FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Stansell, JD Osmond, DH Charlebois, E Lavange, L Wallace, JM Alexander, BV Glassroth, J Kvale, PA Rosen, MJ Reichman, LB Turner, JR Hopewell, PC Turner, J Merrifield, C Mossar, M Hirschtick, R Meiselman, L Manghisi, KK Cardozo, C Kalb, TH Mangura, BT Barnes, S Shapiro, B LeMaire, B Richer, B Au, J Coulson, A Markowitz, N Saravolatz, LD Johnson, C Huitsing, J Krystoforski, AM Poole, WK Rao, AV Clayton, K Hansen, NI Jordan, MC Thompson, J Myers, D Katzin, J Fulkerson, W Wilcosky, T Kalica, AR Wittes, J Follmann, DA Wise, R AF Stansell, JD Osmond, DH Charlebois, E Lavange, L Wallace, JM Alexander, BV Glassroth, J Kvale, PA Rosen, MJ Reichman, LB Turner, JR Hopewell, PC Turner, J Merrifield, C Mossar, M Hirschtick, R Meiselman, L Manghisi, KK Cardozo, C Kalb, TH Mangura, BT Barnes, S Shapiro, B LeMaire, B Richer, B Au, J Coulson, A Markowitz, N Saravolatz, LD Johnson, C Huitsing, J Krystoforski, AM Poole, WK Rao, AV Clayton, K Hansen, NI Jordan, MC Thompson, J Myers, D Katzin, J Fulkerson, W Wilcosky, T Kalica, AR Wittes, J Follmann, DA Wise, R TI Predictors of Pneumocystis carinii pneumonia in HIV-infected persons SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Thoracic-Society CY MAY 21-25, 1994 CL BOSTON, MA SP Amer Thorac Soc ID HUMAN-IMMUNODEFICIENCY-VIRUS; PULMONARY COMPLICATIONS; MEN AB The Pulmonary Complications of HIV Infection Study is a prospective, multicenter, observational study evaluating pulmonary disease among HIV-infected persons. For approximately 52 mo, 1,182 HIV-infected subjects were followed. Ail participants were evaluated for pulmonary disease on a predetermined schedule. There were 145 episodes of Pneumocystis carinii pneumonia (PCP). Low CD4 count correlated with risk of PCP (p < 0.0001); 79% had CD4 counts less than 100/mu l and 95% had CD4 counts less than 200/mu l. Subtle changes in diffusing capacity for carbon monoxide (DL(CO)) were associated with PCP. Univariate analysis identified recurrent undiagnosed fevers, night sweats, oropharyngeal thrush, and unintentional weight loss to be associated with risk among persons with CD4 counts above 200/mu l. Subjects in whom CD4 counts declined to below 200/mu l and who were not receiving preventive therapy were nine times more likely to develop PCP within 6 mo compared with subjects who received such therapy. A strong trend toward differences between the sexes was detected. black subjects had less than one third the risk of developing PCP as did white subjects (p < 0.0001). There was no significant difference in risk by HIV transmission category, study site, frequency of follow-up, age, education, smoking history, or use of antiretroviral therapy. Multivariable analysis revealed low CD4 lymphocyte count (p < 0.0001), use of prophylaxis (p < 0.0001), racial differences (p < 0.0001), and declining DL(CO) (p = 0.015) to influence risk. Constitutional signs and symptoms indicate increased risk for PCP among HIV-infected persons with CD4 counts above 200/mu l. C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. MED COLL PENN & HAHNEMANN UNIV,PHILADELPHIA,PA. HENRY FORD HOSP,DETROIT,MI 48202. BETH ISRAEL HOSP,MED CTR,NEW YORK,NY. NORTHWESTERN UNIV,EVANSTON,IL 60208. BETH ISRAEL MED CTR,MT SINAI MED CTR,NEW YORK,NY 10003. NHLBI,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. RES TRIANGLE INST,DATA COORDINATING CTR,RES TRIANGLE PK,NC. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,NEWARK,NJ 07103. OI Johnson, Christine Cole/0000-0002-6864-6604; Wise, Robert/0000-0002-8353-2349 FU PHS HHS [N01 H47-6031, N01 H47-6030, N01 H47-6029] NR 12 TC 76 Z9 80 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN PY 1997 VL 155 IS 1 BP 60 EP 66 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA WC670 UT WOS:A1997WC67000012 PM 9001290 ER PT J AU Rosen, MJ Clayton, K Schneider, RF Fulkerson, W Rao, AV Stansell, J Kvale, PA Glassroth, J Reichman, LB Wallace, JM Hopewell, PC Turner, J Osmond, D Merrifield, C Mossar, M Hirschtick, R Meiselman, L Manghisi, KK Schneider, R Mangura, BT Barnes, S Richer, B Au, J Coulson, A Clemente, V Markowitz, N Saravolatz, LD Johnson, C Huitsing, J Krystoforski, A Poole, WK Hansen, N Jordon, M Thompson, J Myers, D LaVange, L Katzin, J Wilcosky, T Lou, Y Kalica, AR Wittes, J Follmann, DA Cherniak, R Ware, JH Bartlett, JG Connett, JE Daniele, RP French, JF Goebel, FD Snider, DE Turino, GN AF Rosen, MJ Clayton, K Schneider, RF Fulkerson, W Rao, AV Stansell, J Kvale, PA Glassroth, J Reichman, LB Wallace, JM Hopewell, PC Turner, J Osmond, D Merrifield, C Mossar, M Hirschtick, R Meiselman, L Manghisi, KK Schneider, R Mangura, BT Barnes, S Richer, B Au, J Coulson, A Clemente, V Markowitz, N Saravolatz, LD Johnson, C Huitsing, J Krystoforski, A Poole, WK Hansen, N Jordon, M Thompson, J Myers, D LaVange, L Katzin, J Wilcosky, T Lou, Y Kalica, AR Wittes, J Follmann, DA Cherniak, R Ware, JH Bartlett, JG Connett, JE Daniele, RP French, JF Goebel, FD Snider, DE Turino, GN TI Intensive care of patients with HIV infection - Utilization, critical illnesses, and outcomes SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; RESPIRATORY-FAILURE; AIDS PATIENTS; MORTALITY; UNIT AB To examine intensive care unit (ICU) admission rates and diagnoses of patients with HIV infection, and to determine the outcomes of different critical illnesses, we analyzed data derived from the 63 patients who were admitted to an ICU from among the 1,130 adults with HIV infection who did not have AIDS at the time of enrollment in a multicenter prospective study. Patients were admitted and treated according to the judgment of their physicians. During 4,298 patient-yea rs of follow-up for the entire cohort, there were 1,320 hospital admissions, of which 68 (5%) included admission to an ICU. Twenty-five (40%) of the patients admitted to the ICU died during that admission. Twenty-four patients (38%) were admitted with a principal diagnosis of lung disease; 1 1 had Pneumocystis carinii pneumonia (PCP), one of whom was coinfected with Aspergillus fumigatus and Legionella pneumophilia, a nd six of them (55%) died. Four had bacterial pneumonia, two had pulmonary edema caused by renal failure, and one each had pulmonary tuberculosis, pulmonary Kaposi's sarcoma, pneumothorax, adult respiratory distress syndrome, severe pulmonary fibrosis, cytomegalovirus pneumonitis, and metastatic adenocarcinoma to the lungs. Eleven of these 14 patients (79%) died. Thirty-nine patients had 44 admissions for nonpulmonary diagnoses, including gastrointestinal disorders (14 admissions), cardiovascular disorders (nine), sepsis syndrome (six), neurologic disorders (four), monitoring and ICU nursing care during or after a procedure (four), metabolic disorders (three), trauma (two), drug overdose (one), and unknown reasons (one). Nine (23%) of these patients died. Twenty-eight patients underwent mechanical ventilation, and 16 (57%) died. Seven (25%) had PCP (five died), seven had other primary pulmonary diseases (six died), and 14 were placed on mechanical ventilation for nonpulmonary disorders (five died). Survival did not correlate with CD4 count determined within 6 mo of admission to the ICU. In conclusion, the range of indications for critical care in patients with HIV infection is diverse. PCP accounted for only 16% of the ICU admissions, and mechanical ventilation for PCP and other pulmonary disorders was associated with a high mortality rate. In contrast, mechanical ventilation for nonpulmonary disorders, and admission to the ICU for nonpulmonary diagnoses was associated with a more favorable outcome. C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. HENRY FORD HOSP,DETROIT,MI 48202. NORTHWESTERN UNIV,EVANSTON,IL. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,NEWARK,NJ 07103. NHLBI,BETHESDA,MD 20892. RP Rosen, MJ (reprint author), BETH ISRAEL MED CTR,DEPT MED,1ST AVE & 16TH ST,NEW YORK,NY 10003, USA. RI Andrade, Hugo/M-6631-2013; OI Andrade, Hugo/0000-0001-6781-6125; Johnson, Christine Cole/0000-0002-6864-6604 FU NHLBI NIH HHS [1-HR7-6029, 1-HR7-6030, 1-HR7-6031] NR 21 TC 48 Z9 49 U1 1 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN PY 1997 VL 155 IS 1 BP 67 EP 71 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA WC670 UT WOS:A1997WC67000013 PM 9001291 ER PT J AU Wallace, JM Hansen, NI Lavange, L Glassroth, J Browdy, BL Rosen, MJ Kvale, PA Mangura, BT Reichman, LB Hopewell, PC Stansell, J Turner, J Merrifield, C Osmond, D Mossar, M Hirschtick, R Meiselman, L Manghisi, KK Schneider, RF Barnes, S LeMaire, B Richer, B Clemente, V Au, J Coulson, A Sayre, J Markowitz, N Saravolatz, LD Johnson, C Huitsing, J Krystoforski, A Poole, WK Rao, AV Clayton, K Jordan, M Thompson, J Myers, D Katzin, J Fulkerson, W Lou, Y Wilcosky, T Kalica, AR Wittes, J Follman, D AF Wallace, JM Hansen, NI Lavange, L Glassroth, J Browdy, BL Rosen, MJ Kvale, PA Mangura, BT Reichman, LB Hopewell, PC Stansell, J Turner, J Merrifield, C Osmond, D Mossar, M Hirschtick, R Meiselman, L Manghisi, KK Schneider, RF Barnes, S LeMaire, B Richer, B Clemente, V Au, J Coulson, A Sayre, J Markowitz, N Saravolatz, LD Johnson, C Huitsing, J Krystoforski, A Poole, WK Rao, AV Clayton, K Jordan, M Thompson, J Myers, D Katzin, J Fulkerson, W Lou, Y Wilcosky, T Kalica, AR Wittes, J Follman, D TI Respiratory disease trends in the pulmonary complications of HIV infection study cohort SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PNEUMOCYSTIS-CARINII PNEUMONIA; LONGITUDINAL DATA-ANALYSIS; BLOOD-INSTITUTE WORKSHOP; TRIMETHOPRIM SULFAMETHOXAZOLE; AEROSOLIZED PENTAMIDINE; BACTERIAL PNEUMONIA; CONTROLLED TRIAL; NATIONAL-HEART; PROPHYLAXIS AB We examined trends in the incidence of specific respiratory disorders in a multicenter cohort with progressive human immunodeficiency virus (HIV) disease during a 5-yr period. individuals with a wide range of HIV disease severity belonging to three transmission categories were evaluated at regular intervals and for episodic respiratory symptoms using standard diagnostic algorithms. Yearly incidence rates of respiratory diagnoses were assessed in the cohort as a whole and according to CD4 count or HIV transmission category. The most frequent respiratory disorders were upper respiratory tract infections, but the incidence of lower respiratory tract infections increased as CD4 counts declined. Specific lower respiratory infections followed distinctive patterns according to study-entry CD4 count and transmission category. Acute bronchitis was the predominant lower respiratory infection of cohort members with entry CD4 counts greater than or equal to 200 cells/mm(3). In cohort members with entry CD4 counts of 200 to 499 cells/mm(3), the incidence of bacterial and Pneumocystis carinii pneumonia each increased an average of 40% per year. In members with entry CD4 counts < 200 cells/mm(3), acute bronchitis, bacterial pneumonia, and P. carinii pneumonia occurred at high rates without discernible time trends, despite chemoprophylaxis in more than 80% after Year 1, and the rate of other pulmonary opportunistic infections increased over time. Each year, injecting drug users had a higher incidence of bacterial pneumonia than did homosexual men. The yearly rate of tuberculosis was < 3 episodes/100 person-yr in each entry CD4 and HIV-transmission group. We conclude that the time trends of HIV-associated respiratory disorders are determined by HIV disease stage and influenced by transmission category. Whereas acute bronchitis is prevalent during all stages of HIV infection, incidence rates of bacterial pneumonia and P. carinii pneumonia rise continuously during progression to advanced disease. In advanced disease, the incidence of acute bronchitis, bacterial pneumonia and P. carinii pneumonia is high despite widespread chemoprophylaxis. C1 NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. BETH ISRAEL MED CTR,NEW YORK,NY 10003. HENRY FORD HOSP,DETROIT,MI 48202. UNIV MED & DENT NEW JERSEY,NEWARK,NJ 07103. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RES TRIANGLE INST,DATA COORDINATING CTR,RES TRIANGLE PK,NC. NHLBI,DIV LUNG DIS,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. RP Wallace, JM (reprint author), OLIVE VIEW UCLA MED CTR,DEPT MED,14445 OLIVE VIEW DR,RM 2B-182,SYLMAR,CA 91342, USA. OI Johnson, Christine Cole/0000-0002-6864-6604; Wise, Robert/0000-0002-8353-2349 FU NHLBI NIH HHS [N01-HR7-6030, N01-HR7-6031, N01-HR7-6029] NR 32 TC 131 Z9 138 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN PY 1997 VL 155 IS 1 BP 72 EP 80 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA WC670 UT WOS:A1997WC67000014 PM 9001292 ER PT J AU Kumar, S Kumar, D Kaldjian, EP Bauserman, S Raffeld, M Jaffe, ES AF Kumar, S Kumar, D Kaldjian, EP Bauserman, S Raffeld, M Jaffe, ES TI Primary low-grade B-cell lymphoma of the dura - A mucosa associated lymphoid tissue-type lymphoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE primary meningeal low-grade; B-cell lymphoma; MALT ID CENTRAL NERVOUS-SYSTEM; NON-HODGKINS LYMPHOMA; SOLITARY INTRACRANIAL PLASMACYTOMA; INVOLVEMENT AB The clinicopathologic findings in five patients with primary low-grade B-cell lymphoma of the intracranial dura are described. All patients were women, 40-62 years of age, who presented with focal neurologic symptoms. Radiologic studies showed a well-localized dural mass in each case, raising a preoperative diagnosis of meningioma. Cytologically these were composed of a diffuse infiltrate of small lymphocytes with plasmacytoid differentiation, with a variable admixture of centrocytelike cells. Lambda light chain restriction was found in three cases, and kappa light chain in one. VJ polymerase chain reaction for immunoglobulin heavy-chain rearrangement was positive in three of four cases, including one case in which immunostaining results were equivocal. Staging procedures did not show involvement at any other site. Therapy consisted of radiation (n = 3), chemotherapy (n = 1), or both (n = 1), with excellent response. There was no evidence of recurrence or subsequent dissemination at follow-up of up to 63 months. Low-grade B-cell lymphomas arising in the intracranial dura are rare but appear to be similar to other low-grade B-cell lymphomas arising in extranodal sites in terms of clinical presentation as stage 1E disease, indolent behavior, and favorable response to treatment, suggesting that they may be part of the mucosa associated lymphoid tissue (MALT) lymphoma spectrum. They appear to arise at dural sites where meningothelial cells are concentrated. C1 NCI,HEMATOPATHOL SECT,NIH,BETHESDA,MD 20892. UNIV MARYLAND MED SYST,BALTIMORE,MD. NR 26 TC 90 Z9 92 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 1997 VL 21 IS 1 BP 81 EP 87 DI 10.1097/00000478-199701000-00009 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA WB243 UT WOS:A1997WB24300009 PM 8990144 ER PT J AU Jaffe, ES AF Jaffe, ES TI Introduction to the WHO classification SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 67 Z9 92 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 1997 VL 21 IS 1 BP 114 EP 115 DI 10.1097/00000478-199701000-00014 PG 2 WC Pathology; Surgery SC Pathology; Surgery GA WB243 UT WOS:A1997WB24300013 ER PT J AU Kamchonwongpaisan, S McKeever, P Hossler, P Ziffer, H Meshnick, SR AF Kamchonwongpaisan, S McKeever, P Hossler, P Ziffer, H Meshnick, SR TI Artemisinin neurotoxicity: Neuropathology in rats and mechanistic studies in vitro SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID MALARIA PARASITES; OXYGEN RADICALS; NERVOUS-SYSTEM; IRON; TRANSFERRIN; FERRITIN; CULTURE; BRAIN; TOXICITY AB Despite the wide use of artemisinin and its derivatives, concerns have been raised about their potential neurotoxicity. Accordingly, studies were undertaken on rats treated with high doses of arteether and on mouse neuroblastoma cells (Neu2a) treated with H-3-dihydroartemisinin. Rats uniformly developed neurologic symptoms following intramuscular administration of 50 mg/kg/day of arteether for 5-6 days. Acute neuronal necrosis associated with vacuolization and focal axonal swelling in the neuropil was observed in specific areas of the brain, especially the vestibular nuclei and red nuclei. Scattered swollen neurons were also evident in the cerebellar nuclei and the reticular formation. No neurologic symptoms, neuronal nuclei necrosis, nor gliosis was observed in rats administered 25 or 30 mg/kg/day for six or eight days. In vitro, Neu2a cells took up much less H-3-dihydroartemisinin than Plasmodium falciparum-infected red blood cells when incubated under identical conditions for 4 hr with 4.2 mu M H-3-dihydroartemisinin. This selective uptake may explain why the artemisinin derivatives are selectively toxic to malaria parasites. Autoradiograms of sodium dodecyl sulfate-polyacrylamide gels run from H-3-dihydroartemisinin-treated cells showed that neuronal proteins with molecular weights of 27, 32, 40, and 81 kD were alkylated, although not nearly as strongly or rapidly as the P. falciparum proteins. The results indicate that while artemisinin derivatives have neurotoxic effects in rats and alkylate proteins in neuroblastoma cells, these effects only occur at high doses or after prolonged exposure. C1 UNIV MICHIGAN,DEPT EPIDEMIOL,SCH PUBL HLTH,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,DEPT PATHOL,ANN ARBOR,MI. NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-35827, NIAID 26848] NR 26 TC 71 Z9 74 U1 1 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JAN PY 1997 VL 56 IS 1 BP 7 EP 12 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA WL889 UT WOS:A1997WL88900002 PM 9063352 ER PT J AU Ramachandran, S Gam, AA Neva, FA AF Ramachandran, S Gam, AA Neva, FA TI Molecular differences between several species of Strongyloides and comparison of selected isolates of S-stercoralis using a polymerase chain reaction-linked restriction fragment length polymorphism approach SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID RIBOSOMAL-RNA GENE; CAENORHABDITIS; HYPERINFECTION; EVOLUTION; ELEGANS; DOGS; RDNA; DNA AB The relationships between the parasitic nematodes of medical importance belonging to the genus Strongyloides was studied using a polymerase chain reaction (PCR)-linked restriction fragment length polymorphism approach. We used several human and dog isolates of S. stercoralis, a monkey isolate of S. fulleborni, and S. ratti, a rodent parasite. The molecular analysis was based on amplification of the internal transcribed spacer and the 5' portion of the 23S-like rRNA gene followed by restriction enzyme digests. The length of the PCR product was specific to each species and varied around 1.5 kilobase pairs. Using nine restriction enzymes, we were able to analyze both interspecific and intraspecific variations. With four restriction enzymes (Taq I, Dde I, Dra I, and Mwo I), human isolates of S. stercoralis from different parts of the world showed identical patterns and could be differentiated from the dog isolate of S. stercoralis. Interspecific differences were readily observed with these and other enzymes. In addition to providing new information on the genomic characteristics of Strongyloides parasites, the results suggest that this technique could be useful for diagnostic and epidemiologic investigations. RP Ramachandran, S (reprint author), NIAID,PARASIT DIS LAB,CLIN PARASITOL UNIT,NIH,9000 ROCKVILLE PIKE,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 23 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JAN PY 1997 VL 56 IS 1 BP 61 EP 65 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA WL889 UT WOS:A1997WL88900013 PM 9063363 ER PT J AU Howcroft, TK Kirshner, SL Singer, DS AF Howcroft, TK Kirshner, SL Singer, DS TI Measure of transient transfection efficiency using beta-galactosidase protein SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID GENE; IDENTIFICATION; TRANSCRIPTION; SUBUNIT; CELLS AB Although the control elements which regulate the transcriptional activity of promoter sequences are largely determined by the use of reporter plasmids in transient transfection analyses, controlling variability in these experiments can often be a vexing problem. Problems arise when the promoter of the internal control plasmid, used to correct for transfection efficiency, either affects test promoter strength or is itself regulated by trans-acting factors of inducing agents used to study the test promoter. Here we report the use of beta-galactosidase protein as an unbiased standard of transfection efficiency. beta-Galactosidase protein is readily internalized by adherent cell lines when incorporated into a calcium phosphate precipitate; significant enzyme activity can be recovered up to 72 h after transfection. Use of beta-galactosidase protein as a control obviates the concerns associated with promoter dependent reporter plasmids as controls. (C) 1997 Academic Press, Inc. RP Howcroft, TK (reprint author), NCI,EXPT IMMUNOL BRANCH,NIH,BLDG 10,ROOM 4B-17,10 CTR DR MSC 1360,BETHESDA,MD 20892, USA. NR 10 TC 20 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 1 PY 1997 VL 244 IS 1 BP 22 EP 27 DI 10.1006/abio.1996.9868 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WC060 UT WOS:A1997WC06000003 PM 9025902 ER PT J AU Hawkins, ME Pfleiderer, W Balis, FM Porter, D Knutson, JR AF Hawkins, ME Pfleiderer, W Balis, FM Porter, D Knutson, JR TI Fluorescence properties of pteridine nucleoside analogs as monomers and incorporated into oligonucleotides SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID KLENOW FRAGMENT; BASE PAIR; ECO-RI; 2-AMINOPURINE; SPECTROSCOPY; KINETICS; DYNAMICS; DNA AB Eighteen fluorescent pteridine-based nucleoside analogs have been prepared that are suitable for synthesis as phosphoramidites and site-specific incorporation into oligonucleotides. Their quantum yields ranged from less than or equal to 0.03 to 0.88. The maximum excitation and emission wavelengths of seven selected probes with quantum yields >0.15 ranged from 334 to 358 and 400 to 444 nm,respectively. Fluorescence decay curves of the seven probes were biexponential, and the mean intensity-weighted lifetimes ranged from 0.87 to 6.54 ns. Incorporation of probes 4 and 17 (3-methylisoxanthopterin and 6-methylisoxanthopterin) into oligonucleotides significantly quenched their fluorescence signal, and the degree of quench correlated with the number and proximity of purines in the of oligonucleotide. Incorporation also resulted in a shift in absorbance-, emission-, and decay-associated spectra for 6-methylisoxanthopterin. An increase in the complexity of the decay curve and a decrease in the mean lifetime occurred for both probes. Formation of double-stranded oligonucleotides did not substantially increase the degree of quenching but generally increased the complexity of decay curves and decreased the mean lifetimes. Melting temperature, T-m, depression equivalent to that of a single base pair mismatch was observed in 3-methylisoxanthopterin-containing double-stranded oligonucleotides, while the T-m of 6-methylisoxanthopterin-containing double-stranded oligonucleotides were unperturbed, e.g., equivalent to unlabeled double-stranded oligonucleotides. This new class of fluorophore yields promising probes for the study of protein/DNA interactions. (C) 1997 Academic Press, Inc. C1 NHLBI,NIH,BETHESDA,MD 20892. UNIV KONSTANZ,FAK CHEM,D-7750 CONSTANCE,GERMANY. RP Hawkins, ME (reprint author), NCI,PEDIAT BRANCH,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 31 TC 119 Z9 119 U1 0 U2 9 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 1 PY 1997 VL 244 IS 1 BP 86 EP 95 DI 10.1006/abio.1996.9879 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WC060 UT WOS:A1997WC06000014 PM 9025913 ER PT J AU Oliver, GW Leferson, JD StetlerStevenson, WG Kleiner, DE AF Oliver, GW Leferson, JD StetlerStevenson, WG Kleiner, DE TI Quantitative reverse zymography: Analysis of picogram amounts of metalloproteinase inhibitors using gelatinase A and B reverse zymograms SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID TISSUE INHIBITOR; IV COLLAGENASE; MATRIX METALLOPROTEINASES; METASTASIS; EXPRESSION; INVASION; TIMP-2 AB Matrix metalloproteinases are a growing family of neutral pH optima, zinc atom-dependent endopeptidases that collectively degrade all components of the extracellular matrix. This family of related proteases is further defined by their inhibition of protease activity by a class of low-molecular-weight endogenous inhibitors known as tissue inhibitors of metalloproteinases or TIMPs, Reverse zymography is an electrophoretic technique used to identify TIMP inhibitory activity within acrylamide gels. Previous methods have generally used biochemically complex sources of proteolytic activity (such as cell culture conditioned media) copolymerized with a proteinase substrate in the gel to identify the zones of inhibited proteolysis. We describe a novel system for reverse zymography using purified recombinant human gelatinase A or gelatinase B in place of conditioned media. These reverse zymograms using recombinant gelatinase have sensitivities for TIMPs that are favorable in comparison to immunoblotting techniques but have the benefit of visualizing multiple inhibitors simultaneously. We have developed and characterized these methods for the evaluation of inhibitors and have shown them to be highly sensitive, convenient, and reproducible. Both systems detect TIMPs 1, 2, and 3 simultaneously, but with differential sensitivities for TIMPs 1 and 2. Using gelatinase A the system can detect as little as 1 pg of rTIMP-8, but the limit of detection for rTIMP-1 is 40 pg. Gelatinase B shows less differential activity in that the limits of detection are 60 and 40 pg for TIMP-2 and TIMP-1, respectively. We demonstrate how these varied sensitivities of the gelatinases for the TIMPs can contribute to potential pitfalls in systems using uncharacterized reagents (i.e., conditioned media). (C) 1997 Academic Press, Inc. C1 NCI,EXTRACELLULAR MATRIX PATHOL SECT,PATHOL LAB,NIH,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Kleiner, David/0000-0003-3442-4453 NR 19 TC 141 