the control substances (cytochrome c or PBS vehicle) were continuously infused into the rat frontoparietal cortex using an osmotic minipump. One week later, rats were subcutaneously administered PCA (10 mg/kg) or vehicle, and the 5-HT innervation was evaluated after two more weeks of neurotrophin infusion. As revealed with 5-HT immunocytochemistry, BDNF infusions into the neocortex of intact (non-PCA-lesioned) rats caused a substantial increase in 5-HT axon density in a 3 mm diameter region surrounding the cannula tip. In PCA-lesioned rats, intracortical infusions of BDNF completely prevented the severe neurotoxin-induced loss of 5-HT axons near the infusion cannula. In contrast, cortical infusions of vehicle or the control protein cytochrome c did not alter the density of serotonergic axons in intact animals, nor did control infusions prevent the loss of 5-HT axons in PCA-treated rats. NT-3 caused only a modest sparing of the 5-HT innervation in PCA-treated rats, and NGF failed to prevent the loss of 5-HT axon density. The immunocytochemical data were supported by neurochemical evaluations which showed that BDNF attenuated the PCA-induced loss of 5-HT and 5-HIAA contents and H-3-5-HT uptake near the infusion cannula. Thus, BDNF can promote the sprouting of mature, uninjured serotonergic axons and dramatically enhance the survival or sprouting of 5-HT axons normally damaged by the serotonergic neurotoxin PCA. C1 JOHNS HOPKINS UNIV,SCH MED,KENNEDY KRIEGER RES INST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. REGENERON PHARMACEUT INC,TARRYTOWN,NY 10591. RP Mamounas, LA (reprint author), NIA,GERONTOL RES CTR,MOLEC & CELLULAR BIOL LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Siuciak, Judith/K-2759-2016 OI Siuciak, Judith/0000-0002-3945-3555 FU NINDS NIH HHS [NS29167] NR 65 TC 326 Z9 335 U1 3 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC PY 1995 VL 15 IS 12 BP 7929 EP 7939 PG 11 WC Neurosciences SC Neurosciences & Neurology GA TP154 UT WOS:A1995TP15400015 PM 8613731 ER PT J AU Gerfen, CR Keefe, KA Gauda, EB AF Gerfen, CR Keefe, KA Gauda, EB TI D1 and D2 dopamine receptor function in the striatum: Coactivation of D1- and D2-dopamine receptors on separate populations of neurons results in potentiated immediate early gene response in D1-containing neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE basal ganglia; striatum; dopamine receptor; synergy; gene regulation; immediate early genes; c-fos; zif268; Parkinson's disease ID C-FOS EXPRESSION; SUBSTANTIA-NIGRA; STRIATOPALLIDAL NEURONS; INTRACELLULAR INJECTION; STRIATONIGRAL NEURONS; MATRIX COMPARTMENTS; PARKINSONS-DISEASE; RAT NEOSTRIATUM; SYNERGISM; ACTIVATION AB D1- and D2-dopamine receptor-mediated regulation of immediate early gene levels in identified populations of neurons in the striatum was examined with quantitative in situ hybridization histochemical techniques. Levels of messenger RNA (mRNA) encoding the immediate early genes zif268 and c-fos were examined in two experiments in rats with unilateral lesions of the nigrostriatal dopamine pathway. In a dose-response study, animals were treated with doses of 0.5, 1.0, and 1.5 mg/kg of the D1 agonist SKF-38393 either alone or in combination with the D2 agonist quinpirole (1 mg/kg). Levels of immediate early gene mRNAs 60 min following drug treatments showed a dose-related increase to the D1 agonist alone and a potentiation to combined D1 and D2 agonist treatment. In a second experiment, in animals receiving 1 mg/kg SKF-38393 either alone or in combination with 1 mg/kg quinpirole, the level of zif268 mRNA was measured with a double-labeling method in striatal neurons containing enkephalin mRNA, a marker of Da-containing neurons, and in neurons not containing enkephalin, putative D1-containing neurons. In the dopamine-depleted striatum, D1 agonist treatment alone did not affect enkephalin-positive neurons but significantly elevated zif268 mRNA levels in nearly all enkephalin-negative neurons. Combined D1 and D2 agonist treatment further increased zif268 mRNA levels in this population of enkephalin-negative neurons and decreased zif-268 mRNA levels in enkephalin-positive neurons. These data indicate that the synergistic response to combined D1- and DP-receptor stimulation is mediated by interneuronal interactions involving the activation of D1 and D2 receptors on separate populations of striatal neurons. C1 JOHNS HOPKINS MED INST,DEPT PEDIAT,BALTIMORE,MD 21205. RP Gerfen, CR (reprint author), NIMH,NEUROPHYSIOL LAB,BLDG 36,ROOM 2D-10,BETHESDA,MD 20892, USA. NR 41 TC 214 Z9 217 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC PY 1995 VL 15 IS 12 BP 8167 EP 8176 PG 10 WC Neurosciences SC Neurosciences & Neurology GA TP154 UT WOS:A1995TP15400035 PM 8613751 ER PT J AU Brew, BJ Corbeil, J Pemberton, L Evans, L Saito, K Penny, R Cooper, DA Heyes, MP AF Brew, BJ Corbeil, J Pemberton, L Evans, L Saito, K Penny, R Cooper, DA Heyes, MP TI Quinolinic acid production is related to macrophage tropic isolates of HIV-1 SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE quinolinic acid; excitotoxin; macrophages; AIDS dementia; HIV ID IMMUNODEFICIENCY-VIRUS TYPE-1; IMMUNE-DEFICIENCY-SYNDROME; L-TRYPTOPHAN; RAT-BRAIN; INFECTION; AIDS; ENVELOPE; DEMENTIA; SYSTEM; DAMAGE AB We sought to determine whether the neurotoxin quinolinic acid (QUIN) was produced by macrophages or lymphocytes infected with isolates of HIV-1 with varying degrees of macrophage tropism derived from patients with varying stages of AIDS dementia complex (ADC). Highly macrophage tropic isolates and minimally macrophage tropic isolates were used to inoculate macrophages and QUIN production was measured. Similarly, QUIN production from macrophages was monitored using a purified cell free highly macrophage tropic isolate and laboratory isolates SF33 and SF2. Each of these experiments was also performed with lymphocytes. We found that macrophages infected with macrophage tropic isolates of HIV-1 led to QUIN production while lymphocytes did not produce QUIN, The ability of the HIV-1 infected macrophages to produce QUIN was related to the viral inoculum and the degree of macrophage tropism of the isolate. The severity of ADC in the patient from whom a particular isolate was derived was not per se a determining factor for QUIN production. Purified cell free ADC isolates also led to QUIN production by macrophages thereby suggesting that HIV-1 infection alone is capable of inducing QUIN production. C1 ST VINCENTS HOSP,DEPT NEUROL,SYDNEY,NSW 2010,AUSTRALIA. NATL CTR HIV EPIDEMIOL & CLIN RES,SYDNEY,NSW,AUSTRALIA. NIMH,BETHESDA,MD 20892. RP Brew, BJ (reprint author), ST VINCENTS HOSP,CTR IMMUNOL,SYDNEY,NSW 2010,AUSTRALIA. RI Brew, Bruce/J-6513-2012 NR 22 TC 36 Z9 38 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 1995 VL 1 IS 5-6 BP 369 EP 374 DI 10.3109/13550289509111026 PG 6 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA TZ699 UT WOS:A1995TZ69900008 PM 9222379 ER PT J AU CHEN, CC SKARULIS, MC FRAKER, DL ALEXANDER, HR MARX, SJ SPIEGEL, AM AF CHEN, CC SKARULIS, MC FRAKER, DL ALEXANDER, HR MARX, SJ SPIEGEL, AM TI TECHNETIUM-99M-SESTAMIBI IMAGING BEFORE REOPERATION FOR PRIMARY HYPERPARATHYROIDISM SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE IODINE-123/TECHNETIUM-99M-SESIAMIBI; SUBTRACTION; HYPERPARATHYROIDISM ID ABNORMAL PARATHYROID-GLANDS; TECHNETIUM 99M SESTAMIBI; PREOPERATIVE LOCALIZATION; TC-99M MIBI; VISUALIZATION; TISSUE AB Recent studies have reported high sensitivities for parathyroid localization with Tc-99m-sestamibi and have been performed using either I-123/Tc-99m-sestamibi or a double-phase sestamibi scanning technique. These studies have focused primarily on patients undergoing initial surgery. We studied 35 patients prior to reoperative surgery to investigate the relative sensitivities of these two techniques in this patient population, Methods: Double-phase sestamibi scanning (early and delayed imaging) was performed in all patients. Evaluable I-123/Tc-99m-sestamibi subtraction studies were also obtained in 25 patients. Results were correlated with surgical findings in 32 patients and with clinical outcome in 3 patients in whom mediastinal lesions were radiographically ablated. Results: Overall, double-phase sestamibi imaging detected 23 of 39 abnormal parathyroid glands (59%), whereas I-123/Tc-99m-sestamibi detected 19 of 27 (70%). Oblique imaging, delayed imaging and I-123 subtraction all contributed to sensitivity, and I-123 subtraction also proved useful in patients with partial thyroid suppression. Two patients had lesions visible on the early sestamibi images that were not seen at all on the delayed scans. There were four false-positive findings. Conclusion: No significant differences between double-phase sestamibi and I-123/Tc-99m-sestamibi subtraction scanning were found, although the latter tended to be more sensitive. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 12 TC 63 Z9 63 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 1995 VL 36 IS 12 BP 2186 EP 2191 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TK409 UT WOS:A1995TK40900012 PM 8523102 ER PT J AU ARAI, T WAKABAYASHI, SI CHANNING, MA DUNN, BB DER, MG BELL, JM HERSCOVITCH, P ECKELMAN, WC RAPOPORT, SI CHANG, MC AF ARAI, T WAKABAYASHI, SI CHANNING, MA DUNN, BB DER, MG BELL, JM HERSCOVITCH, P ECKELMAN, WC RAPOPORT, SI CHANG, MC TI INCORPORATION OF [1-CARBON-11]PALMITATE IN MONKEY BRAIN USING PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; BRAIN; PALMITIC ACID; METHYL PALMOXIRATED ID POSITRON-EMISSION TOMOGRAPHY; CEREBRAL PALMITATE INCORPORATION; FATTY-ACID OXIDATION; UNANESTHETIZED RATS; CARBON-DIOXIDE; BLOOD-VOLUME; INVIVO; AWAKE; 2-TETRADECYLGLYCIDATE; PHOSPHOLIPIDS AB We determined regional incorporation coefficients (k*) of plasma [1-C-11]palmitate into stable brain lipids of anesthetized monkeys with PET. Methods: Carbon-11-palmitate was injected intravenously in untreated animals and in animals pretreated with methyl palmoxirate (MEP), an inhibitor of beta-oxidation of palmitate in the brain and periphery. Plasma radioactivity was followed, and brain radioactivity was determined at various times using PET. A least-squares method was used to fit the data to an operational equation to obtain regional values of k* and of cerebral blood volume (V-b) in individual experiments. Results: MEP significantly decreased the integral of plasma [C-11]CO2 following C-11-paalmtate infusion. Mean values of k* in monkeys not given MEP were 4.9, 4.2, 4.9, 4.0 and 2.9 x 10(-5) ml/sec g for the temporal, frontal, parietal and occipital cortices and white matter, respectively. With the exception of k* in white matter, which was increased by MEP, k* in the other brain regions was not significantly changed by MEP. The V-b ranged from 0.035 ml/g to 0.048 ml/g in gray matter regions and equaled 0.022 ml/g in white matter. Conclusion: PET can be used to determine regional incorporation coefficients of C-11-palmitate into the primate brain in vivo. Combined with MEP, C-11-palmitate could be used with PET to examine regional brain phospholipid metabolism in humans in normal and pathological conditions. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NATL INST HLTH,CTR CLIN,DEPT PET,BETHESDA,MD. TOKYO MED & DENT UNIV,DEPT NEUROSURG,TOKYO 113,JAPAN. NR 49 TC 25 Z9 25 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 1995 VL 36 IS 12 BP 2261 EP 2267 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TK409 UT WOS:A1995TK40900027 PM 8523117 ER PT J AU Witkin, JM Brave, S French, D GeterDouglass, B AF Witkin, JM Brave, S French, D GeterDouglass, B TI Discriminative stimulus effects of R-(+)-3-amino-1-hydroxypyrrolid-2-one, [(+)-HA-966], a partial agonist of the strychnine-insensitive modulatory site of the N-methyl-D-aspartate receptor SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NMDA RECEPTOR; D-CYCLOSERINE; GLYCINE RECEPTOR; 7-CHLOROKYNURENIC ACID; EXHIBIT ANTIDEPRESSANT; XENOPUS OOCYTES; ANTAGONISTS; CONVULSIONS; COMPLEX; HA-966 AB The strychnine-insensitive glycine site on the N-methyl-D-aspartate (NMDA) receptor complex is a target for development of a host of therapeutic agents including anxiolytics, antidepressants, antiepileptics, anti-ischemics and cognitive enhancers. In the present experiments, the discriminative stimulus effects of (+)-HA-966 [R-(+)-5-amino-1-hydroxypyrrolid-2-one], a low-efficacy partial agonist of the glycine site, was explored. Male, Swiss-Webster mice were trained to discriminate (+)-HA-966 (170 mg/kg i.p.) from saline in a T-maze under which behavior was controlled by food. Other glycine partial agonists, 1-amino-1-cyclopropanecarboxilic acid and D-cycloserine, fully substituted for the discriminative stimulus effects of (+)-HA-966 despite known differences in other pharmacological effects of these compounds. The glycine site antagonist, 7-chlorkynurenic acid, did not substitute for (+)-HA-966. Likewise other functional NMDA antagonists acting at nonglycine sites of the NMDA receptor also did not substitute: neither the high (dizocilpine) or low affinity (ibogaine) ion-channel blocker, the competitive antagonist, NPC 17742 [2R,4R,5S-2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid], nor the polyamine antagonist, ifenprodil, substituted for (+)-HA-966. Although the full agonist, glycine, did riot substitute, this compound fully blocked the discriminative stimulus effects of (+)-HA-966. In a separate group of mice trained to discriminate 0.17 mg/kg of dizocilpine from saline, (+)-HA-966 produced a maximum of only 50% dizocilpine-appropriate responses. These data suggest that the discriminative stimulus effects of (+)-HA-966 are based upon its partial agonist actions at the strychnine-insensitive glycine site. Furthermore, the lack of substitution of compounds with phencyclidine-like effects (dizocilpine, ibogaine and NPC 17742) or sedative properties (NPC 17742 and (-)-HA-966) suggests that these side-effects may not be part of the subjective effect profile of glycine partial agonists. RP Witkin, JM (reprint author), NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,DRUG DEV GRP,POB 5180,BALTIMORE,MD 21224, USA. FU NIMH NIH HHS [N01 MH30003]; PHS HHS [278-90-0007] NR 74 TC 17 Z9 17 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1995 VL 275 IS 3 BP 1267 EP 1273 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL757 UT WOS:A1995TL75700026 PM 8531091 ER PT J AU Zhong, Z Connor, HD Mason, RP Qu, W Gao, WS Lemasters, JJ Thurman, RG AF Zhong, Z Connor, HD Mason, RP Qu, W Gao, WS Lemasters, JJ Thurman, RG TI Role of Kupffer cells in reperfusion injury in fat-loaded livers from ethanol-treated rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CAROLINA RINSE SOLUTION; GASTRIC-MUCOSAL DAMAGE; LIPID-PEROXIDATION; GRAFT FAILURE; SURVIVAL-TIME; TRANSPLANTATION; STORAGE; LEUKOTRIENES; ACTIVATION; MACROPHAGES AB Reperfusion injury was studied in blood-free perfused livers from fat-loaded, ethanol-treated rats. Rats were pair-fed a modified Lieber-DeCarli liquid diet containing 36% calories as ethanol or isocaloric maltose-dextrin for 4 to 5 weeks. Reperfusion injury to the liver, which occurs in previously hypoxic regions upon reintroduction of oxygen, was studied in a low-flow, reflow perfusion model. Lactate dehydrogenase in effluent perfusate increased from basal levels of < 1 to 17 IU/g/h in livers from controls, whereas prior alcohol treatment elevated values to 37 IU/g/h. Pretreatment of rats with gadolinium chloride (GdCl3, 20 mg/kg i.v.), a selective Kupffer cell toxicant, minimized lactate dehydrogenase release during reperfusion to 7 to 8 IU/g/h in livers from both groups. Rates of malondialdehyde production were 144 and 166 nmol/g/h during reperfusion in control and alcohol-treated rats, respectively, but values reached only 54 and 79 nmol/g/h after GdCl3 treatment. Interestingly, a typical PBN/carbon-centered free radical adduct signal was detected in bile of livers from ethanol-treated rats, but not in controls or ethanol-treated rats given GdCl3. Portal pressure increased during the reperfusion period in livers from alcohol-treated rats, although not in controls, and GdCl3 reduced it significantly. Taken together, these data indicate that reperfusion injury is greater in fatty livers from alcohol-treated rats in a blood-free model. Inactivation of Kupffer cells minimized reperfusion injury in both control and alcohol-treated rats, most likely by diminishing lipid peroxidation thereby improving hepatic microcirculation. C1 UNIV N CAROLINA,FAC LAB OFF BLDG,DEPT PHARMACOL,HEPATOBIOL & TOXICOL LAB,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27599. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. KENTUCKY WESLEYAN COLL,DEPT CHEM,OWENSBORO,KY 42301. FU NIAAA NIH HHS [AA-03624, AA-09156] NR 36 TC 28 Z9 28 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1995 VL 275 IS 3 BP 1512 EP 1517 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL757 UT WOS:A1995TL75700058 PM 8531123 ER PT J AU Suh, HW Hudson, PM McMillian, MK Das, KP Wilson, BC Wu, GC Hong, JS AF Suh, HW Hudson, PM McMillian, MK Das, KP Wilson, BC Wu, GC Hong, JS TI Long-term stimulation of nicotinic receptors is required to increase proenkephalin A mRNA levels and the delayed secretion of [Met(5)]-enkephalin in bovine adrenal medullary chromaffin cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID A GENE-EXPRESSION; TYROSINE-HYDROXYLASE; MESSENGER-RNA; CATECHOLAMINE SECRETION; CALMODULIN INHIBITORS; CA-2+ CHANNELS; ENKEPHALIN; PEPTIDES; RELEASE; CALCIUM AB The effects of nicotine on the transcriptional activity of the proENK gene, proenkephalin A (proENK) mRNA levels, and the secretion of [Met(5)]-enkephalin (ME) were studied in bovine adrenal medullary chromaffin (BAMC) cells. Nicotine (10 mu M) caused an immediate secretion (within 1 hr) of ME followed by a delayed secretion (12-24 hr after treatment) into the medium. Posttreatment with the cholinergic antagonists, hexamethonium (1 mM) and atropine (1 mu M), up to 6 hr after the nicotine treatment significantly inhibited the delayed secretion of ME induced by nicotine. However, nicotine-induced long-term secretion of ME was not affected when cholinergic antagonists were added 9 or 12 hr after the nicotine treatment. Long-term (24 hr) stimulation of BAMC cells with nicotine also increased proENK mRNA level. This nicotine-induced response was inhibited by posttreatment with cholinergic antagonists 0.5, 1, 3 and 6 hr after the nicotine treatment. As with the secretion experiments, these cholinergic antagonists did not affect the nicotine-induced responses when they were added at 9 and 12 hr. Posttreatment with nimodipine(1 mu M), calmidazolium (1 mu M) or KN-62 (5 mu M) up to 6 hr after the nicotine treatment significantly inhibited the increases of the long-term secretion of ME and proENK mRNA level induced by nicotine. However, these agents were ineffective in blocking the long-term secretion of ME and proENK mRNA level induced by nicotine when BAMC cells were posttreated after 9 and 12 hr. Nuclear run-on assays showed that nicotine increases the transcriptional rate for the proENK gene after 30 min and the response continues for up to 9 hr with a maximal increase of 2- to 2.5-fold at 1 and 3 hr. Our results suggest that the long-term stimulation (for at least 6 hr) of nicotinic receptors is required for the increases in proENK mRNA levels and the delayed secretion of ME in BAMC cells. The nicotine-induced delayed secretion of ME followed an increased biosynthesis of ME during the first 6 hr which appeared to result from increased transcription of the proENK gene. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,NEUROPHARMACOL SECT,RES TRIANGLE PK,NC 27709. HALLYM UNIV,COLL MED,DEPT PHARMACOL,CHUNCHON 200702,SOUTH KOREA. NR 39 TC 15 Z9 15 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1995 VL 275 IS 3 BP 1663 EP 1670 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL757 UT WOS:A1995TL75700077 PM 8531142 ER PT J AU Nye, HE Hope, BT Kelz, MB Iadarola, M Nestler, EJ AF Nye, HE Hope, BT Kelz, MB Iadarola, M Nestler, EJ TI Pharmacological studies of the regulation of chronic FOS-related antigen induction by cocaine in the striatum and nucleus accumbens SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TRANSCRIPTION FACTOR GENES; C-FOS; RAT STRIATUM; BEHAVIORAL SENSITIZATION; RECEPTOR ACTIVATION; TIME-COURSE; EXPRESSION; DOPAMINE; AMPHETAMINE; PROTEINS AB Previous work has demonstrated that chronic administration of cocaine induces apparently novel Fos-like transcription factors, termed chronic Fras (Fos-related antigens), in the rat striatum and nucleus accumbens. induction of these proteins is associated with prolonged increases in AP-1 DNA binding activity that parallel the long half-life of the chronic Fras in brain. The goal of the present study was to characterize pharmacologically the regulation of chronic Fra induction by cocaine. Chronic Fra induction was examined with respect to the cocaine dose, time course and administration intervals used. Cocaine was found to induce the chronic Fras over widely differing treatment regimens in the striatum and nucleus accumbens, although clear differences between the two brain regions were observed. In general, maximal induction occurred with moderate treatment conditions, with more or less intensive treatments resulting in lower levels of chronic Fras. The pharmacological mechanisms underlying cocaine induction of the chronic Fras were also investigated. Pretreatment with a DI receptor antagonist, which did not affect chronic Fra levels by itself, attenuated cocaine induction of the chronic Fras in striatum and nucleus accumbens. in contrast, treatment with a D2 receptor antagonist alone greatly induced chronic Fra levels, with no further increase seen in response to combined treatment with cocaine. Combined treatment with D1 and D2 receptor agonists, or with amphetamine, led to a strong induction of chronic Fras. Similarly, repeated treatment with a specific dopamine transporter inhibitor increased chronic Fra levels, whereas treatment with a specific serotonin or norepinephrine transporter inhibitor failed to produce this effect. These results support an important role for dopaminergic neurotransmission in the induction of chronic Fras by cocaine. Taken together, the results of the present study provide a more complete understanding of the pharmacological properties underlying cocaine regulation of the chronic Fras, which will assist in identifying the functional role played by these proteins in cocaine action. C1 YALE UNIV,SCH MED,CONNECTICUT MENTAL HLTH CTR,DEPT PSYCHIAT,NEW HAVEN,CT 06508. YALE UNIV,SCH MED,CONNECTICUT MENTAL HLTH CTR,DEPT PHARMACOL,NEW HAVEN,CT 06508. YALE UNIV,SCH MED,MOLEC PSYCHIAT LAB,NEW HAVEN,CT 06508. NIDR,NEUROBIOL & ANESTHESIA BRANCH,BETHESDA,MD 20892. RI Kelz, Max/E-4054-2010; Hope, Bruce/A-9223-2010 OI Kelz, Max/0000-0002-2803-6078; Hope, Bruce/0000-0001-5804-7061 FU NIDA NIH HHS [DA00203, DA07359] NR 49 TC 153 Z9 155 U1 1 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1995 VL 275 IS 3 BP 1671 EP 1680 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL757 UT WOS:A1995TL75700078 PM 8531143 ER PT J AU Grill, SE Hallett, M AF Grill, SE Hallett, M TI Velocity sensitivity of human muscle spindle afferents and slowly adapting type II cutaneous mechanoreceptors SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID DYNAMIC-RESPONSE; POSITION SENSE; HAIRY SKIN; HUMAN HAND; MOVEMENTS; JOINT; RECEPTORS; INFORMATION; KINESTHESIA; VIBRATION AB 1. Velocity information is used in the performance of movement. This study evaluated the ability of peripheral receptors to signal velocity in human subjects. 2. The velocity sensitivity of human muscle spindle afferents from the extensor digitorum muscles and slowly adapting type II cutaneous mechanoreceptors on the dorsum of the hand was evaluated with recordings from the radial nerve during imposed flexion movements about the metacarpophalangeal joint. Twenty-degree movements at velocities ranging from 5 to 80 deg s(-1) were used. 3. Three measures of dynamic response were calculated: the dynamic positional sensitivity (the relation between discharge rate and joint angle during the dynamic phase of movement), the dynamic index (the discharge rate just before ramp completion minus the rate 0.5 s later), and the incremental response (the discharge rate just before ramp completion minus the rate just before ramp onset). 4. Both muscle spindle afferents and slowly adapting type II cutaneous mechanoreceptors demonstrated significant velocity sensitivity. The magnitudes of the relations between dynamic response measures and velocity were similar in the two receptor types. 5. These findings are consistent with the view that both muscle spindle afferents and slowly adapting type II cutaneous mechanoreceptors provide reasonable velocity signals. RP Grill, SE (reprint author), NINCDS, MED NEUROL BRANCH, HUMAN MOTOR CONTROL SECT, BETHESDA, MD 20892 USA. NR 39 TC 51 Z9 52 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 1 PY 1995 VL 489 IS 2 BP 593 EP 602 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA TM781 UT WOS:A1995TM78100025 PM 8847650 ER PT J AU KASTE, LM BOLDEN, AJ AF KASTE, LM BOLDEN, AJ TI DENTAL-CARIES IN HOMELESS ADULTS IN BOSTON SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Note DE HOMELESS; DENTAL CARIES; ADULTS ID HEALTH-STATUS; CHILDREN; FAMILIES; SHELTERS; SAMPLE AB Objectives: Information about the oral health status of the homeless is limited. The purpose of this study is to characterize the dental caries status among users of a dental treatment and referral program at homeless shelters in Boston, MA. Methods: Persons attending the program during a one-year period were assessed for evidence of dental caries experience by a single examiner. DMFT counts were abstracted from patient records. Results: The population examined (n=73) was 66 percent male with a mean age of 36 years. The racial composition was 51 percent African-American, 34 percent Caucasian, and 14 percent Hispanic. The 70 dentate people examined had a mean DFT of 11.1 (SD=6.1). The mean percent of DFT that was DT per person was 55.7 percent. Untreated caries was defected in 91.4 percent of those examined. Conclusions: These findings show evidence of previous dental services utilization by these homeless individuals, but demonstrate a high need for preventive and restorative dental therapy. C1 UNIV IOWA,DEPT PREVENT & COMMUNITY DENT,IOWA CITY,IA. RP KASTE, LM (reprint author), NIDR,EODPP,ASHAB,NATCHER BLDG,ROOM 4AS-25B,45 CTR DR MSC 6401,BETHESDA,MD 20892, USA. NR 15 TC 10 Z9 10 U1 1 U2 3 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 1995 VL 55 IS 1 BP 34 EP 36 DI 10.1111/j.1752-7325.1995.tb02328.x PG 3 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA QM956 UT WOS:A1995QM95600008 PM 7776290 ER PT J AU McCrae, RR Costa, PT AF McCrae, RR Costa, PT TI Positive and negative valence within the five-factor model SO JOURNAL OF RESEARCH IN PERSONALITY LA English DT Article; Proceedings Paper CT 102nd Annual Convention of the American-Psychological-Association CY AUG 12-16, 1994 CL LOS ANGELES, CA SP Amer Psychol Assoc ID 5-FACTOR MODEL; PERSONALITY-INVENTORY; SOCIAL DESIRABILITY; CONSTRUCT-VALIDITY; FACET SCALES AB Tellegen and Waller (in press) have argued that highly evaluative adjectives provide significant information about personality and should not be excluded from trait taxonomic studies. Their analyses have identified two evaluative dimensions labeled Positive Valence (PV) and Negative Valence (NV). This study examines the meaning of these evaluative dimensions from the perspective of the five-factor model. Participants in the Baltimore Longitudinal Study of Aging (N = 412) completed Tellegen, Grove, and Waller's (1991) Inventory of Personal Characteristics 7; self-reports and spouse and peer ratings on the Revised NEO Personality Inventory (NEO-PI-R) were also available. PV and NV were not related to measures of response bias and did not moderate self/observer agreement. Joint factor analysis showed that in a five-factor solution, PV and NV had substantial communality and defined several factors. Correlations with NEO-PI-R facet scales suggested that PV and NV are associated with substantive aspects of personality, with PV related especially to Assertiveness and low Modesty, and NV related to Depression and low Competence. Although PV and NV are not fundamental factors in the description of personality, they are potentially important in understanding self-appraisals and social evaluations. RP McCrae, RR (reprint author), NIA,GERONTOL RES CTR,PERSONAL STRESS & COPING SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Costa, Paul/0000-0003-4375-1712 NR 52 TC 46 Z9 46 U1 3 U2 16 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0092-6566 J9 J RES PERS JI J. Res. Pers. PD DEC PY 1995 VL 29 IS 4 BP 443 EP 460 DI 10.1006/jrpe.1995.1026 PG 18 WC Psychology, Social SC Psychology GA TL302 UT WOS:A1995TL30200005 ER PT J AU VASAN, RS BENJAMIN, EJ LEVY, D AF VASAN, RS BENJAMIN, EJ LEVY, D TI PREVALENCE, CLINICAL-FEATURES AND PROGNOSIS OF DIASTOLIC HEART-FAILURE - AN EPIDEMIOLOGIC PERSPECTIVE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID VENTRICULAR SYSTOLIC FUNCTION; CORONARY-ARTERY DISEASE; NORMAL EJECTION FRACTION; ACUTE PULMONARY-EDEMA; ELDERLY PATIENTS; MITRAL REGURGITATION; UNITED-STATES; ECHOCARDIOGRAPHIC INSIGHTS; MYOCARDIAL-INFARCTION; NATURAL-HISTORY AB Numerous reports suggest that about one-third of patients with congestive heart failure do not have any abnormality of left ventricular systolic function, These patients presumably have heart failure on the basis of ventricular diastolic dysfunction. Our objective was to develop a comprehensive overview of published reports of the prevalence, clinical features and prognosis of diastolic heart failure and to offer recommendations for future studies. Thirty-one studies of patients with congestive heart failure with normal left ventricular systolic function were published in the time period from January 1970 through March 1995, These studies were identified with the use of computer-based searches in relevant data bases, Among patients with congestive heart failure, the prevalence of normal ventricular systolic performance in the published reports varies widely from 13% to 74%; the reported annual mortality rate also varies from 1.3% to 17.5%. The criteria for congestive heart failure, its chronicity and the age of the study sample affect the reported prevalence and prognosis of the disorder, The clinical signs and symptoms of diastolic heart failure are similar to those of patients with systolic heart failure, underscoring the need for evaluation of ventricular systolic function in patients with congestive heart failure, In the absence of any large-scale randomized clinical trial targeting these patients, the optimal treatment of diastolic heart failure is unclear. We conclude that the heterogeneity in previous studies of diastolic heart failure hinders the comparison of published reports, There is a need to conduct prospective, community-based investigations to better characterize the incidence, prevalence and natural history of diastolic heart failure, Randomized clinical trials are needed to determine optimal treatment strategies. (J Am Coll Cardiol 1995;26:1565-74) C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. BOSTON UNIV,SCH MED,BOSTON,MA 02118. BOSTON CITY HOSP,CARDIOL SECT,BOSTON,MA 02118. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. NHLBI,BETHESDA,MD 20892. OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N0I-HC-38038]; NINDS NIH HHS [2-ROI-NS-17950-11] NR 86 TC 555 Z9 584 U1 1 U2 9 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 1995 VL 26 IS 7 BP 1565 EP 1574 DI 10.1016/0735-1097(95)00381-9 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TH124 UT WOS:A1995TH12400001 PM 7594087 ER PT J AU KLUES, HG SCHIFFERS, A MARON, BJ AF KLUES, HG SCHIFFERS, A MARON, BJ TI PHENOTYPIC SPECTRUM AND PATTERNS OF LEFT-VENTRICULAR HYPERTROPHY IN HYPERTROPHIC CARDIOMYOPATHY - MORPHOLOGIC OBSERVATIONS AND SIGNIFICANCE AS ASSESSED BY 2-DIMENSIONAL ECHOCARDIOGRAPHY IN 600 PATIENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID SYSTOLIC ANTERIOR MOTION; TRACT PRESSURE-GRADIENT; M-MODE ECHOCARDIOGRAPHY; CLINICAL MANIFESTATIONS; PATHO-PHYSIOLOGY; WALL THICKNESS; EXTENT; INTERRELATIONS; PROGRESSION; OBSTRUCTION AB Objectives. This study sought to achieve an understanding of the true structural heterogeneity of hypertrophic cardiomyopathy. Background. The diversity and clinical significance of the morphologic expression of hypertrophic cardiomyopathy have not been fully defined within this broad disease spectrum. Methods. Patterns of left ventricular hypertrophy were characterized by two-dimensional echocardiography in a large study cohort of 600 patients (7 to 79 years old, mean age 45; 393 [66%] men) consecutively studied at two referral centers. Results. Left ventricular wall thickness was 15 to 52 mm (mean [+/- SD] 22.3 +/- 5), A multitude of patterns of asymmetric left ventricular hypertrophy were identified, with the most common showing diffuse involvement of substantial portions of both ventricular septum and free wall, Of 16 possible patterns of left ventricular hypertrophy, 12 (78%) were identified among the 600 patients, Hypertrophy most commonly involved two left ventricular segments (228 patients [38%]) or three or more segments (202 patients [34%]), but was also localized to one segment in a substantial number of patients (170 [28%]), The anterior portion of the ventricular septum was the region of the left ventricle that most frequently shelved thickening (573 patients [96%]), and,vas also the predominant site of hypertrophy in most patients (492 patients [83%]), Patterns of wall thickening that were either concentric (i,e,, symmetric) or confined to the apex were particularly uncommon (in 1% each). Conclusions. 1) In hypertrophic cardiomyopathy, the distribution of left ventricular hypertrophy is characteristically asymmetric and particularly heterogeneous, encompassing most possible patterns of wall thickening, from extensive and diffuse to mild and segmental, and,vith no single morphologic expression considered typical or classic, 2) A greater extent of left ventricular hypertrophy was associated with younger age and more marked mitral valve systolic anterior motion and outflow obstruction but showed no relation to either magnitude of symptoms or gender. C1 MINNEAPOLIS HEART INST FDN,DIV CARDIOVASC RES,MINNEAPOLIS,MN 55407. UNIV HOSP AACHEN,RHEIN WESTFAL TH AACHEN,DEPT CARDIOL,MED CLIN 1,AACHEN,GERMANY. NHLBI,BETHESDA,MD 20892. NR 53 TC 352 Z9 367 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 1995 VL 26 IS 7 BP 1699 EP 1708 DI 10.1016/0735-1097(95)00390-8 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TH124 UT WOS:A1995TH12400020 PM 7594106 ER PT J AU RODGERS, RPC AF RODGERS, RPC TI AUTOMATED RETRIEVAL FROM MULTIPLE DISPARATE INFORMATION-SOURCES - THE WORLD-WIDE-WEB AND THE NLMS SOURCERER PROJECT SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE LA English DT Article AB The burgeoning amount of information available via the Internet has heightened awareness of the need for improved tools for resource identification. The U.S. National Library of Medicine's (NLM) Sourcerer project is developing software which accepts a user query, automatically identifies appropriate information resources, and facilitates connection to those sources far information retrieval. The current Sourcerer prototype utilizes the multimedia/multiplatform/multiprotocol network-based hypertext system known as World Wide Web. It also relies upon the knowledge sources of the Unified Medical Language System (UMLS). The UMLS is the result of a long-term project of NLM. It comprises a large Metathesaurus of biomedical concepts (coupled with a semantic network and syntactical/lexical software tools) and the Information Sources Map(ISM), a database of records describing specific biomedical information resources. Recent advances in the standardization of information exchange over computer networks, coupled with the tools provided by UMLS, facilitate query refinement and augmentation, connection to resources, and retrieval from resources. Daunting challenges remain with respect to optimizing resource descriptions, defining optimal algorithms for searching for sources, optimizing user interface design, and organizing retrieved information. RP RODGERS, RPC (reprint author), US NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,BLDG 38A,ROOM 9S-916,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 28 TC 9 Z9 9 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0002-8231 J9 J AM SOC INFORM SCI JI J. Am. Soc. Inf. Sci. PD DEC PY 1995 VL 46 IS 10 BP 755 EP 764 DI 10.1002/(SICI)1097-4571(199512)46:10<755::AID-ASI7>3.0.CO;2-# PG 10 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA TG675 UT WOS:A1995TG67500007 ER PT J AU Ijames, CF Dutky, RC Fales, HM AF Ijames, CF Dutky, RC Fales, HM TI Iron carboxylate oxygen-centered-triangle complexes detected during electrospray use of organic acid modifiers with a comment on the Finnigan TSQ-700 electrospray inlet system SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID IONIZATION AB Use of infusion methods rather than high-performance liquid chromatography allowed us to confirm the observation that solutions of propionic acid-isopropanol restore sensitivity lost due to trifluoroacetic acid in electrospray mass spectra of basic substances, particularly peptides. In this work, when propionic acid-isopropanol was used, we detected an abundant ion with m/z 622 that shifted to m/z 538 when we substituted acetic acid-methanol for the propionic acid-isopropanol. Via accurate mass measurement and tandem mass spectrometry the origin of the ion was identified as the complex Fe3O(O(2)CR)(6)(L)(0-3), where L is one of several ligands from solvent or water. The grounding arrangement of the Finnigan TSQ-700 electrospray source produces electrolytic currents that may accentuate the abundance of this complex and specifically produces observable gas bubbles that adversely affect the spray stability. C1 NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,CHEM STRUCT SECT,BETHESDA,MD 20892. NR 12 TC 13 Z9 13 U1 0 U2 1 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 DEC PY 1995 VL 6 IS 12 BP 1226 EP 1231 DI 10.1016/1044-0305(95)00579-X PG 6 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA TL530 UT WOS:A1995TL53000011 PM 24214074 ER PT J AU Liu, JS Neuwald, AF Lawrence, CE AF Liu, JS Neuwald, AF Lawrence, CE TI Bayesian models for multiple local sequence alignment and Gibbs sampling strategies SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Bernoulli sampling; dinucleotide binding; Dirichlet distribution; fragmentation; Gibbs sampling; metropolis algorithm; product multinomial; ranks test ID MAXIMUM-LIKELIHOOD ALIGNMENT; DNA-SEQUENCES; ALGORITHM; PROTEINS; SITES AB A wealth of data concerning life's basic molecules, proteins and nucleic acids, has emerged from the biotechnology revolution. The human genome project has accelerated the growth of these data. Multiple observations of homologous protein or nucleic acid sequences from different organisms are often available. But because mutations and sequence errors misalign these data, multiple sequence alignment has become an essential and valuable tool for understanding structures and functions of these molecules. A recently developed Gibbs sampling algorithm has been applied with substantial advantage in this setting. In this article we develop a full Bayesian foundation for this algorithm and present extensions that permit relaxation of two important restrictions. We also present a rank test for the assessment of the significance of multiple sequence alignment. As an example, we study the set of dinucleotide binding proteins and predict binding segments for dozens of its members. C1 NIH,NLM,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,BIOMETR LAB,ALBANY,NY 12201. HARVARD UNIV,DEPT STAT,CAMBRIDGE,MA 02138. RP Liu, JS (reprint author), STANFORD UNIV,DEPT STAT,STANFORD,CA 94305, USA. NR 34 TC 188 Z9 196 U1 0 U2 7 PU AMER STATIST ASSN PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 1995 VL 90 IS 432 BP 1156 EP 1170 DI 10.2307/2291508 PG 15 WC Statistics & Probability SC Mathematics GA TK534 UT WOS:A1995TK53400003 ER PT J AU Vymazal, J Brooks, RA Patronas, N Hajek, M Bulte, JWM DiChiro, G AF Vymazal, J Brooks, RA Patronas, N Hajek, M Bulte, JWM DiChiro, G TI Magnetic resonance imaging of brain iron in health and disease SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Satellite Symposium on Normal and Pathological Brain Iron CY SEP 17, 1994 CL NIAGARA FALLS, NY DE brain iron; diffusion; Hallervorden-Spatz disease; magnetic resonance imaging; Parkinson's disease ID HALLERVORDEN-SPATZ DISEASE; DIFFERENT FIELD STRENGTHS; PARKINSONS-DISEASE; TRANSVERSE RELAXATION; BASAL GANGLIA; SIGNAL INTENSITY; OXYGEN RADICALS; TRACE-METALS; AGING BRAIN; MR IMAGES AB Brain iron is a major contributor to magnetic resonance imaging (MRI) contrast in normal gray matter, and its role in the pathogenesis of different neurological disorders has also become apparent. Non-heme brain iron is present in the brain mainly in the form of ferritin, The unique magnetic properties of ferritin determine different signal changes on both T1- and T2 weighted images, and the T2 relaxation rates have a linear dependence on applied field strength, This finding is typical for ferric oxyhydroxide cores. The resulting T2-shortening also depends on echo-spacing used in the imaging sequence as well as on the water diffusion coefficient and the size of the ferritin cluster, Quantitation of non-heme brain iron by MRI aids in the diagnosis and monitoring of different neurological diseases. C1 NIH, CTR CLIN, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. NIH, LAB DIAGNST RADIOL RES, OIR, OFF DIRECTOR, BETHESDA, MD 20892 USA. RP Vymazal, J (reprint author), NINCDS, NIH, NEUROIMAGING BRANCH, BLDG 10, ROOM 1C451, BETHESDA, MD 20892 USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 55 TC 59 Z9 60 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD DEC PY 1995 VL 134 SU S BP 19 EP 26 DI 10.1016/0022-510X(95)00204-F PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TT811 UT WOS:A1995TT81100004 PM 8847541 ER PT J AU WALTHER, MM LUBENSKY, IA VENZON, D ZBAR, B LINEHAN, WM AF WALTHER, MM LUBENSKY, IA VENZON, D ZBAR, B LINEHAN, WM TI PREVALENCE OF MICROSCOPIC LESIONS IN GROSSLY NORMAL RENAL PARENCHYMA FROM PATIENTS WITH VON HIPPEL-LINDAU DISEASE, SPORADIC RENAL-CELL CARCINOMA AND NO RENAL-DISEASE - CLINICAL IMPLICATIONS SO JOURNAL OF UROLOGY LA English DT Article DE HIPPEL-LINDAU DISEASE; KIDNEY NEOPLASMS; CARCINOMA, RENAL CELL; KIDNEY CYSTS ID CHROMOSOME-3; MUTATION; REGION; GENE AB Purpose: We sought to describe the earliest renal lesions in patients with von Hippel-Lindau disease to gain insight into the genesis of renal neoplasms in this condition. Materials and Methods: Grossly normal renal parenchyma from von Hippel-Lindau disease patients was examined microscopically and compared to findings in similar tissues obtained from patients with sporadic renal cancer and from autopsy subjects with no renal disease. Results: Microscopic renal cystic and solid neoplasms containing only clear cell cytological features were found in patients with von Hippel-Lindau disease. Benign cysts with clear cell cytological features were found only in patients with von Hippel-Lindau disease. Benign cysts lined by cuboidal cells with eosinophilic cytoplasm, similar to renal tubular cells, were present only in patients with renal cancer. The extrapolated number of clear cell lesions in an average kidney with von Hippel-Lindau disease was estimated as 1,100 cysts (benign or atypical) with clear cell lining and 600 clear cell neoplasms. Conclusions: These findings support the hypothesis that abnormalities in the von Hippel-Lindau gene in a kidney results in the cytological cell type of clear cell renal cancer as the initial product of cellular transformation. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD. RP WALTHER, MM (reprint author), NCI,PATHOL LAB,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 28 TC 103 Z9 105 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 1995 VL 154 IS 6 BP 2010 EP 2014 DI 10.1016/S0022-5347(01)66674-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA TD947 UT WOS:A1995TD94700006 PM 7500446 ER PT J AU SCHUBERT, U CLOUSE, KA STREBEL, K AF SCHUBERT, U CLOUSE, KA STREBEL, K TI AUGMENTATION OF VIRUS SECRETION BY THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VPU PROTEIN IS CELL-TYPE INDEPENDENT AND OCCURS IN CULTURED HUMAN PRIMARY MACROPHAGES AND LYMPHOCYTES SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTIOUS MOLECULAR CLONE; ENVELOPE GLYCOPROTEIN; CYTOPLASMIC DOMAIN; MONONUCLEAR PHAGOCYTES; PRODUCTIVE INFECTION; INDUCED DEGRADATION; AIDS VIRUS; GENE; CD4; MONOCYTES AB The human immunodeficiency virus type 1-specific Vpu protein is a small integral membrane phosphoprotein that induces degradation of the virus receptor CD4 in the endoplasmic reticulum and, independently, increases the release of progeny virions from infected cells. To address the importance of Vpu for virus replication in primary human cells such as peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM), we used three different sets of monocyte-tropic molecular clones of human immunodeficiency virus type 1: a primary isolate, AD8(+), and two chimeric variants of the T-cell-tropic isolate NL4-3 carrying the env determinants of either AD8(+) or SF162 monocyte-tropic primary isolates. Isogenic variants of these chimeric viruses were constructed to express either wild-type Vpu or various mutants of Vpu. The effects of these mutations in the vpu gene on virus particle secretion from infected MDM or PBMC were assessed by determination of the release of virion-associated reverse transcriptase into culture supernatants, Western blot (immunoblot) analysis of pelleted virions, and steady-state or pulse-chase metabolic labeling. Wild-type Vpu increased virus release four- to sixfold in MDM and two- to threefold in PBMC, while nonphosphorylated Vpu and a C-terminal truncation mutant of Vpu were partially active on virus release in primary cells. These results demonstrate that Vpu regulates virus release in primary lymphocyte and macrophage cultures in a similar manner and to a similar extent to those previously observed in HeLa cells or CD4(+) T-cell lines. Thus, our findings provide evidence that Vpu functions in a variety of human cells, both primary cells and continuous cell lines, and mutations in Vpu affect its biological activity independent of the cell type and virus isolate used. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP SCHUBERT, U (reprint author), NIAID,MOLEC MICROBIOL LAB,BLDG 4,RM 314,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 68 TC 94 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 DEC PY 1995 VL 69 IS 12 BP 7699 EP 7711 PG 13 WC Virology SC Virology GA TE366 UT WOS:A1995TE36600038 PM 7494279 ER PT J AU TOUCHMAN, JW DSOUZA, I HECKMAN, CA ZHOU, R BIGGART, NW MURPHY, EC AF TOUCHMAN, JW DSOUZA, I HECKMAN, CA ZHOU, R BIGGART, NW MURPHY, EC TI BRANCHPOINT AND POLYPYRIMIDINE TRACT MUTATIONS MEDIATING THE LOSS AND PARTIAL RECOVERY OF THE MOLONEY MURINE SARCOMA-VIRUS MUSVTS110 THERMOSENSITIVE SPLICING PHENOTYPE SO JOURNAL OF VIROLOGY LA English DT Article ID PRE-MESSENGER-RNA; BASE-PAIRING INTERACTION; SITE SELECTION; MAMMALIAN INTRONS; BINDING PROTEIN; VIRAL RNAS; U6 SNRNA; U1 SNRNA; SEQUENCES; SPLICEOSOME AB Balanced splicing of retroviral RNAs is mediated by weak signals at the 3' splice site (ss) acting in concert with other cia elements. Moloney murine sarcoma virus MuSVts110 shows a similar balance between unspliced and spliced RNAs, differing only in that the splicing of its RNA is, in addition, growth temperature sensitive. We have generated N-nitroso-N-methylurea (NMU)-treated MuSVts110 revertants in which splicing was virtually complete at all temperatures and have investigated the molecular basis of this reversion on the assumption that the findings would reveal cis-acting elements controlling MuSVts110 splicing thermosensitivity. In a representative revertant (NMU-20), we found that complete splicing was conferred by a G-to-A substitution generating a consensus branchpoint (BP) signal (-CCCUG (G) under bar GC- to -CCCUG (A) under bar AC- [termed G(-25)A]) at -25 relative to the 3' ss. Weakening this BP to -CCC (C) under bar CGAC- [G(-25)A,U(-27)C] moderately reduced splicing at the permissive temperature and sharply inhibited splicing at the originally nonpermissive temperature, arguing that MuSVts110 splicing thermosensitivity depends on a suboptimal BP-U2 small nuclear RNA interaction. This conclusion was Supported by results indicating that lengthening the short MnSVts110 polypyrimidine tract and altering its uridine content doubled splicing efficiency at Permissive temperatures and nearly abrogated splicing thermosensitivity. In vitro splicing experiments showed that MuSVts110 G(-25)A RNA intermediates were far more efficiently ligated than RNAs carrying the wild-type BP, the G(-25)A,U (-27)C BP, or the extended polypyrimidine tract, The efficiency of ligation in vitro roughly paralleled splicing efficiency in vivo [G(-25)A BP > extended polypyrimidine tract > G(-25)A,U(-27)C BP > wild-type BP]. These results suggest that MuSVts110 RNA splicing is balanced by cis elements similar to those operating in other retroviruses and, in addition, that its splicing thermosensitivity is a response to the presence of multiple suboptimal splicing signals. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT TUMOR BIOL,MOLEC VIROL SECT,HOUSTON,TX 77030. NATL INST HLTH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. SAN DIEGO STATE UNIV,DEPT BIOL,SAN DIEGO,CA 92182. FU NCI NIH HHS [CA-16672, CA-34734]; NIEHS NIH HHS [ES-05323] NR 71 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1995 VL 69 IS 12 BP 7724 EP 7733 PG 10 WC Virology SC Virology GA TE366 UT WOS:A1995TE36600041 PM 7494282 ER PT J AU YAMADA, T WHEELER, CM HALPERN, AL STEWART, ACM HILDESHEIM, A JENISON, SA AF YAMADA, T WHEELER, CM HALPERN, AL STEWART, ACM HILDESHEIM, A JENISON, SA TI HUMAN PAPILLOMAVIRUS TYPE-16 VARIANT LINEAGES IN UNITED-STATES POPULATIONS CHARACTERIZED BY NUCLEOTIDE-SEQUENCE ANALYSIS OF THE E6, L2, AND L1 CODING SEGMENTS SO JOURNAL OF VIROLOGY LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; COTTONTAIL RABBIT PAPILLOMAVIRUS; VIRUS-LIKE PARTICLES; OPEN READING FRAME; CAPSID PROTEINS; GENE-PRODUCTS; DNA-SEQUENCE; HPV E6; CANCER; ANTIBODIES AB Human papillomavirus type 16 (HPV16) nucleotide sequence variations in the E6 (nucleotide positions [nt] 104 to 559), L2 (nt 4272 to 5657), and L1 (nt 5665 to 7148) open reading frames (ORFs), and the long control region (nt 7479 to 7842), were examined in 29 selected United States isolates. Of 3,690 nucleotide positions, 129 (3.5%) varied. The maximum pairwise distance was 66 nucleotide differences, or 1.8%. Nucleotide variations within different genome segments were phylogenetically compatible, and nucleotide changes within E6, L2, and L1 contained phylogenetic information beyond that provided in the long control region. Most isolates were classified as members of HPV16 lineages that have been described previously. However, two novel phylogenetic branches were identified. The L2 ORF was the most variable coding segment. L2 synonymous and nonsynonymous nucleotide changes were distributed asymmetrically. The amino-terminal half of the L2 protein was remarkably conserved-among all isolates, suggesting that the region is under evolutionary constraint. The amino terminal region of the E6 ORF was relatively varied, especially at E6 amino acid positions 10 and 14. Several amino acid differences in the L1 ORF were observed between lineages. Forty-nine amino acid variations across all sequenced coding regions were observed. These amino acid differences may be relevant to differences in the generation of humoral or cell-mediated immune responses to HPV16 variants. Our data form a basis for considering HPV16 sequence variation in the rational design of vaccine strategies and as an epidemiologic correlate of cervical cancer risk. C1 UNIV NEW MEXICO,CTR CANC RES & TREATMENT,DEPT CELL BIOL,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,SCH MED,DEPT MED,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,SCH MED,DEPT MICROBIOL,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,SCH MED,DEPT CELL BIOL,ALBUQUERQUE,NM 87131. LOS ALAMOS NATL LAB,DIV THEORET,LOS ALAMOS,NM 87545. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. FU NCI NIH HHS [CA57975]; NIAID NIH HHS [AI32917] NR 78 TC 172 Z9 180 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1995 VL 69 IS 12 BP 7743 EP 7753 PG 11 WC Virology SC Virology GA TE366 UT WOS:A1995TE36600043 PM 7494284 ER PT J AU PRIOLA, SA CHESEBRO, B AF PRIOLA, SA CHESEBRO, B TI A SINGLE HAMSTER PRP AMINO-ACID BLOCKS CONVERSION TO PROTEASE-RESISTANT PRP IN SCRAPIE-INFECTED MOUSE NEUROBLASTOMA-CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID CREUTZFELDT-JAKOB DISEASE; PRION PROTEIN; TRANSGENIC MICE; CULTURED-CELLS; AGENT; GENE; LINKAGE; ACCUMULATION; POLYMORPHISM; TRANSMISSION AB Neurodegeneration caused by the transmissible spongiform encephalopathies is associated with the conversion of a normal host protein, PrP-sen, into an abnormal aggregated protease-resistant form, PrP-res. In scrapie-infected mouse neuroblastoma cells, mouse PrP-sen is converted into PrP-res but recombinant hamster PrP-sen expressed in these cells is not. In the present studies, recombinant hamster/mouse PrP-sen molecules were expressed in these scrapie-infected cells to define specific PrP amino acid residues critical for the conversion to PrP-res. The results showed that homology to the region of mouse PrP-sen from amino acid residues 112 to 138 was required for conversion of recombinant PrP-sen to PrP-res in scrapie-infected mouse cells. Furthermore, a single hamster-specific PrP amino acid at residue 138 could inhibit the conversion of the recombinant PrP-sen into PrP-res. The data are consistent,vith studies in humans which show that specific amino acid residue changes within PrP can influence disease pathogenesis and transmission of transmissible spongiform encephalopathies across species barriers. RP PRIOLA, SA (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 41 TC 102 Z9 106 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1995 VL 69 IS 12 BP 7754 EP 7758 PG 5 WC Virology SC Virology GA TE366 UT WOS:A1995TE36600044 PM 7494285 ER PT J AU DOWHANICK, JJ MCBRIDE, AA HOWLEY, PM AF DOWHANICK, JJ MCBRIDE, AA HOWLEY, PM TI SUPPRESSION OF CELLULAR PROLIFERATION BY THE PAPILLOMAVIRUS E2 PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID HPV18 REGULATORY REGION; LARGE T-ANTIGEN; GENE-PRODUCT; DNA-BINDING; HUMAN KERATINOCYTES; MUTATIONAL ANALYSIS; TRANSFORMED CELLS; TRANS-ACTIVATION; MAMMALIAN-CELLS; TERMINAL DOMAIN AB Carcinogenic progression of a human papillomavirus (HPV)-infected cell is often associated with integration of the viral genome in a manner which results in the loss of expression of the viral regulatory protein E2. One function of E2 is the regulation of expression of the viral oncogenes, E6 and E7. Introduction of the bovine papillomavirus type 1 (BPV-1) E2 transactivator (E2-TA) in HeLa cells, an HPV type 18 (HPV-IS)-positive cervical carcinoma cell line results in growth arrest. In this study, we have found that the HPV-16 and HPV-18 E2 proteins share with BPV-1 E2-TA the ability to suppress HeLa cell growth. This property was not observed for the BPV-1 E2 transcriptional repressor (E2-TR). Analysis of various mutant E2 proteins for growth suppression revealed a requirement for the intact transactivation and DNA binding domains. A HeLa cell line (HeLa-tsE2) which expressed a conditional mutant E2 protein that was functional only at the permissive temperature (32 degrees C) was established, permitting an analysis of the molecular and cellular consequences of E2 expression. Our data indicate that one mechanism by which E2 suppresses cellular growth is through repression of E6 and E7 expression, thereby enabling the cellular targets of E6 and E7 to resume regulation of the cell cycle. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NIH,VIRAL DIS LAB,BETHESDA,MD 20892. OI McBride, Alison/0000-0001-5607-5157 NR 62 TC 162 Z9 165 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1995 VL 69 IS 12 BP 7791 EP 7799 PG 9 WC Virology SC Virology GA TE366 UT WOS:A1995TE36600049 PM 7494290 ER PT J AU HUI, RT CURTIS, JF SUMNER, MT SHEARS, SB GLASGOW, WC ELING, TE AF HUI, RT CURTIS, JF SUMNER, MT SHEARS, SB GLASGOW, WC ELING, TE TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE PROTEIN DOES NOT STIMULATE EITHER PROSTAGLANDIN FORMATION OR THE EXPRESSION OF PROSTAGLANDIN-H SYNTHASE IN THP-1 HUMAN MONOCYTES MACROPHAGES SO JOURNAL OF VIROLOGY LA English DT Article ID TYROSINE KINASE P56LCK; ARACHIDONIC-ACID; G/H SYNTHASE; T-CELLS; GP120; CYCLOOXYGENASE; INDUCTION; CD4; LIPOPOLYSACCHARIDE; PHOSPHORYLATION AB Prostaglandin E(2) is observed at elevated levels during human immunodeficiency virus (HIV) infection and thus may contribute to the HIV-dependent immunosuppression. The mechanisms responsible for this increase are not understood. Evidence indicates that the viral envelope proteins perturb membrane signaling mediated by the CD4 receptor, suggesting that the free envelope protein and/or the intact virus may be responsible for the increase in prostaglandin E(2) levers. In this study, we have used THP-1 human monocytes and THP-1 cells differentiated by 12-O-tetradecanoylphorbol-13-acetate treatment into macrophages to determine if the HIV envelope protein, gp120, or an anti-CD4 receptor antibody stimulates prostaglandin formation by interacting with the CD4 receptor. Incubation of THP-1 cells with OKT4A antibody greatly stimulated the CD4-p56(lck): receptor complex as estimated by enhanced p56(lck) autophosphorylation, whit the gp120 gave small but significant responses. Monocytic THP-1 cells poorly metabolized arachidonic acid to prostaglandin E(2) and thromboxane B-2 as measured by high-pressure liquid chromatography analysis. Western blot (immunoblot) and Northern (RNA) blot analyses revealed that unstimulated monocytes expressed little prostaglandin H synthase 1 and 2 (PGHS-1 and -2). Incubation of the monocytes with lipopolysaccharide, OKT4A, or gp120 did not increase the formation of prostaglandins. The expression of PGHS-1 or PGHS-2 was also not increased. Differentiation of the monocytes to macrophages by 12-O-tetradecanoylphorbol-13-acetate treatment resulted in increased expression of PGHS-1 and increased formation of prostaglandins compared with that for the monocytes. Lipopolysaccharide stimulation of the macrophages increased the formation of prostaglandins and increased the expression of PGHS-2 in the macrophages. However, OKT4A or gp120 preparation, at concentrations that stimulated p56(lck) autophosphorylation, did not enhance the formation of prostaglandins or the expression of PGHS-1 or PGHS-2. OKT4A and gp120 also did not stimulate the release of arachidonic acid, indicating that phospholipase A(2) was not activated by the CD4 receptor in either the THP-I monocytes or macrophages. These results indicate that activation of the CD4-p56(lck) receptor signal transduction pathway by the HIV envelope protein does not increase prostaglandin formation. C1 NIEHS, MOLEC BIOPHYS LAB, EICOSANOID BIOCHEM SECT, RES TRIANGLE PK, NC 27709 USA. NIEHS, CELLULAR & MOLEC PHARMACOL LAB, RES TRIANGLE PK, NC 27709 USA. NR 38 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1995 VL 69 IS 12 BP 8020 EP 8026 PG 7 WC Virology SC Virology GA TE366 UT WOS:A1995TE36600074 PM 7494315 ER PT J AU SECCHIERO, P NICHOLAS, J DENG, HY TANG, XP VANLOON, N RUVOLO, VR BERNEMAN, ZN REITZ, MS DEWHURST, S AF SECCHIERO, P NICHOLAS, J DENG, HY TANG, XP VANLOON, N RUVOLO, VR BERNEMAN, ZN REITZ, MS DEWHURST, S TI IDENTIFICATION OF HUMAN TELOMERIC REPEAT MOTIFS AT THE GENOME TERMINI OF HUMAN HERPESVIRUS-7 - STRUCTURAL-ANALYSIS AND HETEROGENEITY SO JOURNAL OF VIROLOGY LA English DT Note ID MAREKS-DISEASE VIRUS; A-SEQUENCE; DNA; PREVALENCE; INVERSION; CLEAVAGE; CHILDREN; SIGNALS; STRAIN; SITE AB Human herpesvirus 6 (HHV-6) and HHV-7 are closely related T-lymphotropic betaherpesviruses which share a common genomic organization and are composed of a single unique component (U) that is bounded by direct repeats (DR(L) and DR(R)). In HHV-6, a sequences have been identified at each end of the DR motifs, resulting in the arrangement aDR(L)a-U-aDR(R)a, In order to determine whether HHV-7 contains similar a sequences, we have sequenced the DR(L)-U and U-DR(R) junctions of HHV-7 strain JI, together with the DR(R) . DR(L) junction from the head-to-tail concatamer that is generated during productive virus infection. In addition, we have sequenced the genomic termini of an independent isolate of HHV-7, As in HHV-6, a (GGGTTA)(n) motif identical to the human telomeric repeat sequence (TRS) was identified adjacent to, but not at, the genome termini of HHV-7, The left genome terminus and the U-DR(R) junction contained a homolog of the consensus herpesvirus packaging signal, pac-1, followed by short tandem arrays of TRSs separated by single copies of a second 6-bp repeat, This organization is similar to the arrangement found at U-DR(R) in HHV-6 but differs from it in that the TRS arrays are considerably shorter in HHV-7. The right genome terminus and the DR(L)-U junction contained a homolog of the consensus herpesvirus packaging signal, pac-2, followed by longer tandem arrays of TRSs separated by single copies of either a 6-bp or a 14-bp repeat. This arrangement is considerably more complex than the simple tandem array of TRSs that is present at the corresponding genomic location in HHV-6 and corresponds to a site of both inter- and intrastrain heterogeneity in HHV-7. The presence of TRSs in lymphotropic herpesviruses from humans (HHV-6 and HHV-7), horses (equine herpesvirus 2), and birds (Marek's disease virus) is striking and suggests that these sequences may have functional or structural significance. C1 UNIV ROCHESTER,MED CTR,DEPT MICROBIOL & IMMUNOL,ROCHESTER,NY 14642. NIH,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21231. UNIV ANTWERP HOSP,B-2650 EDEGEM,BELGIUM. HUNAN MED UNIV,AFFILIATED HOSP 2,CHANGSHA,PEOPLES R CHINA. RI secchiero, paola/G-9689-2015; OI secchiero, paola/0000-0003-4101-7987; Dewhurst, Stephen/0000-0001-7729-7920 FU NIAID NIH HHS [KO4 AI01240, R01 AI34231] NR 44 TC 33 Z9 35 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1995 VL 69 IS 12 BP 8041 EP 8045 PG 5 WC Virology SC Virology GA TE366 UT WOS:A1995TE36600077 PM 7494318 ER PT J AU KORDON, EC SMITH, GH CALLAHAN, R GALLAHAN, D AF KORDON, EC SMITH, GH CALLAHAN, R GALLAHAN, D TI A NOVEL NON-MOUSE MAMMARY-TUMOR VIRUS-ACTIVATION OF THE INT-3 GENE IN A SPONTANEOUS MOUSE MAMMARY-TUMOR SO JOURNAL OF VIROLOGY LA English DT Note ID INTRACISTERNAL-A-PARTICLE; PROVIRAL INSERTION; TRANSGENIC MICE; HOMEOBOX GENE; EXPRESSION; REGION; CELLS; TRANSFORMATION; IDENTIFICATION; TUMORIGENESIS AB In a mouse mammary tumor model system in which carcinogenic progression can be investigated, we have found a unique mutation of Int-3 associated with progression from premalignant lobular hyperplasia to tumor. Sequence analysis of the rearranged fragment revealed an insertion of an intracisternal type A particle (IAP) within the Int-3 gene. Int-3 is mutated frequently in mouse mammary tumor virus (MMTV)-induced mammary tumors by insertion of MMTV proviral DNA into this intragenic region. In these mutations, the insertion produces a chimeric Int-3 transcript encoding the cytoplasmic portion of the Int-3 protein driven by the MMTV long terminal repeat promoter. In this case, the IAP DNA was inserted in the opposite transcriptional orientation relative to Int-3; nevertheless, a similar chimeric RNA transcript driven by a cryptic promoter in the oppositely oriented 5' IAP long terminal repeat was generated. This is the first demonstration that an insertional mutation unrelated to MMTV activates an Int gene commonly associated with mammary tumorigenesis. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 28 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1995 VL 69 IS 12 BP 8066 EP 8069 PG 4 WC Virology SC Virology GA TE366 UT WOS:A1995TE36600082 PM 7494323 ER PT J AU PORTIS, JL CZUB, S ROBERTSON, S MCATEE, F CHESEBRO, B AF PORTIS, JL CZUB, S ROBERTSON, S MCATEE, F CHESEBRO, B TI CHARACTERIZATION OF A NEUROLOGIC DISEASE INDUCED BY A POLYTROPIC MURINE RETROVIRUS - EVIDENCE FOR DIFFERENTIAL TARGETING OF ECOTROPIC AND POLYTROPIC VIRUSES IN THE BRAIN SO JOURNAL OF VIROLOGY LA English DT Note ID CENTRAL-NERVOUS-SYSTEM; INDUCED SPONGIFORM ENCEPHALOPATHY; LEUKEMIA-VIRUS; INFECTION; CELLS; MICE; PATHOGENESIS; EXPRESSION; MYELOENCEPHALOPATHY; NEUROVIRULENCE AB A variety of ecotropic murine leukemia viruses cause neurodegenerative disease. We describe here the clinical and histopathological features of a neurologic disease induced by a polytropic murine leukemia virus, FMCF98. Clinical disease was dominated by hyperexcitability and ataxia, and the histopathology was characterized primarily by astrocytosis and astrocytic degeneration. The viral envelope gene harbored the determinants of neurovirulence, since the chimeric virus Fr98(E), which contained the envelope gene of FMCF98 on a background of the nonneurovirulent virus FB29, caused a similar disease. The disease caused by Fr98(E) differed from that induced by the coisogenic neurovirulent ecotropic virus FrCas(E) in clinical presentation, histopathology, and distribution of virus in the central nervous system. Since Fr98(E) contains;a polytropic envelope gene and FrCas(E) contains an ecotropic envelope gene, these phenotypic differences appeared to be determined by envelope sequences and may reflect differences in virus receptor usage in the central nervous system. RP PORTIS, JL (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 38 TC 39 Z9 39 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1995 VL 69 IS 12 BP 8070 EP 8075 PG 6 WC Virology SC Virology GA TE366 UT WOS:A1995TE36600083 PM 7494324 ER PT J AU HEINEMAN, TC CONNELLY, BL BOURNE, N STANBERRY, LR COHEN, J AF HEINEMAN, TC CONNELLY, BL BOURNE, N STANBERRY, LR COHEN, J TI IMMUNIZATION WITH RECOMBINANT VARICELLA-ZOSTER VIRUS EXPRESSING HERPES-SIMPLEX VIRUS TYPE-2 GLYCOPROTEIN-D REDUCES THE SEVERITY OF GENITAL HERPES IN GUINEA-PIGS SO JOURNAL OF VIROLOGY LA English DT Note ID DNA-SEQUENCE; INFECTION; PROTECTION; VACCINE; ANTIGEN; DISEASE; GENE AB Varicella-zoster virus (VZV) is an attractive candidate for a live-virus vector for the delivery of foreign antigens. The Oka vaccine strain of VZV is safe and effective in humans, and recombinant Oka VZV (ROka) can be generated by transfecting cells with a set of overlapping cosmid DNAs. By this method, the herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) gene was inserted into an intergenic site in the unique short region of the Oka VZV genome. Expression of gD2 in cells infected,vith the recombinant Oka strain VZV (ROka-gD2) was confirmed by antibody staining of fixed cells and by immunoblot analysis. Immune electron microscopy demonstrated the presence of gD2 in the envelope of ROka-gD2 virions. The ability of ROka-gD2 to protect guinea pigs against HSV 2 challenge was assessed by inoculating animals with three doses of uninfected human fibroblasts, fibroblasts infected with ROka VZV, or fibroblasts infected with ROka-gD2. Neutralizing antibodies specific for HSV-2 developed in animals immunized with ROka-gD2. Forty days after the third inoculation, animals were challenged intravaginally with HSV-2. Inoculation of guinea pigs,vith ROka-gD2 significantly reduced the severity of primary HSV 2 infection (P < 0.001). These experiments demonstrate that the Oka strain of VZV can be used as a live virus vector to protect animals from disease with a heterologous virus. C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892. CHILDRENS HOSP RES FDN,CINCINNATI,OH 45229. FU NIAID NIH HHS [AI15101, AI29687, AI22667] NR 32 TC 42 Z9 44 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1995 VL 69 IS 12 BP 8109 EP 8113 PG 5 WC Virology SC Virology GA TE366 UT WOS:A1995TE36600090 PM 7494331 ER PT J AU KAKIZAKI, Y WAGA, S SUGIMOTO, K TANAKA, H NUKII, K TAKEYA, M YOSHIMURA, T YOKOYAMA, M AF KAKIZAKI, Y WAGA, S SUGIMOTO, K TANAKA, H NUKII, K TAKEYA, M YOSHIMURA, T YOKOYAMA, M TI PRODUCTION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 BY BOVINE GLOMERULAR ENDOTHELIAL-CELLS SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the American-Society-of-Nephrology CY OCT 26-29, 1994 CL ORLANDO, FL SP Amer Soc Nephrol ID STIMULATING FACTOR-I; MESANGIAL CELLS; INTERFERON-GAMMA; EXPRESSION; MCP-1; CHEMOTAXIS; INDUCTION; ACID; GENE; JE AB To explore the role of glomerular endothelial cells (GEN) in the pathogenesis of glomerulonephritis, the in vitro production of monocyte chemoattractant protein-1 (MCP-1) by bovine GEN was determined by chemotaxis assay. Northern and Western blot analysis, and immunocytochemistry. Monocyte chemotactic activity of GEN-conditioned media was detectable by a chemotaxis assay using human peripheral blood monocytes. Exposure to human recombinant interleukin-1 beta (IL-1 beta) and phorbol myristate acetate (PMA) significantly increased the chemotactic activity of GEN-conditioned media. A checkerboard analysis showed that the response of monocytes to GEN-conditioned media was truly chemotactic. Immunoadsorption with a monoclonal antibody to human MCP-1 reduced the chemotactic activity of GEN-conditioned media by 85%. Northern blot analysis revealed that MCP-1 mRNA was constitutively expressed by GEN and that IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) increased MCP-1 mRNA levels in a dose- and time-dependent manner. Furthermore, PMA induced an increase in MCP-1 mRNA levels, whereas dibutyryl cyclic AMP and forskolin had minimal effects. Inhibition study using protein kinase inhibitors revealed that MCP-1 mRNA expression induced by IL-1 beta and TNF-alpha was suppressed by the tyrosine kinase inhibitor genistein, not by the protein kinase C inhibitors staurosporine or H-7, or the protein kinase A inhibitor H-89, suggesting an important role of tyrosine kinase in the cytokine-induced MCP-1 gene expression. Dexamethasone had a small inhibitory effect on constitutive MCP-1 mRNA expression, but no effect on the induction by TNF-alpha. By immunoperoxidase staining and Western blot analysis using an anti-MCP-1 monoclonal antibody, MCP-1 protein was detected in untreated GEN and increased by exposure to TNF-alpha. These results demonstrate the cytokine-induced production of MCP-1 by GEN at gene and protein levels as well as bioactivity, and suggest that GEN may participate in the development of glomerulonephritis through the production of MCP-1. C1 KUMAMOTO UNIV,SCH MED,DEPT PATHOL,KUMAMOTO 860,JAPAN. NCI,IMMUNOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21701. RP KAKIZAKI, Y (reprint author), HIROSAKI UNIV,SCH MED,DEPT PEDIAT,5 ZAIFU CHO,HIROSAKI,AOMORI 036,JAPAN. NR 47 TC 43 Z9 44 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1995 VL 48 IS 6 BP 1866 EP 1874 DI 10.1038/ki.1995.485 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA TF645 UT WOS:A1995TF64500020 PM 8587246 ER PT J AU Brown, SES Guzelian, CP Schuetz, E Quattrochi, LC Kleinman, HK Guzelian, PS AF Brown, SES Guzelian, CP Schuetz, E Quattrochi, LC Kleinman, HK Guzelian, PS TI Critical role of extracellular matrix oil induction by phenobarbital of cytochrome P450 2B1/2 in primary cultures of adult rat hepatocytes SO LABORATORY INVESTIGATION LA English DT Article DE Matrigel; YIGSR; SIKVAV; laminin ID GENE-EXPRESSION; BASEMENT-MEMBRANE; GROWTH-HORMONE; A-CHAIN; LAMININ; RECEPTOR; LIVER; PROTEIN; INVITRO; CELLS AB BACKGROUND: Although it has been known for more than three decades that administration of lipophilic chemicals, including phenobarbital, produces liver hypertrophy, proliferation of smooth endoplasmic reticulum, and induction of liver microsomal enzymes such as cytochromes P450 (CYP) 2B1 and 2B2, the mechanism of this adaptive response remains largely unknown. An important advance was the recognition that, unlike cultures of continuously proliferating liver cell lines or cultures of primary non-proliferating adult rat hepatocytes maintained on either plastic or collagen-coated dishes, hepatocytes cultured on a basement membrane gel, Matrigel, formed rounded clusters and permitted phenobarbital-mediated induction in vitro of CYP 2B1/2 mRNAs and immunoreactive proteins (1). EXPERIMENTAL DESIGN AND RESULTS: We cultured adult rat hepatocytes on Type I collagen (Vitrogen) and allowed the cells to spread, flatten, and firmly attach to the substratum. Subsequent incubation in medium containing Matrigel as a soluble component, fully restored, in a dose-dependent manner, the ability to respond to phenobarbital with induction of CYP 2B1/2 mRNAs. Repeating this experiment with medium containing equivalent amounts of purified laminin, a major component of Matrigel, or with YIGSR or SIKVAV, two peptides known to mimic various activities of laminin, similarly restored phenobarbital responsiveness to hepatocytes cultured on Vitrogen. In contrast, use of equal amounts of SHA-23, a scrambled peptide relevant to SIKVAV, produced no such effect. None of these treatments caused a rounding or any other observable change in the flattened, cellular morphology, making it unlikely that cell spreading or alterations in cell shape account for loss of such differentiated liver functions as phenobarbital induction of CYP 2B1/2 mRNAs in cultured hepatocytes on Vitrogen. Hepatocytes cultured on Matrigel in the presence of either colchicine, cytochalasins B and D, nocodazole, or taxol did not show induction of 2B1/2 mRNAs by phenobarbital specifically, while the amounts of both albumin and glucose-6-phosphate dehydrogenase (G6PD) mRNAs were unaffected. CONCLUSIONS: We conclude that the process by which phenobarbital induces 2B1/2 mRNAs in hepatocytes appears to require highly concerted effects of specific extracellular components prominently involving laminin. This likely occurs through a signal transduction process requiring probably both microfilament and microtubular integrity. C1 ST JUDE CHILDRENS RES HOSP, DEPT PHARMACEUT SCI, MEMPHIS, TN USA. NIDR, BETHESDA, MD 20892 USA. RP Brown, SES (reprint author), UNIV COLORADO, HLTH SCI CTR,HEPATOBILIARY RES CTR, SECT MED TOXICOL,4200 E 9TH AVE, BOX B-146, DENVER, CO 80262 USA. FU NIDDK NIH HHS [5 P30 DK34914]; NIEHS NIH HHS [5PO1-ES04238, 5RO1-ES05744] NR 47 TC 21 Z9 21 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 1995 VL 73 IS 6 BP 818 EP 827 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TL725 UT WOS:A1995TL72500010 PM 8558843 ER PT J AU Giuliani, A Vernole, P DAtri, S DelPoeta, G DOnofrio, C Faraoni, I Greiner, JW Bonmassar, E Graziani, G AF Giuliani, A Vernole, P DAtri, S DelPoeta, G DOnofrio, C Faraoni, I Greiner, JW Bonmassar, E Graziani, G TI In vitro infection of leukemic bone marrow with HTLV-I generates immortalized cell lines expressing T or myeloid cell phenotype SO LEUKEMIA LA English DT Article DE HTLV-I; AML; triazenes; immortalization; bone marrow ID VIRUS TYPE-I; BLOOD MONONUCLEAR-CELLS; PERIPHERAL-BLOOD; INTERFERON-GAMMA; TUMOR-CELLS; TAX GENE; HLA-GENE; LYMPHOMA; INVITRO; TRANSFORMATION AB Leukemic bone marrow cells (>90% blasts) of a patient with acute myeloblastic leukemia (AML), non-treated or pretreated in vitro with a mutagenic triazene compound, were infected with HTLV-I by coculture with irradiated virus-donor cells. Immortalized, HTLV-I+, double-positive CD4/CD8 euploid T cell lines, expressing HLA class I/II monomorphic determinants, and inappropriate myeloid and progenitor cell markers (ie CD13, CD14, CD15 and CD33 antigens) were obtained. In one out of 10 triazene-pretreated samples, HTLV-I infection resulted in the appearance of a rapidly growing triploid cell line tie MTLC1 line) showing: (1) myeloid but not lymphoid phenotype; (2) beta and delta T cell receptor in germline configuration; (3) integrated, complete and incomplete HTLV-I provirus genome (also detected in a number of MTLC1 clones); (4) a high percentage of cells positive for non-specific cross-reacting antigen (a CEA-related molecule present on myeloid cells) under the influence of gamma-interferon; (5) absence of HLA class I/II antigen expression; (6) absence of tax gene transcription. Blast cell proliferation was marginal or absent when leukemic marrow was not subjected to retroviral infection. These results show that exposure of leukemic bone marrow to HTLV-I can be followed by immortalization of T and myeloid cells. Although no data are available to establish whether tax expression played a role in the early phase of the immortalization process of MTLC1 line, fax gene product was not required for maintaining longterm growth of MTLC1 cells. C1 CNR,INST EXPTL MED,ROME,ITALY. UNIV ROMA TOR VERGATA,SCH MED,CHAIR PHARMACOL,DEPT EXPTL MED & BIOCHEM SCI,I-00133 ROME,ITALY. UNIV ROMA TOR VERGATA,DEPT PUBL HLTH & CELL BIOL,I-00133 ROME,ITALY. IST DERMOPAT IMMACOLATA,ROME,ITALY. S EUGENIO HOSP,DEPT INTERNAL MED,CHAIR HEMATOL,ROME,ITALY. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RI Graziani, Grazia/G-5747-2012; OI D'Atri, Stefania/0000-0001-9852-7377; DEL POETA, GIOVANNI/0000-0003-2443-1422; GRAZIANI, GRAZIA/0000-0002-0221-768X NR 58 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 DEC PY 1995 VL 9 IS 12 BP 2071 EP 2081 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA TQ154 UT WOS:A1995TQ15400014 PM 8609719 ER PT J AU ZHOU, XH MARONPOT, RR HEDLUND, LW COFER, GP JOHNSON, GA AF ZHOU, XH MARONPOT, RR HEDLUND, LW COFER, GP JOHNSON, GA TI DETECTION OF BROMOBENZENE-INDUCED HEPATOCELLULAR NECROSIS USING MAGNETIC-RESONANCE MICROSCOPY SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MR MICROSCOPY; IN VIVO HISTOLOGY; HEPATOCELLULAR NECROSIS ID INDUCED LIVER-DAMAGE; MR MICROSCOPY; DIFFUSION; SUSCEPTIBILITY; SPECTROSCOPY; NMR; RAT AB The authors used magnetic resonance (MR) microscopy to assess hepatic tissue damage induced by bromobenzene both in living rats and in fixed rat liver tissues, Experiments were conducted at 7 Tesla on three groups of Fisher rats treated with bromobenzene at a single dose of 68, 135, and 269 mg/kg, respectively, Optical microscopy of hematoxylin and eosin stained sections showed liver damage only at the highest dose, whereas with MR microscopy, tissue alterations were detected at all three doses both in vivo and ex vivo, The contrast mechanism of the superior sensitivity of MR microscopy is believed to be related to the changes in local diffusion coefficients that accompany cellular degeneration and death, although other contrast mechanisms may also be involved, The superior sensitivity of MR microscopy, as demonstrated in this study, has many implications for potential use of MR techniques to perform in vivo histology. C1 DUKE UNIV,MED CTR,DEPT RADIOL,CTR VIVO MICROSCOPY,DURHAM,NC 27710. NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC. OI Hedlund, Laurence/0000-0001-5275-0397; Johnson, G.Allan/0000-0002-7606-5447 FU NIEHS NIH HHS [R02 ES04187]; PHS HHS [P41 05959] NR 18 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD DEC PY 1995 VL 34 IS 6 BP 853 EP 857 DI 10.1002/mrm.1910340610 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TH396 UT WOS:A1995TH39600009 PM 8598812 ER PT J AU WEN, H JAFFER, FA AF WEN, H JAFFER, FA TI AN IN-VIVO AUTOMATED SHIMMING METHOD TAKING INTO ACCOUNT SHIM CURRENT CONSTRAINTS SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE COMPUTERIZED; SHIMMING; MAGNETIC FIELD ID BONE AB Many in vivo imaging techniques require magnetic field homogeneity in the volume of interest, Shim coils of the second and third order spherical harmonics have been used successfully to compensate for complicated field variations caused by the human anatomy itself, The available currents of these coils are invariably limited. In this note we demonstrate that these limits significantly affect the optimal shim condition, We propose an automated in vivo shimming method for arbitrary volumes of interest using 3-dimensional (3D) field maps, This method is a modification of previous works using least-squares criteria, The main difference is that a constrained optimization is performed in vivo under the current limits of the shim coils, which improved the field homogeneity significantly over simple truncations of the least-squares solutions, This shimming method was used with head scans of five normal volunteers on a 4.0 tesla scanner. A fast double-echo sequence was used to obtain field maps, and a new field uniformity measure was derived for this method, The field mapping sequence was tested against a standard single-echo Dixon sequence used by previous investigators, and the stability of the shimming method was tested by repeated studies on the same subject. C1 NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [Z01 HL004606-12] NR 18 TC 35 Z9 35 U1 0 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD DEC PY 1995 VL 34 IS 6 BP 898 EP 904 DI 10.1002/mrm.1910340616 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TH396 UT WOS:A1995TH39600015 PM 8598818 ER PT J AU BROAD, TE LEWIS, PE BURKIN, DJ GLEESON, AJ CARPENTER, MA JONES, C PEARCE, PD MAHER, DW ANSARI, HA AF BROAD, TE LEWIS, PE BURKIN, DJ GLEESON, AJ CARPENTER, MA JONES, C PEARCE, PD MAHER, DW ANSARI, HA TI 13 LOCI PHYSICALLY ASSIGNED TO SHEEP CHROMOSOME-2 BY CELL HYBRID ANALYSIS AND IN-SITU HYBRIDIZATION SO MAMMALIAN GENOME LA English DT Article ID TROPHOBLAST INTERFERON GENES; CELLULOSE-ACETATE GEL; ENZYME ELECTROPHORESIS; SUBUNIT PRECURSOR; ZYMOGRAM PATTERNS; CDNA SEQUENCE; MAN-MOUSE; LOCALIZATION; EXPRESSION; GENOME AB Sheep x hamster cell hybrids containing sheep metacentric Chromosome (Chr) 2 were produced by fusing blood leukocytes from normal sheep with hamster auxotrophic Ade F-minus mutants. Cell clones that were isocitrate dehydrogenase I (IDH1) positive were cytogenetically characterized, confirming that they contained sheep Chr 2. The following loci were newly assigned by Southern hybridization to sheep Chr 2: lipoprotein lipase (LPL), glycoprotein-4-beta galactosyltransferase 2 (GGT82), neurofilament light polypeptide (68 kDa; NEFL), surfactant-associated protein 2 (SFTP2), lymphocyte-specific protein tyrosine kinase (LCK), and nebulin (NEB). These new assignments and the in situ localization of grelsolin (GSN) to sheep Chr 2pter-p24 are consistent with the predicted homology of cattle Chr 8 (U18) with sheep Chr 2p, and of cattle Chr 2 (U17) with sheep 2q. In addition, the assignment by cell hybrid analysis of loci previously mapped to Chr 2 in sheep, viz., cholinergic receptor, nicotinic, delta polypeptide (CHRND), collagen type III alpha 1 (COL3AI), fibronectin 1 (FN1), isocitrate dehydrogenase (IDH1), and villin 1 (VIL1), confirmed the localization of sheep syntenic group U11 to this chromosome. By nutritional selection and complementation of the hamster auxotrophic Ade F mutation, the multifunctional enzyme locus phosphoribosylaminoimidazolecarboxamide formy/transferase (AICAR transformylase)/IMP cyclohydrolase (inosinicase) (provisionally given the symbol PRACFT) has also been newly assigned to sheep Chr 2. This report significantly extends the number of loci physically mapped to sheep Chr 2 and confirms its close homology with cattle Chrs 2 and 8. C1 AGRES GRASSLANDS RES CTR,PALMERSTON NORTH,NEW ZEALAND. ELEANOR ROOSEVELT INST CANC RES,DENVER,CO 80206. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. UNIV COLORADO,HLTH SCI CTR,DEPT BIOCHEM BIOPHYS & GENET,DENVER,CO 80206. NR 48 TC 5 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 1995 VL 6 IS 12 BP 862 EP 866 DI 10.1007/BF00292436 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TK272 UT WOS:A1995TK27200008 PM 8747925 ER PT J AU KWON, OJ ADAMSON, MC CHIN, H KOZAK, CA AF KWON, OJ ADAMSON, MC CHIN, H KOZAK, CA TI GENETIC-MAPPING OF 5 MOUSE GENES ENCODING SYNAPTOTAGMINS SO MAMMALIAN GENOME LA English DT Note ID RECEPTOR; KINASE C1 NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 15 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 1995 VL 6 IS 12 BP 880 EP 881 DI 10.1007/BF00292439 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TK272 UT WOS:A1995TK27200011 PM 8747928 ER PT J AU YOUNG, DR SHARP, DS CURB, JD AF YOUNG, DR SHARP, DS CURB, JD TI ASSOCIATIONS AMONG BASE-LINE PHYSICAL-ACTIVITY AND SUBSEQUENT CARDIOVASCULAR RISK-FACTORS SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE CORONARY HEART DISEASE; EXERCISE; COHORT STUDY; JAPANESE AMERICANS ID CORONARY HEART-DISEASE; LEISURE-TIME; LIPOPROTEIN LEVELS; ELDERLY MEN; EXERCISE; HAWAII; TRIAL AB To determine stability of cross-sectional associations between physical activity and cardiovascular risk factors and provide information regarding possible independent effects of physical activity on reduced cardiovascular disease, this report examined associations among baseline physical activity and risk factors measured over 15 yr. Subjects were 1,379 Honolulu Heart Program participants who were evaluated at baseline and three subsequent examinations. For men initially 45-54 yr, higher physical activity level was significantly associated cross-sectionally and at 2 yr with lower diastolic blood pressure, body mass index, and skinfold thicknesses, and at 5 yr with higher high density lipoprotein (HDL) cholesterol. By the 15-yr examination, only associations between physical activity level and skinfold thicknesses remained significant. For men 55-68 yr, significant cross-sectional and 2-yr associations were found between higher physical activity level and lower skinfold thicknesses, and higher HDL cholesterol at 5 yr. Higher physical activity continued to be associated with lower skinfold thicknesses and was related to lower systolic blood pressure by the 15-yr examination. Results suggest that most cross-sectional associations between physical activity and risk factors diminish over time, providing support for prospective investigations that find physical activity has a beneficial effect on reduced cardiovascular disease partially independent of traditional risk factors. C1 UNIV HAWAII MANOA,JOHN A BURNS SCH MED,HONOLULU,HI. NHLBI,HONOLULU HEART PROGRAM,HONOLULU,HI. KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI. NR 33 TC 11 Z9 11 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD DEC PY 1995 VL 27 IS 12 BP 1646 EP 1654 PG 9 WC Sport Sciences SC Sport Sciences GA TJ499 UT WOS:A1995TJ49900011 PM 8614321 ER PT J AU Cada, A GonzalezLima, F Rose, GM Bennett, MC AF Cada, A GonzalezLima, F Rose, GM Bennett, MC TI Regional brain effects of sodium azide treatment on cytochrome oxidase activity: A quantitative histochemical study SO METABOLIC BRAIN DISEASE LA English DT Article DE cytochrome oxidase; quantitative histochemistry; sodium azide; correlations; learning; memory ID ALZHEIMERS-DISEASE; ENERGY-METABOLISM; VISUAL-SYSTEM; RAT-BRAIN; 2-DEOXYGLUCOSE; FLUORODEOXYGLUCOSE; MARKER AB The objective of the present study was to determine if regional variation in brain cytochrome oxidase activity was observed following systemic administration of sodium azide. An image analysis system calibrated with internal standards of known cytochrome oxidase activity was used to quantify cytochrome oxidase in histochemically stained brain sections. Rats receiving chronic infusion of sodium azide (400 mu g/hr), which were sacrificed after two weeks, showed a substantial decrease in brain cytochrome oxidase activity over those infused with saline. All of the 22 regions sampled from telencephalic, diencephalic, and mesencephalic levels, showed a significant activity reduction which ranged between 26% and 37%. The regions that appeared significantly more vulnerable to the sodium azide effects were the mesencephalic reticular formation and the central amygdala, which displayed the largest decrease in activity. In addition, interregional correlations of activity showed a deeply modified pattern of correlative metabolic activity between hippocampal, amygdaloid and cortical areas after azide treatment. The regional effects found were consistent with azide-induced learning and memory dysfunctions. C1 UNIV TEXAS,INST NEUROSCI,AUSTIN,TX 78712. UNIV TEXAS,DEPT PSYCHOL,AUSTIN,TX 78712. VAMC,DENVER,CO. NIA,NEUROSCI LAB,BETHESDA,MD 20892. FU NIA NIH HHS [AG10755]; NIMH NIH HHS [R0 MH43353] NR 54 TC 41 Z9 42 U1 1 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD DEC PY 1995 VL 10 IS 4 BP 303 EP 320 DI 10.1007/BF02109361 PG 18 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA TR963 UT WOS:A1995TR96300006 PM 8847994 ER PT J AU JAMES, SL AF JAMES, SL TI ROLE OF NITRIC-OXIDE IN PARASITIC INFECTIONS SO MICROBIOLOGICAL REVIEWS LA English DT Review ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; ENDOTHELIUM-DEPENDENT RELAXATION; MACROPHAGE CELL-LINE; ENTAMOEBA-HISTOLYTICA TROPHOZOITES; INTRACELLULAR TRYPANOSOMA-CRUZI; MURINE PERITONEAL-MACROPHAGES; EXPERIMENTAL CEREBRAL MALARIA; LEISHMANIA-MAJOR AMASTIGOTES; HUMAN MONONUCLEAR PHAGOCYTES AB Nitric oxide is produced by a number of different cell types in response to cytokine stimulation and thus has been found to play a role in immunologically mediated protection against a growing list of protozoan and helminth parasites in vitro and in animal models. The biochemical basis of its effects on the parasite targets appears to involve primarily inactivation of enzymes crucial to energy metabolism and growth, although it has other biologic activities as well. NO is produced not only by macrophages and macrophage-like cells commonly associated with the effector arm of cell-mediated immune reactivity but also by cells commonly considered to lie outside the immunologic network, such as hepatocytes and endothelial cells, which are intimately involved in the life cycle of a number of parasites. NO production is stimulated by gamma interferon in combination with tumor necrosis factor alpha or other secondary activation signals and is regulated by a number of cytokines (especially interleukin-4, interleukin-10, and transforming growth factor beta) and other mediators, as well as through its own inherent inhibitory activity. The potential for design of prevention and/or intervention approaches against parasitic infection (e.g., vaccination or combination chemo- and immunotherapy strategies) on the basis of induction of cell-mediated immunity and NO production appears to be great, but the possible pathogenic consequences of overproduction of NO must be taken into account. Moreover, more research on the role and regulation of NO in human parasitic infection is needed before its possible clinical relevance can be determined. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NR 204 TC 246 Z9 253 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0146-0749 J9 MICROBIOL REV JI Microbiol. Rev. PD DEC PY 1995 VL 59 IS 4 BP 533 EP & PG 0 WC Microbiology SC Microbiology GA TH960 UT WOS:A1995TH96000001 PM 8531884 ER PT J AU Williamson, KC Keister, DB Muratova, O Kaslow, DC AF Williamson, KC Keister, DB Muratova, O Kaslow, DC TI Recombinant Pfs230, a Plasmodium falciparum gametocyte protein, induces antisera that reduce the infectivity of Plasmodium falciparum to mosquitoes SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; malaria; transmission-blocking vaccine; Pfs230; sexual-stage parasites ID TRANSMISSION-BLOCKING ANTIBODIES; GAMETE SURFACE-ANTIGENS; TARGET ANTIGEN; EXPRESSION; BIOSYNTHESIS; MALARIA; CLONING; GENES AB Six regions of malaria transmission-blocking target antigen, Pfs230, encoding 80% of the 363-kDa protein, were expressed as recombinant proteins in E. coli as fusions with maltose-binding protein (MBP). Antisera generated against amylose-purified recombinant Pfs230/MBP fusion proteins (r230/MBP.A-r230/MBP.F) all recognized the 360-kDa form of parasite-produced Pfs230 by immunoblot. However, only antisera against the four carboxy regions (C-F) of Pfs230 and not the two amino regions (A and B) recognized the 310-kDa form of Pfs230, the form expressed on the surface of gametes. The data suggest that the 310-kDa form of Pfs230 arises from the cleavage of 50 kDa from the amino terminus of the 360-kDa form, Furthermore, antisera against r230/MBP.C bound to the surface of intact gametes and significantly reduced (by 71.2-89.8% (rank sum analysis, P < 0.01)) the infectivity of P. falciparum parasites to mosquitoes. This is the first report of a recombinant form of a P. falciparum gametocyte protein capable of inducing antisera that reduce malaria parasite infectivity to mosquitoes. C1 NIAID,PARASIT DIS LAB,MALARIA VACCINE SECT,BETHESDA,MD 20892. RP Williamson, KC (reprint author), LOYOLA UNIV,DEPT BIOL,DH1007,6525 N SHERIDAN RD,CHICAGO,IL 60626, USA. NR 20 TC 76 Z9 77 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD DEC PY 1995 VL 75 IS 1 BP 33 EP 42 DI 10.1016/0166-6851(95)02507-3 PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA TQ605 UT WOS:A1995TQ60500004 PM 8720173 ER PT J AU TRIESCHMANN, L POSTNIKOV, YV RICKERS, A BUSTIN, M AF TRIESCHMANN, L POSTNIKOV, YV RICKERS, A BUSTIN, M TI MODULAR STRUCTURE OF CHROMOSOMAL-PROTEINS HMG-14 AND HMG-17 - DEFINITION OF A TRANSCRIPTIONAL ENHANCEMENT DOMAIN DISTINCT FROM THE NUCLEOSOMAL BINDING DOMAIN SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MOBILITY GROUP PROTEIN-17; HUMAN CDNA SEQUENCE; CORE PARTICLE; MULTIGENE FAMILY; HISTONE TAILS; CHROMATIN; DNA; GENES AB Chromosomal proteins HMG-14 and HMG-17 are the only known nuclear proteins which specifically bind to the nucleosome core particle and are implicated in the generation and/or maintenance of structural features Specific to active chromatin. The two proteins facilitate polymerase II and III transcription from in vitro- and in vivo-assembled circular chromatin templates. Here we used deletion mutants and specific peptides to identify the transcriptional enhancement domain and delineate the nucleosomal binding domain of the HMG-14 and -17 proteins. Deletion of the 22 C-terminal amino acids of HMG-17 or 26 C-terminal amino acids of HMG-14 reduces significantly the ability of the proteins to enhance transcription from chromatin templates. In contrast, N-terminal truncation mutants had the same transcriptional enhancement activity as the full-length proteins. We conclude that the negatively charged C-terminal region of the proteins is required for transcriptional enhancement. Chromatin transcription enhancement assays, which involve binding competition between the full-length proteins and peptides derived from their nucleosomal binding regions, indicate that the minimal nucleosomal binding domain of human HMG-17 is 24 amino acids long and spans residues 17 to 40. The results suggest that HMG-14 and -17 proteins have a modular structure and contain distinct functional domains. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Bustin, Michael/G-6155-2015 NR 43 TC 56 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1995 VL 15 IS 12 BP 6663 EP 6669 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TF653 UT WOS:A1995TF65300020 PM 8524231 ER PT J AU SZENTGYORGYI, C AF SZENTGYORGYI, C TI A BIPARTITE OPERATOR INTERACTS WITH A HEAT-SHOCK ELEMENT TO MEDIATE EARLY MEIOTIC INDUCTION OF SACCHAROMYCES-CEREVISIAE HSP82 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVATION DOMAIN; POLYMERASE CHAIN-REACTION; MEIOSIS-SPECIFIC GENE; YEAST HSP70 GENE; CHROMATIN STRUCTURE; PROTEIN-BINDING; REPRESSION SITE; FACTOR CONTAINS; TATA ELEMENTS; GERM-CELLS AB Although key genetic regulators of early meiotic transcription in Saccharomyces cerevisae have been well characterized, the activation of meiotic genes is still poorly understood in terms of cis-acting DNA elements and their associated factors, I report here that induction of HSP82 is regulated by the early meiotic IME1-IME2 transcriptional Cascade, Vegetative repression and meiotic induction depend on interactions of the promoter-proximal heat shock element (HSE) with a nearby bipartite repression element, composed of the ubiquitous early meiotic motif, URS1 (upstream repression sequence 1), and a novel ancillary repression element. The ancillary repression element is required for efficient vegetative repression, is spatially separable from URS1, and continues to facilitate repression during sporulation, In contrast, URS1 also functions as a vegetative repression element but is converted early in meiosis into an HSE-dependent activation element. An early step in this transformation may be the antagonism of URS1-mediated repression by IME1. The HSE also nonspecifically supports a second major mode of meiotic activation that does not require URS1 but does require expression of IME2 and concurrent starvation. Interestingly, increased rather than decreased URS1-mediated vegetative transcription can be artificially achieved by introducing rare point mutations into URS1 or by deleting the UME6 gene. These lesions offer insight into mechanisms of URS-dependent repression and activation, Experiments suggest that URS1-bound factors functionally modulate heat shock factor during vegetative transcription and early meiotic induction but not during heat shock. The loss of repression and activation observed when the IME2 activation element, T4C, is substituted for the HSE suggests specific requirements for URS1-upstream activation sequence interactions. RP NIDDKD, CELLULAR & DEV BIOL LAB, BETHESDA, MD 20892 USA. NR 82 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1995 VL 15 IS 12 BP 6754 EP 6769 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TF653 UT WOS:A1995TF65300030 PM 8524241 ER PT J AU MOL, PC WANG, RH BATEY, DW LEE, LA DANG, CV BERGER, SL AF MOL, PC WANG, RH BATEY, DW LEE, LA DANG, CV BERGER, SL TI DO PRODUCTS OF THE MYC PROTOONCOGENE PLAY A ROLE IN TRANSCRIPTIONAL REGULATION OF THE PROTHYMOSIN-ALPHA GENE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID C-MYC; DNA-BINDING; ACTIVATES TRANSCRIPTION; NUCLEAR-LOCALIZATION; MESSENGER-RNA; CELL-DIVISION; PROTEINS; EXPRESSION; SEQUENCE; MAX AB The Myc protein has been reported to activate transcription of the rat prothymosin a gene by binding to an enhancer element or E box (CACGTG) located in the first intron (S. Gaubatz et al., Mel. Cell. Biol. 14:3853-3862, 1994). The human prothymosin or gene contains two such motifs: in the promoter region at kb -1.2 and in intron 1, similar to 2 kb downstream of the transcriptional start site in a region which otherwise bears little homology to the rat gene. Using chloramphenicol acetyltransferase (CAT) reporter constructs driven either by the 5-kb human prothymosin ru promoter or py a series of truncated promoters, we showed that removal of the E-box sequence had no effect on transient expression of CAT activity in mouse L cells. When intron 1 of the prothymosin alpha gene was inserted into the most extensive promoter construct downstream of the CAT coding region, a diminution in transcription, which remained virtually unchanged upon disruption of the E boxes, was observed. CAT constructs driven by the native prothymosin or promoter or the native promoter and intron were indifferent to Myc; equivalent CAT activity was observed in the presence of ectopic normal or mutant Myc genes. Similarly, expression of a transiently transfected wild-type prothymosin cu gene as the reporter was not affected by a repertoire of myc-derived genes, including nye itself and dominant or recessive negative myc mutants. In COS-1 cells, equivalent amounts of the protein were produced from transfected prothymosin alpha genes regardless of whether genomic E boxes were disrupted, intron 1 was removed, or a repertoire of myc-derived genes was included in the transfection cocktail. More importantly, cotransfection of a dominant negative Max gene failed to reduce transcription of the endogenous prothymosin or gene in COS cells or the wild-type transfected gene in COS or L cells. Taken together, the data do not support the idea that Myc activates transcription of the intact human prothymosin cr gene or reporter constructs that mimic its structure. Rather, they suggest that the human prothymosin or promoter and downstream elements are buffered so as to respond poorly, if at all, to transient fluctuations in transcription factors which regulate other genes. C1 NCI, GENES & GENE PROD SECT, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MOLEC BIOL & GENET, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, JOHNS HOPKINS ONCOL CTR, BALTIMORE, MD 21205 USA. NR 60 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1995 VL 15 IS 12 BP 6999 EP 7009 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TF653 UT WOS:A1995TF65300056 PM 8524267 ER PT J AU GOPALSRIVASTAVA, R HAYNES, JI PIATIGORSKY, J AF GOPALSRIVASTAVA, R HAYNES, JI PIATIGORSKY, J TI REGULATION OF THE MURINE ALPHA-B-CRYSTALLIN SMALL HEAT-SHOCK PROTEIN GENE IN CARDIAC-MUSCLE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RAT MYOCARDIAL-CELLS; LOOP-HELIX PROTEINS; ACTIN GENE; SKELETAL-MUSCLE; BINDING-SITE; DNA-BINDING; CHAIN GENE; IMMUNOGLOBULIN ENHANCER; LENS CRYSTALLINS; UPSTREAM REGIONS AB The murine alpha beta-crystallin/small heat shock protein gene is expressed at high levels in the lens and at lower levels in the heart, skeletal muscle, and numerous other tissues. Previously we have found a skeletal-muscle-preferred enhancer at positions -427 to -259 of the alpha beta-crystallin gene containing at least four cis-acting regulatory elements (alpha BE-1, alpha BE-2, alpha BE-3, and MRF, which has an E box). Here we show that in transgenic mice, the alpha beta-crystallin enhancer directs the chloramphenicol acetyltransferase reporter gene driven by the alpha beta-crystallin promoter specifically to myocardiocytes of the heart. The alpha beta-crystallin enhancer was active in conjugation with the herpes simplex virus thymidine kinase promoter/human growth hormone reporter gene in transfected rat myocardiocytes. DNase I footprinting and site-specific mutagenesis experiments showed that alpha BE-1, alpha BE-2, alpha BE-3, MRF, and a novel, heart-specific element called alpha BE-4 are required for alpha beta-crystallin enhancer activity in transfected myocardiocytes. By contrast, alpha BE-4 is not utilized for enhancer activity in transfected lens or skeletal muscle cell lines. alpha BE-4 contains an overlapping heat shock sequence and a reverse CArG box [5'-GG(A/T)(6)CC-3']. Electrophoretic mobility lift assays with an antibody to serum response factor and a CArG-box-competing sequence from the c-fos promoter indicated that a cardiac-specific protein with DNA-binding and antigenic similarities to serum response factor binds to alpha BE-4 via the reverse CArG box; electrophoretic mobility shift assays and antibody experiments with anti-USF antiserum and heart nuclear extract also raised the possibility that the MRF E box utilizes USF or an antigenically related protein. We conclude that the activity of the alpha beta-crystallin enhancer in the heart utilizes a reverse CArG box and an E-box-dependent pathway. C1 NEI, MOLEC & DEV BIOL LAB, BETHESDA, MD 20892 USA. NR 79 TC 50 Z9 50 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1995 VL 15 IS 12 BP 7081 EP 7090 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TF653 UT WOS:A1995TF65300064 PM 8524275 ER PT J AU PENNYPACKER, KR LENNARD, DE HUDSON, PM HONG, JS MCMILLIAN, MK AF PENNYPACKER, KR LENNARD, DE HUDSON, PM HONG, JS MCMILLIAN, MK TI BASAL EXPRESSION OF 35 KDA FOS-RELATED ANTIGEN IN OLFACTORY-BULB SO MOLECULAR BRAIN RESEARCH LA English DT Note DE AP-1; TRANSCRIPTION FACTOR; KAINATE; NEURONAL PLASTICITY; DNA BINDING ID AP-1 DNA-BINDING; KAINIC ACID; INDUCTION; REGENERATION; NEURONS; BRAIN AB Recently, there have been a number of reports showing a long-term increased expression of fos-related antigens (fra), molecular weight of 35 kDa, after brain injury or chronic treatment of rats with various drugs. We report elevated basal levels of this transcription factor in the olfactory bulb relative to other brain regions. The expression of this protein is further enhanced in the olfactory bulb as long as 3 months after a single injection of kainate, an effect similar to that we previously observed in the hippocampus. The AP-1 DNA binding activity in olfactory bulb from kainate-treated rats contains fra and jun immunoreactivity suggesting that the 35 kDa fra dimerizes with jun protein, probably junD, to bind to AP-1 sites. Elevated basal levels of this transcription factor in the olfactory bulb appear to be related to the constant reinnervation and synaptogenesis which occurs in this brain region. The 35 kDa fra may be involved in long-term genomic program changes required to adapt to an altered biochemical environment. C1 NATL INST ENVIRONM HLTH SCI,ENVIRONM NEUROSCI LAB,RES TRIANGLE PK,NC 27709. RI Pennypacker, Keith/I-5092-2012 NR 27 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC 1 PY 1995 VL 34 IS 1 BP 161 EP 165 DI 10.1016/0169-328X(95)00164-N PG 5 WC Neurosciences SC Neurosciences & Neurology GA TF868 UT WOS:A1995TF86800018 PM 8750873 ER PT J AU DAS, R VONDERHAAR, BK AF DAS, R VONDERHAAR, BK TI TRANSDUCTION OF PROLACTINS (PRL) GROWTH SIGNAL THROUGH BOTH LONG AND SHORT FORMS OF THE PRL RECEPTOR SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID BETA-CASEIN GENE; MOLECULAR-CLONING; CHLORAMPHENICOL ACETYLTRANSFERASE; TYROSINE KINASE; MULTIPLE FORMS; EXPRESSION; PROTEIN; HORMONE; CELLS; RAT AB The genes for the long form of the human and the short form of the mouse PRL receptors were transfected independently into NIH 3T3 cells. Reverse transcriptase-polymerase chain reaction indicated that the transfectant designated LFH contained message for only the long form and the transfectant designated SFM had message for only the short form of the receptor. Both transfectant cell lines specifically bound lactogenic hormones with high affinity and responded to PRL in culture with a 2- to 3-fold increase in cell number preceded by transient activation of mitogen-activated protein kinase. After a PRL-responsive casein-chloramphenicol acetyl transferase (CAT) construct was introduced into both LFH and SFM cells, CAT activity was induced by PRL only in the LFH-CAT cells. Thus, while the long form of the receptor can transduce the differentiation signal, both the long and the short forms of the receptor can signal the cells to grow. RP DAS, R (reprint author), NCI, TUMOR IMMUNOL & BIOL LAB, MOLEC & CELLULAR ENDOCRINOL SECT,BLDG 10,5B56, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 56 TC 114 Z9 118 U1 0 U2 0 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 DEC PY 1995 VL 9 IS 12 BP 1750 EP 1759 DI 10.1210/me.9.12.1750 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TJ308 UT WOS:A1995TJ30800012 PM 8614411 ER PT J AU Kanda, P Fritz, DA Gage, DA Shuler, KR AF Kanda, P Fritz, DA Gage, DA Shuler, KR TI Dependence of the murine-antibody response to an anti-CD4 CDR2 V-H peptide on immunogen formulation SO MOLECULAR IMMUNOLOGY LA English DT Article DE monoclonal antibody; PAM(3)Cys; anti-peptide; MAP; CDR2; ELISA reactivity; IgG ID SYNTHETIC PEPTIDE; MONOCLONAL ANTI-CD4; MOUTH-DISEASE; MAP SYSTEM; ANTIGEN; IDIOTYPE; ANTIPEPTIDE; INDUCTION; LIPOSOMES AB A peptide corresponding to the second complementarity determining region of the heavy chain (CDR2 V-H) from a murine anti-CD4 monoclonal antibody, designated L202, was synthesized by solid phase methodology in a number of different antigenic forms, for the purpose of comparing the effectiveness of different adjuvant-carrier systems in the induction of a murine antibody response against the immunizing peptide and parent antibody molecule. Two of the synthetic constructs contained the palmitoyl and N-palmitoyl-cysteinyl-S-(2,3-palmitoyloxy)-propanediol (PAM(3)Cys) moieties, respectively, attached to the peptide amino terminus with the immunogen comprising liposomal formulations of each. A third immunogen consisted of the CDR2 V-H peptide admired with the PAM(3)Cys non-covalently and incorporated into liposomes (PAM(3)Cys + CDR2 V-H). A fourth composition comprised the CDR2 V-H peptide conjugated to KLH via the sulfhydryl of an added N terminal cysteine (KLH-CDR2 V-H) and injected with Complete Freund's adjuvant (CFA). A fifth immunogen consisted of the CDR2V(H) peptide synthesized on an octameric, branched polylysine core as a multiple antigenic peptide (MAP-CDR2 V-H) injected in the presence of Freund's adjuvant. Groups of five mice were injected intramuscularly with each of these immuno ens and bled at two week intervals. The highest anti-peptide gamma-immunoglobulin (IgG) responses (against uncoupled peptide by ELISA) after 56 days were obtained with mice receiving the PAM(3)Cys-CDR2 V-H peptide. However, when screened against the CDK2 V-H peptide present as the MAP derivative by ELISA, IgG raised against the cognate MAP-CDR2 peptide was much more reactive than IgG raised against the liposomal PAM(3)Cys-CDR2 V-H immunogen. In either case, IgG raised against the KLH-CDR2 V-H conjugate was poorly reactive. These differences in reactivity to the two forms of the CDR2 V-H peptide by ELISA did not correspond to major differences in reactivities to the intact L202 Ab by ELISA. Although the IgG against the MAP immunogen was slightly more reactive than the other antisera against the L202 Ab, all titers were less than 1:100. These data illustrate some limitations of using anti-peptide responses as indicators of potential reactivity against the native protein, but suggest that alternate formulations including lipoidal peptides are more effective than corresponding KLH-peptide conjugates in eliciting Ab responses against poorly immunogenic epitopes. C1 MICHIGAN STATE UNIV,DEPT BIOCHEM,NIH,MASS SPECT FACIL,E LANSING,MI 48824. RP Kanda, P (reprint author), SW FDN BIOMED RES,DEPT VIROL & IMMUNOL,SAN ANTONIO,TX 78228, USA. FU NIAID NIH HHS [AI-26462] NR 23 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 1995 VL 32 IS 17-18 BP 1319 EP 1328 DI 10.1016/0161-5890(95)00117-4 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA TY786 UT WOS:A1995TY78600003 PM 8643101 ER PT J AU Kurucz, I Titus, JA Jost, CR Segal, DM AF Kurucz, I Titus, JA Jost, CR Segal, DM TI Correct disulfide pairing and efficient refolding of detergent-solubilized single-chain Fv proteins from bacterial inclusion bodies SO MOLECULAR IMMUNOLOGY LA English DT Article DE protein folding; disulfide bonds; antibody; affinity; recombinant protein ID SODIUM DODECYL-SULFATE; ESCHERICHIA-COLI; FAB-FRAGMENTS; PURIFICATION; ANTIBODIES; RECEPTOR; ANALOGS; ENZYMES; CELL AB In vitro folding of denatured proteins has remained an inefficient and empirical process that has limited the use of bacterially expressed recombinant proteins. In this paper we show that in vitro folding of recombinant single-chain Fv (sFv) proteins is markedly facilitated when disulfide bonds are formed in detergent solution, sFv proteins from three different antibodies were expressed as bacterial cytoplasmic inclusion bodies and solubilized in the weak ionic detergent, sodium lauroylsarcosine (SLS). Upon oxidation in air in the presence of metal ion catalysts, all three sFvs quantitatively formed intrachain disulfide bonds which ran as a single band in SDS-polyacrylamide gel electrophoresis under non-reducing conditions. By contrast, oxidation from 6 M urea gave large amounts of disulfide linked aggregates, and three closely spaced bands of monomeric protein. Detergent was removed from the oxidized sFvs by addition of 6 M urea and absorption with an ion gen exchange resin. After dialysis and gel filtration in non-denaturing solution, moderate to high yields of monomeric sFv were obtained, depending upon the sFv. All three sFvs gave single bands on isoelectric focussing and SDS-PAGE gels and had similar or identical binding specificities and affinities as the parental Fabs, implying that the final products contained correctly paired disulfide bonds. The correct disulfide pairing suggests that the disulfide loops within the detergent-solubilized sFvs adopt a native-like structure. C1 NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. NR 30 TC 60 Z9 74 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 1995 VL 32 IS 17-18 BP 1443 EP 1452 DI 10.1016/0161-5890(95)00105-0 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA TY786 UT WOS:A1995TY78600015 PM 8643113 ER PT J AU Mialhe, E Bachere, E Boulo, V Cadoret, JP Rousseau, C Cedeno, V Saraiva, E Carrera, L Calderon, J Colwell, RR AF Mialhe, E Bachere, E Boulo, V Cadoret, JP Rousseau, C Cedeno, V Saraiva, E Carrera, L Calderon, J Colwell, RR TI Future of biotechnology-based control of disease in marine invertebrates SO MOLECULAR MARINE BIOLOGY AND BIOTECHNOLOGY LA English DT Article ID BONAMIA-OSTREAE ASCETOSPORA; POLYMERASE CHAIN-REACTION; TRANSPOSABLE ELEMENT; TRANSGENIC MICE; MONOCLONAL-ANTIBODIES; PECTEN-MAXIMUS; GENETIC-TRANSFORMATION; EDULIS MOLLUSCA; AEDES-AEGYPTI; DNA AB Infectious disease is the single most devastating problem in mollusc and shrimp aquaculture. Pathogens causing the greatest problems have been identified as viruses, prokaryotes, and protozoans. Two approaches employing methods of biotechnology have been proposed to prevent, manage, and control mollusc and shrimp diseases. The first is development of a diagnostic scheme for detection and identification of pathogens, using molecular probes. This offers the opportunity for prophylactic measures to be taken. Molecular probes have been prepared for the major pathogens of molluscs, but in the case of shrimp pathogens, only a few are available. Monoclonal antibodies have also been prepared and are used in immunodiagnosis, e.g., immunofluorescence detection. Such diagnostic tools are relatively new to aquaculture, but have enormous potential. A second approach to the control of disease in marine invertebrates, notably shrimp, involves use of genetically transformed strains resistant to specific pathogens. Pathogen-resistant transgenic animals have been developed, but such research has only just begun for molluscs and shrimp. Transfection methods applied to mollusc and shrimp embryos have been successful, with preliminary data showing efficiency of heterologous promoters in controlling expression of reporter genes. Other transformation systems also show promise, including transposable elements and densoviruses. C1 UNIV MONTPELLIER, IFREMER, F-34059 MONTPELLIER, FRANCE. NIH, PARASIT DIS LAB, BETHESDA, MD 20892 USA. CENAIM, ESPOL, GUAYAQUIL, ECUADOR. UNIV MARYLAND, INST BIOTECHNOL, COLLEGE PK, MD 20740 USA. NR 77 TC 25 Z9 25 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1053-6426 J9 MOL MAR BIOL BIOTECH JI Mol. Mar. Biol. Biotechnol. PD DEC PY 1995 VL 4 IS 4 BP 275 EP 283 PG 9 WC Biotechnology & Applied Microbiology; Marine & Freshwater Biology SC Biotechnology & Applied Microbiology; Marine & Freshwater Biology GA TL673 UT WOS:A1995TL67300001 PM 8541979 ER PT J AU Abeles, AL Reaves, LD YoungrenGrimes, B Austin, SJ AF Abeles, AL Reaves, LD YoungrenGrimes, B Austin, SJ TI Control of P1 plasmid replication by iterons SO MOLECULAR MICROBIOLOGY LA English DT Article ID COPY NUMBER CONTROL; ESCHERICHIA-COLI; REPEATING SEQUENCES; HOST STRAINS; DNA; PARTITION; INCOMPATIBILITY; PROTEIN; ORIGIN; SEQUESTRATION AB The incA locus of plasmid P1 controls plasmid copy number by inhibiting the replication origin, oriR. Both loci contain repeat sequences (iterons) that bind the P1 RepA protein. Regulation appears to occur by contact of incA and oriR loci of daughter plasmids mediated by RepA-bound iterons. Synthetic incA iteron arrays were constructed with altered numbers, sequences or spacing of iterons. Using these in in vitro and in vivo assays, we examined two models: (i) that the origin and incA loci form a stable 1:1 complex in which multiple iterons of each locus are paired with those of the other, and (ii) that individual incA iterons act as freely diffusing nucleoprotein units that contact origin iterons in a random and dynamic fashion. The data presented here strongly favour the latter case. The origin, with its five iterons, acts as a target but not as an effector of regulation. We present a model for replication control based on random, dynamic contacts between incA iterons and the origin. This system would display randomness with respect to choice of templates and timing of initiation if multiple replicon copies were present, but would tend to act in a machine-like fashion in concert with the cell cycle if just two copies were present in a dividing cell. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHROMOSOME BIOL LAB,FREDERICK,MD 21702. NR 36 TC 26 Z9 26 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 1995 VL 18 IS 5 BP 903 EP 912 DI 10.1111/j.1365-2958.1995.18050903.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA TM843 UT WOS:A1995TM84300012 PM 8825094 ER PT J AU Palmer, TM Poucher, SM Jacobson, KA Stiles, GL AF Palmer, TM Poucher, SM Jacobson, KA Stiles, GL TI I-125-4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo{2,3-a}{1,3,5}triazin-5-yl -amino]ethyl)phenol, a high affinity antagonist radioligand selective for the A(2a) adenosine receptor SO MOLECULAR PHARMACOLOGY LA English DT Note ID MOLECULAR-CLONING; BINDING; ACTIVATION; BRAIN AB The A(2a) adenosine receptor (AR) mediates several important physiological effects of adenosine, including vasodilation and inhibition of platelet aggregation. Until recently, no antagonist radioligand of sufficient selectivity or affinity was available. We describe the synthesis and characterization by radioligand binding of I-125-4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo{2,3-a}-{1,3,5}triazin-5-yl-amino]ethyl)phenol (I-125-ZM241385) in membranes from two cell types that express A(2a) ARs. Membranes from Chinese hamster ovary (CHO) cells expressing a recombinant canine A(2a) AR bound I-125-ZM241385 with high affinity, and agonist competition experiments with 2-(p-carboxyethyl)phenylamino-5 '-N-carboxamidoadenosine, 5'-N-ethylcarboxamidoadenosine, and (-)-N-6-[(R)-phenylisopropyl]adenosine revealed a potency order characteristic of an A(2A) AR binding site. Membranes from bovine striatum, which contain a native A(2a) AR, also bound I-125-ZM241385 with similarly high affinity and also displayed a pharmacological profile for displacement of radioligand binding that was consistent with that of an A(2a) AR. Also, under conditions in which I-125-ZM241385 bound with high affinity to a recombinant rat A(2a) AR expressed in CHO cells, no specific binding was detectable in membranes from CHO cells expressing functional rat A(1), A(2b), or A(3) ARs, indicating that over the range of concentrations used in radioligand binding assays, I-125-ZM241385 is a highly selective antagonist radioligand for study of A(2a) ARs within a given species. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. ZENECA PHARMACEUT,MACCLESFIELD,CHESHIRE,ENGLAND. NIDDKD,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. RI Palmer, Timothy/C-4975-2009; Jacobson, Kenneth/A-1530-2009; Palmer, Timothy/E-7290-2013 OI Jacobson, Kenneth/0000-0001-8104-1493; Palmer, Timothy/0000-0002-9803-7164 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999]; NHLBI NIH HHS [P50HL54314, R01HL35134] NR 23 TC 75 Z9 75 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 DEC PY 1995 VL 48 IS 6 BP 970 EP 974 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL655 UT WOS:A1995TL65500002 PM 8848012 ER PT J AU Fossom, LH Basile, AS Skolnick, P AF Fossom, LH Basile, AS Skolnick, P TI Sustained exposure to 1-aminocyclopropanecarboxylic acid, a glycine partial agonist, alters N-methyl-D-aspartate receptor function and subunit composition SO MOLECULAR PHARMACOLOGY LA English DT Article ID NMDA-RECEPTORS; EXHIBIT ANTIDEPRESSANT; XENOPUS OOCYTES; COMPLEX; BRAIN; SITE; RAT; ANTAGONISTS; LIGANDS; CONVULSIONS AB Partial agonists at the strychnine-insensitive glycine sites coupled to N-methyl-D-aspartate (NMDA) receptors reduce both glutamate-induced neurotoxicity in vitro and ischemia-induced neurodegeneration in vivo. Paradoxically, sustained exposure of cultured cerebellar granule cell neurons to glycinergic ligands, including glycine and the glycine partial agonists (+/-)-3-amino-1 -hydroxy-2-pyrrolidone, 1-aminocyclopropanecarboxylic acid (ACPC), and D-cycloserine, attenuates the neuroprotective effects of (+/-)-3-amino-1-hydroxy-2-pyrrolidone and ACPC. In the present study, we investigated the mechanisms responsible for this attenuated neuroprotection. Three NMDA receptor-mediated responses were examined after sustained exposure to ACPC: glutamate-induced neurotoxicity, NMDA-stimulated increases in cGMP levels, and NMDA-stimulated increases in [Ca+2](i). Consistent with previous findings, coincubation with ACPC blocked glutamate-induced neurotoxicity, whereas sustained (24 hr) exposure to ACPC attenuated its protective effects. Moreover, sustained exposure to ACPC caused an apparent similar to 2-fold increase in the potency of both glutamate to act as a neurotoxin and NMDA to stimulate cGMP formation. Sustained exposure to ACPC also increased NMDA-stimulated [Ca+2](i) similar to 3-fold compared with control granule cell cultures but did not affect basal [Ca+2](i). This apparent increase in glutamate sensitivity may be attributable to a change in NMDA receptor subunit composition as sustained ACPC exposure resulted in a similar to 2.5-fold increase in NMDA receptor 2C RNA levels, without concomitant changes in the amounts of RNA encoding the NMDA receptor 2A, 2B, or I subunit. This is the first demonstration that sustained exposure to a glycinergic ligand can alter the expression of RNAs encoding NMDA receptor subunits. Because glycinergic ligands are potential clinical candidates, these results may have important implications for the treatment of neurodegenerative disorders. C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. NR 43 TC 20 Z9 20 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1995 VL 48 IS 6 BP 981 EP 987 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL655 UT WOS:A1995TL65500004 PM 8848014 ER PT J AU Abbracchio, MP Brambilla, R Ceruti, S Kim, HO vonLubitz, DKJE Jacobson, KA Cattabeni, F AF Abbracchio, MP Brambilla, R Ceruti, S Kim, HO vonLubitz, DKJE Jacobson, KA Cattabeni, F TI G protein-dependent activation of phospholipase C by adenosine A(3) receptors in rat brain SO MOLECULAR PHARMACOLOGY LA English DT Article ID STIMULATED PHOSPHOINOSITIDE METABOLISM; CEREBRAL CORTICAL SLICES; MOLECULAR-CLONING; ARACHIDONIC-ACID; ISCHEMIA; CELLS; MODULATION; ANTAGONIST; EXPOSURE; RELEASE AB The recently cloned G protein-coupled adenosine A(3) receptor has been proposed to play a role in the pathophysiology of cerebral ischemia. Because phospholipase C activation occurs as a very early response to brain ischemia, we evaluated the ability of A(3)-selective and nonselective adenosine analogues to elicit phosphoinositide hydrolysis. In myo-[H-3]inositol-labeled rat striatal and hippocampal slices, A(3) agonists stimulated formation of [H-3]inositol phosphates in a concentration-dependent manner. In striatum, the potency order was 2-chloro-N-6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide greater than or equal to N-6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide >> N-methyl-1,3-di-n-butylxanthine-7-beta-D-ribofuronamide greater than or equal to 5'-N-ethylcarboxamidoadenosine greater than or equal to N-6-2-(4-aminophenyl)-ethyladenosine > N-6-(p-sulfophenyl)-adenosine = 1,3-dibutylxanthine-7-riboside, which is identical to the potency order in binding studies at cloned rat A(3) receptors. Stimulation of phospholipase C activity was abolished by guanosine-5'-O-(2-thiodiphosphate), confirming the involvement of a G protein-coupled receptor. Activation of phospholipase C was higher in the striatum than in the hippocampus, consistent with A(3) receptor densities. Stimulation of phospholipase C activity by adenosine analogues was only modestly antagonized by xanthine derivatives and at much higher concentrations than needed for blocking adenosine A(1), A(2A), and A(2B) receptors. In the presence of an A(1)/A(2) antagonist, a selective A(3) agonist only weakly inhibited forskolin-stimulated adenylyl cyclase activity in rat striatum. Thus, stimulation of phospholipase C activity represents a principal transduction mechanism for A(3) receptors in mammalian brain, and perhaps A, receptor-mediated increases of inositol phosphates in the ischemic brain contribute to neurodegeneration by raising intracellular calcium levels. C1 UNIV MILAN, SCH PHARM, INST PHARMACOL SCI, I-20133 MILAN, ITALY. NIDDKD, BIOORGAN CHEM LAB, MOLEC RECOGNIT SECT, BETHESDA, MD 20892 USA. RI Ceruti, Stefania/A-6376-2008; Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014 OI Ceruti, Stefania/0000-0003-1663-4211; Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 46 TC 150 Z9 150 U1 0 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1995 VL 48 IS 6 BP 1038 EP 1045 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL655 UT WOS:A1995TL65500011 PM 8848003 ER PT J AU FULCHER, KD WELCH, JE KLAPPER, DG OBRIEN, DA EDDY, EM AF FULCHER, KD WELCH, JE KLAPPER, DG OBRIEN, DA EDDY, EM TI IDENTIFICATION OF A UNIQUE MU-CLASS GLUTATHIONE-S-TRANSFERASE IN MOUSE SPERMATOGENIC CELLS SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE FIBROUS SHEATH; TESTES; GENE EXPRESSION; SPERMATOGENESIS ID MORPHOLOGICAL CHARACTERIZATION; MOLECULAR-CLONING; ROUND SPERMATIDS; FIBROUS SHEATH; MESSENGER-RNA; SERTOLI CELLS; RAT-BRAIN; LOCALIZATION; TESTIS; DNA AB The fibrous sheath is a major cytoskeletal structure in the principal piece of the mammalian sperm flagellum. Two peptide sequences obtained from a tryptic digest of mouse fibrous sheath proteins exhibited high homology with mu-class glutathione S-transferases (GSTs). Using a DNA probe amplified from degenerate polymerase chain reaction (PCR) primers predicted from these two peptide sequences, a similar to 1.1 kb cDNA clone for fibrous sheath component 2 (Fsc2) was isolated which had 84% nucleic acid and 89% amino acid sequence identity with a previously reported mu-class human GST gene (hGSTM3; Campbell et al., 1990: J Biol Chem 265:4188-9193). Sequences corresponding to those of the two fibrous sheath peptides were present in the protein encoded by the Fsc2 cDNA. Northern analysis with the full length Fsc2 cDNA detected a similar to 1.1 kb mRNA in 12 of 15 somatic tissues examined, as well as in testis and isolated spermatogenic cells. However, 5'(nt -96 to 12) or 3' (nt 637 to 808) Fsc2 probes, containing mostly noncoding sequences, detected a similar to 1.1 kb mRNA abundant in testis and isolated spermatogenic cells, but absent or present at low levels in somatic tissues. Northern analysis with RNA from testes of mice of different postnatal ages and purified spermatogenic cell populations indicated that this transcript is first present during the meiotic phase of germ cell development. These results suggest that a previously unreported mu-class GST gene (mGSTM5*) is expressed at a specific time during the development of spermatogenic cells in the mouse. Immunoblot analysis indicated that a mu-class GST protein is associated with the fibrous sheath, suggesting that it becomes an integral part of the mouse sperm cytoskeleton. (C) 1995 Wiley-Liss, Inc. C1 NIEHS,LRDT,GAMETE BIOL SECT,RES TRIANGLE PK,NC 27709. POINT LOMA NAZARENEN COLL,DEPT SCI BIOL,SAN DIEGO,CA. US EPA,HLTH EFFECTS RES LAB,REPROD TOXICOL BRANCH,RES TRIANGLE PK,NC 27711. UNIV N CAROLINA,DEPT MICROBIOL & IMMUNOL,CHAPEL HILL,NC. UNIV N CAROLINA,REPROD BIOL LABS,CHAPEL HILL,NC. UNIV N CAROLINA,DEPT PEDIAT,CHAPEL HILL,NC. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC. FU NCI NIH HHS [CA16086]; NICHD NIH HHS [P30-HD-18968, HD-26485, R01 HD026485] NR 48 TC 47 Z9 48 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 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD DEC PY 1995 VL 42 IS 4 BP 415 EP 424 DI 10.1002/mrd.1080420407 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA TH643 UT WOS:A1995TH64300006 PM 8607970 ER PT J AU MORRISON, DK AF MORRISON, DK TI MECHANISMS REGULATING RAF-1 ACTIVITY IN SIGNAL-TRANSDUCTION PATHWAYS SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article; Proceedings Paper CT Intracellular Signaling From Ras to Genes - An MCDB/ISU Symposium CY SEP 22-25, 1994 CL IOWA STATE UNIV, AMES, IA SP MCDB, Iowa State Univ HO IOWA STATE UNIV DE SIGNAL TRANSDUCTION; SERINE/THREONINE KINASES; CANCER ID MAP KINASE; PHOSPHORYLATION; MUTAGENESIS; ACTIVATION; DEFINITION; DOMAIN AB Raf-1 is a key protein involved in the transmission of developmental and proliferative signals generated by receptor and nonreceptor tyrosine kinases. Biochemical and genetic studies have demonstrated that Raf-1 functions downstream of activated tyrosine kinases and Ras and upstream of mitogen-activated protein kinase (MAPK) and MAPK kinase (MKK or MEK) in many signaling pathways. A major objective of our laboratory has been to determine how Raf-1 becomes activated in response to signaling events. Using mammalian, baculovirus, and Xenopus systems, we have examined the roles that phosphorylation and protein-protein interactions play in regulating the biological and biochemical activity of Raf-1. Our studies have provided evidence that the activity of Raf-1 can be modulated by both Ras-dependent and Ras-independent pathways. Recently, we reported that Arg89 of Raf-1 is a residue required for the association of Raf-1 and Ras. Mutation of this residue disrupted interaction with Ras and prevented Ras-mediated, but not protein kinase Cor tyrosine kinase-mediated, enzymatic activation of Raf-1 in the baculovirus expression system. Further analysis of this mutant demonstrated that kinase-defective Raf-1 proteins interfere with the propagation of proliferative and developmental signals by binding to Ras and blocking Ras function. Our findings have also shown that phosphorylation events play a role in regulating Raf-1. We have identified sites of in vivo phospholylation that positively and negatively alter the biological and enzymatic activity of Raf-1. In addition, we have found that some of these phosphorylation sites are involved in mediating the interaction of Raf-1 with potential activators (Fyn and Src) and with other cellular proteins (14-3-3). Results from our work suggest that Raf-1 is regulated at multiple levels by several distinct mechanisms. (C) 1995 Wiley-Liss, Inc. RP MORRISON, DK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC MECHANISMS CARCINOGENESIS LAB,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-46000] NR 27 TC 62 Z9 62 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 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD DEC PY 1995 VL 42 IS 4 BP 507 EP 514 DI 10.1002/mrd.1080420420 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA TH643 UT WOS:A1995TH64300019 PM 8607983 ER PT J AU Sewall, CH Lucier, GW AF Sewall, CH Lucier, GW TI Receptor-mediated events and the evaluation of the Environmental Protection Agency (EPA) of dioxin risks SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT Joint ECETOC/IARC/ICPEMC/IPCS Workshop on Receptor Mediated Mechanisms in Chemical Carcinogenesis CY NOV 14-16, 1994 CL LYON, FRANCE SP European Ctr Ecotoxicol & Toxicol Chem, Int Agcy Res Canc, Int Comm Protect Against Environm Mutagens & Carcinogens, Int Programme Chem Safety DE 2,3,7,8-tetrachlorodibenzo-p-dioxin risk; receptor-mediated response ID EPIDERMAL GROWTH-FACTOR; DOSE-RESPONSE RELATIONSHIPS; RAT-LIVER; UDP-GLUCURONOSYLTRANSFERASES; HUMAN KERATINOCYTES; CELL-PROLIFERATION; MECHANISTIC MODEL; FACTOR BINDING; AH-RECEPTOR; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN C1 UNIV N CAROLINA, CURRICULUM TOXICOL, CHAPEL HILL, NC 27599 USA. RP Sewall, CH (reprint author), NIEHS, BIOCHEM RISK ANAL LAB, RES TRIANGLE PK, NC 27709 USA. NR 53 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC PY 1995 VL 333 IS 1-2 BP 111 EP 122 DI 10.1016/0027-5107(95)00137-9 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA TL835 UT WOS:A1995TL83500014 PM 8538618 ER PT J AU Barrett, JC AF Barrett, JC TI Mechanisms for species differences in receptor-mediated carcinogenesis SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article; Proceedings Paper CT Joint ECETOC/IARC/ICPEMC/IPCS Workshop on Receptor Mediated Mechanisms in Chemical Carcinogenesis CY NOV 14-16, 1994 CL LYON, FRANCE SP European Ctr Ecotoxicol & Toxicol Chem, Int Agcy Res Canc, Int Comm Protect Against Environm Mutagens & Carcinogens, Int Programme Chem Safety DE estrogen receptor; dioxin receptor; peroxisome proliferation activated receptor; protein kinase C ID PROTEIN-KINASE-C; PROLIFERATOR-ACTIVATED RECEPTOR; HUMAN BREAST-CANCER; SIGNAL TRANSDUCTION PATHWAYS; DNA-BINDING ACTIVITY; ESTROGEN-RECEPTOR; PEROXISOME PROLIFERATOR; DIOXIN RECEPTOR; SKIN CARCINOGENESIS; TUMOR PROMOTION AB Species differences resulting from a number of mechanisms are common in receptor-mediated chemical carcinogenesis. In this review, examples of possible mechanisms underlying these differences are discussed, including ligand metabolism, receptor polymorphisms, receptor isoforms, receptor levels, and crosstalk between signal transduction pathways. In addition, a number of other mechanisms also are likely to be important. The developmental state of the animal will determine the expression of receptors in different tissues. The regulatory pathways for cell proliferation and cell death and cell cycle check point controls can vary among species and tissues. Adaptation or potentiation of responses during chronic exposures to chemicals can greatly influence species differences. The mechanisms of adaptive processes are poorly understood but probably highly important for chronic toxicities such as cancer. Finally, different species may have different stem cell populations that are the targets for neoplastic transformation, and this will influence receptor-mediated carcinogenic responses. The implications of species differences in receptor-mediated responses for risk assessment are discussed. RP Barrett, JC (reprint author), NIEHS, MOLEC CARCINOGENESIS LAB, ENVIRONM CARCINOGENESIS PROGRAM, RES TRIANGLE PK, NC 27709 USA. NR 111 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 EI 1873-135X J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC PY 1995 VL 333 IS 1-2 BP 189 EP 202 DI 10.1016/0027-5107(95)00145-X PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA TL835 UT WOS:A1995TL83500022 PM 8538627 ER PT J AU Generoso, WM Witt, KL Cain, KT Hughes, L Cacheiro, NLA Lockhart, AMC Shelby, MD AF Generoso, WM Witt, KL Cain, KT Hughes, L Cacheiro, NLA Lockhart, AMC Shelby, MD TI Dominant lethal and heritable translocation tests with chlorambucil and melphalan in male mice SO MUTATION RESEARCH-GENETIC TOXICOLOGY LA English DT Article DE chemotherapeutic agent; chromosome damage; germ cell; sperm; mutagenicity ID MOUSE BONE-MARROW; BREAST-CANCER; MULTIPLE-MYELOMA; CYTOGENETIC ABNORMALITIES; OVARIAN-CARCINOMA; ACUTE-LEUKEMIA; CHEMOTHERAPY; THERAPY; REARRANGEMENTS; MUTATIONS AB Chemicals used in the treatment of cancer include several that are potent mutagens in a range of in vitro and in vivo assays. For some, genetic effects have also been demonstrated in humans, detected as chromosomal aberrations in peripheral lymphocytes. Because (1) many of these agents are confirmed mutagens, (2) humans are exposed to them in relatively high doses, and (3) an increasing number of early cancer victims are surviving to reproductive age, it is important that information be available on the genetic and reproductive hazards associated with exposure to these agents. Chlorambucil and melphalan are structurally related chemicals that are included in our efforts to identify and assess such hazards among cancer chemotherapy agents. To date, both have been reported to induce specific locus mutations in germ cells of male mice (Russell et al., 1989; Russell et al., 1992b) and melphalan is one of very few chemicals shown to induce such mutations in spermatogonial stem cells. More recently, both chemicals were found to have strong reproductive effects in female mice (Bishop and Generoso, 1995, in preparation). In the present studies, these chemicals were tested for the induction of dominant lethal mutations and heritable translocations in male mice. Both chemicals were found to have reproductive effects attributable to cytotoxicity in specific male germ cell stages and to induce dominant lethal mutations and heritable translocations in postmeiotic germ cells, particularly in mid to early stage spermatids. Thus, relatively extensive data are now available for assessing the genetic and reproductive hazards that may result from therapeutic exposures to these chemicals. C1 ORISE, DIV MED SCI, OAK RIDGE, TN 37831 USA. RTP, COMP SCI CORP, OAK RIDGE, NC 27709 USA. NIEHS, RTP, EXPTL TOXIXOL PROGRAM, OAK RIDGE, NC 27709 USA. RP OAK RIDGE NATL LAB, DIV BIOL, POB 2009, OAK RIDGE, TN 37831 USA. NR 53 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1218 J9 MUTAT RES-GENET TOX JI Mutat. Res.-Genet. Toxicol. PD DEC PY 1995 VL 345 IS 3-4 BP 167 EP 180 DI 10.1016/0165-1218(95)90052-7 PG 14 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA TR093 UT WOS:A1995TR09300009 PM 8552138 ER PT J AU MARX, SJ AF MARX, SJ TI CALCIUM SENSING COMES FULL CIRCLE SO NATURE GENETICS LA English DT Editorial Material ID FAMILIAL BENIGN HYPERCALCEMIA; HYPOCALCIURIC HYPERCALCEMIA; CELL-FUNCTION RP MARX, SJ (reprint author), NIDDKD,METAB DIS BRANCH,GENET & ENDOCRINOL SECT,BETHESDA,MD 20892, USA. NR 14 TC 3 Z9 3 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 DEC PY 1995 VL 11 IS 4 BP 357 EP 358 DI 10.1038/ng1295-357 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA TH629 UT WOS:A1995TH62900005 PM 7493009 ER PT J AU AVRAHAM, KB HASSON, T STEEL, KP KINGSLEY, DM RUSSELL, LB MOOSEKER, MS COPELAND, NG JENKINS, NA AF AVRAHAM, KB HASSON, T STEEL, KP KINGSLEY, DM RUSSELL, LB MOOSEKER, MS COPELAND, NG JENKINS, NA TI THE MOUSE SNELLS WALTZER DEAFNESS GENE ENCODES AN UNCONVENTIONAL MYOSIN REQUIRED FOR STRUCTURAL INTEGRITY OF INNER-EAR HAIR-CELLS SO NATURE GENETICS LA English DT Article ID SUPERFAMILY; SEQUENCES; HEARING; CLONES; LOCUS AB The mouse represents an excellent model system for the study of genetic deafness in humans. Many mouse deafness mutants have been identified and the anatomy of the mouse and human ear is similar. Here we report the use of a positional cloning approach to identify the gene encoded by the mouse recessive deafness mutation, Snell's waltzer (sv). We show that sv encodes an unconventional myosin heavy chain, myosin VI, which is expressed within the sensory hair cells of the inner ear, and appears to be required for maintaining their structural integrity. The requirement for myosin VI in hearing makes this gene an excellent candidate for a human deafness disorder. C1 YALE UNIV,DEPT CELL BIOL,NEW HAVEN,CT 06511. YALE UNIV,DEPT PATHOL,NEW HAVEN,CT 06511. MRC,INST HEARING RES,NOTTINGHAM NG7 2RD,ENGLAND. STANFORD UNIV,SCH MED,DEPT DEV BIOL,STANFORD,CA 94305. OAK RIDGE NATL LAB,DIV BIOL,OAK RIDGE,TN 37831. YALE UNIV,DEPT BIOL,NEW HAVEN,CT 06511. RP AVRAHAM, KB (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702, USA. FU NIDDK NIH HHS [DK-25387, DK-38979]; NIGMS NIH HHS [5F32GM15909-02] NR 28 TC 344 Z9 349 U1 0 U2 10 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1995 VL 11 IS 4 BP 369 EP 375 DI 10.1038/ng1295-369 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA TH629 UT WOS:A1995TH62900012 PM 7493015 ER PT J AU RICHARD, G DELAURENZI, V DIDONA, B BALE, SJ COMPTON, JG AF RICHARD, G DELAURENZI, V DIDONA, B BALE, SJ COMPTON, JG TI KERATIN-13 POINT MUTATION UNDERLIES THE HEREDITARY MUCOSAL EPITHELIA DISORDER WHITE SPONGE NEVUS SO NATURE GENETICS LA English DT Note ID EXPRESSION; PATTERNS C1 NIAMSD,SKIN BIOL LAB,BETHESDA,MD 20892. UNIV ROMA TOR VERGATA,DEPT EXPTL MED,BIOCHEM LAB,IRCCS,IST DERMOPATICO IMMACOLATA,I-00167 ROME,ITALY. IRCCS,IST DERMOPATICO IMMACOLATA,I-00167 ROME,ITALY. NR 25 TC 74 Z9 76 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 DEC PY 1995 VL 11 IS 4 BP 453 EP 455 DI 10.1038/ng1295-453 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA TH629 UT WOS:A1995TH62900028 PM 7493031 ER PT J AU WEINSTATSASLOW, D MERINO, MJ MANROW, RE LAWRENCE, JA BLUTH, RF WITTENBEL, KD SIMPSON, JF PAGE, DL STEEG, PS AF WEINSTATSASLOW, D MERINO, MJ MANROW, RE LAWRENCE, JA BLUTH, RF WITTENBEL, KD SIMPSON, JF PAGE, DL STEEG, PS TI OVEREXPRESSION OF CYCLIN-D MESSENGER-RNA DISTINGUISHES INVASIVE AND IN-SITU BREAST CARCINOMAS FROM NONMALIGNANT LESIONS SO NATURE MEDICINE LA English DT Article ID ATYPICAL HYPERPLASIAS; ESTROGEN-RECEPTOR; EXPRESSION; CANCER; INSITU; AMPLIFICATION; DISEASE; RISK AB The elucidation of molecular alterations that occur during human breast cancer progression may contribute to the development of preventative strategies. Using in situ hybridizations on a cohort of 94 biopsy lesions, quantitatively increased cyclin D mRNA expression levels were observed in only 18% of benign lesions, which confer no or slightly increased breast cancer risk, and 18% of premalignant atypical ductal hyperplasias, which confer a four to fivefold increase in breast cancer risk. The transition to carcinoma was accompanied by frequent cyclin D mRNA overexpression in 76% of low-grade ductal carcinomas in situ, 87% of higher grade comedo ductal carcinomas in situ and 83% of infiltrating ductal breast carcinomas. The data identify a molecular event that may separate benign and premalignant human breast lesions from any form of breast carcinoma. C1 NCI,DIV CLIN SCI,PATHOL LAB,SURG PATHOL SECT,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,DEPT PATHOL,MCN,NASHVILLE,TN 37232. CITY HOPE NATL MED CTR,DIV PATHOL,DUARTE,CA 91010. RP WEINSTATSASLOW, D (reprint author), NCI,DIV CLIN SCI,PATHOL LAB,WOMENS CANC SECT,BLDG 10,ROOM 2A33,BETHESDA,MD 20892, USA. NR 26 TC 246 Z9 250 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 1995 VL 1 IS 12 BP 1257 EP 1260 DI 10.1038/nm1295-1257 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA TH786 UT WOS:A1995TH78600036 PM 7489405 ER PT J AU GLUSHAKOVA, S BAIBAKOV, B MARGOLIS, LB ZIMMERBERG, J AF GLUSHAKOVA, S BAIBAKOV, B MARGOLIS, LB ZIMMERBERG, J TI INFECTION OF HUMAN TONSIL HISTOCULTURES - A MODEL FOR HIV PATHOGENESIS SO NATURE MEDICINE LA English DT Editorial Material ID AIDS RP GLUSHAKOVA, S (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892, USA. NR 12 TC 131 Z9 131 U1 2 U2 11 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 1995 VL 1 IS 12 BP 1320 EP 1322 DI 10.1038/nm1295-1320 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA TH786 UT WOS:A1995TH78600048 PM 7489416 ER PT J AU GARIN, EH WEST, L BLANCHARD, K MATSUSHIMA, K DJEU, JY AF GARIN, EH WEST, L BLANCHARD, K MATSUSHIMA, K DJEU, JY TI EFFECT OF LYMPHOKINES ON (35)SULFATE UPTAKE BY THE GLOMERULAR-BASEMENT-MEMBRANE SO NEPHRON LA English DT Article DE GLOMERULAR BASEMENT MEMBRANE; INTERLEUKIN 8; (35)SULFATE UPTAKE ID BLOOD MONONUCLEAR-CELLS; RECOMBINANT INTERLEUKIN-2; EXTRACELLULAR-MATRIX; NEPHROTIC SYNDROME; MESANGIAL CELLS; ANIONIC SITES; INVITRO; INVIVO; PERMEABILITY; EXPRESSION AB We have previously shown that lymphocytes from idiopathic minimal-lesion nephrotic patients produce a lymphokine (supernatant factor) that increases the (35)sulfate uptake in the glomerular basement membrane (GEM), The purpose of this report was to further characterize the supernatant factor by studying the effects of interleukins (IL) 2-4, 6, and 8, granulocyte-macrophage colony stimulating factor, and tumor necrosis factor on the (35)sulfate incorporation by rat glomeruli in vitro. A significant increase in GEM (35)sulfate uptake was only seen when the glomeruli were cultured with the addition of IL-8 as compared with control cultures: 10.8 +/- (SEM) 1.7 and 7.9 +/- 1.4 cpm/mu g GEM protein, respectively (p < 0.005), IL-8 reproduces the effect of the reported supernatant factor on the GEM (35)sulfate uptake. Because IL-8 was detected in the supernatant of peripheral mononuclear cell cultures from idiopathic minimal-lesion nephrotic syndrome patients in relapse and because the increased GEM (35)sulfate incorporation induced by the supernatant factor has been abolished by the addition to the culture media of anti-IL-8 neutralizing antibodies, we postulate that IL-8 is the previously described supernatant factor. C1 H LEE MOFFITT CANC CTR,TAMPA,FL. NATL CANC INST,FREDERICK,MD. RP GARIN, EH (reprint author), UNIV S FLORIDA,DEPT PEDIAT,DIV NEPHROL,17 DAVIS BLVD,2ND FLOOR,TAMPA,FL 33606, USA. NR 34 TC 5 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-2766 J9 NEPHRON JI Nephron PD DEC PY 1995 VL 71 IS 4 BP 442 EP 447 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA TG893 UT WOS:A1995TG89300010 PM 8587625 ER PT J AU Lippa, CF Smith, TW Flanders, KC AF Lippa, CF Smith, TW Flanders, KC TI Transforming growth factor-beta: Neuronal and glial expression in CNS degenerative diseases SO NEURODEGENERATION LA English DT Article DE cytokine; degenerative disease; neurofibrillary tangle; progressive supranuclear palsy; TGF-beta ID PROGRESSIVE SUPRANUCLEAR PALSY; AMYLOID PRECURSOR PROTEIN; PAIRED HELICAL FILAMENTS; TAU-POSITIVE GLIA; ALZHEIMERS-DISEASE; NERVOUS-SYSTEM; RAT-BRAIN; TGF-BETA; FACTOR-BETA-1; ANTIBODIES AB We have previously shown that the brains of patients with Alzheimer's disease (AD) express transforming growth factor (TGF)-beta 2 in neurofibrillary tangle (NFT)-bearing neurons and reactive astrocytes. The present study was undertaken to determine whether other neurodegenerative diseases were also associated with an alteration of the TGF-beta's. The immunohistochemical expression of TGF-beta 1, -2 and -3 was assessed in the brains of patients with progressive supranuclear palsy (n = 2), amyotrophic lateral sclerosis (n = 3), Lewy body disease (n = 5), Parkinson's disease (n = 1), Shy-Drager syndrome (n = 1), Pick's disease (n = 3), lobar atrophy (n = 1), and corticobasal degeneration (n = 2). Our results were compared to norms for controls (n = 8). We found expression of TGF-beta 2 in both NFT bearing neurons and tangle-bearing glial cells in progressive supranuclear palsy and in neurons with age-related NET formation. Widespread staining of reactive astrocytes for TGF-beta 2 was observed in all degenerative diseases. TGF-beta 1 and -3 staining was not selectively altered in these diseases. We conclude that induction of TGF-beta 2 may be an intrinsic part of the processes that underlie NFT formation and reactive gliosis in a variety of neurodegenerative diseases. (C) 1995 Academic Press Limited. C1 UNIV MASSACHUSETTS,MED CTR,DEPT PATHOL,WORCESTER,MA 01655. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP Lippa, CF (reprint author), UNIV MASSACHUSETTS,MED CTR,DEPT NEUROL,WORCESTER,MA 01655, USA. NR 50 TC 36 Z9 37 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1055-8330 J9 NEURODEGENERATION JI Neurodegeneration PD DEC PY 1995 VL 4 IS 4 BP 425 EP 432 DI 10.1006/neur.1995.0051 PG 8 WC Neurosciences SC Neurosciences & Neurology GA TL636 UT WOS:A1995TL63600010 PM 8846236 ER PT J AU Anouar, Y Eiden, LE AF Anouar, Y Eiden, LE TI Rapid and long-lasting increase in galanin mRNA levels in rat adrenal medulla following insulin-induced reflex splanchnic nerve stimulation SO NEUROENDOCRINOLOGY LA English DT Article DE galanin; adrenal gland; splanchnic nerve; insulin; gene regulation; in situ hybridization ID MESSENGER-RNA; ANTERIOR-PITUITARY; SIGNALING PATHWAYS; HORMONE NEURONS; GENE-EXPRESSION; ESTROGEN; CELLS; IMMUNOREACTIVITY; SECRETION; INVITRO AB Expression of the neuropeptide galanin in the adrenal gland is rapidly induced by reflex stimulation of the splanchnic nerve following insulin-induced hypoglycemia. Here, we examine the cellular localization and mechanism of galanin mRNA upregulation in the adrenal gland after insulin administration, by Northern blot and in situ histochemical hybridization analysis. A 5- to 16-fold increase in galanin mRNA levels, measured by Northern blot hybridization using a rat galanin cRNA probe, was observed after insulin-induced hypoglycemia. An increase in galanin mRNA levels could be detected as early as two hours after administration of a single dose (10 U/kg) of insulin (Iletin II), consistent with the increase in galanin peptide levels in the adrenal gland within 24 h of insulin shock. Insulin-induced galanin mRNA upregulation was confined to the rat adrenal: neither hypothalamic nor pituitary levels of GAL mRNA were altered by insulin treatment. Adrenal galanin mRNA levels were maximally increased by 4 h, remained maximally elevated for at least 48 h, and had returned to baseline 6 days after insulin administration. In situ hybridization analysis localized galanin mRNA induction to scattered groups of chromaffin cells throughout the medulla. These data demonstrate that regulation of GAL biosynthesis in the adrenal medulla occurs at a pretranslational level, and in a subpopulation of chromaffin cells. Rapid and robust upregulation of galanin biosynthesis in chromaffin cells upon insulin-induced splanchnic nerve stimulation suggests a hormonal or paracrine role for galanin in the adrenomedullary response to hypoglycemic shock. C1 NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BETHESDA,MD 20892. OI Eiden, Lee/0000-0001-7524-944X NR 33 TC 24 Z9 24 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD DEC PY 1995 VL 62 IS 6 BP 611 EP 618 DI 10.1159/000127057 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA TL251 UT WOS:A1995TL25100009 PM 8751287 ER PT J AU VanMeter, JW Maisog, JM Zeffiro, TA Hallett, M Herscovitch, P Rapoport, SI AF VanMeter, JW Maisog, JM Zeffiro, TA Hallett, M Herscovitch, P Rapoport, SI TI Parametric analysis of functional neuroimages: Application to a variable-rate motor task SO NEUROIMAGE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; DIMENSIONAL ARM MOVEMENTS; PET IMAGES; CORTICAL MECHANISMS; AUTOMATED ALGORITHM; CORTEX; PERFORMANCE; CEREBELLUM; DIRECTION AB Positron emission tomography (PET) has proven to be a powerful tool in identifying the functional neuroanatomy underlying cognitive and sensorimotor processing. In this paper, we present a method for mathematically modeling the changes in regional cerebral blood flow (rCBF) as a function of experimental parameters using step and linear functions. PET was used to measure rCBF in six subjects who tracked a target moving with constant amplitude across a computer screen at four different frequencies. Each subject tracked the target by flexing and extending the wrist. Two scans were performed at each frequency. The data for each subject were normalized by the mean blood how in each scan and scaled to the mean blood how at rest. Scaled rCBF was regressed onto movement frequency to identify voxels which had either a significant linear or step function response to the frequency of movement. A group analysis was also performed to identify significant functional changes common to all subjects. Significant rCBF increases in relation to movement frequency were found in the supplementary motor area, primary motor cortex, premotor cortex, thalamus, and cerebellum and localized using the Talairach atlas. Habituation of responses was not observed. (C) 1995 Academic Press, Inc. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NIMH,SECT FUNCT BRAIN IMAGING,BETHESDA,MD 20892. NIH,LAB DIAGNOST RADIOL,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,PET IMAGING SECT,BETHESDA,MD 20892. RP VanMeter, JW (reprint author), SENSOR SYST INC,103A CARPENTER DR,STERLING,VA 20164, USA. NR 40 TC 39 Z9 39 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 1995 VL 2 IS 4 BP 273 EP 283 DI 10.1006/nimg.1995.1035 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA TN225 UT WOS:A1995TN22500005 PM 9343612 ER PT J AU Giedd, JN Rapoport, JL Kruesi, MJP Parker, C Schapiro, MB Allen, AJ Leonard, HL Kaysen, D Dickstein, DP Marsh, WL Kozuch, PL Vaituzis, AC Hamburger, SD Swedo, SE AF Giedd, JN Rapoport, JL Kruesi, MJP Parker, C Schapiro, MB Allen, AJ Leonard, HL Kaysen, D Dickstein, DP Marsh, WL Kozuch, PL Vaituzis, AC Hamburger, SD Swedo, SE TI Sydenham's chorea: Magnetic resonance imaging of the basal ganglia SO NEUROLOGY LA English DT Article ID SYMPTOMS; MRI AB Analysis of cerebral magnetic resonance images of 24 subjects with Sydenham's chorea and 48 age-, height-, weight-, gender-, and handedness-matched controls demonstrated increased sizes of the caudate, putamen, and globus pallidus in the Sydenham's chorea group. In contrast, neither total cerebral, prefrontal, or midfrontal volumes or thalamic area were increased. These results indicate the selective involvement of the basal ganglia in Sydenham's chorea. C1 NIA,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. RP Giedd, JN (reprint author), NIMH,CHILD PSYCHIAT BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 6N240,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Dickstein, Daniel/L-3210-2016; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Dickstein, Daniel/0000-0003-1647-5329; kozuch, patricia/0000-0002-7465-9671 NR 27 TC 122 Z9 126 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1995 VL 45 IS 12 BP 2199 EP 2202 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA TL374 UT WOS:A1995TL37400014 PM 8848193 ER PT J AU Meier, JL Straus, SE AF Meier, JL Straus, SE TI Interactions between varicella-zoster virus IE62 and cellular transcription factor USF in the coordinate activation of genes 28 and 29 SO NEUROLOGY LA English DT Article; Proceedings Paper CT 2nd International Conference on the Varicella-Zoster Virus CY SEP, 1994 CL PARIS, FRANCE SP VZV Res Fdn AB Varicella-zoster virus (VZV) gene 28 encodes the viral DNA polymerase, while 29 encodes the major DNA-binding protein. Because of the central importance of these proteins to productive replication of VZV and because, of these, only gene 29 seems to be expressed in latency, we sought to understand how their expression is controlled. We recently reported that the divergent gene 28 and gene 29 transcripts are coordinately upregulated by IE62. Deletions in the 221-bp promoter domain shared by genes 28 and 29 comparably diminish the expression of both genes. By a variety of transient expression, competition gel shift, and super-shift assays, we now show that cellular transcription factor USF binds to a palindromic recognition sequence lying equidistant from transcription start sites for both genes 28 and 29. In the presence of IE62, USF fully activates transcription of genes 28 and 29. Site-specific mutation of three bases in the USF core binding hexamer abrogates activation of the gene 28 and 29 promoters by IE62. USF is important for expression of genes 28 and 29 in productive VZV infection. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NR 5 TC 16 Z9 16 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1995 VL 45 IS 12 SU 8 BP S30 EP S32 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA TQ882 UT WOS:A1995TQ88200011 PM 8545014 ER PT J AU Straus, SE AF Straus, SE TI From molecular biology to medicine: Two decades of achievement in varicella-zoster virus research SO NEUROLOGY LA English DT Article; Proceedings Paper CT 2nd International Conference on the Varicella-Zoster Virus CY SEP, 1994 CL PARIS, FRANCE SP VZV Res Fdn ID DNA; GENE; GLYCOPROTEINS; EXPRESSION; GANGLIA RP Straus, SE (reprint author), NIAID,CLIN INVEST LAB,BLDG 10,ROOM 11N228,BETHESDA,MD 20892, USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1995 VL 45 IS 12 SU 8 BP S11 EP S12 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA TQ882 UT WOS:A1995TQ88200004 PM 8545007 ER PT J AU Krempels, K Usdin, TB Harta, G Mezey, E AF Krempels, K Usdin, TB Harta, G Mezey, E TI PACAP acts through VIP type 2 receptors in the rat testis SO NEUROPEPTIDES LA English DT Article ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE INTESTINAL POLYPEPTIDE; ADENYLATE-CYCLASE; FUNCTIONAL EXPRESSION; TISSUE DISTRIBUTION; NERVOUS-SYSTEM; PITUITARY; NEUROPEPTIDE; LOCALIZATION; PEPTIDE AB Pituitary adenylate cyclase-activating peptide (PACAP) is present and synthesized in the testis in large amounts. Messenger RNA encoding the peptide is expressed in a stage specific manner in the developing germ cells. PACAP regulates a variety of physiological actions, among them, paracrine modulation of spermatogenesis. The PACAP peptides are potential ligands of at least three receptor types, the type I PACAP receptor, VIP1 and VIP2 receptors. Although PACAP27 binding sites have found in the testis, the receptor at which it acts has not been identified. We used in situ hybridization with riboprobes to identify the PACAP binding receptor present in the testis. Neither type I PACAP receptor, nor VIP1 receptor mRNA was present within the germ cells. Using the VIP2 receptor probe there was strong labelling within some cross sections of the seminiferous tubuli, while others were not labelled. The in situ results were also confirmed using reverse-transcription PCR (RT-PCR). Our data suggest that PACAP mediates its possible paracrine effect in the testis through the VIP2 receptor. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP Krempels, K (reprint author), NINCDS,CLIN NEUROSCI BRANCH,BLDG 36,3A17,BETHESDA,MD 20892, USA. NR 22 TC 29 Z9 29 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD DEC PY 1995 VL 29 IS 6 BP 315 EP 320 DI 10.1016/0143-4179(95)90001-2 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA TN713 UT WOS:A1995TN71300002 PM 8837957 ER PT J AU HERMAN, BH VOCCI, F BRIDGE, P AF HERMAN, BH VOCCI, F BRIDGE, P TI THE EFFECTS OF NMDA RECEPTOR ANTAGONISTS AND NITRIC-OXIDE SYNTHASE INHIBITORS ON OPIOID TOLERANCE AND WITHDRAWAL - MEDICATION DEVELOPMENT ISSUES FOR OPIATE ADDICTION SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE NMDA RECEPTOR; NITRIC OXIDE; TOLERANCE; WITHDRAWAL; OPIATE ADDICTION; MORPHINE ID D-ASPARTATE RECEPTOR; LONG-TERM POTENTIATION; LOCUS-COERULEUS NEURONS; PREVENTS MORPHINE-TOLERANCE; GLYCINE RECOGNITION SITE; 7-NITRO INDAZOLE; GLUTAMATE NEUROTOXICITY; FUNCTIONAL EXPRESSION; ALPHA-AMINOADIPATE; MOLECULAR-CLONING AB This article is an exploration of the National Institute on Drug Abuse (NIDA) Technical Review on the role of glutamatergic systems in the development of opiate addiction. The effects of ''glutamate antagonist'' medications on opioid tolerance and withdrawal are examined. In rodents, mu opioid tolerance cart be inhibited by noncompetitive N-methyl D-aspartate (NMDA) receptor antagonists [MK801, dextromethorphan (DM), ketamine, phencyclidine (PCP)], competitive NMDA receptor antagonists (LY274614, NPC17742, LY235959), partial glycine agonists (ACPC), glycine antagonists (ACEA-1328), and nitric oxide synthase (NOS) inhibitors [L-NNA, L-NMMA, methylene blue (MB)]. Similarly, some of the symptoms of opioid withdrawal observed in opioid-dependent rodents also can be inhibited by noncompetitive NMDA receptor antagonists (MK801, DM, ketamine), competitive NMDA receptor antagonists (LY274614), glycine antagonists (felbamate), and NOS inhibitors (L-NNA, L-NMMA, L-NAME, L-NIO, 7-NI, MB). There are some serious toxicological effects associated with the administration of some of the noncompetitive NMDA receptor antagonists in rodent but not in squirrel monkey brain, and some medications induce PCP-like behavioral effects. The medications with the most immediate clinical appeal are those that could be coadministered with methadone to decrease mu opioid tolerance and dependence; they include DM, MB, 7-NI, ACPC, and ACEA-1328. RP HERMAN, BH (reprint author), NATL INST HLTH,NATL INST DRUG ABUSE,DIV MEDICAT DEV,CLIN TRIALS BRANCH,ROCKVILLE,MD 20857, USA. NR 165 TC 143 Z9 144 U1 1 U2 7 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 1995 VL 13 IS 4 BP 269 EP 293 DI 10.1016/0893-133X(95)00140-9 PG 25 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA TJ367 UT WOS:A1995TJ36700002 PM 8747752 ER PT J AU VAUPEL, DB KIMES, AS LONDON, ED AF VAUPEL, DB KIMES, AS LONDON, ED TI NITRIC-OXIDE SYNTHASE INHIBITORS - PRECLINICAL STUDIES OF POTENTIAL USE FOR TREATMENT OF OPIOID WITHDRAWAL SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE NITRIC OXIDE; NITRIC OXIDE SYNTHASE INHIBITORS; OPIOID WITHDRAWAL; OPIATE WITHDRAWAL; MORPHINE; HYPERTENSION; RATS ID RECEPTOR ANTAGONIST MK-801; MORPHINE-WITHDRAWAL; METHYL-ESTER; TOLERANCE; CLONIDINE; ARGININE; BRAIN; SIGNS; RATS AB Four inhibitors of nitric oxide synthase (NOS), administered as acute pretreatments, attenuated several signs of naloxone-precipitated opioid withdrawal in morphine-dependent rats. Profiles of these drugs for inhibiting the expression of withdrawal were similar to that of clonidine, a drug used clinically to treat opioid withdrawal. The nonselective NOS inhibitors, N-G-nitro-L-arginine and N-G-nitro-L-arginine methyl ester, and N(5)-(1-iminoethyl)-L-ornithine, a selective inhibitor of endothelial NOS, increased blood pressure in awake, morphine-naive and morphine-dependent rats not undergoing withdrawal. 7-Nitroindazole, a selective inhibitor of neuronal NOS, did not elevate blood pressure. Insofar as hypertension is a component of opioid withdrawal in humans, the ability of 7-nitroindazole to attenuate morphine withdrawal in rats without eliciting a vasopressor response suggests that 7-nitroindazole may have human therapeutic potential. Research directions for the continued development of 7-nitroindazole as a therapeutic modality are discussed with respect to issues of physical dependence, tolerance, and safety. C1 JOHNS HOPKINS MED INST,DEPT RADIOL,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. RP VAUPEL, DB (reprint author), NATL INST HLTH,NIDA,DIV INTRAMURAL RES,NEUROIMAGING & DRUG ACT SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 27 TC 73 Z9 77 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 1995 VL 13 IS 4 BP 315 EP 322 DI 10.1038/sj.npp.1380297 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA TJ367 UT WOS:A1995TJ36700006 PM 8747756 ER PT J AU KOLACHANA, BS SAUNDERS, RC WEINBERGER, DR AF KOLACHANA, BS SAUNDERS, RC WEINBERGER, DR TI AUGMENTATION OF PREFRONTAL CORTICAL MONOAMINERGIC ACTIVITY INHIBITS DOPAMINE RELEASE IN THE CAUDATE-NUCLEUS - AN IN-VIVO NEUROCHEMICAL ASSESSMENT IN THE RHESUS-MONKEY SO NEUROSCIENCE LA English DT Article DE AMPHETAMINE; COCAINE; PREFRONTAL CORTEX; PRIMATE; STRIATUM; TETRODOTOXIN ID AMINO-ACID NEUROTRANSMITTERS; EXTRACELLULAR DOPAMINE; FRONTAL-CORTEX; RAT-BRAIN; INTRACEREBRAL DIALYSIS; KETAMINE ANESTHESIA; INVIVO MEASUREMENT; CEREBRAL-CORTEX; GLUTAMIC-ACID; D-AMPHETAMINE AB Prefrontal cortical modulation of caudate nucleus dopamine release was investigated in the rhesus monkey using the in vivo microdialysis technique. Reliable and stable basal caudate nucleus dopamine levels were quickly attained within hours following insertion of the dialysis probes. High-pot assium (60 mM) or tetrodotoxin (10 mu M) infusions significantly altered caudate nucleus dopamine levels in the dialysate indicating that measured dopamine levels reflected impulse-dependent release from the presynaptic pool. Pharmacological augmentation of monoaminergic transmission in the sulcus principalis region of the prefrontal cortex resulted in significant alterations in caudate nucleus dopamine levels. Increase of monoaminergic activity by infusion of either D-amphetamine (100 mu M) or cocaine hydrochloride (100 mu M) resulted in a gradual and prolonged decrease in caudate nucleus dopamine levels. Similar decreases were noticed in caudate nucleus dopamine metabolite levels. The present results indicate that in non-human primates modulation of dorsolateral prefrontal cortical monoaminergic transmission results in alterations in dopamine levels in subcortical structures. This observation may have clinical implications for therapeutic management of certain neuropsychiatric disorders, particularly schizophrenia. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 88 TC 74 Z9 74 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1995 VL 69 IS 3 BP 859 EP 868 DI 10.1016/0306-4522(95)00246-F PG 10 WC Neurosciences SC Neurosciences & Neurology GA TE431 UT WOS:A1995TE43100016 PM 8596654 ER PT J AU Bergamaschi, S Binetti, G Govoni, S Wetsel, WC Battaini, F Trabucchi, M Bianchetti, A Racchi, M AF Bergamaschi, S Binetti, G Govoni, S Wetsel, WC Battaini, F Trabucchi, M Bianchetti, A Racchi, M TI Defective phorbol ester-stimulated secretion of beta-amyloid precursor protein from Alzheimer's disease fibroblasts SO NEUROSCIENCE LETTERS LA English DT Article DE Alzheimer's disease; human skin fibroblasts; amyloid precursor protein; protein kinase C; phorbol esters ID PHOSPHORYLATION AB The present study shows that cultured fibroblasts from sporadic Alzheimer's disease patients are deficient in protein kinase C-regulated secretion of amyloid precursor protein. In particular, Alzheimer fibroblasts show a reduced basal secretion and a reduced response at low concentrations of phorbol-12,13-dibutyrate, with an EC(50) twofold higher than control fibroblasts. Furthermore, we observed that such defective regulation of the amyloid precursor secretion can possibly bi: correlated to a specific defect in protein kinase C alpha in fibroblasts from Alzheimer patients. C1 UNIV MILAN,INST PHARMACOL SCI,I-20133 MILAN,ITALY. OSPED S CUORE GESU,ALZHEIMERS DIS RES UNIT,BRESCIA,ITALY. UNIV PAVIA,INST PHARMACOL,I-27100 PAVIA,ITALY. NIEHS,RES TRIANGLE PK,NC 27709. UNIV ROMA TOR VERGATA,DEPT EXPTL MED & BIOCHEM SCI,ROME,ITALY. OSPED S CUORE GESU,CELLULAR & MOLEC NEUROBIOL LAB,BRESCIA,ITALY. RI Battaini , Fiorenzo/H-2617-2012; Govoni, Stefano/K-2965-2015; Binetti, Giuliano/K-4519-2016 OI Govoni, Stefano/0000-0002-7243-6837; Binetti, Giuliano/0000-0003-2759-5844 NR 22 TC 46 Z9 46 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD DEC 1 PY 1995 VL 201 IS 1 BP 1 EP 4 DI 10.1016/0304-3940(95)12168-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA TK808 UT WOS:A1995TK80800001 PM 8830300 ER PT J AU VARRICCHIO, CG AF VARRICCHIO, CG TI CANCER IN ADULTS - A FOCUS ON PREVENTION AND DETECTION IN THE NURSE PRACTITIONERS PRACTICE SO NURSE PRACTITIONER FORUM-CURRENT TOPICS AND COMMUNICATIONS LA English DT Article AB This article provides a very general overview of the group of diseases called cancer. The clinical practice of the nurse practitioner emphasizes health maintenance and promotion of a healthy life style. This focus can carry over into the survival phase of the cancer experience. Counseling about risk status and risk reduction are an integral part of the total approach to cancer care. These activities can be integrated into standard care delivered by the nurse practitioner. Copyright (C) 1995 by W.B. Saunders Company RP VARRICCHIO, CG (reprint author), NCI,DIV CANC PREVENT & CONTROL,900 ROCKVILLE PIKE,EPN 300,BETHESDA,MD 20892, USA. NR 13 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 1045-5485 J9 NURS PRACT FORUM JI Nurse Pract. Forum-Curr. Top. Commun. PD DEC PY 1995 VL 6 IS 4 BP 215 EP 220 PG 6 WC Nursing SC Nursing GA TJ370 UT WOS:A1995TJ37000009 PM 8547811 ER PT J AU Walton, RC Whitcup, SM Mueller, BU Lewis, LL Pizzo, PA Nussenblatt, RB AF Walton, RC Whitcup, SM Mueller, BU Lewis, LL Pizzo, PA Nussenblatt, RB TI Combined intravenous ganciclovir and foscarnet for children with recurrent cytomegalovirus retinitis SO OPHTHALMOLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; VIRUS RETINITIS; COMBINATION; AIDS; RETINOPATHY; RESISTANCE; THERAPY; DISEASE; INVITRO AB Purpose: Children with the acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis may not complain of symptoms despite the presence of advanced sight-threatening disease. Although little data exist regarding CMV retinitis in this population, the treatment of this disease may be difficult because of frequent, extensive recurrences after reduction of drug dose from induction to maintenance levels. The authors reported the results of the use of combined ganciclovir and foscarnet for treatment of recurrent CMV retinitis in three children with AIDS. Methods: Three children with recurrent CMV retinitis were treated with combined ganciclovir and foscarnet administered intravenously. All patients initially received induction dosages of ganciclovir followed by maintenance therapy, at which time they experienced reactivation of their disease. The dosing regimen for induction with the combined therapy was foscarnet (60 mg/kg every 8 hours) and ganciclovir (5 mg/kg daily for 3 weeks), Maintenance with combined therapy consisted of foscarnet (90 mg/kg daily) and ganciclovir (5 mg/kg daily). Results: All patients showed complete healing of the retinitis during the first 3 weeks of combined therapy. Median survival after initiation of combined therapy was 15 weeks(range, 12-33 weeks), None of the children experienced reactivation of CMV retinitis during combined therapy with ganciclovir and foscarnet. Combined therapy was well tolerated in all patients without major side effects. No patient required discontinuation or interruption of either drug during combined therapy. Conclusion: Children with recurrent CMV retinitis may not report visual symptoms, which can delay therapeutic intervention. Therefore, recurrent disease in children should be treated aggressively to avoid potentially devastating visual loss. A combination of ganciclovir and foscarnet appears to be a safe and effective therapeutic option for treatment of recurrent CMV retinitis in children with AIDS. This approach causes no additional toxic reactions and may provide improved long-term control of recurrent CMV retinitis in children. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 29 TC 12 Z9 14 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 1995 VL 102 IS 12 BP 1865 EP 1870 PG 6 WC Ophthalmology SC Ophthalmology GA TL783 UT WOS:A1995TL78300027 PM 9098289 ER PT J AU Raynor, E Robison, WG Garrett, CG McGuirt, WT Pillsbury, HC Prazma, J AF Raynor, E Robison, WG Garrett, CG McGuirt, WT Pillsbury, HC Prazma, J TI Consumption of a high-galactose diet induces diabetic-like changes in the inner ear SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID ALDOSE-REDUCTASE INHIBITOR; RETINAL CAPILLARIES; RATS; TOLRESTAT; MELLITUS; SORBITOL; COMPLICATIONS; MYOINOSITOL; PREVENTION; NEUROPATHY AB Diabetes mellitus is a disease that affects multiple organ systems, In our laboratory it has been shown that there is a significant loss of outer hair cells in genetically;diabetic rats. Galactosemia can also produce diabetic-like changes, This study was performed to demonstrate whether these changes also occur in the cochlea. Three groups of Sprague-Dawley rats were used and fed either a control diet, a 50% galactose diet, or a 50% galactose diet with the addition of an aldose reductase inhibitor, After 5 months the animals were killed, and the cochleas were removed, fixed, and stained, Diabetes-induced damage was assessed by counting the hair cells and calculating the neuroganglion cell density, The histopathologic changes induced by galactose were manifested as outer hair cell loss and a decrease in neuroganglion cell density. Control animals had the least amount of hair cell loss and the greatest neuroganglion cell density of all three groups, Galactose-only animals demonstrated the most pronounced changes in both hair cell loss and neuroganglion cell degeneration; however, only changes of neuroganglion cell density in the basal turn were significant, the addition of an aldose reductase inhibitor provided inconclusive results in both hair cell determination and neuroganglion cell density; however, generally the inhibitor partially prevented the damage produced by galactose, These results suggest that a high-galactose diet can induce diabetic-like changes in the cochlea. C1 UNIV N CAROLINA,SCH MED,DIV OTOLARYNGOL HEAD & NECK SURG,CHAPEL HILL,NC 27599. NEI,BETHESDA,MD 20892. RI Raynor, Eileen/F-7572-2013 NR 29 TC 10 Z9 10 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 1995 VL 113 IS 6 BP 748 EP 754 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA TK813 UT WOS:A1995TK81300015 PM 7501387 ER PT J AU Max, MB AF Max, MB TI Thirteen consecutive well-designed randomized trials show that antidepressants reduce pain in diabetic neuropathy and postherpetic neuralgia SO PAIN FORUM LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIAL; TOOTH-PULP SENSATIONS; DOUBLE-BLIND; IMIPRAMINE TREATMENT; RATIO SCALES; AMITRIPTYLINE; SYMPTOMS; DESIPRAMINE; RELIEVES; DESCRIPTORS C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NR 40 TC 33 Z9 33 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 1058-9139 J9 PAIN FORUM JI Pain Forum PD WIN PY 1995 VL 4 IS 4 BP 248 EP 253 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TK974 UT WOS:A1995TK97400008 ER PT J AU Melez, KA Cherry, J Sanchez, C Ettinger, RB Walsh, TJ AF Melez, KA Cherry, J Sanchez, C Ettinger, RB Walsh, TJ TI Successful outpatient treatment of Trichosporon beigelii peritonitis with oral fluconazole SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Note DE Trichosporon beigelii; peritonitis; fluconazole; antifungal therapy ID FUNGAL PERITONITIS; AMPHOTERICIN-B; INFECTION; DIALYSIS; MYCOSIS C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA. NR 20 TC 12 Z9 13 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD DEC PY 1995 VL 14 IS 12 BP 1110 EP 1113 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA TK447 UT WOS:A1995TK44700019 PM 8745028 ER PT J AU SEASHORE, MR CHO, S DESPOSITO, F SHERMAN, J WAPPNER, RS WILSON, MG AF SEASHORE, MR CHO, S DESPOSITO, F SHERMAN, J WAPPNER, RS WILSON, MG TI HEALTH SUPERVISION FOR CHILDREN WITH TURNER SYNDROME SO PEDIATRICS LA English DT Article ID DYSGENETIC GONAD; SEX-CHROMOSOME; X-CHROMOSOME; GROWTH; ABNORMALITIES; MOSAICISM; MONOSOMY; GIRLS C1 NIH,BETHESDA,MD 20892. US HLTH RESOURCES & SERV ADM,ROCKVILLE,MD. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC 20024. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. AMER ACAD PEDIAT,GENET & BIRTH DEFECTS SECT,ELK GROVE VILLAGE,IL 60009. RP SEASHORE, MR (reprint author), AMER ACAD PEDIAT,COMM GENET,ELK GROVE VILLAGE,IL 60009, USA. NR 36 TC 22 Z9 22 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 1995 VL 96 IS 6 BP 1166 EP 1173 PG 8 WC Pediatrics SC Pediatrics GA TJ133 UT WOS:A1995TJ13300030 ER PT J AU Long, RM AF Long, RM TI What information about the NIGMS is presently available on the World Wide Web? What is coming next? SO PHARMACEUTICAL RESEARCH LA English DT News Item RP Long, RM (reprint author), NIGMS,PHARMACOL PHYSIOL & BIOL CHEM DIV,PHARMACOL & PHYSIOL SCI BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD DEC PY 1995 VL 12 IS 12 BP 1820 EP 1820 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA TN604 UT WOS:A1995TN60400001 ER PT J AU Anderson, LM Ruskie, S Carter, J Pittinger, S Kovatch, RM Riggs, CW AF Anderson, LM Ruskie, S Carter, J Pittinger, S Kovatch, RM Riggs, CW TI Fetal mouse susceptibility to transplacental carcinogenesis: Differential influence of Ah receptor phenotype on effects of 3-methylcholanthrene, 12-dimethylbenz[a]anthracene, and benzo[a]pyrene SO PHARMACOGENETICS LA English DT Article DE Ahr phenotype; transplacental carcinogenesis; polycyclic aromatic hydrocarbons ID BETA-NAPHTHOFLAVONE; DEPENDENT DIFFERENCES; GENETIC-DIFFERENCES; MICE; METABOLISM; LUNG; TUMORIGENESIS; INDUCTION; LOCUS; DNA AB Genetic backcrosses of C57BL/6 and DBA/2 mice were used to examine the influence of maternal and fetal polymorphisms at the Ahr locus on susceptibility to transplacental carcinogenesis by 3-methylcholanthrene, 7,12-dimethylbenz[a]anthracene, and benzo[a]pyrene, (C57BL/6 x DBA/2) F-1 mothers were backcrossed to DBA/2 males, and DBA/2 females to F-1 males to produce both Ahr-responsive (Ah(+)) and nonresponsive (Ah(-)) fetuses carried by mothers that were themselves either Ah(+) or Ah(-), 3-Methylcholanthrene was given intragastrically on gestation days 13-18 and 7,12-dimethylbenz[a]anthracene or benzo[a]pyrene on day 17 as a single intraperitoneal dose. Ahr phenotype was determined by the zoxazolamine sleeping time test after beta-naphthoflavone pretreatment at 6 weeks of age, The offspring were examined for rumours at 1 year, Both 3-methylcholanthrene and 7,12-dimethylbenz[a]anthracene treatments resulted in a two- to five-fold greater incidence and multiplicity of lung and liver rumours in the Ah(+) offspring compared with that in Ah(-) littermates. By contrast, there was no difference between Ah(+) and Ah(-) offspring with regard to numbers of tumours caused by benzo[a]pyrene, Maternal Ahr phenotype appeared to play a role also, in that the offspring of the Ahr-responsive F-1 mothers developed fewer tumours per unit dose than those of the nonresponsive DBA/2 mothers. The effect of maternal phenotype on risk was three- to five-fold. Fetal and maternal phenotype combined yielded a 10- to 20-fold risk differential for transplacental carcinogenesis by the methylated compounds, with greatest risk experienced by responsive fetuses in nonresponsive mothers, and least by nonresponsive progeny of responsive mothers. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. PATHOL ASSOCIATES INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. RP Anderson, LM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,DIV CANC ETIOL,FREDERICK,MD 21702, USA. NR 32 TC 21 Z9 21 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 1995 VL 5 IS 6 BP 364 EP 372 DI 10.1097/00008571-199512000-00005 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA TM965 UT WOS:A1995TM96500005 PM 8747408 ER PT J AU Furuya, H FernandezSalguero, P Gregory, W Taber, H Steward, A Gonzalez, FJ Idle, JR AF Furuya, H FernandezSalguero, P Gregory, W Taber, H Steward, A Gonzalez, FJ Idle, JR TI Genetic polymorphism of CYP2C9 and its effect on warfarin maintenance dose requirement in patients undergoing anticoagulation therapy SO PHARMACOGENETICS LA English DT Article DE genetic polymorphism; CYP2C9; warfarin; anticoagulation therapy ID PREDICTION; CDNA C1 MED SCH NEWCASTLE UPON TYNE,DEPT PHARMACOL SCI,PHARMACOGENET RES UNIT,NEWCASTLE TYNE NE2 4HH,TYNE & WEAR,ENGLAND. NIH,NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. GENOTYPE LTD,NEWCASTLE TYNE NE2 4HE,TYNE & WEAR,ENGLAND. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027; Idle, Jeff/0000-0002-6143-1520 NR 11 TC 214 Z9 221 U1 0 U2 5 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 1995 VL 5 IS 6 BP 389 EP 392 DI 10.1097/00008571-199512000-00008 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA TM965 UT WOS:A1995TM96500008 PM 8747411 ER PT J AU Reszka, K Eldred, GE Wang, RH Chignell, C Dillon, J AF Reszka, K Eldred, GE Wang, RH Chignell, C Dillon, J TI The photochemistry of human retinal lipofuscin as studied by EPR SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article AB Fluorescent material generated in the human retina accumulates within lipofuscin (HLF) granules of the retinal pigment epithelium (RPE) during aging. We have been investigating the possible light-induced contribution of these fluorophores to various diseases including age-related macular de generation. Our studies have shown that some of the fluorescent components of HLF are products of the reaction of retinaldehyde with ethanolamine and that synthetic mixtures of this reaction can serve as a useful model for photophysical studies. Previous research by us has demonstrated that irradiation of either natural or synthetic lipofuscin resulted in the formation of a triplet state and possibly a free radical. Here EPR studies were performed to verify the formation of that radical. The UV irradiation of either synthetic or natural human retinal lipofuscin extracts in oxygen-free methanol led to the formation of a 5,5-dimethylpyrroline-N-oxide (DMPO) spin-trapped carbon-centered radical resulting from either hydrogen atom or electron abstraction from solvent molecules. In the presence of oxygen superoxide was formed, which was observed as a DMPO adduct. It is concluded that certain components of the chloroform-soluble fluorophores of human RPE lipofuscin granules and the fluorescent reaction products of retinaldehyde and ethanolamine are photophysically similar but not the same. Electron or hydrogen abstraction from a substrate by these fluorophores in vivo and the resulting radical products may contribute to the age-related decline of RPE function and blue light damage in the retina. C1 COLUMBIA UNIV,DEPT OPHTHALMOL,NEW YORK,NY 10032. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. UNIV MISSOURI,MASON INST OPHTHALMOL,COLUMBIA,MO 65212. NR 14 TC 47 Z9 47 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD DEC PY 1995 VL 62 IS 6 BP 1005 EP 1008 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TQ245 UT WOS:A1995TQ24500010 PM 8570736 ER PT J AU Soares, JH Kerr, JM Gray, RW AF Soares, JH Kerr, JM Gray, RW TI 25-hydroxycholecalciferol in poultry nutrition SO POULTRY SCIENCE LA English DT Review DE vitamin D; 25-hydroxycholecalciferol; chicken; endocrine function ID EGG-SHELL CALCIFICATION; D-BINDING PROTEIN; INTESTINAL CALCIUM TRANSPORT; VITAMIN-D; RAT-KIDNEY; 1,25-DIHYDROXYVITAMIN-D3 SYNTHESIS; PHOSPHATE DEPRIVATION; EMBRYONIC-DEVELOPMENT; BIOLOGICAL-ACTIVITY; MESSENGER-RNA AB Vitamin D is a complex of secosteroids that must undergo metabolic alterations to reach optimal biological activity. The parent compounds 1) ergocalciferol (D-2) and 2) cholecalciferol (D-3) can be synthesized in the leaves of many plants or in the skin of most animals, respectively. Transport of vitamin D steroids after absorption is associated with vitamin D binding proteins (DBP). In general, the relative binding affinities of the vitamin D steroids are: 25-hydroxy vitamin D-3 [25-(OH)D-3] = 24,25-dihydroxy vitamin D-3 [24,25-(OH)(2)D-3] 25,26-dihydroxy vitamin D-3 [25,26-(OH)(2)D-3] > 25-hydroxy vitamin D-2 (25-(OH)D-2) > 1, 25-dihydroxy vitamin D-3 [1,25-(OH)(2)D-3] > vitamin D-3 The DBP in poultry does not bind D-2 forms effectively, and therefore poultry can not use this form of vitamin D adequately. The concentration of 25-(OH)D, in blood seems to be well correlated with dietary vitamin D intake or exposure to ultraviolet light. The 1 alpha hydroxylase enzyme in the kidney is subject to negative feedback regulation and is critical for formation of the active metabolite 1,25-(OH)(2)D-3. The intracellular vitamin D receptor (VDR) specifically binds 1,25-(OH)(2)D-3 and is necessary for cellular action. Increased levels of two to three orders of magnitude are required for 25-(OH)D-3 to compete with 1,25(OH)(2)D-3 for binding on VDR Feeding studies with 25-(OH)D-3 suggest it has nearly twice the activity of vitamin D-3. Hatchability studies have shown that 25-(OH)D-3 supports good fertility and hatchability, whereas hens fed only 1,25-(OH)(2)D-3 did not have normal hatchability. Likewise, 1,25-(OH)(2)D-3 seems to reach toxic levels at dietary concentrations only two to three times optimal dietary levels whereas feeding 25-(OH)D-3 for extended periods at levels 8 to 10 times requirement seems to have no adverse effects. It seems that 25-(OH)D-3 is the most active metabolite of vitamin D-3, ultimately capable of supporting both cellular functions and embryonic development in chickens and turkeys when fed as the sole source of vitamin D-3. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. AMOCO BIOPROD CORP,AMOCO RES CTR,NAPERVILLE,IL 60566. RP Soares, JH (reprint author), UNIV MARYLAND,DEPT ANIM SCI,COLLEGE PK,MD 20742, USA. NR 102 TC 45 Z9 48 U1 3 U2 11 PU POULTRY SCIENCE ASSN INC PI CHAMPAIGN PA 309 W CLARK ST, CHAMPAIGN, IL 61802 SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD DEC PY 1995 VL 74 IS 12 BP 1919 EP 1934 PG 16 WC Agriculture, Dairy & Animal Science SC Agriculture GA TR044 UT WOS:A1995TR04400001 PM 8825582 ER PT J AU Reiter, Y Brinkmann, U Jung, SH Pastan, I Lee, B AF Reiter, Y Brinkmann, U Jung, SH Pastan, I Lee, B TI Disulfide stabilization of antibody Fv: Computer predictions and experimental evaluation SO PROTEIN ENGINEERING LA English DT Article DE B3; dsFv; immunotoxin; Pseudomonas exotoxin ID SINGLE-CHAIN FV; PSEUDOMONAS EXOTOXIN; RECOMBINANT IMMUNOTOXIN; FUSION PROTEINS; BINDING AB Using molecular modeling technology we have recently identified positions in conserved framework regions of Fvs which can be used td stabilize antibody Fvs by an interchain disulfide bond engineered in between the structurally conserved framework positions of the variable domains of heavy (V-H) and light (V-L) immunoglobulin chains (disulfide-stabilized Fv; dsFv). The computer model indicated the existence of other potential sites in the framework regions that might be suitable for disulfide bond formation between V-H and V-L The possibility of obtaining dsFvs using these positions is evaluated here experimentally by constructing dsFv immunotoxins in which the Fv moiety is fused to a truncated form of Pseudomonas exotoxin. We analyzed the extent of dsFv formation and the activity of the resulting dsFv immunotoxins, and compared various dsFv molecules with the scFv immunotoxin, Our results demonstrate that position H44-L105 is the only one which gives high production yields of active dsFv. All other positions gave either low yields and activity or completely failed to produce active dsFv. With one exception, the formation and activities of the dsFvs corresponded to the C-alpha-C-alpha distance between the V-H and V-L positions, with an. optimal distance of 5.7 Angstrom producing the best dsFv, Distances of 6.O-6.9 Angstrom resulted in a low yield of protein that was still capable of binding antigen, whereas distances > 7.0 Angstrom resulted in molecules in which dsFv formation was not obtained. C1 NCI, NIH, DIV CANC BIOL DIAG & CTR, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. RI Lee, Byungkook/E-4564-2011 OI Lee, Byungkook/0000-0002-3339-4582 NR 28 TC 38 Z9 40 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD DEC PY 1995 VL 8 IS 12 BP 1323 EP 1331 DI 10.1093/protein/8.12.1323 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA UB454 UT WOS:A1995UB45400016 PM 8869646 ER PT J AU FRANK, MK CLORE, GM GRONENBORN, AM AF FRANK, MK CLORE, GM GRONENBORN, AM TI STRUCTURAL AND DYNAMIC CHARACTERIZATION OF THE UREA DENATURED STATE OF THE IMMUNOGLOBULIN BINDING DOMAIN OF STREPTOCOCCAL PROTEIN-G BY MULTIDIMENSIONAL HETERONUCLEAR NMR-SPECTROSCOPY SO PROTEIN SCIENCE LA English DT Article DE B1 DOMAIN; BACKBONE DYNAMICS; N-15 RELAXATION; PROTEIN G; STRUCTURE; UNFOLDED STATE ID MODEL-FREE APPROACH; L-ALA-OH; BACKBONE DYNAMICS; AQUEOUS-SOLUTIONS; LARGER PROTEINS; CHEMICAL-SHIFTS; 434 REPRESSOR; N-15; RELAXATION; SPECTRA AB The structure and dynamics of the urea-denatured B1 immunoglobulin binding domain of streptococcal protein G (GB1) has been investigated by multidimensional heteronuclear NMR spectroscopy. Complete H-1, N-15, and C-13 assignments are obtained by means of sequential through-bond correlations. The nuclear Overhauser enhancement, chemical shift, and (3)J(HN alpha) coupling constant data provide no evidence for the existence of any significant population of residual native or nonnative ordered structure. N-15 relaxation measurements at 500 and 600 MHz, however, provide evidence for conformationally restricted motions in three regions of the polypeptide that correspond to the second beta-hairpin, the N-terminus of the alpha-helix, and the middle of the alpha-helix in the native protein. The time scale of these motions is longer than the apparent overall correlation time (similar to 3 ns) and could range from about 6 ns in the case of one model to between 4 mu s and 2 ms in another; it is not possible to distinguish between these two cases with certainty because the dynamics are highly complex and hence the analysis of the time scale of this slower motion is highly model dependent. It is suggested that these three regions may correspond to nucleation sites for the folding of the GB1 domain. With the exception of the N- and C-termini, where end effects predominate, the amplitude of the subnanosecond motions, on the other hand, are fairly uniform and model independent, with an overall order parameter S-2 ranging from 0.4 to 0.5. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 56 TC 119 Z9 119 U1 1 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD DEC PY 1995 VL 4 IS 12 BP 2605 EP 2615 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TH430 UT WOS:A1995TH43000018 PM 8580852 ER PT J AU SCHOOLER, NR KEITH, SJ SEVERE, JB MATTHEWS, SN AF SCHOOLER, NR KEITH, SJ SEVERE, JB MATTHEWS, SN TI MAINTENANCE TREATMENT OF SCHIZOPHRENIA - A REVIEW OF DOSE REDUCTION AND FAMILY TREATMENT STRATEGIES SO PSYCHIATRIC QUARTERLY LA English DT Article ID INTERMITTENT NEUROLEPTIC PROPHYLAXIS; RANDOMIZED CLINICAL-TRIAL; FOLLOW-UP; BEHAVIORAL INTERVENTION; COMMUNITY MANAGEMENT; SOCIAL-INTERVENTION; AFTERCARE TREATMENT; EXPRESSED EMOTION; RELATIVES GROUP; THERAPY AB Maintenance treatment in schizophrenia requires the integration of both medication and psychosocial treatment interventions for maximum effect. We review the recent evidence for strategies drawn from both domains. For the use of anti-psychotic medication we focus on studies of dose reduction using two strategies that differ in assumptions regarding the action of medication. They are: continuous low-dose and targeted, early intervention or intermittent treatment. For psychosocial interventions we focus on studies of family treatment. Regarding dose reduction, we conclude that both strategies are feasible but the targeted strategy incurs higher relapse and rehospitalization rates. Regarding family treatment, we conclude that family treatment provides benefits beyond other psychosocial interventions or usual care, but that there is no evidence for differences in efficacy among family treatments. C1 NIMH,DIV CLIN & TREATMENT RES,ROCKVILLE,MD. RP SCHOOLER, NR (reprint author), UNIV PITTSBURGH,SCH MED,WESTERN PSYCHIAT INST & CLIN,DEPT PSYCHIAT,3811 OHARA ST,PITTSBURGH,PA 15213, USA. NR 41 TC 14 Z9 14 U1 5 U2 6 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0033-2720 J9 PSYCHIAT QUART JI Psychiatr. Q. PD WIN PY 1995 VL 66 IS 4 BP 279 EP 292 DI 10.1007/BF02238750 PG 14 WC Psychiatry SC Psychiatry GA TF643 UT WOS:A1995TF64300002 PM 8584586 ER PT J AU Trull, TJ Useda, JD Costa, PT McCrae, RR AF Trull, TJ Useda, JD Costa, PT McCrae, RR TI Comparison of the MMPI-2 personality psychopathology five (PSY-5), the NEO-PI, and the NEO-PI-R SO PSYCHOLOGICAL ASSESSMENT LA English DT Article ID 5-FACTOR MODEL; DEPRESSION; EXPERIENCE; DISORDERS AB This study examined relations between Minnesota Multiphasic Personality Inventory Personality Psychopathology Five (PSY-5; A. R. Harkness, J. L. McNulty, & Y. S. Ben-Porath, 1995), NEO Personality Inventory(NEO-PI; P. T. Costa & R. R. McCrae, 1985), and the revised NEO-PI (NEOPI-R; P. T. Costa & R. R. McCrae, 1992b) scores in community (N = 170) and clinical (N = 57) samples. In the clinical sample, the temporal stability of the scales and their associations with personality disorder symptom counts were also assessed. Correlations between the two instruments demonstrated meaningful relations between the two sets of constructs in both samples. Both instruments showed substantial stability over 6 months, and both were significant and substantial predictors of symptom counts for most personality disorders. The data support the reinterpretation of personality disorders in terms of underlying dimensions of personality. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP Trull, TJ (reprint author), UNIV MISSOURI,DEPT PSYCHOL,210 MCALESTER HALL,COLUMBIA,MO 65211, USA. OI Costa, Paul/0000-0003-4375-1712 NR 35 TC 78 Z9 78 U1 2 U2 17 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD DEC PY 1995 VL 7 IS 4 BP 508 EP 516 DI 10.1037/1040-3590.7.4.508 PG 9 WC Psychology, Clinical SC Psychology GA TL180 UT WOS:A1995TL18000012 ER PT J AU HAWKINS, MJ GRAY, C HAWKINS, WE AF HAWKINS, MJ GRAY, C HAWKINS, WE TI GENDER DIFFERENCES OF REPORTED SAFER SEX BEHAVIORS WITHIN A RANDOM SAMPLE OF COLLEGE-STUDENTS SO PSYCHOLOGICAL REPORTS LA English DT Article ID AIDS; KNOWLEDGE AB This study investigated the frequency of safer sex behaviors with a random sample of sexually active college students (N=315) at a university in the Northwest. The most frequent safer sex behaviors were discussion of contraceptives (58.6%), being more selective (46.5%), and reducing the number of sexual partners (43.6%). The least frequent safer sex behaviors included discussion of partner's sexual health prior to sexual behavior (26.1%), using condoms or dental dams (24.4%), one sexual partner (22.6%), and abstaining from sex as a safer sex practice (12.3%). The only two behaviors which indicated gender differences were (a) if they were being more selective as a safer sex practice and (b) reducing number of sexual partners as a safer sex practice. Women were more likely to state that they were ''almost always'' more selective than their male peers. Findings from this study indicated that a substantial number of students reported ''at risk'' sexual practices. These findings indicated a need for HIV-prevention efforts. C1 NATL INST DRUG ABUSE,BALTIMORE,MD. RP HAWKINS, MJ (reprint author), CATHOLIC UNIV AMER,NATL CATHOLIC SCH SOCIAL SERV,WASHINGTON,DC 20064, USA. NR 10 TC 6 Z9 6 U1 1 U2 3 PU PSYCHOLOGICAL REPORTS PI MISSOULA PA P O BOX 9229, MISSOULA, MT 59807 SN 0033-2941 J9 PSYCHOL REP JI Psychol. Rep. PD DEC PY 1995 VL 77 IS 3 BP 963 EP 968 PN 1 PG 6 WC Psychology, Multidisciplinary SC Psychology GA TJ037 UT WOS:A1995TJ03700048 ER PT J AU NEEDLE, R FISHER, DG WEATHERBY, N CHITWOOD, D BROWN, B CESARI, H BOOTH, R WILLIAMS, ML WATTERS, J ANDERSEN, M BRAUNSTEIN, M AF NEEDLE, R FISHER, DG WEATHERBY, N CHITWOOD, D BROWN, B CESARI, H BOOTH, R WILLIAMS, ML WATTERS, J ANDERSEN, M BRAUNSTEIN, M TI RELIABILITY OF SELF-REPORTED HIV RISK BEHAVIORS OF DRUG-USERS SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; SEXUAL-BEHAVIOR; INFECTION; VALIDITY; PREVALENCE; ADDICTS AB In AIDS research, relatively little attention has been paid to reliability of self-report of drug users. The authors examined the test-retest reliability of the Risk Behavior Assessment (NIDA 1991) questionnaire. This structured-interview questionnaire was administered twice to 196 drug users in 5 cities over a 48-hr period. Findings indicated that respondents consistently self-report drug use, injection practices, and sexual behaviors; discrepancies do not appear to reflect systematic decreases or increases in self-report; unreliability is associated with poorly worded questions and respondent characteristics; and discrepant reports warrant attention in analysis and interpretation of data. Measurement error has implications for estimating risks, understanding relationships between behavior and HIV transmission, and interpreting change after interventions. Items with low reliability have been revised, and further reliability studies are examining whether revisions have led to improved reliability. C1 UNIV ALASKA,DEPT PSYCHOL,ANCHORAGE,AK 99508. NIDA,ROCKVILLE,MD. UNIV MIAMI,COMPREHENS DRUG RES CTR,CORAL GABLES,FL 33124. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA 94143. PERSONALIZED NURSING CORP,DETROIT,MI. AFFLIATED SYST CORP,HOUSTON,TX. UNIV COLORADO,ADDICT RES & TREATMENT SERV,BOULDER,CO 80309. NR 33 TC 322 Z9 324 U1 0 U2 4 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD DEC PY 1995 VL 9 IS 4 BP 242 EP 250 DI 10.1037/0893-164X.9.4.242 PG 9 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA TK322 UT WOS:A1995TK32200004 ER PT J AU MINER, LL MARLEY, RJ AF MINER, LL MARLEY, RJ TI CHROMOSOMAL MAPPING OF THE PSYCHOMOTOR STIMULANT EFFECTS OF COCAINE IN BXD RECOMBINANT INBRED MICE SO PSYCHOPHARMACOLOGY LA English DT Article DE COCAINE; CHROMOSOMAL MAPPING; PSYCHOSTIMULANT EFFECTS; RECOMBINANT INBRED MICE ID STRAINS; AMPHETAMINE; MOUSE; RATS AB To elucidate genes associated with cocaine's locomotor stimulant effects, we used recombinant inbred-quantitative trait loci (RI-QTL) analyses to identify chromosomal loci associated with locomotor activity before (baseline) and after cocaine treatment. RI-QTL analyses seek to identify associations between a quantitative measure of a phenotype and one or more previously mapped marker loci across a panel of RI strains. In the present study, 11 BXD RI strains were used to identify several putative QTLs for each phenotype. Both baseline locomotor activity and cocaine's locomotor stimulant effects are polygenic, with both unique and overlapping genetic influences. The largest associations for baseline activity were observed on chromosomes 5 and 9 and the largest associations for cocaine's psychomotor stimulant effects on chromosomes 3 and 17. C1 NIDA,ADDICT RES CTR,DIV INTRAMURAL RES,MOLEC NEUROBIOL BRANCH,GENET SECT,BALTIMORE,MD 21224. NR 22 TC 29 Z9 29 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 1995 VL 122 IS 3 BP 209 EP 214 DI 10.1007/BF02246541 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA TJ462 UT WOS:A1995TJ46200001 PM 8748389 ER PT J AU Bahro, M Schreurs, BG Sunderland, T Molchan, SE AF Bahro, M Schreurs, BG Sunderland, T Molchan, SE TI The effects of scopolamine, lorazepam, and glycopyrrolate on classical conditioning of the human eyeblink response SO PSYCHOPHARMACOLOGY LA English DT Article DE classical conditioning; eyeblink; scopolamine; lorazepam; glycopyrrolate; learning; memory; human ID NICTITATING-MEMBRANE RESPONSE; CENTRAL CHOLINERGIC BLOCKADE; HUMAN-MEMORY; INDUCED AMNESIA; DISRUPTION; DEMENTIA; MODELS; BENZODIAZEPINES; SENSITIVITY; HIPPOCAMPUS AB Human eyeblink conditioning, a relatively simple form of learning and memory, has previously been shown to be impaired by the central and peripheral anticholinergic scopolamine. The present study compared the behavioral effects of scopolamine with the benzodiazepine lorazepam and a peripherally active anticholinergic, glycopyrrolate. Thirty-six healthy normal volunteers (mean age: 23.7 years) were studied with 12 assigned double-blind to each of three drug conditions (0.5 mg scopolamine IV, 2 mg lorazepam PO, or 0.2 mg glycopyrrolate IV). Subjects underwent classical conditioning of the eyeblink response in which the conditioned stimulus was an 80 dB binaural tone, and the unconditioned stimulus was a 2 psi airpuff to the right eye. Ten trials of unpaired stimulus presentations were followed by 60 paired trials and finally by an extinction period of five tone-alone presentations. An eyeblink response that occurred during the tone but before the airpuff was scored as a conditioned response (CR), Subjects treated with lorazepam (43% mean CRs) and scopolamine (51% mean CRs) exhibited a significantly lower asymptotic level of conditioning than those treated with glycopyrrolate (85% mean CRs; P < 0.01), However, during extinction, lorazepam-treated subjects (35% CRs) showed a lower overall level of responding to the tone than either scopolamine (60% CRs) or glycopyrrolate (62% CRs) treated subjects (P < 0.05). It seems unlikely that these differences could be accounted for by drug-induced alterations in motor responses because there were no significant differences between the three drug conditions in the frequency,latency, or amplitude of unconditioned responses to the airpuff. Overall, our data indicate that scopolamine and lorazepam impair eyeblink conditioning and suggest that some of the effects of benzodiazepines and anticholinergics on learning and memory can be differentiated using this paradigm. C1 NIH,NINDS,LAB ADAPT SYST,BETHESDA,MD 20892. RP Bahro, M (reprint author), NIH,NIMH,CTR CLIN,LAB CLIN SCI,SECT GERIATR PSYCHIAT,BETHESDA,MD 20892, USA. OI Schreurs, Bernard/0000-0002-5776-0807 NR 36 TC 23 Z9 23 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 1995 VL 122 IS 4 BP 395 EP 400 DI 10.1007/BF02246273 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA TM460 UT WOS:A1995TM46000013 PM 8657840 ER PT J AU Najavits, LM Griffin, ML Luborsky, L Frank, A Weiss, RD Liese, BS Thompson, H Nakayama, E Siqueland, L Daley, F Onken, LS AF Najavits, LM Griffin, ML Luborsky, L Frank, A Weiss, RD Liese, BS Thompson, H Nakayama, E Siqueland, L Daley, F Onken, LS TI Therapists' emotional reactions to substance abusers: A new questionnaire and initial findings SO PSYCHOTHERAPY LA English DT Article ID ALCOHOLISM COUNSELORS; ADDICTION; SUCCESS; COUNTERTRANSFERENCE; PSYCHOTHERAPY; PATIENT; STAFF AB Therapists' emotional responses to substance abuse patients have long been hypothesized to impact on treatment, but have rarely been studied, This article reports results for a new scale developed for this purpose, Ratings of Emotional Attitudes to Clients by Treaters (REACT). The REACT was administered to 52 therapists and 140 cocaine-dependent outpatients, at sessions 2, 5, and 24 of psychotherapy. It was found to have high internal consistency at each time point, moderately high convergent validity with therapists' (but not patients') therapeutic alliance ratings, and a factor structure that appeared to meaningfully derive four factors: ''therapist in conflict with self,'' ''therapist focused on own needs,'' ''positive connection,'' and ''therapist in conflict with the patient.'' Therapists' emotional responses were found to become more negative over the course of treatment, and, when compared by theoretical orientation, were found more positive for 12-step drug counselors than for cognitive or supportive-expressive therapists. C1 BROOKSIDE HOSP,SAN PABLO,CA. UNIV KANSAS,MED CTR,LAWRENCE,KS 66045. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA 15260. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NATL INST DRUG ABUSE,LEXINGTON,KY 40583. RP Najavits, LM (reprint author), HARVARD UNIV,MCLEAN HOSP,SCH MED,ALCOHOL & DRUG ABUSE PROGRAM,115 MILL ST,BELMONT,MA 02178, USA. NR 35 TC 22 Z9 24 U1 2 U2 4 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI PHOENIX PA 3900 E CAMELBACK RD #200, PHOENIX, AZ 85018 SN 0033-3204 J9 PSYCHOTHER JI Psychotherapy PD WIN PY 1995 VL 32 IS 4 BP 669 EP 677 DI 10.1037/0033-3204.32.4.669 PG 9 WC Psychology, Clinical SC Psychology GA UM338 UT WOS:A1995UM33800016 ER PT J AU LUBIN, JH BOICE, JD SAMET, JM AF LUBIN, JH BOICE, JD SAMET, JM TI ERRORS IN EXPOSURE ASSESSMENT, STATISTICAL POWER AND THE INTERPRETATION OF RESIDENTIAL RADON STUDIES SO RADIATION RESEARCH LA English DT Article ID LUNG-CANCER; INDOOR RADON; WOMEN; RN AB To date, epidemiological studies of risk from residential radon have not convincingly demonstrated an association with lung cancer. These case-control studies, however, have inherent limitations due to errors in estimates of exposure to indoor radon. These errors take on special significance because the level of residential risk predicted from studies of underground miners is relatively low and possibly at the limit detectable by current epidemiological methods. To illustrate the problem caused by errors in exposure assessment, a series of case-control studies were simulated and resulting dose-response relationships evaluated. For each of four assumed error distributions for exposure to radon progeny, 10 indoor radon studies of 700 cases and 700 controls were generated randomly from a population with a risk of radon-induced lung cancer based on extrapolations from studies of underground miners. When exposures were assumed as known without error, 6 of 10 studies failed to find a significant dose response, in accord with the theoretical power of the study of 0.47. For simulations in which exposures were measured with error, the situation was worse, as the power of the study was reduced further and it was even less likely that a single study would result in a significant finding. For each error scenario, combining data from the 10 simulated studies did result in a significant dose response, However, the pooled results are somewhat misleading, because the effects of mobility, missing radon measurements, residential occupancy and potential confounding variables such as cigarette smoking were not taken into account. Empirical estimates of power were computed using 1,000 simulated case-control studies. When mobility and missing radon measurements in prior homes were incorporated into the design, the power of the study decreased, reducing the chance of detecting a significant effect of exposure. Enlarging study size to 2,000 cases and 2,000 controls increased the power of the study to 0.90 when exposure error was absent and subjects lived in one home only, but power was below 0.40 under realistic conditions for exposure error and mobility. When studies were generated under an assumption that exposure does not increase risk, up to 15% of simulated studies with 700 cases and 700 controls resulted in an estimated dose-response parameter in excess of the dose response from studies of miners. With increasing mobility and exposure error, it became virtually impossible to distinguish between the distributions of risk estimates from simulated studies based on an underlying excess relative risk of 0.015/working level month from estimates based on no risk from exposure. This exercise reveals the substantial contribution that errors in exposure assessment and incomplete measurements must play in explaining the inconsistency of current residential radon studies and highlights the intrinsic difficulty with such studies. Further, these simulations imply that it is unlikely that case-control studies alone will be able to determine precise estimates of risk from indoor radon, and that even future efforts at pooling epidemiological studies may not adequately address issues of risk from residential radon exposure. (C) 1995 by Radiation Research Society C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. RP LUBIN, JH (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 31 TC 66 Z9 70 U1 0 U2 6 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 1995 VL 144 IS 3 BP 329 EP 341 DI 10.2307/3578953 PG 13 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA TH825 UT WOS:A1995TH82500011 PM 7494877 ER PT J AU LEIDY, NK TRAVER, GA AF LEIDY, NK TRAVER, GA TI PSYCHOPHYSIOLOGICAL FACTORS CONTRIBUTING TO FUNCTIONAL PERFORMANCE IN PEOPLE WITH COPD - ARE THERE GENDER DIFFERENCES SO RESEARCH IN NURSING & HEALTH LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; SICKNESS IMPACT PROFILE; CHRONIC PHYSICAL ILLNESS; CHRONIC LUNG-DISEASE; AIR-FLOW LIMITATION; HOSPITALIZED-PATIENTS; CHRONIC-BRONCHITIS; OUTCOME MEASURE; QUALITY; LIFE AB The purpose of this study was to compare the functional performance profiles of men and women with chronic obstructive pulmonary disease, describe the extent to which physiologic impairment, physical symptoms, and psychosocial resources contribute in a cumulative manner to performance, and outline the extent to which these contributions differ across gender. Secondary data analyses were employed. Although women (n = 45) reported more functional difficulty than men (n = 44) in 9 of 12 Sickness Impact Profile categories, the differences were not significant. Using hierarchical regression procedures, physiologic, symptomatic, and interactive variables predicted total (R(2) = .64) and physical performance (R(2) = .52), while symptomatic and psychosocial variables predicted psychosocial performance (R(2) = .53). Results indicate that models of functional performance may be different for men and women. (C) 1995 John Wiley & Sons, Inc. C1 UNIV ARIZONA,TUCSON,AZ 85721. RP LEIDY, NK (reprint author), NATL INST NURSING RES,DIV INTRAMURAL RES,BLDG 301,ROOM 5B10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 58 TC 28 Z9 28 U1 2 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD DEC PY 1995 VL 18 IS 6 BP 535 EP 546 DI 10.1002/nur.4770180609 PG 12 WC Nursing SC Nursing GA TG571 UT WOS:A1995TG57100007 PM 7480854 ER PT J AU Khoja, I Herranz, AS Williams, JR CannonSpoor, HE Heim, RC Freed, WJ Poltorak, M AF Khoja, I Herranz, AS Williams, JR CannonSpoor, HE Heim, RC Freed, WJ Poltorak, M TI Localization of gliosis in the corpus striatum of mice following cortical lesions SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE cortical lesion; deafferentation; GFAP; striatum; astrocytes; synapse ID FIBRILLARY ACIDIC PROTEIN; SUBSTANTIA-NIGRA; COMPARTMENTAL ORGANIZATION; DOPAMINERGIC-NEURONS; REACTIVE ASTROCYTES; NEURITE OUTGROWTH; MATURATION FACTOR; GROWTH-FACTOR; GLIAL GROWTH; BRAIN INJURY AB Localized lesions of the medial and lateral frontal cortex were used to study gliosis, neurofilament content and changes in synaptic density in the mouse striatum. Relationships between the sites of cortical lesions and the localization of changes in different regions of the striatum were examined after 3 and 12 weeks. Independent of the location of frontal cortex lesions, glial fibrillary acidic protein (GFAP) immunoreactivity was increased throughout the entire striatum after 3 weeks. Twelve weeks after lesioning, increases in GFAP were confined to the dorsomedial (DM) striatum following medial cortical lesions, and to the dorsolateral (DL) striatum following lateral cortical lesions, suggesting persistent gliosis only in areas of striatal deafferentation. It appears, therefore, that the mechanisms which induce gliosis after short and long time periods are different. C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,SECT PRECLIN NEUROSCI,WASHINGTON,DC 20032. BETHESDA NAVAL HOSP,DEPT NEUROSURG,BETHESDA,MD 20814. NR 39 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PD DEC PY 1995 VL 9 IS 2 BP 113 EP 119 PG 7 WC Neurosciences SC Neurosciences & Neurology GA TN973 UT WOS:A1995TN97300006 PM 21551839 ER PT J AU Hedges, S ElMallakh, RS Carvey, PM Suddath, RL Wyatt, RJ AF Hedges, S ElMallakh, RS Carvey, PM Suddath, RL Wyatt, RJ TI Dopamine-responsive neurotrophic factor in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article ID INVITRO MATURATION; NEURONS C1 UNIV LOUISVILLE,SCH MED,DEPT PSYCHIAT & BEHAV SCI,MOOD DISORDERS RES PROGRAM,LOUISVILLE,KY 40292. NIMH,NEUROPSYCHIAT BRANCH,NEUROPSYCHIAT RES HOSP,WASHINGTON,DC 20032. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT NEUROL SCI,SECT MOVEMENT DISORDERS,CHICAGO,IL 60612. NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 1995 VL 18 IS 1 BP 83 EP 84 DI 10.1016/0920-9964(95)00066-6 PG 2 WC Psychiatry SC Psychiatry GA UE364 UT WOS:A1995UE36400011 PM 8929765 ER PT J AU Wolters, PL Brouwers, P Moss, HA AF Wolters, PL Brouwers, P Moss, HA TI Pediatric HIV disease: Effect on cognition, learning, and behavior SO SCHOOL PSYCHOLOGY QUARTERLY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFUSION ZIDOVUDINE THERAPY; INFECTED CHILDREN; AIDS; TRANSMISSION; ADOLESCENTS; RISK; ABNORMALITIES; INFANTS AB As more infants are infected with human immunodeficiency virus (HIV) and new medical treatments improve quality of life and lengthen survival time, the number of HIV-infected children attending school will continue to grow. Children with symptomatic HIV infection may develop a range of neuropsychological abnormalities associated with the direct effects of HIV on the central nervous system (CNS). Furthermore, behavioral and social-emotional difficulties may result from the indirect effects of HIV, which include the psychological reactions to living with the disease. Such cognitive and behavioral impairments may result in learning problems and academic difficulties. Thus, infants, children, and adolescents infected with HIV may require a range of developmental, rehabilitative, and special services. The purpose of this paper is to provide information about pediatric HIV infection to professionals working in educational settings. The primary focus is on the neurological, cognitive, motor, and behavioral impairments associated with the direct effects of HIV on the CNS, which may impede learning and school performance. The role of school psychology in pediatric HIV disease also is discussed. C1 MED ILLNESS COUNSELING CTR,CHEVY CHASE,MD. RP Wolters, PL (reprint author), NCI,PEDIAT BRANCH,NIH,BLDG 10,ROOM 13N-240,BETHESDA,MD 20892, USA. NR 83 TC 14 Z9 15 U1 0 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 1045-3830 J9 SCHOOL PSYCHOL QUART JI Sch. Psychol. Q. PD WIN PY 1995 VL 10 IS 4 BP 305 EP 328 DI 10.1037/h0088312 PG 24 WC Psychology, Educational SC Psychology GA TZ084 UT WOS:A1995TZ08400004 ER PT J AU BUCHER, JR RAO, GN ABDO, K AF BUCHER, JR RAO, GN ABDO, K TI DIET AND TEST ANIMALS SO SCIENCE LA English DT Letter RP BUCHER, JR (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27510, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 1 PY 1995 VL 270 IS 5241 BP 1421 EP 1422 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TH375 UT WOS:A1995TH37500004 PM 7491480 ER PT J AU HUDSON, K COLLINS, F AF HUDSON, K COLLINS, F TI GENETIC DISCRIMINATION - ACTUARIAL ASPECTS - RESPONSE SO SCIENCE LA English DT Letter RP HUDSON, K (reprint author), NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 1 PY 1995 VL 270 IS 5241 BP 1423 EP 1423 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TH375 UT WOS:A1995TH37500006 ER PT J AU MISHKIN, B LESHNER, AI BERRY, RS DISTLERATH, LM DUSTIRA, AK GARDNER, WP GOLDSTEIN, P KLEMM, R BLACK, B FRAENKEL, AH GILBERT, F POTENZA, JM ROSENBAUM, JI SMOOT, OR LOEVINGER, L AF MISHKIN, B LESHNER, AI BERRY, RS DISTLERATH, LM DUSTIRA, AK GARDNER, WP GOLDSTEIN, P KLEMM, R BLACK, B FRAENKEL, AH GILBERT, F POTENZA, JM ROSENBAUM, JI SMOOT, OR LOEVINGER, L TI HOW DOES THE TEXACO CASE AFFECT PHOTOCOPYING BY SCIENTISTS SO SCIENCE LA English DT Editorial Material C1 NIDA,ROCKVILLE,MD. UNIV CHICAGO,CHICAGO,IL 60637. MERCK RES LABS,RAHWAY,NJ. OFF RES INTEGR,ROCKVILLE,MD. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV TEXAS,AUSTIN,TX 78712. KLEMM ANAL GRP,WASHINGTON,DC. WEINBERG & GREEN,BALTIMORE,MD. ALTHEIMER & GRAY,CHICAGO,IL. BANNER & ALLEGRETTI LTD,WASHINGTON,DC. INFORMAT TECHNOL IND COUNCIL,WASHINGTON,DC. RP MISHKIN, B (reprint author), HOGAN & HARTSON,555 13TH ST NW,WASHINGTON,DC 20004, USA. NR 4 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 1 PY 1995 VL 270 IS 5241 BP 1450 EP 1451 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TH375 UT WOS:A1995TH37500024 ER PT J AU BUEY, FF MUNTANER, C AF BUEY, FF MUNTANER, C TI MARXISMS AGAINST THE CURRENT - WEIGHING THE DECADE OF THE EIGHTIES SO SCIENCE & SOCIETY LA English DT Note ID AUTOMOBILE-INDUSTRY; PARIS COMMUNE; UNITED-STATES; SOCIAL-CLASS; WORK C1 NIMH,HLTH & HUMAN SERV LAB,BETHESDA,MD 20892. RP BUEY, FF (reprint author), UNIV PAMPEU FABRA,FAC HUMANIDADES,BALMES 132,E-08008 BARCELONA,SPAIN. RI Muntaner, C/A-5043-2010 NR 74 TC 0 Z9 0 U1 1 U2 2 PU GUILFORD PRESS PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0036-8237 J9 SCI SOC JI Sci. Soc. PD WIN PY 1995 VL 58 IS 4 BP 471 EP 481 PG 11 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA QE093 UT WOS:A1995QE09300005 ER PT J AU Irvine, KR Restifo, NP AF Irvine, KR Restifo, NP TI The next wave of recombinant and synthetic anticancer vaccines SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE tumor-associated antigen; recombinant vaccines; immunotherapy; recombinant fowlpox; recombinant adenovirus ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-CELLS; HUMAN PAPILLOMAVIRUS TYPE-16; DIRECT GENE-TRANSFER; EPSTEIN-BARR VIRUS; SURFACE PROTEIN-A; CARCINOEMBRYONIC ANTIGEN; LYMPHOCYTE-T; LISTERIA-MONOCYTOGENES; IMMUNE-RESPONSES AB The identification of tumor-associated antigens (TAA) recognized by T lymphocytes makes the development of antigen-specific synthetic and recombinant vaccines possible. The expression of TAA within a recombinant vector increases control over the Kinetics and quantity, the molecular form, and the subcellular location of the immunogen delivered. The next generation of antitumor vaccines employs cytokines and costimulatory molecules expressed in concert with TAA that are capable of augmenting the activation and proliferation of antitumor immune responses. The ultimate goal of these new strategies, the treatment of established cancer, is now being realized in animal models. RP Irvine, KR (reprint author), NCI,SURG BRANCH,BLDG 10,BETHESDA,MD 20892, USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 121 TC 12 Z9 12 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 DEC PY 1995 VL 6 IS 6 BP 337 EP 347 DI 10.1016/1044-579X(95)90003-9 PG 11 WC Oncology SC Oncology GA TV117 UT WOS:A1995TV11700004 PM 8938272 ER PT J AU Arbuck, SG AF Arbuck, SG TI Paclitaxel: Current developmental approaches of the National Cancer Institute SO SEMINARS IN ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; PHASE-II; TAXOL; CISPLATIN RP Arbuck, SG (reprint author), NCI,DIV CANC TREATMENT,NIH,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,6130 EXECUT BLVD,ROCKVILLE,MD 20862, USA. NR 31 TC 10 Z9 10 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 DEC PY 1995 VL 22 IS 6 SU 15 BP 55 EP 63 PG 9 WC Oncology SC Oncology GA TV453 UT WOS:A1995TV45300011 PM 8643972 ER PT J AU MACFARLANE, MP FRAKER, DL ALEXANDER, HR NORTON, JA LUBENSKY, I JENSEN, RT AF MACFARLANE, MP FRAKER, DL ALEXANDER, HR NORTON, JA LUBENSKY, I JENSEN, RT TI PROSPECTIVE-STUDY OF SURGICAL RESECTION OF DUODENAL AND PANCREATIC GASTRINOMAS IN MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 SO SURGERY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 23-25, 1995 CL PHILADELPHIA, PA SP Amer Assoc Endocrine Surgeons ID ZOLLINGER-ELLISON SYNDROME; ISLET-CELL TUMORS; MANAGEMENT AB Background. The role of surgical resection of gastrinoma in multiple endocrine neoplasia type 1 (MEN 1) is controversial because of low biochemical cure rates, but with adequate duodenal exploration higher cure rates may be possible. Methods. We have prospectively evaluated this proposal in ten consecutive patients with MEN 1 and Zollinger-Ellison syndrome who underwent surgical exploration for gastrinoma resection including a detailed evaluation of the duodenum by palpation, intraoperative endoscopy with transillumination, and duodenotomy. Results. Duodenal tumors were present in seven patients. Six of seven patients had metastatic deposits in lymph nodes, and two of seven had synchronous pancreatic tumors. Three patients had a single duodenal tumor, one patient had two tumors, and three patients had more than 20 duodenal tumors. positive gastrin staining by use of immunohistochemistry was seen in all duodenal tumors. None of these seven patients were biochemically cured. Of three patients with negative duodenal explorations, two had single pancreatic tumors removed and one had only lymph node gastrinoma. No patients were biochemically cured. Conclusions. Not all patients with MEN 1 and Zollinger-Ellison syndrome have duodenal gastrinomas. In the 70% of patients with duodenal tumors, even extensive duodenal exploration with removal of positive lymph nodes does not result in cures because C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NIDDKD,DEPT PATHOL,CTR CLIN,METAB DIS BRANCH,BETHESDA,MD 20892. NR 20 TC 82 Z9 83 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1995 VL 118 IS 6 BP 973 EP 980 DI 10.1016/S0039-6060(05)80102-3 PG 8 WC Surgery SC Surgery GA TH947 UT WOS:A1995TH94700009 PM 7491542 ER PT J AU YU, KC ALEXANDER, HR ZIESSMAN, HA NORTON, JA DOPPMAN, JL BUELL, JF NIEMAN, LK CUTLER, GB CHROUSOS, GP FRAKER, DL AF YU, KC ALEXANDER, HR ZIESSMAN, HA NORTON, JA DOPPMAN, JL BUELL, JF NIEMAN, LK CUTLER, GB CHROUSOS, GP FRAKER, DL TI ROLE OF PREOPERATIVE IODOCHOLESTEROL SCINTISCANNING IN PATIENTS UNDERGOING ADRENALECTOMY FOR CUSHINGS-SYNDROME SO SURGERY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 23-25, 1995 CL PHILADELPHIA, PA SP Amer Assoc Endocrine Surgeons ID DIAGNOSIS; DISEASE; HORMONE AB Background. Iodocholesterol scintiscanning (IS) is a noninvasive, functional diagnostic test. We report our experience with IS as an adjunct for adrenal surgery for Cushing's syndrome. Methods. Between April 1983 and October 1994, 23 patients with Cushing's syndrome from benign primary adrenal disease underwent IS and computed tomography (CT) and/or magnetic resonance imaging (MRI). Twelve patients had unilateral adrenal involvement with a solitary adenoma (n = 11) or unilateral multinodular disease (n = 1), and 11 patients had bilateral adrenal disease. Results. In patients with Cushing's syndrome caused by unilateral adrenal disease, IS was 100% specific and 100% sensitive, whereas in two cases CT/MRI incorrectly showed bilateral disease. In patients with Cushing's syndrome with bilateral adrenal involvement, IS had one false-negative result with nonvisualization. CT/MRI showed unilateral disease in four cases and no abnormalities in two. All patients in this series were cured of Cushing's syndrome after unilateral adrenalectomy in 11 cases and bilateral adrenalectomy in 12 cases. Conclusions. IS is a highly sensitive and specific imaging modality and is an essential adjunct to biochemical testing in planning adrenal resections for Cushing's syndrome caused by primary adrenal disease. C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DIV NUCL MED,WASHINGTON,DC 20007. UNIV WASHINGTON,SCH MED,DEPT SURG,ST LOUIS,MO. NR 13 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1995 VL 118 IS 6 BP 981 EP 987 PG 7 WC Surgery SC Surgery GA TH947 UT WOS:A1995TH94700010 PM 7491543 ER PT J AU CHEN, H DOPPMAN, JL CHROUSOS, GP NORTON, JA NIEMAN, LK UDELSMAN, R AF CHEN, H DOPPMAN, JL CHROUSOS, GP NORTON, JA NIEMAN, LK UDELSMAN, R TI ADRENOCORTICOTROPIC HORMONE-SECRETING PHEOCHROMOCYTOMAS - THE EXCEPTION TO THE RULE SO SURGERY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 23-25, 1995 CL PHILADELPHIA, PA SP Amer Assoc Endocrine Surgeons ID ECTOPIC ACTH SYNDROME; CUSHINGS-SYNDROME; MANAGEMENT AB Background. Operative management of pheochromocytomas dictates resection of the involved adrenal and exploration-resection of the contralateral gland if enlarged. We describe an exception to this rule. Methods. We report the largest series of patients with adrenocorticotropic hormone (ACTH)-secreting pheochromocytomas and review the world literature. Results. Four patients presented with findings of adrenocorticoid and catecholamine excess, as well as elevated levels of plasma ACTH, urinary metanephrines, and urinary free cortisol. Abdominal computed tomography scans revealed bilateral adrenal hyperplasia, and magnetic resonance imaging scans showed a unilateral adrenal mass with a bright T2 signal suggesting a pheochromocytoma. Two patients underwent adrenal venous sampling localizing ACTH secretion to the pheochromocytoma. All underwent unilateral adrenalectomy for a benign tumor without morbidity or death, leaving the contralateral hyperplastic adrenal in situ. After operation all patients experienced normalization of their levels of plasma ACTH, urinary metanephrines, and urinary free cortisol with resolution of symptoms. Combining our series with previously reported cases of ACTH-secreting pheochromocytomas, almost all are benign (20 of 21) in contrast to most ACTH-secreting tumors. Conclusions. ACTH-secreting pheochromocytomas are the exception to the rule; unilateral adrenalectomy is curative and the contralateral hyperplastic adrenal can be preserved. This approach results in resolution of both syndromes of hormone excess and preserves long-term adrenal function. C1 JOHNS HOPKINS UNIV HOSP,DIV ENDOCRINE & ONCOL SURG,BALTIMORE,MD 21287. NIH,DEPT RADIOL,BETHESDA,MD 20892. NIH,DEPT ENDOCRINOL,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT SURG,ST LOUIS,MO. NR 19 TC 20 Z9 22 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1995 VL 118 IS 6 BP 988 EP 995 DI 10.1016/S0039-6060(05)80104-7 PG 8 WC Surgery SC Surgery GA TH947 UT WOS:A1995TH94700011 PM 7491544 ER PT J AU AMIKURA, K ALEXANDER, HR NORTON, JA DOPPMAN, JL JENSEN, RT NIEMAN, L CUTLER, G CHROUSOS, G FRAKER, DL AF AMIKURA, K ALEXANDER, HR NORTON, JA DOPPMAN, JL JENSEN, RT NIEMAN, L CUTLER, G CHROUSOS, G FRAKER, DL TI ROLE OF SURGERY IN MANAGEMENT OF ADRENOCORTICOTROPIC HORMONE-PRODUCING ISLET-CELL TUMORS OF THE PANCREAS SO SURGERY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 23-25, 1995 CL PHILADELPHIA, PA SP Amer Assoc Endocrine Surgeons ID CUSHINGS-SYNDROME; DIFFERENTIAL-DIAGNOSIS AB Background. Ectopic adrenocorticotropic hormone-producing islet cell tumors of the pancreas (ACTH-ICT) are a rare cause of Cushing's syndrome with a severe and rapidly progressive clinical course. Methods. Charts were reviewed on all patients evaluated and treated for proven Cushing's syndrome caused by ACTH-ICT (n = 12), specifically for the role of surgery in the management of this disease. Results. Ten (83%) of twelve patients with ACTH-ICT had liver metastases at the time of diagnosis (eight of eight with Zollinger-Ellison syndrome, two of four without Zollinger-Ellison syndrome). Surgical management of the primary tumor included three patients who underwent distal pancreatectomy combined with hepatic resection and one patient who underwent laparoscopic enucleation of a tumor from the pancreatic tail. Eight of twelve patients underwent bilateral adrenalectomy to control symptoms of Cushing's syndrome, including three patients who underwent concurrent distal pancreatectomy and hepatic resection. Six of twelve patients died of the disease within 21/2 years of diagnosis, four are alive with progressive hepatic metastases, and one has biochemical evidence of disease. Conclusions. ACTH-ICT of the pancreas is an aggressive tumor, particularly when there is coproduction of gastrin. The benefit of aggressive surgical resection of primary or metastatic ACTH-ICT has not been established. However, palliative bilateral adrenalectomy is justified, because no patients had biochemical cures after aggressive surgical resection in this series. C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. NR 15 TC 28 Z9 28 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1995 VL 118 IS 6 BP 1125 EP 1130 DI 10.1016/S0039-6060(05)80123-0 PG 6 WC Surgery SC Surgery GA TH947 UT WOS:A1995TH94700030 PM 7491532 ER PT J AU HENDERSON, DK AF HENDERSON, DK TI POSTEXPOSURE PROPHYLAXIS FOR OCCUPATIONAL EXPOSURES TO HEPATITIS-B, HEPATITIS-C, AND HUMAN-IMMUNODEFICIENCY-VIRUS SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID HEALTH-CARE WORKERS; HIV-INFECTED BLOOD; SCID-HU MICE; ZIDOVUDINE PROPHYLAXIS; NEEDLESTICK INJURIES; ACCIDENTAL EXPOSURE; HOSPITAL PERSONNEL; MEDICAL PERSONNEL; IMMUNE GLOBULIN; FINAL REPORT AB The magnitudes of risk for occupational infection with hepatitis B, hepatitis C, and HIV are beginning to be clarified. As more information about these risks becomes available, clinicians have begun to search for optimal management strategies for occupational exposures to these bloodborne pathogens. This article discusses these occupational risks its well as the various approaches to management of occupational exposure to these bloodborne pathogens. C1 NCI,HOSP EPIDEMIOL SERV,BETHESDA,MD 20892. RP HENDERSON, DK (reprint author), NCI,WARREN G MAGNUSON CLIN CTR,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2C146,BETHESDA,MD 20892, USA. NR 51 TC 12 Z9 12 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD DEC PY 1995 VL 75 IS 6 BP 1175 EP & PG 0 WC Surgery SC Surgery GA TD984 UT WOS:A1995TD98400012 PM 7482143 ER PT J AU STALEY, JK BOJA, JW CARROLL, FI SELTZMAN, HH WYRICK, CD LEWIN, AH ABRAHAM, P MASH, DC AF STALEY, JK BOJA, JW CARROLL, FI SELTZMAN, HH WYRICK, CD LEWIN, AH ABRAHAM, P MASH, DC TI MAPPING DOPAMINE TRANSPORTERS IN THE HUMAN BRAIN WITH NOVEL SELECTIVE COCAINE ANALOG [I-125] RTI-121 SO SYNAPSE LA English DT Article DE AUTORADIOGRAPHY; HUMAN; DOPAMINE TRANSPORTER; COCAINE ANALOGS ID CENTRAL NERVOUS-SYSTEM; I-125 RTI-55; RECOGNITION SITES; MONKEY BRAIN; H-3 CFT; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; BINDING-SITES; RAT STRIATUM; AUTORADIOGRAPHY AB The novel cocaine analog RTI-121 [3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester] was evaluated as a probe for the in vitro labeling and localization of the dopamine transporter in the human brain. Saturation binding experiments conducted in sucrose-phosphate buffer (10 mM sodium phosphate, pH 7.4, 0.32 M sucrose) revealed high- and low-affinity binding components with affinity values (K-D) of 0.25 +/- 0.04 and 4.9 +/- 1.6 nM (mean +/- SE) and densities (B-max) of 56.8 +/- 13.8 and 147.7 +/- 23.4 pmol/g tissue, respectively. In contrast, when saturation binding experiments were performed in phosphate-buffered saline (10 mM Na2HPO4, 1.8 mM KH2PO4, 136 mM NaCl, 2.8 mM KCl, 10 mM NaI, pH 7.4), a 9-fold decrease in the density of the low-affinity component was noted, suggesting that the low-affinity RTI-121 binding site is associated with the region of the transporter involved in the ionic dependence of substrate recognition and/or uptake. The rank order of potency for inhibition of [I-125]RTI-121 binding to human caudate membranes demonstrates that the radioligand selectively labels the dopamine transporter (GBR 12909 > RTI-121 > mazindol > nomifensine >(-)cocaine > desipramine > citalopram). Autoradiographic mapping of [I-125]RTI-121 revealed very high densities of cocaine recognition sites over areas known to be rich in dopaminergic innervation, including the caudate, putamen, and nucleus accumbens. Moderate densities were also observed over the substantia nigra and the ventral tegmental area. Low-to-background labeling of [(12)5]RTI-121 was seen throughout the cerebral cortex, amygdaloid nuclei, globus pallidus, and thalamus. In comparison with the autoradiographic distribution of the cocaine analogs [H-3]WIN 35, 428 (or CFT) and [I-125]RTI-55 (or beta-CIT), the labeling pattern for [I-125]RTI-121 was more restricted. These studies demonstrate that [I-125]RTI-121 labels dopamine-rich brain regions with greater selectivity than other currently available cocaine analogs, which makes it a potentially superior imaging probe for mapping the dopamine transporter in the human brain. (C) 1995 Wiley-Liss, Inc. C1 UNIV MIAMI,SCH MED,DEPT PHARMACOL,MIAMI,FL 33101. NIDA,ADDICT RES CTR,MOLEC PHARMACOL SECT,BALTIMORE,MD 21224. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. RP STALEY, JK (reprint author), UNIV MIAMI,SCH MED,DEPT NEUROL,MIAMI,FL 33101, USA. FU NIDA NIH HHS [DA 06227] NR 55 TC 61 Z9 61 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 0887-4476 J9 SYNAPSE JI Synapse PD DEC PY 1995 VL 21 IS 4 BP 364 EP 372 DI 10.1002/syn.890210412 PG 9 WC Neurosciences SC Neurosciences & Neurology GA TH484 UT WOS:A1995TH48400011 PM 8869167 ER PT J AU Hunter, ES Tugman, JA AF Hunter, ES Tugman, JA TI Inhibitors of glycolytic metabolism affect neurulation-staged mouse conceptuses in vitro SO TERATOLOGY LA English DT Article ID EMBRYOS INVITRO; EARLY EMBRYOGENESIS; ARACHIDONIC-ACID; RAT; HYPOGLYCEMIA; GLUCOSE; ORGANOGENESIS; CULTURE; TERATOGENESIS; MALFORMATIONS AB In order to evaluate the apparent discordance between altered glucose metabolism and embryonic energy production, the effects of inhibitors of glucose utilization on morphological development and biochemical changes in mouse embryos in culture were evaluated. Day 9 ICR mouse conceptuses having 3-6 pairs of somites were prepared for culture as previously described. 2-Deoxyglucose (2DG) produced a concentration-dependent effect on development. A 25 mu M 2DG concentration did not induce neural tube closure defects (NTDs) but 100 mu M, 100% of embryos exhibited this defect. A 17% reduction in the rate of lactate production by the conceptus was produced by a 24-hr exposure period to 100 mu M 2DG. lodoacetate, which inhibits glyceraldehyde-3-phosphate dehydrogenase in adult tissues, produced high rates of NTDs at concentrations greater than or equal to 2.5 mu M. Following a 24 hour exposure to iodoacetate, lactate production was inhibited at 10 and 25 mu M. The effects of 2DG on embryonic ATP content were assessed to test the hypothesis that effects on glucose utilization would effect embryonic ATP content. De spite using 2DG concentrations that alter development and inhibit glycolysis, there were no effects on whole embryo or visceral yolk sac (VYS) ATP content. However, when the embryo was divided into regions, there was a specific reduction in ATP content in the head following a 24-hr exposure period. No effect of 2DG on head ATP content was produced after 12 hr of exposure. To determine if there were region specific differences in 2DG uptake and distribution that could account for the differential effects of 2DG on ATP content, C-14-2DG accumulation in different regions of the embryo and VYS was determined over the 24-hr culture period. The uptake of 2DG was dependent on the medium 2DG concentration and suggested a higher accumulation in regions with decreased ATP. However, when the uptake was monitored for a 1-hr period after a 24-hr exposure, there was no region specific differences in 2DG uptake. These studies further document the adverse developmental effects of inhibitors of glucose utilization during the early stage of neurulation. The biochemical mechanism for induction of these defects is unclear, but an effect on ATP content does not appear to be solely responsible for the dysmorphogenesis. (C) 1996 Wiley-Liss, Inc. C1 NIEHS,NIH,SYST TOX BRANCH,RES TRIANGLE PK,NC 27709. NR 28 TC 28 Z9 30 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD DEC PY 1995 VL 52 IS 6 BP 317 EP 323 DI 10.1002/tera.1420520602 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA TX643 UT WOS:A1995TX64300001 PM 8711618 ER PT J AU WYSHOCK, EG SUFFREDINI, AF PARRILLO, JE COLMAN, RW AF WYSHOCK, EG SUFFREDINI, AF PARRILLO, JE COLMAN, RW TI COFACTOR-V AND COFACTOR-VIII AFTER ENDOTOXIN ADMINISTRATION TO HUMAN VOLUNTEERS SO THROMBOSIS RESEARCH LA English DT Article DE ENDOTOXIN; FACTOR V; FACTOR VIII; PROTEIN C ID COAGULATION FACTOR-V; ACTIVATED PROTEIN-C; THROMBIN-CATALYZED ACTIVATION; INTRAVASCULAR COAGULATION; VONWILLEBRAND-FACTOR; SEPTIC SHOCK; FACTOR-XA; INACTIVATION; PLASMA; ANTIGEN AB Coagulation factor V (FV) and factor VIII (FVIII) are usually decreased in septicemic DIG. Low doses of endotoxin administered to healthy volunteers stimulate activation of the fibrinolytic, contact and coagulation systems, but not clinical DIG. Following the administration of endotoxin (4 ng/kg) to normal volunteers (n = 15), we applied new assays for FV antigens using monoclonal antibodies to the activation peptide (C1) and to the light chain of FV. At 5 hours, FV coagulant activity was significantly decreased (64 +/- 9%), as was the FV light chain antigen (74 +/- 6%), without a change in factor V C1 antigen or total protein C. In contrast, FVIII coagulant activity was greater than preinfusion levels at 2-5 hours. The decrease in FV activity may be due to APC cleavage of FV heavy chain, but the loss of light chain antigen suggests that plasmin and/or calpain also contribute. APC may not be the only enzyme responsible for cofactor inactivation. FV is one of the most sensitive markers, even reflecting subclinical activation of coagulation. C1 TEMPLE UNIV,SCH MED,SOL SHERRY THROMBOSIS RES CTR,PHILADELPHIA,PA 19140. NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL07828] NR 53 TC 12 Z9 12 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD DEC 1 PY 1995 VL 80 IS 5 BP 377 EP 389 DI 10.1016/0049-3848(95)00190-3 PG 13 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA TD122 UT WOS:A1995TD12200002 PM 8588199 ER PT J AU Weintraub, BD AF Weintraub, BD TI Van Meter Prize SO THYROID LA English DT Editorial Material RP Weintraub, BD (reprint author), NIH,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD DEC PY 1995 VL 5 IS 6 BP 493 EP 493 DI 10.1089/thy.1995.5.493 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TT209 UT WOS:A1995TT20900011 ER PT J AU Harris, CC AF Harris, CC TI 1995 Deichmann Lecture - p53 tumor suppressor gene: At the crossroads of molecular carcinogenesis, molecular epidemiology and cancer risk assessment SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 7th International Congress of Toxicology CY JUL 02-06, 1995 CL SEATTLE, WA SP Boeing Co, NIEHS, NIH, Soc Toxicol, USA, Dow Chem, FDA, Natl Ctr Toxicol Res, NHLBI, Sanofi Winthrop Inc, USA Med Res & Med Command, US DOE, US EPA, Natl Ctr Environm Assessment, BP Amer Inc, Battelle Mem Inst, Battelle Pacific NW Labs, Burroughts Wellcome Fund, Bristol Myers Squibb, DowElanco, ECETOC, Eli Lilly & Co, Genentech Inc, Hoffmann LaRoche, Johnson & Johnson, Nutrasweet, Owens Corning, Rhone Poulenc Inc, Schering Plough Res Inst, Atlantic Richfield Co, CanTox Incorp, Coca Cola Co, Colgate Palmolive, Chem Manufacturers Assoc, DuPont, Eastman Kodak Co, Hoechst Celanese, NIH, Pfizer, Proctor & Gamble, R J Reynolds Tobacco Co, Syntex Corp, TSI Corp, Warner Lambert, Zeneca Cent Toxicol Lab & Safety Med Grp, Alcon Labs, BP Goodrich Co, FMC Corp, Rhone Poulenc Rorer, Marck Res Labs, Rohm & Hass Co, Searle, SmithKline Beecham Pharm DE p53 tumor suppressor gene; carcinogenesis; cancer risk assessment; mutagenesis ID CELL-CYCLE CHECKPOINT; WILD-TYPE P53; DNA-REPAIR; MUTATIONS; TRANSCRIPTION; AMPLIFICATION; FIBROBLASTS; CARCINOMA; APOPTOSIS; ONCOGENE AB Carcinogenesis is a multistage process involving activation of protooncogenes, e.g., ras, and inactivation of tumor suppressor genes, e.g., p53 and p16(INK4).p53 is a prototype tumor suppressor gene that is well suited for analysis of mutational spectrum in human cancers; it is the most common genetic lesion in human cancers, it is a reasonable size for a molecular target, and it may indicate selection of mutations with pathobiological significance. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain and lymphoid malignancies. Mutational hotspots at CpG dinucleotides in codons 175, 245, 248, 273 and 282 may reflect endogenous mutagenic mechanisms, e.g., deamination of 5-methylcytosine to thymidine. Oxy-radicals including nitric oxide may enhance the rate of deamination. G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung, breast, esophagus and liver, and are more likely to be due to bulky carcinogen-DNA adducts. G to T transversion is more common in lung cancers from smokers when compared to never smokers. The high frequency of p53 mutations in the nontranscribed DNA strand is a reflection of strand specific repair. p53 mutation and/or accumulation of p53 protein can be preinvasive events in bronchial or esophageal carcinogenesis. p53 mutations also generally indicate a poor prognosis. In geographic areas where hepatitis B virus (HBV) and aflatoxin B-1 are cancer risk factors, most mutations are at the third nucleotide pair of codon 249. In geographic areas where hepatitis B and C virsus - but not aflatoxin B-1 - are risk factors, the p53 mutations are distributed in numerous codons. HBV X protein complexes with the p53 protein and inhibits its sequence specific DNA binding, transactivating and apoptotic capacity. The mutation load of 249(Ser) mutant cells in nontumorous liver is positively correlated with dietary aflatoxin B-1 exposure. The induction of skin carcinoma by ultraviolet light is indicated by the occurrence of p53 mutations at dipyrimidine sites including CC to TT double base changes. In summary, these differences in mutational frequency and spectrum among human cancer types suggest the etiological contributions in both exogenous and endogenous factors to human carcinogenesis and have implications for human cancer risk assessment. RP Harris, CC (reprint author), NCI,NIH,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 43 TC 41 Z9 41 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC PY 1995 VL 82-3 BP 1 EP 7 DI 10.1016/0378-4274(95)03643-1 PG 7 WC Toxicology SC Toxicology GA TU514 UT WOS:A1995TU51400002 PM 8597035 ER PT J AU Cunningham, ML Matthews, HB AF Cunningham, ML Matthews, HB TI Cell proliferation as a determining factor for the carcinogenicity of chemicals: Studies with mutagenic carcinogens and mutagenic noncarcinogens SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 7th International Congress of Toxicology CY JUL 02-06, 1995 CL SEATTLE, WA SP Boeing Co, NIEHS, NIH, Soc Toxicol, USA, Dow Chem, FDA, Natl Ctr Toxicol Res, NHLBI, Sanofi Winthrop Inc, USA Med Res & Med Command, US DOE, US EPA, Natl Ctr Environm Assessment, BP Amer Inc, Battelle Mem Inst, Battelle Pacific NW Labs, Burroughts Wellcome Fund, Bristol Myers Squibb, DowElanco, ECETOC, Eli Lilly & Co, Genentech Inc, Hoffmann LaRoche, Johnson & Johnson, Nutrasweet, Owens Corning, Rhone Poulenc Inc, Schering Plough Res Inst, Atlantic Richfield Co, CanTox Incorp, Coca Cola Co, Colgate Palmolive, Chem Manufacturers Assoc, DuPont, Eastman Kodak Co, Hoechst Celanese, NIH, Pfizer, Proctor & Gamble, R J Reynolds Tobacco Co, Syntex Corp, TSI Corp, Warner Lambert, Zeneca Cent Toxicol Lab & Safety Med Grp, Alcon Labs, BP Goodrich Co, FMC Corp, Rhone Poulenc Rorer, Marck Res Labs, Rohm & Hass Co, Searle, SmithKline Beecham Pharm DE cell proliferation; mutagenic noncarcinogens; mutagenic carcinogens; diaminotoluenes; nitropropanes; organophosphates; Big Blue(R) transgenic mouse system ID HEPATOCELLULAR PROLIFERATION; HEPATOCARCINOGENICITY; LIVER; RATS; 2,6-DIAMINOTOLUENE; 1-NITROPROPANE; 2-NITROPROPANE; METABOLISM; RODENTS; ASSAY AB Recent work in our laboratory has examined mechanisms whereby chemicals produce mutagenicity in short-term in vitro assays yet fail to produce carcinogenesis in 2-year rodent bioassays. These studies have used mutagenic structural analogs of carcinogenic and noncarcinogenic chemicals for comparison. Our previous studies have determined that differences in the metabolism and disposition of these chemicals were not responsible for their observed carcinogenic differences, but that carcinogenicity correlated with the ability of the respective isomer to induce cell proliferation in the target organ. Mutagenic noncarcinogens such as 2,6-diaminotoluene (DAT), 1-nitropropane (NP), dimethoate, dioxathion, and dichlorvos failed to induce an increase in cell turnover in the target organs. An increase in cell proliferation was observed following exposure to the mutagenic carcinogen analogs 2,4-DAT (liver), 2-NP (liver), and tris(2,3-dibromopropyl)phosphate (kidney). Our recent studies have used transgenic (Big Blue(R)) mice to detect in vivo mutagenesis induced by DAT isomers. Results of these studies demonstrate that administration of the carcinogenic isomer, 2,4-DAT, resulted in an increase in in vivo mutation frequency, whereas administration of the noncarcinogenic isomer, 2,6-DAT, failed to do so. These results indicate that cell proliferation may be requisite for expression of chemical-induced mutagenicity in vivo and thereby accommodate expression of carcinogenicity. RP Cunningham, ML (reprint author), NIEHS,CHEM BRANCH,POB 12233 MD B3-10,RES TRIANGLE PK,NC 27709, USA. NR 25 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC PY 1995 VL 82-3 BP 9 EP 14 DI 10.1016/0378-4274(95)03464-1 PG 6 WC Toxicology SC Toxicology GA TU514 UT WOS:A1995TU51400003 PM 8597159 ER PT J AU Gonzalez, FJ FernandezSalguero, P Lee, SST Pineau, T Ward, JM AF Gonzalez, FJ FernandezSalguero, P Lee, SST Pineau, T Ward, JM TI Xenobiotic receptor knockout mice SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 7th International Congress of Toxicology CY JUL 02-06, 1995 CL SEATTLE, WA SP Boeing Co, NIEHS, NIH, Soc Toxicol, USA, Dow Chem, FDA, Natl Ctr Toxicol Res, NHLBI, Sanofi Winthrop Inc, USA Med Res & Med Command, US DOE, US EPA, Natl Ctr Environm Assessment, BP Amer Inc, Battelle Mem Inst, Battelle Pacific NW Labs, Burroughts Wellcome Fund, Bristol Myers Squibb, DowElanco, ECETOC, Eli Lilly & Co, Genentech Inc, Hoffmann LaRoche, Johnson & Johnson, Nutrasweet, Owens Corning, Rhone Poulenc Inc, Schering Plough Res Inst, Atlantic Richfield Co, CanTox Incorp, Coca Cola Co, Colgate Palmolive, Chem Manufacturers Assoc, DuPont, Eastman Kodak Co, Hoechst Celanese, NIH, Pfizer, Proctor & Gamble, R J Reynolds Tobacco Co, Syntex Corp, TSI Corp, Warner Lambert, Zeneca Cent Toxicol Lab & Safety Med Grp, Alcon Labs, BP Goodrich Co, FMC Corp, Rhone Poulenc Rorer, Marck Res Labs, Rohm & Hass Co, Searle, SmithKline Beecham Pharm DE peroxisome proliferators; dioxin; Ah receptor; hepatic fibrosis ID PEROXISOME PROLIFERATORS; ACTIVATED RECEPTOR; FATTY-ACIDS; HETERODIMER; MECHANISMS; DRUGS AB Administration of certain foreign chemicals to animals elicits responses that are due to receptor-mediated activation of gene expression. Among the most well studied receptors are the Ah receptor (AHR) that binds 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds and the peroxisome proliferator-activated receptors, PPARs, that mediate gene activation by the diverse group of peroxisome proliferators. These receptors may also have critical roles in development or physiological homeostasis in addition to their abilities to allow animals to interact with exogenous chemicals or xenobiotics. To explore the function of AHR and PPAR alpha and to determine whether they participate in the adverse effects of dioxins and peroxisome proliferators, gene knockout mice were developed. RP Gonzalez, FJ (reprint author), NCI,NIH,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 11 TC 44 Z9 44 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC PY 1995 VL 82-3 BP 117 EP 121 DI 10.1016/0378-4274(95)03548-6 PG 5 WC Toxicology SC Toxicology GA TU514 UT WOS:A1995TU51400017 PM 8597038 ER PT J AU Wink, DA Cook, JA Pacelli, R Liebmann, J Krishna, MC Mitchell, JB AF Wink, DA Cook, JA Pacelli, R Liebmann, J Krishna, MC Mitchell, JB TI Nitric oxide (NO) protects against cellular damage by reactive oxygen species SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 7th International Congress of Toxicology CY JUL 02-06, 1995 CL SEATTLE, WA SP Boeing Co, NIEHS, NIH, Soc Toxicol, USA, Dow Chem, FDA, Natl Ctr Toxicol Res, NHLBI, Sanofi Winthrop Inc, USA Med Res & Med Command, US DOE, US EPA, Natl Ctr Environm Assessment, BP Amer Inc, Battelle Mem Inst, Battelle Pacific NW Labs, Burroughts Wellcome Fund, Bristol Myers Squibb, DowElanco, ECETOC, Eli Lilly & Co, Genentech Inc, Hoffmann LaRoche, Johnson & Johnson, Nutrasweet, Owens Corning, Rhone Poulenc Inc, Schering Plough Res Inst, Atlantic Richfield Co, CanTox Incorp, Coca Cola Co, Colgate Palmolive, Chem Manufacturers Assoc, DuPont, Eastman Kodak Co, Hoechst Celanese, NIH, Pfizer, Proctor & Gamble, R J Reynolds Tobacco Co, Syntex Corp, TSI Corp, Warner Lambert, Zeneca Cent Toxicol Lab & Safety Med Grp, Alcon Labs, BP Goodrich Co, FMC Corp, Rhone Poulenc Rorer, Marck Res Labs, Rohm & Hass Co, Searle, SmithKline Beecham Pharm DE nitric oxide; oxidative stress; oxygen radicals ID SUPEROXIDE; PEROXYNITRITE; INJURY AB Since the discovery of nitric oxide (NO) as an endogenously formed radical, its effect on numerous physiological processes has been intensively investigated. Some studies have suggested NO to be cytotoxic while others have demonstrated it protective under various biological conditions. Though NO shows minimal cytotoxicity to a variety mammalian cell cultures, it does modulate the toxicity of some agents such as reactive oxygen species. Often, NO is generated in the presence of these reactive oxygen species in response to foreign pathogens or under various pathophysiological conditions. We will show that NO can play a protective role under oxidative stress resulting from superoxide, hydrogen peroxide and alkyl peroxides. It was found by measuring the time-concentration profiles of NO released from various NO donor compounds that only mu M levels of NO were required for protection against the toxicity of these reactive species. It was found that there are several chemical reactions which may account for these protective effects such as NO preventing heme oxidation, inhibition of Fenton-type oxidation of DNA, and abatement of lipid peroxidation. Taken together, NO at low concentrations clearly protects against peroxide-mediated toxicity. RP Wink, DA (reprint author), NCI,NIH,RADIOL BIOL BRANCH,TUMOR BIOL SECT,BLDG 10,ROOM B3-B69,BETHESDA,MD 20892, USA. NR 25 TC 126 Z9 135 U1 1 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC PY 1995 VL 82-3 BP 221 EP 226 DI 10.1016/0378-4274(95)03557-5 PG 6 WC Toxicology SC Toxicology GA TU514 UT WOS:A1995TU51400034 PM 8597056 ER PT J AU Boorman, GA Sills, RC Grumbein, S Hailey, R Miller, RA Herbert, RA AF Boorman, GA Sills, RC Grumbein, S Hailey, R Miller, RA Herbert, RA TI Long-term toxicity studies of ozone in F344/N rats and B6C3F1 mice SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 7th International Congress of Toxicology CY JUL 02-06, 1995 CL SEATTLE, WA SP Boeing Co, NIEHS, NIH, Soc Toxicol, USA, Dow Chem, FDA, Natl Ctr Toxicol Res, NHLBI, Sanofi Winthrop Inc, USA Med Res & Med Command, US DOE, US EPA, Natl Ctr Environm Assessment, BP Amer Inc, Battelle Mem Inst, Battelle Pacific NW Labs, Burroughts Wellcome Fund, Bristol Myers Squibb, DowElanco, ECETOC, Eli Lilly & Co, Genentech Inc, Hoffmann LaRoche, Johnson & Johnson, Nutrasweet, Owens Corning, Rhone Poulenc Inc, Schering Plough Res Inst, Atlantic Richfield Co, CanTox Incorp, Coca Cola Co, Colgate Palmolive, Chem Manufacturers Assoc, DuPont, Eastman Kodak Co, Hoechst Celanese, NIH, Pfizer, Proctor & Gamble, R J Reynolds Tobacco Co, Syntex Corp, TSI Corp, Warner Lambert, Zeneca Cent Toxicol Lab & Safety Med Grp, Alcon Labs, BP Goodrich Co, FMC Corp, Rhone Poulenc Rorer, Marck Res Labs, Rohm & Hass Co, Searle, SmithKline Beecham Pharm DE ozone; toxicity; carcinogenicity; bioassay; lung; neoplasia ID LUNG-TUMORS; CARCINOGENESIS; INHALATION; EXPOSURE AB The toxicity and carcinogenicity of ozone was evaluated in Fischer 344/N rats and B6C3F1 mice exposed to 0, 0.12 (2 years only), 0.5 or 1.0 ppm ozone by inhalation for 2-year and lifetime exposures. A 2-year cocarcinogenicity study (male rats only) included the subcutaneous administration of 0, 0.1 or 1.0 mg/kg/body wt. of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) for the first 20 weeks along with inhalation exposure to 0 or 0.5 ppm ozone followed by additional 84 weeks of ozone exposure alone. Ozone exposure in rats did not cause an increased incidence of lung neoplasms. In the cocarcinogenicity study? ozone exposure did not have an additive carcinogenic effect. Lifetime and 2-year ozone exposure was associated with a marginal increase in lung tumors in male B6C3F1 mice and a more pronounced increase in females. Unique mutations in the K-ras gene were found in the mouse lung neoplasms from the ozone-exposed mice. C1 PACIFIC NW LAB, RICHLAND, WA 99352 USA. RP Boorman, GA (reprint author), NIEHS, ENVIRONM TOXICOL PROGRAM, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 19 TC 9 Z9 9 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC PY 1995 VL 82-3 BP 301 EP 306 DI 10.1016/0378-4274(95)03483-8 PG 6 WC Toxicology SC Toxicology GA TU514 UT WOS:A1995TU51400045 PM 8597069 ER PT J AU Luster, ML Wilmer, JL Germolec, DR Spalding, J Yoshida, T Gaido, K Simeonova, PP Burleson, FG Bruccoleri, A AF Luster, ML Wilmer, JL Germolec, DR Spalding, J Yoshida, T Gaido, K Simeonova, PP Burleson, FG Bruccoleri, A TI Role of keratinocyte-derived cytokines in chemical toxicity SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 7th International Congress of Toxicology CY JUL 02-06, 1995 CL SEATTLE, WA SP Boeing Co, NIEHS, NIH, Soc Toxicol, USA, Dow Chem, FDA, Natl Ctr Toxicol Res, NHLBI, Sanofi Winthrop Inc, USA Med Res & Med Command, US DOE, US EPA, Natl Ctr Environm Assessment, BP Amer Inc, Battelle Mem Inst, Battelle Pacific NW Labs, Burroughts Wellcome Fund, Bristol Myers Squibb, DowElanco, ECETOC, Eli Lilly & Co, Genentech Inc, Hoffmann LaRoche, Johnson & Johnson, Nutrasweet, Owens Corning, Rhone Poulenc Inc, Schering Plough Res Inst, Atlantic Richfield Co, CanTox Incorp, Coca Cola Co, Colgate Palmolive, Chem Manufacturers Assoc, DuPont, Eastman Kodak Co, Hoechst Celanese, NIH, Pfizer, Proctor & Gamble, R J Reynolds Tobacco Co, Syntex Corp, TSI Corp, Warner Lambert, Zeneca Cent Toxicol Lab & Safety Med Grp, Alcon Labs, BP Goodrich Co, FMC Corp, Rhone Poulenc Rorer, Marck Res Labs, Rohm & Hass Co, Searle, SmithKline Beecham Pharm DE inflammatory cytokines; dermatotoxicity; skin immunity; keratinocyte-derived cytokines ID TRANSGENIC MOUSE; TGF-ALPHA; SKIN; OVEREXPRESSION; INDUCTION; MICE AB Following appropriate stimulation, such as with tumor promoters, ultraviolet light or various chemical agents, keratinocytes synthesize and secrete cytokines which can mediate or participate in dermatotoxic responses such as inflammation, hyperkeratosis, hypersensitivity and skin cancer. We have determined the qualitative and quantitative cytokine response in primary human keratinocyte cultures following exposure to several non-sensitizing contact irritants, sensitizers and ulcerative agents as well as a skin carcinogen. The chemicals were also administered to mice to assess whether the dermatotoxic response correlated with the in vitro production of keratinocyte-derived cytokines. Due to the complex cellular interactions that occur in the skin, it was not possible to identify specific cytokine profiles for most of the classes of dermatotoxic agents studied. However, the non-sensitizing contact irritants produced relative increases in the synthesis and secretion of the proinflammatory cytokines, interleukin-1 and tumor necrosis factor-alpha, as well as the neutrophil chemotactic cytokine, interleukin-8 compared to the other chemical agents, While ulcerative compounds as well as irritants elicited neutrophils to the site of chemical application when applied to the mouse skin, time-dependent and chemical-specific patterns of inflammation were detected. Treatment of human keratinocyte cultures with arsenic, a human skin carcinogen, resulted in a unique cytokine profile characterized by induction of growth factors, including transforming growth factor-alpha and granulocyte-macrophage colony stimulating factor. Treatment of v-Ha-ras transgenic mice, an animal model for skin cancer, with arsenic caused an increase in the number of papillomas as well as overexpression of these growth factors suggesting that they participate in arsenic-induced skin papilloma development. These studies indicate a diverse role exists for keratinocyte-derived cytokines in dermatotoxic actions. C1 NIEHS,NIH,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. TOKAI UNIV,DEPT ENVIRONM MED,KANAGAWA,JAPAN. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. RP Luster, ML (reprint author), NIEHS,NIH,ENVIRONM IMMUNOL & NEUROBIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 13 TC 30 Z9 31 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC PY 1995 VL 82-3 BP 471 EP 476 DI 10.1016/0378-4274(95)03577-X PG 6 WC Toxicology SC Toxicology GA TU514 UT WOS:A1995TU51400070 PM 8597097 ER PT J AU Ommaya, AK Atwater, I Yanez, A SzpakGlasman, W Bacher, J Arriaza, C Baer, L Parraguez, V Navia, A Oberti, C Cea, R Moraga, F Riquelme, R Llanos, A AF Ommaya, AK Atwater, I Yanez, A SzpakGlasman, W Bacher, J Arriaza, C Baer, L Parraguez, V Navia, A Oberti, C Cea, R Moraga, F Riquelme, R Llanos, A TI Lama glama (the South American camelid, llama): A unique model for evaluation of xenogenic islet transplants in a cerebral spinal fluid driven artificial organ SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 5th Congress of the International-Pancreas-and-Islet-Transplant-Association on Cure of Diabetes by Transplantation CY JUN 18-22, 1995 CL MIAMI BEACH, FL SP Int Pancreas & Islet Transplant Assoc C1 NIDDKD,CELL BIOL & GENET LAB,VET RESOURCES PROGRAM,NATL CTR RES RESOURCES,BETHESDA,MD 20892. NIH,SURG RADIOL & PHARM SECT,VET RESOURCES PROGRAM,NCRR,BETHESDA,MD 20892. UNIV CHILE,DEPT MED,SANTIAGO,CHILE. UNIV CHILE,DEPT NEUROL & NEUROSURG,SANTIAGO,CHILE. UNIV CHILE,JJ AGUIRRE CLIN HOSP,DEPT ANAT,FAC MED,SANTIAGO,CHILE. UNIV CHILE,FAC VET SCI,SANTIAGO,CHILE. UNIV CHILE,FAC MED,DEPT EXPTL MED,SANTIAGO 7,CHILE. RP Ommaya, AK (reprint author), CYBORGAN INC,8006 GLENBROOK RD,BETHESDA,MD 20814, USA. RI Parraguez, Victor/I-5415-2013 OI Parraguez, Victor/0000-0002-3621-2705 NR 5 TC 15 Z9 15 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1995 VL 27 IS 6 BP 3304 EP 3307 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA TM692 UT WOS:A1995TM69200168 PM 8539964 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - FLOATIES IN THE GENE POOL SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Note RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 1995 VL 20 IS 12 BP 522 EP 523 DI 10.1016/S0968-0004(00)89121-5 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ869 UT WOS:A1995TJ86900009 PM 8571455 ER PT J AU SRIVASTAVA, S KATAYOSE, D TONG, YA CRAIG, CR MCLEOD, DG MOUL, JW COWAN, KH SETH, P AF SRIVASTAVA, S KATAYOSE, D TONG, YA CRAIG, CR MCLEOD, DG MOUL, JW COWAN, KH SETH, P TI RECOMBINANT ADENOVIRUS VECTOR EXPRESSING WILD-TYPE P53 IS A POTENT INHIBITOR OF PROSTATE-CANCER CELL-PROLIFERATION SO UROLOGY LA English DT Article ID CARCINOMA; SUPPRESSION; GROWTH; GENE; PROTEIN; MUTANT AB Objectives. A recombinant adenovirus vector (AdWTp53) expressing wild-type p53 was evaluated for its cell growth inhibitory effects on metastatic human prostate cancer cells. Methods. Human prostate cancer cells LNCaP, DU145, PC3, 1LN, and DUPro-1 were infected with AdWTp53 vector and expression of exogenous p53 in these cells was analyzed by immunoprecipitation and western blot assays. The cell growth inhibitory effects of AdWTp53 were determined by counting cell number on a hemocytometer or by crystal violet staining of cells after infection with AdWTp53. The p53-regulated gene WAF1 and DNA fragmentation were also analyzed in prostate cancer cells infected with AdWTp53. Results. High levels of the AdWTp53 vector-derived p53 protein were present in metastatic prostate cancer cells, and the p53-regulated gene WAF1 was induced in these cells. Infection of these tumor cell lines with AdWTp53 vector resulted in severe growth inhibition and cell death in comparison to untreated or control adenovirus vector-infected cells. Furthermore, fragmentation of genomic DNA, a property associated with apoptosis, was also observed in prostate cancer cells infected with AdWTp53. Conclusions. AdWTp53 vector exhibited a potent inhibitory effect on the growth of all of human metastatic prostate cancer cells, and both cytostatic and cytotoxic effects of AdWTp53 were observed. The induction of p53-regulated gene WAF1 in AdWTp53-infected prostate cancer cells suggests the involvement of cellular p53 pathway in the cell growth inhibition. These results provide a molecular basis for further evaluation of antitumorigenic effects of AdWTp53 vector in animal models of prostate cancer. C1 WALTER REED ARMY MED CTR,UROL SERV,WASHINGTON,DC 20307. NCI,MED BRANCH,MED BREAST SECT,BETHESDA,MD 20892. RP SRIVASTAVA, S (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT SURG,CTR PROSTATE DIS RES,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. NR 32 TC 41 Z9 42 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD DEC PY 1995 VL 46 IS 6 BP 843 EP 848 DI 10.1016/S0090-4295(99)80355-0 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA TJ347 UT WOS:A1995TJ34700017 PM 7502427 ER PT J AU MORIUCHI, H MORIUCHI, M COHEN, JI AF MORIUCHI, H MORIUCHI, M COHEN, JI TI THE VARICELLA-ZOSTER VIRUS IMMEDIATE-EARLY 62-PROMOTER CONTAINS A NEGATIVE REGULATORY ELEMENT THAT BINDS TRANSCRIPTIONAL FACTOR NF-Y SO VIROLOGY LA English DT Note ID NUCLEAR FACTOR-I; DNA-BINDING; EARLY GENE; PROTEIN; EXPRESSION; RECOGNITION; SEQUENCE; CLONING; IDENTIFICATION; REPLICATION AB The varicella-zoster virus (VZV) immediate-early (IE) open reading frame 62 (ORF62) promoter sequence contains a CCAAT box, located between positions -117 and -113. Mutation of this motif resulted in a five-fold increase of promoter activity. In mobility shift assays, we demonstrated that NF-Y, a CCAAT box-binding protein critical for the expression of diverse eukaryotic genes, binds to this motif. Thus, the VZV IE ORF62 promoter contains a negative regulatory element that binds the ubiquitous transcriptional factor NF-Y. (C) 1995 Academic Press, Inc. RP MORIUCHI, H (reprint author), NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892, USA. NR 37 TC 14 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 1 PY 1995 VL 214 IS 1 BP 256 EP 258 DI 10.1006/viro.1995.9932 PG 3 WC Virology SC Virology GA TK274 UT WOS:A1995TK27400030 PM 8525624 ER PT J AU CLEMENS, KE BRENT, R GYURIS, J MUNGER, K AF CLEMENS, KE BRENT, R GYURIS, J MUNGER, K TI DIMERIZATION OF THE HUMAN PAPILLOMAVIRUS E7 ONCOPROTEIN IN-VIVO SO VIROLOGY LA English DT Note ID RETINOBLASTOMA GENE-PRODUCT; HUMAN KERATINOCYTES; PROTEIN DOMAINS; TRANSCRIPTION FACTOR; ESCHERICHIA-COLI; ZINC-BINDING; DNA-BINDING; TYPE-16; TRANSFORMATION; E6 AB We have used a yeast two-hybrid system to show that human papillomavirus E7 proteins can form oligomeric complexes in vivo. The carboxyl-terminal cysteine-rich metal-binding domain is critical for this activity although amino-terminal sequences also contribute to oligomerization. Our experiments also reveal that E7 possesses an intrinsic transcription activation activity in yeast, which resides in the amino terminus of the protein. (C) 1995 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. OI Munger, Karl/0000-0003-3288-9935 NR 44 TC 44 Z9 47 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 1 PY 1995 VL 214 IS 1 BP 289 EP 293 DI 10.1006/viro.1995.9926 PG 5 WC Virology SC Virology GA TK274 UT WOS:A1995TK27400036 PM 8525630 ER PT J AU Subbarao, K Webster, RG Kawaoka, Y Murphy, BR AF Subbarao, K Webster, RG Kawaoka, Y Murphy, BR TI Are there alternative avian influenza viruses for generation of stable attenuated avian-human influenza A reassortant viruses? SO VIRUS RESEARCH LA English DT Article DE avian human reassortant influenza A viruses; gull influenza A viruses; vaccines; gene incompatibility ID A VIRUSES; SQUIRREL-MONKEYS; RESPIRATORY-TRACT; ADULT VOLUNTEERS; LIVE; H3N2; GENE; REPLICATION; CHIMPANZEES; VACCINES AB The present study evaluated gull influenza A viruses as donors of attenuating genes for the production of live, attenuated influenza A H1N1 and H3N2 avian-human (ah) reassortant viruses for use as vaccines to prevent disease due to influenza A viruses in humans. The previously evaluated duck influenza A viruses were abandoned as donors of attenuating avian influenza virus genes because clinical evaluation of H1N1 and H3N2 ah reassortant virus vaccines derived from duck viruses documented residual virulence of H1N1 reassortants for seronegative infants and young children. Gull influenza A viruses occupy an independent ecologic niche and are rarely isolated from species other than gulls. The possibility of using gull influenza A viruses as donors of internal gene segments in ah reassortant viruses was evaluated in the present study using three different gull viruses and three human influenza A viruses. Gull-human H3N2 reassortant influenza A viruses with the desired 6-2 genotype (six internal avian influenza virus genes and the two human influenza virus surface glycoprotein genes) were readily generated and were found to be attenuated for squirrel monkeys and chimpanzees. However, ah reassortant viruses with gull and human influenza A H1N1 genes were difficult to generate, and reassortants that had the desired genotype of six gull virus genes with human influenza A H1 and N1 genes were not isolated despite repeated attempts. The gull PB2, NP and NS genes were not present in any of the gull-human H1N1 reassortants generated. The under-representation of these three gene segments suggests that reassortants bearing one or more of these three gene segments might have reduced viability indicative of a functional incompatibility in their gene products. The difficulties encountered in the generation of a 6-2 gull-human H1N1 reassortant virus are sufficient to conclude that the gull influenza A viruses tested would not be useful as donors of sets of six internal genes to attenuate human influenza A viruses. This study also identifies influenza virus gene segments that appear to be incompatible for generation of reassortants. Elucidation of the molecular basis of this restriction may provide information on intergenic interactions involved in virion assembly or packaging. C1 ST JUDE CHILDRENS RES HOSP, DEPT VIROL & MOLEC BIOL, MEMPHIS, TN 38105 USA. RP Subbarao, K (reprint author), NIAID, NIH,INFECT DIS LAB,RESP VIRUSES SECT,BLDG 7, ROOM 106, 7 CTR DR MSC 0720, BETHESDA, MD USA. FU NCI NIH HHS [CA-21765]; NIAID NIH HHS [AI-29680] NR 27 TC 15 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD DEC PY 1995 VL 39 IS 2-3 BP 105 EP 118 DI 10.1016/0168-1702(95)00082-8 PG 14 WC Virology SC Virology GA TU783 UT WOS:A1995TU78300002 PM 8837878 ER PT J AU OPTICAN, LM AF OPTICAN, LM TI A FIELD-THEORY OF SACCADE GENERATION - TEMPORAL-TO-SPATIAL TRANSFORM IN THE SUPERIOR COLLICULUS SO VISION RESEARCH LA English DT Article; Proceedings Paper CT Binocular Oculomotor Coordination and Plasticity Symposium CY OCT 12-14, 1994 CL SANTORINI, GREECE DE SACCADE; SUPERIOR COLLICULUS; CONTROL SYSTEMS; COORDINATE MAPS ID NEURAL NETWORK MODEL; ALERT RHESUS-MONKEY; EYE-MOVEMENTS; GAZE SHIFTS; BURST NEURONS; STIMULATION; FEEDBACK; SYSTEM AB Recent models have placed the superior colliculus inside the local feedback loop that generates the pulse of innervation needed to make a saccade. Such closed-loop models need to take into account the different coordinate systems of visual and motor signals. This paper presents a computational model showing how the superior colliculus can bring the visual and motor information together in a common reference frame. RP OPTICAN, LM (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 49,ROOM 2A50,BETHESDA,MD 20892, USA. NR 39 TC 47 Z9 47 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0042-6989 J9 VISION RES JI Vision Res. PD DEC PY 1995 VL 35 IS 23-24 BP 3313 EP 3320 DI 10.1016/0042-6989(95)00129-3 PG 8 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA TE460 UT WOS:A1995TE46000012 PM 8560802 ER PT J AU Wickner, RB Masison, DC Edskes, HK AF Wickner, RB Masison, DC Edskes, HK TI [PSI] and [URE3] as yeast prions SO YEAST LA English DT Article DE nitrogen repression; translation termination; suppressor; non-Mendelian; ureidosuccinate uptake ID SACCHAROMYCES-CEREVISIAE; SCRAPIE PRION; FRAMESHIFT SUPPRESSION; DIFFERENT STRAINS; MOUSE SCRAPIE; SUP35 GENE; PRP 27-30; PROTEIN; MICE; MUTATION AB [URE3] is a non-Mendelian genetic element that mimics recessive mutations in the chromosomal URE2 gene making cells derepressed for nitrogen catabolic enzymes. [PSI] is a non-Mendelian enhancer of readthrough of translational termination similar in its effects to some mutations in the chromosomal SUP35 gene. Three Lines of evidence led to the proposal(75) that both [URES] and [PSI] are prions, infectious proteins analogous to the scrapie agent mediating transmissible spongiform encephalopathies of mammals. 1) Both [PSI] and [URE3] are reversibly curable. 2) [PSI] propagation requires SUP35 and [URE3] propagation requires URE2 with recessive chromosomal mutants having the same phenotypes as the presence of the respective dominant non-Mendelian element. 3) Overproduction of Sup35p and Ure2p increases the frequency of cells acquiring [PSI] or [URE3], respectively. RP Wickner, RB (reprint author), NIDDKD, SECT GENET SIMPLE EUKARYOTES,BLDG 8,ROOM 225, 8 CTR DR, MSC 0830, BETHESDA, MD 20892 USA. NR 79 TC 103 Z9 104 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0749-503X J9 YEAST JI Yeast PD DEC PY 1995 VL 11 IS 16 BP 1671 EP 1685 DI 10.1002/yea.320111609 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA TQ241 UT WOS:A1995TQ24100007 PM 8720070 ER PT J AU Popik, P Lewin, A Berrang, B Nowak, G Layer, R Skolnick, P AF Popik, P Lewin, A Berrang, B Nowak, G Layer, R Skolnick, P TI [H-3]1-aminocyclopropanecarboxylic acid, a novel probe for strychnine-insensitive glycine receptors SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE ACPC (1-aminocyclopropanecarboxylic acid); glycine receptor, strychnine-insensitive; NMDA receptor ID METHYL-D-ASPARTATE; NMDA RECEPTOR; RAT-BRAIN; RECOGNITION SITE; H-3 GLYCINE; STRUCTURAL REQUIREMENTS; FUNCTIONAL ANTAGONISTS; EXHIBIT ANTIDEPRESSANT; CORTICAL MEMBRANES; IONOPHORE COMPLEX AB [H-3]1-Aminocyclopropanecarboxylic acid (ACPC) exhibits high affinity, specific binding to strychnine-insensitive glycine receptors. In extensively washed rat forebrain membranes, the specific binding of [H-3]ACPC was optimal at 25 degrees C in the presence of 10 mM MgCl2. Comparable levels of specific [H-3]ACPC binding were obtained using centrifugation and filtration for separation of bound from free radioligand. [H-3]ACPC labels two sites with K-d1 and B-max1 values of 129 +/- 34 nM and 2.30 +/- 0.37 pmol/mg protein and K-d2 and B-max2 values of 7.26 +/- 1.69 mu M and 20.6 +/- 2.2 pmol/mg protein for the high and low affinity sites, respectively. The K-d of [H-3]ACPC (66 nor?) estimated under non-equilibrium conditions (k(off) = 8.91 +/- 0.78 X 10(-3) s(-1); k(on) = 1.35 X 10(-4) nM(-1) s(-1)) was similar to the value obtained for the high affinity site obtained by equilibrium binding. The K-d1 of [H-3]ACPC is in good agreement with the previously reported K-i values of ACPC to inhibit the binding of other glycinergic ligands including [H-3]glycine, [H-3]5,7-dichlorokynurenic acid (5,7-DCKA) and [H-3]L-689,560 ((+/-)-4-(trans)-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline). Moreover, the potencies of a series of glycine site ligands, including glycine, ACPC, 1-aminocyclobutanecarboxylic acid (ACBC), 5,7-DCKA, 7-chlorokynurenic acid (7-CKA), R(+)-3-amino-1-hydroxy-2-pyrrolidine (HA-966) and D-serine, to inhibit [H-3]ACPC binding were highly correlated with their potencies to inhibit [H-3]glycine and [H-3]5,7-DCKA binding (r(2) = 0.98-0.51). These results demonstrate that [H-3]ACPC is a useful tool for examining the neurochemical and pharmacological properties of strychnine-insensitive glycine receptors. C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. UNIV MISSISSIPPI,MED CTR,DEPT PSYCHIAT & HUMAN BEHAV,NEUROBEHAV PHARMACOL & IMMUNOL LAB,JACKSON,MS 39216. RI Popik, Piotr/R-5383-2016 OI Popik, Piotr/0000-0003-0722-1263 FU NINDS NIH HHS [5 ROI NS27859] NR 45 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD NOV 30 PY 1995 VL 291 IS 3 BP 221 EP 227 DI 10.1016/0922-4106(95)90061-6 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL546 UT WOS:A1995TL54600001 PM 8719405 ER PT J AU Kusama, T Sakurai, M Kizawa, Y Uhl, GR Murakami, H AF Kusama, T Sakurai, M Kizawa, Y Uhl, GR Murakami, H TI GABA p(1) receptor: Inhibition by protein kinase C activators SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE GABA p(1) receptor; protein kinase C; Xenopus oocyte; down-regulation; phorbol ester; staurosporine ID XENOPUS OOCYTES; RHO-1; PHOSPHORYLATION AB The effects of protein kinase C (PKC) activators on gamma-aminobutyric acid (GABA) rho(1) receptor function were studied in rho(1)-expressing Xenopus oocytes. The PKC activator phorbol 12-myristate 13-acetate (PMA) but not the inactive analog phorbol 12-mono-myristate inhibited the GABA-gated chloride currents. Mezerein, a non-phorbol ester type PKC activator, also inhibited the rho(1) responses, but 8-chlorophenylthio-cyclic AMP, a protein kinase A activator, had no effect. The effect of PMA was significantly reduced by a PKC inhibitor, staurosporine. These results suggest that GABA rho(1) receptor function can be regulated by PKC-mediated phosphorylation events. C1 NIHON UNIV,COLL PHARM,DEPT PHYSIOL & ANAT,FUNABASHI,CHIBA 274,JAPAN. NIDA,ADDICT RES CTR,DIV INTRAMURAL RES,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. RI Kizawa, Yasuo/E-3031-2010 OI Kizawa, Yasuo/0000-0001-9884-7186 NR 15 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD NOV 30 PY 1995 VL 291 IS 3 BP 431 EP 434 DI 10.1016/0922-4106(95)90086-1 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL546 UT WOS:A1995TL54600026 PM 8719430 ER PT J AU ABE, O ABE, R ASAISHI, K ENOMOTO, K HATTORI, T IINO, Y KIKUCHI, K KOYAMA, H SAWA, K UCHINO, J YOSHIDA, M VANDEVELDE, AO VERMORKEN, JB FOROGLOU, P GIOKAS, G LISSAIOS, B HARVEY, VJ HOLDAWAY, TM KAY, RG MASON, BH FORBES, JF FOCAN, C LOBELLE, JP PEEK, U OATES, GD POWELL, J BASTERT, G RAUSCHECKER, H SAUER, R SAUERBREI, W SCHAUER, A SCHUMACHER, M GELMAN, RS HENDERSON, IC SHAPIRO, CL HANCOCK, AK JACKSON, S RAGAZ, J DELOZIER, T MACELESECH, J HAYBITTLE, JL CIRRINCIONE, C KORZUN, A WEISS, RB WOOD, WC BAUM, M HOUGHTON, J RILEY, D DENT, DM GUDGEON, CA HACKING, A HORGAN, K HUGHES, L STEWART, HJ GORDON, NH DAVIS, HL OWEN, JR MEIER, P HOWELL, A RIBEIRO, GC SWINDELL, R ALBANO, J DEOLIVEIRA, CF GERVASIO, H GORDILHO, J CARSTENSEN, B PALSHOF, T JOHANSEN, H KORZENIOWSKI, S SKOLYSZEWSKI, J ANDERSEN, KW AXELSSON, CK BLICHERTTOFT, M MOURIDSEN, HT OVERGAARD, M ROSE, C CORCORAN, N TRAMPISCH, HJ ABELOFF, MD CARBONE, PC GLICK, J GRAY, R TORMEY, DC BARTELINK, H FENTIMAN, IS PARIDAENS, R VANDRIEL, OJR SYLVESTER, RJ VANDEVELDE, CJH VANDERSCHUEREN, E VANDONGEN, JA WELVAART, K SCANLON, EF SCHURMAN, S DESCHRYVER, A YOSEF, HMA MCARDLE, CS SMITH, DC LARA, PC BOCCARDO, F IZUO, M MORISHITA, Y BENTLEY, A DORAN, Z HAYWARD, JL RUBENS, RD KAUFMANN, M JONAT, W SCHEURLEN, H VONFOURNIER, D KAUFMANN, M KLEFSTROM, P CUZICK, J MARGREITER, R CAVALLI, F COLLINS, J GELBER, RD GOLDHIRSCH, A ISLEY, MR LINDTNER, J PRICE, KN RUDENSTAM, CM BLISS, JM CHILVERS, CED COOMBES, RC MARTY, M BRUFMAN, G HAYAT, H BOROVIK, R ROBINSON, E PANNUTI, F TAKASHIMA, S YASUTOMI, T SONOO, H YAMASHITA, J OGAWA, M NOMURA, Y BONTE, J TENGRUP, I TENNVALLNITTBY, L MARTIN, P ROMAIN, S AHMANN, D SCHAID, DJ BUZDAR, AU SMITH, T HAKES, T NORTON, L WITTES, R DELAHUERTA, R SAINZ, MG BONADONNA, G DELVECCHIO, M VALAGUSSA, P VERONESI, U DUBOIS, JB BIANCO, AR LIPPMAN, ME PIERCE, LJ SIMON, R STEINBERG, SM BROWN, A FISHER, B REDMOND, C WOLMARK, N JACKSON, IM PALMER, MK INGLE, JN BENGTSSON, NO LARSSON, LG LYTHGOE, JP KISSIN, M HANNISDAL, E VARHAUG, JE BLAMEY, RW MITCHELL, AK ROBERTSON, JFR NAKAMURA, Y MATHE, G MISSET, JL CLARKE, EA MCLAUGHLIN, JR CLARK, RM LEVINE, M MORIMOTO, K GUNDERSEN, S HAUERJENSEN, M HOST, H CROSSLEY, E DURRANT, K HARRIS, A BEIGHTON, A CHADBON, D CLARKE, M COLLINS, R DAVIES, C EVANS, V GODWIN, J GREAVES, E HARWOOD, C JAMES, S MEAD, G MULDAHL, A PETO, R TOOTH, A WHEATLEY, K RAMBERT, P ASSELAIN, B SALMON, RJ VILCOQ, JR ARRIAGADA, R HILL, C LAPLANCHE, A LE, MG SPIELMANN, M COCCONI, G DIBLASIO, B CATALANO, R CREECH, RH BROCKSCHMIDT, J COOPER, MR ANDRYSEK, O BARKMANOVA, J TREURNIETDONKER, AD VANPUTTEN, WLJ EASTON, D POWLES, TJ GAZET, JC SEMIGLAZOV, V DESHPANDE, N DIMARTINO, L DOUGLAS, P LINDTNER, A NOTTER, G NISSENMEYER, R FORREST, APM JACK, W MCDONALD, C MOLLER, TR RYDEN, S CARSTENSEN, J HATSCHEK, T SODERBERG, M CARPENTER, JT ALBAIN, K CROWLEY, J GREEN, S OSBORNE, CK RUTQUIST, LE WALLGREN, A HOLM, LE CASTIGLIONE, M FLUCKIGER, H THURLIMANN, B BRENNER, H HERCBERGS, A YOSHIMOTO, M DEBOER, G PATERSON, AHG PRITCHARD, KI MEAKIN, JW PANZARELLA, T NAJA, A BAHI, J REID, M SPITTLER, M SENANAYAKE, F HOLMBERG, L SEVELDA, P ZIELINSKY, CC JAKESZ, R BUCHANAN, RB CROSS, M DUNN, JA GILLESPIE, WM KELLY, K MORRISON, JM LITTON, A CHLEBOWSKI, RT BEZWODA, WR CAFFIER, H AF ABE, O ABE, R ASAISHI, K ENOMOTO, K HATTORI, T IINO, Y KIKUCHI, K KOYAMA, H SAWA, K UCHINO, J YOSHIDA, M VANDEVELDE, AO VERMORKEN, JB FOROGLOU, P GIOKAS, G LISSAIOS, B HARVEY, VJ HOLDAWAY, TM KAY, RG MASON, BH FORBES, JF FOCAN, C LOBELLE, JP PEEK, U OATES, GD POWELL, J BASTERT, G RAUSCHECKER, H SAUER, R SAUERBREI, W SCHAUER, A SCHUMACHER, M GELMAN, RS HENDERSON, IC SHAPIRO, CL HANCOCK, AK JACKSON, S RAGAZ, J DELOZIER, T MACELESECH, J HAYBITTLE, JL CIRRINCIONE, C KORZUN, A WEISS, RB WOOD, WC BAUM, M HOUGHTON, J RILEY, D DENT, DM GUDGEON, CA HACKING, A HORGAN, K HUGHES, L STEWART, HJ GORDON, NH DAVIS, HL OWEN, JR MEIER, P HOWELL, A RIBEIRO, GC SWINDELL, R ALBANO, J DEOLIVEIRA, CF GERVASIO, H GORDILHO, J CARSTENSEN, B PALSHOF, T JOHANSEN, H KORZENIOWSKI, S SKOLYSZEWSKI, J ANDERSEN, KW AXELSSON, CK BLICHERTTOFT, M MOURIDSEN, HT OVERGAARD, M ROSE, C CORCORAN, N TRAMPISCH, HJ ABELOFF, MD CARBONE, PC GLICK, J GRAY, R TORMEY, DC BARTELINK, H FENTIMAN, IS PARIDAENS, R VANDRIEL, OJR SYLVESTER, RJ VANDEVELDE, CJH VANDERSCHUEREN, E VANDONGEN, JA WELVAART, K SCANLON, EF SCHURMAN, S DESCHRYVER, A YOSEF, HMA MCARDLE, CS SMITH, DC LARA, PC BOCCARDO, F IZUO, M MORISHITA, Y BENTLEY, A DORAN, Z HAYWARD, JL RUBENS, RD KAUFMANN, M JONAT, W SCHEURLEN, H VONFOURNIER, D KAUFMANN, M KLEFSTROM, P CUZICK, J MARGREITER, R CAVALLI, F COLLINS, J GELBER, RD GOLDHIRSCH, A ISLEY, MR LINDTNER, J PRICE, KN RUDENSTAM, CM BLISS, JM CHILVERS, CED COOMBES, RC MARTY, M BRUFMAN, G HAYAT, H BOROVIK, R ROBINSON, E PANNUTI, F TAKASHIMA, S YASUTOMI, T SONOO, H YAMASHITA, J OGAWA, M NOMURA, Y BONTE, J TENGRUP, I TENNVALLNITTBY, L MARTIN, P ROMAIN, S AHMANN, D SCHAID, DJ BUZDAR, AU SMITH, T HAKES, T NORTON, L WITTES, R DELAHUERTA, R SAINZ, MG BONADONNA, G DELVECCHIO, M VALAGUSSA, P VERONESI, U DUBOIS, JB BIANCO, AR LIPPMAN, ME PIERCE, LJ SIMON, R STEINBERG, SM BROWN, A FISHER, B REDMOND, C WOLMARK, N JACKSON, IM PALMER, MK INGLE, JN BENGTSSON, NO LARSSON, LG LYTHGOE, JP KISSIN, M HANNISDAL, E VARHAUG, JE BLAMEY, RW MITCHELL, AK ROBERTSON, JFR NAKAMURA, Y MATHE, G MISSET, JL CLARKE, EA MCLAUGHLIN, JR CLARK, RM LEVINE, M MORIMOTO, K GUNDERSEN, S HAUERJENSEN, M HOST, H CROSSLEY, E DURRANT, K HARRIS, A BEIGHTON, A CHADBON, D CLARKE, M COLLINS, R DAVIES, C EVANS, V GODWIN, J GREAVES, E HARWOOD, C JAMES, S MEAD, G MULDAHL, A PETO, R TOOTH, A WHEATLEY, K RAMBERT, P ASSELAIN, B SALMON, RJ VILCOQ, JR ARRIAGADA, R HILL, C LAPLANCHE, A LE, MG SPIELMANN, M COCCONI, G DIBLASIO, B CATALANO, R CREECH, RH BROCKSCHMIDT, J COOPER, MR ANDRYSEK, O BARKMANOVA, J TREURNIETDONKER, AD VANPUTTEN, WLJ EASTON, D POWLES, TJ GAZET, JC SEMIGLAZOV, V DESHPANDE, N DIMARTINO, L DOUGLAS, P LINDTNER, A NOTTER, G NISSENMEYER, R FORREST, APM JACK, W MCDONALD, C MOLLER, TR RYDEN, S CARSTENSEN, J HATSCHEK, T SODERBERG, M CARPENTER, JT ALBAIN, K CROWLEY, J GREEN, S OSBORNE, CK RUTQUIST, LE WALLGREN, A HOLM, LE CASTIGLIONE, M FLUCKIGER, H THURLIMANN, B BRENNER, H HERCBERGS, A YOSHIMOTO, M DEBOER, G PATERSON, AHG PRITCHARD, KI MEAKIN, JW PANZARELLA, T NAJA, A BAHI, J REID, M SPITTLER, M SENANAYAKE, F HOLMBERG, L SEVELDA, P ZIELINSKY, CC JAKESZ, R BUCHANAN, RB CROSS, M DUNN, JA GILLESPIE, WM KELLY, K MORRISON, JM LITTON, A CHLEBOWSKI, RT BEZWODA, WR CAFFIER, H TI EFFECTS OF RADIOTHERAPY AND SURGERY IN EARLY BREAST-CANCER - AN OVERVIEW OF THE RANDOMIZED TRIALS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID REQUIRING PROLONGED OBSERVATION; POSTOPERATIVE RADIOTHERAPY; RECURRENCE; PATIENT; DESIGN AB Background. Randomized trials of radiotherapy and surgery for early breast cancer may have been too small to detect differences in long-term survival and recurrence reliably. We therefore performed a systematic overview (meta-analysis) of the results of such trials. Methods. Information was sought on each subject from investigators who conducted trials that began before 1985 and that compared local therapies for early breast cancer. Data on mortality were available from 36 trials comparing radiotherapy plus surgery with the same type of surgery alone, 10 comparing more-extensive surgery with less-extensive surgery, and 18 comparing more-extensive surgery with less-extensive surgery plus radiotherapy. Information on mortality was available for 28,405 women (97.4 percent of the 29,175 women in the trials). Results. The addition of radiotherapy to surgery resulted in a rate of local recurrence that was three times lower than the rate with surgery alone, but there was no significant difference in 10-year survival; among a total of 17,273 women enrolled in such trials, mortality was 40.3 percent with radiotherapy and 41.4 percent without radiotherapy (P=0.3). Radiotherapy was associated with a reduced risk of death due to breast cancer (odds ratio, 0.94; 95 percent confidence interval, 0.88 to 1.00; P=0.03), which indicates that, after 10 years, there would be about 0 to 5 fewer deaths due to breast cancer per 100 women. However, there was an increased risk of death from other causes (odds ratio, 1.24; 95 percent confidence interval, 1.09 to 1.42; P=0.002). This, together with the age-specific death rates, implies, after 10 years, a few extra deaths not due to breast cancer per 100 older women or per 1000 younger women, During the first decade or two after diagnosis, the excess in the rate of such deaths that was associated with radiotherapy was much greater among women who were over 60 years of age at randomization (15.3 percent vs. 11.1 percent [339 vs. 249 deaths]) than among those under 50 (2.5 percent vs. 2.0 percent [62 vs. 49 deaths]). Breast-conserving surgery involved some risk of recurrence in the remaining tissue, but no significant differences in overall survival at 10 years were found in the studies of mastectomy versus breast-conserving surgery plus radiotherapy (4891 women), more-extensive surgery versus less-extensive surgery (4818 women), or axillary clearance versus radiotherapy as adjuncts to mastectomy (4370 women). Conclusions. Some of the local therapies for breast cancer had substantially different effects on the rates of local recurrence - such as the reduced recurrence with the addition of radiotherapy to surgery - but there were no definite differences in overall survival at 10 years. C1 INTEGRAAL KANKERCENTRUM ZUID, EINDHOVEN, NETHERLANDS. METAXAS MEM HOSP, PIRAEUS, GREECE. AUCKLAND BREAST CANC STUDY GRP, AUCKLAND, NEW ZEALAND. AKAD WISSENSCH BERLIN, BERLIN, GERMANY. BIRMINGHAM GEN HOSP, BIRMINGHAM, W MIDLANDS, ENGLAND. BUNDESMINIST FORSCH & TECHNOL, BONN, GERMANY. FDN BERGONIE, BORDEAUX, FRANCE. DANA FARBER CANC INST, BOSTON, MA 02115 USA. BRADFORD ROYAL INFIRM, BRADFORD, W YORKSHIRE, ENGLAND. BRITISH COLUMBIA CANC AGCY, VANCOUVER, BC, CANADA. ADDENBROOKES HOSP, CAMBRIDGE, ENGLAND. CANC RES CAMPAIGN, LONDON, ENGLAND. GROOTE SCHUUR HOSP, CAPE TOWN, SOUTH AFRICA. CARDIFF SURG TRIALISTS, CARDIFF, S GLAM, WALES. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. CHELTENHAM GEN HOSP, CHELTENHAM, PA USA. UNIV CHICAGO, CHICAGO, IL 60637 USA. CHRISTIE HOSP & HOLT RADIUM INST, MANCHESTER, LANCS, ENGLAND. COIMBRA INST ONCOL, COIMBRA, PORTUGAL. DANISH CANC REGISTRY, COPENHAGEN, DENMARK. COPENHAGEN RADIUM CTR, COPENHAGEN, DENMARK. CRACOW INST ONCOL, KRAKOW, POLAND. DUBLIN ST LUKES HOSP, DUBLIN, IRELAND. UNIV DUSSELDORF, DUSSELDORF, GERMANY. EASTERN COOPERAT ONCOL GRP, BOSTON, MA USA. EUROPEAN ORG RES TREATMENT CANC, AMSTERDAM, NETHERLANDS. EVANSTON HOSP CORP, EVANSTON, IL USA. GLASGOW BEATSON ONCOL CTR, GLASGOW, LANARK, SCOTLAND. GLASGOW VICTORIA INFIRM, GLASGOW, LANARK, SCOTLAND. GRANADA UNIV HOSP, GRANADA, SPAIN. GUNMA UNIV, MAEBASHI, GUMMA, JAPAN. GUYS HOSP, LONDON, ENGLAND. UNIV HEIDELBERG, W-6900 HEIDELBERG, GERMANY. DEACONESS MED CTR, HELSINKI, FINLAND. IMPERIAL CANC RES FUND, LONDON, ENGLAND. UNIV INNSBRUCK, INNSBRUCK, AUSTRIA. INT BREAST CANC STUDY GRP, BERN, SWITZERLAND. CHARING CROSS HOSP, INT COLLABORAT CANC GRP, LONDON, ENGLAND. TECHNION ISRAEL INST TECHNOL, RAMBAM MED CTR, IL-32000 HAIFA, ISRAEL. KAWASAKI MED UNIV, KAWASAKI, KANAGAWA, JAPAN. KUMAMOTO UNIV GRP, KUMAMOTO, JAPAN. ACAD ZIEKENHUIS ST RAFAEL, LOUVAIN, BELGIUM. LUND UNIV, S-22100 LUND, SWEDEN. APM, CANCEROL BIOL LAB, MARSEILLE, FRANCE. MAYO CLIN, ROCHESTER, MN 55905 USA. MD ANDERSON CANC CTR, HOUSTON, TX 77030 USA. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. NATL MED CTR, MEXICO CITY, DF, MEXICO. IST NAZL STUDIO & CURA TUMORI, I-20133 MILAN, ITALY. MONTPELLIER CTR PAUL LAMARQUE, MONTPELLIER, FRANCE. UNIV NAPLES, I-80138 NAPLES, ITALY. NCI, BETHESDA, MD 20892 USA. NATL SURG ADJUVANT BREAST & BOWEL PROJECT, PITTSBURGH, PA USA. NORTHWICK PK HOSP & CLIN RES CTR, HARROW, MIDDX, ENGLAND. CITY HOSP NOTTINGHAM, NOTTINGHAM, ENGLAND. OITA PREFECTURAL HOSP, OITA, JAPAN. ONTARIO CANC TREATMENT & RES FDN, TORONTO, ON, CANADA. ONTARIO CLIN ONCOL GRP, HAMILTON, ON, CANADA. OSAKA CITY MED SCH, OSAKA, JAPAN. OSLO RADIUM HOSP, OSLO, NORWAY. OXFORD CHURCHILL HOSP, OXFORD, ENGLAND. IMPERIAL CANC RES FUND, MRC, CLIN TRIAL SERV UNIT, LONDON, ENGLAND. CTR RENE HUGUENIN, ST CLOUD, FRANCE. INST CURIE, F-75231 PARIS, FRANCE. INST GUSTAVE ROUSSY, F-94805 VILLEJUIF, FRANCE. PARMA HOSP, PARMA, ITALY. FOX CHASE CANC CTR, PHILADELPHIA, PA 19111 USA. PIEDMONT ONCOL ASSOC, WINSTON SALEM, NC USA. CHARLES UNIV, PRAGUE, CZECH REPUBLIC. ROTTERDAM RADIO THERAPEUT INST, ROTTERDAM, NETHERLANDS. ROYAL MARSDEN HOSP, INST CANC RES, LONDON, ENGLAND. ST GEORGE HOSP, LONDON, ENGLAND. ONCOL HOSP A BUSINICO, SARDINIA, ITALY. SASKATCHEWAN CANC FDN, SASKATOON, SK, CANADA. SCOTTISH CANC TRIALS OFF, EDINBURGH, MIDLOTHIAN, SCOTLAND. SW ONCOL GRP, SEATTLE, WA USA. STOCKHOLM BREAST CANC STUDY GRP, STOCKHOLM, SWEDEN. KAROLINSKA HOSP, STOCKHOLM, SWEDEN. TEL AVIV UNIV, IL-69978 TEL AVIV, ISRAEL. CANC INST HOSP, TOKYO, JAPAN. TORONTO EDMONTON BREAST CANC STUDY GRP, TORONTO, ON, CANADA. TOULOUSE CTR CLAUDIUS REGAUD, TOULOUSE, FRANCE. INST SALAH AZAIZ, TUNIS, TUNISIA. UPPSALA OREBRO CANC STUDY GRP, UPPSALA, SWEDEN. UNIV HOSP VIENNA, VIENNA, AUSTRIA. UNIV WITWATERSRAND, JOHANNESBURG 2050, SOUTH AFRICA. RI Jonat, Walter/E-3024-2010; Barkmanova, Jaroslava/A-1411-2017 OI Barkmanova, Jaroslava/0000-0003-1406-7292 NR 14 TC 658 Z9 661 U1 2 U2 25 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 30 PY 1995 VL 333 IS 22 BP 1444 EP 1455 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA TG445 UT WOS:A1995TG44500002 ER PT J AU FISHER, B ANDERSON, S REDMOND, CK WOLMARK, N WICKERHAM, DL CRONIN, WM AF FISHER, B ANDERSON, S REDMOND, CK WOLMARK, N WICKERHAM, DL CRONIN, WM TI REANALYSIS AND RESULTS AFTER 12 YEARS OF FOLLOW-UP IN A RANDOMIZED CLINICAL-TRIAL COMPARING TOTAL MASTECTOMY WITH LUMPECTOMY WITH OR WITHOUT IRRADIATION IN THE TREATMENT OF BREAST-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article AB Background. Previous findings from a clinical trial (Protocol B-06) conducted by the National Surgical Adjuvant Breast and Bower Project (NSABP) indicated the worth of lumpectomy and breast irradiation for treating breast cancer. After the discovery by NSABP staff members of falsified information on patients enrolled in the study by St. Luc Hospital in Montreal, separate audits were conducted at St, Luc Hospital and other participating institutions. We report the results of both audits and update the study findings through an average of 12 years of follow-up. Methods. Patients with either negative or positive axillary nodes and tumors 4 cm or less in diameter were randomly assigned to one of three treatments: total mastectomy, lumpectomy followed by breast irradiation, or lumpectomy without irradiation. Three cohorts of patients were analyzed. The first cohort included all 2105 randomized patients, who were analyzed according to the intention-to-treat principle. The second cohort consisted of 1851 eligible patients in the first cohort with known nodal status who agreed to be followed and who accepted their assigned therapy (among those excluded were 6 patients from St. Luc Hospital who were declared ineligible because of falsified biopsy dates). The third cohort consisted of the patients in the second cohort minus the 322 eligible patients from St. Luc Hospital (total, 1529 patients). Results. Regardless of the cohort, no significant differences were found in overall survival, disease-free survival, or survival free of disease at distant sites between the patients who underwent total mastectomy and those treated by lumpectomy alone or by lumpectomy plus breast irradiation. After 12 years of follow-up, the cumulative incidence of a recurrence of tumor in the ipsilateral breast was 35 percent in the group treated with lumpectomy alone and 10 percent in the group treated with lumpectomy and breast irradiation (P<0.001). Conclusions. Our findings continue to indicate that lumpectomy followed by breast irradiation is appropriate therapy for women with either negative or positive axillary nodes and breast tumors 4 cm or less in diameter. C1 NATL SURG ADJUVANT BREAST & BOWEL PROJECT,PITTSBURGH,PA. OI Anderson, Stewart/0000-0001-8948-0650 FU NCI NIH HHS [U10-CA-12027] NR 17 TC 925 Z9 961 U1 2 U2 19 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 30 PY 1995 VL 333 IS 22 BP 1456 EP 1461 DI 10.1056/NEJM199511303332203 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TG445 UT WOS:A1995TG44500003 PM 7477145 ER PT J AU CHRISTIAN, MC MCCABE, MS KORN, EL ABRAMS, JS KAPLAN, RS FRIEDMAN, MA AF CHRISTIAN, MC MCCABE, MS KORN, EL ABRAMS, JS KAPLAN, RS FRIEDMAN, MA TI THE NATIONAL-CANCER-INSTITUTE AUDIT OF THE NATIONAL-SURGICAL-ADJUVANT-BREAST-AND-BOWEL-PROJECT-PROTOCOL-B-06 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID COMPARING TOTAL MASTECTOMY AB Background. The National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-06, a clinical trial sponsored by the National Cancer Institute (NCI), has provided evidence of the value of lumpectomy and breast irradiation for treating women with breast cancer in an early stage, Publicity generated by the discovery that the study included fraudulent data on patients enrolled by St. Luc Hospital in Montreal aroused concern about the overall accuracy of the data and conclusions. To address this concern, the NCI conducted an audit of other participating institutions. Methods. In 1994, data on 1554 of the 1809 randomized patients (85.9 percent) enrolled by centers other than St, Luc Hospital were audited at 37 clinical sites in North America, The audit included data on eligibility, survival, disease-free survival, the length of time to a recurrence of cancer in the ipsilateral breast, and documentation of signed informed consent. Results. End points were assessed for all 1554 patients, and eligibility was assessed for 1507 patients; 47 patients were excluded because their forms were not complete or not returned. A total of 1429 patients had their eligibility status verified. Of a total of 7770 data points examined with respect to the number of positive nodes at base line, treatment characteristics, first events (excluding death), recurrence of cancer in the ipsilateral breast, and survival, 7577 (97.5 percent) were verified, 123 (1.6 percent) could not be verified, and 70 (0.9 percent) were discrepant with the NSABP file. Of the 1554 patients, 1340 (86.2 percent) had all audited items (including eligibility) verified, 69 (4.4 percent) had at least one discrepant item, and 113 (7.3 percent) had at least one unverified item (as a result of missing or incomplete data); 32 (2.1 percent) were not assessed for eligibility but had no other discrepant or unverifiable items. Written informed consent was documented for 1098 patients before surgery and 210 after surgery; no date appeared on the signed form for 137. The informed-consent status was not verified for 71 patients and could not be determined for 38. The rates of verification of end-point data and documentation of written informed consent were similar among the total-mastectomy group, the lumpectomy group, and the group treated by lumpectomy and breast irradiation. Conclusions. The audit confirms the adequacy of the data on which the reanalysis of Protocol B-06 and the results after 12 years of follow-up are based. RP CHRISTIAN, MC (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,6130 EXECUT BLVD,RM 715,ROCKVILLE,MD 20892, USA. NR 11 TC 38 Z9 43 U1 1 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 30 PY 1995 VL 333 IS 22 BP 1469 EP 1474 DI 10.1056/NEJM199511303332206 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TG445 UT WOS:A1995TG44500006 PM 7477148 ER PT J AU Dunnick, JK Hailey, JR AF Dunnick, JK Hailey, JR TI Experimental studies on the long-term effects of methylphenidate hydrochloride SO TOXICOLOGY LA English DT Article DE methylphenidate hydrochloride; ritalin; carcinogenesis; toxicology; F344/N rats; B6C3F1 mice ID DEFICIT HYPERACTIVITY DISORDER; RAT-LIVER; PEROXISOME PROLIFERATION; ANIMAL CARCINOGENICITY; SPONTANEOUS TUMORS; AMPHETAMINE; MICE AB Toxicology and carcinogenesis studies of methylphenidate hydrochloride, a drug used in the treatment of attention-deficient disorders, were performed in F344 rats and B6C3F1 mice. In these studies, methylphenidate hydrochloride was administered for 2 years at doses of 0, 100, 500 or 1000 ppm in the feed to rats and at doses of 0, 50, 250, 500 ppm to mice in groups that consisted of 50 animals/dose/sex/species. The average amount of methylphenidate consumed per day was estimated to be 4-47 mg/kg/day for rats and 5-67 mg/kg/day for mice. Survival was similar in dosed and control groups. An increase in benign tumors of the liver and increased liver weights were observed in male and female mice at the high dose. An increase in hepatoblastomas was also seen in high dose male mice. Methylphenidate was not mutagenic in the Salmonella assay system, and it is hypothesized that this tumorigenic effect might be due to nongenotoxic effects of the chemical such as an increase in cell proliferation. Increased incidences of neoplasms were not seen in rats. However, there was a notable decrease in mammary gland fibroadenomas in female rats and a marginal decrease in benign pheochromocytomas in male rats. Epidemiology studies of methylphenidate have found no evidence of a carcinogenic effect in humans and like our findings in rats, report a less than expected rate of cancers in patients taking methylphenidate. RP Dunnick, JK (reprint author), NATL INST ENVIRONM HLTH SCI,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 25 TC 30 Z9 30 U1 0 U2 1 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 NOV 30 PY 1995 VL 103 IS 2 BP 77 EP 84 DI 10.1016/0300-483X(95)03109-S PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA TL731 UT WOS:A1995TL73100001 PM 8545847 ER PT J AU Fonger, GC AF Fonger, GC TI Hazardous substances data bank (HSDB) as a source of environmental fate information on chemicals SO TOXICOLOGY LA English DT Article DE hazardous substances data bank; information technology; toxicology data network; environmental fate AB The Hazardous Substances Data Bank (HSDB),a factual data bank on the National Library of Medicine's (NLM) TOXNET (Toxicology Data Network) online system, provides information in areas such as chemical substance identification, chemical and physical properties, safety and handling, toxicology, pharmacology, environmental fate and transformation, regulations, and analytical methodology. This article discusses how environmental fate data is handled in HSDB. RP Fonger, GC (reprint author), NATL LIB MED,DIV SPECIALIZED INFORMAT SERV,TOXICOL & ENVIRONM HLTH INFORMAT PROGRAM,BETHESDA,MD 20894, USA. NR 0 TC 10 Z9 11 U1 0 U2 3 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 NOV 30 PY 1995 VL 103 IS 2 BP 137 EP 145 DI 10.1016/0300-483X(95)03145-6 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA TL731 UT WOS:A1995TL73100007 PM 8545846 ER PT J AU Ozaki, N Rosenthal, NE Myers, F Schwartz, PJ Oren, DA AF Ozaki, N Rosenthal, NE Myers, F Schwartz, PJ Oren, DA TI Effects of season on electro-oculographic ratio in winter seasonal affective disorder SO PSYCHIATRY RESEARCH LA English DT Article DE depression; retina; circannual rhythms ID LIGHT-PEAK; DEPRESSED-PATIENTS; ORIGIN; EYE; SENSITIVITY AB Low electro-oculographic (EGG) ratios have been reported in patients with seasonal affective disorder (SAD) during the winter. This study evaluated the effects of the changing seasons on EOG ratios in SAD patients. Sixteen outpatients with SAD and 16 age-, sex-, and medication-matched normal volunteers had EOG testing during the winter and again during the summer. There was a significant season x group interaction in EOG ratios, with normal subjects showing higher ratios in winter than in summer - a seasonal variation not observed in SAD patients. SAD patients may have a subsensitivity to environmental light that leads them to experience symptoms during the winter. RP Ozaki, N (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Ozaki, Norio/M-8908-2014 OI Ozaki, Norio/0000-0002-7360-4898 NR 32 TC 25 Z9 25 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 29 PY 1995 VL 59 IS 1-2 BP 151 EP 155 DI 10.1016/0165-1781(95)02788-2 PG 5 WC Psychiatry SC Psychiatry GA TY658 UT WOS:A1995TY65800017 PM 8771230 ER PT J AU KUZNICKI, J STRAUSS, KI JACOBOWITZ, DM AF KUZNICKI, J STRAUSS, KI JACOBOWITZ, DM TI CONFORMATIONAL-CHANGES AND CALCIUM-BINDING BY CALRETININ AND ITS RECOMBINANT FRAGMENTS CONTAINING DIFFERENT SETS OF EF HAND MOTIFS SO BIOCHEMISTRY LA English DT Article ID PROTEINS; RAT; BRAIN; LOCALIZATION; CALMODULIN; BACTERIA; SEQUENCE AB Four recombinant fragments, representing different sets of EF-hand motifs of rat calretinin (CR) (I-II, I-III, III-VI, IV-VI), were prepared, and their Ca2+-induced conformational changes were compared with those of full-length recombinant CR. All fragments were able to bind calcium ions as shown by Ca-45(2+) overlay method on nitrocellulose and fluorescence measurements. The intrinsic tryptophan fluorescence intensity (F-I) of apo-CR reversibly increased about 3-fold upon addition of calcium, indicating a change of conformation. The FI of fragments I-II (Trp 25) and I-III (Trp 25 and 116) increased about 1.4-fold on calcium binding, but that of fragment III-VI (Trp 116) increased 3.5-fold. Calcium titration of CR monitored by Trp fluorescence intensity showed that recombinant CR and some fragments bound Ca2+ with high affinity (K-d below 0.4 mu M) and with high cooperativity. An apparent Kill coefficient for Ca2+-induced fluorescence changes in CR was about 3.7. CR bound to organomercurial-agarose independent of Ca2+ concentrations and could be eluted with 2-mercaptoethanol or DTT, indicating that Cys 101 and 266 did not form cystine. The fluorescence intensities of cysteine-linked fluorescent probes 5-iodoacetamidofluorescein and N-(1-pyreneiodoacetamide) were increased approximately 1.3-fold upon calcium binding by CR. These data indicate that CR binds Ca2+ with high affinity and cooperativity and that this binding induces a change of conformation that involves the interaction of different parts of the molecule. Taken together, our results suggest that CR works as an on/off switch within a narrow range of free Ca2+ by interacting with as yet unidentified targets. C1 M NENCKI INST EXPTL BIOL, WARSAW, POLAND. RP KUZNICKI, J (reprint author), NIMH, CLIN SCI LAB, BETHESDA, MD 20892 USA. NR 36 TC 21 Z9 21 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 28 PY 1995 VL 34 IS 47 BP 15389 EP 15394 DI 10.1021/bi00047a001 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TG973 UT WOS:A1995TG97300001 PM 7492538 ER PT J AU Gelboin, HV Krausz, KW Goldfarb, I Buters, JTM Yang, SK Gonzalez, FJ Korzekwa, KR Shou, MG AF Gelboin, HV Krausz, KW Goldfarb, I Buters, JTM Yang, SK Gonzalez, FJ Korzekwa, KR Shou, MG TI Inhibitory and non-inhibitory monoclonal antibodies to human cytochrome P450 3A3/4 SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE human P450 3A4; inhibitory monoclonal antibodies; western blot; p-nitroanisole; phenanthrene; diazepam; taxol; cyclosporin; testosterone ID RAT-LIVER CYTOCHROME-P-450; METABOLISM; SPECIFICITY; EXPRESSION; TISSUES; CELLS AB Cytochromes P450 3A3/4 are inordinately important P450 enzymes catalyzing the metabolism of a large variety of clinically useful drugs, steroids, and carcinogens. Two monoclonal antibodies, MAb 3-29-9 and MAb 275-1-2, were prepared to human P450 3A4 from mice immunized with baculovirus-expressed human P450 3A4. MAb 3-29-9 was a powerful inhibitor of the enzymatic activity of P450 3A3/4/5. MAb 3-29-9 inhibited the P450 3A3, 3A4, and 3A5 catalyzed metabolism of substrates of divergent molecular weights, e.g., p-nitroanisole, phenanthrene, diazepam, testosterone, taxol, and cyclosporin. However, MAb 3-29-9 did not give a western blot with P450 3A3 or 3A4. MAb 275-1-2 was non-inhibitory but yielded a strong western blot with P450 3A3 and 3A4 but not with 3A5, and thus distinguished between 3A3/4 and 3A5. The two MAbs did not cross-react with human 2E1, 1A2, 2B6, 2C8, and 2C9; rat 2A1,3A1/2, 4A1, 4A3, and 2B1; and mouse 1A1 and 1A2. MAb 3-29-9 has been used successfully to measure the quantitative contribution of P450 3A3 and 3A4 to the metabolism of the above-designated substrates in human adult liver. MAb 3-29-9 and MAb 275-1-2 are precise and sensitive reagents for P450 3A studies. C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. RP Gelboin, HV (reprint author), NCI,MOLEC CARCINOGENESIS LAB,9000 ROCKVILLE PIKE,BLDG 37,RM 3E24,BETHESDA,MD 20892, USA. RI Buters, Jeroen/G-5070-2011 NR 27 TC 47 Z9 47 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 27 PY 1995 VL 50 IS 11 BP 1841 EP 1850 DI 10.1016/0006-2952(95)02077-2 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TL149 UT WOS:A1995TL14900014 PM 8615863 ER PT J AU Lin, KH Lin, YW Lee, HF Liu, WL Chen, ST Chang, KSS Cheng, SY AF Lin, KH Lin, YW Lee, HF Liu, WL Chen, ST Chang, KSS Cheng, SY TI Increased invasive activity of human hepatocellular carcinoma cells is associated with an overexpression of thyroid hormone beta 1 nuclear receptor and low expression of the anti-metastatic nm23 gene SO CANCER LETTERS LA English DT Article DE thyroid hormone; invasion; tumors; transcriptional factors; nm23 gene; differentiation ID TUMOR-METASTASIS AB To understand the role of thyroid hormone in metastasis, we studied the expression of the anti-metastatic nm23 gene in eight human hepatocellular carcinoma (HCC) cell lines. These cells differentially expressed the anti-metastatic nm23 gene. A low level of nm23 proteins was found to have a high in vitro invasive activity which correlated closely with an overexpression of the thyroid hormone beta 1 nuclear receptor (h-TR beta 1). Concurrent with the down-regulation of h-TR beta 1, the invasive activity of HCC cells was suppressed by the thyroid hormone, 3,3',5-triiodo-L-thyronine (T-3). These results indicate that the invasive activity of HCC cells was regulated by T-3, suggesting that T-3 could be involved in modulating the functions of nm23. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,GENE REGULAT SECT,BETHESDA,MD 20892. RP Lin, KH (reprint author), CHANG GUNG COLL MED & TECHNOL,GRAD INST CLIN MED,259 WEN HWA 1ST RD,TAYUAN,TAIWAN. NR 13 TC 19 Z9 21 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 27 PY 1995 VL 98 IS 1 BP 89 EP 95 DI 10.1016/S0304-3835(06)80015-7 PG 7 WC Oncology SC Oncology GA TK517 UT WOS:A1995TK51700013 PM 8529211 ER PT J AU KIM, DS CHIN, HM KLEE, WA AF KIM, DS CHIN, HM KLEE, WA TI AGONIST REGULATION OF THE EXPRESSION OF THE DELTA-OPIOID RECEPTOR IN NG108-15 CELLS SO FEBS LETTERS LA English DT Article DE DELTA-OPIOID RECEPTOR; OPIATE; BINDING ACTIVITY; TRANSCRIPTION; DOWN-REGULATION ID MESSENGER-RNA AB Exposure of neuronal cells to the chronic presence of opiates leads to a complex series of biochemical events which reflect the changes that result in tolerance and dependence in animals, To achieve a better understanding of the molecular mechanisms underlying these processes, we have examined the effect of agonist efficacy on the regulation of the delta-opioid receptor mRNA in NG108-15 cells, Incubation with various opiates decreased receptor numbers in the order of their efficacy, Northern blot analysis showed that there are 4 size classes of mRNA coding for the delta-opioid receptor in NG108-15 cells even though only one known protein species is found, Moreover, the amount of each transcript is coordinately decreased by long-term etorphine treatment, but not necessarily to the same extent. The etorphine-induced decrease in receptor mRNA slow in onset, whereas a much more rapid loss of receptor number was observed, This disparity suggests that the induced by etorphine can occur both at the levels of receptor protein modification and receptor gene expression, and that the mechanisms of the two processes may be different. C1 NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NR 10 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 27 PY 1995 VL 376 IS 1-2 BP 11 EP 14 DI 10.1016/0014-5793(95)01233-6 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TH413 UT WOS:A1995TH41300003 PM 8521954 ER PT J AU ONISTO, M RICCIO, MP SCANNAPIECO, P CAENAZZO, C GRIGGIO, L SPINA, M STETLERSTEVENSON, WG GARBISA, S AF ONISTO, M RICCIO, MP SCANNAPIECO, P CAENAZZO, C GRIGGIO, L SPINA, M STETLERSTEVENSON, WG GARBISA, S TI GELATINASE A/TIMP-2 IMBALANCE IN LYMPH-NODE-POSITIVE BREAST CARCINOMAS, AS MEASURED BY RT-PCR SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BASEMENT-MEMBRANE COLLAGEN; POLYMERASE CHAIN-REACTION; TISSUE INHIBITOR; IV COLLAGENASE; CELL-LINES; EXPRESSION; TIMP-2; METALLOPROTEINASES-2; INVASION; GENE AB Over-production of gelatinase A (MMP-2) or under-production of its inhibitor (TIMP-2) may result in the matrix degradation crucial for metastasis, and early evaluation of their expression in primary tumor would offer important prognostic informations. RT-PCR amplicons of MMP-2 and TIMP-2, mRNA from tissue biopsies of 13 breast carcinomas and one fibrocystic mastopathy were quantitated. In comparison with their normal-tissue counterparts, their expression trends were not uniform: in some cases MMP-2 increased in the tumor without changes in TIMP-2, in others TIMP-2 expression also increased, although to a lesser extent than MMP-2; only in 2 cases was it slightly lower in the tumor tissue. Nevertheless, clearer insights were gained from the comparison of the ratio (R) between MMP-2(tumor/normal) and TIMP-2(tumor/normal): as in the fibrocystic mastopathy, the R in carcinomas without lymph-node involvement (LN(-)) was usually lower than I in most cases. In contrast, in 5 out of 6 patients with lymph-node metastasis (LN(+)), the ratio ranged between 2 and 4. While the R magnitude was not related to the frequency of positive lymph nodes out of the total analyzed, nor to relapse status at follow-up (all relapse-free), the clear-cut difference between the LN(-) and LN(+) groups was statistically significant. Results suggest that evaluation of MMP-2/TIMP-2 mRNA balance may constitute an early prognostic approach, which may also be more reliable concerning cancer aggressiveness as compared with the MMP-2 alone, and that boosting TIMP-2 expression may be a therapeutic strategy to prevent metastasis. (C) 1995 Wiley-Liss, Inc. C1 UNIV PADUA,SCH MED,INST HISTOL & GEN EMBRYOL,I-35100 PADUA,ITALY. GEN HOSP,DIV SURG 1,I-35100 PADUA,ITALY. NIH,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 21 TC 60 Z9 66 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 NOV 27 PY 1995 VL 63 IS 5 BP 621 EP 626 DI 10.1002/ijc.2910630504 PG 6 WC Oncology SC Oncology GA TH263 UT WOS:A1995TH26300003 PM 7591276 ER PT J AU CIRIELLI, C RICCIONI, T YANG, CL PILI, R GLOE, T CHANG, J INYAKU, K PASSANITI, A CAPOGROSSI, MC AF CIRIELLI, C RICCIONI, T YANG, CL PILI, R GLOE, T CHANG, J INYAKU, K PASSANITI, A CAPOGROSSI, MC TI ADENOVIRUS-MEDIATED GENE-TRANSFER OF WILD-TYPE P53 RESULTS IN MELANOMA CELL APOPTOSIS IN-VITRO AND IN-VIVO SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GROWTH-FACTOR PRODUCTION; THYMIDINE KINASE GENE; LUNG-CANCER CELLS; TRANSDUCTION; SUPPRESSION; EXPRESSION; PROTEIN; THERAPY; DNA AB Gene transfer techniques may provide efficient treatment for a variety of malignant neoplasms. A replication-deficient adenovirus (Ad) vector which carries the cDNA for wild-type p53 (AdCMV.p53) was tested for its in vitro and in vivo effects on the growth of murine melanoma cell line B16-G3.26 and human melanoma cell line SK-MEL-24. The growth of B16-G3.26 cells infected with AdCMV.p53 was inhibited when compared to the uninfected cells or cells infected with the control vector AdCMV.NLS beta gal. Similarly, the growth of SK-MEL-24 cells infected with AdCMV.p53 was also below that of AdCMV.NLS beta gal-infected and uninfected controls. DNA laddering using agarose gel electrophoresis and in site labeling of DNA fragmentation (TUNEL) showed that AdCMV.p53-infected murine and human melanoma cells underwent apoptosis. Nude mice injected s.c. either with B16-G3.26 cells or with SK-MEL-24 cells developed localized tumors. These tumors were subsequently infiltrated with either AdCMV.p53, AdCMV.NLS beta gal or saline alone. One week after infection, B16-G3.26 tumors exposed to AdCMV.p53 were 2.5 times smaller than control tumors and exhibited DNA fragmentation. A similar growth-inhibitory effect of AdCMV.p53 was observed with SK-MEL-24 tumors. Thus, Ad-mediated wildtype p53 overexpression resulted in melanoma cell apoptosis and inhibition of melanoma growth in vitro and in vivo. These gene therapy approaches may be useful in targeting rapidly growing, malignant melanomas in a clinical setting. (C) 1995 Wiley-Liss, Inc. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,GENE THERAPY UNIT,BALTIMORE,MD 21224. NIA,GERONTOL RES CTR,BIOL CHEM LAB,BALTIMORE,MD 21224. IST DERMOPAT IMMACOLATA,PATOL VASC LAB,ROME,ITALY. NR 32 TC 53 Z9 54 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 NOV 27 PY 1995 VL 63 IS 5 BP 673 EP 679 DI 10.1002/ijc.2910630512 PG 7 WC Oncology SC Oncology GA TH263 UT WOS:A1995TH26300011 PM 7591284 ER PT J AU KAWAMATA, H KAWAI, K KAMEYAMA, S JOHNSON, MD STETLERSTEVENSON, WG OYASU, R AF KAWAMATA, H KAWAI, K KAMEYAMA, S JOHNSON, MD STETLERSTEVENSON, WG OYASU, R TI OVER-EXPRESSION OF TISSUE INHIBITOR OF MATRIX METALLOPROTEINASES (TIMP1 AND TIMP2) SUPPRESSES EXTRAVASATION OF PULMONARY METASTASIS OF A RAT BLADDER-CARCINOMA SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ORGAN ENVIRONMENT; IV COLLAGENASE; CHICK-EMBRYO; CELLS; INVASION; ABILITY; GROWTH; ALPHA AB The balance between matrix metalloproteinases and their inhibitors is a critical factor which affects tumor invasion and metastasis. We have established a rat bladder carcinoma cell line, LMC19, which is tumorigenic, invasive and metastatic to the retroperitoneal lymph nodes and to the lungs in nude mice. LMC19 cells secrete pro-gelatinases A and B as well as tissue inhibitors of matrix metalloproteinase (TIMP1 and TIMP2). We conducted the present study to determine whether or not over-expression of TIMP1 and TIMP2 can affect the metastatic potential of LMC19 cells. We transfected the cells with an expression vector containing TIMP1 or TIMP2 cDNA, isolated several clones over-expressing TIMP1 or TIMP2 and assessed their invasive and metastatic potential by inoculation at an orthotopic site (urinary bladder) in nude mice. Our results show that the transfectants over-expressing TIMP1 and TIMP2 marginally affect primary tumor growth, local invasion or metastasis to the retroperitoneal lymph nodes but significantly inhibit extravascular growth of pulmonary tumor emboli. Our results suggest that the net activity of matrix metalloproteinases of tumor cells may be a critical factor that controls extravasation at this distant metastatic site. (C) 1995 Wiley-Liss, Inc. C1 NORTHWESTERN UNIV,SCH MED,DEPT PATHOL,CHICAGO,IL 60611. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [CA14649] NR 24 TC 56 Z9 58 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 27 PY 1995 VL 63 IS 5 BP 680 EP 687 DI 10.1002/ijc.2910630513 PG 8 WC Oncology SC Oncology GA TH263 UT WOS:A1995TH26300012 PM 7591285 ER PT J AU Horwitz, B McIntosh, AR Haxby, JV Furey, M Salerno, JA Schapiro, MB Rapoport, SI Grady, CL AF Horwitz, B McIntosh, AR Haxby, JV Furey, M Salerno, JA Schapiro, MB Rapoport, SI Grady, CL TI Network analysis of PET-mapped visual pathways in Alzheimer type dementia SO NEUROREPORT LA English DT Article DE positron emission tomography; extrastriate cortex; frontal lobe; network analysis; brain; human; Alzheimer's disease ID PREFRONTAL CORTEX; DISEASE; PLAQUES; OBJECT; TASK AB USING path analysis to determine the systems-level neural networks mediating specific tasks from regional cerebral blood flow (rCBF) data obtained by positron emission tomography (PET), we recently found in young subjects strong functional linkages during a face matching task along a right hemisphere ventral network including occipital, temporal, and frontal regions. In this study, PET data obtained during a face matching task from mildly affected patients with dementia of the Alzheimer type (DAT) and healthy matched controls showed that (1) the neural model obtained in young subjects provides a good fit to data from old subjects; (2) although the DAT patients could perform this task with the same accuracy as controls, they did not use the same functional network. RP Horwitz, B (reprint author), NIA, NEUROSCI LAB, BLDG 10, ROOM 6C-414, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI McIntosh, Anthony/G-4955-2011; Furey, Maura/H-5273-2013; OI McIntosh, Anthony/0000-0002-1784-5662 NR 25 TC 96 Z9 96 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 27 PY 1995 VL 6 IS 17 BP 2287 EP 2292 DI 10.1097/00001756-199511270-00005 PG 6 WC Neurosciences SC Neurosciences & Neurology GA TL993 UT WOS:A1995TL99300005 PM 8747138 ER PT J AU Nichelli, P Grafman, J Pietrini, P Clark, K Lee, KY Miletich, R AF Nichelli, P Grafman, J Pietrini, P Clark, K Lee, KY Miletich, R TI Where the brain appreciates the moral of a story SO NEUROREPORT LA English DT Article DE frontal lobes; story processing; PET ID ANATOMY AB To identify the distributed brain regions used for appreciating the grammatical, semantic and thematic aspects of a story, regional cerebral blood flow was measured with positron emission tomography in nine normal volunteers during the reading of Aesop's fables. In four conditions, subjects had to monitor the fables for font changes, grammatical errors, a semantic feature associated with a fable character, and the moral of the fable. Both right and left prefrontal cortices were consistently, but selectively, activated across the grammatical, semantic, and moral conditions. In particular, appreciating the moral of a story required activating a distributed set of brain regions in the right hemisphere which included the temporal and prefrontal cortices. These findings emphasize that story processing engages a widely distributed network of brain regions, a subset of which become preferentially active during the processing of a specific aspect of the text. C1 NINCDS,COGNIT NEUROSCI SECT,MNB,BETHESDA,MD 20892. UNIV MODENA,NEUROL CLIN,I-41100 MODENA,ITALY. NIA,NEUROSCI LAB,BUFFALO,NY. NINCDS,NEUROIMAGING BRANCH,BUFFALO,NY. MILLARD FILLMORE HOSP,LUCY DENT IMAGING CTR,BUFFALO,NY. RI Nichelli, Paolo/F-7336-2015; OI Nichelli, Paolo/0000-0001-9756-6796; Grafman, Jordan H./0000-0001-8645-4457 NR 16 TC 85 Z9 87 U1 0 U2 6 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 27 PY 1995 VL 6 IS 17 BP 2309 EP 2313 DI 10.1097/00001756-199511270-00010 PG 5 WC Neurosciences SC Neurosciences & Neurology GA TL993 UT WOS:A1995TL99300010 PM 8747143 ER PT J AU Miner, LL Drago, J Chamberlain, PM Donovan, D Uhl, GR AF Miner, LL Drago, J Chamberlain, PM Donovan, D Uhl, GR TI Retained cocaine conditioned place preference in D1 receptor deficient mice SO NEUROREPORT LA English DT Article DE cocaine; conditioned place preference; D1 dopamine receptor; homologous recombination ID DOPAMINE AB THE role of the D1 dopamine receptor subtype in mediating cocaine effects was examined in mice in which the D1 receptor gene had been ablated by homologous recombination. Cocaine reward was assessed by conditioned place preference experiments using mice which had either one allele (+/-) or both alleles (-/-) of the D1 dopamine receptor gene disrupted and in their wild type (+/+) littermates. Cocaine conditioning resulted in similar increases in preference for drug-paired environments in mice of each of the three genotypes. Cocaine did not alter locomotor activity levels in homozygous, D1 knockout mice -/-, whereas increased activity was noted in both +/+ and +/- animals. These results are consistent with the idea that the D1 receptor is involved in the locomotor stimulant effects of cocaine, but has little role in a major test of the rewarding and reinforcing effects of the drug. C1 MONASH UNIV,DEPT ANAT,CLAYTON,VIC 3168,AUSTRALIA. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. RP Miner, LL (reprint author), NIDA,ADDICT RES CTR,DIV INTRAMURAL RES,MOLEC NEUROBIOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 13 TC 95 Z9 96 U1 1 U2 4 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 27 PY 1995 VL 6 IS 17 BP 2314 EP 2316 DI 10.1097/00001756-199511270-00011 PG 3 WC Neurosciences SC Neurosciences & Neurology GA TL993 UT WOS:A1995TL99300011 PM 8747144 ER PT J AU LENSCHOW, DJ ZENG, YJ HATHCOCK, KS ZUCKERMAN, LA FREEMAN, G THISTLETHWAITE, JR GRAY, GS HODES, RJ BLUESTONE, JA AF LENSCHOW, DJ ZENG, YJ HATHCOCK, KS ZUCKERMAN, LA FREEMAN, G THISTLETHWAITE, JR GRAY, GS HODES, RJ BLUESTONE, JA TI INHIBITION OF TRANSPLANT REJECTION FOLLOWING TREATMENT WITH ANTI-B7-2 AND ANTI-B7-1 ANTIBODIES SO TRANSPLANTATION LA English DT Article ID T-CELL PROLIFERATION; CTLA-4 COUNTER-RECEPTOR; COSTIMULATORY SIGNAL; MONOCLONAL-ANTIBODY; CLONAL ANERGY; B-CELLS; ANTIGEN; ACTIVATION; CD28; INTERLEUKIN-2 AB Antigen-specific T cell activation depends initially on the interaction of the T cell receptor (TCR) with peptide/MHC. In addition, a costimulatory signal, mediated by distinct cell surface accessory molecules, is required for complete T cell activation leading to lymphokine production and proliferation. CD28 has been implicated as the major receptor on T cells responsible for delivering the costimulatory signal, Although two distinct ligands for CD28, B7-1 and B7-2, have been identified on antigen-presenting cells (APC), the costimulatory role of each molecule during a physiological immune response remains unresolved. In the present study, the relative roles of B7-1 and B7-2 interactions were evaluated in an allogeneic pancreatic islet transplant setting, In isolation, anti-B7-2 mAbs and, to a much lesser degree, anti-B7-1 mAbs suppressed T cell proliferative responses to allogeneic islets or splenic APC in vitro. Maximal inhibition of the allogeneic response was observed using a combination of the anti-B7-1 and anti-B7-2 mAbs, Administration of anti-B7-2 but not anti-B7-1 mAbs prolonged C3H allograft survival in B6 recipients, with a combination of both mAbs significantly prolonging rejection beyond either mAb alone, The immunosuppressive effects of the in vivo mAb treatment were not manifested in in vitro analyses as T cells isolated from suppressed mice responded normally to allogeneic stimuli in terms of both proliferation and lymphokine production, However, combined mAb therapy in vivo selectively delayed CD4(+) T lymphocyte infiltration into the graft. These data suggest that both B7-1 and B7-2 costimulatory molecules are active in vivo, although B7-2 plays a clearly dominant role in this allograft model. The mechanism of immune suppression in vivo remains unresolved but may occur at sites distinct from the allograft. C1 UNIV CHICAGO,BEN MAY INST,COMM IMMUNOL,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PATHOL,CHICAGO,IL 60637. UNIV CHICAGO,PRITZKER SCH MED,DEPT SURG,TRANSPLANTAT SECT,CHICAGO,IL 60637. UNIV CHICAGO,PRITZKER SCH MED,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. REPLIGEN CORP,CAMBRIDGE,MA 02139. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [P30 CA14599]; NIAID NIH HHS [P01 AI29531] NR 40 TC 137 Z9 138 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 1995 VL 60 IS 10 BP 1171 EP 1178 DI 10.1097/00007890-199511270-00019 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA TH328 UT WOS:A1995TH32800019 PM 7482727 ER PT J AU Ajmani, RS Puniyani, RR Khanuja, VS AF Ajmani, RS Puniyani, RR Khanuja, VS TI Evaluation of haemorheological, biochemical and microcirculatory parameters in young smokers SO CURRENT SCIENCE LA English DT Article ID CIGARETTE-SMOKING; HEMORHEOLOGICAL CHANGES; BLOOD; FIBRINOLYSIS; HEART AB We studied 44 young smokers and 40 controls, all male, for haemorheological, biochemical, physiological and microcirculatory parameters. This study was conducted between January 1994 and December 1994. All the smokers have been smoking 13-18 cigarettes per day for the last three years, None of them were taking any medicine nor did they have any major health problem which could affect the results of our study. The results of our study clearly indicate that smokers have disturbed haemodynamic profile as compared to normal controls. This could result in worsening of blood flow condition, leading to development of various disorders. C1 INDIAN INST TECHNOL,SCH BIOMED ENGN,BOMBAY 400076,MAHARASHTRA,INDIA. RP Ajmani, RS (reprint author), NIA,LCMB,CTR GERONTOL RES,4-B-12,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU CURRENT SCIENCE ASSN PI BANGALORE PA C V RAMAN AVENUE, PO BOX 8005, BANGALORE 560 080, INDIA SN 0011-3891 J9 CURR SCI INDIA JI Curr. Sci. PD NOV 25 PY 1995 VL 69 IS 10 BP 877 EP 880 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TP845 UT WOS:A1995TP84500022 ER PT J AU GOEDERT, JJ AF GOEDERT, JJ TI MORTALITY AND HEMOPHILIA SO LANCET LA English DT Letter RP GOEDERT, JJ (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 20852, USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD NOV 25 PY 1995 VL 346 IS 8987 BP 1425 EP 1426 DI 10.1016/S0140-6736(95)92440-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA TG207 UT WOS:A1995TG20700043 PM 7475837 ER PT J AU GODDE, JS NAKATANI, Y WOLFFE, AP AF GODDE, JS NAKATANI, Y WOLFFE, AP TI THE AMINO-TERMINAL TAILS OF THE CORE HISTONES AND THE TRANSLATIONAL POSITION OF THE TATA BOX DETERMINE TBP/TFIIA ASSOCIATION WITH NUCLEOSOMAL DNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA POLYMERASE-II; TRANSCRIPTION FACTOR ACCESS; TUMOR VIRUS PROMOTER; CRYSTAL-STRUCTURE; 5S RNA; BINDING-PROTEIN; FACTOR-TFIIB; MAJOR LATE; GENE; INITIATION AB We establish that the TATA binding protein (TBP) in the presence of TFIIA recognizes the TATA box in nucleosomal DNA dependent on the dissociation of the amino-terminal tails of the core histones from the nucleosome and the position of the TATA box within the nucleosome. We examine TBP/TFIIA access to the TATA box with this sequence placed in four distinct rotational frames with reference to the histone surface and at three distinct translational positions at the edge, side and dyad axis of the nucleosome. Under our experimental conditions, we find that the preferential translational position at which TBP/TFIIA can bind the TATA box is within linker DNA at the edge of the nucleosome and that binding is facilitated if contacts made by the amino-terminal tails of the histones with nucleosomal DNA are eliminated. TBP/TFIIA binding to DNA at the edge of the nucleosome occurs with the TATA box in all four rotational positions. This is indicative of TBP/TFIIA association directing the dissociation of the TATA box from the surface of the histone octamer. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. NR 59 TC 74 Z9 75 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 25 PY 1995 VL 23 IS 22 BP 4557 EP 4564 DI 10.1093/nar/23.22.4557 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ817 UT WOS:A1995TJ81700004 PM 8524642 ER PT J AU LUSTIG, B JERNIGAN, RL AF LUSTIG, B JERNIGAN, RL TI CONSISTENCIES OF INDIVIDUAL DNA BASE-AMINO ACID INTERACTIONS IN STRUCTURES AND SEQUENCES SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CRYSTAL-STRUCTURE; CRO REPRESSOR; RECOGNITION; COMPLEX AB Amino acid-amino acid interaction energies have been derived from crystal structure data for a number of years. Here is reported the first derivation of normalized relative interaction from binding data for each of the four bases interacting with a specific amino acid, utilizing data from combinatorial multiplex DNA binding of zinc finger domains [Desjarlais, J. R. and Berg, J. M. (1994) Proc. Natl. Acad. Sci. USA, 91, 11099-11103]. The five strongest interactions are observed for lysine-guanine, lysine-thymine, arginine-guanine, aspartic acid-cytosine and asparagine-adenine. These rankings for interactions with the four bases appear to be related to base-amino acid partial charges. Also, similar normalized relative interaction energies are derived by using DNA binding data for Cro and lambda repressors and the R2R3 c-Myb protein domain [Takeda, Y., Sarai, A. and Rivera, V. M. (1989) Proc. Natl. Acad. Sci, USA, 86, 439-443; Sarai, A. and Takeda, Y. (1989) Proc. Natl. Acad. Sci. USA, 86, 6513-6517; Ogata, K. et al. (1995) submitted]. These energies correlate well with the combinatorial multiplex energies, and the strongest cases are similar between the two sets. They also correlate well with similar relative interaction energies derived directly from frequencies of bases in the bacteriophage lambda operator sequences. These results suggest that such potentials are general and that extensive combinatorial binding studies can be used to derive potential energies for DNA-protein interactions. C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RI Jernigan, Robert/A-5421-2012 NR 18 TC 42 Z9 43 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 25 PY 1995 VL 23 IS 22 BP 4707 EP 4711 DI 10.1093/nar/23.22.4707 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TJ817 UT WOS:A1995TJ81700026 PM 8524664 ER PT J AU ZHAN, SL SHAPIRO, D ZHAN, SX ZHANG, LJ HIRSCHFELD, S ELASSAL, J HELMAN, LJ AF ZHAN, SL SHAPIRO, D ZHAN, SX ZHANG, LJ HIRSCHFELD, S ELASSAL, J HELMAN, LJ TI CONCORDANT LOSS OF IMPRINTING OF THE HUMAN-INSULIN-LIKE-GROWTH-FACTOR-II GENE PROMOTERS IN CANCER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID UNIPARENTAL PATERNAL DISOMY; WILMS-TUMOR; RELAXATION; H19 AB The human insulin-like growth factor II (IGFII) gene has been shown to be imprinted for the promoters P2, P3, and P4 but not for the promoter P1 in liver and chondrocytes. Loss of imprinting of the IGFII gene has been found in a variety of human tumors including rhabdomyosarcoma and lung cancer, In this report, we determined whether loss of imprinting in tumors displays a promoter-specific pattern. We examined allelic expression of all four IGFII promoters in rhabdomyosarcoma, lung cancer, and normal skeletal muscle. We demonstrate that the imprinting of all IGFII promoters is relaxed in rhabdomyosarcoma and lung cancer, These data suggest that loss of imprinting of IGFII gene promoters may be regulated coordinately by a common mechanism in these tumors, Unexpectedly, we also found that P1, in addition to P2, P3, and P4 is monoallelically expressed in three informative adult skeletal muscle tissues. This indicates that imprinting of the IGFII promoter P1 occurs in a tissue-specific manner. C1 NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DEPT EXPTL ONCOL, MEMPHIS, TN 38101 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 FU NCI NIH HHS [CA-23099, CA-21765] NR 31 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 24 PY 1995 VL 270 IS 47 BP 27983 EP 27986 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TG210 UT WOS:A1995TG21000001 PM 7499276 ER PT J AU THOMPSON, J HU, HZ SCHARFF, J NEVILLE, DM AF THOMPSON, J HU, HZ SCHARFF, J NEVILLE, DM TI ANTI-CD3 SINGLE-CHAIN IMMUNOTOXIN WITH A TRUNCATED DIPHTHERIA-TOXIN AVOIDS INHIBITION BY PREEXISTING ANTIBODIES IN HUMAN BLOOD SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-SYNTHESIS INACTIVATION; FRAGMENT-A; RECEPTOR; CELLS; INTERLEUKIN-2; CONSTRUCTION; LYMPHOCYTES; CONJUGATE; KINETICS; MUTANTS AB Diphtheria toxin (DT) is often used in the construction of immunotoxins. One potential problem using DT-based immunotoxins is the pre-existing anti-DT antibodies present in human blood due to vaccination. The present study examined the effect of human serum with pre-existing anti-DT antibodies on the toxicity of UCHT1-CRM9, an immunotoxin directed against CD3 molecules on T-lymphocytes. Sera with detectable anti DT antibodies at 1:100 or greater dilutions inhibited the immunotoxin toxicity. Experiments with radiolabeled UCHT1-CRM9 indicate that anti-DT antibodies partially block its binding to the cell surface as well as inhibit the translocation from the endosome to the cytosol. The inhibitory effect could be adsorbed using a full-length DT mutant or B-subfragment. A C-terminal truncation mutant could not adsorb the inhibitory effect, suggesting that the last 150 amino acids contain the epitope(s) recognized by the inhibitory antibodies. Therefore, an anti-CD3 single-chain immunotoxin, sFv-DT390, was made with a truncated DT. The IC50 of sFv-DT390 was 4.8 x 10(-11) M, 1/16 the potency of the divalent UCHT1-CRM9. More importantly, sFv-DT390 toxicity was only slightly affected by the anti-DT antibodies in human sera. C1 NIMH, MOLEC BIOL LAB, BIOPHYS CHEM SECT, BETHESDA, MD 20892 USA. NR 24 TC 37 Z9 38 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 24 PY 1995 VL 270 IS 47 BP 28037 EP 28041 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TG210 UT WOS:A1995TG21000013 PM 7499288 ER PT J AU LLOYD, AR BIRAGYN, A JOHNSTON, JA TAUB, DD XU, LL MICHIEL, D SPRENGER, H OPPENHEIM, JJ KELVIN, DJ AF LLOYD, AR BIRAGYN, A JOHNSTON, JA TAUB, DD XU, LL MICHIEL, D SPRENGER, H OPPENHEIM, JJ KELVIN, DJ TI GRANULOCYTE-COLONY-STIMULATING FACTOR AND LIPOPOLYSACCHARIDE REGULATE THE EXPRESSION OF INTERLEUKIN-8 RECEPTORS ON POLYMORPHONUCLEAR LEUKOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEUTROPHIL-ACTIVATING PROPERTIES; TUMOR-NECROSIS-FACTOR; FUNCTIONAL EXPRESSION; CHEMOTACTIC FACTOR; CYTOKINE FAMILY; HIGH-AFFINITY; SEQUENCE; SECRETE; CLONING; ALPHA AB Interleukin 8 (IL-8) is a potent chemoattractant and activating factor for human polymorphonuclear leukocytes (PMN) and hence plays a critical role in the pathogenesis of acute inflammation, Two unique but homologous receptors for IL-8 have been cloned (IL-8RA and -B), each of which binds the IL-8 ligand with high affinity, PMN stimulated by cytokines or lipopolysaccharide (LPS) exhibit changes in IL-8R mRNA and I-125-IL-8 binding, Granulocyte-colony stimulating factor (G-CSF) treatment of PMN enhances, and LPS inhibits, IL-8R mRNA expression, Similarly, I-125-IL-8 ligand binding to PMN is increased by G-CSF and decreased by LPS treatment, The stimulatory effect of G-CSF on IL-8R expression is transcriptional as it is inhibited by actinomycin D and is evident in nuclear run-on analyses. In contrast, LPS down-regulates IL-8R by both transcriptional and post-transcriptional mechanisms. The alterations in IL-8R expression are associated with similar changes in the IL-8-induced chemotactic responses of PMN. In conclusion, the two types of IL-8 receptor differ in their cellular distribution and are regulated in response to cytokines and LPS, Regulation of IL-8R expression by endogenous and exogenous immunomodulators may be important in the in vivo control of PMN effector functions in inflammation. C1 NCI,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. UNIV WESTERN ONTARIO,JOHN P ROBARTS RES INST,AUTOIMMUN GRP,LONDON,ON N6G 2V4,CANADA. NR 30 TC 99 Z9 100 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 24 PY 1995 VL 270 IS 47 BP 28188 EP 28192 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TG210 UT WOS:A1995TG21000036 PM 7499311 ER PT J AU YIM, HS KANG, SO HAH, YC CHOCK, PB YIM, MB AF YIM, HS KANG, SO HAH, YC CHOCK, PB YIM, MB TI FREE-RADICALS GENERATED DURING THE GLYCATION REACTION OF AMINO-ACIDS BY METHYLGLYOXAL - A MODEL STUDY OF PROTEIN-CROSS-LINKED FREE-RADICALS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NON-ENZYMATIC GLYCOSYLATION; DIABETES-MELLITUS; AUTOXIDATIVE GLYCOSYLATION; PHYSIOLOGICAL CONDITIONS; GLUCOSE AUTOXIDATION; HUMAN COLLAGEN; END-PRODUCTS; COMPLICATIONS; MECHANISM; N-EPSILON-(CARBOXYMETHYL)LYSINE AB The formation of alpha-dicarbonyl compounds seems to be an important step for cross-linking proteins in the glycation or Maillard reaction, To elucidate the mechanism for the cross linking reaction, we studied the reaction between a three-carbon alpha-dicarbonyl compound, methylglyoxal, and amino acids, Our results showed that this reaction generated yellow fluorescent products as formed in some glycated proteins, In addition, three types of free radical species were also produced, and their structures were determined by EPR spectroscopy, These free radicals are 1) the cross-linked radical cation, 2) the methylglyoxal radical anion as the counterion, and 3) the superoxide radical anion produced only in the presence of oxygen. The generation of the cross-linked radical cations and the methylglyoxal radical anions does not require metal ions or oxygens, These results indicate that dicarbonyl compounds cross-link free amino groups of protein by forming Schiff bases, which donate electrons directly to dicarbonyl compounds to form the cross-linked radical cations and the methylglyoxal radical anions, Oxygen can accept an electron from the radical anion to generate a superoxide radical anion, which can initiate damaging chain reactions, Time course studies suggest that the cross linked radical cation is a precursor of yellow fluorescent glycation end products. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. SEOUL NATL UNIV,COLL NAT SCI,DEPT MICROBIOL,SEOUL 151742,SOUTH KOREA. SEOUL NATL UNIV,MOLEC MICROBIOL RES CTR,SEOUL 151742,SOUTH KOREA. NR 43 TC 192 Z9 198 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 24 PY 1995 VL 270 IS 47 BP 28228 EP 28233 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TG210 UT WOS:A1995TG21000043 PM 7499318 ER PT J AU BOUVET, P MATSUMOTO, K WOLFFE, AP AF BOUVET, P MATSUMOTO, K WOLFFE, AP TI SEQUENCE-SPECIFIC RNA RECOGNITION BY THE XENOPUS Y-BOX PROTEINS - AN ESSENTIAL ROLE FOR THE COLD SHOCK DOMAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OOCYTE-SPECIFIC PROTEINS; MESSENGER-RNA; ESCHERICHIA-COLI; DNA-BINDING; CONSENSUS SEQUENCE; BACILLUS-SUBTILIS; TRANSCRIPTION; RIBONUCLEOPROTEIN; IDENTIFICATION; TRANSLATION AB The Xenopus Y-box protein FRGY2 has a role in the translational silencing of masked maternal mRNA. Here, we determine that FRGY2 will recognize specific RNA sequences. The evolutionarily conserved nucleic acid-binding cold shock domain is required for sequence-specific interactions with RNA. However, RNA binding by FRGY2 is facilitated by N- and C-terminal regions flanking the cold shock domain. The hydrophilic C-terminal tail domain of FRGY2 interacts with RNA independent of the cold shock domain but does not determine sequence specificity. Thus, both sequence-specific and nonspecific RNA recognition domains are contained within the FRGY2 protein. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. RI Matsumoto, Ken/F-9083-2013 OI Matsumoto, Ken/0000-0002-7864-3394 NR 39 TC 116 Z9 116 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 24 PY 1995 VL 270 IS 47 BP 28297 EP 28303 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TG210 UT WOS:A1995TG21000053 PM 7499328 ER PT J AU BERTHA, CM VILNER, BJ MATTSON, MV BOWEN, WD BECKETTS, K XU, H ROTHMAN, RB FLIPPENANDERSON, JL RICE, KC AF BERTHA, CM VILNER, BJ MATTSON, MV BOWEN, WD BECKETTS, K XU, H ROTHMAN, RB FLIPPENANDERSON, JL RICE, KC TI (E)-8-BENZYLIDENE DERIVATIVES OF 2-METHYL-5-(3-HYDROXYPHENYL)MORPHANS - HIGHLY SELECTIVE LIGANDS FOR THE SIGMA(2) RECEPTOR SUBTYPE SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GUINEA-PIG BRAIN; INDUCED NEURONAL ACTIVATION; OPIOID BINDING-SITES; ANTIPSYCHOTIC-DRUGS; OPIATE RECEPTOR; HIGH-AFFINITY; RAT-BRAIN; AUTORADIOGRAPHIC VISUALIZATION; PHENCYCLIDINE RECEPTOR; IMMUNE-SYSTEMS AB The determination of the structure and function of the sigma receptor subtypes and their physiological role(s) has been impeded by the unavailability of selective ligands. We have developed a new class of sigma subtype selective receptor ligands that are (E)-8-benzylidene derivatives of the synthetic opioid (+/-)-, (+)-, and (-)-2-methyl-5-(3-hydroxyphenyl)morphan-7-one (1). The derivatives can be prepared by reaction of 1, (+)-1, and (-)-1 with the appropriate benzaldehyde under Claisen-Schmidt conditions. Incorporation of substituted (E)-8-benzylidene moieties onto the 7-keto precursor of (+)-2-methyl-5-(3-hydroxyphenyl)morphan, (+)-1, produces compounds (-)-2 through (-)-7 (5.8-32.0 nM, sigma(1)), which have between a 25- and 131-fold increase in affinity for the sigma(1) receptor subtype relative to the keto precursor (+)-1 (K-i 762 nM, sigma(1)). Compound (-)-2 is the most selective of this group (16-fold) for the sigma(1) subtype versus sigma(2). Substitution of an (E)-8-benzylidene moiety onto the 7-keto precursor of(-)-2-methyl-5-(3-hydroxyphenyl)morphan, (-)-1, produces compounds (+)-2-(+)-9 (6.4-52.6 nM, sigma(2)), which have at least a 475-3906-fold increase in affinity for the sigma(2) receptor subtype relative to the keto precursor (-)-1 (K-i = 25 x 10(3) nM). This enhancement of sigma(2) receptor affinity is accompanied by substantial selectivity of all of these dextrorotatory products for the sigma(2) relative to the sigma(1) subtype (32-238-fold), and thus, they are among the most sigma(2) subtype selective compounds currently known. Furthermore, the sigma(1) subtype is highly enantioselective for the levorotatory isomers, (-)-2-(-)-7 (41-1034-fold), whereas the sigma(2) subtype is only somewhat enantioselective for the dextrorotatory isomers, (+)-2-(+)-7 (2.6-9.3-fold). All of these derivatives retain substantial affinity for the mu opioid receptor. Despite the high affinity of the dextrorotatory derivatives for the mu opioid receptor, the high affinity and selectivity for sigma(2) over sigma(1) sites will surely prove beneficial as tools for the delineation of the function and physiological role of sigma(2) receptors. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. NR 104 TC 13 Z9 15 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 24 PY 1995 VL 38 IS 24 BP 4776 EP 4785 DI 10.1021/jm00024a005 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA TH093 UT WOS:A1995TH09300005 PM 7490727 ER PT J AU ITOH, K STEVENS, B SCHACHNER, M FIELDS, RD AF ITOH, K STEVENS, B SCHACHNER, M FIELDS, RD TI REGULATED EXPRESSION OF THE NEURAL CELL-ADHESION MOLECULE L1 BY SPECIFIC PATTERNS OF NEURAL IMPULSES SO SCIENCE LA English DT Article ID MONOCLONAL-ANTIBODY; NERVOUS-SYSTEM; SCHWANN-CELLS; SURFACE; GROWTH; NEURONS; STEP; ACID AB Development of the mammalian nervous system is regulated by neural impulse activity, but the molecular mechanisms are not well understood. If cell recognition molecules [for example, L1 and the neural cell adhesion molecule (NCAM)] were influenced by specific patterns of impulse activity, cell-cell interactions controlling nervous system structure could be regulated by nervous system function at critical stages of development. Low frequency electrical pulses delivered to mouse sensory neurons in culture (0.1 hertz for 5 days) down-regulated expression of L1 messenger RNA and protein (but not NCAM). Fasciculation of neurites, adhesion of neuroblastoma cells, and the number of Schwann cells on neurites was reduced after 0.1-hertz stimulation, but higher frequencies or stimulation after synaptogenesis were without effect. C1 NICHHD,NEUROCYTOL & PHYSIOL UNIT,BETHESDA,MD 20892. ETH HONGGERBERG,DEPT NEUROBIOL,CH-8093 ZURICH,SWITZERLAND. NR 22 TC 139 Z9 140 U1 0 U2 3 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 24 PY 1995 VL 270 IS 5240 BP 1369 EP 1372 DI 10.1126/science.270.5240.1369 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF899 UT WOS:A1995TF89900042 PM 7481827 ER PT J AU ROSENBERG, PS AF ROSENBERG, PS TI SCOPE OF THE AIDS EPIDEMIC IN THE UNITED-STATES SO SCIENCE LA English DT Article ID INCUBATION PERIOD; HOMOSEXUAL MEN; HIV-INFECTION; SAN-FRANCISCO; COHORT; PREVALENCE; THERAPY; AGE AB Two-dimensional deconvolution techniques are used here to reconstruct age-specific human immunodeficiency virus(HIV) infection rates in the United States from surveillance data on acquired immunodeficiency syndrome (AIDS). This approach suggests that 630,000 to 897,000 adults and adolescents in the United States were living with HIV infection as of January 1993, including 107,000 to 150,000 women. The estimated incidence of HIV infection declined markedly over time among white males, especially those older than 30 years. In contrast, HIV incidence appears to have remained relatively constant among women and minorities. As of January 1993, prevalence was highest among young adults in their late twenties and thirties and among minorities. An estimated 3 percent of black men and 1 percent of black women in their thirties were living with HIV infection as of that date. If infection rates remain at these levels, HIV must be considered as endemic in the United States. RP ROSENBERG, PS (reprint author), NCI,ROCKVILLE,MD 20852, USA. NR 24 TC 146 Z9 148 U1 0 U2 1 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 24 PY 1995 VL 270 IS 5240 BP 1372 EP 1375 DI 10.1126/science.270.5240.1372 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF899 UT WOS:A1995TF89900043 PM 7481828 ER PT J AU PARSEGIAN, VA AF PARSEGIAN, VA TI SOLVATION - HOPES FOR HOFMEISTER SO NATURE LA English DT Editorial Material ID WATER; ASSOCIATION C1 NIDDKD,BETHESDA,MD 20892. RP PARSEGIAN, VA (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. NR 10 TC 56 Z9 58 U1 7 U2 23 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD NOV 23 PY 1995 VL 378 IS 6555 BP 335 EP 336 DI 10.1038/378335a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF893 UT WOS:A1995TF89300025 ER PT J AU BEZRUKOV, SM VODYANOY, I AF BEZRUKOV, SM VODYANOY, I TI NOISE-INDUCED ENHANCEMENT OF SIGNAL-TRANSDUCTION ACROSS VOLTAGE-DEPENDENT ION CHANNELS SO NATURE LA English DT Article ID ALAMETHICIN; CONDUCTANCE AB THE presence of noise in a signal transduction system usually interferes with its ability to transfer information reliably. But many nonlinear systems can use noise to enhance performance(1), and this phenomenon, called stochastic resonance, may underlie the extraordinary ability of some biological systems to detect and amplify small signals in noisy environments(2-5). Previous work has demonstrated the occurrence of stochastic resonance in a complex system of biological transducers and neural signal pathways(6), but the possibility that it could occur at the sub-cellular level has remained open. Here we report the observation of stochastic resonance in a system of voltage-dependent ion channels formed by the peptide alamethicin. A hundred-fold increase in signal transduction induced by external noise is accompanied by a growth in the output signal-to-noise ratio. The system of ion channels considered here represents the simplest biological system yet known to exhibit stochastic resonance. C1 OFF NAVAL RES, LONDON NW1 5TH, ENGLAND. ST PETERSBURG NUCL PHYS INST, GATCHINA 188350, RUSSIA. UCL, LONDON, ENGLAND. RP BEZRUKOV, SM (reprint author), NIH, DIV COMP RES & TECHNOL, BETHESDA, MD 20892 USA. NR 14 TC 290 Z9 292 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 23 PY 1995 VL 378 IS 6555 BP 362 EP 364 DI 10.1038/378362a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF893 UT WOS:A1995TF89300049 PM 7477370 ER PT J AU CHUANG, TK KILLAM, KF CHUANG, LF KUNG, HF SHENG, WS CHAO, CC YU, L CHUANG, RY AF CHUANG, TK KILLAM, KF CHUANG, LF KUNG, HF SHENG, WS CHAO, CC YU, L CHUANG, RY TI MU-OPIOID RECEPTOR GENE-EXPRESSION IN IMMUNE CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MORPHINE-SULFATE AB We have previously demonstrated that administering morphine sulfate to rhesus monkeys alters the cell-mediated as well as humoral immune responses of these primates. Furthermore, morphine treatment greatly reduces the chemotactic and phagocytotic activities of primate polymorphonuclear (PMN) cells. The present study describes the identification and isolation of mRNA encoding the mu opioid receptor gene sequence from human and monkey immune cells. Through the use of primer sequences designed from the human brain mu opioid receptor cDNA sequence, specific opioid receptor segments in mRNA transcripts were amplified, cloned, and sequenced. The mu opioid receptor gene was therefore found expressed in the following cell types: CEM x174 (a hybrid of human T and B cells), Raji (human B cells), human CD4(+) cells, human monocytes/macrophages, human PMN, monkey peripheral blood mononuclear cells (PBMC), and monkey PMN. These studies present the first evidence to demonstrate that cells of human and monkey immune systems constitutively express mil opioid receptor mRNA. (C) 1995 Academic Press, Inc. C1 UNIV CALIF DAVIS,DEPT MED PHARMACOL & TOXICOL,DAVIS,CA 95616. NCI,FREDERICK,MD 21701. MINNEAPOLIS MED RES FDN INC,MINNEAPOLIS,MN 55404. INDIANA UNIV,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN 46202. FU NIDA NIH HHS [DA05901, DA04381, DA09924] NR 24 TC 124 Z9 131 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 22 PY 1995 VL 216 IS 3 BP 922 EP 930 DI 10.1006/bbrc.1995.2709 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TF713 UT WOS:A1995TF71300026 PM 7488213 ER PT J AU CHEN, L WU, L OTAKA, A SMYTH, MS ROLLER, PP BURKE, TR DENHERTOG, J ZHANG, ZY AF CHEN, L WU, L OTAKA, A SMYTH, MS ROLLER, PP BURKE, TR DENHERTOG, J ZHANG, ZY TI WHY IS PHOSPHONODIFLUOROMETHYL PHENYLALANINE A MORE POTENT INHIBITORY MOIETY THAN PHOSPHONOMETHYL PHENYLALANINE TOWARD PROTEIN-TYROSINE PHOSPHATASES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SOLID-PHASE SYNTHESIS; PHOSPHOTYROSYL PEPTIDE; SH2 DOMAIN; PURIFICATION; ANALOGS; SPECIFICITY; PP60(C-SRC); EXPRESSION; RESIDUES; CLEAVAGE AB The phosphonodifluoromethyl phenylalanine (F(2)Pmp) is superior to phosphonomethyl phenylalanine (Pmp) as a non-hydrolyzable phosphotyrosine (pTyr) mimetic. The difluoromethyl moiety increases the inhibitory potency of a F(2)Pmp-containing peptide over a Pmp-containing counterpart by 1000-fold toward the protein tyrosine phosphatase (PTPase), PTP1. Fluorine substitution at the methylene carbon have the double effect of lowering the phosphonate pK(a2) as well as introducing hydrogen bonding interactions similar to the phosphate ester oxygen in pTyr. The inhibition of PTP1-catalyzed dephosphorylation reaction by both the F(2)Pmp and Pmp-containing peptides did not vary as a function of pH. The data indicate that both the monoanion and the dianion forms of the phosphonate bind PTP1 with equal efficiency. Thus, the better binding by the F(2)Pmp-peptide as compared to the Pmp-peptide is not due to the difference in pK(a2). Taken together, these results offer an explanation for the increased affinity of F(2)Pmp for PTP1. The two fluorine atoms in F(2)Pmp may be able to interact with active site residues in PTP1 in a fashion analogous to that involving the phenolic oxygen and side chains in the active site of PTP1. K-i measurements for a simple phosphonic acid, Pmp- and F(2)Pmp-containing peptides suggest that although the principal recognition element is F(2)Pmp itself, the surrounding amino acids are required for high affinity binding. Comparative analysis of the inhibition of PTP1, PTP alpha and LAR by F(2)Pmp-containing peptides suggests that selective, tight-binding PTPase inhibitors can be developed. (C) 1995 Academic Press, Inc. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MOLEC PHARMACOL,BRONX,NY 10461. NCI,DIV BASIC SCI,MED CHEM LAB,BETHESDA,MD 20892. NETHERLANDS INST DEV BIOL,HUBRECHT LAB,3584 CT UTRECHT,NETHERLANDS. RI Burke, Terrence/N-2601-2014 FU NIDDK NIH HHS [5P60 DK20541-17] NR 41 TC 122 Z9 123 U1 0 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 22 PY 1995 VL 216 IS 3 BP 976 EP 984 DI 10.1006/bbrc.1995.2716 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TF713 UT WOS:A1995TF71300033 PM 7488220 ER PT J AU OGAWA, Y LEI, PS KOVAC, P AF OGAWA, Y LEI, PS KOVAC, P TI SYNTHESIS OF THE 2-DEOXY ANALOG OF THE METHYL ALPHA-GLYCOSIDE OF THE MONOSACCHARIDE REPEATING UNIT OF THE O-POLYSACCHARIDE OF VIBRIO-CHOLERAE O/1 SO CARBOHYDRATE RESEARCH LA English DT Note DE POLYSACCHARIDE; VIBRIO CHOLERAE O/1; GLYCOSIDE; SYNTHESIS ID ANTIGENIC DETERMINANTS; BLOCK SYNTHESIS; LIPOPOLYSACCHARIDE; PENTASACCHARIDE; THIOGLYCOSIDE; BINDING C1 NIDDK,BETHESDA,MD 20892. NR 16 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV 22 PY 1995 VL 277 IS 2 BP 327 EP 331 DI 10.1016/0008-6215(95)00213-D PG 5 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA TF864 UT WOS:A1995TF86400011 PM 8556740 ER PT J AU OPTENBERG, SA THOMPSON, IM FRIEDRICHS, P WOJCIK, B STEIN, CR KRAMER, B AF OPTENBERG, SA THOMPSON, IM FRIEDRICHS, P WOJCIK, B STEIN, CR KRAMER, B TI RACE, TREATMENT, AND LONG-TERM SURVIVAL FROM PROSTATE-CANCER IN AN EQUAL-ACCESS MEDICAL-CARE DELIVERY SYSTEM SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RACIAL-DIFFERENCES; UNITED-STATES; BLACK; ADENOCARCINOMA; MORTALITY; STAGE; POPULATIONS; CARCINOMA; DIAGNOSIS; PATTERNS AB Objective.-To evaluate long-term survival of black and white prostate cancer patients in an equal-access medical care system to help distinguish biological from medical and social explanations of mortality differences. Design and Setting.-Retrospective study of US Department of Defense tumor registry patients with prostate cancer. Ethnicity, age, diagnosis, staging, risk factors, treatment, and survival end points were extracted. Patients.-Prostate cancer patients (N=1606; 7.5% black, 92.5% white) who were active-duty personnel, dependents, or retirees eligible for care in the military medical system. Main Outcome Measuress-Racial differences in tumor stage and grade, risk factors, recurrence, and treatment wait time (time between initial diagnosis and initial treatment); influence of stage, grade, treatment, wait time, age, and race on survival. Results.-No differences were found in behavioral risk factors or tumor grade or size, but blacks entered active treatment (P<.001) and exhibited a higher relative risk of cancer (P=.01) in younger age groups, presented with higher stage (P<.001), and demonstrated increased progression in distant metastatic disease (P=.01). No significant differences were detected in overall wait time. When adjusted for stage, no difference was found in type of treatment. Overall, stage, grade, and age were found to affect survival (P=.04 to P<.001), but race did not, When analyzed by stage, blacks demonstrated a clear trend of longer survival for distant metastatic disease (P=.04 to P=.06). This trend was confirmed using Kaplan-Meier estimates (P=.04, likelihood ratio), Conclusions.-This analysis suggests that in an equal-access medical care system there are no stage-specific differences in treatment between black and white prostate cancer patients, Survival among blacks is similar to that among whites and may surpass it for high-stage disease. C1 USA,MED DEPT CTR & SCH,CTR HLTHCARE EDUC & STUDIES,SAN ANTONIO,TX. BROOKE ARMY MED CTR,UROL SERV,SAN ANTONIO,TX. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD. NR 43 TC 179 Z9 182 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 22 PY 1995 VL 274 IS 20 BP 1599 EP 1605 DI 10.1001/jama.274.20.1599 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA TE738 UT WOS:A1995TE73800024 PM 7474244 ER PT J AU HU, Y KOSTOV, K PERICO, A SMITHLINE, S FREED, KF AF HU, Y KOSTOV, K PERICO, A SMITHLINE, S FREED, KF TI EXTENDED MOLECULAR-DYNAMICS AND OPTIMIZED ROUSE-ZIMM MODEL STUDIES OF A SHORT PEPTIDE - VARIOUS FRICTION APPROXIMATIONS SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID DILUTE POLYMER-SOLUTIONS; HYDROGEN-BOND INTERACTIONS; OCCURRING AMINO-ACIDS; VISCOELASTIC RELAXATION; SEGMENT ORIENTATION; NONBONDED INTERACTIONS; POLYPEPTIDE DYNAMICS; ENERGY PARAMETERS; FLUORESCENCE; MACROMOLECULES AB Developing a theory for the long time dynamics of polypeptides requires not only a proper choice of the relevant dynamic variables, but also a meaningful definition of friction coefficients for the individual atoms or groups of atoms in the reduced system. We test various aspects of the optimized Rouse-Zimm model for describing the long time rotational dynamics of a peptide fragment. The necessary equilibrium input information is constructed from a 1 ns molecular dynamics simulation for the solvated peptide by using a parallel Gray version of CHARMm, whose new features are described here. The simulations also provide time autocorrelation functions for comparisons with both theoretical predictions and with experiment. Two atomic friction models (van der Waals radii and accessible surface area) are chosen, and tests are made of the applicability of two combining rules for calculating the group friction coefficients. While the rotational dynamics of the peptide is insensitive to the friction models used, the combining rules are found to impact profoundly upon the theoretical descriptions for the behavior of the peptide dynamics for the reduced descriptions with fewer variables. The calculations study the role of the memory functions, neglected in this dynamical theory, and the interatomic hydrodynamic interactions in constructing the group friction coefficients. While the I ns trajectory is longer than customarily used for very complex systems, there are nontrivial influences of the duration of the molecular dynamics trajectory on the description of the dynamics. (C) 1995 American Institute of Physics. C1 UNIV CHICAGO,DEPT BIOCHEM & MOLEC BIOL,CHICAGO,IL 60637. UNIV CHICAGO,JAMES FRANCK INST,CHICAGO,IL 60637. NATL RES COUNCIL,INST STUDI CHIMICOFIS MACROMOLEC SINTETICHE & NAT,GENOA,ITALY. CRAY RES INC,EAGAN,MN 55121. UNIV CHICAGO,DEPT CHEM,CHICAGO,IL 60637. RP HU, Y (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. NR 39 TC 13 Z9 13 U1 0 U2 2 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD NOV 22 PY 1995 VL 103 IS 20 BP 9091 EP 9100 DI 10.1063/1.470020 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA TF298 UT WOS:A1995TF29800033 ER PT J AU MAZUMDER, A GAZIT, A LEVITZKI, A NICKLAUS, M YUNG, J KOHLHAGEN, G POMMIER, Y AF MAZUMDER, A GAZIT, A LEVITZKI, A NICKLAUS, M YUNG, J KOHLHAGEN, G POMMIER, Y TI EFFECTS OF TYRPHOSTINS, PROTEIN-KINASE INHIBITORS, ON HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE SO BIOCHEMISTRY LA English DT Article ID SITE-SPECIFIC HYDROLYSIS; DNA INTEGRATION; HIV DNA; ANTIPROLIFERATIVE AGENTS; INVITRO; IDENTIFICATION; RECOMBINATION; ALCOHOLYSIS; MECHANISM; CLEAVAGE AB Efficient replication of HIV-1 requires establishment of the proviral state, i.e., the integration of a DNA copy of the viral genome, synthesized by reverse transcriptase, into a chromosome of the host cell. Integration is catalyzed by the viral integrase protein. We have previously reported that phenolic moieties in compounds such as napthoquinones, flavones, caffeic acid phenethyl ester (CAPE), and curcumin confer inhibitory activity against HIV-1 integrase. We have extended these findings by examining the effects of tyrphostins, tyrosine kinase inhibitors. The catalytic activities of HIV-1 integrase and the formation of enzyme-DNA complexes using photocross-linking were examined. Both steps of the integration reaction, 3'-processing and strand transfer, were inhibited by tyrphostins at micromolar concentrations. The DNA binding activity of integrase was inhibited at higher concentrations of tyrphostins. Disintegration, an apparent reversal of the strand transfer reaction, catalyzed by an integrase mutant lacking the N-terminal zinc finger and C-terminal DNA binding domains is also inhibited by tyrphostins, indicating that the binding site for these compounds resides in the central catalytic core of HIV-1 integrase. Binding of tyrphostins at or near the integrase catalytic site was also suggested by experiments showing a global inhibition of the choice of attacking nucleophile in the 3'-processing reaction. None of the tyrphostins tested inhibited eukaryotic topoisomerase I, even at 100 mu M, suggesting selectivity for integrase inhibition. Molecular-modeling studies have revealed that, after energy minimization, several tyrphostins may adopt folded conformations. The similarity of the tyrphostin family to other families of inhibitors is discussed. Tyrphostins may provide lead compounds for development of novel antiviral agents for the treatment of acquired immunodeficiency syndrome based upon inhibition of HIV-1 integrase. C1 NCI,DIV BASIC SCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NCI,DIV BASIC SCI,MED CHEM LAB,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,DEPT ORGAN CHEM,JERUSALEM,ISRAEL. NR 53 TC 74 Z9 76 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 21 PY 1995 VL 34 IS 46 BP 15111 EP 15122 DI 10.1021/bi00046a018 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TF763 UT WOS:A1995TF76300018 PM 7578125 ER PT J AU RIVOLTA, MN URRUTIA, R KACHAR, B AF RIVOLTA, MN URRUTIA, R KACHAR, B TI SOLUBLE MOTOR FROM THE ALGA NITELLA SUPPORTS FAST MOVEMENT OF ACTIN-FILAMENTS IN-VITRO SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Note DE ACTIN; MYOSIN; MOTILITY; VIDEO MICROSCOPY ID MYOSIN; BINDING AB In the streaming cytoplasm of the Characean algae cell, the movement of organelles along actin bundles occurs at a striking rate of up to 60 mu m s(-1). To further characterize the molecular mechanisms responsible for this phenomenon, we have reconstituted the movement of actin filaments in vitro using defined biochemical components. We report that only a soluble cytoplasmic fraction devoid of organelles and filamentous material supports the movement of fluorescent-labeled actin filaments on glass at a rate of up to 60 mu m s(-1) This fraction also contains the K+-EDTA ATPase and the actin-activated Mg2+ ATPase activities characteristic of myosin proteins. Therefore, on the basis of these observations, we conclude that Nitella cells have a soluble pool of non-filamentous myosin molecules with the mechanochemical properties expected for a motor responsible for cytoplasmic streaming in vivo. The preparation and conditions described here should be useful for the purification of this translocator. C1 NIDCD,CELLULAR BIOL LAB,ROCKVILLE,MD 20850. MAYO CLIN,CTR BASIC RES DIGEST DIS,ROCHESTER,MN 55905. FU NINDS NIH HHS [NS 32882-01] NR 12 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD NOV 21 PY 1995 VL 1232 IS 1-2 BP 1 EP 4 DI 10.1016/0005-2728(95)00107-1 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TJ290 UT WOS:A1995TJ29000001 PM 7495833 ER PT J AU EHRLICH, A BARNETT, VA CHEN, HC SCHOENBERG, M AF EHRLICH, A BARNETT, VA CHEN, HC SCHOENBERG, M TI THE SITE AND STOICHIOMETRY OF THE N-PHENYLMALEIMIDE REACTION WITH MYOSIN WHEN WEAKLY-BINDING CROSSBRIDGES ARE FORMED IN SKINNED RABBIT PSOAS FIBERS SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article DE MUSCLE; ALKYLATION; ESSENTIAL SULFHYDRYL; MYOSIN HEAVY CHAIN ID AMINO-ACID-SEQUENCE; SKELETAL-MUSCLE; HEAVY-CHAIN; SUBFRAGMENT-1; NUCLEOTIDE; ACTIN; FRAGMENT; SH1 AB Treatment of relaxed skinned rabbit psoas muscle fibers with 0.1 mM N-phenylmaleimide (NPM) for 1 h locks all of the crossbridges in a weakly-binding state resembling that of the myosin ATP crossbridge. Under these conditions, NPM reacts mainly with myosin heavy chain (Barnett et al. (1992) Biophys. J. 61, 358-367). Here the specific sites for that reaction are explored. Small bundles of rabbit psoas muscle fibers were treated with Triton X-100 to make the fiber sarcolemmas permeable. The bundles were treated with 0.1 mM [C-14]NPM for 1 h, and homogenized for SDS-PAGE. 43 +/- 2.2% of the muscle fiber protein ran in the myosin heavy chain band, the same as for untreated fibers. An alkylating stoichiometry of 2.2 +/- 0.33 moles NPM per mole myosin heavy chain was determined. Exhaustive trypsin digestion followed by two-dimensional thin-layer chromatography and reverse-phase HPLC revealed two major sites on myosin heavy chain for NPM binding, The sites contained about the same amount of linked NPM, suggesting that the reaction stoichiometry of each site under the conditions studied is approx. 1 mol NPM/mol myosin heavy chain, Comparison of the labeled tryptic peptides with NPM-reacted synthetic SH1 and SH2 tryptic peptides and analysis of the treated Fiber bundles' ATPase activity suggested that the sites for NPM reaction on myosin heavy chain when it locks crossbridges in a weakly-binding state are Cys-697 (SH2) and Cys-707 (SH1). C1 NIAMSD,PHYS BIOL LAB,BETHESDA,MD 20892. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. FU NCRR NIH HHS [1 S10RR05554-01] NR 29 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD NOV 21 PY 1995 VL 1232 IS 1-2 BP 13 EP 20 DI 10.1016/0005-2728(95)00094-6 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TJ290 UT WOS:A1995TJ29000003 PM 7495834 ER PT J AU VONAGOSTON, D PALKOVITS, CG FITZGERALD, SF BRENNEMAN, DE AF VONAGOSTON, D PALKOVITS, CG FITZGERALD, SF BRENNEMAN, DE TI DEVELOPMENTAL-CHANGES IN THE INDUCIBILITY OF FOS-LIKE IMMUNOREACTIVITY IN PRIMARY EMBRYONIC SPINAL-CORD CULTURES SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE FOS; IMMEDIATE EARLY GENE; ONTOGENY; EPIGENETIC SIGNAL; SPINAL CORD NEURON; MOUSE ID IMMEDIATE-EARLY GENES; NERVE GROWTH-FACTOR; MULTIPLE SIGNALING PATHWAYS; SENSITIVE CALCIUM CHANNELS; DEPENDENT PROTEIN-KINASE; RAT CEREBRAL-CORTEX; C-FOS; HIPPOCAMPAL-NEURONS; CORTICAL-NEURONS; BINDING-SITES AB The immediate early gene (IEG) transcription factor c-fos coordinates changes in the pattern of long term gene expression and, therefore, it may be involved in mediating epigenetic control during neurodevelopment. We used pharmacological treatments mimicking various environmental and intracellular signals and assessed the inducibility of fos-like immunoreactivity (LIR) at various stages of neurodifferentiation in a primary embryonic spinal cord culture system by immunohistochemistry. Constitutive fos LIR exclusively found in neurons, was driven by the onset and extent of spontaneous electrical activity, as it was blockable by tetrodotoxin (TTX) at all developmental stages. Phorbol myristate 13 acetate (PMA) increased the number of fos-LIR cells equally effectively at all stages, but the predominant cellular localization of fos-LIR changed through ontogeny. The effect of veratridine, kainate and serum-derived factors in significantly inducing fos-LIR was restricted to the earliest developmental stage (4 days in vitro; DIV) investigated; whereas forskolin, the GABA(A) antagonist picrotoxin and NMDA failed to induce fos-LIR at this stage, but increased the number of fos-LIR neurons at later stages. Dihydropyridine agonists of the voltage-sensitive calcium channels (VSCC) raised the number of fos-LIR neurons and also prevented ?TX-mediated down-regulation; whereas antagonists markedly reduced fos-LIR at all ages. Either type of NMDA antagonists (AP5 and MK801) and the GABA(A) agonist muscimol significantly reduced fos-LIR at all ages. These findings demonstrate that the inducibility of fos-LIR is substantially different in embryonic neurons than in adult ones and that inducibility by various first and second messengers is dependent on the developmental stage. C1 NICHHD, DEV MOLEC PHARMACOL SECT, BETHESDA, MD 20892 USA. RP NICHHD, DEV NEUROBIOL LAB,MCN,NIH BLDG 49,ROOM 5A38, 49 CONVENT DR MSC 4480, BETHESDA, MD 20892 USA. NR 87 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD NOV 21 PY 1995 VL 89 IS 2 BP 173 EP 186 PG 14 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA TG034 UT WOS:A1995TG03400003 ER PT J AU COLLINS, FS AF COLLINS, FS TI AHEAD OF SCHEDULE AND UNDER BUDGET - THE GENOME PROJECT PASSES ITS 5TH BIRTHDAY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material RP COLLINS, FS (reprint author), NIH,NATL CTR HUMAN GENOME RES,31 CTR DR,BLDG 31,ROOM 4B09,BETHESDA,MD 20892, USA. NR 14 TC 22 Z9 23 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 NOV 21 PY 1995 VL 92 IS 24 BP 10821 EP 10823 DI 10.1073/pnas.92.24.10821 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100002 PM 7479891 ER PT J AU GUYER, MS COLLINS, FS AF GUYER, MS COLLINS, FS TI HOW IS THE HUMAN GENOME PROJECT DOING, AND WHAT HAVE WE LEARNED SO FAR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Review ID EXPRESSED SEQUENCE TAGS; POSITIONAL CLONING; MYOTONIC-DYSTROPHY; DNA POLYMORPHISMS; RET PROTOONCOGENE; POINT MUTATION; CTG REPEAT; GENE; CLONES; REGION AB In this paper, we describe the accomplishments of the initial phase of the Human Genome Project, with particular attention to the progress made toward achieving the defined goals for constructing genetic and physical maps of the human genome and determining the sequence of human DNA, identifying the complete set of human genes, and analyzing the need for adequate policies for using the information about human genetics in ways that maximize the benefits for individuals and society. RP GUYER, MS (reprint author), NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 92 TC 52 Z9 52 U1 1 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 NOV 21 PY 1995 VL 92 IS 24 BP 10841 EP 10848 DI 10.1073/pnas.92.24.10841 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100006 PM 7479895 ER PT J AU DIETRICH, WF COPELAND, NG GILBERT, DJ MILLER, JC JENKINS, NA LANDER, ES AF DIETRICH, WF COPELAND, NG GILBERT, DJ MILLER, JC JENKINS, NA LANDER, ES TI MAPPING THE MOUSE GENOME - CURRENT STATUS AND FUTURE-PROSPECTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Review ID GENETIC-LINKAGE MAP; YEAST ARTIFICIAL CHROMOSOME; POLYMERASE CHAIN-REACTION; INTERSPECIFIC BACKCROSS; DNA POLYMORPHISMS; ARBITRARY PRIMERS; INBRED STRAINS; PCR; IDENTIFICATION; CONSTRUCTION AB The mouse is the best model system for the study of mammalian genetics and physiology, Because of the feasibility and importance of studying genetic crosses, the mouse genetic map has received tremendous attention in recent years, It currently contains over 14,000 genetically mapped markers, including 700 mutant loci, 3500 genes, and 6500 simple sequence length polymorphisms (SSLPs). The mutant loci and genes allow insights and correlations concerning physiology and development. The SSLPs provide highly polymorphic anchor points that allow inheritance to be traced in any cross and provide a scaffold for assembling physical maps, Adequate physical mapping resources-notably large-insert yeast artificial chromosome (YAC) libraries-are available to support positional cloning projects based on the genetic map, but a comprehensive physical map is still a few years away. Large-scale sequencing efforts have not yet begun in mouse, but comparative sequence analysis between mouse and human is Likely to provide tremendous information about gene structure and regulation. C1 MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE CTR 9,CAMBRIDGE,MA 02142. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,BASIC RES PROGRAM,ADV BIOSCI LABS,FREDERICK,MD 21702. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. NR 68 TC 46 Z9 50 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 21 PY 1995 VL 92 IS 24 BP 10849 EP 10853 DI 10.1073/pnas.92.24.10849 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100007 PM 7479896 ER PT J AU KINTER, AL BENDE, SM HARDY, EC JACKSON, R FAUCI, AS AF KINTER, AL BENDE, SM HARDY, EC JACKSON, R FAUCI, AS TI INTERLEUKIN-2 INDUCES CD8(+) T-CELL-MEDIATED SUPPRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION IN CD4(+) T-CELLS AND THIS EFFECT OVERRIDES ITS ABILITY TO STIMULATE VIRUS EXPRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTI-HIV ACTIVITY; CD8+ LYMPHOCYTES; INFECTION; RECEPTOR; INVITRO; DISEASE; IL-12 AB The nonlytic suppression of human immunodeficiency virus (HIV) production from infected CD4(+) T cells by CD8(+) lymphocytes from HIV-infected individuals is one of the most potent host-mediated antiviral activities observed in vitro. We demonstrate that the pleiotropic cytokine interleukin 2 (IL-2), but not IL-12, is a potent inducer of the CD8(+) HIV suppressor phenomenon. IL-2 induces HIV expression in peripheral blood or lymph node mononuclear cells from HIV-infected individuals in the absence of CD8(+) T cells. However, IL-2 induces CD8(+) T cells to suppress HIV expression when added back to these cultures, and this effect dramatically supersedes the ability of IL-2 to induce HIV expression. Five to 25 times fewer CD8(+) cells were required to obtain comparable levels of inhibition of viral production if they were activated in the presence of IL-2 as compared with IL-12 or no exogenous cytokine. Furthermore, IL-2 appeared either to induce a qualitative increase in HIV suppressor cell activity or to increase the relative frequency of suppressor cells in the activated (CD25(+)) CD8(+) populations. Analyses of proviral levels in peripheral blood mononuclear cells suggest that CD8(+) T cell-mediated lysis of in vivo infected cells is not induced by IL-2. These results have implications for our understanding of the effects of impaired IL-2 production during HIV disease as well as the overall effects of IL-2-based immunotherapy on HIV replication in vivo. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 23 TC 71 Z9 71 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 21 PY 1995 VL 92 IS 24 BP 10985 EP 10989 DI 10.1073/pnas.92.24.10985 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100034 PM 7479922 ER PT J AU WENG, NP LEVINE, BL JUNE, CH HODES, RJ AF WENG, NP LEVINE, BL JUNE, CH HODES, RJ TI HUMAN NAIVE AND MEMORY T-LYMPHOCYTES DIFFER IN TELOMERIC LENGTH AND REPLICATIVE POTENTIAL SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN FIBROBLASTS; CELLS; SUBSETS AB The present study has assessed the replicative history and the residual replicative potential of human naive and memory T cells, Telomeres are unique terminal chromosomal structures whose length has been shown to decrease with cell division in vitro and with increased age in vivo for human somatic cells, We therefore assessed telomere length as a measure of the in vivo replicative history of naive and memory human T cells. Telomeric terminal restriction fragments were found to be 1.4 +/- 0.1 kb longer in CD4(+) naive T cells than in memory cells from the same donors, a relationship that remained constant over a wide range of donor age. These findings suggest that the differentiation of memory cells from naive precursors occurs with substantial clonal expansion and that the magnitude of this expansion is, on average, similar over a wide range of age. In addition, when replicative potential was assessed in vitro, it was found that the capacity of naive cells for cell division,vas 128-fold greater as measured in mean population doublings than the capacity of memory cells from the same individuals. Human CD4(+) naive and memory cells thus differ in in vivo replicative history, as reflected in telomeric length, and in their residual replicative capacity. C1 NIA,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. RP WENG, NP (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. RI Levine, Bruce/D-1688-2009; Slagboom, P. Eline/R-4790-2016 OI Slagboom, P. Eline/0000-0002-2875-4723 NR 23 TC 306 Z9 312 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 21 PY 1995 VL 92 IS 24 BP 11091 EP 11094 DI 10.1073/pnas.92.24.11091 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100056 PM 7479943 ER PT J AU GNABRE, JN BRADY, JN CLANTON, DJ ITO, Y DITTMER, J BATES, RB HUANG, RCC AF GNABRE, JN BRADY, JN CLANTON, DJ ITO, Y DITTMER, J BATES, RB HUANG, RCC TI INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TRANSCRIPTION AND REPLICATION BY DNA SEQUENCE-SELECTIVE PLANT LIGNANS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTI-HUMAN IMMUNODEFICIENCY VIRUS; SP1 SITE-SPECIFIC; 3'-O-METHYLNORDIHYDROGUAIARETIC ACID ID INVITRO; EXPRESSION; CELLS AB A plant lignan, 3'-O-methyl nordihydroguaiaretic acid (3'-O-methyl NDGA, denoted Malachi 4:5-6 or Mal.4; molecular weight 316), was isolated from Larrea tridentata and found to be able to inhibit human immunodeficiency virus (HIV) Tat-regulated transactivation in vivo, induce protection of lymphoblastoid CEM-SS cells from HIV (strain IIIB) killing, and suppress the replication of five HIV-1 strains (WM, MN, VS, JR-CSF, and IlI(B)) in mitogen-stimulated peripheral blood mononuclear cells, all in a dose-dependent manner. Mal.4 inhibits both basal transcription and Tat-regulated transactivation in vitro. The target of Mal.4 has been localized to nucleotides -87 to -40 of the HIV long terminal repeat, Mal.4 directly and specifically interferes with the binding of Spl to Spl sites in the HIV long terminal repeat, By inhibiting proviral expression, Mal.4 may be able to interrupt the life cycles of both wild-type and reverse transcriptase or protease mutant viruses in HIV-infected patients. C1 JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. UNIV ARIZONA,DEPT CHEM,TUCSON,AZ 85721. RI Dittmer, Juergen/G-1160-2011 FU PHS HHS [5RO132301] NR 29 TC 68 Z9 72 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 NOV 21 PY 1995 VL 92 IS 24 BP 11239 EP 11243 DI 10.1073/pnas.92.24.11239 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100086 PM 7479972 ER PT J AU PARK, SJ SADEGHNASSERI, S WILEY, DC AF PARK, SJ SADEGHNASSERI, S WILEY, DC TI INVARIANT CHAIN MADE IN ESCHERICHIA-COLI HAS AN EXPOSED N-TERMINAL SEGMENT THAT BLOCKS ANTIGEN-BINDING TO HLA-DR1 AND A TRIMERIC C-TERMINAL SEGMENT THAT BINDS EMPTY HLA-DR1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II; ANTIGEN PROCESSING ID CLASS-II MOLECULES; ALPHA-BETA-HETERODIMERS; HLA-DR; ENDOPLASMIC-RETICULUM; MICE LACKING; PEPTIDES; TRANSPORT; COMPARTMENTS; ASSOCIATION; EXPRESSION AB Invariant chain (Ii), a membrane glycoprotein, binds class II major histocompatibility complex (MHC) glycoproteins, probably via its class II-associated Ii peptide (CLIP) segment, and escorts them toward antigen-containing endosomal compartments, We find that a soluble, trimeric ectodomain of Ii expressed and purified from Escherichia coli blocks peptide binding to soluble HLA-DR1. Proteolysis indicates that Ii contains two structural domains, The C-terminal two-thirds forms an alpha-helical domain that trimerizes and interacts with empty HLA-DR1 molecules, augmenting rather than blocking peptide binding, The N-terminal one-third, which inhibits peptide binding, is proteolytically susceptible over its entire length, In the trimer, the N-terminal domains act independently,vith each CLIP segment exposed and free to bind an MHC class II molecule, while the C-terminal domains act as a trimeric unit. C1 HARVARD UNIV,DEPT MOLEC & CELLULAR BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02138. NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892. OI Sadegh-Nasseri, Scheherazade/0000-0002-8127-1720 NR 41 TC 45 Z9 45 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 NOV 21 PY 1995 VL 92 IS 24 BP 11289 EP 11293 DI 10.1073/pnas.92.24.11289 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TF891 UT WOS:A1995TF89100096 PM 7479981 ER PT J AU KENWORTHY, L CHARNAS, L AF KENWORTHY, L CHARNAS, L TI EVIDENCE FOR A DISCRETE BEHAVIORAL-PHENOTYPE IN THE OCULOCEREBRORENAL SYNDROME OF LOWE SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE AGGRESSION; BEHAVIOR; MANNERISMS; STEREOTYPY; TANTRUMS ID FRAGILE-X SYNDROME; LINKED MENTAL-RETARDATION; AUTISTIC DISORDER; CLOMIPRAMINE; DESIPRAMINE; CHECKLIST; CHILDREN; GENE; FAMILIES AB The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by congenital cataracts, cognitive impairment, and renal tubular dysfunction. Although there is a wide range of intellectual function in affected individuals, it is often compromised by a high prevalence of maladaptive behaviors, including tantrums, stubbornness, and stereotypy. Whether these behaviors simply reflect the multiple disabilities found in some developmentally impaired individuals with or without OCRL, or a specific genetically-determined behavioral phenotype of OCRL, is unknown. Controls were matched for sex, age, visual impairment, and adaptive functioning and compared with OCRL patients on three standardized measures of adaptive/maladaptive behaviors. Forty-three matched pairs of OCRL and control subjects were identified. Both groups were similar in communication, daily living, socialization, and motor skills, in socioeconomic status, and in measures of parental stress. Individuals with OCRL displayed significantly more severe maladaptive behaviors than control boys, as measured by the Vineland Adaptive Behavior Scales (VABS), with 41% of the difference between the two groups attributable to the diagnosis of OCRL. Twelve maladaptive behaviors measured on the VABS appeared more frequently in OCRL than in controls. Five of these 12 behaviors, i.e., temper tantrums, irritability, complex repetitive behaviors (stereotypy)/mannerisms, obsessions/unusual preoccupations, and negativism, were identified by discriminant function analysis to significantly distinguish between controls and OCRL individuals. The diagnosis of OCRL is associated with a behavioral phenotype consisting of temper tantrums, stereotypy, stubbornness, and obsessions/unusual preoccupations. This phenotype cannot be attributed solely to the visual, motor, and intellectual disabilities characteristic of OCRL, and may represent a specific effect of the OCRL gene on the central nervous system. (C) 1995 Wiley-Liss, Inc. C1 NICHHD,HUMAN GENET BRANCH,NEUROGENET UNIT,BETHESDA,MD 20892. NR 57 TC 17 Z9 17 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 20 PY 1995 VL 59 IS 3 BP 283 EP 290 DI 10.1002/ajmg.1320590304 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA TE948 UT WOS:A1995TE94800003 PM 8599350 ER PT J AU FUJIMOTO, A TAYEBI, N SIDRANSKY, E AF FUJIMOTO, A TAYEBI, N SIDRANSKY, E TI CONGENITAL ICHTHYOSIS PRECEDING NEUROLOGIC SYMPTOMS IN 2 SIBS WITH TYPE-2 GAUCHER-DISEASE SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE COLLODION BABY; GLUCOCERBROSIDASE DEFICIENCY; EPIDERMAL ABNORMALITIES ID GLUCOCEREBROSIDASE GENE; TARGETED DISRUPTION; BARRIER FUNCTION; MODEL AB We describe 2 sibs who presented with ichthyotic skin at birth and subsequently developed neurologic manifestations of type 2 Gaucher disease. Type 2 Gaucher patients with and without ichthyosis manifest ultrastructural and biochemical abnormalities in the epidermis. The 2 patients described here clearly demonstrate that epidermal involvement in type 2 Gaucher disease may precede neurologic symptoms and substantiate the prognostic significance of early skin abnormalities in Gaucher patients. Gaucher disease should be considered in the differential diagnosis of congenital ichthyosis, even if the scaling resolves spontaneously. (C) 1995 Wiley-Liss, Inc. C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. UNIV SO CALIF,SCH MED,DEPT PEDIAT,DIV GENET,LOS ANGELES,CA 90033. NR 18 TC 23 Z9 23 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 20 PY 1995 VL 59 IS 3 BP 356 EP 358 DI 10.1002/ajmg.1320590315 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA TE948 UT WOS:A1995TE94800014 PM 8599361 ER PT J AU WARNER, DR BASI, NS REBOIS, RV AF WARNER, DR BASI, NS REBOIS, RV TI CELL-FREE SYNTHESIS OF FUNCTIONAL TYPE-IV ADENYLYL-CYCLASE SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID BETA-GAMMA-SUBUNITS; PROTEINS AB Type IV adenylyl cyclase was synthesized in a cell-free coupled transcription and translation system. Radiolabeled type TV adenylyl cyclase was specifically immune precipitated with anti-ACIV antibodies. The molecular weight of in vitro translated type IV adenylyl cyclase was 110,000, similar to that for type IV adenylyl cyclase produced in the baculovirus system [B. Gao and A. G;. Gilman, (1991) Proc. Natl. Acad. Sci. USA 88, 10178-10182]. Dimyristoyl phosphatidylcholine was required for efficient stimulation of activity by both forskolin and Gs, with a maximum specific activity of 700 +/- 100 nmol cAMP . min(-1). mg(-1) attained with both effecters combined, Both bovine brain Gs and in vitro translated Gs alpha activated in vitro translated type IV adenylyl cyclase; however, G beta gamma only enhanced stimulation in the presence of in vitro translated Gs alpha. Forskolin maximally activated at concentrations from 200 to 400 mu M in the absence or presence of Gs The in vitro translated product was very stable as production of cAMP by forskolin/G(s) activated type IV adenylyl cyclase was linear for up to 90 min at 30 degrees C. (C) 1995 Academic Press, Inc. C1 NIH,BETHESDA,MD 20892. NR 15 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 20 PY 1995 VL 232 IS 1 BP 31 EP 36 DI 10.1006/abio.1995.9965 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA TG921 UT WOS:A1995TG92100004 PM 8600828 ER PT J AU TRINH, L SHILOACH, J AF TRINH, L SHILOACH, J TI RECOVERY OF INSECT CELLS USING HOLLOW-FIBER MICROFILTRATION SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article; Proceedings Paper CT 7th International Conference on Recovery of Biological Products CY SEP 25-30, 1994 CL SAN DIEGO, CA SP Engn Fdn, Amer Chem Soc DE INSECT CELLS; MICROFILTRATION; HOLLOW FIBER ID FILTRATION; PROTEINS; CULTURES AB An efficient method was developed for media separation and cell collection for eukaryotic cells growing in suspension. The method is based on tangential flow microfiltration using an open channel arrangement in a hollow fiber configuration. Best results (highest processing flux rate) for polysulfone hollow fibers were obtained using fibers with internal diameter of 0.75 mm, 0.45 mu m pore size, and a cell suspension flow at a shear rate of 14000 s(-1) (0.032 L/min per fiber). A flux rate of 500 L/m(2) h can be obtained by maintaining the surface area/cell ratio at 0.05 m(2)/10 L of cells at a concentration of 2.5 x 10(6) cells/mL. Forty liters of infected insect cells can be concentrated 10 times in 20 min without affecting cell viability. (C) 1995 John Wiley & Sons, Inc. C1 NIDDK,BIOTECHNOL UNIT,BETHESDA,MD 20892. NR 16 TC 5 Z9 5 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD NOV 20 PY 1995 VL 48 IS 4 BP 401 EP 405 DI 10.1002/bit.260480412 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA TB190 UT WOS:A1995TB19000011 PM 18623500 ER PT J AU REN, K THOMAS, DA DUBNER, R AF REN, K THOMAS, DA DUBNER, R TI NERVE GROWTH-FACTOR ALLEVIATES A PAINFUL PERIPHERAL NEUROPATHY IN RATS SO BRAIN RESEARCH LA English DT Article DE NERVE GROWTH FACTOR; NEUROPATHIC PAIN; OSMOTIC PUMP; THERMAL HYPERALGESIA; MECHANICAL ALLODYNIA; RAT ID DORSAL-ROOT GANGLION; ADULT SENSORY NEURONS; SCIATIC-NERVE; SPONTANEOUS DISCHARGE; SUBSTANCE-P; SPINAL-CORD; FIBER LOSS; HYPERALGESIA; TRANSPORT; INJURY AB Nerve growth factor (NGF) reverses some effects of axotomy and prevents toxic neuropathy in adult rodents. We tested the effect of NGF on behavioral hyperalgesia resulting from a chronic constriction injury (CCI) of the sciatic nerve in the rat [5]. CCI rats exhibit thermal hyperalgesia as demonstrated by a reduction of paw withdrawal latency to a noxious thermal stimulus applied to the paw on the side of injury. The mechanical sensitivity of the ipsilateral hindpaw, assessed with von Frey filaments, was also significantly increased. There were no significant changes in nociceptive thresholds on the contralateral side. When NGF was infused directly on the ligated nerve via an osmotic pump (0.5 mu g/mu l/h for 7 days) immediately after the ligation, thermal hyperalgesia was abolished from postoperative days 5 up to at least two weeks. The CCI-induced decrease in mechanical threshold was also abolished by NGF. However, NGF had only a minor effect on the abnormally long response duration, a second measure of mechanical sensitivity, to the mechanical stimulus. Delayed infusion of NGF four days after the ligation failed to block hyperalgesia. Infusion of NGF on the sciatic nerve of rats that had no CCI had no significant effect on paw withdrawal latency. Infusion of anti-NGF antiserum did not enhance hyperalgesia in CCI rats. These results suggest that alterations in neurotrophic factor(s) contribute to the development of behavioral hyperalgesia in an animal model of neuropathy and that NGF may have therapeutic value in the treatment of neuropathic pain in humans. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NR 43 TC 59 Z9 61 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 20 PY 1995 VL 699 IS 2 BP 286 EP 292 DI 10.1016/0006-8993(95)00920-L PG 7 WC Neurosciences SC Neurosciences & Neurology GA TF869 UT WOS:A1995TF86900015 PM 8616632 ER PT J AU REINER, O BARAM, I SAPIR, T SHMUELI, O CARROZZO, R LINDSAY, EA BALDINI, A LEDBETTER, DH CAHANA, A AF REINER, O BARAM, I SAPIR, T SHMUELI, O CARROZZO, R LINDSAY, EA BALDINI, A LEDBETTER, DH CAHANA, A TI LIS2, GENE AND PSEUDOGENE, HOMOLOGOUS TO LIS1 (LISSENCEPHALY-1), LOCATED ON THE SHORT AND LONG ARMS OF CHROMOSOME-2 SO GENOMICS LA English DT Article ID CLONES; PROTEIN; PCR AB We report here the isolation of a novel cDNA, designated LIS2, that maps to chromosome 2p11.2 by in situ hybridization and demonstrates extremely high sequence similarity to the recently identified LIS1 gene involved in Miller-Dieker lissencephaly at 17p13.3. Specific probes for LIS2 revealed a pattern of expression resembling that of LIS1, although LIS2 is less abundant. Surprisingly, LIS2 detected an additional, higher molecular weight transcript in adult skeletal muscle. Isolated YAC clones and P1 clones mapped by in situ hybridization to two loci on chromosome 2, 2p11.2 and 2q13-q14. This hybridization was due to the existence of LIS2 pseudogene LIS2P on the long arm of chromosome 2. (C) 1995 Academic Press, Inc. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT MED,IL-69978 RAMAT AVIV,ISRAEL. IST GIANNINA GASLINI,MED LAB 2,I-16145 GENOA,ITALY. BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP REINER, O (reprint author), WEIZMANN INST SCI,DEPT MOLEC GENET & VIROL,IL-76100 REHOVOT,ISRAEL. RI genes, anthony/F-2541-2012 NR 24 TC 19 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 20 PY 1995 VL 30 IS 2 BP 251 EP 256 DI 10.1006/geno.1995.9880 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TG447 UT WOS:A1995TG44700014 PM 8586424 ER PT J AU HANNENHALLI, S CHAPPEY, C KOONIN, EV PEVZNER, PA AF HANNENHALLI, S CHAPPEY, C KOONIN, EV PEVZNER, PA TI GENOME SEQUENCE COMPARISON AND SCENARIOS FOR GENE REARRANGEMENTS - A TEST-CASE SO GENOMICS LA English DT Article ID EPSTEIN-BARR-VIRUS; VARICELLA-ZOSTER VIRUS; COMPLETE DNA-SEQUENCE; MITOCHONDRIAL GENOME; HERPESVIRUS SAIMIRI; HUMAN CYTOMEGALOVIRUS; BOVINE HERPESVIRUS-1; UNIQUE REGION; EVOLUTION; SEGMENTS AB As large portions of related genomes are being sequenced, methods for comparing complete or nearly complete genomes, as opposed to comparing individual genes, are becoming progressively more important. A major, widespread phenomenon in genome evolution is the rearrangement of genes and gene blocks. There is, however, no consistent method for genome sequence comparison combined with the reconstruction of the evolutionary history of highly rearranged genomes. We developed a schema for genome sequence comparison that includes three successive steps: (i) comparison of all proteins encoded in different genomes and generation of genomic similarity plots; (ii) construction of an alphabet of conserved genes and gene blocks; and (iii) generation of most parsimonious genome rearrangement scenarios. The approach is illustrated by a comparison of the herpesvirus genomes that constitute the largest set of relatively long, complete genome sequences available to date. Herpesviruses have from 70 to about 200 genes; comparison of the amino acid sequences encoded in these genes results in an alphabet of about 30 conserved genes comprising 7 conserved blocks that are rearranged in the genomes of different herpesviruses. Algorithms to analyze rearrangements of multiple genomes were developed and applied to the derivation of most parsimonious scenarios of herpesvirus evolution under different evolutionary models. The developed approaches to genome comparison will be applicable to the comparative analysis of bacterial and eukaryotic genomes as soon as their sequences become available. (C) 1995 Academic Press,Inc. C1 PENN STATE UNIV, DEPT COMP SCI & ENGN, UNIVERSITY PK, PA 16802 USA. NIH, NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. FU NHGRI NIH HHS [1R01 HG00987-01] NR 60 TC 70 Z9 70 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 20 PY 1995 VL 30 IS 2 BP 299 EP 311 DI 10.1006/geno.1995.9873 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TG447 UT WOS:A1995TG44700021 PM 8586431 ER PT J AU MOON, C WILLIAMS, JB PRESTON, GM COPELAND, NG GILBERT, DJ NATHANS, D JENKINS, NA AGRE, P AF MOON, C WILLIAMS, JB PRESTON, GM COPELAND, NG GILBERT, DJ NATHANS, D JENKINS, NA AGRE, P TI THE MOUSE AQUAPORIN-1 GENE SO GENOMICS LA English DT Note ID INTEGRAL MEMBRANE-PROTEIN; INTRINSIC PROTEIN; ORGANIZATION; SEQUENCES; GENOME; CHIP AB Members of the aquaporin family of molecular water transporters are expressed in diverse epithelia and in complex developmental patterns. Using a cDNA for mouse Aqp1, the structural gene was isolated and a restriction map was constructed. The 13-kb Aqp1 gene contains four exons with intronic boundaries corresponding to other known aquaporin genes. Transcription begins 67 bp 5' to the translation initiation site and 20 bp 3' from a TATAA consensus sequence. Aqp1 was localized by interspecific mouse backcross mapping to the central region of mouse chromosome 6 syntenic with human chromosome 7p14, where AQP1 had previously been localized. These studies have revealed marked structural similarities between the mouse Aqp1 and the human AQP1 genes, suggesting that further comparative studies may provide molecular insight into genetic regulatory features shared by both species. (C) 1995 Academic Press, Inc. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. VANDERBILT UNIV,SCH MED,DEPT MED,DIV ENDOCRINOL,NASHVILLE,TN 37232. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-46000]; NHLBI NIH HHS [HL48268, HL33991] NR 21 TC 19 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 20 PY 1995 VL 30 IS 2 BP 354 EP 357 DI 10.1006/geno.1995.0029 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TG447 UT WOS:A1995TG44700029 PM 8586439 ER PT J AU OKABE, I NUSSBAUM, RL AF OKABE, I NUSSBAUM, RL TI IDENTIFICATION AND CHROMOSOMAL MAPPING OF THE MOUSE INOSITOL POLYPHOSPHATE 1-PHOSPHATASE GENE SO GENOMICS LA English DT Note ID HETEROLOGOUS EXPRESSION AB A mouse inositol polyphosphate 1-phosphatase (Inpp1) cDNA fragment (348 bp) was amplified by means of the polymerase chain reaction using a mouse cDNA library as template with primers designed from published human and bovine cDNA sequences. We isolated a 1623-bp full-length Inpp1 cDNA from a mouse brain cDNA library using this amplified cDNA fragment as probe. Amino acid sequences of mouse, human, and bovine inositol polyphosphate 1-phosphatase are highly conserved. Northern blot analysis shows a major transcript of 1.65-kb mRNA and several higher molecular weight mRNAs that are expressed in a variety of mouse tissues. Utilizing the Jackson Lab backcross DNA panel map service, we mapped Inpp1 to chromosome 1, 1.06 cM proximal to Ctla4. (C) 1995 Academic Press, Inc. C1 NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892. NR 8 TC 2 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 20 PY 1995 VL 30 IS 2 BP 358 EP 360 DI 10.1006/geno.1995.0030 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TG447 UT WOS:A1995TG44700030 PM 8586440 ER PT J AU DILLNER, J KNEKT, P SCHILLER, JT HAKULINEN, T AF DILLNER, J KNEKT, P SCHILLER, JT HAKULINEN, T TI PROSPECTIVE SEROEPIDEMIOLOGICAL EVIDENCE THAT HUMAN PAPILLOMAVIRUS TYPE-16 INFECTION IS A RISK FACTOR FOR ESOPHAGEAL SQUAMOUS-CELL CARCINOMA SO BRITISH MEDICAL JOURNAL LA English DT Article ID CANCER C1 NATL PUBL HLTH INST,HELSINKI,FINLAND. FINNISH SOCIAL INSURANCE INST,HELSINKI,FINLAND. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. KAROLINSKA INST,DEPT CANC EPIDEMIOL,STOCKHOLM,SWEDEN. FINNISH CANC REGISTRY,SF-00170 HELSINKI,FINLAND. RP DILLNER, J (reprint author), KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. NR 5 TC 62 Z9 64 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD NOV 18 PY 1995 VL 311 IS 7016 BP 1346 EP 1346 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TF901 UT WOS:A1995TF90100026 PM 7496288 ER PT J AU GODDE, JS WOLFFE, AP AF GODDE, JS WOLFFE, AP TI DISRUPTION OF RECONSTITUTED NUCLEOSOMES - THE EFFECT OF PARTICLE CONCENTRATION, MGCL2 AND KCL CONCENTRATION, THE HISTONE TAILS, AND TEMPERATURE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID TRANSCRIPTION FACTOR ACCESS; CHROMATIN CORE PARTICLES; TUMOR VIRUS PROMOTER; RNA POLYMERASE-II; 5S RNA; IONIC-STRENGTH; TATA-BOX; DNA; BINDING; COMPLEX AB We find that reconstituted nucleosome cores containing specific DNA sequences dissociate on dilution. This disruption of histone-DNA contacts leading to the re lease of free DNA is facilitated by the presence of the core histone tails, MgCl2 (5 mM), KCl (60 mM), and temperatures above 0 degrees C. Under reaction conditions that are commonly used to assess trans-acting factor access to nucleosomal DNA histone-DNA contacts are on the threshold of instability. We demonstrate how dilution of reconstituted nucleosomes containing a TATA box can facilitate TBP access to DNA. RP GODDE, JS (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. NR 43 TC 34 Z9 34 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 NOV 17 PY 1995 VL 270 IS 46 BP 27399 EP 27402 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE736 UT WOS:A1995TE73600003 PM 7499192 ER PT J AU RAJAGOPAL, I AHN, BY MOSS, B MATHEWS, CK AF RAJAGOPAL, I AHN, BY MOSS, B MATHEWS, CK TI ROLES OF VACCINIA VIRUS RIBONUCLEOTIDE REDUCTASE AND GLUTAREDOXIN IN DNA PRECURSOR BIOSYNTHESIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID RNA-POLYMERASE; REPLICATION; EXPRESSION; HOMOLOG AB To examine the possible role of the vaccinia virus glutaredoxin as a cofactor for viral ribonucleotide reductase, viral growth, DNA synthesis, and dNTP pools were measured in infections of B-SC-40 monkey kidney cells with wild type vaccinia virus and with mutants of vaccinia that lacked a functional reductase or glutare-doxin. In infections of untreated host cells, the lack of viral ribonucleotide reductase or glutaredoxin had only small effects upon virus growth. When host cells were pretreated with a-amanitin, which blocks host RNA polymerase II but not viral transcription, viral DNA synthesis was markedly reduced in infections with either of the mutants when compared with wild type infections. Relative to dNTP levels in wild type infections, pools of dCTP, but not of the other dNTPs, were significantly reduced in infections of amanitin-treated cells with either mutant, The parallel depletion of dCTP in the two mutants suggests that the role of glutaredoxin may be to function as a cofactor for viral ribonucleotide reductase. The data suggest that both viral proteins become essential for DNA replication only when levels of the corresponding host cell proteins are depleted. C1 OREGON STATE UNIV,DEPT BIOCHEM & BIOPHYS,CORVALLIS,OR 97331. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. KOREA UNIV,DEPT GENET ENGN,SEOUL 136701,SOUTH KOREA. FU NIGMS NIH HHS [R0I-GM-37508] NR 14 TC 25 Z9 26 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 17 PY 1995 VL 270 IS 46 BP 27415 EP 27418 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE736 UT WOS:A1995TE73600007 PM 7499196 ER PT J AU MAHADEVAN, D YU, JC SALDANHA, JW THANKI, N MCPHIE, P UREN, A LAROCHELLE, WJ HEIDARAN, MA AF MAHADEVAN, D YU, JC SALDANHA, JW THANKI, N MCPHIE, P UREN, A LAROCHELLE, WJ HEIDARAN, MA TI STRUCTURAL ROLE OF EXTRACELLULAR DOMAIN-1 OF ALPHA-PLATELET-DERIVED GROWTH-FACTOR (PDGF) RECEPTOR FOR PDGF-AA AND PDGF-BB BINDING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-RECEPTOR; CRYSTAL-STRUCTURE; LIGAND-BINDING; DIMERIZATION; IDENTIFICATION; ACTIVATION; DEFINE; OCCURS; DIMER; AB AB The purpose of this study was to bacterially express, purify, and refold combinations of the extracellular immunoglobulin (Ig)-like domains (2-3, 1-3, and 1-5) of the human alpha-platelet-derived growth factor receptor (alphaPDGFR) to characterize molecular interactions with its ligand, platelet-derived growth factor (PDGF). The far UV circular dichromism spectroscopy of the alpha-PDGFR extracellular domains (ECDs) revealed a predominantly beta-sheet protein, with a structure consistent with folded Ig-like domains. The addition of PDGF-BB to these ECD types changed the conformation of all three types with a decrease in mean residue ellipticity in the following rank order: 1-5=1-3 greater than 2-3. In striking contrast, addition of PDGF-AA to these ECD types markedly changed the conformation of ECD 2-3, by an increased mean residue ellipticity but no changes were observed for ECDs 1-3 and 1-5. PDGF-AA bound to the immobilized ECD types 2-3, 1-3, and 1-5 at concentrations of 20, 11, and 7.5nM, respectively. In contrast, PDGF-BB bound the ECD types 2-3, 1-3, and 1-5 at concentrations of 3,3, and 2.2 nM, respectively. Scatchard analysis of binding studies using labeled ECDs indicated that PDGF-BB bound ECD 1-3 and ECD 2-3 with K-D values of 74 and 72 nM, respectively. While, PDGF-AA bound ECD 1-3 and ECD 2-3 with K-D values of 33 and 87 nM, respectively. Therefore, our results indicated that the loss of ECD 1 impaired the binding affinity of alphaPDGFR ECD 1-3 toward PDGF-AA without having a similar effect on PDGF-BB binding. Together all of our data suggest that ECD 1 is differentially required for proper orientation of PDGF-AA but not PDGF-BB binding determinant within ECDs 2 and 3 C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NIDDK,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892. MRC,CTR COLLABORAT,LONDON,ENGLAND. NR 32 TC 20 Z9 21 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 17 PY 1995 VL 270 IS 46 BP 27595 EP 27600 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE736 UT WOS:A1995TE73600033 PM 7499222 ER PT J AU UNSON, CG CYPESS, AM KIM, HN GOLDSMITH, PK CARRUTHERS, CJL MERRIFIELD, RB SAKMAR, TP AF UNSON, CG CYPESS, AM KIM, HN GOLDSMITH, PK CARRUTHERS, CJL MERRIFIELD, RB SAKMAR, TP TI CHARACTERIZATION OF DELETION AND TRUNCATION MUTANTS OF THE RAT GLUCAGON RECEPTOR - 7 TRANSMEMBRANE SEGMENTS ARE NECESSARY FOR RECEPTOR TRANSPORT TO THE PLASMA-MEMBRANE AND GLUCAGON BINDING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; BETA-ADRENERGIC-RECEPTOR; HORMONE-RELATED PEPTIDE; EXPRESSION CLONING; BOVINE RHODOPSIN; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; PARATHYROID-HORMONE; ACTIVATION; GENE AB Glucagon receptor mutants were characterized with the aim of elucidating minimal structural requirements for proper biosynthesis, ligand binding, and adenylyl cyclase coupling. One N-terminal deletion mutant and five truncation mutants with progressively shorter C termini were expressed in transiently transfected monkey kidney (COS-1) cells. Each truncation mutant was designed so that the truncated C-terminal tail would remain on the cytoplasmic surface of the receptor. In order to characterize the cellular location of the expressed receptor mutants, a highly specific, high affinity antipeptide antibody was prepared against the extracellular, N-terminal tail of the receptor, Immunoblot analysis and immunofluorescence microscopy showed that the presence of all seven putative transmembrane segments, but not an intact N-terminal tail, was required for cell surface expression of the receptor, Membranes from cells expressing receptor mutants lacking a large portion of the N-terminal tail or any of the seven putative transmembrane segments failed to bind glucagon. Membranes from cells expressing the C-terminal tail truncation mutants, which retained all seven transmembrane segments, bound glucagon with affinities similar to that of the native receptor and activated cellular adenylyl cyclase in response to glucagon. These results indicate that all seven helices are necessary for the proper folding and processing of the glucagon receptor, Glycosylation is not required for the receptor to reach the cell surface, and it may not be required for ligand binding, However, the N-terminal extracellular portion of the receptor is required for ligand binding, Most of the distal C-terminal tail is not necessary for ligand binding, and the absence of the tail may increase slightly the receptor binding affinity for glucagon. The C-terminal tail is also not necessary for adenylyl cyclase coupling and therefore does not play a direct role in G protein (G(s)) activation by the glucagon receptor. C1 ROCKEFELLER UNIV,NEW YORK,NY 10021. HOWARD HUGHES MED INST,MOLEC BIOL & BIOCHEM LAB,NEW YORK,NY 10021. NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. RI Sakmar, Thomas/D-1833-2015 OI Sakmar, Thomas/0000-0002-2836-8953 FU NIDDK NIH HHS [DK24039] NR 54 TC 91 Z9 91 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 17 PY 1995 VL 270 IS 46 BP 27720 EP 27727 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE736 UT WOS:A1995TE73600050 PM 7499239 ER PT J AU BARR, VA SCOTT, LJ HUBBARD, AL AF BARR, VA SCOTT, LJ HUBBARD, AL TI IMMUNOADSORPTION OF HEPATIC VESICLES CARRYING NEWLY SYNTHESIZED DIPEPTIDYL PEPTIDASE-IV AND POLYMERIC IGA RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPATOCYTE PLASMA-MEMBRANE; CARBOHYDRATE RECOGNITION SYSTEMS; TRANS-CELLULAR TRANSPORT; RAT-LIVER; MEDIATED ENDOCYTOSIS; SUBCELLULAR FRACTIONATION; IMMUNOELECTRON MICROSCOPY; TRANSCYTOTIC VESICLES; ENDOPLASMIC-RETICULUM; SECRETORY COMPONENT AB Hepatocytes must transport newly synthesized apical membrane proteins from the basolateral to the apical plasma membrane, Our earlier morphological study showed that the apical proteins share a late (subapical) part of the transcytotic pathway with the well characterized polymeric immunoglobulin A receptor (Barr, V. A., and Hubbard, A. L. (1993) Gastroenterology 105, 554-571), Starting with crude microsomes from the livers of [S-35]methionine-labeled rats, we sequentially immuno-adsorbed first vesicles containing the endocytic asialoglycoprotein receptor and then (from the depleted supernatant) vesicles containing the polymeric IgA receptor, Biochemical characterization indicated that early basolateral and late endosomes were present in the first population but not in the second. Neither Golgi, apical plasma membrane (PM)-, nor basolateral PM-derived vesicles were significant contaminants of either population. Both vesicle populations contained S-35-labeled receptor and S-35-labeled-dipeptidyl peptidase TV, Importantly, the elevated relative specific activity of the dipeptidyl peptidase (% of S-35-labeled/% immunoblotted) in the second population indicated that these vesicles must transport newly synthesized dipeptidyl peptidase IV. A distinct kind of vesicle was immunoadsorbed from a ''carrier-vesicle fraction''; surprisingly, these vesicles contained little S-35-receptor and virtually no dipeptidyl peptidase IV. These results, together with previous kinetic data from in vivo experiments, are consistent with a computer-generated model predicting that newly synthesized dipeptidyl peptidase IV is delivered to basolateral endosomes, which also contain newly synthesized polymeric immunoglobulin A receptor. The two proteins are then transcytosed together to the subapical region. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. NIH,DIABET BRANCH,BETHESDA,MD 20892. UNIV MICHIGAN,SCH PUBL HLTH,ANN ARBOR,MI 48109. NR 74 TC 34 Z9 34 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 17 PY 1995 VL 270 IS 46 BP 27834 EP 27844 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE736 UT WOS:A1995TE73600066 PM 7499255 ER PT J AU KUNO, K ISHIKAWA, Y ERNST, MK OGATA, M RICE, NR MUKAIDA, N MATSUSHIMA, K AF KUNO, K ISHIKAWA, Y ERNST, MK OGATA, M RICE, NR MUKAIDA, N MATSUSHIMA, K TI IDENTIFICATION OF AN I-KAPPA-B-ALPHA-ASSOCIATED PROTEIN-KINASE IN A HUMAN MONOCYTIC CELL-LINE AND DETERMINATION OF ITS PHOSPHORYLATION SITES ON I-KAPPA-B-ALPHA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; TRANSCRIPTION FACTOR; ACTIVATION; PRECURSOR; P105; MACROPHAGES; INVITRO; P50 AB Nuclear factor kappa B (NF-kappa B) is stored in the cytoplasm as an inactive form through interaction with I kappa B, Stimulation of cells leads to a rapid phosphorylation of I kappa B alpha, which is presumed to be important for the subsequent degradation, We have recently reported the establishment of a lipopolysaccharide (LPS)-dependent cell free activation system of NF-kappa B in association with the induction of I kappa B alpha phosphorylation, In this study, we have identified a kinase in cell extracts from the LPS stimulated human monocytic cell line, THP-1, that specifically binds and phosphorylates I kappa B alpha. LPS stimulation transiently enhanced the I kappa B alpha-bound kinase activity in THP-1 cells, Mutational analyses of I kappa B alpha and competition experiments with the synthetic peptides identified major phosphorylation sites by the bound kinase as Ser and Thr residues in the C-terminal acidic domain of I kappa B alpha, Moreover, we show that the peptide, corresponding to the C-terminal acidic domain of I kappa B alpha, blocked the LPS induced NF-kappa B activation as well as inducible phosphorylation of endogenous I kappa B alpha in a cell-free system using THP-1 cells. These results suggested that the bound kinase is involved in the signaling pathway of LPS by inducing the phosphorylation of the C terminal region of I kappa B alpha and subsequent dissociation of the NF-kappa B . I kappa B alpha complex. C1 KANAZAWA UNIV,CANC RES INST,DEPT PHARMACOL,KANAZAWA,ISHIKAWA 920,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Mukaida, Naofumi/D-7623-2011 OI Mukaida, Naofumi/0000-0002-4193-1851 NR 41 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 17 PY 1995 VL 270 IS 46 BP 27914 EP 27919 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE736 UT WOS:A1995TE73600077 PM 7499266 ER PT J AU WANG, ZY BRZESKA, H BAINES, IC KORN, ED AF WANG, ZY BRZESKA, H BAINES, IC KORN, ED TI PROPERTIES OF ACANTHAMOEBA MYOSIN-I HEAVY-CHAIN KINASE BOUND TO PHOSPHOLIPID-VESICLES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIN-BINDING-SITES; COFACTOR PROTEIN; PLASMA-MEMBRANES; LOCALIZATION; CASTELLANII; AUTOPHOSPHORYLATION; PHOSPHORYLATION; ACTIVATION; PURIFICATION; SPECIFICITY AB The actin activated Mg2+-ATPase and in vitro motility activities of the three Acanthamoeba myosin I isozymes depend upon phosphorylation of their single heavy chains by myosin I heavy chain kinase, Previously, the kinase had been shown to be activated by autophosphorylation, which is enhanced by acidic phospholipids, or simply by binding to purified plasma membranes in the absence of significant autophosphorylation, Tn this paper, we show that the rate of phosphorylation of myosin I by unphosphorylated kinase is similar to 20-fold faster when both the myosin I and the kinase are bound to acidic phospholipid vesicles than when both are soluble, This activation is not due to an increase in the local concentrations of vesicle-bound kinase and myosin I, Thus, acidic phospholipids, like membranes, can activate myosin I heavy chain kinase in the absence of significant autophosphorylation, i.e. membrane proteins are not required, Kinetic studies show that both binding of kinase to phospholipid vesicles and autophosphorylation of kinase in the absence of phospholipid increase the V-max relative to soluble, unphosphorylated kinase with either an increase in the apparent K-m (when myosin I is the substrate) or no significant change in K-m (when a synthetic peptide is the substrate), Kinetic data showed that autophosphorylation of phospholipid bound kinase is both intermolecular and intervesicular, and that phosphorylation of phospholipid-bound myosin I by phospholipid-bound kinase is also intervesicular even when the kinase and myosin are bound to the same vesicles. The relevance of these results to the activation of myosin I heavy chain kinase and phosphorylation of myosin I isozymes in situ are discussed. C1 NHLBI, CELL BIOL LAB, BETHESDA, MD 20892 USA. RI Korn, Edward/F-9929-2012 NR 33 TC 11 Z9 12 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 17 PY 1995 VL 270 IS 46 BP 27969 EP 27976 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TE736 UT WOS:A1995TE73600085 PM 7499274 ER PT J AU SUNAGA, K TAKAHASHI, H CHUANG, DM ISHITANI, R AF SUNAGA, K TAKAHASHI, H CHUANG, DM ISHITANI, R TI GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE IS OVER-EXPRESSED DURING APOPTOTIC DEATH OF NEURONAL CULTURES AND IS RECOGNIZED BY A MONOCLONAL-ANTIBODY AGAINST AMYLOID PLAQUES FROM ALZHEIMERS BRAIN SO NEUROSCIENCE LETTERS LA English DT Article DE 38-KDA PARTICULATE PROTEIN; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; OVER-EXPRESSION; APOPTOTIC NEURONAL DEATH; ANTIDEMENTIA DRUG; BETA-AMYLOID PRECURSOR PROTEIN; ALZHEIMERS DISEASE ID CEREBELLAR GRANULE CELLS; PROTEIN-PRECURSOR; DEPOSITS; DISEASE AB The age-induced apoptotic death of cerebellar neurons in culture is associated with over-expression of a 38-kDa particulate protein identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Both the age-induced apoptosis and the 38-kDa protein overexpression were effectively suppressed by the presence of tetrahydroaminoacridine, an antidementia drug, or aurintricarboxylic acid. This over-expressed 38-kDa protein and purified GAPDH were found to react with a monoclonal antibody (mAb), Am-3, which was raised against amyloid plaques from Alzheimer's brain, but not with a mAb, AmT-1, which was produced using synthetic amyloid beta peptide. These results raise the possibility that GAPDH is also involved in the neurodegeneration during the development of Alzheimer's disease. C1 JOSAI UNIV,CELLULAR NEUROBIOL GRP,SAKADO,SAITAMA 35002,JAPAN. TOKYO METROPOLITAN INST GERONTOL,DEPT PATHOL,ITABASHI KU,TOKYO 173,JAPAN. NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. NR 18 TC 80 Z9 85 U1 0 U2 2 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 17 PY 1995 VL 200 IS 2 BP 133 EP 136 DI 10.1016/0304-3940(95)12098-O PG 4 WC Neurosciences SC Neurosciences & Neurology GA TH950 UT WOS:A1995TH95000016 PM 8614562 ER PT J AU RICE, WG SUPKO, JG MALSPEIS, L BUCKHEIT, RW CLANTON, D BU, M GRAHAM, L SCHAEFFER, CA TURPIN, JA DOMAGALA, J GOGLIOTTI, R BADER, JP HALLIDAY, SM COREN, L SOWDER, RC ARTHUR, LO HENDERSON, LE AF RICE, WG SUPKO, JG MALSPEIS, L BUCKHEIT, RW CLANTON, D BU, M GRAHAM, L SCHAEFFER, CA TURPIN, JA DOMAGALA, J GOGLIOTTI, R BADER, JP HALLIDAY, SM COREN, L SOWDER, RC ARTHUR, LO HENDERSON, LE TI INHIBITORS OF HIV NUCLEOCAPSID PROTEIN ZINC FINGERS AS CANDIDATES FOR THE TREATMENT OF AIDS SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; TYPE-1; RETROVIRUSES; INFECTIVITY; SEQUENCES; CLONE; RNA AB Strategies for the treatment of human immunodeficiency virus-type 1 (HIV-1) infection must contend with the obstacle of drug resistance. HIV-1 nucleocapsid protein zinc fingers are prime antiviral targets because they are mutationally into lerant and are required both for acute infection and virion assembly. Nontoxic disulfide-substituted benzamides were identified that attack the zinc fingers, inactivate cell-free virions, inhibit acute and chronic infections, and exhibit broad antiretroviral activity. The compounds were highly synergistic with other antiviral agents, and resistant mutants have not been detected. Zinc finger-reactive compounds may offer an anti-HIV strategy that restricts drug-resistance development. C1 NCI,DIV CANC TREATMENT,PHARMACEUT CHEM LAB,DEV THERAPEUT PROGRAM,FREDERICK,MD 21701. SO RES INST FREDERICK RES CTR,VIROL RES GRP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,ANTI AIDS VIRUS DRUG SCREENING LAB,FREDERICK,MD 21702. WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,DEPT CHEM,ANN ARBOR,MI 48105. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,ANTIVIRAL EVALUAT BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. RP RICE, WG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,ANTIVIRAL DRUG MECHANISMS LAB,FREDERICK,MD 21702, USA. NR 30 TC 210 Z9 212 U1 2 U2 12 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 17 PY 1995 VL 270 IS 5239 BP 1194 EP 1197 DI 10.1126/science.270.5239.1194 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TE905 UT WOS:A1995TE90500055 PM 7502043 ER PT J AU TSAI, CC FOLLIS, KE SABO, A BECK, TW GRANT, RF BISCHOFBERGER, N BENVENISTE, RE BLACK, R AF TSAI, CC FOLLIS, KE SABO, A BECK, TW GRANT, RF BISCHOFBERGER, N BENVENISTE, RE BLACK, R TI PREVENTION OF SIV INFECTION IN MACAQUES BY (R)-9-(2-PHOSPHONYLMETHOXYPROPYL)ADENINE SO SCIENCE LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; ACYCLIC NUCLEOSIDE PHOSPHONATES; RHESUS-MONKEYS; ANTIRETROVIRAL AGENTS; INVITRO; PROPHYLAXIS; RESISTANCE; ZIDOVUDINE; LENTIVIRUS; METABOLISM AB The efficacy of pre- and postexposure treatment with the antiviral compound (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) was tested against simian immunodeficiency virus (SIV) in macaques as a model for human immunodeficiency virus (HIV). PMPA was administered subcutaneously once daily beginning either 48 hours before, 4 hours after, or 24 hours after virus inoculation. Treatment continued for 4 weeks and the virologic, immunologic, and clinical status of the macaques was monitored for up to 56 weeks. PMPA prevented SIV infection in all macaques without toxicity, whereas all control macaques became infected. These results suggest a potential role for PMPA prophylaxis against early HIV infection in cases of known exposure. C1 GILEAD SCI INC,FOSTER CITY,CA 94404. NCI,FREDERICK,MD 21701. NIAID,DIV AIDS,BETHESDA,MD 20852. RP TSAI, CC (reprint author), UNIV WASHINGTON,REG PRIMATE RES CTR,SEATTLE,WA 98195, USA. FU NCRR NIH HHS [RR00166]; NIAID NIH HHS [N01-AI-15120] NR 30 TC 415 Z9 424 U1 5 U2 16 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 17 PY 1995 VL 270 IS 5239 BP 1197 EP 1199 DI 10.1126/science.270.5239.1197 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TE905 UT WOS:A1995TE90500056 PM 7502044 ER PT J AU KESTLER, HW JEANG, KT AF KESTLER, HW JEANG, KT TI ATTENUATED RETROVIRUS VACCINES AND AIDS SO SCIENCE LA English DT Article C1 NIAID,MOLEC MICROBIOL LAB,MOLEC VIROL SECT,BETHESDA,MD 20892. RP KESTLER, HW (reprint author), CLEVELAND CLIN FDN,RES INST,9500 EUCLID AVE,NC20,CLEVELAND,OH 44195, USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 3 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 17 PY 1995 VL 270 IS 5239 BP 1219 EP 1219 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TE905 UT WOS:A1995TE90500065 PM 7502052 ER PT J AU SHEARER, GM LUCEY, DR CLERICI, M AF SHEARER, GM LUCEY, DR CLERICI, M TI ATTENUATED RETROVIRUS VACCINES AND AIDS SO SCIENCE LA English DT Article ID NEF GENE C1 UNIV MILAN,MILAN,ITALY. RP SHEARER, GM (reprint author), NCI,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 17 PY 1995 VL 270 IS 5239 BP 1219 EP 1219 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TE905 UT WOS:A1995TE90500064 PM 7502053 ER PT J AU CUSHMAN, M GOLEBIEWSKI, M BUCKHEIT, RW GRAHAM, L RICE, WG AF CUSHMAN, M GOLEBIEWSKI, M BUCKHEIT, RW GRAHAM, L RICE, WG TI SYNTHESIS AND BIOLOGICAL EVALUATION OF AN ALKENYLDIARYLMETHANE (ADAM) WHICH ACTS AS A NOVEL NONNUCLEOSIDE HIV-1 REVERSE-TRANSCRIPTASE INHIBITOR SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1 AB ADAM, a novel non-nucleoside HIV-1 reverse transcriptase inhibitor, was synthesized and found to inhibit a variety of HIV-1 strains. In common with other known NNRTIs, ADAM is inactive against HIV-2 and it is much more active as an inhibitor of HIV-1 reverse transcriptase with poly(rC).oligo(dG) as the template/primer than it is with poly(rA).oligo(dT) as the template/primer. C1 FREDERICK RES CTR,SO RES INST,VIROL RES GRP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,ANTIVIRAL DRUG MECHANISMS LAB,FREDERICK,MD 21702. RP CUSHMAN, M (reprint author), PURDUE UNIV,SCH PHARM & PHARMACAL SCI,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907, USA. NR 13 TC 24 Z9 24 U1 0 U2 0 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 NOV 16 PY 1995 VL 5 IS 22 BP 2713 EP 2716 DI 10.1016/0960-894X(95)00465-6 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA TF704 UT WOS:A1995TF70400023 ER PT J AU CHEN, IT SMITH, ML OCONNOR, PM FORNACE, AJ AF CHEN, IT SMITH, ML OCONNOR, PM FORNACE, AJ TI DIRECT INTERACTION OF GADD45 WITH PCNA AND EVIDENCE FOR COMPETITIVE INTERACTION OF GADD45 AND P2L(WAF1/CIP1) WITH PCNA SO ONCOGENE LA English DT Article DE GADD45; PCNA; P21; WAF1; CIP1; P53; XP-A ID CELL NUCLEAR ANTIGEN; DNA POLYMERASE-DELTA; GENE-TRANSCRIPTION; AUXILIARY PROTEIN; CYCLIN PCNA; P53; REPLICATION; INHIBITOR; IRRADIATION; COMPONENT AB We have previously shown (Smith et al., 1994) that antibodies raised against the growth arrest and DNA damage inducible protein Gadd45 co-precipitate proliferating cell nuclear antigen (PCNA), a protein involved in DNA replication and repair. Here we demonstrate that Gadd45 can directly bind to PCNA using a Far-western blotting approach. In this assay, a Gadd45 bacterial expression vector was modified to allow synthesis of purified P-32-labeled Gadd45 fusion protein. This protein was used to detect filter bound PCNA protein, while filter bound Gadd45 protein could also be detected by free PCNA molecules. Using recombinant proteins in conjunction with immunoprecipitation and immunoblotting, we show that Gadd45 competes with p21 for binding to PCNA and conversely, p21 blocks the ability of Gadd45 to bind PCNA. In addition, p21 appears to disrupt PCNA trimers whereas Gadd45 has a lesser effect. PCNA trimer disruption was also observed in UV-irradiated cells but not in repair-defective xeroderma pigmentosum group A (XP-A) cells. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 45 TC 117 Z9 121 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 16 PY 1995 VL 11 IS 10 BP 1931 EP 1937 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TF297 UT WOS:A1995TF29700001 PM 7478510 ER PT J AU KWON, TK BUCHHOLZ, MA GABRIELSON, EW NORDIN, AA AF KWON, TK BUCHHOLZ, MA GABRIELSON, EW NORDIN, AA TI A NOVEL CYTOPLASMIC SUBSTRATE FOR CDK4 AND CDK6 IN NORMAL AND MALIGNANT EPITHELIAL DERIVED CELLS SO ONCOGENE LA English DT Article DE CYCLIN-DEPENDENT KINASE; G1 CYCLINS; CELL CYCLE; BREAST CELL CARCINOMA; LUNG CELL CARCINOMA ID RETINOBLASTOMA SUSCEPTIBILITY GENE; BREAST-CANCER; PROTEIN; EXPRESSION; CYCLINS; IDENTIFICATION; AMPLIFICATION AB Cyclins and cyclin-dependent kinases (cdk) have been identified as important regulators of cell replication. Molecular alteration in the cdk pathways appear to be important in cancer with some cyclins (eg cyclin D and E) proposed to be oncogenes and some inhibitors of cdk (eg p16) proposed to be tumor suppressor genes, In human breast carcinoma cell line MDA361 both cyclin D and E are overexpressed and cdk 4 and 6 are the predominate kinases which phosphorylate retinoblastoma protein and to a greater extent a novel 88 kDa protein. This 88 kDa protein was detected as a significant substrate in five of seven breast carcinoma cell lines, three lung carcinoma cell lines as well as in primary breast and lung epithelium. Normal human and murine T lymphocytes and established lymphoid cell lines are devoid of this protein and minimal amounts were detected in normal human fibroblast. In contrast to retinoblastoma protein, the 88 kDa protein appears to be more prevalent in the cytosolic than the nuclear subfraction. The phosphorylation of this 88 kDa protein by the G(1) associated cdks suggest that this protein may represent another targeted substrate regulating the G(1) phase of the cell cycle. C1 NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21224. FU NCI NIH HHS [P20 CA-ES 66204] NR 33 TC 17 Z9 17 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 16 PY 1995 VL 11 IS 10 BP 2077 EP 2083 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TF297 UT WOS:A1995TF29700018 PM 7478527 ER PT J AU THOMAS, RS TYMMS, MJ SETH, A SHANNON, MF KOLA, I AF THOMAS, RS TYMMS, MJ SETH, A SHANNON, MF KOLA, I TI ETS1 TRANSACTIVATES THE HUMAN GM-CSF PROMOTER IN JURKAT T-CELLS STIMULATED WITH PMA AND IONOMYCIN SO ONCOGENE LA English DT Article DE GRANULOCYTE-MACROPHAGE; COLONY-STIMULATING FACTOR; GM-CSF; ETS1; ELF1; TRANSCRIPTION ID LONG TERMINAL REPEAT; VIRUS TYPE-I; DNA-BINDING; LEUKEMIA-VIRUS; INFLAMMATORY RESPONSES; TRANSCRIPTION FACTORS; C-ETS-1 PROTEIN; GENE PROMOTER; ACTIVATION; EXPRESSION AB Activation of T helper cells results in coordinate expression of a number of cytokines involved in differentiation, proliferation and activation of the haematopoietic system. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one such cytokine whose increased expression results partly from increases in transcription. Cis-acting elements with NF kappa B, AP-1 and ETS-like motifs have been identified in the promoter region of the GM-CSF gene, which are important for transcriptional activity following PMA and ionomycin stimulation. A number of the ETS family of transcription factors are expressed in T cells, including ETS1 and ELF1. Here we describe the ability of these factors to interact with a site (GM5), located within the CLE0 element, -47 to -40 upstream of the GM-CSF transcription initiation site. Exogenous ETS1, but not ELF1, can transactivate GM-CSF, through the GM5 site, in a PMA/ionomycin dependent manner. Other unidentified ETS-like factors present in Jurkat cells are also capable of binding GM5. Mutation of the core ETS binding site from -GGAA- to -GGAT- prevents the binding of ETS-like factors with the exception of ETS1. The GM-CSF promoter, modified in this way to be ETS1 specific, is fully responsive to PMA/ionomycin induction, in addition to ETS1 transactivation in the presence of PMA and ionomycin. Together these data suggest that ETS1 may be involved in mediating the increased GM-CSF production associated with T cell activation. C1 MONASH UNIV,MONASH MED CTR,INST REPROD & DEV,MOLEC GENET & DEV GRP,MELBOURNE,VIC 3168,AUSTRALIA. NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. INST MED & VET SCI,HANSON CTR CANC RES,DIV HUMAN IMMUNOL,ADELAIDE,SA 5000,AUSTRALIA. RI Thomas, Ross/C-6434-2008; Kola, Ismail/C-5254-2013 NR 54 TC 39 Z9 39 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 16 PY 1995 VL 11 IS 10 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 TF297 UT WOS:A1995TF29700025 PM 7478534 ER PT J AU GU, J DUBNER, R FORNACE, AJ IADAROLA, MJ AF GU, J DUBNER, R FORNACE, AJ IADAROLA, MJ TI UREB1, A TYROSINE-PHOSPHORYLATED NUCLEAR-PROTEIN, INHIBITS P53 TRANSACTIVATION SO ONCOGENE LA English DT Note DE UREB1; P53; TRANSACTIVATION; SUPPRESSION; TUMOR SUPPRESSOR; TYROSINE PHOSPHORYLATION ID WILD-TYPE; E6-AP; E6; UBIQUITINATION; TRANSFORMATION; EXPRESSION; COMPLEX; MUTANT; GROWTH; FORMS AB Tumor suppressor p53 is a transcription activator that upregulates target genes containing the p53 binding site, UREB1, a DNA binding protein that is tyrosine phosphorylated in vivo, shares a significant homology with the human papilloma virus E6 associated protein (E6-AP). E6-AP forms a ternary complex with E6 and p53 and participates in the ubiquitination of p53. Based on the homology with E6-AP, but taking into account the nuclear localization of UREB1 and its smaller size, the present study used a transient transfection system to examine whether UREB1 influenced p53-stimulated transcription. Co-transfection of a vector expressing wildtype UREB1 with one expressing p53 into H1299, a p53 negative cell line, resulted in a pronounced suppression of p53 transactivation. The inhibitory effect was significantly attenuated by mutation of a tyrosine residue in the consensus tyrosine phosphorylation sequence of UREB1. These data suggest that optimal suppression of p53 transactivation requires tyrosine phosphorylated UREB1 and that tyrosine phosphorylation and dephosphorylation processes may be involved in the regulation of p53 transactivation. C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP GU, J (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 49,RM 1A11,49 CONVENT DR,MSC-4410,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 27 TC 18 Z9 21 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 16 PY 1995 VL 11 IS 10 BP 2175 EP 2178 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA TF297 UT WOS:A1995TF29700030 PM 7478539 ER PT J AU HAVERKOS, HW STEIN, MD AF HAVERKOS, HW STEIN, MD TI IDENTIFYING SUBSTANCE-ABUSE IN PRIMARY-CARE SO AMERICAN FAMILY PHYSICIAN LA English DT Article AB Family physicians have an opportunity to identify substance abusers years before they have medical complications or present for drug treatment. Occult substance abuse can be effectively identified by simple screening questions and careful attention to clinical indicators during the history and physical examination. Early intervention may have dramatic effects on substance-abusing behavior and may prevent the many adverse medical, psychologic and social effects of substance abuse in these patients. RP HAVERKOS, HW (reprint author), NIDA,OFF AIDS,PARKLAWN BLDG,ROOM 9A-30,ROCKVILLE,MD 20857, USA. NR 0 TC 13 Z9 13 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD NOV 15 PY 1995 VL 52 IS 7 BP 2029 EP 2035 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA TF112 UT WOS:A1995TF11200009 PM 7484704 ER PT J AU GUETTA, V LUSH, RM FIGG, WD WACLAWIW, MA CANNON, RO AF GUETTA, V LUSH, RM FIGG, WD WACLAWIW, MA CANNON, RO TI EFFECTS OF THE ANTIESTROGEN TAMOXIFEN ON LOW-DENSITY-LIPOPROTEIN CONCENTRATIONS AND OXIDATION POSTMENOPAUSAL WOMEN SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note AB The antiestrogen tamoxifen, when administered to postmenopausal women at conventional dosages, reduces low-density lipoprotein levels and protects low-density lipoproteins from oxidation, These effects may account for the reduction in cardiovascular events noted in breast cancer treatment trials. RP GUETTA, V (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B15,10 CTR DR MSC-1650,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 5 TC 48 Z9 48 U1 1 U2 2 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 1995 VL 76 IS 14 BP 1072 EP & DI 10.1016/S0002-9149(99)80302-6 PG 0 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TE778 UT WOS:A1995TE77800021 PM 7484866 ER PT J AU MELTZER, AA EVERHART, JE AF MELTZER, AA EVERHART, JE TI UNINTENTIONAL WEIGHT-LOSS IN THE UNITED-STATES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE AGE FACTORS; BODY MASS INDEX; EDUCATIONAL STATUS; HEALTH STATUS; HEALTH SURVEYS; RISK FACTORS; SMOKING; WEIGHT LOSS ID HEALTH CONSEQUENCES; LIFE EXPECTANCY; BODY-WEIGHT; MORTALITY; SMOKING; ADULTS; EDUCATION; BENEFITS; DISEASES; SUCCESS AB Lower weight is usually considered advantageous to health, yet weight loss has been associated with increased mortality. An explanation for this paradox might be that the benefits of weight loss may depend on whether the loss is intentional or unintentional. The authors investigated whether intentional and unintentional weight loss differed in their associations with known risk factors for morbidity and mortality in a nationally representative sample of the US population, The sample consisted of 9,144 persons, aged 45 years and older, who answered questions regarding I-year weight change in the diabetes risk factor Current Health Topic of the 1989 National Health interview Survey (NHIS), Statistical analyses incorporated the sample weights and characteristics of the survey design, Relative to a common referent group, the factors associated with weight loss differed depending on whether the loss was defined as intentional loss, as unintentional loss, or regardless of intention, Restricting analysis to the 1,999 persons who lost weight, unintentional relative to intentional weight loss was significantly (p < 0.05) associated with older age, poorer health status, smoking, lower body mass index, and, in men only, widowhood and less education, Thus, unintentional weight loss may serve as a marker for factors that characterize persons at greater risk of mortality than persons undergoing intentional weight loss, Also, intention to lose weight may help clarify the relation between weight loss and mortality that, to this point, has shown counterintuitive results. Studies of the relation between weight loss and mortality should incorporate intention as a factor in the analysis. C1 NIDDKD,BETHESDA,MD. RP MELTZER, AA (reprint author), SOCIAL & SCI SYST INC,7101 WISCONSIN AVE,SUITE 1300,BETHESDA,MD 20814, USA. FU NIDDK NIH HHS [N01-DK-1-2282] NR 37 TC 53 Z9 53 U1 2 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 1995 VL 142 IS 10 BP 1039 EP 1046 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TE777 UT WOS:A1995TE77700005 PM 7485049 ER PT J AU BALTZ, JK AF BALTZ, JK TI VACCINES IN THE TREATMENT OF CANCER SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID ACTIVE SPECIFIC IMMUNOTHERAPY; II MALIGNANT-MELANOMA; CARCINOEMBRYONIC ANTIGEN; IMMUNE-SYSTEM; VIRUS; ONCOLYSATE; RESPONSES; IMMUNIZATION; RECOGNITION; EXPRESSION AB The development of vaccines for treating cancer is discussed. The central hypothesis behind active specific immunotherapy for cancer is that tumor cells express unique antigens that tell the immune system that something about these cells is foreign. A vaccine is a way of delivering an antigen to the immune system such that immune cells recognize the antigen as foreign and destroy any cells bearing that antigen. Early trials of vaccines for treating cancer were limited by technical problems related to poor knowledge of the immune system. Recent research has focused on expression on the surfaces of antigen-presenting cells of antigenic peptides bound to major histocompatibility complex (MHC) molecules, peptide recognition by cytotoxic T cells, and the requirement for a second signal, such as the costimulatory molecule B7, for T-cell activation. Antigenic peptides constitute the ''keys'' that open the ''locks'' of T cells; the problem is that researchers have difficulty choosing the right keys from among the myriad available. Administering an adjuvant enhances the immune response by making the antigen more recognizable as foreign. Vaccine preparation techniques include peptide pulsing (a method for boosting cell-surface expression of the antigenic peptide-MHC combinations), intramuscular injections of DNA plasmids encoding the desired antigen, and gene insertion into vaccinia virus by recombinant DNA technology. Cancer vaccines may be administered by scarification, by subcutaneous and intramuscular injection, and intranasally. Clinical trials of cancer vaccines continue to encounter problems because of the many variables in administration routes, dosages, patient populations, and methods for evaluating responses. There have been some promising results but also many treatment failures. Antigen targets in trials today include normal antigens that have a limited normal-tissue distribution or expression (e.g., carcinoembryonic antigen), viral proteins (e.g., E6 protein of human papillomavirus), and mutated oncogenes. Toxicities have been mild. Better understanding of the immune system and better technology have led to advances in the development of vaccines for treating cancer, but there is still much progress to achieve. RP BALTZ, JK (reprint author), NCI,EPN ROOM 804,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 37 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD NOV 15 PY 1995 VL 52 IS 22 BP 2574 EP 2585 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TG518 UT WOS:A1995TG51800012 PM 8590245 ER PT J AU VIEIRA, NE YERGEY, AL AF VIEIRA, NE YERGEY, AL TI EXTRACTION OF SERUM AND URINE CALCIUM WITH ION-EXCHANGE MEMBRANE FILTERS FOR ISOTOPE ENRICHMENT DETERMINATION USING THERMAL IONIZATION MASS-SPECTROMETRY SO ANALYTICAL CHEMISTRY LA English DT Note AB The extraction of calcium from water, serum, and urine using Bio-Rex 25 mm ion exchange membrane filters was compared with the oxalate precipitation procedure currently used in our laboratory. Total recoveries of a known quantity of calcium loaded onto the membrane filters for water, serum and urine were as follows: (a) cation exchange filter, 85%, 74%, and 66%; (b) Chelex, 65%, 98%, and 20%; and (c) oxalate precipitation, 93%, 100%, and 96%, respectively, Regression analysis for precipitation versus ion exchange isotope ratio measurements of standards prepared using highly enriched calcium-44 showed slopes of unity. An improvement of automated sample analysis was observed for water and urine calcium samples extracted with ion exchange filters. RP VIEIRA, NE (reprint author), NICHHD,THEORET & PHYS BIOL LAB,10 CTR DR,MSC 1580,BLDG 10,ROOM 6C208,BETHESDA,MD 20892, USA. NR 11 TC 2 Z9 2 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 15 PY 1995 VL 67 IS 22 BP 4217 EP 4219 DI 10.1021/ac00118a028 PG 3 WC Chemistry, Analytical SC Chemistry GA TD958 UT WOS:A1995TD95800028 PM 8633769 ER PT J AU SOKOLOFF, AV WHALLEY, T ZIMMERBERG, J AF SOKOLOFF, AV WHALLEY, T ZIMMERBERG, J TI CHARACTERIZATION OF N-ETHYLMALEIMIDE-SENSITIVE THIOL-GROUPS REQUIRED FOR THE GTP-DEPENDENT FUSION OF ENDOPLASMIC-RETICULUM MEMBRANES SO BIOCHEMICAL JOURNAL LA English DT Article ID LIVER MICROSOMAL VESICLES; VESICULAR TRANSPORT; RAT-LIVER; BIOLOGICAL-MEMBRANES; ROUGH MICROSOMES; GOLGI TRANSPORT; CA-2+ EFFLUX; PROTEIN; RECEPTOR; INVITRO AB The GTP-dependent fusion activity of endoplasmic reticulum membranes is thought to be required for the structural maintenance and post-mitotic regeneration of the endoplasmic reticulum. This fusion is sensitive to the thiol-alkylating agent N-ethylnaleimide. In many intracellular fusion events N-ethylmaleimide-sensitivity is associated with a homotrimeric ATPase called N-ethylmaleimide-sensitive fusion protein or NSF. The addition of cytosol containing NSF is known to restore fusion activity to N-ethylmaleimide-treated membranes. We found that the inhibition of fusion of rat liver endoplasmic reticulum membranes (microsomes) by N-ethylmaleimide was not reversed by the addition of untreated cytosol. Fusion was also unaffected by treatment with a buffer known to remove NSF from membranes. Accordingly, no membrane-associated NSF was detected by immunoblot analysis. These data suggest that microsome fusion requires an N-ethylmaleimide-sensitive component distinct from NSF. This component was tightly associated with the membranes, so we used a number of chemical probes to characterize it in situ. Its thiol groups did not appear to be part of a GTP-binding site. They showed relatively low reactivity with sodium periodate, which induces the formation of disulphide bonds between proximate thiol groups. The thiols were not protected against N-ethylmaleimide by Zn2+, a potent inhibitor of fusion which is known to efficiently co-ordinate thiol groups. To characterize the topology of the fusion-related thiol groups we used bulky thiol-specific reagents prepared by conjugating BSA or 10 kDa aminodextran to the bifunctional reagent N-succinimidyl 3-(2-pyridyldithio)propionate. The inhibition of fusion by these reagents indicated that these thiols are highly exposed on the membranes. This exposure might be important for the function of these groups during GTP-triggered fusion. RP SOKOLOFF, AV (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,ROOM 6C215,BETHESDA,MD 20892, USA. OI Whalley, Tim/0000-0003-3362-0006 NR 45 TC 8 Z9 8 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 15 PY 1995 VL 312 BP 23 EP 30 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TF371 UT WOS:A1995TF37100004 PM 7492317 ER PT J AU DIVECHA, N LETCHER, AJ BANFIC, HH RHEE, SG IRVINE, RF AF DIVECHA, N LETCHER, AJ BANFIC, HH RHEE, SG IRVINE, RF TI CHANGES IN THE COMPONENTS OF A NUCLEAR INOSITIDE CYCLE DURING DIFFERENTIATION IN MURINE ERYTHROLEUKEMIA-CELLS SO BIOCHEMICAL JOURNAL LA English DT Article ID SWISS 3T3 CELLS; DNA POLYMERASE-ALPHA; PROTEIN-KINASE-C; RAT-LIVER NUCLEI; GROWTH FACTOR-I; PHOSPHOLIPASE-C; STIMULATION; INSULIN; DIACYLGLYCEROL; LOCALIZATION AB Differentiation of murine erythroleukaemia cells with the chemical agent DMSO leads to a cessation of proliferation and the production of a number of erythrocyte markers such as haemoglobin. We have previously demonstrated that activation of proliferation leads to an increase in the production of nuclear diacylglycerol (DAG). Here we demonstrate that differentiation leads to a decrease in the levels of nuclear DAG and the activity of the nuclear-associated phosphoinositidase C (PIC). The change in activity appears to be due to a decrease in the mass levels of the beta 1 isoform, as demonstrated by the use of isoform-specific antibodies. Moreover, the changes correlate with the cessation of proliferation and an increase in the number of cells in G(1) phase of the cell cycle, rather than with the number of cells which have differentiated. Indeed, although treatment of the cells with phorbol 12-myristate 13-acetate (PMA) inhibits the differentiation programme as assessed by haemoglobin staining, it does not inhibit the number of cells blocking in G, of the cell cycle or the changes in nuclear DAG or PIC activity. The possible involvement of this nuclear inositide cycle during progression through the cell cycle is discussed. C1 UNIV ZAGREB,SCH MED,DEPT PHYSIOL,ZAGREB 41000,CROATIA. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RP DIVECHA, N (reprint author), BABRAHAM INST,DEPT DEV & SIGNALLING,INOSITIDE LAB,CAMBRIDGE CB2 4AT,ENGLAND. NR 34 TC 64 Z9 65 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 15 PY 1995 VL 312 BP 63 EP 67 PN 1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TF371 UT WOS:A1995TF37100009 PM 7492336 ER PT J AU Tang, DC Ebb, D Rodgers, GP AF Tang, DC Ebb, D Rodgers, GP TI Phylogenetic footprinting and mutagenesis analysis reveal important regulatory elements in the human delta globin gene SO BLOOD LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,MOLEC HEMATOL SECT,BETHESDA,MD. MASSACHUSETTS GEN HOSP,DEPT PEDIAT HEMATOL ONCOL,BOSTON,MA 02114. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2 EP 2 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000002 ER PT J AU Li, J Schechter, AN Noguchi, CT AF Li, J Schechter, AN Noguchi, CT TI Multiple negative control elements regulate expression of the human epsilon globin gene. SO BLOOD LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 3 EP 3 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000003 ER PT J AU Orlic, D Girard, L Lee, D Anderson, S Puck, J Bodine, D AF Orlic, D Girard, L Lee, D Anderson, S Puck, J Bodine, D TI Differential expression of the Y-common chain and its partners, IL-2R, IL-7R and IL-9R in pluripotent hematopoietic stem cells (PHSC), thymocytes and developing cells in mouse bone marrow SO BLOOD LA English DT Meeting Abstract C1 NCHGR,GENE TRANSFER LAB,HEMATOPOIESIS SECT,BETHESDA,MD. NCHGR,GENE TRANSFER LAB,IMMUNOL GENET SECT,BETHESDA,MD. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 29 EP 29 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000029 ER PT J AU Broxmeyer, HE Cooper, S Lu, L Wang, MH Sarris, A Donner, DB Leonard, EJ AF Broxmeyer, HE Cooper, S Lu, L Wang, MH Sarris, A Donner, DB Leonard, EJ TI Macrophage-stimulating protein (MSP), a ligand for the RON tyrosine kinase receptor, suppresses immature myeloid progenitor cell proliferation in vitro, and synergizes in this effect with vascular endothelial cell growth factor (VEGF) SO BLOOD LA English DT Meeting Abstract C1 INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. UNIV TEXAS,HOUSTON,TX. NCI,FREDERICK,MD 21701. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 38 EP 38 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000038 ER PT J AU Petropavlovskaia, MS Roberts, SJ Elwood, PC AF Petropavlovskaia, MS Roberts, SJ Elwood, PC TI TGF beta 1 and retinoic acid induce the adherence of leukemic cells to bone marrow stroma. SO BLOOD LA English DT Meeting Abstract C1 NCI,MED BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 92 EP 92 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000092 ER PT J AU Vazquez, N Lyman, CA Friedman, D Walsh, TJ Chanock, SJ AF Vazquez, N Lyman, CA Friedman, D Walsh, TJ Chanock, SJ TI Interleukin 15 augments human monocyte activation. SO BLOOD LA English DT Meeting Abstract C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 118 EP 118 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000118 ER PT J AU Izraeli, S Bertness, VL Mani, KM Aplan, PD Kirsch, IR AF Izraeli, S Bertness, VL Mani, KM Aplan, PD Kirsch, IR TI SIL, the most frequent ''dysregulator'' of SCL (TAL1) in T-cell acute lymphoblastic leukemia (T-ALL), is an immediate early response gene expressed in proliferating cells. SO BLOOD LA English DT Meeting Abstract C1 USN,MED ONCOL BRANCH,NATL CANC INST,BETHESDA,MD. ROSWELL PK CANC INST,DEPT PEDIAT,BUFFALO,NY 14263. ROSWELL PK CANC INST,DEPT MOLEC MED,BUFFALO,NY 14263. RI Aplan, Peter/K-9064-2016 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 124 EP 124 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000124 ER PT J AU Wijmenga, C Hajra, A Adya, N Blake, T Gregory, P Collins, FS Liu, PP AF Wijmenga, C Hajra, A Adya, N Blake, T Gregory, P Collins, FS Liu, PP TI Analysis of CBFB-MYH11, the fusion gene produced by chromosome 16 inversion in human leukemias SO BLOOD LA English DT Meeting Abstract C1 NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD 20892. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 163 EP 163 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000164 ER PT J AU Shad, A Mueller, B Adde, M Avila, N Pizzo, P Magrath, IT AF Shad, A Mueller, B Adde, M Avila, N Pizzo, P Magrath, IT TI Preliminary results of a protocol for the treatment of Non-Hodgkin's Lymphoma (NHL) in children with immunodeficiency syndromes SO BLOOD LA English DT Meeting Abstract C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,DIAGNOST RADIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 198 EP 198 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000199 ER PT J AU Bergsagel, PL Chesi, M Brents, LA Kuehl, WM AF Bergsagel, PL Chesi, M Brents, LA Kuehl, WM TI Dysregulation of C-MYC in multiple myeloma: Selective expression of one allele. SO BLOOD LA English DT Meeting Abstract C1 CORNELL UNIV,COLL MED,DIV HEMATOL ONCOL,NEW YORK,NY. USN,MED ONCOL BRANCH,NCI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 222 EP 222 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000223 ER PT J AU Bergsagel, PL Chesi, M Brents, LA Kuehl, WM AF Bergsagel, PL Chesi, M Brents, LA Kuehl, WM TI Translocations into IgH switch regions: The genetic hallmark of multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 CORNELL UNIV,COLL MED,DIV HEMATOL ONCOL,NEW YORK,NY. USN,MED ONCOL BRANCH,NCI,BETHESDA,MD. NR 0 TC 6 Z9 7 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 NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 223 EP 223 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000224 ER PT J AU Anderson, SM Yu, G Miller, JL AF Anderson, SM Yu, G Miller, JL TI Intercellular transfer of a GPI-linked protein: Secretion and uptake of soluble CD4-GPI from rAAV-transduced HeLa cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD. NIDDKD,BIOL CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 263 EP 263 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000264 ER PT J AU Williams, S McKeown, L Krutzch, H Gralnick, HR AF Williams, S McKeown, L Krutzch, H Gralnick, HR TI Glycocalicin derived peptides inhibit von Willebrand platelet interactions. SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 328 EP 328 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000329 ER PT J AU Stein, D Mackall, C Bare, C Brown, M Carter, C Casey, N Yu, M Fleisher, T Leitman, S Shearer, G Wexler, L Gress, R AF Stein, D Mackall, C Bare, C Brown, M Carter, C Casey, N Yu, M Fleisher, T Leitman, S Shearer, G Wexler, L Gress, R TI Impaired immune reconstitution post sequential high dose chemotherapy and peripheral blood progenitor cell (PBPC) infusion. SO BLOOD LA English DT Meeting Abstract C1 NCI,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 402 EP 402 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000404 ER PT J AU CottlerFox, M Couriel, D Dunbar, C Carter, C Yu, M Barrett, AJ AF CottlerFox, M Couriel, D Dunbar, C Carter, C Yu, M Barrett, AJ TI Counterflow centrifugal elutriation (CCE) of bone marrow reveals two patterns of hematopoietic progenitor-stem cell (HPSC) distribution in normal donors. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 474 EP 474 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000475 ER PT J AU Flake, AW Puck, JM AlmeidaPorada, G Evans, MI Johnson, MP Roncarolo, MG Zanjani, ED AF Flake, AW Puck, JM AlmeidaPorada, G Evans, MI Johnson, MP Roncarolo, MG Zanjani, ED TI Successful treatment of X-linked recessive severe combined immunodeficiency (X-SCID) by the in utero transplantation of CD34 enriched paternal bone marrow cells. SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP MICHIGAN,DETROIT,MI 48201. HUTZEL HOSP,DETROIT,MI 48201. NCHGR,BETHESDA,MD. DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA. UNIV NEVADA,DEPT VET AFFAIRS MED CTR,RENO,NV. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 487 EP 487 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000488 ER PT J AU Sloand, EM Yu, M Anderson, S Maciejewski, JP AF Sloand, EM Yu, M Anderson, S Maciejewski, JP TI Effects of glycosylphosphatidylinositol 1-deficiency on the phenotype of platelets of patients with paroxysmal nocturnal hemoglobinuria. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 508 EP 508 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000508 ER PT J AU Gralnick, HR Vail, M McKeown, LP Merryman, P Wilson, O Chu, I Kimball, J AF Gralnick, HR Vail, M McKeown, LP Merryman, P Wilson, O Chu, I Kimball, J TI Platelet activation in paroxysmal nocturnal hemoglobinuria. SO BLOOD LA English DT Meeting Abstract C1 CTR CLIN,SERV HEMATOL,BETHESDA,MD. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 515 EP 515 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000515 ER PT J AU Dunn, D Yu, J Nagarajan, S Devetten, M Medof, E Young, N Liu, J AF Dunn, D Yu, J Nagarajan, S Devetten, M Medof, E Young, N Liu, J TI A ''knock-out'' model for PNH: PIG-A negative embryonic stem cells show aberrant embryogenesis but apparently normal intrinsic hematopoietic potential. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 518 EP 518 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000518 ER PT J AU Connor, E FolenaWasserman, G Alfonso, C Bowen, S Kajigaya, S Tsao, E Oliver, C Schenerman, M Anderson, S Top, FH Young, NS AF Connor, E FolenaWasserman, G Alfonso, C Bowen, S Kajigaya, S Tsao, E Oliver, C Schenerman, M Anderson, S Top, FH Young, NS TI A phase 1 vaccine trial with recombinant parvovirus B19 virus-like particles in seronegative healthy adult volunteers. SO BLOOD LA English DT Meeting Abstract C1 MEDIMMUNE INC,GAITHERSBURG,MD 20878. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 528 EP 528 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000528 ER PT J AU Maikovska, V Cigel, F Sondel, P Parker, K AF Maikovska, V Cigel, F Sondel, P Parker, K TI Synthetic peptides derived from the CD19 protein bind to the class I HLA-A2.1. SO BLOOD LA English DT Meeting Abstract C1 WASHINGTON HOSP CTR,WASHINGTON CANC INST,CHILDRENS NATL MED CTR,CTR CANC & TRANSPLANTAT BIOL,WASHINGTON,DC. UNIV WISCONSIN,DEPT PEDIAT,MADISON,WI. NIAID,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 616 EP 616 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000616 ER PT J AU Jiang, YZ Mavroudis, DA Dermime, S Hensel, NF Couriel, D Molldrem, J Mahoney, MH Barrett, AJ AF Jiang, YZ Mavroudis, DA Dermime, S Hensel, NF Couriel, D Molldrem, J Mahoney, MH Barrett, AJ TI Exogenous antigen processing and presentation with induction of cytotoxic CD4+ T-lymphocytes by chronic myelogenous leukemia cells SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BONE MARROW TRANSPLANTAT UNIT,BETHESDA,MD 20892. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 618 EP 618 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000618 ER PT J AU Dermime, S Molldrem, J Parker, KC Jiang, YZ Mavroudis, D Hensel, N Couriel, D Mahoney, M Coligan, JE Barrett, AJ AF Dermime, S Molldrem, J Parker, KC Jiang, YZ Mavroudis, D Hensel, N Couriel, D Mahoney, M Coligan, JE Barrett, AJ TI Human CD8(+) T lymphocytes recognize the fusion region of BCR/ABL hybrid protein present in chronic myelogenous leukemia SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BONE MARROW TRANSPLANTAT UNIT,BETHESDA,MD 20892. NIAID,MOLEC STRUCT LAB,BETHESDA,MD 20892. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 620 EP 620 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000620 ER PT J AU Mansoor, A Ptaszynski, K Wang, J Hendrix, MJC StetlerStevenson, WG StetlerStevenson, M AF Mansoor, A Ptaszynski, K Wang, J Hendrix, MJC StetlerStevenson, WG StetlerStevenson, M TI Expression of TIMP-1 in Burkitt's cell lines. Correlation with aggressive phenotype. SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 719 EP 719 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000720 ER PT J AU Lim, MS Mansoor, A Ptaszynski, K Wang, J Fukushima, P StetlerStevenson, WG StetlerStevenson, M AF Lim, MS Mansoor, A Ptaszynski, K Wang, J Fukushima, P StetlerStevenson, WG StetlerStevenson, M TI Expression of matrix: Metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs) in reactive and neoplastic lymphoid cells. SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 722 EP 722 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000723 ER PT J AU Munshi, NC Wijdenes, J Fassas, A Vesole, D Jagannath, SJ Cheson, B Butch, A Dhodapkar, M Tricot, G Barlogie, B AF Munshi, NC Wijdenes, J Fassas, A Vesole, D Jagannath, SJ Cheson, B Butch, A Dhodapkar, M Tricot, G Barlogie, B TI Anti-IL-6 monoclonal antibody (BE-8) and suramin for treatment of Castleman's disease (CD) SO BLOOD LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. JOHN L MCCLELLAN MEM VET ADM MED CTR,LITTLE ROCK,AR 72205. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 745 EP 745 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000746 ER PT J AU Bell, WR Kwon, SW Chung, SI AF Bell, WR Kwon, SW Chung, SI TI Massive hemorrhage, isoniazid, factor XIII deficiency; An acquired autoimmune hemorrhagic disorder. SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 764 EP 764 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000765 ER PT J AU Couriel, D Canosa, J Engler, H Molldrem, J Mavroudis, D Dunbar, C Collins, A Wesley, B Barrett, AJ AF Couriel, D Canosa, J Engler, H Molldrem, J Mavroudis, D Dunbar, C Collins, A Wesley, B Barrett, AJ TI Factors predicting outcome following reactivation of cytomegalovirus after T-depleted BMT for hematological malignancy. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BMT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 853 EP 853 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000854 ER PT J AU Bodine, DM Seidel, NE Cline, AP Gale, MS Orlic, D AF Bodine, DM Seidel, NE Cline, AP Gale, MS Orlic, D TI The repopulating ability of bone marrow from mice treated with the combination of granulocyte colony stimulating factor (G-CSF) and stem cell factor (SCF) is increased approximately 15 fold. SO BLOOD LA English DT Meeting Abstract C1 NCHGR,LGT,HEMATOPOIESIS SECT,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 893 EP 893 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000894 ER PT J AU Wexler, LH WeaverMcClure, L Carter, CS Yu, M CottlerFox, M Leitman, S AF Wexler, LH WeaverMcClure, L Carter, CS Yu, M CottlerFox, M Leitman, S TI Use of CD34-selected peripheral blood progenitor cell collections (PBPCC) to allow dose intensification in pediatric sarcoma patients. SO BLOOD LA English DT Meeting Abstract C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 916 EP 916 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000918 ER PT J AU Rund, D Dagan, M Schoenlein, P Gottesman, M Oppenheim, A AF Rund, D Dagan, M Schoenlein, P Gottesman, M Oppenheim, A TI SV40/MDR1 vector for gene delivery into human hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 HADASSAH UNIV HOSP,DEPT HEMATOL,IL-91120 JERUSALEM,ISRAEL. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 932 EP 932 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000934 ER PT J AU Yu, JM Soma, T Dunbar, CE AF Yu, JM Soma, T Dunbar, CE TI Neutralizing antibody abrogation of TGF-beta activity during retroviral transduction improves gene transfer efficiency. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 934 EP 934 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000936 ER PT J AU Emmons, RVB Doren, S Hines, K Carter, CS CottlerFox, M OShaughnessy, JA Leitman, SF Cowan, K Dunbar, CE AF Emmons, RVB Doren, S Hines, K Carter, CS CottlerFox, M OShaughnessy, JA Leitman, SF Cowan, K Dunbar, CE TI Comparison of retroviral transduction conditions for gene marking of adult peripheral blood or marrow-derived CD34(+) cells in a clinical trial. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 940 EP 940 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000942 ER PT J AU Nelson, DM Metzger, ME Donahue, RE Morgan, RA AF Nelson, DM Metzger, ME Donahue, RE Morgan, RA TI In vivo retroviral-mediated gene transfer into multiple hematopoietic lineages in rabbits without preconditioning. SO BLOOD LA English DT Meeting Abstract C1 NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,GENE TRANSFER TECHNOL SECT,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 941 EP 941 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000943 ER PT J AU Mizukami, H Muramatsu, S Young, NS Brown, KE AF Mizukami, H Muramatsu, S Young, NS Brown, KE TI Adeno-associated virus type 2 binds to a 150 kilodalton cell membrane glycoprotein. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 947 EP 947 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000949 ER PT J AU Bunnell, BA Morgan, RA Byrne, ER Agricola, BA Metzger, ME Sellers, SE Donahue, RE AF Bunnell, BA Morgan, RA Byrne, ER Agricola, BA Metzger, ME Sellers, SE Donahue, RE TI In vivo gene transfer into non-human primate CD34(+) cells using the gibbon ape leukemia virus packaging cell line, PG13. SO BLOOD LA English DT Meeting Abstract C1 NCHGR,CLIN GENE THERAPY BRANCH,BETHESDA,MD. NHLBI,HEMATOL BRANCH,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 950 EP 950 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000952 ER PT J AU Walsh, CE Xiao, X Wang, S Li, L Samulski, RI Kim, S Chao, E Byrne, ER Sellers, SE Agricola, B Liu, LM Donahue, RE AF Walsh, CE Xiao, X Wang, S Li, L Samulski, RI Kim, S Chao, E Byrne, ER Sellers, SE Agricola, B Liu, LM Donahue, RE TI Successful in vivo gene transfer of the Fanconi anemia group C gene (FAC) into primate CD34-immunoselected hematopoietic cells using a recombinant adeno-associated viral vector. SO BLOOD LA English DT Meeting Abstract C1 CTR CLIN,DEPT CLIN PATHOL,SERV HEMATOL,BETHESDA,MD. UNIV N CAROLINA,CTR GENE THERAPY,CHAPEL HILL,NC. NHLBI,HEMATOL BRANCH,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 953 EP 953 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000955 ER PT J AU Frisch, VL Wang, S Malech, HL Walsh, CE AF Frisch, VL Wang, S Malech, HL Walsh, CE TI Phenotypic correction of human hematopoietic progenitor cells from a patient with X-linked chronic granulomatous disease using a recombinant adeno-associated virus vector. SO BLOOD LA English DT Meeting Abstract C1 NIAID,CC,CPD,SERV HEMATOL,BETHESDA,MD 20892. NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 955 EP 955 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000957 ER PT J AU Licht, T Aran, JM Goldenberg, SK Vieira, WD Gottesman, MM Pastan, J AF Licht, T Aran, JM Goldenberg, SK Vieira, WD Gottesman, MM Pastan, J TI Cytotoxic drug selection of murine bone marrow cells following transfer of the MDR1 (multidrug resistance) gene increases gene expression and chemoresistance in vivo. SO BLOOD LA English DT Meeting Abstract C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 960 EP 960 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91000962 ER PT J AU Roesler, J Gorlach, A Rae, J Hopkins, PJ Patino, P Lee, P Curnutte, JT Chanock, SJ AF Roesler, J Gorlach, A Rae, J Hopkins, PJ Patino, P Lee, P Curnutte, JT Chanock, SJ TI Recombination events between the normal p47-phox gene and a highly homologous pseudogene are the main cause of autosomal recessive chronic granulomatous disease SO BLOOD LA English DT Meeting Abstract C1 GENENTECH INC, S SAN FRANCISCO, CA 94080 USA. SCRIPPS RES INST, LA JOLLA, CA USA. NCI, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1025 EP 1025 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001027 ER PT J AU Gorlach, A Roesler, J Hopkins, PJ Christensen, BL Lee, P Green, ED Chanock, SJ Curnutte, JT AF Gorlach, A Roesler, J Hopkins, PJ Christensen, BL Lee, P Green, ED Chanock, SJ Curnutte, JT TI The p47-phox gene has a pseudogene carrying the most common mutation for p47-phox deficient chronic granulomatous disease. SO BLOOD LA English DT Meeting Abstract C1 SCRIPPS RES INST, LA JOLLA, CA USA. GENENTECH INC, S SAN FRANCISCO, CA 94080 USA. NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1027 EP 1027 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001029 ER PT J AU Zhan, S Vazquez, N Zhan, S Green, E Chanock, SJ AF Zhan, S Vazquez, N Zhan, S Green, E Chanock, SJ TI Gene structure and expression of the newly defined component of the NADPH-oxidase, p40-phox SO BLOOD LA English DT Meeting Abstract C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1029 EP 1029 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001031 ER PT J AU Lin, A Dale, J Fleisher, T Fisher, G Rosenberg, F Lenardo, M Puck, J Middelton, L Corden, B Tucker, M Straus, S AF Lin, A Dale, J Fleisher, T Fisher, G Rosenberg, F Lenardo, M Puck, J Middelton, L Corden, B Tucker, M Straus, S TI Familial aggregation of Hodgkin's disease (HD), autoimmune lymphoproliferative syndrome (ALPS) and germline Fas mutations SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Tucker, Margaret/B-4297-2015 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1072 EP 1072 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001074 ER PT J AU Alvarez, M Wilson, WH Setser, A Goldspiel, B Steinberg, S Longo, D Wittes, R AF Alvarez, M Wilson, WH Setser, A Goldspiel, B Steinberg, S Longo, D Wittes, R TI Phase II study of epoch chemotherapy (CT) in previously untreated intermediate-grade (IG) non-Hodgkin's lymphomas (NHL) SO BLOOD LA English DT Meeting Abstract C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. NCI,FREDERICK,MD 21701. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1083 EP 1083 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001085 ER PT J AU Warren, MK Rose, WL Cone, JL Rice, WG Turpin, JA AF Warren, MK Rose, WL Cone, JL Rice, WG Turpin, JA TI Differential infection of CD34+ cell-derived dendritic cells and monocytes with lymphocyte-tropic and monocytetropic HIV-1 strains. SO BLOOD LA English DT Meeting Abstract C1 OTSUKA AMER PHARMACEUT INC,ROCKVILLE,MD. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,ANTIVIRAL DRUG MECHANISMS LAB,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1137 EP 1137 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001139 ER PT J AU Sloand, EM Weichold, FF Kumar, P Young, NS Maciejewski, JP AF Sloand, EM Weichold, FF Kumar, P Young, NS Maciejewski, JP TI Involvement of Fas receptor in the mechanism of T-cell depletion in aids. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT INFECT DIS,WASHINGTON,DC. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1138 EP 1138 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001140 ER PT J AU Davis, BR Bauer, G Saitta, FP Bunnell, BA Morgan, RA Schwartz, DH AF Davis, BR Bauer, G Saitta, FP Bunnell, BA Morgan, RA Schwartz, DH TI Genetic modification of stem/progenitor cells to protect macrophage progeny from HIV infection SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT MOLEC MICROBIOL & IMMUNOL,BALTIMORE,MD. UNIV TEXAS,MED BRANCH,DEPT MICROBIOL & IMMUNOL,SEALY CTR ONCOL & HEMATOL,GALVESTON,TX 77550. NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1140 EP 1140 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001142 ER PT J AU Grossi, CE Ciccone, E Favre, A Moresco, L Meszaros, P Luzzi, P Truini, M Rizzo, F Tacchetti, C AF Grossi, CE Ciccone, E Favre, A Moresco, L Meszaros, P Luzzi, P Truini, M Rizzo, F Tacchetti, C TI HIV-containing immune complexes are responsible for virus trapping and masking in lymph node follicular dendritic cells. SO BLOOD LA English DT Meeting Abstract C1 UNIV GENOA,NATL CANC INST,DEPT HUMAN ANAT & CLIN & EXP ONCOL,GENOA,ITALY. OSPED SAN MARTINO GENOVA,DIV PATHOL & INFECT DIS,GENOA,ITALY. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1142 EP 1142 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001144 ER PT J AU Malech, HL Sekhsaria, S WhitingTheobald, N Linton, GF Vowells, SJ Li, F Miller, JA Holland, SM Leitman, SF Carter, CS Read, EJ Butz, R Wannebo, C Fleisher, TA Deans, RJ Spratt, SK Maack, CA Rokovich, JA Cohen, LK Maples, PB Gallin, JI AF Malech, HL Sekhsaria, S WhitingTheobald, N Linton, GF Vowells, SJ Li, F Miller, JA Holland, SM Leitman, SF Carter, CS Read, EJ Butz, R Wannebo, C Fleisher, TA Deans, RJ Spratt, SK Maack, CA Rokovich, JA Cohen, LK Maples, PB Gallin, JI TI Development of a phase I clinical trial of gene therapy for chronic granulomatous disease SO BLOOD LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,SERV IMMUNOL,BETHESDA,MD 20892. BAXTER HLTHCARE CORP,DIV IMMUNOTHERAPY,ROUND LAKE,IL. BAXTER HLTHCARE CORP,DIV IMMUNOTHERAPY,DUARTE,CA. SOMATIX THERAPY CORP,ALAMEDA,CA. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1167 EP 1167 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001169 ER PT J AU Kohn, DB Weinberg, KI Lenarsky, C Crooks, GM Heiss, LN Nolta, JA Smogorzewska, EM Bastian, J Wara, D Elder, M Bowen, T Hershfield, M Blaese, RM Parkman, R AF Kohn, DB Weinberg, KI Lenarsky, C Crooks, GM Heiss, LN Nolta, JA Smogorzewska, EM Bastian, J Wara, D Elder, M Bowen, T Hershfield, M Blaese, RM Parkman, R TI Selective accumulation of ADA gene-transduced T lymphocytes upon PEG-ADA dosage reduction after gene therapy with transduced CD34+ umbilical cord blood cells SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. CHILDRENS HOSP SAN DIEGO,SAN DIEGO,CA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. DUKE UNIV,DURHAM,NC. NIH,BETHESDA,MD 20892. NR 0 TC 6 Z9 6 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 NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1168 EP 1168 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001170 ER PT J AU Liu, JM Young, NS Carter, CS Read, EJ Pensiero, M Glader, B Grompe, M Walsh, CE AF Liu, JM Young, NS Carter, CS Read, EJ Pensiero, M Glader, B Grompe, M Walsh, CE TI A trial of gene therapy in a patient with complementation group C Fanconi anemia (FAC) SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. DTM,BETHESDA,MD. CPD CC,BETHESDA,MD. GENET THERAPY INC,GAITHERSBURG,MD. STANFORD UNIV,SCH MED,STANFORD,CA 94305. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1169 EP 1169 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001171 ER PT J AU Bunnell, BA Metzger, ME Clements, J Morgan, RA Donahue, RE AF Bunnell, BA Metzger, ME Clements, J Morgan, RA Donahue, RE TI High-efficiency gene transfer into non-human primate lymphocytes permits testing of anti-HIV gene therapy strategies in vivo SO BLOOD LA English DT Meeting Abstract C1 NCHGR,CLIN GENE THERAPY BRANCH,BETHESDA,MD. JOHNS HOPKINS UNIV,SCH MED,DIV COMPARAT MED,BALTIMORE,MD 21205. NHLBI,HEMATOL BRANCH,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 6 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 NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1171 EP 1171 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001173 ER PT J AU Bregni, M DiNicola, M Siena, S Shammah, S Belli, N Milanesi, M Evans, L Gianni, AM AF Bregni, M DiNicola, M Siena, S Shammah, S Belli, N Milanesi, M Evans, L Gianni, AM TI Peripheral blood mobilized CD34+ cells express more amphotropic retrovirus receptor than steady-state bone marrow CD34+ cells SO BLOOD LA English DT Meeting Abstract C1 IST NAZL TUMORI,DIV MED ONCOL,I-20133 MILAN,ITALY. NIH,PERSISTENT VIRAL DIS LAB,HAMILTON,MT. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1173 EP 1173 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001175 ER PT J AU Berger, M Orlofsky, A Cohen, S Taub, D AF Berger, M Orlofsky, A Cohen, S Taub, D TI The chemokine C10: Removal of the sequence encoded by the novel second exon leads to loss of the major antigenic site and to increased potency for monocyte chemoattraction. SO BLOOD LA English DT Meeting Abstract C1 UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. VET ADM MED CTR,PHILADELPHIA,PA 19104. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1226 EP 1226 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001228 ER PT J AU Ding, I Matsubara, H Wu, T Huang, KD Okunieff, P AF Ding, I Matsubara, H Wu, T Huang, KD Okunieff, P TI Enhanced CFU-S and marrow repopulation after radiation in basic fibroblast growth factor treated C3H/HEN mice SO BLOOD LA English DT Meeting Abstract C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1230 EP 1230 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001232 ER PT J AU Okazaki, IJ Kim, HJ McElvaney, NG Moss, J AF Okazaki, IJ Kim, HJ McElvaney, NG Moss, J TI Molecular characterization of a glycosylphosphatidyinositol-linked ADP-ribosyltransferase from lymphocytes. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,PULM CRIT CARE MED BRANCH,BETHESDA,MD 20892. RI McElvaney, Noel/A-6809-2010 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1282 EP 1282 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001283 ER PT J AU Grant, S Freemerman, AJ Birrer, MJ Chelliah, J Jarvis, WD AF Grant, S Freemerman, AJ Birrer, MJ Chelliah, J Jarvis, WD TI Differential role of c-jun in 1-beta-D-arabinofuranosylcytosine-induced differentiation versus apoptosis in U937 human myeloid leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,DIV HEMATOL ONCOL,RICHMOND,VA. NCI,DIV BIOMARKERS & PREVENT,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1299 EP 1299 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001300 ER PT J AU Naresh, K Bhatia, K Venkatesh, H Soman, C Pai, S Advani, S Adde, M Magrath, I AF Naresh, K Bhatia, K Venkatesh, H Soman, C Pai, S Advani, S Adde, M Magrath, I TI The majority of primary lymphoblastic lymphomas express p53. SO BLOOD LA English DT Meeting Abstract C1 TATA MEM HOSP,BOMBAY 400012,MAHARASHTRA,INDIA. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1349 EP 1349 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001350 ER PT J AU Venkatesh, C Bhatia, K LopezCorella, E Mesa, C RiveraLuna, R OConnor, G Magrath, I AF Venkatesh, C Bhatia, K LopezCorella, E Mesa, C RiveraLuna, R OConnor, G Magrath, I TI P53 expression in childhood non-Hodgkin's lymphoma in Mexico is more frequent in B cell non-lymphoblastic lymphomas than in lymphoblastic lymphomas. SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. INST NACL PEDIAT,MEXICO CITY,DF,MEXICO. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1362 EP 1362 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001363 ER PT J AU Emmons, RVB Shulman, NR Reid, DM Young, NS Meng, YG Lee, WL Cohen, RL Dunbar, CE AF Emmons, RVB Shulman, NR Reid, DM Young, NS Meng, YG Lee, WL Cohen, RL Dunbar, CE TI Thrombocytopenic patients with aplastic anemia have high TPO levels whereas those with immune thrombocytopenia are much lower. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NIDDK,CLIN HEMATOL BRANCH,BETHESDA,MD. GENENTECH INC,S SAN FRANCISCO,CA 94080. NR 0 TC 2 Z9 2 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1475 EP 1475 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001475 ER PT J AU LunardiIskandar, Y Bryant, JL Zeman, RA Lam, VH Samaniego, F Besnier, JM Hermans, P Thierry, AR Gill, P Gallo, RC AF LunardiIskandar, Y Bryant, JL Zeman, RA Lam, VH Samaniego, F Besnier, JM Hermans, P Thierry, AR Gill, P Gallo, RC TI Human chorionic gonadotropin (hCG) induces apoptosis of neoplastic Kaposi's sarcoma cell lines (KS Y-1 and KS SLK). SO BLOOD LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NIDR,ANIM CARE UNIT,BETHESDA,MD 20892. GYNECOL & OBSTET MED CTR,PARIS,FRANCE. FREE UNIV BRUSSELS,ST PIERRE HOSP,DEPT INFECT DIS,BRUSSELS,BELGIUM. UNIV SO CALIF,SCH MED,LOS ANGELES,CA. RI thierry, alain/F-9492-2014 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1514 EP 1514 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001514 ER PT J AU Couriel, D Mahoney, M Hensel, N Mavroudis, D Jiang, YZ Dermime, S Molldrem, J Barrett, AJ AF Couriel, D Mahoney, M Hensel, N Mavroudis, D Jiang, YZ Dermime, S Molldrem, J Barrett, AJ TI Donor-versus-recipient helper T lymphocyte precursor numbers given but not their frequency predicts GVHD in HLA matched sibling BMT. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BMT UNIT,BETHESDA,MD 20892. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1575 EP 1575 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001576 ER PT J AU Kollia, P Fibach, E Noguchi, CT Schechter, AN AF Kollia, P Fibach, E Noguchi, CT Schechter, AN TI Hemin affects RNA processing and mRNA levels of embryonic and fetal globin genes in human adult erythroid cells. SO BLOOD LA English DT Meeting Abstract C1 UNIV ATHENS,DEPT INTERNAL MED 1,ATHENS,GREECE. NIDDK,CHEM BIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1659 EP 1659 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001661 ER PT J AU GambacortiPasserini, C Bertazzoli, C Dermime, S Marchesi, E Ravagnani, F Rammensee, HG Stefanovic, S Schendel, D Parmiani, G AF GambacortiPasserini, C Bertazzoli, C Dermime, S Marchesi, E Ravagnani, F Rammensee, HG Stefanovic, S Schendel, D Parmiani, G TI Mapping of HLA class I binding motifs in fusion proteins involved in human cancers. SO BLOOD LA English DT Meeting Abstract C1 IST NAZL TUMORI,I-20133 MILAN,ITALY. NHLBI,BETHESDA,MD 20892. ATV,HEIDELBERG,GERMANY. UNIV MUNICH,MUNICH,GERMANY. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1693 EP 1693 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001695 ER PT J AU Molldrem, J Dermime, S Parker, K Couriel, D Hensel, N Jiang, YZ Mavroudis, D Mahoney, M Barrett, J AF Molldrem, J Dermime, S Parker, K Couriel, D Hensel, N Jiang, YZ Mavroudis, D Mahoney, M Barrett, J TI Cytotoxic T cells show specificity to MHC class I-restricted peptide derived from proteinase 3, a leukemia-associated protein SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BONE MARROW TRANSPLANT UNIT,BETHESDA,MD 20892. NIAID,MOLEC STRUCT LAB,BETHESDA,MD 20892. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1695 EP 1695 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001697 ER PT J AU Delwel, R Hol, S Vankan, Y Lowenberg, B Ihle, JN Copeland, NG Valk, P AF Delwel, R Hol, S Vankan, Y Lowenberg, B Ihle, JN Copeland, NG Valk, P TI The gene encoding the peripheral cannabinoid receptor is located in a new virus integration site (EVI-5) and is a candidate oncogene involved in myeloid transformation. SO BLOOD LA English DT Meeting Abstract C1 ERASMUS UNIV ROTTERDAM, INST HEMATOL, ROTTERDAM, NETHERLANDS. ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN USA. NCI, FREDERICK CANC & DEV CTR, FREDERICK, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1709 EP 1709 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001711 ER PT J AU Sato, T Selleri, C Anderson, S Young, NS Maciejewski, JP AF Sato, T Selleri, C Anderson, S Young, NS Maciejewski, JP TI Expression of cellular receptors for interferon-gamma, tumor necrosis factor-alpha and Fas on BM CD34(+) cells SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1760 EP 1760 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001762 ER PT J AU Dunbar, CE Seidel, N Doren, S Cline, A Donahue, R Bodine, D AF Dunbar, CE Seidel, N Doren, S Cline, A Donahue, R Bodine, D TI In vivo priming of peripheral blood and bone marrow cells with SCF and G-CSF allows efficient gene transfer to long-term repopulating cells. SO BLOOD LA English DT Meeting Abstract C1 NIH,NATL CTR HUMAN GENOME RES,HEMATOPOIESIS SECT,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1845 EP 1845 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001847 ER PT J AU Bloom, ML Stoos, KL AF Bloom, ML Stoos, KL TI Transfer of anemia to normal mice from the hemoglobin deficit mutant by bone marrow transplantation SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1883 EP 1883 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001884 ER PT J AU Liu, JM Devetten, M Walsh, CE AF Liu, JM Devetten, M Walsh, CE TI The Fanconi anemia complementation group C (FAC) gene may have a tumor suppressor function. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. CC,CPD,SERV HEMATOL,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1884 EP 1884 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001885 ER PT J AU Wang, JX Kim, S Devetten, M Yu, J Liu, JM AF Wang, JX Kim, S Devetten, M Yu, J Liu, JM TI Overexpression of the human Fanconi anemia C (FAC) complementation group cDNA in transgenic mice confers mitomycin C resistance to erythroid progenitors. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1891 EP 1891 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001892 ER PT J AU Maciejewski, JP Sato, T Selleri, C Anderson, SA Young, NS AF Maciejewski, JP Sato, T Selleri, C Anderson, SA Young, NS TI Long term culture-initiating cell numbers in aplastic anemia SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1894 EP 1894 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001895 ER PT J AU Rosenfeld, SJ Kimball, J Young, NS AF Rosenfeld, SJ Kimball, J Young, NS TI Long-term outcomes after treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NHLBI,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,HEMATOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1895 EP 1895 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001896 ER PT J AU Selleri, C Maciejewski, JP Young, NS AF Selleri, C Maciejewski, JP Young, NS TI Interferon-gamma, constitutively expressed in the stromal microenviroment of human bone marrow cultures, mediates potent hematopoietic inhibition. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1900 EP 1900 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001901 ER PT J AU Issaragrisil, S Kaufman, DW Young, NS AF Issaragrisil, S Kaufman, DW Young, NS TI The epidemiology of acquired aplastic anemia (AA) in Thailand. SO BLOOD LA English DT Meeting Abstract C1 MAHIDOL UNIV,SIRIRAJ HOSP,DEPT MED,BANGKOK 10700,THAILAND. BOSTON UNIV,SLONE EPIDEMIOL UNIT,BOSTON,MA 02215. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1901 EP 1901 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001902 ER PT J AU Huang, SZ Fibach, E Gu, XF Schechter, AN Rodgers, GP Zeng, YT AF Huang, SZ Fibach, E Gu, XF Schechter, AN Rodgers, GP Zeng, YT TI Hydroxyurea enhances beta-globin expression and decreases aberrant splicing in cultured beta(+)-thalassemia cells. SO BLOOD LA English DT Meeting Abstract C1 HADASSAH UNIV HOSP,DEPT HEMATOL,IL-91120 JERUSALEM,ISRAEL. SHANGHAI INST MED GENET,SHANGHAI,PEOPLES R CHINA. NIDDK,BIOL CHEM LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 1916 EP 1916 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001917 ER PT J AU Yang, J Galipeau, J Kozak, C Furie, BC Furie, B AF Yang, J Galipeau, J Kozak, C Furie, BC Furie, B TI Mouse P-selectin glycoprotein ligand-1 is a functional P-selectin receptor SO BLOOD LA English DT Meeting Abstract C1 TUFTS UNIV,SCH MED,NEW ENGLAND MED CTR,BOSTON,MA 02111. NATL INST HLTH,MOLEC MICROBIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2000 EP 2000 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91001999 ER PT J AU Koo, HM Monks, A Mikheev, A Rubinstein, LV GrayGoodrich, M McWilliams, MJ Oie, HK Gazdar, AF Paull, KD Zarbl, H VandeWoude, GF AF Koo, HM Monks, A Mikheev, A Rubinstein, LV GrayGoodrich, M McWilliams, MJ Oie, HK Gazdar, AF Paull, KD Zarbl, H VandeWoude, GF TI Enhanced sensitivity to cytosine arabinoside and topoisomerase II inhibitors in tumor cell lines harboring mutations in ras oncogenes. SO BLOOD LA English DT Meeting Abstract C1 NCI,FCRDC,ABL BRP & SAIC FREDERICK,FREDERICK,MD. NCI,DCT,BETHESDA,MD. MIT,CAMBRIDGE,MA 02139. UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2037 EP 2037 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002037 ER PT J AU Fest, T Hernandez, L TeruyaFeldstein, J Cazorla, M Bosch, F Peinado, MA Piris, MA Montserrat, E Cardesa, A Jaffe, ES Raffeld, M Campo, E AF Fest, T Hernandez, L TeruyaFeldstein, J Cazorla, M Bosch, F Peinado, MA Piris, MA Montserrat, E Cardesa, A Jaffe, ES Raffeld, M Campo, E TI p53 gene mutations and protein overexpression are associated with aggressive variants of mantle cell lymphomas. SO BLOOD LA English DT Meeting Abstract C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. UNIV BARCELONA,HOSP CLIN,DEPT PATHOL ANAT,BARCELONA,SPAIN. UNIV BARCELONA,HOSP CLIN,DEPT HEMATOL,BARCELONA,SPAIN. NR 0 TC 0 Z9 0 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 NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2112 EP 2112 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002112 ER PT J AU Zhu, YX Kang, LY Luo, W Li, CC Yang, L Yang, YC AF Zhu, YX Kang, LY Luo, W Li, CC Yang, L Yang, YC TI Identification of critical regulatory regions in human interleukin 9 gene promoter. SO BLOOD LA English DT Meeting Abstract C1 INDIANA UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,INDIANAPOLIS,IN. INDIANA UNIV,SCH MED,DEPT HAEMATOL & MED ONCOL,INDIANAPOLIS,IN. NCI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2150 EP 2150 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002150 ER PT J AU Yang, X Lee, SB Lee, KH Sun, L Bae, YS Ghosh, S Rhee, SG Rao, AK AF Yang, X Lee, SB Lee, KH Sun, L Bae, YS Ghosh, S Rhee, SG Rao, AK TI Human platelet signaling defect characterized by diminished inositol triphosphate production, pleckstrin phosphorylation and expression of phospholipase C-beta 2 isozyme. SO BLOOD LA English DT Meeting Abstract C1 TEMPLE UNIV,THROMBOSIS RES CTR,PHILADELPHIA,PA 19122. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2175 EP 2175 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002175 ER PT J AU Horne, MK Alkins, BR AF Horne, MK Alkins, BR TI Platelet binding of IgG from patients with heparin-induced thrombocytopenia. SO BLOOD LA English DT Meeting Abstract C1 NIH,CTR CLIN,CPD,HEMATOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2189 EP 2189 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002190 ER PT J AU Otsuki, T Colombini, S Kumar, S Ensoli, B Kingma, D StetlerStevenson, M Jaffe, ES Raffeld, M AF Otsuki, T Colombini, S Kumar, S Ensoli, B Kingma, D StetlerStevenson, M Jaffe, ES Raffeld, M TI Detection of human herpesvirus-like DNA sequences in AIDS-associated extranodal lymphoid malignancies SO BLOOD LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2215 EP 2215 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002216 ER PT J AU Sloand, EM Young, NS Kumar, P Weichold, FF Pierce, P Maciejewski, JP AF Sloand, EM Young, NS Kumar, P Weichold, FF Pierce, P Maciejewski, JP TI Numbers of circulating progenitor and stem cells in patients with HIV infection. SO BLOOD LA English DT Meeting Abstract C1 GEORGETOWN UNIV,WASHINGTON,DC. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2223 EP 2223 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002224 ER PT J AU Mayroudis, D Jiang, YZ Hensel, N Couriel, D Dermime, S Mahoney, M Barrett, AJ AF Mayroudis, D Jiang, YZ Hensel, N Couriel, D Dermime, S Mahoney, M Barrett, AJ TI Specific depletion of donor-versus-recipient alloreactivity to prevent GVHD after marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BMT UNIT,BETHESDA,MD 20892. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2267 EP 2267 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002268 ER PT J AU Vallera, DA Eide, CR Jost, CR Blazar, BR AF Vallera, DA Eide, CR Jost, CR Blazar, BR TI In vivo infusion of DT390/CD3scFV, a scFV fusion immunotoxin directed against CD3 epsilon for GVHD treatment. SO BLOOD LA English DT Meeting Abstract C1 NIH,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2285 EP 2285 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002286 ER PT J AU Winter, IN Lazarus, HM Rademaker, AF Bauman, A Cooper, B Thomas, R Gordon, LI Tallman, MS Rubin, H Gerson, S Miller, LL AF Winter, IN Lazarus, HM Rademaker, AF Bauman, A Cooper, B Thomas, R Gordon, LI Tallman, MS Rubin, H Gerson, S Miller, LL TI Comparison of PIXY321 and GM-CSF for mobilization of peripheral blood progenitor cells (PBPC) in advanced breast cancer. SO BLOOD LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,CHICAGO,IL. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NCI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2301 EP 2301 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002302 ER PT J AU Sekhsaria, S Fleisher, TA Vowells, SJ Brown, M Miller, JA Gordon, I Blaese, RM Leitman, SF Malech, HL AF Sekhsaria, S Fleisher, TA Vowells, SJ Brown, M Miller, JA Gordon, I Blaese, RM Leitman, SF Malech, HL TI Kinetics of G-CSF recruitment of peripheral blood Cd34+ cells: Normal volunteers and two patient groups with inherited SO BLOOD LA English DT Meeting Abstract C1 NIAID,DEPT TRANSFUS MED,HOST DEF LAB,BETHESDA,MD 20892. NCHGR,SERV IMMUNOL,BETHESDA,MD. NCHGR,CLIN GENE THERAPY BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2321 EP 2321 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002322 ER PT J AU Brown, KE Green, SW Wong, S Sferra, TJ Fishbein, M Desai, SM Coleman, P Dawson, GJ Mushahwar, IK Young, NS AF Brown, KE Green, SW Wong, S Sferra, TJ Fishbein, M Desai, SM Coleman, P Dawson, GJ Mushahwar, IK Young, NS TI A novel hepatitis virus implicated in the etiology of hepatitis/aplasia syndrome and seronegative fulminant hepatitis. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. CHILDRENS HOSP,DEPT GASTROENTEROL,COLUMBUS,OH. ABBOTT LABS,VIRUS DIS GRP,N CHICAGO,IL 60064. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2326 EP 2326 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002327 ER PT J AU Maciejewski, JP Sloand, E Sato, T Anderson, S Young, NS AF Maciejewski, JP Sloand, E Sato, T Anderson, S Young, NS TI Impaired hematopoiesis in PNH/aplasia is not associated with a selective proliferative defect in the GPI-protein deficient clone. SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2331 EP 2331 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002332 ER PT J AU Smith, S Isakov, J Jahn, T Puck, J Weinberg, K Taylor, N AF Smith, S Isakov, J Jahn, T Puck, J Weinberg, K Taylor, N TI Defective Jak1 and Jak3 signaling in cells with a mutant gamma(c) chain. SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RI Taylor, Naomi/H-4016-2014 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2366 EP 2366 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002367 ER PT J AU Silberstein, LE George, A Durdik, JM Kipps, TJ AF Silberstein, LE George, A Durdik, JM Kipps, TJ TI The V4-34 encoded anti-i autoantibodies recognize a large subset of B-cells and induce the production of secondary immunoglobulin isotypes SO BLOOD LA English DT Meeting Abstract C1 UNIV PENN,MED CTR,PHILADELPHIA,PA 19104. NIH,BETHESDA,MD 20892. UNIV ARKANSAS,FAYETTEVILLE,AR 72701. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2371 EP 2371 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002372 ER PT J AU Funakoshi, S Longo, DL Asai, O Beckwith, M Klinke, R Fanslow, WC Murphy, WJ AF Funakoshi, S Longo, DL Asai, O Beckwith, M Klinke, R Fanslow, WC Murphy, WJ TI Inhibition of aggressive histology human B-cell lymphoma growth by soluble recombinant human CD40 ligand. SO BLOOD LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,DCT,BRMP,LLB,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BCDP,FREDERICK,MD. IMMUNEX CORP,SEATTLE,WA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2397 EP 2397 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002398 ER PT J AU Levitsky, HI Montgomery, J Ahmadzadeh, M Longo, DL Kwak, LW AF Levitsky, HI Montgomery, J Ahmadzadeh, M Longo, DL Kwak, LW TI Immunization with GM-CSF-transduced, but not B7-1-transduced lymphoma cells primes idiotype: Specific T cells and generates potent systemic anti-tumor immunity SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BALTIMORE,MD 21205. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2399 EP 2399 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002400 ER PT J AU Hursting, SD Ward, JM Perkins, SN Haines, DC Frederickson, T Phang, JM AF Hursting, SD Ward, JM Perkins, SN Haines, DC Frederickson, T Phang, JM TI p53-knockout mice: A model of spontaneous lymphoma for testing chemopreventive strategies. SO BLOOD LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2403 EP 2403 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002404 ER PT J AU Straus, D Huang, J Testa, M Levine, A Kaplan, L AF Straus, D Huang, J Testa, M Levine, A Kaplan, L TI Prognostic factors in the treatment of HIV-associated non-Hodgkin lymphoma (HANHL): Analysis of ACTG 142 (low-dose vs standard-dose mBACOD plus GM-CSF). SO BLOOD LA English DT Meeting Abstract C1 NIAID,AIDS CLIN TRIALS GRP,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2404 EP 2404 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002405 ER PT J AU Rai, KR Peterson, B Kolitz, J Elias, L Shepherd, L Hines, J Cheson, B Schiffer, C AF Rai, KR Peterson, B Kolitz, J Elias, L Shepherd, L Hines, J Cheson, B Schiffer, C TI Fludarabine induces a high complete remission rate in previously-untreated patients with active chronic lymphocytic leukemia (CLL). A randomized Inter-group study. SO BLOOD LA English DT Meeting Abstract C1 ECOG,NCIC,CTG,SWOG,CALGB,CHICAGO,IL. NCI,CHICAGO,IL. 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 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2414 EP 2414 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002415 ER PT J AU Brown, KE Wong, S Desai, SM Coleman, P Dawson, GJ Mushahwar, IK Mat, B Binh, TV Be, TV Young, NS AF Brown, KE Wong, S Desai, SM Coleman, P Dawson, GJ Mushahwar, IK Mat, B Binh, TV Be, TV Young, NS TI High rate of GBC-C-A novel hepatitis virus-viremia in normal individuals in Ho Chi Minh City, Vietnam. SO BLOOD LA English DT Meeting Abstract C1 BLOOD TRANSFUS & HEMATOL CTR, VIRUS DISCOVERY GRP, HO CHI MINH CITY, 60064, VIETNAM. ABBOTT LABS, HEMATOL BRANCH, N CHICAGO, IL 20892 USA. NHLBI, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2420 EP 2420 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002421 ER PT J AU Barrett, AJ Couriel, D Dunbar, C Fox, M Young, NS OKunnief, P AF Barrett, AJ Couriel, D Dunbar, C Fox, M Young, NS OKunnief, P TI Low incidence of acute GVHD following delayed T-cell add-back after T-depleted BMT for hematologic malignancies SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BMT UNIT,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2463 EP 2463 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002464 ER PT J AU Migita, M Medin, JA Pawliuk, R Anderson, S Stahl, SK Amiri, M Humphries, RK Karlsson, S AF Migita, M Medin, JA Pawliuk, R Anderson, S Stahl, SK Amiri, M Humphries, RK Karlsson, S TI Selection and enzymatic correction of transduced cells from Gaucher patients using bicistronic vectors containing the genes for glucocerebrosidase and the selectable cell surface antigen, CD24. SO BLOOD LA English DT Meeting Abstract C1 NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. BRITISH COLUMBIA CANC AGCY,TERRY FOX LAB,VANCOUVER,BC V5Z 1L3,CANADA. NHLBI,HEMATOL BRANCH,GAITHERSBURG,MD. GENET THERAPY INC,GAITHERSBURG,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2492 EP 2492 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002493 ER PT J AU Gutierrez, MI Judde, JG Seam, N Magrath, IT Bhatia, KG AF Gutierrez, MI Judde, JG Seam, N Magrath, IT Bhatia, KG TI EBNA-1 dependent induction of cell lysis: A novel therapeutic approach specific for EBV associated lymphomas. SO BLOOD LA English DT Meeting Abstract C1 NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1995 VL 86 IS 10 SU 1 BP 2494 EP 2494 PG 1 WC Hematology SC Hematology GA TH910 UT WOS:A1995TH91002495 ER EF