Z9 148 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 1 PY 1997 VL 244 IS 1 BP 161 EP 166 DI 10.1006/abio.1996.9895 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WC060 UT WOS:A1997WC06000023 PM 9025922 ER PT J AU Simmons, BR Bauer, KS McCall, NA Kohn, EC Figg, WD AF Simmons, BR Bauer, KS McCall, NA Kohn, EC Figg, WD TI An optimized method for the quantitation of carboxyamido-triazole (CAI) in human plasma with solid phase extraction and reversed phase HPLC SO ANALYTICAL LETTERS LA English DT Article DE CAI; HPLC; plasma; chromatography; carboxyamido-triazole pharmacokinetics ID CALCIUM INFLUX; RECEPTOR; INHIBITION; L651582; AGENT AB The anticancer agent CAI was quantitated from human plasma using a C-18 column with a mobile phase consisting of acetonitrile and water (each containing 0.01 M ammonium acetate) pumped over a gradient at a now rate of 1.0 mL/min. The detection of CAI and the internal standard, harmine, was accomplished using a photodiode-array detector set at 264 and 323 nm, respectively. The chromatographic run time was 17.5 minutes. The plasma samples were prepared for HPLC analysis using a C-18 solid phase extraction procedure. Two calibration curves were prepared, and the assay was shown to be linear in the concentration range of 0.02 to 0.5 mu g/mL for the low curve and 0.25 to 10.0 mu g/mL for the high curve, with average correlation coefficients of 0.9933 and 0.9938, respectively. Intraassay and Inter-assay imprecisions were less than 10.0% with an error of accuracy of less than 11.0%. The assay was reproducible with the sensitivity needed for the prediction of CAI levels in the plasma of cancer patients. RP Simmons, BR (reprint author), NCI,CLIN PHARMACOL BRANCH,DIV CLIN SCI,NIH,BLDG 10,ROOM 5A01,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 7 TC 3 Z9 3 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0003-2719 J9 ANAL LETT JI Anal. Lett. PY 1997 VL 30 IS 11 BP 2009 EP 2021 PG 13 WC Chemistry, Analytical SC Chemistry GA XU214 UT WOS:A1997XU21400004 ER PT S AU Minton, AP AF Minton, AP BE Jaenicke, R Durchschlag, H TI Alternative strategies for the characterization of associations in multicomponent solutions via measurement of sedimentation equilibrium SO ANALYTICAL ULTRACENTRIFUGATION IV SE PROGRESS IN COLLOID AND POLYMER SCIENCE LA English DT Proceedings Paper CT 10th Symposium on Analytical Ultracentrifugation CY MAR 13-14, 1997 CL REGENSBURG, GERMANY SP BASF AG, Ludwigshafen, Beckman Instruments GmbH, Munich, Biacore AB, Freiburg, Merck KGaA, Darmstadt, Pharmacia Biotech Europe GmbH, Freiburg, Regensburger Universitatsstift Hans Vielberth DE self-association; heteroassociation AB Four strategies for the analysis of sedimentation equilibrium of solutions containing two solute components in the context of models for equilibrium association are described: (1) Direct modeling of the equilibrium gradients of a single experimentally measurable signal measured in each of several samples of differing composition; (2) Direct modeling of the equilibrium gradients of two (or more) signals measured in each of several samples of differing composition; (3) Calculation of the independent component concentration gradients in individual samples via analysis of the gradients of two or more signals in the sample. followed by modeling of the component concentration gradients from several samples of differing composition; and (4) Calculation of the signal-average buoyant molar mass as a function of solution composition, followed by modeling of the composition dependence of the signal-average buoyant molar mass in the context of an association model. Examples of the application of each strategy are presented and compared, and conclusions are drawn regarding the relative utility of each method for different types of experiments and systems studied. C1 NIH, Bethesda, MD 20892 USA. RP Minton, AP (reprint author), NIH, Bldg 8,Room 226, Bethesda, MD 20892 USA. NR 0 TC 33 Z9 34 U1 0 U2 0 PU STEINKOPFF DARMSTADT PI BERLIN 33 PA C/O SPRINGER VERLAG, HEIDELBERGER PLATZ 3, 1000 BERLIN 33, GERMANY SN 0340-255X BN 3-7985-1106-3 J9 PROG COLL POL SCI S PY 1997 VL 107 BP 11 EP 19 PG 9 WC Chemistry, Physical; Polymer Science SC Chemistry; Polymer Science GA BK32A UT WOS:000071775100002 ER PT S AU Dimitriadis, EK Lewis, MS AF Dimitriadis, EK Lewis, MS BE Jaenicke, R Durchschlag, H TI Non-linear curve-fitting methods for data from the XL-A analytical ultracentrifuge SO ANALYTICAL ULTRACENTRIFUGATION IV SE PROGRESS IN COLLOID AND POLYMER SCIENCE LA English DT Proceedings Paper CT 10th Symposium on Analytical Ultracentrifugation CY MAR 13-14, 1997 CL REGENSBURG, GERMANY SP BASF AG, Ludwigshafen, Beckman Instruments GmbH, Munich, Biacore AB, Freiburg, Merck KGaA, Darmstadt, Pharmacia Biotech Europe GmbH, Freiburg, Regensburger Universitatsstift Hans Vielberth DE ultracentrifugation; Gaussian noise curve-fitting; least-squares estimation; maximum-likelihood estimation AB In equilibrium or velocity sedimentation experiments with the XL-A analytical ultracentrifuge it is customary to acquire absorbance data, The least-squares method is most widely used for fitting non-linear models to such collected data. It is here shown that due to the non-Gaussian characteristics of the noise in the absorbance data, the least-squares method is not optimal and introduces a systematic bias to the estimated parameters. This bias can be eliminated by either using the maximum-likelihood. method on the absorbance data or otherwise by fitting the intensity data directly. The probability distribution of the noise in the latter is Gaussian and the least-squares estimation is equivalent to maximum likelihood. The methodology for using the intensity data is developed and simulations for a variety of systems are performed. C1 NIH, NCRR, Biomed Engn & Instrumentat Program, Bethesda, MD 20892 USA. RP Dimitriadis, EK (reprint author), NIH, NCRR, Biomed Engn & Instrumentat Program, Bldg 13,Room 3N17,13 South Dr,MSC 5766, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU STEINKOPFF DARMSTADT PI BERLIN 33 PA C/O SPRINGER VERLAG, HEIDELBERGER PLATZ 3, 1000 BERLIN 33, GERMANY SN 0340-255X BN 3-7985-1106-3 J9 PROG COLL POL SCI S PY 1997 VL 107 BP 20 EP 26 PG 7 WC Chemistry, Physical; Polymer Science SC Chemistry; Polymer Science GA BK32A UT WOS:000071775100003 ER PT J AU Njoku, D Laster, MJ Gong, DH Eger, EI Reed, GF Martin, JL AF Njoku, D Laster, MJ Gong, DH Eger, EI Reed, GF Martin, JL TI Biotransformation of halothane, enflurane, isoflurane, and desflurane to trifluoroacetylated liver proteins: Association between protein acylation and hepatic injury SO ANESTHESIA AND ANALGESIA LA English DT Article ID HEPATOTOXICITY; METABOLITES; NEOANTIGENS; ANTIBODIES; ANESTHESIA; NECROSIS; EXPOSURE AB In susceptible patients, halothane, enflurane, isoflurane, and desflurane can produce severe hepatic injury by an immune response directed against reactive anesthetic metabolites covalently bound to hepatic proteins. The incidence of hepatotoxicity appears to directly correlate with anesthetic metabolism catalyzed by cytochrome P450 2E1 to trifluoroacetylated hepatic proteins. Ln the present study, we examined whether the extent of acylation of hepatic proteins in rats by halothane, enflurane, isoflurane, and desflurane correlated with reported relative rates of metabolism. After pretreatment with the P450 2E1 inducer isoniazid, five groups of 10 rats breathed 1.25 minimum alveolar anesthetic concentration (MAC) of halothane, enflurane, isoflurane, or desflurane in oxygen, or oxygen alone, each for 8 h. Immunochemical analysis of livers harvested 18 h after anesthetic exposure showed tissue acylation (greatest to least) after exposure to halothane, enflurane, or isoflurane. Reactivity was not different between isoflurane as compared to desflurane or oxygen alone. An enzyme-linked immunosorbent assay showed halothane reactivity was significantly greater than that of enflurane, isoflurane, desflurane, or oxygen, and that enflurane reactivity was significantly greater than desflurane or oxygen. Sera from patients with a clinical diagnosis of halothane hepatitis showed antibody reactivity against hepatic proteins from rats exposed to halothane or enflurane. No reactivity was detected in rats exposed to isoflurane, desflurane, or oxygen alone. These results indicate that production of acylated proteins may be an important mediator of anesthetic-induced hepatotoxicity. C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. UNIV CALIF SAN FRANCISCO,DEPT ANESTHESIOL,SAN FRANCISCO,CA 94143. NIAID,DIV MICROBIOL & INFECT DIS,BIOMETRY BRANCH,NIH,BETHESDA,MD 20892. NR 25 TC 106 Z9 113 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 1997 VL 84 IS 1 BP 173 EP 178 DI 10.1097/00000539-199701000-00031 PG 6 WC Anesthesiology SC Anesthesiology GA WA795 UT WOS:A1997WA79500032 PM 8989020 ER PT J AU Wheeler, DM Rice, RT duBell, WH Spurgeon, HA AF Wheeler, DM Rice, RT duBell, WH Spurgeon, HA TI Initial contractile response of isolated rat heart cells to halothane, enflurane, and isoflurane SO ANESTHESIOLOGY LA English DT Article DE anesthetics, volatile, enflurane, halothane, isoflurane; heart, calcium current, contractility, sarcoplasmic reticulum; ions, calcium ID CARDIAC SARCOPLASMIC-RETICULUM; PAPILLARY-MUSCLE TENSION; DECREASE CALCIUM CONTENT; VOLATILE ANESTHETICS; VENTRICULAR CELLS; INHALATION ANESTHETICS; MYOCYTES; TRANSIENTS; POTENTIALS; SOLUBILITY AB Background: In several beating cardiac muscle preparations, a short-lived increase in twitch tension or amplitude has been observed when they were exposed abruptly to solutions containing halothane or enflurane. As exposure to the anesthetics was continued, the expected negative inotropic effect became evident after the short-lived increase in twitch. No such increase in twitch has been reported during exposure to isoflurane. It has been hypothesized that this short-lived increase in twitch is caused by an enhancement of calcium release from the sarcoplasmic reticulum, but other mechanisms have not been excluded. Methods: Freshly isolated, single rat ventricular cells were stimulated to beat at room temperature and abruptly exposed to solutions containing halothane (0.25-0.64 mM), enflurane (0.69-1 mM), or isoflurane (0.31-0.54 mM). During these exposures, twitch amplitude was measured and intracellular calcium concentration was followed using the calcium-sensitive dye indo-1, In some experiments, the whole-cell patch-clamp technique was used to measure membrane current. In addition, in several cells the sarcoplasmic reticulum calcium content was assessed through the response to brief pulses of caffeine. Results: Both the twitch amplitude and the intracellular calcium transient were increased temporarily in cells abruptly exposed to halothane or enflurane, No such behavior was found with isoflurane. After continued exposure to all three agents, both the twitch amplitude and the calcium transient were less than control. During the beats exhibiting an increase in twitch, no alteration in the relation between cell length (twitch amplitude) and the intracellular calcium transient was found compared with control conditions. In addition, the temporary increase in twitch amplitude occurred in cells contracting under voltage-clamp control when halothane was introduced, and it was not associated with any increase in the calcium current. The sarcoplasmic reticulum calcium content at the time of the halothane-induced increase in twitch also was not increased, Conclusions: The short-lived increase in twitch after abrupt exposure to halothane or enflurane is related to increased intracellular calcium during the beat and not to any changes in myofilament sensitivity to calcium, Because these results eliminate most alternative explanations for this phenomenon, the authors conclude that halothane, and probably also enflurane, increases the fraction of calcium released from the sarcoplasmic reticulum with each heart beat. Isoflurane appears to lack this action. C1 JOHNS HOPKINS MED INST, DEPT ANESTHESIOL & CRIT CARE MED, BALTIMORE, MD 21205 USA. NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. FU NIGMS NIH HHS [R29 GM39568] NR 34 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 1997 VL 86 IS 1 BP 137 EP 146 DI 10.1097/00000542-199701000-00018 PG 10 WC Anesthesiology SC Anesthesiology GA WB868 UT WOS:A1997WB86800018 PM 9009949 ER PT J AU Baumrind, S Bravo, LA BenBassat, Y Curry, S Korn, EL AF Baumrind, S Bravo, LA BenBassat, Y Curry, S Korn, EL TI Lower molar and incisor displacement associated with mandibular remodeling SO ANGLE ORTHODONTIST LA English DT Article DE cephalometrics; metallic implants; mandibular modeling remodeling; alveolar modeling remodeling; craniofacial growth ID METALLIC IMPLANTS; SUPERIMPOSITION; QUANTITATION; CEPHALOGRAMS; AGE AB The purpose of this study was to quantify the amount of alveolar modeling at the apices of the mandibular incisor and first molar specifically associated with appositional and resorptive changes on the lower border of the mandible during growth and treatment. Cephalometric data from superimpositions on anterior cranial base, mandibular implants of the Bjork type, and anatomical ''best fit'' of mandibular border structures were integrated using a recently developed strategy, which is described. Data were available at annual intervals between 8.5 and 15.5 years for a previously described sample of approximately 30 children with implants. The average magnitudes of the changes at the root apices of the mandibular first molar and central incisor associated with modeling/remodeling of the mandibular border and symphysis were unexpectedly small. At the molar apex, mean values approximated zero in both anteroposterior and vertical directions. At the incisor apex, mean values approximated zero in the anteroposterior direction and averaged less than 0.15 mm/year in the vertical direction. Standard deviations were roughly equal for the molar and the incisor in both the anteroposterior and vertical directions. Dental displacement associated with surface modeling plays a smaller role in final tooth position in the mandible than in the maxilla. It may also be reasonably inferred that anatomical best-fit superimpositions made in the absence of implants give a more complete picture of hard tissue turnover in the mandible than they do in the maxilla. C1 UNIV MED & DENT NEW JERSEY,NEWARK,NJ 07103. UNIV PACIFIC,SAN FRANCISCO,CA. UNIV MURCIA,FAC MED,SCH STOMATOL,E-30001 MURCIA,SPAIN. HEBREW UNIV JERUSALEM,DEPT ORTHODONT,HADASSAH SCH DENT MED,JERUSALEM,ISRAEL. NCI,CLIN TRIALS SECT,BIOMETR RES BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,CRANIOFACIAL RES INSTRUMENTAT LAB,DEPT GROWTH & DEV,SCH DENT,SAN FRANCISCO,CA 94143. FU NIDCR NIH HHS [DE07332, DE08713] NR 33 TC 1 Z9 3 U1 0 U2 1 PU ANGLE ORTHODONTISTS RES EDUC FOUNDATION INC PI APPLETON PA 100 W LAWRENCE ST, SUITE 406, APPLETON, WI 54911 SN 0003-3219 J9 ANGLE ORTHOD JI Angle Orthod. PY 1997 VL 67 IS 2 BP 93 EP 102 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WT635 UT WOS:A1997WT63500011 PM 9107373 ER PT B AU Chhabra, RS Bucher, JR Stokes, WS AF Chhabra, RS Bucher, JR Stokes, WS BE vanZutphen, LFM Balls, M TI US National Toxicology Program strategies for use of alternate test systems SO ANIMAL ALTERNATIVES, WELFARE, AND ETHICS SE DEVELOPMENTS IN ANIMAL AND VETERINARY SCIENCES LA English DT Proceedings Paper CT 2nd World Congress on Alternatives and Animal Use in the Life Sciences CY OCT 20-24, 1996 CL UTRECHT, NETHERLANDS SP Johns Hopkins Univ, Ctr Alternat Anim Testing, European Cosmet Toiletry & Perfumery Assoc, European Commiss DGXI, European Commiss ECVAM, L Oreal, Procter & Gamble, Solvay Duphar, Wella AB US National Toxicology Program (NTP), toxicity and carcinogenicity study designs seek maximum toxicology information on chemicals, while following the philosophy of the Three Rs: using reduced (optimum) numbers of animals, replacing animals with nonanimal methods where possible, and refining animal procedures to minimize discomfort. Chemicals selected for toxicologic and carcinogenic evaluation are examined in a sequence of acute (single exposure), subacute (14-day exposure), subchronic (90-day exposure) and chronic (2-year exposure) studies. The NTP rarely performs acute studies, limits 14-day studies, and evaluates multiple toxicity endpoints in a common set of animals for 90-day studies. This integrated 90-day toxicology study design provides data to determine the need for further genetic, reproductive, neurobehavioral, immunotoxicity and mechanistic studies. Transgenic mouse and fish models are under evaluation. This may reduce the number of 2-year rodent studies necessary. Recent toxicity studies on dicyclohexylcarbodiimide (DCC) and diisopropylcarbodiimide (DIG) illustrate the testing strategy the NTP has adopted to strengthen the database on the alternative test systems. RP Chhabra, RS (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-82424-3 J9 DEV AN VET PY 1997 VL 27 BP 607 EP 615 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy; Toxicology; Veterinary Sciences; Zoology SC Research & Experimental Medicine; Pharmacology & Pharmacy; Toxicology; Veterinary Sciences; Zoology GA BJ87M UT WOS:A1997BJ87M00079 ER PT B AU Kohn, MC Lucier, GW AF Kohn, MC Lucier, GW BE vanZutphen, LFM Balls, M TI Mechanism-based toxicology in cancer risk assessment: biologically based models SO ANIMAL ALTERNATIVES, WELFARE, AND ETHICS SE DEVELOPMENTS IN ANIMAL AND VETERINARY SCIENCES LA English DT Proceedings Paper CT 2nd World Congress on Alternatives and Animal Use in the Life Sciences CY OCT 20-24, 1996 CL UTRECHT, NETHERLANDS SP Johns Hopkins Univ, Ctr Alternat Anim Testing, European Cosmet Toiletry & Perfumery Assoc, European Commiss DGXI, European Commiss ECVAM, L Oreal, Procter & Gamble, Solvay Duphar, Wella AB Because of inadequate information, many risk assessment models are highly simplified and fail to reflect the biological processes responsible for a chemical's observed toxicity. Therefore, they do not provide a scientific basis for reliable toxicological evaluations, emphasizing uncertainties in predicted exposure-response relationships. When adequate mechanistic data are available, these uncertainties can be reduced by representing the responses of the animal in a mathematical model that realistically reproduces the animal's physiology and the biochemical mechanisms producing the toxicity. If the model accurately reproduces a variety of observed responses in the animal and the chemical has the same mechanism of action in humans, substituting parameter values appropriate for humans into the model's equations should reliably estimate responses of humans at their typically lower exposures. A mechanistic model of the disposition of 1,3-butadiene predicted up to 50-fold higher blood concentrations of its carcinogenic metabolite 1,2-epoxy-3-butene in mice compared to humans at equivalent exposures. However, at equivalent computed cumulative absorbed butadiene/kg body weight, the model predicts only a 5-fold species difference in blood epoxide. As a result of its accurate representation of physiological differences between the species, the mathematical model supports use of the mouse as a biological model for human responses to butadiene. A mechanistic model of the disposition and biochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat accurately reproduces observed alterations in cellular proteins which may be indicative of this compound's carcinogenic effects. By predicting and quantitating biomarkers for cancer outcomes, mechanistic models can focus toxicological research and make more efficient use of animals. RP Kohn, MC (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-82424-3 J9 DEV AN VET PY 1997 VL 27 BP 617 EP 625 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy; Toxicology; Veterinary Sciences; Zoology SC Research & Experimental Medicine; Pharmacology & Pharmacy; Toxicology; Veterinary Sciences; Zoology GA BJ87M UT WOS:A1997BJ87M00080 ER PT B AU Stokes, WS AF Stokes, WS BE vanZutphen, LFM Balls, M TI Criteria for the validation and acceptance of toxicological test methods SO ANIMAL ALTERNATIVES, WELFARE, AND ETHICS SE DEVELOPMENTS IN ANIMAL AND VETERINARY SCIENCES LA English DT Proceedings Paper CT 2nd World Congress on Alternatives and Animal Use in the Life Sciences CY OCT 20-24, 1996 CL UTRECHT, NETHERLANDS SP Johns Hopkins Univ, Ctr Alternat Anim Testing, European Cosmet Toiletry & Perfumery Assoc, European Commiss DGXI, European Commiss ECVAM, L Oreal, Procter & Gamble, Solvay Duphar, Wella AB An international workshop on harmonization of validation and acceptance criteria for alternative toxicological test methods was convened by the Test Guidelines Programme of the Organisation for Economic Cooperation and Development (OECD) on 22-24 January 1996, in Solna, Sweden. The objective for the first of the three subjects discussed was to reach consensus on harmonized principles and criteria for the validation and acceptance of any new or revised test methods, including both animal and nonanimal methods. Background references included recent documents from the European Center for Validation of Alternative Methods (ECVAM), and the US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). Specific criteria were developed that new and revised test methods should meet in order to be considered as having undergone adequate validation or to be considered acceptable for regulatory use. Recommendations were developed for other considerations, including: the need for flexibility, validation of test methods in a battery approach, validation of adjunct tests, parallel submission of data from existing and new methods, and acceptance of patented test methods. Internationally harmonized criteria for validation and regulatory acceptance are expected to facilitate worldwide review and adoption of improved toxicological test methods that will support enhanced protection of human health and the environment, and benefit animal welfare by the replacement, reduction, and refinement of animal use. RP Stokes, WS (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-82424-3 J9 DEV AN VET PY 1997 VL 27 BP 1199 EP 1206 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy; Toxicology; Veterinary Sciences; Zoology SC Research & Experimental Medicine; Pharmacology & Pharmacy; Toxicology; Veterinary Sciences; Zoology GA BJ87M UT WOS:A1997BJ87M00162 ER PT B AU Stokes, WS Ono, H AF Stokes, WS Ono, H BE vanZutphen, LFM Balls, M TI The harmonization of criteria for validation and regulatory acceptance of alternative toxicological tests. A synopsis of the follow-up to the OECD Workshop SO ANIMAL ALTERNATIVES, WELFARE, AND ETHICS SE DEVELOPMENTS IN ANIMAL AND VETERINARY SCIENCES LA English DT Proceedings Paper CT 2nd World Congress on Alternatives and Animal Use in the Life Sciences CY OCT 20-24, 1996 CL UTRECHT, NETHERLANDS SP Johns Hopkins Univ, Ctr Alternat Anim Testing, European Cosmet Toiletry & Perfumery Assoc, European Commiss DGXI, European Commiss ECVAM, L Oreal, Procter & Gamble, Solvay Duphar, Wella AB The OECD Workshop, held on 22-24 January 1996 in Solna, Sweden, was an important first step to achieve internationally harmonized principles and criteria for the validation and acceptance of alternative toxicological test methods. There was broad participation from all interested parties, including over 50 representatives from animal welfare organizations, government regulatory and research agencies, industry and academia. The Workshop used existing work on criteria from many organizations, including recent publications from CAAT, ECVAM and ICCVAM. The Workshop participants a) reached consensus on harmonized principles and criteria for the validation and acceptance of toxicological test methods, with an emphasis on alternative tests; b) developed guidance for Validation procedures; c) developed general principles for testing strategies and tiered testing schemes that could incorporate alternative tests; and d) developed draft tiered testing schemes for dermal and ocular irritation that will be proposed in revised OECD testing guidelines. The OECD Workshop report will form the basis for an OECD Guidance Document that will describe the validation process in greater detail. The proposals and recommendations of the OECD Workshop were discussed during a World Congress Workshop in Utrecht. This contribution presents a synopsis of this Workshop. C1 HATANO RES INST,FOOD & DRUG SAFETY CTR,HADANO,KANAGAWA,JAPAN. RP Stokes, WS (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-82424-3 J9 DEV AN VET PY 1997 VL 27 BP 1215 EP 1219 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy; Toxicology; Veterinary Sciences; Zoology SC Research & Experimental Medicine; Pharmacology & Pharmacy; Toxicology; Veterinary Sciences; Zoology GA BJ87M UT WOS:A1997BJ87M00165 ER PT B AU Shiloach, J Kaufman, J Trinh, L Kemp, C AF Shiloach, J Kaufman, J Trinh, L Kemp, C BE Carrondo, MJT Griffiths, B Moreira, JLP TI Continuous production of the extracellular domain of recombinant human Ca++ receptor from HEK 293 cells using novel serum free medium. SO ANIMAL CELL TECHNOLOGY: FROM VACCINES TO GENETIC MEDICINE LA English DT Proceedings Paper CT 14th Meeting of the ESACT on Animal Cell Technology - From Vaccines to Genetic Medicine CY MAY, 1996 CL VILAMOURA, PORTUGAL SP European Soc Anim Cell Technol, Bayer, Baxter, Boehringer Ingelheim, Genentech, Hoffmann La Roche, Hyclone Europe, Microbiol Associates, Novo Nordisk, Pharm Biotech, SmithKline Beecham, Akzo Nobel Pharm, Boehringer Mannheim, Ciba Geigy, E Merck, Glaxo Wellcome, Intervet, Pasteur Merieux Serums & Vaccins, Schering, ATCC, Celltech Biol, IBET, European Commiss, DGXII Biol, Caloste Gulbenkian Fdn, F C G, Luso Amer Dev Fdn, Junta Nacl Investig Cient & Tecnol, Aber Instruments Ltd, Amicon, Ashby Sci Ltd, B Braum Biotech Int, Bayer Corp, Diagnost Div, US, Bibby Sterilin, BioInvent Int AB, Bioproc Ltd qq, Cansera Int Inc, Corning Hazleton, Costar Europe Ltd, E C A C C, Greiner GmbH, Hucoa Erloss, Inceltech France, Inst Pasteur, Inversek Res, JRH Biosci, Life Technol Ltd, LSL Biolafitte, Cellex Biosci, MicroSafe B V, Molec Devices, Nalge Nunc Int, Nature, Macmillan Magazines Ltd, PAA Labs GmbH, Pall Europe Ltd, Q One Biotech Ltd, Qual Biotech NV, Sarstedt, Scharfe Syst GmbH, Sigma BioSci, Sorvall Centrifuge Prod, TC Tech Corp, Unisyn Technol Inc RP Shiloach, J (reprint author), NIDDK,NIH,BIOTECHNOL,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4321-2 PY 1997 BP 535 EP 540 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology; Research & Experimental Medicine GA BH07Q UT WOS:A1997BH07Q00085 ER PT J AU Selker, HP Zalenski, RJ Antman, EM Aufderheide, TP Bernard, SA Bonow, RO Gibler, WB Hagen, MD Johnson, P Lau, J McNutt, RA Ornato, J Schwartz, JS Scott, JD Tunick, PA Weaver, WD AF Selker, HP Zalenski, RJ Antman, EM Aufderheide, TP Bernard, SA Bonow, RO Gibler, WB Hagen, MD Johnson, P Lau, J McNutt, RA Ornato, J Schwartz, JS Scott, JD Tunick, PA Weaver, WD TI An evaluation of technologies for identifying acute cardiac ischemia in the emergency department: Executive summary of a National Heart Attack Alert Program Working Group report SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID CORONARY-CARE-UNIT; ACUTE MYOCARDIAL-INFARCTION; PREDICTIVE INSTRUMENT; CLINICAL-TRIAL; CHEST PAIN; MULTICENTER; ADMISSION; TIME; TIPI RP Selker, HP (reprint author), NHLBI,NATL HEART ATTACK ALERT PROGRAM,NIH,BLDG 31,ROOM 4A18,31 CTR DR,MSC 2480,BETHESDA,MD 20892, USA. NR 15 TC 66 Z9 67 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JAN PY 1997 VL 29 IS 1 BP 1 EP 12 DI 10.1016/S0196-0644(97)70297-X PG 12 WC Emergency Medicine SC Emergency Medicine GA WC259 UT WOS:A1997WC25900001 PM 8998085 ER PT J AU Selker, HP Zalenski, RJ Antman, EM Aufderheide, TP Bernard, SA Bonow, RO Gibler, WB Hagen, MD Johnson, P Lau, J McNutt, RA Ornato, J Schwartz, JS Scott, JD Tunick, PA Weaver, WD AF Selker, HP Zalenski, RJ Antman, EM Aufderheide, TP Bernard, SA Bonow, RO Gibler, WB Hagen, MD Johnson, P Lau, J McNutt, RA Ornato, J Schwartz, JS Scott, JD Tunick, PA Weaver, WD TI An evaluation of technologies for identifying acute cardiac ischemia in the emergency department: A report from a National Heart Attack Alert Program Working Group SO ANNALS OF EMERGENCY MEDICINE LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; CREATINE-KINASE-MB; ACUTE CHEST PAIN; UNSTABLE ANGINA-PECTORIS; RIGHT VENTRICULAR INFARCTION; ST-SEGMENT DEPRESSION; CARE-UNIT ADMISSION; SERUM TROPONIN-T; EXERCISE RADIONUCLIDE VENTRICULOGRAPHY RP Selker, HP (reprint author), NHLBI,NATL HEART ATTACK ALERT PROGRAM,NIH,BLDG 31,ROOM 4A18,31 CTR DR,MSC 2480,BETHESDA,MD 20892, USA. NR 306 TC 120 Z9 125 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JAN PY 1997 VL 29 IS 1 BP 13 EP 87 DI 10.1016/S0196-0644(97)70298-1 PG 75 WC Emergency Medicine SC Emergency Medicine GA WC259 UT WOS:A1997WC25900002 PM 8998086 ER PT J AU Scheirer, CJ Geller, RG AF Scheirer, CJ Geller, RG TI NIH reinvention activities: Status report SO ANNALS OF EPIDEMIOLOGY LA English DT Editorial Material RP Scheirer, CJ (reprint author), NHLBI,DIV EXTRAMURAL AFFAIRS,NIH,BETHESDA,MD 20892, USA. NR 0 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 1997 VL 7 IS 1 BP 1 EP 2 DI 10.1016/S1047-2797(96)00153-6 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WH069 UT WOS:A1997WH06900001 ER PT J AU Ludwig, EH Borecki, IB Ellison, RC Folsom, AR Heiss, G Higgins, M Lalouel, JM Province, MA Rao, DC AF Ludwig, EH Borecki, IB Ellison, RC Folsom, AR Heiss, G Higgins, M Lalouel, JM Province, MA Rao, DC TI Associations between candidate loci angiotensin-converting enzyme and angiotensinogen with coronary heart disease and myocardial infarction: The NHLBI Family Heart Study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE ACE; AGT; case-control study; epistasis; gene interactions; Caucasian; Black ID DELETION POLYMORPHISM; RISK FACTOR; GENE; HYPERTENSION; JAPANESE; GENOTYPE; VARIANT AB Angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) are major components of the renin-angiotensin systems. An association between myocardial infarction (MI) and the ACE DD genotype of the insertion/deletion (ID) polymorphism in intron 16 of the ACE gene has been reported. However, other similarly designed studies have not found such an association. Angiotensin II, the product of AGT, has a direct effect on vascular tone; and a variant in the AGT gene has been found to be associated with MI in the Japanese. This case-control study was initiated to investigate whether the ACEI/D and AGT M235T polymorphisms are associated with an increased risk for coronary heart disease (CHD) and MI. Our study groups were composed of participants in the National Heart Lung Blood Institute (NHLBI) Family Heart Study (FHS) selected from. three population-based studies: two Atherosclerosis Risk in Communities (ARIC) centers (Forsyth County, NC, and Minneapolis, MN), and the Framingham Heart Study. In multivariate analysis within ARIC Caucasians, a significant positive association was found between CHD (controls = 230, cases = 232) and the AGT TT genotype (P = 0.022; OR = 1.84, 1.09-3.10 95% CI). When we restricted the analysis to a low-risk group for CHD (controls = 70, cases = 35) an interaction between the ACE DD and AGT TT genotypes was significant (P = 0.025; OR = 5.02 1.22-20.6 95% CI). After further subsetting low-risk cases to those with a definite MI (controls = 74, cases = 16), we found that the association with the ACE DD genotype was also significant (P = 0.013, OR = 3.94, 1.28-12.2 95% CI). Comparable tests in the Framingham sample failed to support an association of these markers with CHD. In conclusion, within selected groups the ACE D and AGT 2353 alleles are statistically associated with CHD and MI, and there is a synergistic interaction between the two alleles. These results and those from previous studies together suggest that the association of these two loci is neither strong nor consistent and involves a complex interaction among risk factors and genotypes. (C) 1997 by Elsevier Science Inc. C1 UNIV WASHINGTON,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO. UNIV WASHINGTON,SCH MED,DEPT GENET,ST LOUIS,MO. BOSTON UNIV,SCH MED,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02118. UNIV MINNESOTA,DIV EPIDEMIOL,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC. NHLBI,BETHESDA,MD. RP Ludwig, EH (reprint author), UNIV UTAH,HOWARD HUGHES MED INST,ECCLES INST HUMAN GENET,DEPT HUMAN GENET,BLDG 533,SUITE 6200,SALT LAKE CITY,UT 84112, USA. FU NHLBI NIH HHS [N01-HC-25108, N01-HC-55019, N01-HC-55018] NR 32 TC 43 Z9 45 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 1997 VL 7 IS 1 BP 3 EP 12 DI 10.1016/S1047-2797(96)00105-6 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WH069 UT WOS:A1997WH06900002 PM 9034401 ER PT J AU Borecki, IB Province, MA Ludwig, EH Ellison, RC Folsom, AR Heiss, G Lalouel, JM Higgins, M Rao, DC AF Borecki, IB Province, MA Ludwig, EH Ellison, RC Folsom, AR Heiss, G Lalouel, JM Higgins, M Rao, DC TI Associations of candidate loci angiotensinogen and angiotensin-converting enzyme with severe hypertension: The NHLBI Family Heart Study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE angiotensinogen; angiotensin-converting enzyme; epistasis; hypertension; genotypes; case-control study; Blacks; Caucasians ID BLOOD-PRESSURE; DELETION POLYMORPHISM; MYOCARDIAL-INFARCTION; AFRICAN-AMERICANS; RISK FACTOR; GENE; VARIANTS; PREECLAMPSIA; LINKAGE; WHITE AB PURPOSE: In studies conducted in several different populations, the M235T substitution in the antiotensinogen (AGT) locus has been associated with hypertension. METHODS: A case-control study was initiated in an attempt to replicate this finding. Persons with hypertension, age- and sex-matched normotensive controls, and randomly sampled individuals were probands from the Family Heart Study of the National Heart, Lung, and Blood Institute. Subjects were recruited from the Atherosclerosis Risk in Communities study (ARIC) in North Carolina and Minneapolis, MN, and from the Framingham Heart Study in Massachusetts. Genotypes were determined for the M235T substitution in the AGT locus and for the insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) locus. Simple association tests as well as logistic regression analyses were performed. RESULTS: The association of AGT-T235 with hypertension was replicated in the Framingham sample (odds ratio, 1.60; 95% confidence interval, 1.11-2.30), but not in the ARIC white or black subjects. However, logistic regression analysis suggested a significant association of AGT with hypertension in both the ARIC white and Framingham samples when the effects of body mass index, triglycerides, and the presence of significant coronary heart disease were controlled. These analyses further suggested that, in the ARIC data, the relationship with the AGT locus is stronger in women than men and that there may be interaction (epistasis) between homozygotes for T235 and ACE-DD in the Framingham data. While the small sample size precluded logistic regression analysis, the frequency of the T235 allele in the black random sample was much higher than in the comparable white sample. CONCLUSIONS: These results are compatible with the presence of a genetic risk factor for hypertension in or near the angiotensinogen locus. (C) 1997 by Elsevier Science Inc. C1 WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT & GENET,ST LOUIS,MO 63110. UNIV UTAH,DEPT HUMAN GENET,SALT LAKE CITY,UT. UNIV UTAH,HOWARD HUGHES MED INST,SALT LAKE CITY,UT. BOSTON UNIV,SCH MED,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02118. UNIV MINNESOTA,DIV EPIDEMIOL,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC. NHLBI,BETHESDA,MD 20892. RP Borecki, IB (reprint author), WASHINGTON UNIV,SCH MED,DIV BIOSTAT,BOX 8067,660 S EUCLID AVE,ST LOUIS,MO 63110, USA. FU NHLBI NIH HHS [N01-HC-55019, N01-HC-55018, N0I-HC-25108] NR 26 TC 62 Z9 65 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 1997 VL 7 IS 1 BP 13 EP 21 DI 10.1016/S1047-2797(97)00155-5 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WH069 UT WOS:A1997WH06900003 PM 9034402 ER PT J AU Kafadar, K AF Kafadar, K TI Geographic trends in prostate cancer mortality: An application of spatial smoothers and the need for adjustment SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE bivariate smoothing; direct age standardization; mapping; residuals; risk factor; statistical analysis AB Prostate cancer mortality among whites and nonwhites in U.S. counties are analyzed for geographic effects. To better visualize geographical effects, the data are smoothed with a bivariate smoother using age-specific rates. Among nonwhites, an important explanatory variable is the proportion of African Americans. A relationship between the mortality rate and this variable is derived, and the data are adjusted for this variable using this relationship. When the rates are adjusted for age only, among whites there is a north-south gradient: rates are higher in the north, lower in the south. Among nonwhites, the gradient runs east to west: higher in the east, lower in the west. The latter gradient disappears when the rates are further adjusted for African Americans. The study reveals the importance of both smoothing the data to visualize patterns in geography and adjusting the data for an important variable to identify underlying patterns. The additional adjustment pennies the identification of other areas of the country with elevated or depressed rates. (C) 1997 by Elsevier Science Inc. C1 NCI,BIOMETRY BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP Kafadar, K (reprint author), UNIV COLORADO,DEPT MATH,DENVER,CO 80217, USA. NR 18 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 1997 VL 7 IS 1 BP 35 EP 45 DI 10.1016/S1047-2797(96)00101-9 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WH069 UT WOS:A1997WH06900006 PM 9034405 ER PT J AU Corti, MC Gaziano, M Hennekens, CH AF Corti, MC Gaziano, M Hennekens, CH TI Iron status and risk of cardiovascular disease SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE iron; ferritin; oxidative stress; cardiovascular disease; coronary heart disease ID LOW-DENSITY LIPOPROTEIN; ISCHEMIC-HEART-DISEASE; HYDROXYL RADICAL PRODUCTION; MYOCARDIAL-INFARCTION; STORED IRON; FOAM CELLS; MACROPHAGES; SUPEROXIDE; HEMOCHROMATOSIS; ATHEROGENESIS AB Free Iron, as well as other transition metals, can catalyze free radical formation. For this reason iron is tightly bound to transport and storage proteins to prevent their involvement in free radical formation. It has been hypothesized that increased iron intake or iron stores may promote atherogenesis by increasing free radical formation and oxidative stress. While a coherent, plausible hypothesis as to how transition metals, such as iron, might accelerate the progression of atherosclerosis has been generated from basic research, iron status, measured as dietary iron intake, serum iron, serum ferritin, and transferrin saturation, has been inconsistently associated with cardiovascular disease in human epidemiologic research. In addition, limited data suggest that iron overload states do not appear to be strongly associated with increased risk of atherosclerotic disease. One real limitation of the existing data is the lack of a generally agreed upon and logistically feasible means of assessing iron status in free liking humans. Further research, including basic research and large-scale epidemiologic studies, is needed to fully assess the association between iron status and the risk of CVD and other advserse outcomes. At present the currently available darn do not support radical changes in dietary recommendations or screening to detect high normal levels nor do they support the need for large-scale randomized trials of dietary restriction or phlebotomy as a means of lowering iron stores. (C) 1997 by Elsevier Science, Inc. C1 HARVARD UNIV, SCH MED,DIV PREVENT MED,BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED,DIV CARDIOVASC,BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02215 USA. NIA, EPIDEMIOL DEMOG & BIOMETRY PROGRAM, BETHESDA, MD 20892 USA. HARVARD UNIV, SCH MED, DEPT AMBULATORY CARE & PREVENT, CAMBRIDGE, MA 02138 USA. HARVARD UNIV, VET AFFAIRS MED CTR, DEPT MED, BROCKTON, MA 02401 USA. NR 48 TC 83 Z9 84 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 1997 VL 7 IS 1 BP 62 EP 68 DI 10.1016/S1047-2797(96)00112-3 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WH069 UT WOS:A1997WH06900009 PM 9034408 ER PT J AU Jiang, YZ Barrett, AJ Goldman, JM Mavroudis, DA AF Jiang, YZ Barrett, AJ Goldman, JM Mavroudis, DA TI Association of natural killer cell immune recovery with a graft-versus-leukemia effect independent of graft-versus-host disease following allogeneic bone marrow transplantation SO ANNALS OF HEMATOLOGY LA English DT Article DE graft-vs-leukemia (GVL); graft-vs-host disease (GVHD); bone marrow transplantation (BMT); NK cells; CD4 cells; CD8 cells; immune recovery; chronic myeloid leukemia (CML) ID CHRONIC MYELOID-LEUKEMIA; MHC CLASS-I; T-CELLS; PERIPHERAL-BLOOD; TUMOR-CELLS; NK CELLS; DONOR; INTERLEUKIN-2; RECOGNITION; REACTIVITY AB There is good evidence that T lymphocytes play an important role in the graft-versus-leukemia (GVL) effect following allogeneic bone marrow transplantation (BMT) for hematologic malignancies. However, the role of natural killer (NK) cells in GVL is less clear. To further investigate a possible association of NK cells with GVL we studied 15 patients undergoing BMT for chronic myeloid leukemia (CML), correlating T-cell (CD4+ and CD8+) and NK-cell (CD16+ 56+) recovery with relapse and graft-versus-host disease (GVHD). Patients were studied on three occasions up to 9 months after BMT, for lymphocyte surface phenotype and for spontaneous and IL-2-stimulated (LAR cell) cytotoxic function. Circulating CDS + and NK but not CD4+ cell numbers were significantly lower in five patients who relapsed compared with those remaining in remission after BMT (mean 0.03 vs 0.32x10(9)/1. p=0.002 for CD8+ cells; mean 0.03 vs 0.11x10(9)/1, p=0.002 for NK cells), There was no correlation of CD4+, CD8+, or NK cell numbers and development of grade-II or more acute GVHD. Spontaneous NK cytotoxic function rose to within the normal range in the first month after BMT, LAK function remained low during the study period. These results link NK cell recovery more closely with a GVL than with a GVH effect. C1 ROYAL POSTGRAD MED SCH,DEPT HEMATOL,LONDON,ENGLAND. RP Jiang, YZ (reprint author), NIH,BONE MARROW TRANSPLANTAT UNIT,HEMATOL BRANCH,BLDG 10,ROOM 7C-103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 27 TC 80 Z9 80 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD JAN PY 1997 VL 74 IS 1 BP 1 EP 6 DI 10.1007/s002770050246 PG 6 WC Hematology SC Hematology GA WE922 UT WOS:A1997WE92200001 PM 9031607 ER PT J AU Laureno, R Karp, BI AF Laureno, R Karp, BI TI Myelinolysis after correction of hyponatremia SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CENTRAL PONTINE MYELINOLYSIS; BLOOD-BRAIN-BARRIER; RAPID CORRECTION; EXTRAPONTINE MYELINOLYSIS; LIVER-TRANSPLANTATION; SERUM SODIUM; RATS; DEMYELINATION; MANAGEMENT; DIAGNOSIS AB Myelinolysis is a neurologic disorder that can occur after rapid correction of hyponatremia. Initially named ''central pontine myelinolysis,'' this disease is now known to also affect extrapontine brain areas. Manifestations of myelinolysis usually evolve several days after correction of hyponatremia. Typical features are disorders of upper motor neurons, spastic quadriparesis and pseudobulbar palsy, and mental disorders ranging from mild confusion to coma. Death may occur. The motor and localizing signs of myelinolysis differ from the generalized encephalopathy that is caused by untreated hyponatremia. Experiments have duplicated the clinical and pathologic features of myelinolysis by rapidly reversing hyponatremia in animals. Myelinolysis is more likely to occur after the treatment of chronic rather than acute hyponatremia and is more likely to occur with a rapid rate of correction. The exact pathogenesis of myelinolysis has not been determined. Optimal management of hyponatremic patients involves weighing the risk for illness and death from untreated hyponatremia against the risk for myelinolysis due to correction of hyponatremia. Experiments in animals and clinical experience suggest that correction of chronic hyponatremia should be kept at a rate less than 10 mmol/L in any 24-hour period. C1 NINCDS,NIH,OFF CLIN DIRECTOR,BETHESDA,MD 20892. RP Laureno, R (reprint author), WASHINGTON HOSP CTR,ROOM 2A44,110 IRVING ST NW,WASHINGTON,DC 20010, USA. NR 49 TC 217 Z9 228 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 1 PY 1997 VL 126 IS 1 BP 57 EP 62 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WA165 UT WOS:A1997WA16500008 PM 8992924 ER PT J AU Sneller, MC Walther, MM TalarWilliams, C AF Sneller, MC Walther, MM TalarWilliams, C TI Cyclophosphamide-induced bladder cancer - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP Sneller, MC (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 1 PY 1997 VL 126 IS 1 BP 86 EP 86 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WA165 UT WOS:A1997WA16500015 ER PT J AU Dalakas, MC Illa, I Gallardo, E Juarez, C AF Dalakas, MC Illa, I Gallardo, E Juarez, C TI Inclusion body myositis and paraproteinemia: Incidence and immunopathologic correlations SO ANNALS OF NEUROLOGY LA English DT Article ID AMYLOID POLYNEUROPATHY; AUTOANTIBODIES; POLYMYOSITIS; DEPOSITS; PROTEIN; CELLS AB Serum from 70 patients with sporadic inclusion body myositis (IBM) was subjected to agarose gel immunofixation electrophoresis. The IgG extracted from 9 patients with monoclonal proteins, 3 without, and 2 control subjects and was purified, biotinylated, and applied to muscle biopsy sections for immunocytochemistry and to purified muscle protein fractions for immunoblots. Sixteen of 70 (22.8%) patients with IBM, compared with 2% of age-matched controls, had a monoclonal gammopathy characterized as IgG lambda in 9 patients, IgG kappa in 4, IgM kappa in 2, and IgA lambda in 1. The mean age of IBM patients with gammopathy was 60.6 years (range, 35-77 years), compared with 66.1 years (range, 42-80 years) of the IBM patients without gammopathy. The IgG of the patients, more often than that of the control subjects, immunostained myonuclei and recognized various muscle proteins of 35 to 145 kd. We conclude that IBM, regardless of age, is frequently associated with monoclonal gammopathies, which often recognize various muscle components, especially myonuclei, suggesting disturbed immunoregulation. C1 UNIV SANTA CREU & ST PAU,BARCELONA,SPAIN. RP Dalakas, MC (reprint author), NINCDS,NIH,NEUROMUSCULAR DIS SECT,BLDG 10,ROOM 4N248,10 CTR DR,MSC 1382,BETHESDA,MD 20892, USA. OI Gallardo, Eduard/0000-0002-3942-3436 NR 16 TC 35 Z9 36 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 1997 VL 41 IS 1 BP 100 EP 104 DI 10.1002/ana.410410116 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WD974 UT WOS:A1997WD97400015 PM 9005871 ER PT J AU Evans, AC Frank, JA Antel, J Miller, DH AF Evans, AC Frank, JA Antel, J Miller, DH TI The role of MRI in clinical trials of multiple sclerosis: Comparison of image processing techniques SO ANNALS OF NEUROLOGY LA English DT Article ID STATUS SCALE EDSS; DISEASE-ACTIVITY; DISABILITY; LESIONS; BRAIN AB Magnetic resonance imaging (MRT) has received considerable attention in recent years over its potential for providing indices of multiple sclerosis activity and progression in clinical trials of new pharmaceuticals. The perceived advantages of MRT-derived measurements include greater objectivity, sensitivity, and reproducibility when compared with clinical rating scales. Clinical scales are also somewhat biased toward lesions affecting locomotion. However, the myriad permutations of MRI acquisition parameters, analysis methodologies, and disease indices demand careful consideration when employing MRT. Moreover, the use of MRT in research into the basic mechanisms of a disease may have different requirements than its use in a clinical trial setting. Consequently, a conference was held, sponsored by the US and Canadian multiple sclerosis societies, to review the present status of various MRI processing strategies and their potential role in clinical trials. Thirteen laboratories from North America and Europe as well as regulatory agencies and statistical consultants made formal presentations followed by extended discussion. This report presents the conclusions reached and recommendations for further action that emerged from the meeting. C1 NATL INST HLTH,LAB DIAGNOST RADIOL RES,WASHINGTON,DC. MCGILL UNIV,MONTREAL NEUROL INST,DEPT NEUROL NEUROSURG,MONTREAL,PQ,CANADA. NATL HOSP,INST NEUROL,LONDON WC1N 3BG,ENGLAND. RP Evans, AC (reprint author), MCGILL UNIV,MONTREAL NEUROL INST,MCCONNELL BRAIN IMAGING CTR,3801 UNIV,MONTREAL,PQ H3A 2B4,CANADA. NR 14 TC 71 Z9 71 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 1997 VL 41 IS 1 BP 125 EP 132 DI 10.1002/ana.410410123 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WD974 UT WOS:A1997WD97400022 PM 9005878 ER PT J AU Kaler, SG AF Kaler, SG TI Early copper histidine therapy in classic Menkes disease - Reply SO ANNALS OF NEUROLOGY LA English DT Letter ID OCCIPITAL HORN SYNDROME; MUTATIONS C1 CHILDRENS HOSP,WASHINGTON,DC. RP Kaler, SG (reprint author), NINCDS,CLIN NEUROSCI BRANCH,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 16 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 1997 VL 41 IS 1 BP 134 EP 136 DI 10.1002/ana.410410126 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WD974 UT WOS:A1997WD97400025 ER PT J AU Magrath, IT AF Magrath, IT TI The treatment of pediatric lymphomas: Paradigms to plagiarize? SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference on Malignant Lymphoma CY JUN 05-08, 1996 CL LUGANO, SWITZERLAND DE childhood; diagnosis; lymphomas; targeted therapy; treatment ID CHILDHOOD HODGKINS-DISEASE; CELL LYMPHOMA; CHEMOTHERAPY; EXPERIENCE AB The excellent results in pediatric lymphomas presented at the Sixth International Conference on Malignant Lymphoma in Lugano encompass several emerging themes and provide paradigms which it may be possible to extrapolate to at least some adult lymphomas. In pediatric Hodgkin's disease, there is mounting evidence that radiation adds nothing except toxicity to effective chemotherapy regimens, with the possible exception that patients with bulky disease, particularly in the mediastinum, may benefit from involved-field radiation. This is of particular importance in view of the recently recognized high rate of late-occurring second solid tumors and cardiac infarction, largely referable to radiotherapy. It is likely that there will be greater efforts to eliminate radiation from treatment protocols wherever possible. In pediatric non-Hodgkin's lymphomas, the intensive regimens used by several cooperative groups in Europe and the United Stares have resulted in very high event-free survival rates - 90% in B-cell lymphomas, and only slightly lower in T-cell lymphomas. These results stand in striking contrast to those obtained in adults with the same diseases, except those treated with the same treatment protocols, who appear to have a similar prognosis. Finally, progress in the characterization of the molecular abnormalities and viral association of pediatric lymphomas is leading to new approaches to diagnosis and the detection of minimal residual disease, as well as to the development of targeted treatment approaches. RP Magrath, IT (reprint author), NCI,HEART LYMPHOMA BIOL SECT,PEDIAT ONCOL BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 36 TC 8 Z9 8 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1997 VL 8 SU 1 BP 7 EP 14 DI 10.1023/A:1008225127815 PG 8 WC Oncology SC Oncology GA XB824 UT WOS:A1997XB82400003 PM 9187422 ER PT J AU Jaffe, ES Krenacs, L Raffeld, M AF Jaffe, ES Krenacs, L Raffeld, M TI Classification of T-cell and NK-cell neoplasms based on the REAL, classification SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference on Malignant Lymphoma CY JUN 05-08, 1996 CL LUGANO, SWITZERLAND DE cytotoxic T cells; T-cell lymphoma ID EPSTEIN-BARR-VIRUS; POLYMERASE CHAIN-REACTION; NON-HODGKINS-LYMPHOMA; ANGIO-IMMUNOBLASTIC LYMPHADENOPATHY; ANGIOIMMUNOBLASTIC LYMPHADENOPATHY; MALIGNANT HISTIOCYTOSIS; LEUKEMIA-LYMPHOMA; KI-1 LYMPHOMA; B-CELL; HTLV-I AB Mature or peripheral T-cell lymphomas are uncommon, accounting for only 10%-15% of all non-Hodgkin's lymphomas. The classification of these neoplasms has been controversial. In contrast to B-cell lymphomas, cytologic grade has not been very useful in predicting the clinical course. This finding may result from the generally aggressive clinical course associated with T-cell lymphomas. Prior studies have suggested that stage of disease may be more important than cytologic subtype. Clinical presentation is very important in the classification of T-cell malignancies. For T-cell lymphomas, cytologic features alone are not sufficient to distinguish among disease entities. For example, adult T-cell leukemia/lymphoma (ATLL) often cannot be distinguished morphologically from HTLV-l-negative T-cell lymphomas. Most extranodal T-cell lymphomas appear to be derived from cytotoxic T cells, which express perforin, TIA-1, and granzyme B. Three broad groups of T-cell malignancies can be identified: (1) leukemic or systemic disease; (2) nodal disease; (3) extranodal disease. Anaplastic large-cell lymphoma (ALCL) is probably the single most common subtype of T-cell lymphoma. Classical ALCL should be distinguished from primary cutaneous ALCL (CD30+ lymphoproliferative disease of the shin), which is a distinct disease entity. C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. RI Krenacs, Laszlo/L-8063-2014 OI Krenacs, Laszlo/0000-0001-6541-3031 NR 77 TC 46 Z9 47 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1997 VL 8 SU 2 BP 17 EP 24 DI 10.1023/A:1008249325615 PG 8 WC Oncology SC Oncology GA XH399 UT WOS:A1997XH39900004 PM 9209634 ER PT J AU Kirsch, IR AF Kirsch, IR TI Trans-rearrangements and the risk of lymphoid malignancy SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference on Malignant Lymphoma CY JUN 05-08, 1996 CL LUGANO, SWITZERLAND DE biomarkers; genetic instability; lymphomagenesis; trans-rearrangements; V(D)J recombination ID CELL RECEPTOR-BETA; HODGKINS-DISEASE; ATAXIA-TELANGIECTASIA; CHROMOSOME-14 INVERSION; V(D)J RECOMBINATION; GENE REARRANGEMENT; PROTEIN-KINASE; LYMPHOCYTES; IMMUNOGLOBULIN; MUTATION AB Background: Antigen receptor 'trans-rearrangements' occur in all individuals and represent a particular type of genetic instability whose mechanism, V(D)J recombination, is the same as that required for the development of a normal immune response. Design: We have measured the level of trans-rearrangements in a variety of populations characterized by increased risk for the development of lymphoid malignancy. The human populations studied include those with an inherited predisposition to lymphomagenesis (ataxia-telangiectasia patients), as well as populations at increased risk because of an occupational (agriculture workers) or iatrogenic (Hodgkin's disease patients) exposure. In addition, we have developed a mouse model for the more controlled analysis of these events. Results: There is a correlation between the absolute number of trans-rearrangements (as a population mean or median) and risk of lymphoma, whether that risk is based on an inherited predisposition or acquired exposure. Conclusion: This assay may serve as an easily measurable biomarker of lymphoma risk. If so, it is more than a fortuitous biomarker since the same mechanism responsible for the formation of trans-rearrangements is, at least in part, responsible for the majority of presumably 'malevolent' translocations associated with the transformation of lymphocytes. RP Kirsch, IR (reprint author), NCI,NMOB,NATL NAVAL MED CTR,NIH,8901 WISCONSIN AVE,BLDG 8,ROOM 5101,BETHESDA,MD 20889, USA. NR 37 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1997 VL 8 SU 2 BP 45 EP 48 DI 10.1023/A:1008217913319 PG 4 WC Oncology SC Oncology GA XH399 UT WOS:A1997XH39900010 PM 9209640 ER PT J AU Jaffe, ES Burg, G AF Jaffe, ES Burg, G TI Report of the Symposium on Cutaneous Lymphomas: Sixth International Conference on Malignant Lymphoma SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference on Malignant Lymphoma CY JUN 05-08, 1996 CL LUGANO, SWITZERLAND DE cutaneous lymphoma; T cell; B cell; lymphocyte biology; skin AB The symposium discussed the pathobiology, classification, and treatment of cutaneous lymphomas. Drs. Burg and Kadin commented on the pathophysiology of mycosis fungoides/Sezary syndrome and cutaneous CD30+ lymphoproliferative disorders, respectively. A proposed classification of primary cutaneous lymphomas from the EORTC was presented by Drs. Kerl and Sterry. Dr. Jaffe presented a classification of cutaneous lymphomas based on the REAL classification. All speakers agreed that primary cutaneous lymphomas are usually distinctive in their clinical behavior and biology, and differ from their nodal counterparts. The symposium concluded with remarks from Drs. Vonderheid and Hoppe on the therapeutic approach to primary cutaneous lymphoid malignancies. C1 UNIV ZURICH HOSP,DERMATOL CLIN,CH-8091 ZURICH,SWITZERLAND. RP Jaffe, ES (reprint author), NCI,DIV CLIN SCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892, USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1997 VL 8 SU 1 BP 83 EP 84 DI 10.1023/A:1008266220063 PG 2 WC Oncology SC Oncology GA XB824 UT WOS:A1997XB82400018 PM 9187437 ER PT J AU Arbuck, SG Sorensen, JM Christian, MC Ho, P Pluda, JM Cheson, BD AF Arbuck, SG Sorensen, JM Christian, MC Ho, P Pluda, JM Cheson, BD TI New drugs in non-Hodgkin's lymphoma SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference on Malignant Lymphoma CY JUN 05-08, 1996 CL LUGANO, SWITZERLAND DE bryostatin; chemotherapy; cladrabine; docetaxel; fludarabine; 506U; irinotecan; lymphoma; 9-aminocamptothecin; paclitaxel; suramin; topotecan ID PROTEIN-KINASE-C; LOW-GRADE LYMPHOMA; PROMYELOCYTIC LEUKEMIA-CELLS; PHASE-I TRIAL; FLUDARABINE PHOSPHATE; PURINE ANALOGS; PHORBOL ESTER; LYMPHOPROLIFERATIVE DISORDERS; HUMAN-LYMPHOCYTES; BRYOSTATIN 1 AB While novel agents designed to target molecular abnormalities involved in lymphoma pathogenesis are most likely to improve current therapeutic results, cytotoxic therapy remains the mainstay of therapy. Several new chemotherapy agents, including purine antimetabolites, taxanes, camptothecins, suramin, and protein kinase C inhibitors, are discussed. Other issues important in lymphoma drug development, including the limited patient population available for evaluation of investigational agents, are also considered. RP Arbuck, SG (reprint author), NCI,INVEST DRUG BRANCH,DIV CANC TREATMENT DIAGNOSIS & CTR,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892, USA. NR 99 TC 9 Z9 9 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1997 VL 8 SU 1 BP 119 EP 128 DI 10.1023/A:1008290925515 PG 10 WC Oncology SC Oncology GA XB824 UT WOS:A1997XB82400026 PM 9187445 ER PT J AU Dixon, SC Soriano, BJ Lush, RM Borner, MM Figg, WD AF Dixon, SC Soriano, BJ Lush, RM Borner, MM Figg, WD TI Apoptosis: Its role in the development of malignancies and its potential as a novel therapeutic target SO ANNALS OF PHARMACOTHERAPY LA English DT Review ID PROGRAMMED CELL-DEATH; TUMOR-NECROSIS-FACTOR; CALCIUM-DEPENDENT ENDONUCLEASE; MOLECULAR MECHANISMS; HUMAN-LYMPHOCYTES; HUMAN-ENDOMETRIUM; FACTOR RECEPTOR; CANCER-THERAPY; MICE DEFICIENT; T-CELLS AB OBJECTIVE: To review the current literature regarding the role of apoptosis in the development of malignant cells and how the induction of this pathway could be used in cancer therapy. DATA SOURCE: A MEDLINE search of basic science articles pertinent to the understanding of the normal physiologic process of apoptosis was conducted. STUDY SELECTION: Because of the rapidly growing literature regarding apoptosis, only articles describing key processes in the biology of the cell and the genetic control of apoptosis were included. DATA SYNTHESIS: Apoptosis is imperative for host survival since it discards unwanted, damaged, and atypical cells. The process is therefore implicated in the continuous regulation of development differentiation, and homeostasis. Furthermore, apoptosis is a response to physiologic and pathologic stresses that disrupt the balanced rates of cell generation and elimination, In a disease such as cancer, there is a lack of equilibrium between the rates of cell division and cell death; agents that promote or suppress apoptosis can manipulate these rates, influencing the anomalous accumulation of neoplastic cells. Pharmacologic manipulation of apoptosis represents a novel approach in targeting malignant cells and has far-reaching implications for new directions in cancer therapy. CONCLUSIONS: Apoptosis is a highly organized physiologic mechanism of destroying injured and abnormal cells as well as maintaining homeostasis in multicellular organisms. Both the activation and inhibition of apoptosis are tightly controlled, Pharmacologic manipulation of this pathway is a novel therapeutic target in cancer therapy. C1 NCI,DIV CLIN RES,CLIN PHARMACOL BRANCH,CLIN PHARMACOKINET SECT,NIH,BETHESDA,MD 20892. UNIV BERN,INST MED ONCOL,BERN,SWITZERLAND. RI Borner, Markus/B-7583-2011; Figg Sr, William/M-2411-2016 NR 80 TC 58 Z9 60 U1 2 U2 3 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JAN PY 1997 VL 31 IS 1 BP 76 EP 82 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WC261 UT WOS:A1997WC26100013 PM 8997471 ER PT J AU Buell, JF Alexander, HR Norton, JA Yu, KC Fraker, DL AF Buell, JF Alexander, HR Norton, JA Yu, KC Fraker, DL TI Bilateral adrenalectomy for Cushing's syndrome - Anterior versus posterior surgical approach SO ANNALS OF SURGERY LA English DT Article ID HYPERCORTISOLISM; EXPERIENCE AB Objective This study evaluates the intraoperative and postoperative complications in patients With Cushing's syndrome who underwent bilateral adrenalectomy comparing the posterior or anterior operative approach. Background The posterior approach for bilateral adrenalectomy has been advocated over the anterior approach because of rapid recovery and decreased morbidity, but the long-term complications associated with each procedure are not well described. Methods The intraoperative profiles and morbidity in 48 patients undergoing bilateral adrenalectomy for Cushing's disease through either the anterior or posterior approach from 1985 to the present were reviewed comparing the intraoperative complication and early and late postoperative complication rate and morbidity. Results Twenty-seven patients underwent an anterior transabdominal procedure, whereas 21 underwent a posterior retroperitoneal procedure via bilateral incisions. Age, weight, and diagnostic categories of Cushing's syndrome were similar between the two groups as well as serum cortisol and 24-hour urinary cortisol levels. Operative time, estimated blood loss, and transfusion requirements were not different between the groups, even though adrenal glands excised through the anterior approach were significantly larger. Acute morbidity was similar between the groups. However, 17 (81%) of 21 patients who underwent posterior bilateral adrenalectomy suffered from chronic back pain, compared with 2 (7%) of 27 via the anterior approach. Five of these patients in the posterior group considered the pain incapacitating, and the mean time to return to work was significantly longer in the posterior group because of back pain. Conclusions The anterior approach to bilateral adrenalectomy has comparable intraoperative complications and early morbidity compared to the posterior approach. The posterior approach has a very high incidence of chronic incision-related back pain. The anterior approach is the preferred open surgical technique in most patients undergoing bilateral adrenalectomy for Cushing's syndrome without other contraindications for undergoing laparotomy. C1 UNIV PENN, DEPT SURG, SURG BRANCH, PHILADELPHIA, PA 19104 USA. NCI, SURG METAB SECT, SURG BRANCH, BETHESDA, MD 20892 USA. WASHINGTON UNIV, DEPT SURG, ST LOUIS, MO USA. NR 15 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 1997 VL 225 IS 1 BP 63 EP 68 DI 10.1097/00000658-199701000-00007 PG 6 WC Surgery SC Surgery GA WB879 UT WOS:A1997WB87900009 PM 8998121 ER PT J AU Masi, AT Chrousos, GP AF Masi, AT Chrousos, GP TI Dilemmas of low dosage glucocorticoid treatment in rheumatoid arthritis: Considerations of timing SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-6 IL-6; CELLS; THERAPY; EXPRESSION; MEDICINE; RECEPTOR C1 NICHHD,SECT PEDIAT ENDOCRINOL,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20205. RP Masi, AT (reprint author), UNIV ILLINOIS,COLL MED,DEPT MED,1 ILLINI DR,PEORIA,IL 61605, USA. OI Masi, Alfonse/0000-0002-9695-6634 NR 40 TC 18 Z9 18 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 1997 VL 56 IS 1 BP 1 EP 4 DI 10.1136/ard.56.1.1 PG 4 WC Rheumatology SC Rheumatology GA WF388 UT WOS:A1997WF38800001 PM 9059132 ER PT J AU Rios, E Stern, MD AF Rios, E Stern, MD TI Calcium in close quarters: Microdomain feedback in excitation-contraction coupling and other cell biological phenomena SO ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE LA English DT Review DE ion channels; sarcoplasmic reticulum; signal transduction; diffusion; calcium buffers ID FROG SKELETAL-MUSCLE; INTRAMEMBRANOUS CHARGE MOVEMENT; CUT TWITCH FIBERS; PIG VENTRICULAR MYOCYTES; SARCOPLASMIC-RETICULUM; CA2+ CHANNELS; CARDIAC MYOCYTES; HUMP COMPONENT; HEART-MUSCLE; Q-GAMMA AB Researchers have made good progress in unraveling the molecular mechanisms of excitation-contraction (EC) coupling in striated muscle. Despite this progress, paradoxes abound. In skeletal muscle, the existence of a mechanical coupling between membrane charge movement and activation of sarcoplasmic reticulum (SR) release channels is essentially established, but the contribution of Ca2+-induced Ca2+ release (CICR) to the transient and steady-state components of Ca2+ release remains controversial. In cardiac muscle, the role of CICR as the primary mechanism of EC coupling is well established, but the stability and tight coupling between membrane Ca2+ current and release are paradoxical. Answers may lie in microdomain issues, and in the examination of discrete elementary release events, although quantitative treatments are needed. This review explores the theoretical and experimental methods used and the observations made in the study of microdomain Ca2+. C1 NIA,CARDIOVASC SCI LAB,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. RP Rios, E (reprint author), RUSH UNIV,DEPT MOL BIOPHYS & PHYSIOL,CHICAGO,IL 60612, USA. NR 106 TC 109 Z9 110 U1 0 U2 3 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 1056-8700 J9 ANNU REV BIOPH BIOM JI Annu. Rev. Biophys. Biomolec. Struct. PY 1997 VL 26 BP 47 EP 82 DI 10.1146/annurev.biophys.26.1.47 PG 36 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XD141 UT WOS:A1997XD14100004 PM 9241413 ER PT J AU Schuck, P AF Schuck, P TI Use of surface plasmon resonance to probe the equilibrium and dynamic aspects of interactions between biological macromolecules SO ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE LA English DT Review DE evanescent wave biosensor; grating coupler sensor; resonant mirror; reversible interactions; binding kinetics ID BIOMOLECULAR INTERACTION ANALYSIS; TYROSINE-PHOSPHORYLATED PEPTIDES; BIOSPECIFIC INTERACTION ANALYSIS; COMPETITIVE KINETIC-ANALYSIS; BINDING CONSTANTS; BIOSENSOR TECHNOLOGY; DNA INTERACTIONS; SH2 DOMAINS; MONOCLONAL-ANTIBODIES; RECOMBINANT PROTEINS AB Surface plasmon resonance biosensors have become increasingly popular for the qualitative and quantitative characterization of the specific binding of a mobile reactant to a binding partner immobilized on the sensor surface. This article reviews the use of this new technique to measure the binding affinities and the kinetic constants of reversible interactions between biological macromolecules. Immobilization techniques, the most commonly employed experimental strategies, and various analytical approaches are summarized. In recent years, several sources of potential artifacts have been identified: immobilization of the binding partner, steric hindrance of binding to adjacent binding sites at the sensor surface, and finite rate of mass transport of the mobile reactant to the sensor surface. Described here is the influence of these artifacts on the measured binding kinetics and equilibria, together with suggested control experiments. RP Schuck, P (reprint author), NIDDKD,SECT PHYS BIOCHEM,BIOCHEM PHARMACOL LAB,NATL CTR RES RESOURCES,BETHESDA,MD 20892, USA. OI Schuck, Peter/0000-0002-8859-6966 FU NCI NIH HHS [R01 CA140624] NR 118 TC 460 Z9 466 U1 11 U2 82 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 1056-8700 J9 ANNU REV BIOPH BIOM JI Annu. Rev. Biophys. Biomolec. Struct. PY 1997 VL 26 BP 541 EP 566 DI 10.1146/annurev.biophys.26.1.541 PG 26 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XD141 UT WOS:A1997XD14100020 PM 9241429 ER PT J AU Tedder, TF Tuscano, J Sato, S Kehrl, JH AF Tedder, TF Tuscano, J Sato, S Kehrl, JH TI CD22, a B lymphocyte-specific adhesion molecule that regulates antigen receptor signaling SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE B lymphocyte; signal transduction; intercellular adhesion; immunoglobulin; differentiation antigen ID PROTEIN-TYROSINE-PHOSPHATASE; MYELIN-ASSOCIATED GLYCOPROTEIN; IMMUNOGLOBULIN-LIKE DOMAINS; HUMAN ENDOTHELIAL-CELLS; ACID-BINDING-RECEPTOR; MONOCLONAL-ANTIBODY; SIALIC ACIDS; T-CELLS; DIFFERENTIATION ANTIGEN; TRANSDUCTION MOLECULE AB The development of B lymphocytes is a highly regulated process that depends in part on lineage-specific cell surface molecules. In addition, transmembrane signals generated through the B cell antigen receptor and other surface molecules regulate B cell responses to foreign antigens. Recent studies reveal CD22 to be a functionally significant receptor during these processes. CD22 is first expressed in the cytoplasm of pro-B and pre-B cells, and on the surface as B cells mature to become IgD(+). CD22 is a member of the Ig superfamily that serves as an adhesion receptor for sialic acid-bearing ligands expressed on erythrocytes and all leukocyte classes. In addition to its potential role as a mediator of intercellular interactions, signal transduction through CD22 can activate B cells and modulate antigen receptor signaling in vitro. CD22 signaling is mediated via interactions with a number of kinases and phosphatases that bind the cytoplasmic domain through phosphorylated tyrosine residues located within consensus TAM and TIM motifs. The phenotype of CD22-deficient mice suggests that CD22 is primarily involved in the generation of mature B cells within the bone marrow, blood, and marginal zones of lymphoid tissues. Most notable in CD22-deficient mice is a significant diminution of surface Ig levels in these B cell subpopulations, which suggests that CD22 functions in vivo to adjust the signaling threshold of cell surface antigen receptors. A further understanding of CD22 function is required and may reveal roles for CD22 in disease susceptibility or the development of autoimmunity. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. RP Tedder, TF (reprint author), DUKE UNIV,MED CTR,DEPT IMMUNOL,DURHAM,NC 27710, USA. OI Kehrl, John/0000-0002-6526-159X FU NIAID NIH HHS [R01AI31678, R01AI35987, R01AI37180] NR 99 TC 210 Z9 216 U1 2 U2 6 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1997 VL 15 BP 481 EP 504 DI 10.1146/annurev.immunol.15.1.481 PG 24 WC Immunology SC Immunology GA WT669 UT WOS:A1997WT66900019 PM 9143697 ER PT J AU Brown, KE Young, NS AF Brown, KE Young, NS TI Parvovirus B19 in human disease SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE human parvovirus B19; erythema infectiosum; hematological disease; pregnancy complications; infectious arthritis; pathogenesis ID ERYTHROCYTE-P-ANTIGEN; INFECTION; ANEMIA; ANTIBODY; RECEPTOR; INVITRO; ADULTS AB Parvovirus B19, the only known human pathogenic parvovirus, is associated with a wide range of disease manifestations. In healthy individuals, the major presentation of B19 infection is erythema infectiosum. In patients with underlying hemolytic disorders, infection is the primary cause of transient aplastic crisis. In immunosuppressed patients, persistent infection may develop that presents as pure red cell aplasia and chronic anemia. In utero infection may result in hydrops fetalis or congenital anemia. Diagnosis is based on examination of bone marrow and virologic studies. Much is known of the pathophysiology of the virus, and studies are in progress to develop a vaccine to prevent this widespread infection. RP Brown, KE (reprint author), NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 30 TC 80 Z9 92 U1 0 U2 2 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1997 VL 48 BP 59 EP 67 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA WH486 UT WOS:A1997WH48600006 PM 9046945 ER PT J AU Wise, SP Boussaoud, D Johnson, PB Caminiti, R AF Wise, SP Boussaoud, D Johnson, PB Caminiti, R TI Premotor and parietal cortex: Corticocortical connectivity and combinatorial computations SO ANNUAL REVIEW OF NEUROSCIENCE LA English DT Review ID PREPARATORY NEURONAL-ACTIVITY; PRIMATE FRONTAL-CORTEX; RHESUS-MONKEY; ARM MOVEMENTS; PRIMARY MOTOR; CORTICAL CONNECTIONS; REACHING MOVEMENTS; MACAQUE MONKEY; NEURAL REPRESENTATIONS; PREFRONTAL CORTEX AB The dorsal premotor cortex is a functionally distinct cortical field or group of fields in the primate frontal cortex. Anatomical studies have confirmed that most parietal input to the dorsal premotor cortex originates from the superior parietal lobule. However, these projections arise not only from the dorsal aspect of area 5, as has long been known, but also from newly defined areas of posterior parietal cortex, which are directly connected with the extrastriate visual cortex. Thus, the dorsal premotor cortex receives much more direct visual input than previously accepted. It appears that this fronto-parietal network functions as a visuomotor controller--one that makes computations based on proprioceptive, visual, gaze, attentional, and other information to produce an output that reflects the selection, preparation, and execution of movements. C1 INSERM,U94,F-69500 BRON,FRANCE. DUKE UNIV,MED CTR,DIV NEUROSURG,DURHAM,NC 27710. UNIV ROMA LA SAPIENZA,INST FISIOL UMANA,I-00185 ROME,ITALY. RP Wise, SP (reprint author), NIMH,NEUROPHYSIOL LAB,POB 608,POOLESVILLE,MD 20837, USA. RI Boussaoud, Driss/B-6932-2008 NR 70 TC 595 Z9 598 U1 1 U2 30 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0147-006X J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 1997 VL 20 BP 25 EP 42 DI 10.1146/annurev.neuro.20.1.25 PG 18 WC Neurosciences SC Neurosciences & Neurology GA WL507 UT WOS:A1997WL50700002 PM 9056706 ER PT J AU Walsh, PJ AF Walsh, PJ TI Evolution and regulation of urea synthesis and ureotely in (Batrachoidid) fishes SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE urea excretion; fish; ornithine-urea cycle; toadish; elasmobranchs ID TOADFISH OPSANUS-BETA; MEDULLARY COLLECTING DUCT; LAKE MAGADI TILAPIA; NITROGEN-METABOLISM; GLUTAMINE-SYNTHETASE; ALKALINE ENVIRONMENT; CARBAMOYL-PHOSPHATE; SQUALUS-ACANTHIAS; SUBCELLULAR-LOCALIZATION; MICROPTERUS-SALMOIDES AB Selected teleostean (bony) fish species of the family Batrachoididae (toadfishes and midshipmen) possess high titers of all enzymes of the ornithine-urea cycle in their livers. These species have proven valuable in understanding the short-term regulation of urea synthesis, urea permeability, and transport across epithelial tissues, and how urea synthesis and excretion have evolved among vertebrates. One species in particular, the gulf toadfish (Opsanus beta), has been shown to rapidly switch from ammonia excretion to urea synthesis and excretion during a variety of stress conditions (including confinement). The transition is accompanied by an upregulation of hepatic glutamine synthetase activity, and a switch to pulsatile urea excretion from the anterior end of the fish. In fact, a single day's excretion can be voided in a period of <3 h. Hypotheses on the environmental significance of these patterns of urea synthesis and excretion are discussed. RP Walsh, PJ (reprint author), UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,DIV MARINE BIOL & FISHERIES,NIEHS,MIAMI,FL 33149, USA. FU NIEHS NIH HHS [ES05075] NR 111 TC 62 Z9 65 U1 3 U2 15 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 1997 VL 59 BP 299 EP 323 DI 10.1146/annurev.physiol.59.1.299 PG 25 WC Physiology SC Physiology GA WM922 UT WOS:A1997WM92200014 PM 9074766 ER PT J AU Burg, MB Kwon, ED Kultz, D AF Burg, MB Kwon, ED Kultz, D TI Regulation of gene expression by hypertonicity SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE sorbitol; aldose reductase; betaine; inositol; taurine ID ALDOSE REDUCTASE GENE; RENAL MEDULLARY CELLS; PIGMENT EPITHELIAL-CELLS; ACTIVATED PROTEIN-KINASE; CANINE KIDNEY-CELLS; MAP KINASE; INOSITOL COTRANSPORTER; ORGANIC OSMOLYTES; OSMOTIC-STRESS; MDCK CELLS AB Adaptation of cells to hypertonicity often involves changes in gene expression. Since the concentration of salt in the interstitial fluid surrounding renal inner medullary cells varies with operation of the renal concentrating mechanism and generally is very high, the adaptive mechanisms of these cells are of special interest. Renal medullary cells compensate for hypertonicity by accumulating variable amounts of compatible organic osmolytes, including sorbitol, myo-inositol, glycine betaine, and taurine. In this review we consider how these solutes help relieve the stress of hypertonicity and the nature of transporters and enzymes responsible for their variable accumulation. We emphasize recent developments concerning the molecular basis for osmotic regulation of these genes, including identification and characterization of osmotic response elements. Although osmotic stresses are much smaller in other parts of the body than in the renal medulla, similar mechanisms operate throughout, yielding important physiological and pathophysiological consequences. RP Burg, MB (reprint author), NHLBI,NATL INST HLTH,BLDG 10,BETHESDA,MD 20892, USA. NR 70 TC 287 Z9 290 U1 0 U2 10 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 1997 VL 59 BP 437 EP 455 DI 10.1146/annurev.physiol.59.1.437 PG 19 WC Physiology SC Physiology GA WM922 UT WOS:A1997WM92200020 PM 9074772 ER PT J AU Longnecker, MP Rogan, WJ Lucier, G AF Longnecker, MP Rogan, WJ Lucier, G TI The human health effects of DDT (dichlorodiphenyl-trichloroethane) and PCBS (polychlorinated biphenyls) and an overview of organochlorines in public health SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Review DE DDT; DDE; polychlorinated biphenyls; dioxin; adverse effects ID TRANSFORMER REPAIR WORKERS; NON-HODGKINS-LYMPHOMA; SOFT-TISSUE SARCOMA; CAPACITOR MANUFACTURING WORKERS; AGRICULTURAL RISK-FACTORS; BREAST-CANCER; OCCUPATIONAL EXPOSURE; SERUM ORGANOCHLORINES; SPONTANEOUS-ABORTION; POSTNATAL EXPOSURE AB Organochlorines are a diverse group of persistent synthetic compounds, some of which are detectable in nearly everyone. Many organochlorines are endocrine disrupters or carcinogens in experimental assays. p,p'-DDE (dichlorodiphenyl-dichloroethene) and PCBs (polychlorinated biphenyls) comprise the bulk of organochlorine residues in human tissues. We reviewed relevant human data cited in the 1991-1995 Medline database and elsewhere. High-level exposure to selected organochlorines appears to cause abnormalities of liver function, skin (chloracne), and the nervous system. Of more general interest, however, is evidence suggesting insidious effects of background exposure. Of particular concern is the finding of neonatal hypotonia or hyporeflexia in relation to PCB exposure. The epidemiologic data reviewed, considered in isolation, provide no convincing evidence that organochlorines cause a large excess number of cancers. A recent risk assessment that considered animal data, however, gives a cancer risk estimate for background exposure to dioxin and dioxin-like compounds (e.g. some PCBs) with an upper bound in the range of 10(-4) per year. C1 NIEHS,OFF CLIN RES,RES TRIANGLE PK,NC 27709. NIEHS,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP Longnecker, MP (reprint author), NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709, USA. RI Rogan, Walter/I-6034-2012; OI Rogan, Walter/0000-0002-9302-0160; Longnecker, Matthew/0000-0001-6073-5322 NR 128 TC 286 Z9 293 U1 19 U2 101 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0163-7525 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 1997 VL 18 BP 211 EP 244 DI 10.1146/annurev.publhealth.18.1.211 PG 34 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA185 UT WOS:A1997XA18500009 PM 9143718 ER PT J AU Krieger, N Williams, DR Moss, NE AF Krieger, N Williams, DR Moss, NE TI Measuring social class in US public health research: Concepts, methodologies, and guidelines SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Review DE geocoding; methodology; social class; social inequalities in health; socioeconomic factors ID CHILDHOOD SOCIOECONOMIC-STATUS; BLACK-WHITE DIFFERENCES; BREAST-CANCER; BLOOD-PRESSURE; UNITED-STATES; MORTALITY DIFFERENCES; RACIAL-DIFFERENCES; INCOME INEQUALITY; WOMEN; POVERTY AB Increasing social inequalities in health in the United States and elsewhere, coupled with growing inequalities in income and wealth, have refocused attention on social class as a key determinant of population health. Routine analysis using conceptually coherent and consistent measures of socioeconomic position in US public health research and surveillance, however, remains rare. This review discusses concepts and methodologies concerning, and guidelines for measuring, social class and other aspects of socioeconomic position (e.g. income, poverty, deprivation, wealth, education). These data should be collected at the individual, household, and neighborhood level, to characterize both childhood and adult socioeconomic position; fluctuations in economic resources during these time periods also merit consideration. Guidelines for linking census-based socioeconomic measures and health data are presented, as are recommendations for analyses involving social class, race/ethnicity, and gender. Suggestions for research on socioeconomic measures are provided, to aid monitoring steps toward social equity in health. C1 UNIV MICHIGAN,DEPT SOCIOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,INST SOCIAL RES,ANN ARBOR,MI 48109. NIA,BEHAV & SOCIAL RES PROGRAM,BETHESDA,MD 20892. RP Krieger, N (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH & SOCIAL BEHAV,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. NR 201 TC 1182 Z9 1197 U1 28 U2 197 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0163-7525 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 1997 VL 18 BP 341 EP 378 DI 10.1146/annurev.publhealth.18.1.341 PG 38 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA185 UT WOS:A1997XA18500014 PM 9143723 ER PT J AU Heinz, A AF Heinz, A TI Savage thought and thoughtful savages - On the context of the evaluation of logical thought by Levy-Bruhl and Evans-Pritchard SO ANTHROPOS LA English DT Article DE prelogical thought; magic; evolutionism; changing paradigms; colonialism AB Evans-Pritchard's ''Witchcraft, Oracles, and Magic among the Azande'' promoted a fundamental change in the way anthropology views the logic of ''primitive'' mind. This change was achieved by implicitly refuting Levy-Bruhl's concept of ''prelogical mentality.'' Disputing the formal inconsistency and the incomprehensibility of ''primitive'' thought implied far-reaching social consequences. Evans-Pritchard belonged to a new generation of anthropologists who tried to explain their change of paradigm by pointing to their direct encounter with ''primitive'' men. However, the barely mentioned background of this experience is set by different patterns of colonial rule, interacting with the produced anthropological discourse. RP Heinz, A (reprint author), NIMH,CTR NEUROSCI,ST ELIZABETHS,WASHINGTON,DC 20032, USA. NR 24 TC 8 Z9 8 U1 1 U2 8 PU ANTHROPOS INST PI FIBOURG PA EDITIONS ST-PAUL, PEROLLES 42, CH-1700 FIBOURG, SWITZERLAND SN 0257-9774 J9 ANTHROPOS JI Anthropos PY 1997 VL 92 IS 1-3 BP 165 EP 173 PG 9 WC Anthropology SC Anthropology GA WL885 UT WOS:A1997WL88500013 ER PT J AU Turpin, JA Schaeffer, CA Terpening, SJ Graham, L Bu, M Rice, WG AF Turpin, JA Schaeffer, CA Terpening, SJ Graham, L Bu, M Rice, WG TI Reverse transcription of human immunodeficiency virus type 1 is blocked by retroviral zinc finger inhibitors SO ANTIVIRAL CHEMISTRY & CHEMOTHERAPY LA English DT Article DE nucleocapsid protein; HIV-1; antivirals; DIBAs; cross-linkage; reverse transcription ID NUCLEOCAPSID PROTEIN; STRAND TRANSFER; VIRAL-DNA; IN-VITRO; INFECTIVITY; LYMPHOCYTES; HIV; VIRIONS; RNA; REPRODUCTION AB The Cys-Xaa(2)-Cys-Xaa(4)-His-Xaa(4)-Cys zinc fingers of retroviral nucleocapsid (NC) proteins are prime antiviral targets due to conservation of the Cys and His chelating residues and the absolute requirement of these fingers in both early and late phases of retroviral replication. Certain 2,2'-dithiobisbenzamides (DIBAs) chemically modify the Cys residues of the fingers, thereby inhibiting in vitro replication of human immunodeficiency virus type 1 (HIV-1). We examined the consequences of DIBA interaction with cell-free virions and their subsequent ability to initiate new rounds of infection. The DIBAs entered intact virions and chemically modified the p7NC proteins, resulting in extensive disulphide cross-linkage among zinc fingers of adjacent p7NC molecules. likewise, treatment of Pr55(gag)-laden pseudovirions, used as a model of virion particles, with DIBAs resulted in Pr55(gag) cross-linkage. In contrast, monomeric p7NC protein did not form cross-linkages after DIBA treatment indicating that the retroviral zinc Finger proteins must exist in close proximity For cross-linkage to occur Cross-linkage of p7NC in virions correlated with loss of infectivity and decreased proviral DNA synthesis during acute infection, even though DIBAs did not inhibit virus attachment to host cells or reverse transcriptase enzymatic activity. Thus, DIBA-type molecules impair the ability of HIV-1 virions to initiate reverse transcription through their action an the retroviral zinc finger, thereby blocking further rounds of replication. RP Turpin, JA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,LAB ANTIVIRAL DRUG MECHANISMS,FREDERICK,MD 21702, USA. NR 37 TC 22 Z9 23 U1 1 U2 1 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON, ENGLAND WC1V 6QA SN 0956-3202 J9 ANTIVIR CHEM CHEMOTH JI Antivir. Chem. Chemother. PD JAN PY 1997 VL 8 IS 1 BP 60 EP 69 PG 10 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology GA WF469 UT WOS:A1997WF46900008 ER PT J AU Dworkin, RH Carrington, D Cunningham, A Kost, RG Levin, MJ McKendrick, MW Oxman, MN Rentier, B Schmader, KE Tappeiner, G Wassilew, SW Whitley, RJ AF Dworkin, RH Carrington, D Cunningham, A Kost, RG Levin, MJ McKendrick, MW Oxman, MN Rentier, B Schmader, KE Tappeiner, G Wassilew, SW Whitley, RJ TI Assessment of pain in herpes zoster: Lessons learned from antiviral trials SO ANTIVIRAL RESEARCH LA English DT Review DE clinical trials; herpes zoster; pain analyses; post-herpetic neuralgia; primary endpoint; zoster-associated pain ID POSTHERPETIC NEURALGIA; ACYCLOVIR; FAMCICLOVIR; EFFICACY; THERAPY AB Pain typically accompanies acute herpes tester and, in a proportion of patients, it persists well beyond rash healing. Pain must therefore be analyzed in trials of antiviral agents in herpes tester, but different methods have been used to analyze pain in recent published trials. These reports are reviewed and their methodological strengths and weaknesses examined. Based on this review? recommendations for the design and analysis of future trials of antiviral agents in herpes tester are proposed. The principal recommendation is that antiviral efficacy should be evaluated both by distinguishing post-herpetic neuralgia from acute pain and by considering pain as a continuum. The primary endpoint should address both the prevalence and duration of post-herpetic neuralgia and should be examined in those patients who have post-herpetic neuralgia. Adopting the proposed recommendations in design and analysis of future trials should facilitate comparison across trials of the efficacy of antiviral agents in the treatment of herpes tester. Copyright (C) 1997 Elsevier Science B.V. C1 ST GEORGE HOSP,LONDON,ENGLAND. WESTMEAD HOSP,DEPT VIROL,WESTMEAD,NSW 2145,AUSTRALIA. NIH,BETHESDA,MD 20892. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. ROYAL HALLAMSHIRE HOSP,SHEFFIELD S10 2JF,S YORKSHIRE,ENGLAND. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. UNIV LIEGE,LIEGE,BELGIUM. DUKE UNIV,MED CTR,DURHAM,NC. UNIV VIENNA,DERMATOL KLIN,ALLGEMEINES KRANKENHAUS WIEN,VIENNA,AUSTRIA. KLINIKUM KREFELD,DERMATOL KLIN,KREFELD,GERMANY. UNIV ALABAMA,BIRMINGHAM,AL. RP Dworkin, RH (reprint author), COLUMBIA PRESBYTERIAN MED CTR,NEW YORK,NY 10032, USA. OI Cunningham, Anthony/0000-0002-6744-5667 NR 41 TC 59 Z9 65 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JAN PY 1997 VL 33 IS 2 BP 73 EP 85 DI 10.1016/S0166-3542(96)01007-8 PG 13 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA WF667 UT WOS:A1997WF66700001 PM 9021049 ER PT J AU Gulakowski, RJ McMahon, JB Buckheit, RW Gustafson, KR Boyd, MR AF Gulakowski, RJ McMahon, JB Buckheit, RW Gustafson, KR Boyd, MR TI Antireplicative and anticytopathic activities of prostratin, a non-tumor-promoting phorbol ester, against human immunodeficiency virus (HIV) SO ANTIVIRAL RESEARCH LA English DT Article DE prostratin; anti-HIV; phorbol ID CD-1 MOUSE SKIN; REVERSE-TRANSCRIPTASE; ESCHERICHIA-COLI; T-CELLS; NONPROMOTING PHORBOL; MYRISTATE ACETATE; EXPRESSION; PHOSPHORYLATION; BRYOSTATIN-1; INFECTION AB Prostratin, a non-tumor-promoting phorbol ester, inhibited human immunodeficiency virus (HIV) 3-induced cell killing and viral replication in a variety of acutely-infected cell systems. The potency and degree of cytoprotection was dependent on both Viral strain and host cell type. Prostratin activated Viral expression in two latently-infected cell lines, but had little or no effect on chronically-infected cell lines. Prostratin caused a dose-dependent, but reversible, decrease in CD4 expression in the CEM-SS and MT-2 cell lines. This down-regulation of CD4 was inhibited in a dose-dependent manner by the protein kinase C (PKC) antagonist, staurosporine. In addition, the cytoprotective and cytostatic effects of prostratin in CEM-SS cells acutely infected with HIV-1(RF) were reversed by bryostatin-1, a PKC agonist. Prostratin had no effect on reverse transcriptase or HIV-1 protease, nor did it inhibit the binding of gp120 to CD4. We conclude that prostratin inhibits HIV cytopathicity and replication through mechanism(s) involving PKC enzyme(s). Copyright (C) 1997 Elsevier Science B.V. C1 NCI,FREDERICK CANC RES & DEV CTR,LDDRD,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTRS,FREDERICK,MD 21702. FREDERICK RES CTR,SO RES INST,VIROL RES DIV,FREDERICK,MD 21701. NR 22 TC 63 Z9 66 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JAN PY 1997 VL 33 IS 2 BP 87 EP 97 DI 10.1016/S0166-3542(96)01004-2 PG 11 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA WF667 UT WOS:A1997WF66700002 PM 9021050 ER PT B AU Thoma, GR Pipkin, R Mitra, S AF Thoma, GR Pipkin, R Mitra, S BE Bosacchi, B Bezdek, JC Fogel, DB TI Comparative color space analysis of difference images from adjacent visible human slices for lossless compression SO APPLICATIONS OF SOFT COMPUTING SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Applications of Soft Computing CY JUL 28-29, 1997 CL SAN DIEGO, CA SP Soc Photo Opt Instrumentat Engineers DE Visible Human image; entropy coding; color plane model; YIQ; HSV; RGB; image compression AB This paper reports the compression ratio performance of the RGB, YIQ, and HSV color plane models for the lossless coding of the National Library of Medicine's Visible Human (VH) color data set. In a previous study [1] the correlation between adjacent VH slices was exploited using the RGB color plane model. The results of that study suggested an investigation into possible improvements using the other two color planes, and alternative differencing methods. YIQ and HSV, also known as HSI, both represent the image by separating the intensity from the color information, and we anticipated higher correlation between the intensity components of adjacent VH slices. However the compression ratio did not improve by the transformation from RGB into the other color plane models, since in order to maintain lossless performance, YIQ and HSV both require more bits to store each pixel. This increase in file size is not offset by the increase in compression due to the higher correlation of the intensity value, the best performance being achieved with the RGB color plane model. This study also explored three methods of differencing: Average Reference Image, Alternating Reference Image, and Cascaded Difference from Single Reference. The best method proved to be the first iteration of the Cascaded Difference from Single Reference. In this method, a single reference image is chosen, and the difference between it and its neighbor is calculated. Then the difference between the neighbor and its next neighbor is calculated. This method requites that all preceding images up to the reference image be reconstructed before the target image is available. The compression ratios obtained from this method are significantly better than the competing methods. RP Thoma, GR (reprint author), NATL LIB MED,COMMUN ENGN BRANCH,LISTER HILL NATL CTR BIOMED COMMUN,NIH,BETHESDA,MD 20894, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2587-7 J9 P SOC PHOTO-OPT INS PY 1997 VL 3165 BP 180 EP 185 DI 10.1117/12.284212 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Optics SC Computer Science; Optics GA BJ78S UT WOS:A1997BJ78S00018 ER PT S AU Bezrukov, SM Vodyanoy, I AF Bezrukov, SM Vodyanoy, I BE Kadtke, JB Bulsara, A TI Stochastic resonance at molecular level: The Poisson wave model SO APPLIED NONLINEAR DYNAMICS AND STOCHASTIC SYSTEMS NEAR THE MILLENNIUM SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT Conference on Applied Nonlinear Dynamics and Stochastic Systems near the Millennium CY JUL, 1997 CL SAN DIEGO, CA AB Noise-facilitated signal transduction or the 'stochastic resonance' (SR) phenomenon, originally proposed as an explanation of the periodic recurrences of the Earth's ice ages [1], has been attracting rapidly growing interest from researchers working in different areas of science from physics to biology [2,3]. Only a few years ago it was generally accepted that SR can occur only in dynamical systems subjected to random forcing. Later it was hypothesized [4], and then shown both experimentally and theoretically [5,6], that the simplest 'stochastic resonator' consists only of signal, noise, and a threshold device. We introduce yet another class of systems where a noise-induced increase in the output signal-to-noise ratio can be observed [7]. These systems are both non-dynamical and threshold-free. We find SR in a very general model - a random pulse train where the probability of pulse generation is exponentially dependent on an input which is composed of a sine-wave signal plus random noise. We demonstrate that SR is a fundamental property of a wide variety of 'kT-driven' systems ranging from semiconductor p-n junctions [8] to modern mesoscopic electronic devices and voltage-dependent ion channels [9,10]. C1 NIH, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), NIH, Bldg 5,Rm 405, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 1-56396-736-7 J9 AIP CONF PROC PY 1997 IS 411 BP 175 EP 178 PG 4 WC Multidisciplinary Sciences; Physics, Applied; Physics, Multidisciplinary SC Science & Technology - Other Topics; Physics GA BK19E UT WOS:000071453600027 ER PT J AU Sood, VK Lee, KS Boulay, SF Rayeq, MR McRee, RC Cohen, EI Zeeberg, BR He, XS Weinberger, DR Rice, K Reba, RC AF Sood, VK Lee, KS Boulay, SF Rayeq, MR McRee, RC Cohen, EI Zeeberg, BR He, XS Weinberger, DR Rice, K Reba, RC TI In vivo autoradiography of radioiodinated (R)-3-quinuclidinyl (S)-4-iodobenzilate [(R,S)-IQNB] and (R)-3-quinuclidinyl (R)-4-iodobenzilate [(R,R)-IQNB]. Comparison of the radiolabelled products of a novel tributylstannyl precursor with those of the established triazene and exchange methods SO APPLIED RADIATION AND ISOTOPES LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; RAT-BRAIN; ALZHEIMERS-DISEASE; POTENTIAL RADIOPHARMACEUTICALS; INVIVO; SELECTIVITY; TOMOGRAPHY; INVITRO; SUBTYPE AB Radioiodinated (R,S)-IQNB and (R,R)-IQNB are prepared either from a triazene precursor or using an exchange reaction. In both cases the radiochemical yield is low. The product of the exchange reaction also suffers from having a fairly low specific activity. A new method for preparing radioiodinated (R,S)-IQNB and (R,R)-IQNB from a tributylstannyl precursor has recently been developed. This method is more convenient and much faster than the triazene and exchange methods, and it reliably results in a high radiochemical yield of a high specific activity product. In rat brain, the in vivo properties of the radioiodinated products of the tributylstannyl method are identical to those of the corresponding radioiodinated (R,S)-IQNB and (R,R)-IQNB prepared using the triazene and exchange methods. Dissection studies of selected brain regions show that at 3 h post injection (R,S)-[I-125]IQNB prepared by all three methods have indistinguishable %dose g(-1) values in all brain regions studied. Autoradiographic comparison of coronal slices through the anteroventral nucleus of the thalamus, through the hippocampus and through the pens at 2 h post injection shows that (R,S)-[I-125]IQNB prepared by the triazene and tributylstannyl methods have indistinguishable patterns of binding. Copyright (C) 1997 Elsevier Science Ltd C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT RADIOL,SECT RADIOPHARMACEUT CHEM,WASHINGTON,DC 20037. ST ELIZABETH HOSP,NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. UNIV CHICAGO HOSP,DEPT RADIOL,NUCL MED SECT,CHICAGO,IL 60637. NIDDK,LAB MED,NIH,BETHESDA,MD 20892. RI Sood, Vinay/B-7109-2008 FU NINDS NIH HHS [NS22215] NR 29 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD JAN PY 1997 VL 48 IS 1 BP 27 EP 35 DI 10.1016/S0969-8043(96)00125-X PG 9 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA WD773 UT WOS:A1997WD77300006 PM 9022211 ER PT J AU Brown, DJ Clarke, GC VanBeneden, RJ AF Brown, DJ Clarke, GC VanBeneden, RJ TI Halogenated aromatic hydrocarbon-binding proteins identified in several invertebrate marine species SO AQUATIC TOXICOLOGY LA English DT Article DE marine invertebrate; photoaffinity label; aryl hydrocarbon receptor; TCDD; 2,3,7,8-tetrachlorodibenzo-p-dioxin; dioxin; bivalve; clam ID HEAT-SHOCK PROTEIN; AH RECEPTOR; DIOXIN RECEPTOR; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; MERCENARIA; VERTEBRATE; TOXICITY; CLAM; FORM AB The vertebrate aryl hydrocarbon receptor (AhR) is a cytosolic protein which binds halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), In vertebrates, the AhR-ligand complex, in association with other proteins, binds specific DNA sequences and modifies the expression of a number of genes. Most of the toxic effects of halogenated aromatic hydrocarbon exposure are mediated through this receptor. A similar receptor system has not yet been identified in invertebrates. The current study investigated whether proteins which specifically bind halogenated aromatic hydrocarbons were present in marine invertebrates. We used the photoaffinity TCDD-analog, 2-azido-3-[I-125]iodo-7,8-dibromodibenzo-p-dioxin ([I-125]N(3)Br(2)DpD), to detect the presence of cytosolic proteins which specifically bound this ligand. Specific binding was defined as labeling which could be competed off by an excess of unlabeled ligand. Eleven species of marine invertebrates were examined which represented six different phyla: Cnidaria, Mollusca, Annelida, Arthropoda, Chordata, and Echinodermata. Cytosols prepared from gill and gonad in the soft-shell clam (Mya arenaria), the eastern oyster (Crassostrea virginica), and hard-shell clam (Mercenaria mercenaria), as well as the hepatopancreas of the blue crab (Callinectes sapidus), contained proteins in the same size range (28-39 kDa) which were specifically labeled with the dioxin analog. No proteins of the size expected for vertebrate Ah receptors (95-146 kDa) were seen in any of the invertebrates. The biological function of these dioxin-binding proteins is not yet known. C1 UNIV MAINE,DEPT ZOOL,ORONO,ME 04469. DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. NIEHS,RES TRIANGLE PK,NC 27709. NR 26 TC 17 Z9 17 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-445X J9 AQUAT TOXICOL JI Aquat. Toxicol. PD JAN PY 1997 VL 37 IS 1 BP 71 EP 78 DI 10.1016/S0166-445X(96)00804-1 PG 8 WC Marine & Freshwater Biology; Toxicology SC Marine & Freshwater Biology; Toxicology GA WL880 UT WOS:A1997WL88000006 ER PT J AU Berrettini, WH Ferraro, TN Goldin, LR DeteraWadleigh, SD Choi, H Muniec, D Guroff, JJ Kazuba, DM Nurnberger, JI Hsieh, WT Hoehe, MR Gershon, ES AF Berrettini, WH Ferraro, TN Goldin, LR DeteraWadleigh, SD Choi, H Muniec, D Guroff, JJ Kazuba, DM Nurnberger, JI Hsieh, WT Hoehe, MR Gershon, ES TI A linkage study of bipolar illness SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID X-CHROMOSOME MARKERS; OLD-ORDER AMISH; ALZHEIMERS-DISEASE LOCUS; MANIC-DEPRESSIVE ILLNESS; PROCOLLAGEN GENE COL2A1; AFFECTIVE-DISORDER; DNA MARKERS; MILD CHONDRODYSPLASIA; SUSCEPTIBILITY LOCUS; FAMILIAL BREAST AB Background: Although genetic epidemiological studies of bipolar (BP) illness are consistent with a heritable component, inherited risk factors remain unknown. The goal of the present study is to describe the localization of BP susceptibility loci through linkage strategies, including a genome-wide search. Methods: A linkage study of 22 BP families has been performed. These BP families include almost 400 persons, 173 of whom have been diagnosed as having BP I, schizoaffective, BP II with major depression, or recurrent unipolar illness. Using an autosomal dominant disease model with 85% or 50% age-dependent penetrance, and a recessive model with 85% penetrance, linkage analyses were performed assuming a narrow (BP and schizoaffective) or a broad (BP, schizoaffective, or unipolar) definition of the BP spectrum. Affected sibling pairs and affected pedigree member analyses were performed when positive lod scores were observed in multiple pedigrees. The present article describes linkage analysis of 310 DNA markers on chromosomes 1, 5p, 6, 8, 10q, 11q, and 12 to 18. Results: None of the loci examined disclosed compelling evidence for linkage using lod score analyses. Model-independent analysis by multilocus affected pedigree member method in the pericentromeric chromosome 18 region disclosed statistically significant evidence (P<.0001) for a BP susceptibility gene in this region. Multilocus analysis by affected sibling pair method also disclosed evidence for linkage (P<.00008). Conclusions: Our results imply that a BP susceptibility gene exists near the centromere of chromosome 18. Confirmation of this finding (by independent investigators studying different pedigrees) has been published, suggesting that a valid BP disease linkage may have been discovered. C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. INDIANA UNIV,DEPT PSYCHIAT,INST PSYCHIAT RES,INDIANAPOLIS,IN. RP Berrettini, WH (reprint author), THOMAS JEFFERSON UNIV,DEPT PSYCHIAT & HUMAN BEHAV,JEFFERSON MED COLL,1025 WALNUT ST,312 COLL,PHILADELPHIA,PA 19107, USA. OI Nurnberger, John/0000-0002-7674-1767 FU NCRR NIH HHS [1 P41 RR03655]; NIMH NIH HHS [MH 49181] NR 79 TC 79 Z9 80 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1997 VL 54 IS 1 BP 27 EP 35 PG 9 WC Psychiatry SC Psychiatry GA WC697 UT WOS:A1997WC69700005 PM 9006397 ER PT J AU Ram, A Guedj, F Cravchik, A Weinstein, L Cao, QH Badner, JA Goldin, LR Grisaru, N Manji, HK Belmaker, RH Gershon, ES Gejman, PV AF Ram, A Guedj, F Cravchik, A Weinstein, L Cao, QH Badner, JA Goldin, LR Grisaru, N Manji, HK Belmaker, RH Gershon, ES Gejman, PV TI No abnormality in the gene for the G protein stimulatory alpha subunit in patients with bipolar disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; CEREBRAL-CORTEX; SIGNAL TRANSDUCTION; ADENYLATE-CYCLASE; LINKAGE ANALYSIS; DNA FRAGMENTS; RAT CORTEX; LITHIUM; MODULATION; G(S)ALPHA AB Background: The available evidence for an involvement of the heterotrimeric guanine-nucleotide-binding proteins (G proteins) in bipolar disorder relies primarily on the effects of lithium salts on G protein function and on alterations in the concentration or function of G proteins (most notably G(s)-alpha) in peripheral leukocytes and in postmortem tissues of patients with bipolar disorder. Methods: The hypothesis that a mutation in G(s)-alpha gene confers an increased susceptibility to bipolar disorder was tested by the following strategies: (1) mutational screening of the G(s)-alpha subunit gene coding sequences and promoter sequences by denaturing gradient gel electrophoresis in unrelated individuals with bipolar disorder and (2) association and linkage analyses with a common silent exonic polymorphism, using genetic allelic information from American families with at least 1 affected child. For association analysis, the transmission test for linkage disequilibrium was used; for linkage analysis, nonparametric methods were used. Results: No structural or regulatory mutations in this gene were found in bipolar disorder; the results of association and genetic linkage were negative. Conclusion: Our results do not support the speculation that the G(s)-alpha protein gene has a role in the genetic predisposition to bipolar disorder. C1 NIMH,CLIN NEUROGENET BRANCH,UNIT MOL CLIN INVEST,BETHESDA,MD 20892. NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. BEN GURION UNIV NEGEV,BEER SHEVA MENTAL HLTH CTR,IL-84105 BEER SHEVA,ISRAEL. NR 33 TC 41 Z9 44 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1997 VL 54 IS 1 BP 44 EP 48 PG 5 WC Psychiatry SC Psychiatry GA WC697 UT WOS:A1997WC69700007 PM 9006399 ER PT J AU Ayala, A Cutler, RG AF Ayala, A Cutler, RG TI Preferential use of less toxic detoxification pathways by long-lived species SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE cytochrome P-450; epoxide hydrolase; glutathione-S-transferase; malic enzyme; primate species; detoxification pathways; protein oxidation ID OXIDATIVELY MODIFIED PROTEINS; MIXED-FUNCTION OXIDATION; RAT-LIVER; MONOOXYGENASE REACTIONS; GENE-EXPRESSION; GLUTATHIONE; REDUCTASE; ENZYME; CYTOCHROME-P-450; CARCINOGENS AB This study was undertaken to determine whether the detoxification pathways producing the least oxidative stress appear to be favored in longer-lived mammalian species. Firstly, we focused on the cytochrome P-450 monooxygenase system. Although this system is an important component of the defenses that protect living organisms against toxic chemicals, some reactions catalyzed by the cytochrome P-450 system result in the formation of products that are highly reactive as well as active oxygen species. Our results suggest that the lower amount of hepatic cytochrome P-450 content found in longer-lived species may have evolved to reduce the toxic side-effect of this detoxification system. Support of the idea that the cytochrome P-450 system is an important source of oxidative stress is the positive correlation between cytochrome P-450 content and the amount of oxidized proteins found in liver of different human individuals. Secondly, we have measured the specific activity of other detoxification enzymes as a function of life span. Instead of a direct comparison of detoxification capabilities of the species, the approach used in this study was: (1) to select those detoxification enzymes which utilize the same substrate but differ in toxicity of the intermediate compounds formed in the reaction, and (2) to measure the levels of these enzymes in the two pathways to determine which pathway is dominant for each species. Our results suggest that the detoxification pathways producing the least oxidative stress do appear to be favored in longer-lived species. Copyright (C) 1997 Elsevier Science Ireland Ltd. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 48 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-4943 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD JAN-FEB PY 1997 VL 24 IS 1 BP 87 EP 102 DI 10.1016/S0167-4943(96)00757-1 PG 16 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA WF665 UT WOS:A1997WF66500010 PM 15374139 ER PT J AU Henson, DE Oberman, HA Hutter, RVP AF Henson, DE Oberman, HA Hutter, RVP TI Practice protocol for the examination of specimens removed from patients with cancer of the breast - A publication of the Cancer Committee, College of American Pathologists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CARCINOMA IN-SITU; S-PHASE FRACTION; DUCTAL CARCINOMA; PROGNOSTIC-SIGNIFICANCE; CELL-PROLIFERATION; HISTOLOGIC GRADE; VESSEL INVASION; FOLLOW-UP; DISEASE; EXPRESSION C1 UNIV MICHIGAN,SCH MED,ANN ARBOR,MI. ST BARNABAS HOSP,DEPT PATHOL,LIVINGSTON,NJ 07039. RP Henson, DE (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,EPN BLDG,ROOM 330,BETHESDA,MD 20892, USA. NR 38 TC 16 Z9 17 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 1997 VL 121 IS 1 BP 27 EP 33 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA WF153 UT WOS:A1997WF15300006 PM 9111089 ER PT J AU AlboresSaavedra, J Gersell, D Gilks, CB Henson, DE Lindberg, G Santiago, H Scully, RE Silva, E Sobin, LH Tavassoli, FJ Travis, WD Woodruff, JM AF AlboresSaavedra, J Gersell, D Gilks, CB Henson, DE Lindberg, G Santiago, H Scully, RE Silva, E Sobin, LH Tavassoli, FJ Travis, WD Woodruff, JM TI Terminology of endocrine tumors of the uterine cervix - Results of a workshop sponsored by the College of American Pathologists and the National Cancer Institute SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SMALL-CELL-CARCINOMA; LIGHT; ADENOCARCINOMA; ACTH C1 BARNES HOSP,ST LOUIS,MO 63110. VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL,VANCOUVER,BC V5Z 1M9,CANADA. NCI,EARLY DETECT BRANCH,DEPT PATHOL,BETHESDA,MD 20892. IMSS,HOSP ONCOL CENT MED,DEPT PATHOL,MEXICO CITY,DF,MEXICO. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT PATHOL,HOUSTON,TX 77030. ARMED FORCES INST PATHOL,DEPT PATHOL,WASHINGTON,DC 20306. MEM SLOAN KETTERING CANC CTR,DEPT PATHOL,NEW YORK,NY 10021. RP AlboresSaavedra, J (reprint author), UNIV TEXAS,SW MED CTR,DEPT PATHOL,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. NR 32 TC 127 Z9 139 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 1997 VL 121 IS 1 BP 34 EP 39 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA WF153 UT WOS:A1997WF15300007 PM 9111090 ER PT J AU Schuierer, S Bloom, ME Kaaden, OR Truyen, U AF Schuierer, S Bloom, ME Kaaden, OR Truyen, U TI Sequence analysis of the lymphotropic Aleutian disease parvovirus ADV-SL3 SO ARCHIVES OF VIROLOGY LA English DT Article ID MINK; VIRUS; INFECTION; EVOLUTION; CLONES AB About 98% of the DNA sequence of the lymphotropic Aleutian disease parvovirus isolate ADV-SL3 was determined and analysed. The sequence revealed that this isolate was a type-1. ADV strain, supporting that the currently used typing of ADV viruses does not correlate with virulence or pathogenicity. ADV-SL3 had a very high overall homology of 99.5% to the prototype strain ADV-G at the DNA level. Comparative sequence analyses with various ADV isolates of known virulence did not reveal a consensus sequence that could obviously be responsible for the apparently unique biological properties of this virus strain. C1 NIAID,ROCKY MT LAB,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. RP Schuierer, S (reprint author), UNIV MUNICH,INST MED MICROBIOL INFECT & EPIDEM DIS,VET STR 13,D-80539 MUNICH,GERMANY. NR 20 TC 18 Z9 19 U1 0 U2 10 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1997 VL 142 IS 1 BP 157 EP 166 DI 10.1007/s007050050066 PG 10 WC Virology SC Virology GA WB845 UT WOS:A1997WB84500012 PM 9155880 ER PT J AU Dworak, LJ Wolfinbarger, JB Bloom, ME AF Dworak, LJ Wolfinbarger, JB Bloom, ME TI Aleutian mink disease parvovirus infection of K562 cells is antibody-dependent and is mediated via an Fc(gamma)RII receptor - Brief report SO ARCHIVES OF VIROLOGY LA English DT Article ID FC-RECEPTORS; HUMAN-MONOCYTES; MONOCLONAL-ANTIBODIES; ADULT MINK; IMMUNOGLOBULIN-G; VIRUS-INFECTION; MOLECULAR-BASIS; LINE; IGG; ENHANCEMENT AB Aleutian mink disease parvovirus (ADV) infects macrophages but infection is restricted. Using the human macrophage cell line U337, we reported infection to be antibody-dependent [22, 23]. Recently, we learned that the U937 cells were contaminated with the human cell line, K562 [12]. To clarify which cell line actually supported ADV infection, we studied the antibody-dependent enhancement (ADE) of ADV infection in pure lines of U937 and K562. After infection with ADV complexed with mink anti-ADV antibody, up to 10% of the K562 cells, but none of the U937 cells showed evidence of infection. These results indicated that K562 cells, but not U937 cells, were susceptible to ADV. ADV-infected cultures of K562 were: sorted by flow cytometry after staining with a murine monoclonal antibody (IV.3) directed against Fc(gamma)RII. Only cells that were IV.3 positive supported ADV gene expression. Also, preincubation of K562 cells with IV.3 blocked ADV infection by more than 90%. These results established that the ADE of ADV in K562 is Fc(gamma)RIIA-mediated. C1 NIH,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 50 TC 18 Z9 19 U1 1 U2 8 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1997 VL 142 IS 2 BP 363 EP 373 DI 10.1007/s007050050082 PG 11 WC Virology SC Virology GA WJ816 UT WOS:A1997WJ81600011 PM 9125049 ER PT J AU Agostini, HT Ryschkewitsch, CF Brubaker, GR Shao, J Stoner, GL AF Agostini, HT Ryschkewitsch, CF Brubaker, GR Shao, J Stoner, GL TI Five complete genomes of JC virus Type 3 from Africans and African Americans SO ARCHIVES OF VIROLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; COMPLETE NUCLEOTIDE-SEQUENCE; DNA-SEQUENCE; HUMAN BRAIN; BK-VIRUS; POLYOMAVIRUS; PAPOVAVIRUS; DISEASE; VARIANTS; PROTEIN AB The central demyelinating disease progressive multifocal leukoencephalopathy (PML) is caused by the human polyomavirus JC virus (JCV). JCV evolved as geographically based genotypes of which Type 3 is an African variant first characterized in HIV-I positive patients from Tanzania. This study reports the complete sequence of five JCV Type 3 strains. The entire JCV genome was PCR amplified from urine specimens of three African and two African-American individuals. The African consensus sequence was compared to the Type 1 and Type 2 prototype strains, JCV (Mad-1) and JCV(GS/B), respectively. Type 3 differed in 2.2% of its coding region genome from JCV (Mad-1) and in 1.3% from JCV(GS/B). Within the coding region the sequence variation among the three types was higher in the capsid protein VP1 and in the regulatory protein large T antigen than in the agnoprotein or in VP2/3. Notable Type 3-specific changes were located at sites adjacent to the zinc finger motif and near the major donor and acceptor splice junctions of large T antigen. Four of the five urinary Type 3 strains had an unrearranged, archetypal regulatory region. African strain #309 showed a 10-bp deletion at a location similar to that previously described for #307 from Tanzania. The African-American Type 3 strain #312 was closely related to the African consensus sequence. The complete genome of a urinary JCV strain from another African-American male, previously reported as a possible Type 5, showed a sequence difference of only 0.52% from the Tanzanian consensus and has been reclassified as a subtype of Type 3. C1 NINCDS,EXPT NEUROPATHOL LAB,NIH,BETHESDA,MD 20892. KILIMANJARO CHRISTIAN MED CTR,MOSHI,TANZANIA. SHIRATI HOSP,SHIRATI,TANZANIA. NR 43 TC 61 Z9 61 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1997 VL 142 IS 4 BP 637 EP 655 DI 10.1007/s007050050108 PG 19 WC Virology SC Virology GA WU855 UT WOS:A1997WU85500001 PM 9170494 ER PT J AU Ray, NB Power, C Lynch, WP Ewalt, LC Lodmell, DL AF Ray, NB Power, C Lynch, WP Ewalt, LC Lodmell, DL TI Rabies viruses infect primary cultures of murine, feline, and human microglia and astrocytes SO ARCHIVES OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; HUMAN CYTOMEGALOVIRUS; GENE-EXPRESSION; BONE-MARROW; MACROPHAGES; CELLS; LENTIVIRUSES; TRANSMISSION; REPLICATION AB Recent studies have reported the detection of rabies viral antigens and virions in astrocytes and microglia of rabies-infected animals. As a first step toward understanding whether these glial cells may be involved in rabies virus replication, persistence, and/or pathogenesis, we explored their potential to be infected in vitro. Primary cultures of murine, feline, and human microglia and astrocytes were infected with several different rabies viruses: two unpassaged street virus isolates, a cell culture-adapted strain, and a mouse brain-passaged strain. Infection, as determined by immunofluorescence, was detected in 15 of the 16 (94%) virus-glial cell combinations. Replication of infectious virus, determined by infectivity assay, was detected in 7 of the 8 (88%) virus-cell combinations. These results show that astrocytes and microglia can be infected by rabies viruses, suggesting that they may have a potential role in disease, perhaps contributing to viral spread, persistence and/or neuronal dysfunction. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. UNIV MANITOBA,DEPT MED MICROBIOL,WINNIPEG,MB,CANADA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Power, Christopher/C-7181-2013; OI Power, Christopher/0000-0002-5131-9711 NR 35 TC 15 Z9 17 U1 1 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1997 VL 142 IS 5 BP 1011 EP 1019 DI 10.1007/s007050050136 PG 9 WC Virology SC Virology GA WZ329 UT WOS:A1997WZ32900012 PM 9191865 ER PT J AU Green, KY AF Green, KY TI The role of human caliciviruses in epidemic gastroenteritis SO ARCHIVES OF VIROLOGY LA English DT Article ID ROUND-STRUCTURED VIRUSES; NORWALK-LIKE VIRUS; IMMUNE ELECTRON-MICROSCOPY; INFECTIOUS NONBACTERIAL GASTROENTERITIS; HUMAN ENTERIC CALICIVIRUSES; PROTEIN ENZYME-IMMUNOASSAY; MOLECULAR CHARACTERIZATION; CAPSID PROTEIN; GENOME ORGANIZATION; FELINE CALICIVIRUS AB Members of the Caliciviridae family of small, positive-sense RNA viruses exhibit a broad host range. The Norwalk and Norwalk-like caliciviruses in this family are major etiologic agents of epidemic gastroenteritis in humans. This illness characteristically lasts 24-48 h and often occurs in group settings such as families, schools, institutions, or communities. The spread of the human caliciviruses is considered to be predominantly by person-to-person contact via the fecal-oral-route. However, the ingestion of calicivirus-contaminated food or water can result in large-scale common-source outbreaks. Many basic features concerning the biology and replication of the human caliciviruses are not known because they have not yet been grown in cell culture and the virus does not appear to replicate in animal models other than the chimpanzee. Sequence analysis of RT-PCR-generated DNA fragments derived from serotypically distinct reference strains (such as the Norwalk, Hawaii, and Snow Mountain viruses) and other circulating strains associated with gastroenteritis has provided evidence for marked genetic diversity among these viruses. Moreover, analysis of the antigenic relationships among these viruses using paired sera from individuals infected with well-characterized reference strains or from animals immunized with recombinant ''virus-like particles'' (VLPs) suggests that several serotypes of these viruses are circulating worldwide. The availability of molecular techniques for the detection of these fastidious viruses has enabled epidemiologic studies that have strengthened the association of human caliciviruses with acute gastroenteritis and has demonstrated a potential role for antigenic diversity in the natural history of these pathogens. RP Green, KY (reprint author), NIAID,INFECT DIS LAB,NIH,BLDG 7,ROOM 129,ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 56 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1997 SU 13 BP 153 EP 165 PG 13 WC Virology SC Virology GA YG396 UT WOS:A1997YG39600016 ER PT J AU Eisenberger, P Rekow, D AF Eisenberger, P Rekow, D TI NIH Workshop Report - Biomaterials and medical implant science: Present and future perspectives SO ASAIO JOURNAL LA English DT Editorial Material RP Eisenberger, P (reprint author), NHLBI,BIOENGN RES GRP,BLDG 10,6701 ROCKLEDGE DR,RM 9178,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1058-2916 J9 ASAIO J JI Asaio J. PD JAN-FEB PY 1997 VL 43 IS 1 BP 95 EP 103 DI 10.1097/00002480-199701000-00017 PG 9 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA WF876 UT WOS:A1997WF87600017 PM 9116362 ER PT B AU Ron, E AF Ron, E BE Kellogg, SL Kirk, EJ TI An overview of radiation health studies: A framework for the Chelyabinsk studies SO ASSESSING HEALTH AND ENVIRONMENTAL RISKS FROM LONG-TERM RADIATION CONTAMINATION IN CHELYABINSK, RUSSIA LA English DT Proceedings Paper CT AAAS Annual Meeting Symposium on Assessing Health and Environmental Risks from Long-Term Radiation Contamination in Chelyabinsk, Russia CY FEB 12, 1996 CL BALTIMORE, MD SP Amer Assoc Adv Sci C1 NCI, Bethesda, MD 20892 USA. RP Ron, E (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1333 H STREET NW, WASHINGTON, DC 20005 USA BN 0-87168-600-7 PY 1997 BP 35 EP 43 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology GA BL61K UT WOS:000076011700005 ER PT J AU Niedzielski, AS Safieddine, S Wenthold, RJ AF Niedzielski, AS Safieddine, S Wenthold, RJ TI Molecular analysis of excitatory amino acid receptor expression in the cochlea SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE glutamate receptor; in situ hybridization; immunocytochemistry; polymerase chain reaction; hair cell; spiral ganglion neuron ID POLYMERASE CHAIN-REACTION; GUINEA-PIG COCHLEA; RAT COCHLEA; MESSENGER-RNAS; IMMUNOCYTOCHEMICAL LOCALIZATION; ACETYLCHOLINE-RECEPTOR; HAIR-CELLS; NMDA; SUBUNITS; AMPA AB Our present understanding of excitatory neurotransmission has expanded enormously in the last decade through the use of molecular biology. In the mammalian cochlea, the analysis of excitatory amino acid receptor expression by the reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization and immunochemistry has provided considerable evidence for glutamate as the afferent neurotransmitter. Using these molecular techniques, the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate, N-methyl-D-aspartic acid (NMDA) and delta receptor subunits and the metabotropic glutamate receptors have all been detected in the cochlea, in either the spiral ganglion neurons, the hair cells or both. Due to the utility of the techniques and the diversity of expressed neurotransmitter receptors, molecular biology will continue to provide important information for researchers of the auditory periphery. C1 NIDCD,NEUROCHEM LAB,NIH,BETHESDA,MD. RP Niedzielski, AS (reprint author), MED UNIV S CAROLINA,DEPT OTOLARYNGOL RS608,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 33 TC 30 Z9 30 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PD JAN-APR PY 1997 VL 2 IS 1-2 BP 79 EP 91 PG 13 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA WM893 UT WOS:A1997WM89300009 PM 9390824 ER PT S AU Mongini, P Highet, P Inman, J AF Mongini, P Highet, P Inman, J BE Chiorazzi, N Lahita, RG Pavelka, K Ferrarini, M TI Requirements for mIgM-triggered activation versus apoptosis in human B cells SO B LYMPHOCYTES AND AUTOIMMUNITY SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on B Lymphocytes and Autoimmunity CY MAY 21-25, 1996 CL PRAGUE, CZECH REPUBLIC SP Inst Rheumatol Prague, New York Acad Sci, Minist Hlth Czech Republic, Harry Winston Fdn Inc, Mucos Pharma, Baxter Biotech, Hyland Div, Commiss European Communities, Czech Rheumatol Inst, Leo Pharm Prod, Rockfeller Univ, Sandoz Pharma Ltd, Sanofi Winthrop, Zeneca Pharm ID AFFINITY C1 NIAID, IMMUNOL LAB, NIH, BETHESDA, MD 20892 USA. RP Mongini, P (reprint author), NYU, HOSP JOINT DIS, MED CTR, DEPT RHEUMATOL, NEW YORK, NY 10003 USA. FU NIGMS NIH HHS [GM35174] NR 5 TC 4 Z9 4 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-076-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 815 BP 469 EP 471 DI 10.1111/j.1749-6632.1997.tb52105.x PG 3 WC Immunology; Multidisciplinary Sciences; Rheumatology SC Immunology; Science & Technology - Other Topics; Rheumatology GA BH93X UT WOS:A1997BH93X00066 PM 9186700 ER PT S AU Zimering, MB Katsumata, N Friesen, HG Eng, J Riley, DJ ThakkerVaria, S Marx, SJ Ezzat, S AF Zimering, MB Katsumata, N Friesen, HG Eng, J Riley, DJ ThakkerVaria, S Marx, SJ Ezzat, S BE Chiorazzi, N Lahita, RG Pavelka, K Ferrarini, M TI Fibroblast growth factor-like autoantibodies in plasma from patients with multiple endocrine neoplasia type 1 and prolactinoma SO B LYMPHOCYTES AND AUTOIMMUNITY SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on B Lymphocytes and Autoimmunity CY MAY 21-25, 1996 CL PRAGUE, CZECH REPUBLIC SP Inst Rheumatol Prague, New York Acad Sci, Minist Hlth Czech Republic, Harry Winston Fdn Inc, Mucos Pharma, Baxter Biotech, Hyland Div, Commiss European Communities, Czech Rheumatol Inst, Leo Pharm Prod, Rockfeller Univ, Sandoz Pharma Ltd, Sanofi Winthrop, Zeneca Pharm C1 VET ADM MED CTR, DEPT MED SERV, LYONS, NJ 07939 USA. UNIV MANITOBA, FAC MED, WINNIPEG, MB R3E 0W3, CANADA. NIDDK, NIH, BETHESDA, MD 20892 USA. VET ADM MED CTR, BRONX, NY 10468 USA. UNIV TORONTO, WELLESLEY HOSP, TORONTO, ON M4Y 1J3, CANADA. RP Zimering, MB (reprint author), UNIV MED & DENT NEW JERSEY, ROBERT WOOD JOHNSON MED SCH, DEPT MED, PISCATAWAY, NJ 08854 USA. NR 5 TC 4 Z9 4 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-076-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 815 BP 520 EP 523 DI 10.1111/j.1749-6632.1997.tb52120.x PG 4 WC Immunology; Multidisciplinary Sciences; Rheumatology SC Immunology; Science & Technology - Other Topics; Rheumatology GA BH93X UT WOS:A1997BH93X00081 PM 9186715 ER PT J AU Brozinick, JT McCoid, SC Reynolds, TH Wilson, CM Stevenson, RW Cushman, SW Gibbs, EM AF Brozinick, JT McCoid, SC Reynolds, TH Wilson, CM Stevenson, RW Cushman, SW Gibbs, EM TI Regulation of cell surface GLUT4 in skeletal muscle of transgenic mice SO BIOCHEMICAL JOURNAL LA English DT Article ID GLUCOSE-TRANSPORTER TRANSLOCATION; INSULIN; RAT; CONTRACTION; INCREASE; DISTINCT AB Marked overexpression of the glucose transporter GLUT4 in skeletal muscle membrane fractions of GLUT4 transgenic (TG) mice is accompanied by disproportionately small increases in basal and insulin-stimulated glucose transport activity. Thus we have assessed cell surface GLUT4 by photolabelling with the membrane-impermeant reagent 2-N-[4-(1-azi-2,2,2-trifluoroethyl)benzoyl]-1,3-bis(D-mannos-4-yloxy) (ATB-BMPA) and measured the corresponding glucose transport activity using 2-deoxyglucose in isolated extensor digitorum longus (EDL) muscles from non-transgenic (NTG) and GLUT4 TG mice in the absence and presence of 13.3 nM (2000 mu units/ml) insulin, without or with hypoxia as a model of muscle contraction. TG mice displayed elevated rates of glucose trans port activity under basal and insulin-stimulated conditions, and in the presence of insulin plus hypoxia, compared with NTG mice. Photoaffinity labelling of cell surface GLUT4 indicated corresponding elevations in plasma membrane GLUT4 in the basal and insulin-stimulated states, and with insulin plus hypoxia, but no difference in cell surface GLUT4 during hypoxia stimulation. Subcellular fractionation of hindlimb muscles confirmed the previously observed 3-fold overexpression of GLUT4 in the TG compared with the NTG mice. These results suggest that: (1) alterations in glucose transport activity which occur with GLUT4 overexpression in EDL muscles are directly related to cell surface GLUT4 content, regardless of the levels observed in the corresponding subcellular membrane fractions, (2) while overexpression of GLUT4 influences both basal and insulin-stimulated glucose transport activity, the response to hypoxia/contraction-stimulated glucose transport is unchanged, and (3) subcellular fractionation provides little insight into the subcellular trafficking of GLUT4, and whatever relationship is demonstrated in EDL muscles from NTG mice is disrupted on GLUT4 overexpression. C1 PFIZER INC,PFIZER CENT RES,GROTON,CT 06340. RP Brozinick, JT (reprint author), NIDDK,EXPT DIABET METAB & NUTR SECT,DB,NIH,BLDG 10,ROOM 5N102,10 CTR DR,MSC 1420,BETHESDA,MD 20892, USA. NR 28 TC 21 Z9 21 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 JAN 1 PY 1997 VL 321 BP 75 EP 81 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WB619 UT WOS:A1997WB61900008 PM 9003403 ER PT J AU GuerreMillo, M Baldini, G Lodish, HF Lavau, M Cushman, SW AF GuerreMillo, M Baldini, G Lodish, HF Lavau, M Cushman, SW TI Rab 3D in rat adipose cells and its overexpression in genetic obesity (Zucker fatty rat) SO BIOCHEMICAL JOURNAL LA English DT Article ID GTP-BINDING PROTEINS; GLUCOSE-TRANSPORTER GLUT4; CARDIAC-MUSCLE; STIMULATED TRANSLOCATION; SUBCELLULAR-DISTRIBUTION; INSULIN; EXPRESSION; ADIPOCYTES; EXOCYTOSIS; TISSUE AB Members of the Rab 3 subfamily of low-molecular-mass GTP-binding proteins have been functionally implicated in regulated exocytosis. The aim of the present study was to examine the subcellular distribution of a member of this family, Rab 3D, in rat adipose cells, given the hypothesis that this protein might be involved in insulin-stimulated GLUT4 exocytosis. We show that Rab 3D immunoreactivity is associated predominantly with the high-density microsomal fraction, where the signal intensity is 3- and 7-fold greater than that in plasma membranes and low-density microsomes respectively. Rab 3D does not co-localize with GLUT4 on immune-isolated intracellular vesicles and, unlike GLUT4, it is not redistributed in response to insulin. Thus, if Rab 3D plays a role in GLUT4 trafficking, it relies on mechanisms independent of relocation. We observed that Rab 3D is overexpressed in adipose cells of obese (fa/fa) Zucker rats, in a tissue- and isoform-specific manner. The pathophysiological significance of this defect remains elusive. This could form the molecular basis for altered adipose secretory function in obesity. C1 NIDDKD,EXPT DIABET METAB & NUTR SECT,DIABET BRANCH,BETHESDA,MD 20892. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. RP GuerreMillo, M (reprint author), INST BIOMED CORDELIERS,INSERM,U177,15 RUE ECOLE MED,F-75006 PARIS,FRANCE. NR 45 TC 11 Z9 11 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 JAN 1 PY 1997 VL 321 BP 89 EP 93 PN 1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WB619 UT WOS:A1997WB61900010 PM 9003405 ER PT J AU Saito, K Seishima, M Heyes, MP Song, H Fujigaki, S Maeda, S Vickers, JH Noma, A AF Saito, K Seishima, M Heyes, MP Song, H Fujigaki, S Maeda, S Vickers, JH Noma, A TI Marked increases in concentrations of apolipoprotein in the cerebrospinal fluid of poliovirus-infected macaques: Relations between apolipoprotein concentrations and severity of brain injury SO BIOCHEMICAL JOURNAL LA English DT Article ID CENTRAL NERVOUS-SYSTEM; A-I; LIPOPROTEINS; REGENERATION; CELLS AB Apolipoproteins in cerebrospinal fluid (CSF) might have important functional roles in the pathophysiology of brain and lipid metabolism in the vascular component. The present study examined apolipoprotein A-I (ape-A-I) and apolipoprotein E (apo-E) levels in CSF and serum from poliovirus-infected macaques. Poliovirus-infected macaques developed motor deficits and were classified into three groups: (1) muscle weakness in one or both legs; (2) partial paralysis in one or both legs; (3) complete paralysis in one or both legs. No motor deficits were evident in the control or sham-treated macaques. Ape-A-I concentrations in CSF were markedly elevated in poliovirus-infected macaques with weakness, partial or complete paralysis, in comparison with either control or sham-treated animals, and were proportional to the severity of motor impairment. Apo-E concentrations in CSF were also significantly elevated in poliovirus-infected macaques with complete paralysis. The magnitude of increase in CSF apo-A-I or apo-E concentrations was also closely associated with the degree of histologic neurological damage and inflammation (lesion scores). However, no changes in serum ape-A-I and apo-E concentrations were observed in the poliovirus-infected macaques compared with control macaques. Furthermore there were no significant correlations ape-A-I or apo-E concentrations between serum and CSF. We hypothesize that the elevation of ape-A-I and apo-E concentrations after poliovirus infection is caused by immune stimulation within the central nervous system (CNS). Measures of CSF ape-A-I and apo-E levels might serve as a useful marker for the severity and/or the range of CNS injury. C1 NIMH,NEUROTOXICOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,PATHOBIOL & PRIMATOL LAB,BETHESDA,MD 20892. RP Saito, K (reprint author), GIFU UNIV,SCH MED,DEPT LAB MED,GIFU 500,JAPAN. NR 19 TC 20 Z9 21 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 JAN 1 PY 1997 VL 321 BP 145 EP 149 PN 1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WB619 UT WOS:A1997WB61900018 PM 9003413 ER PT B AU Hunyady, B Mezey, E Pacak, K Harta, G Palkovits, M AF Hunyady, B Mezey, E Pacak, K Harta, G Palkovits, M BE Gaginella, TS Mozsik, G Rainsford, KD TI Distribution of muscarinic receptor mrnas in the stomachs of normal or immobilized rats SO BIOCHEMICAL PHARMACOLOGY AS AN APPROACH TO GASTROINTESTINAL DISORDERS: BASIC SCIENCE TO CLINICAL PERSPECTIVES (1996) LA English DT Proceedings Paper CT IUPHAR GI Pharmacology Symposium on Biochemical Pharmacology as an Approach to Gastrointestinal Disorders - From Basic Science to Clinical Perspectives CY OCT 10-12, 1995 CL PECS, HUNGARY SP Int Union Pharm, Gastrointestinal Sect, Hungarian Acad Sci DE acetylcholine; muscarinic acetylcholine receptor; stomach; immobilization; in-situ hybridization histochemistry; immunohistochemistry; messenger RNA; rat AB Five subtypes of cholinergic muscarinic receptors (M1-M5) have been cloned and characterized by pharmacological and molecular biological methods during the past decade. The M3 subtype was demonstrated in acid-secreting cells, both by functional measurements and binding assays, while the M1 subtype is reported in the intramural ganglionic cells. In the present study, the distribution of M1-M5 mRNAs was mapped by in-situ hybridization histochemistry. Sections (12-mu m thick, frozen) from different parts of the stomachs from control or immobilized (3 h immobilization on two consecutive days) rats were hybridized with [S-35]UTP labelled ribonucleotides (400-500 nucleotides each) directed to mRNAs of the M1-M5 subtypes. M1 and M3 mRNAs were present in different locations and in different densities in the rat stomach; however, there was a complete lack in detection of mRNAs of the M2, M4 or M5 subtypes. M1 mRNA was found over the enteric ganglionic cells and over some deep epithelial and tunica propria cells of the prepyloric area. No labelling was seen over the epithelial cells of the fundic mucosa. The distribution of M1 mRNA was not changed by immobilization. M3 mRNA was detected over a portion of parietal cells (immunolabelled using a monoclonal antibody) of fundic mucosa and over smooth muscle cells of the tunica muscularis. A large number of tunica propria cells and some enteric ganglions were also labelled for M3 subtype. Weak labelling was seen over the surface mucous cells. The density of the labelling was increased in stressed rats, particularly over the tunica propria cells. These data complete earlier observations obtained by pharmacological and radio ligand binding assays on M1 and M3 subtypes in the rat stomach and support the existence of a non-epithelial, non-neuronal cell regulatory system in the GI tract. C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Palkovits, M (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8719-8 PY 1997 BP 171 EP 185 PG 15 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA BK35K UT WOS:000071892900015 ER PT J AU Tolstikov, VV Cole, R Fang, H Pincus, SH AF Tolstikov, VV Cole, R Fang, H Pincus, SH TI Influence of endosome-destabilizing peptides on efficacy of anti-HIV immunotoxins SO BIOCONJUGATE CHEMISTRY LA English DT Article ID RICIN-A-CHAIN; HUMAN-IMMUNODEFICIENCY-VIRUS; EXOTOXIN HYBRID PROTEIN; GENE-TRANSFER; ANTIBODIES; CELLS; INFECTION; INVITRO AB The effects on immunotoxin efficacy of fusogenic peptides derived from influenza virus hemagglutinin have been studied. These peptides have an amphipathic nature and change conformation from random at pH 7 to helical at pH 5. Fusogenic peptides are reported to destabilize endosomal membranes, resulting in the release of contents into the cytoplasm, The use of two related fusogenic peptides to enhance the efficacy of anti-MN immunotoxins is described. The direct toxicity of the peptides was tested on HN-infected H9/NL4-3 cells. Peptide HA24 was considerably more toxic than HA23, The peptides were mixed with two different immunotoxins. Immunotoxin action was enhanced by both peptides, with HA24 providing greater enhancement than HA23. Immunotoxins were then constructed by coupling HA23 or HA24 to the targeting antibody with disulfide-containing linkers. Peptide HA23 enhanced the activity of the immunotoxin 4-5-fold. Surprisingly, HA24 significantly inhibited immunotoxin activity. Coupling the peptides to the immunotoxin had no effect on antigen binding characteristics or the activity of the toxic moiety. Bafilomycin A(1), an agent that inhibits vacuolar acidification, markedly potentiated the effects of all immunotoxins. These results demonstrate that amphipathic peptides can influence the efficacy of immunotoxins, but in sometimes unpredictable ways. C1 NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. OI Tolstikov, Vladimir/0000-0002-0445-884X NR 20 TC 19 Z9 19 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN-FEB PY 1997 VL 8 IS 1 BP 38 EP 43 DI 10.1021/bc9600729 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA WF232 UT WOS:A1997WF23200007 PM 9026033 ER PT J AU Liu, SY Stadtman, TC AF Liu, SY Stadtman, TC TI A non-radioactive and two radioactive assays for selenophosphate synthetase activity SO BIOFACTORS LA English DT Article AB Selenophosphate synthetase catalyzes the formation of monoselenophosphate (SePO33-) from ATP and selenide (reaction 1). ATP + HSe- --> SePO33- + PO43+ + AMP In one assay frequently used, [8-C-14]AMP formation from [8-C-14]ATP is estimated after separation of the nucleotides by thin-layer chromatography. An alternative non-radioactive assay in which the AMP product is estimated using AMP deaminase is described. The highly oxygen-labile selenophosphate product can be estimated in an assay employing [gamma-P-32]ATP. The P-32-labeled selenophosphate is converted to [P-32]orthophosphate by treatment with iodine and estimated after removal of residual [P-32]ATP on charcoal. C1 NHLBI, Biochem Lab, IR, NIH, Bethesda, MD 20892 USA. RP Stadtman, TC (reprint author), NHLBI, Biochem Lab, IR, NIH, Bldg 3,Room 108,3 Ctr Dr MSC 0320, Bethesda, MD 20892 USA. NR 16 TC 1 Z9 1 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 1997 VL 6 IS 3 BP 305 EP 309 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA V3164 UT WOS:000171771800001 PM 9288401 ER PT J AU Komatsu, F Inoue, K Mogi, M Creveling, CR Karasawa, N Nagatsu, I AF Komatsu, F Inoue, K Mogi, M Creveling, CR Karasawa, N Nagatsu, I TI Activity and immunocytochemical localization of the catecholamine-synthesizing enzymes in human dental pulp SO BIOGENIC AMINES LA English DT Article DE tyrosine hydroxylase; L-aromatic amino acid decarboxylase; dopamine-beta-hydroxylase; phenylethanolamine-N-methyltransferase; human dental pulp ID AMINO-ACID DECARBOXYLASE; PERFORMANCE LIQUID-CHROMATOGRAPHY; DOPAMINE-BETA-HYDROXYLASE; TYROSINE-HYDROXYLASE; CEREBROSPINAL-FLUID; SENSITIVE ASSAY; SEROTONIN; NEURONS; TISSUES; FIBERS AB Local production of catecholamines in the human dental pulp was studied by measurement of activity and immunocytochemical demonstration of tyrosine hydroxylase (TH), L-aromatic amino acid decarboxylase (AADC), dopamine-beta-hydroxylase (DBH) and phenyl-ethanolamine-N-methyltransferase (PNMT), the enzymes catalyzing the formation of DOPA, dopamine, norepinephrine and epinephrine, respectively. A rich innervation of TH- and AADC-immunoreactive nerve fibers was seen around the arterioles, The fine beaded immunoreactive varicosities of the DBH were found on the wall of arterioles. TH-immunoreactive nerve fibers were also observed in the cell rich zone, No specific PNMT immunoreactivity was observed. Higher AADC activity has been found in the human dental pulp. AADC was also present in the smooth muscle cells of the arteriole. The results suggest that some nerve fibers in the human dental pulp may synthesize norepinephrine as an end-product of catecholamine biosynthesis and smooth muscle cells of the arteriole may play a role like APUD cells. C1 MATSUMOTO DENT COLL,INST DENT SCI,LAB ORAL STRUCT & FUNCT,NAGANO 39907,JAPAN. MATSUMOTO DENT COLL,DEPT ORAL & MAXILLOFACIAL SURG 1,NAGANO 39907,JAPAN. AICHI GAKUIN UNIV,SCH DENT,DEPT PHARMACOL,CHIKUSA KU,NAGOYA,AICHI 464,JAPAN. NIDDK,OFF TECHNOL DEV,NIH,BETHESDA,MD 20892. FUJITA HLTH UNIV,SCH MED,DEPT ANAT,TOYOAKE,AICHI 47011,JAPAN. NR 32 TC 1 Z9 1 U1 0 U2 0 PU VSP BV PI ZEIST PA PO BOX 346, 3700 AH ZEIST, NETHERLANDS SN 0168-8561 J9 BIOGENIC AMINES JI Biog. Amines PY 1997 VL 13 IS 3 BP 233 EP 245 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XJ887 UT WOS:A1997XJ88700007 ER PT S AU Krichmar, JL Ascoli, GA Hunter, L Olds, JL AF Krichmar, JL Ascoli, GA Hunter, L Olds, JL BE Mira, J MorenoDiaz, R Cabestany, J TI A model of cerebellar saccadic motor learning using qualitative reasoning SO BIOLOGICAL AND ARTIFICIAL COMPUTATION: FROM NEUROSCIENCE TO TECHNOLOGY SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 4th International Work-Conference on Artificial Neural Networks (IWANN 97) CY JUN 04-06, 1997 CL LANZAROTE, SPAIN SP Univ Nacl Educ Distancia, Univ Palmas Gran Canaria, Univ Politecn Catalunya, Asociac Espanola Redes Neuroanles, IFIP Working Grp Neural Comp Syst, Spanish RIG AERN, IEEE Neural Networks Council, IEEE UK&RI Commun Chapter ID CAUDAL FASTIGIAL NUCLEUS; ACTIVE MEMBRANE MODEL; PURKINJE-CELL; OCULOMOTOR VERMIS; EYE-MOVEMENTS; ADAPTIVE-CONTROL; MACAQUE MONKEYS; SIMULATION; DISCHARGE; GENERATION AB We present a novel approach to modeling neural behavior using a "qualitative reasoning" algorithm. The Qualitative Reasoning Neuron (QRN). is capable of qualitatively reproducing single neuron behavior, but is computationally simple enough to use in large scale neural networks without loss of critical details. QRN simulations of a single Purkinje cell (similar to 1600 compartments) show significant speedup over a recent GENESIS model. A large scale model of the cerebellar cortex (256 neurons, similar to 300,000 compartments) is used to simulate a saccadic eye movement task. The model reproduces in vivo Purkinje cell bursting patterns during saccades. We simulate rapid and gradual adaptation paradigms and show that error correction is possible when climbing fiber input is periodic and contains no error signal. C1 George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA 22030 USA. George Mason Univ, Dept Computat Sci & Informat, Fairfax, VA 22030 USA. Natl Lib Med, Bethesda, MD USA. RP Krichmar, JL (reprint author), George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA 22030 USA. RI Olds, James/D-2867-2011 NR 35 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0302-9743 BN 3-540-63047-3 J9 LECT NOTES COMPUT SC PY 1997 VL 1240 BP 133 EP 145 PG 13 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Multidisciplinary Sciences; Neurosciences SC Computer Science; Science & Technology - Other Topics; Neurosciences & Neurology GA BK96U UT WOS:000073947300014 ER PT J AU Balboni, G Guerrini, R Salvadori, S Tomatis, R Bryant, SD Bianchi, C Attila, M Lazarus, LH AF Balboni, G Guerrini, R Salvadori, S Tomatis, R Bryant, SD Bianchi, C Attila, M Lazarus, LH TI Opioid diketopiperazines: Synthesis and activity of a prototypic class of opioid antagonists SO BIOLOGICAL CHEMISTRY LA English DT Article DE antagonist; diketopiperazine; opioid peptides; peptide synthesis ID THYROTROPIN-RELEASING-HORMONE; HISTIDYL-PROLINE-DIKETOPIPERAZINE; SELECTIVE PEPTIDE ANTAGONISTS; DELTORPHIN ANALOGS; TETRAHYDROISOQUINOLINE-3-CARBOXYLIC ACID; INDUCED HYPOTHERMIA; AROMATIC RING; AMINO-ACIDS; RAT-BRAIN; RECEPTOR AB Discovery of high affinity and ultraselective delta opioid dipeptide antagonists composed of 2',6'-dimethyl-L-tyrosyl (Dmt) and 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tie) served as the basis for the conformationally restricted diketopiperazine cyclo(Dmt-Tlc) and related open chain analogues. These peptides primarily bind to delta opioid receptors: c(Dmt-Tic) displayed 30- to 50-fold higher delta affinity (K-i delta) than its diastereoisomeric analogues and more than 4000-fold greater than its Tyr cognate; all of the c(Tyr-Tic) analogues were essentially inactive; c[(N-methyl)Dmt-Tic] lost 5-fold in K-i delta, while K-i mu increased 10-fold to yield a nonselective peptide; and the c(Dmt-Phe) series exhibited considerably reduced binding which indicated a synergism between Dmt and Tic in the binding mechanism. Whereas acetyl-Dmt-Tic linear peptides weakly interacted with opioid receptors, Ac-Dmt-Tic-NH2, exhibited better delta antagonist activity than c(Dmt-Tic) and greater delta receptor selectivity (K-i mu/K-i delta = 570). A three point attachment hypothesis for the interaction between c(Dmt-Tic) and the delta receptor was proposed: hydrophobicity imparted by the aromatic rings and the methyl groups of Dmt, hydrogen bonding through the tyramine hydroxyl group, and cation-pi interactions were suggested as contributing factors in binding the diketopiperazine in the receptor pocket. Although c(Dmt-Tic) exhibited a weak antagonist activity with mouse vas deferens, this diketopiperazine may provide a scaffolding for the formation of more potent antagonists for potential therapeutic applications. C1 NIEHS,LCBRA,RES TRIANGLE PK,NC 27709. UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. UNIV FERRARA,CTR BIOTECHNOL,I-44100 FERRARA,ITALY. UNIV FERRARA,INST PHARMACOL,I-44100 FERRARA,ITALY. UNIV HELSINKI,DEPT CLIN SCI PHARMACOL & TOXICOL,FAC MED VET,FIN-00014 HELSINKI,FINLAND. OI Guerrini, Remo/0000-0002-7619-0918; SALVADORI, Severo/0000-0002-8224-2358 NR 86 TC 36 Z9 37 U1 0 U2 5 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD JAN PY 1997 VL 378 IS 1 BP 19 EP 29 DI 10.1515/bchm.1997.378.1.19 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WH252 UT WOS:A1997WH25200003 PM 9049061 ER PT J AU Fleming, K Goldberg, TE Binks, S Randolph, C Gold, JM Weinberger, DR AF Fleming, K Goldberg, TE Binks, S Randolph, C Gold, JM Weinberger, DR TI Visuospatial working memory in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Schizophrenia; working memory; neuropsychology; spatial cognition ID DORSOLATERAL PREFRONTAL CORTEX; COGNITIVE DEFICIT; PERFORMANCE; DYSFUNCTION; TESTS; DISORDERS; DOPAMINE; DISEASE AB Recent investigations have documented abnormalities in working memory related processes in schizophrenics on tasks assessing the central executive component of this cognitive model. This preliminary study investigated the function of another component of the working memory system, the visuospatial scratch pad in schizophrenia. The ''scratch pad's'' passive visual store-responsible for the temporary retention of visual material-was assessed via a computerized spatial delayed response task, whereas its active spatial rehearsal subsystem-specialized for retaining the temporal properties-was explored through visual block span, To assess elemental visual spatial abilities we used the Judgment of Line Orientation test. Thirty-two schizophrenics and 27 controls were tested. Although we discovered the basic perceptual abilities of patients to be intact, we determined that whenever memory was necessitated on spatial tasks, patients demonstrated marked deficits. This pattern of cognitive dysfunction is consistent with impairments in a neural network involving prefrontal and/or posterior brain regions in schizophrenia. (C) 1997 Society of Biological Psychiatry. C1 NIMH, CLIN BRAIN DISORDERS BRANCH, NIH, WASHINGTON, DC USA. NR 50 TC 105 Z9 106 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 1997 VL 41 IS 1 BP 43 EP 49 DI 10.1016/S0006-3223(96)00263-6 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WA835 UT WOS:A1997WA83500005 PM 8988794 ER PT J AU Martinez, R Molchan, SE Lawlor, BA Thompson, K Martinson, H Latham, G Weingartner, H Sunderland, T AF Martinez, R Molchan, SE Lawlor, BA Thompson, K Martinson, H Latham, G Weingartner, H Sunderland, T TI Minimal effects of dextroamphetamine on scopolamine-induced cognitive impairments in humans SO BIOLOGICAL PSYCHIATRY LA English DT Article DE scopolamine; dextroamphetamine; stimulant; cholinergic; attention ID THYROTROPIN-RELEASING-HORMONE; AGE-MATCHED CONTROLS; ALZHEIMERS-DISEASE; CHOLINERGIC SYSTEM; MEMORY IMPAIRMENT; TRH; PHYSOSTIGMINE; ACETYLCHOLINE; SENSITIVITY; LORAZEPAM AB The central anticholinergic drug scopolamine has been used to model aspects of the memory impairment that occurs in Alzheimer's disease and in aging, To determine whether nonspecific stimulant effects can attenuate the cognitive impairment induced by scopolamine, we studied the effects of scopolamine and the stimulant dextroamphetamine in 17 young normal volunteers. After a baseline day of cognitive testing, subjects participated in two study days, in which they received dextroamphetamine (d-AMP) (0.25 mg/kg po) + scopolamine (0.5 mg IV) and placebo + scopolamine, in randomized order under double-blind conditions. There were no statistically significant differences in cognitive test performance between the two drug conditions with the exception of one of the category retrieval tasks. Stimulant effects were documented to occur by other measures. We conclude that d-AMP at the dose used does not attenuate the memory impairment induced by scopolamine. (C) 1997 Society of Biological Psychiatry. C1 NIMH,SECT GERIATR PSYCHOPHARMACOL,CLIN SCI LAB,BETHESDA,MD 20892. ST JAMES HOSP,OLD AGE PSYCHIAT SECT,DUBLIN 8,IRELAND. NIAAA,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. NR 41 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 1997 VL 41 IS 1 BP 50 EP 57 DI 10.1016/0006-3223(95)00674-5 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WA835 UT WOS:A1997WA83500006 PM 8988795 ER PT J AU Curtis, GC Abelson, JL Gold, PW AF Curtis, GC Abelson, JL Gold, PW TI Adrenocorticotropic hormone and cortisol responses to corticotropin-releasing hormone: Changes in panic disorder and effects of alprazolam treatment SO BIOLOGICAL PSYCHIATRY LA English DT Article DE panic disorder; cortisol; adrenocorticotropic hormone; corticotropin-releasing hormone; alprazolam ID BETA-ENDORPHIN RELEASE; HPA-AXIS DISTURBANCE; PATHO-PHYSIOLOGY; MAJOR DEPRESSION; STIMULATION TEST; STRESS; ACTH AB This study applied the corticotropin-releasing hormone (CRH) stimulation rest to patients with panic disorder, before and during treatment with alprazolam, and to control subjects. In contrast to some, but not all prior studies, untreated, nondepressed panic disorder patients failed to shaw blunted adrenocorticotropic hormone or cortisol responses to CRH, In fact, the responses were subtly enhanced in that they were more rapid than those of controls. After 12 weeks of alprazolam treatment, repeat testing gave results that were indistinguishable from those of controls. Inconsistency among reports of CRH testing in panic disorder may be related to interactions among illness mechanisms, concurrent subthreshold depressive symptoms, the chronic stress of the illness, and hyperresponsiveness of panic patients to the acute stress of experimental manipulations. Pretreatment abnormalities in hypothalamic-pituitary-adrenal axis function appear to resolve with alprazolam treatment. Preliminary observations suggest that pretreatment dysregulation of the hypothalamic-pituitary-adrenal system may predict a more difficult or less satisfactory treatment. (C) 1997 Society of Biological Psychiatry. C1 UNIV MICHIGAN,DEPT PSYCHIAT,ANXIETY DISORDERS PROGRAM,ANN ARBOR,MI 48109. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. FU NCRR NIH HHS [M01RR00042] NR 30 TC 32 Z9 32 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 1997 VL 41 IS 1 BP 76 EP 85 DI 10.1016/S0006-3223(95)00578-1 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WA835 UT WOS:A1997WA83500009 PM 8988798 ER PT J AU Slayden, OD Rubin, J Lacey, D Brenner, RM AF Slayden, OD Rubin, J Lacey, D Brenner, RM TI Keratinocyte growth factor (KGF) stimulates epithelial cell proliferation in the primate oviduct and vagina. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 OREGON REG PRIMATE RES CTR,DIV REPROD SCI,BEAVERTON,OR 97006. NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. AMGEN INC,THOUSAND OAKS,CA 91320. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1997 VL 56 SU 1 BP 84 EP 84 PG 1 WC Reproductive Biology SC Reproductive Biology GA XG865 UT WOS:A1997XG86500124 ER PT J AU Esta, S Tessarollo, L Johnson, PF AF Esta, S Tessarollo, L Johnson, PF TI Analysis of female sterility in mice deficient for the transcription factor C/EBP beta SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,EUKARYOT TRANSCRIPT REGULAT GRP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,NEURAL DEV GRP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,SPECIAL PROGRAM GERMLINE MUTAT,FREDERICK,MD 21701. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1997 VL 56 SU 1 BP 100 EP 100 PG 1 WC Reproductive Biology SC Reproductive Biology GA XG865 UT WOS:A1997XG86500140 ER PT J AU Gibori, G Sugino, N Telleria, CM Srivastava, RK Risk, M Chou, JY Zilberstein, M AF Gibori, G Sugino, N Telleria, CM Srivastava, RK Risk, M Chou, JY Zilberstein, M TI Establishment and characterization of a simian virus 40-transformed, temperature sensitive rat luteal cell line. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 UNIV ILLINOIS,DEPT PHYSIOL & BIOPHYS,CHICAGO,IL 60680. FAULKNER CTR REPROD MED,BOSTON,MA. NICHHD,HGB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1997 VL 56 SU 1 BP 112 EP 112 PG 1 WC Reproductive Biology SC Reproductive Biology GA XG865 UT WOS:A1997XG86500152 ER PT J AU Diouf, O Bourhim, M Lambert, DM Poupaert, JH Stables, JP Vamecq, J AF Diouf, O Bourhim, M Lambert, DM Poupaert, JH Stables, JP Vamecq, J TI Anticonvulsant and neurotoxicological properties of 4-amino-N-(2-ethylphenyl)benzamide, a potent ameltolide analogue SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE 4-aminobenzamide pharmacophore; 4-amino-N-(2-ethylphenyl)benzamide; anticonvulsant activity; antiepileptic drug; neurotoxicity; ameltolide; phenytoin ID ANTIEPILEPTIC DRUG DEVELOPMENT; MICE; NEUROTOXICITY; LY201116; RATS AB A well documented study on the anticonvulsant properties of 4-amino-N-(2-ethylphenyl)benzamide (4-AEPB) is here provided. Initial screening in mice dosed intraperitoneally and rats dosed orally indicated that 4-AEPB is active against maximal electroshock-induced seizures (MES), bur does not protect animals against subcutaneous pentylenetetrazole (sc Ptz)-induced seizures. Quantitative evaluation of anti-MES activity and neurotoxicity of 4-AEPB: given intraperitoneally to mice provided ED50 and TD50 values amounting to 28.6 and 96.3 mu mol/kg respectively, resulting in a protective index (PI = TD50/ED50) equal to 3.36. Further quantitative evaluation in rats dosed orally indicated that the respective ED50 and TD50 values for 4-AEPB were 29.8 and more than 1,530 mu mol/kg, resulting in a very high PI value of over 51. Comparison of anticonvulsant properties and neurotoxicity of 4-AEPB with those previously reported in the literature for two 4-aminobenzamide derivatives, 4-amino-N-(2,6-dimethylphenyl)benzamide (or ameltolide, an antiepileptic drug prototype developed by Eli Lilly), and phenytoin, underlines the value of 4-AEPB for future pharmacological development. In this perspective, an additional favorable element is represented by the ability of 4-AEPB to increase the seizure threshold in the intravenous Ptz seizure threshold test in mice dosed intraperitoneally. Molecular modeling studies show that the translocation of one carbon unit in the isomerization of the 2,6-dimethylphenyl moiety of ameltolide to the 2-ethylphenyl counterpart succeeds in maintaining the conformational low energy presentation adopted by ameltolide, providing clues as to why the 4-AEPB here described is an anticonvulsant agent derived from the 4-aminobenzamide pharmacophore platform as potent as ameltolide. C1 DOMAINE CERTIA,INSERM,F-59651 VILLENEUVE DASCQ,FRANCE. HOP LILLE,SERV MALADIES & NEUROL INFANTILES,F-59037 LILLE,FRANCE. UNIV CATHOLIQUE LOUVAIN,DEPT CHIM THERAPEUT,ECOLE PHARM,B-1200 BRUSSELS,BELGIUM. NINCDS,PRECLIN PHARMACOL SECT,EPILEPSY BRANCH,DCDND,NATL INST HLTH,BETHESDA,MD 20892. NR 14 TC 9 Z9 10 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 141 RUE JAVEL, 75747 PARIS, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PY 1997 VL 51 IS 3 BP 131 EP 136 DI 10.1016/S0753-3322(97)86911-9 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA WV449 UT WOS:A1997WV44900007 PM 9181049 ER PT J AU Kato, S Onda, M Matsukura, N Tokunaga, A Matsuda, N Yamashita, K Shields, PG AF Kato, S Onda, M Matsukura, N Tokunaga, A Matsuda, N Yamashita, K Shields, PG TI Helicobacter pylori infection and genetic polymorphisms for cancer-related genes in gastric carcinogenesis SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE genetic polymorphism; Helicobacter pylori; gastric cancer susceptibility ID FRAGMENT-LENGTH-POLYMORPHISM; SERUM PEPSINOGEN-I; HUMAN-LUNG-CANCER; STOMACH-CANCER; JAPANESE POPULATION; RISK; CARCINOMA; CYTOCHROME-P450IIE1; ASSOCIATION; METASTASIS AB The development of gastric cancer is a multistep process that is multi-factorial. An association with the Helicobacter pylori infections, gastric atrophy and gastric cancer has received recent attention. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiological techniques for genetic susceptibility, gastric atrophy and serum markers including H pylori infection. We used an age- and gender-matched case-control study, where patients with benign gastric lesions were the controls. Low serum pepsinogen I levels (cut-off < 50 ng/mL) and low pepsinogen I/pepsinogen II ratios (cut-off < 3.0) were significantly associated with the risk of gastric cancer (odds ratio [OR] = 3.53: 95% confidence interval [CI] = 2.46-5.09 and OR = 4.73: 3.26-6.88, respectively). However, seropositivity of serum immunoglobulin G (IgG) antibody against H pylori (OR = 1.09: 0.74-1.61) was nor associated with gastric cancer, even when analyzed by age greater than or less than 50 years. Specific genotypes of the cytochrome p450 2E1 (CYP2E1) RsaI polymorphism and glutathione-S-transferase (GST) M1 gene deletion were determined but were not associated with gastric cancer; however, a L-myc genetic polymorphism was associated with gastric cancer (OR = 1.55: 1.03-2.34). Therefore, in this Japanese study, atrophic mucosal change, indicated by serum pepsinogen levels, is a possible risk factor for gastric cancer. C1 NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RP Kato, S (reprint author), NIPPON MED COLL,DEPT SURG 1,BUNKYO KU,1-1-5 SENDAGI,TOKYO 113,JAPAN. RI Shields, Peter/I-1644-2012 NR 33 TC 27 Z9 30 U1 1 U2 3 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 141 RUE JAVEL, 75747 PARIS, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PY 1997 VL 51 IS 4 BP 145 EP 149 DI 10.1016/S0753-3322(97)85581-3 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA WZ977 UT WOS:A1997WZ97700001 PM 9207980 ER PT J AU Nam, JM AF Nam, JM TI Sample size determination for designing a strata-matched case-control study to detect multiple risk factors SO BIOMETRICAL JOURNAL LA English DT Article DE sample size; multiple risk factors; strata-matched case-control study; optimum design; omnibus test; simultaneous comparison; individual comparison ID SMOKING; MODELS; TESTS; POWER AB Investigations of sample size for planning case-control studies have usually been limited to detecting a single factor. In this paper, we investigate sample size for multiple risk factors in strata-matched case-control studies. We construct an omnibus statistic for testing M different risk factors based on the jointly sufficient statistics of parameters associated with the risk factors. The statistic is non-iterative, and it reduces to the Cochran statistic when M = 1. The asymptotic power function of the test is a non-central chi-square with M degrees of freedom and the sample size required for a specific power can be obtained by the inverse relationship. We find that the equal sample allocation is optimum. A Monte Carlo experiment demonstrates that an approximate formula for calculating sample size is satisfactory in typical epidemiologic studies. An approximate sample size obtained using Bonferroni's method for multiple comparisons is much larger than that obtained using the omnibus test. Approximate sample size formulas investigated in this paper using the omnibus test, as well as the individual tests, can be useful in designing case-control studies for detecting multiple risk factors. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. NR 24 TC 2 Z9 2 U1 0 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1997 VL 39 IS 4 BP 441 EP 454 DI 10.1002/bimj.4710390406 PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA YB352 UT WOS:A1997YB35200005 ER PT J AU Faraggi, D Simon, R Yaskil, E Kramar, A AF Faraggi, D Simon, R Yaskil, E Kramar, A TI Bayesian neural network models for censored data SO BIOMETRICAL JOURNAL LA English DT Article DE Bayesian analysis; feed-forward neural network; maximum likelihood; shrinkage; sufficiency principle ID SURVIVAL-DATA; REGRESSION; CLASSIFICATION; INFORMATION; EFFICIENCY; PREDICTION AB Neural networks are considered by many to be very promising tools for classification and prediction. The flexibility of the neural network models often result in over-fit. Shrinking the parameters using a penalized likelihood is often used in order to overcome such over-fit. In this paper we extend the approach proposed by FARAGGI and SIMON (1995a) to modeling censored survival data using the input-output relationship associated with a single hidden layer feed-forward neural network. Instead of estimating the neural network parameters using the method of maximum likelihood, we place normal prior distributions on the parameters and make inferences based on derived posterior distributions of the parameters. This Bayesian formulation will result in shrinking the parameters of the neural network model and will reduce the over-fit compared with the maximum likelihood estimators. We illustrate our proposed method on a simulated and a real example. C1 UNIV HAIFA,DEPT STAT,IL-31999 HAIFA,ISRAEL. NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. CTR REG DE LUTTE CONTRE CANC,MONTPELLIER,FRANCE. NR 34 TC 5 Z9 5 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1997 VL 39 IS 5 BP 519 EP 532 DI 10.1002/bimj.4710390502 PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA YE351 UT WOS:A1997YE35100001 ER PT J AU Borkowf, CB Gail, MH AF Borkowf, CB Gail, MH TI Parametric methods for bivariate quantile-partitioned tables and the efficiency of corresponding nonparametric methods SO BIOMETRICAL JOURNAL LA English DT Article DE agreement; asymptotic relative efficiency; contingency tables; empirical bivariate quantile-partitioned (EBQP) distribution; kappa; row proportions; weighted kappa ID FOOD FREQUENCY QUESTIONNAIRE; REPRODUCIBILITY; VALIDITY AB In order to study the agreement between two continuous measurements on a sample of individuals, epidemiologists sometimes partition the original bivariate data into categories defined by the empirical quantiles of the two marginal distributions. The counts in the resulting two-way contingency table have the empirical bivariate quantile-partitioned (EBQP) distribution rather than the conventional multinomial distribution. Borkowf et al. (1997) developed the asymptotic theory and inferential procedures for estimates of measures of agreement calculated from EBQP tables. In this paper, we develop parametric methods for bivariate quantile-partitioned (BQP) tables. We use these methods to study the efficiency of nonparametric (EBQP) methods and to improve the precision of estimates of measures of agreement. We present computational methods for estimating certain measures of agreement (kappa, weighted kappa, and row proportions) together with their variances. Numerical studies and an example show that nonparametric (EBQP) estimates of kappa and certain row proportions tend to be quite inefficient compared to parametric estimates, whereas nonparametric estimates of weighted kappa can be relatively more efficient for some underlying distributions. Thus, investigators should weigh the efficiency advantages of parametric estimates against possible biases that can result from choosing an inappropriate parametric model when they employ BQP tables to study agreement. C1 NHLBI, Div Epidemiol & Clin Applicat, Off Biostat Res, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1997 VL 39 IS 8 BP 919 EP 934 DI 10.1002/bimj.4710390805 PG 16 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA ZA936 UT WOS:000072416900004 ER PT J AU Akamatsu, M Roller, PP Chen, L Zhang, ZY Ye, B Burke, TR AF Akamatsu, M Roller, PP Chen, L Zhang, ZY Ye, B Burke, TR TI Potent inhibition of protein-tyrosine phosphatase by phosphotyrosine-mimic containing cyclic peptides SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE phosphatase; inhibitor; signal transduction; mimic; cyclic peptide ID SOLID-PHASE SYNTHESIS; KINASE INHIBITION; O-PHOSPHOTYROSINE; N-BOC; ANALOGS; L-O-(2-MALONYL)TYROSINE; PHENYLALANINE; DISCOVERY; AGENTS AB In an effort to derive potent and bioavailable protein-tyrosine phosphatase inhibitors, we have previously reported hexameric peptides based on the epidermal growth factor receptor sequence EGFR(988-993) (Asp-Ala-Asp-Glu-Xxx-Leu, where Xxx = Tyr), in which the tyrosyl residue has been replaced by the non-hydrolyzable phosphotyrosyl mimics phosphonomethylphenylalanine (Pmp), difluorophosphsnomethylphenylalanine (F(2)Pmp) and O-malonyltyrosine (OMT) Inhibitory potencies (IC50 values) of these peptides against the tyrosine phosphatase PTP 1B were 200, 0.2 and 10 mu M, respectively. Since cellular penetration of peptides containing highly charged phosphonate residues is compromised, and good bioreversible protection strategies for the F(2)Pmp residue have not yet been reported, the OMT residue is of particular interest in that it affords potential new prodrug approaches. In the current study we have prepared cyclized versions of the OMT-containing EGFR(988-993) peptide in order to increase its proteolytic stability and restrain conformational flexibility. Three different cyclic analogues were synthesized. Two of these were cyclized through the peptide backbone ('head to tail') using in one case a single glycine spacer (heptamer peptide) and in the second instance, two glycines (octamer peptide). In a PTP1-based assay the cyclic heptamer experienced a two-fold loss of potency (K-i = 25.2+/-3.9 mu M) relative to the linear hexamer parent (K-i = 13+/-0.9 mu M), while the cyclic octamer demonstrated a five-fold increase in potency (K-i = 2.60+/-0.11 mu M). The third peptide was cyclized by means of a sulfide bridge between the side chain of a C-terminally added cysteine residue and the beta-carbon of a N-terminal acetyl residue. Although the overall size of this ring was identical to that exhibited by the preceding backbone-cyclized octamer, it displayed a three-fold enhancement in potency (K-i = 0.73+/-0.03 mu M). The structural basis for the observed results are discussed. Conformational restrictions induced by cyclization could aid in defining geometries for peptidomimetic design. Finally, it can be speculated that cyclization of other linear PTP-inhibitoly peptides, such as the F(2)Pmp-containing hexamer, may also increase their potency. Published by Elsevier Science Ltd. Science Ltd. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. ALBERT EINSTEIN COLL MED,DEPT MOL PHARMACOL,BRONX,NY 10461. RI Burke, Terrence/N-2601-2014 FU NIDDK NIH HHS [5 P60 DK 20541-18] NR 31 TC 50 Z9 52 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN PY 1997 VL 5 IS 1 BP 157 EP 163 DI 10.1016/S0968-0896(96)00195-2 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA WG219 UT WOS:A1997WG21900015 PM 9043667 ER PT J AU Mienville, JM Clay, JR AF Mienville, JM Clay, JR TI Ion conductance of the Ca2+-activated maxi-K+ channel from the embryonic rat brain SO BIOPHYSICAL JOURNAL LA English DT Article ID PHOSPHOLIPID SURFACE-CHARGE; PLANAR LIPID BILAYERS; SARCOPLASMIC-RETICULUM; POTASSIUM CHANNELS; PERMEATION; SELECTIVITY; MUSCLE; BLOCK; CELLS AB By using single-channel recording techniques, we measured the conductance (g(K)) of the Ca2+-activated Maxi-K+ channel from the embryonic rat brain, and examined its dependence on K+ ions present in equimolar concentrations on both sides of the membrane patch. With ionic strength maintained constant by substitution of N-methyl-D-glucamine for K+, g(K) has a sigmoidal dependence upon [K+]. This result has been obscured in previous work by variations in ionic strength, which has a marked effect on single-channel conductance, especially in the limit for which this variable approaches zero, The g, versus [K+] relationship is described, theoretically, by a three-barrier, two-binding-site model in which the barrier that an ion must cross to leave the channel is decreased as [K+] is increased. C1 NINCDS,NEUROPHYSIOL LAB,NIH,BETHESDA,MD 20892. NR 24 TC 6 Z9 6 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1997 VL 72 IS 1 BP 188 EP 192 PG 5 WC Biophysics SC Biophysics GA WC529 UT WOS:A1997WC52900017 PM 8994603 ER PT J AU Kuznetsova, N Rau, DC Parsegian, VA Leikin, S AF Kuznetsova, N Rau, DC Parsegian, VA Leikin, S TI Solvent hydrogen-bond network in protein self-assembly: Solvation of collagen triple helices in nonaqueous solvents SO BIOPHYSICAL JOURNAL LA English DT Article ID X-RAY-DIFFRACTION; FOLDING THERMODYNAMICS; HYDRATION FORCES; WATER; PACKING; MOLECULES; PEPTIDE; FIBRILS AB Forces between type I collagen triple helices are studied in solvents of varying hydrogen-bonding ability. The swelling of collagen fibers in reconstituted films is controlled by the concentration of soluble polymers that are excluded from the fibers and that compete osmotically with collagen for available solvent. The interaxial spacing between the triple helices as a function of the polymer concentration is measured by x-ray diffraction. Exponential-like changes in the spacing with increasing osmotic stress, qualitatively similar to the forces previously found in aqueous solution, are also seen in formamide and ethylene glycol. These are solvents that, like water, are capable of forming three-dimensional hydrogen-bond networks. In solvents that either cannot form a network or have a greatly impaired ability to form a hydrogen-bonded network, strikingly different behavior is observed. A hard-wall repulsion is seen with collagen solvated by ethanol, 2-propanol, and N,N-dimethylformamide. The spacing between helices hardly changes with increasing polymer concentration until the stress exceeds some threshold where removal of the solvent becomes energetically favorable. No solvation of collagen is observed in dimethoxyethane. In solvents with an intermediate ability to form hydrogen-bonded networks, methanol, 2-methoxyethanol, or N-methylformamide, the change in spacing with polymer concentration is intermediate between exponential-like and hard-wall. These results provide direct evidence that the exponential repulsion observed between collagen helices at 0-8-Angstrom surface separations in water is due to the energetic cost associated with perturbing the hydrogen-bonded network of solvent molecules between the collagen surfaces. C1 NIH, STRUCT BIOL LAB, DIV COMP RES & TECHNOL, BETHESDA, MD 20892 USA. NIDDKD, DIV INTRAMURAL RES, NIH, BETHESDA, MD 20892 USA. RUSSIAN ACAD SCI, ENGELHARDT INST MOL BIOL, MOSCOW, RUSSIA. RI Leikin, Sergey/A-5518-2008 OI Leikin, Sergey/0000-0001-7095-0739 NR 41 TC 47 Z9 48 U1 3 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1997 VL 72 IS 1 BP 353 EP 362 PG 10 WC Biophysics SC Biophysics GA WC529 UT WOS:A1997WC52900034 PM 8994620 ER PT J AU Ding, JP Hughes, SH Arnold, E AF Ding, JP Hughes, SH Arnold, E TI Protein-nucleic acid interactions and DNA conformation in a complex of human immunodeficiency virus type 1 reverse transcriptase with a double-stranded DNA template-primer SO BIOPOLYMERS LA English DT Article DE AIDS; DNA structure; polymerase structure; protein-DNA interaction; x-ray crystallography ID RIBONUCLEASE-H-DOMAIN; CRYSTAL-STRUCTURE; MUTATIONAL ANALYSIS; RNASE-H; ANGSTROM RESOLUTION; ESCHERICHIA-COLI; POLYMERASE-BETA; NONNUCLEOSIDE INHIBITORS; THUMB SUBDOMAIN; LARGE FRAGMENT AB The conformation of the DNA and the interactions of the nucleic acid with the protein in a complex of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and a 19-mer/18-mer double-stranded DNA template-primer (dsDNA) are described. The structure of this HIV-1 RT complex with dsDNA selves as a useful paradigm for studying aspects of nucleotide polymerases such as catalysis, fidelity, drug inhibition, and drug resistance. The bound dsDNA has a bend of approximately 41 degrees at the junction of an A-form region (first-five base pairs near the polymerase active site) and a B-form region (the last nine base pairs toward the RNase H active sire). The 41 degrees bend occurs smoothly over the four base pairs between the A-form portion and the B-form portion in the vicinity of helices alpha H and alpha I of the p66 thumb subdomain. The inter actions between the dsDNA and protein primarily involve the sugar-phosphate backbone of the nucleic acid and structural elements of the palm, thumb, and RNase H of p66, and are not sequence specific. Amino acid residues from the polymerase active site region, including amino acid residues of the conserved Sr-Met-Asp-Asp (YMDD) motif and the ''primer grip,'' interact with 3'-terminal nucleotides of the primer str-and and are involved in positioning the primer terminal nucleotide and its 3'-OH group at the polymerase active site. Amino acid residues of the ''template grip'' have close contacts with the template strand and aid in positioning the template strand near the polymerase active site. Helix alpha H of the p66 thumb is partly inserted into the minor groove of the dsDNA and helix alpha I is directly adjacent to the backbone of the template strand. Amino acid residues of beta 1', alpha A', alpha B', and the loop containing His539 of the RNase H domain interact with the primer strand of the dsDNA. (C) 1997 John Wiley & Sons, Inc. C1 RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08854. NCI,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. FU NIAID NIH HHS [AI 27690] NR 72 TC 56 Z9 57 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 1997 VL 44 IS 2 BP 125 EP 138 DI 10.1002/(SICI)1097-0282(1997)44:2<125::AID-BIP2>3.0.CO;2-X PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YD662 UT WOS:A1997YD66200002 PM 9354757 ER PT J AU Hardy, BJ Bystricky, S Kovac, P Widmalm, G AF Hardy, BJ Bystricky, S Kovac, P Widmalm, G TI Conformational analysis and molecular dynamics simulation of alpha-(1->2) and alpha-(1->3) linked rhamnose oligosaccharides: Reconciliation with optical rotation and NMR experiments SO BIOPOLYMERS LA English DT Article ID COUPLING-CONSTANTS; AQUEOUS-SOLUTION; SHIGELLA-DYSENTERIAE; FORCE-FIELD; D-GLUCOSE; DISACCHARIDE; WATER; SACCHARIDES; CELLOBIOSE; ENERGY AB Molecular mechanics and dynamics calculations were carried out on the disaccharides alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->OMe) (I) and alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->OMe) (2), and the trisaccharide alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->OMe) (3). The semiflexible conformational Behavior of these molecules was characterized by the occupation of a combination of different glycosidic linkage and side-chain conformational positions whose relative occupations were sensitive to dielectric screening. Molecular dynamics simulations of the trisaccharide 3 showed little difference between the linkage conformations in the trisaccharide and the component disaccharides I and 2. Experimental optical rotation data of 1 and 2 were obtained as a function of temperature in varying solvents. The molecular models were combined with the semiempirical theory of Stevens and Sathyanarayana to yield calculated optical rotations. Interpretation of the data of both I and 2 implied that a combination of conformations, both in glycosidic and side-chain positions, could explain the experimental data. Solvents effects were important in influencing the conformational mix and averaged optical rotation. Three-bond heteronuclear coupling constants (3)J(C11) were obtained for the glycosidic linkages of 1 and 2 in D2O and DMSO. Analysis of the coupling constants with a Karplus curve showed that small reductions in the glycosidic torsion angles of the conformations of the models used here of ca. 10 degrees-15 degrees in phi and 5 degrees-10 degrees in psi were required to give better agreement with experiment a combination of conformations for both I and 2 was consistent with the data. There was a negligible influence on the coupling constants of 1 on changing the solvent from D2O to DMSO. (C) 1997 John Wiley & Sons, Inc. C1 NICHHD,NIH,BETHESDA,MD 20892. NIDDKD,NIH,BETHESDA,MD 20892. UNIV STOCKHOLM,ARRHENIUS LAB,DEPT ORGAN CHEM,S-10691 STOCKHOLM,SWEDEN. RP Hardy, BJ (reprint author), UNIV OXFORD,PHYS & THEORET CHEM LAB,S PARKS RD,OXFORD OX1 3QZ,ENGLAND. FU Wellcome Trust NR 50 TC 16 Z9 16 U1 1 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD JAN PY 1997 VL 41 IS 1 BP 83 EP 96 DI 10.1002/(SICI)1097-0282(199701)41:1<83::AID-BIP8>3.0.CO;2-Z PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WA480 UT WOS:A1997WA48000008 PM 8986121 ER PT J AU Ogryzko, VV AF Ogryzko, VV TI A quantum-theoretical approach to the phenomenon of directed mutations in bacteria (hypothesis) SO BIOSYSTEMS LA English DT Article DE quantum theory; measurement; superposition; directed mutation; Lamarckism ID MULTIPLE SPONTANEOUS MUTATIONS; ADAPTIVE REVERSION; ESCHERICHIA-COLI; EVOLUTION; ORIGIN; DELETIONS; SELECTION; MUTANTS; OCCUR; IF AB The Darwinian paradigm of biological evolution is based on the independence of genetic variations from selection which occurs afterwards. However, according to the phenomenon of directed mutations, some genetic variations occur mostly when the conditions favorable for their growth are created. I propose that the explanation of this phenomenon should not rely on any special 'mechanism' for the appearance of directed mutations, but rather should be based on the principles of quantum theory. I consider a physical model of adaptation whereby a polarized photon, passing through a polarizer, changes its polarization according to the angle of the polarizer. This adaptation occurs by selection of the 'fitted' polarized state which exists as a component of superposition in the initial state of the photon. However, since the same state of the incoming photon should be decomposed differently depending on the angle of the polarizer, in this case the set of variations subjected to selection depends upon the selective conditions themselves. This reveals the crucial difference between this model of adaptation and canonical Darwinian selection. Based on this analogy, the capacity of a cell to grow in particular conditions is considered an observable of the cell; the plating experiments are interpreted as measurement of this observable. The only nontrivial suggestion of the paper states that the cell, analogously to the polarized photon, may be in a state of superposition of eigenfunctions of the operator which represents this observable, and with some probability can appear as a mutant upon the measurement. Alternative growth conditions correspond to the decomposition of the same state vector into a different superposition, consistent with measurement of a different observable and appearance of different mutants. Thus, consistent with the suggested analogy, directed mutations are explained as a result of random choice from the set of outcomes determined by the environment. (C) 1997 Elsevier Science Ireland Ltd. RP Ogryzko, VV (reprint author), NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892, USA. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 33 TC 20 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 0303-2647 J9 BIOSYSTEMS JI Biosystems PY 1997 VL 43 IS 2 BP 83 EP 95 DI 10.1016/S0303-2647(97)00030-0 PG 13 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA XL420 UT WOS:A1997XL42000002 PM 9231907 ER PT J AU deMedinaceli, L Hurpeau, JC Merle, M Begorre, H AF deMedinaceli, L Hurpeau, JC Merle, M Begorre, H TI Cold and post-traumatic pain: Modeling of the peripheral nerve message SO BIOSYSTEMS LA English DT Article DE model; nerve injury; cold; pain; allodynia ID STIMULUS-RESPONSE FUNCTIONS; GLABROUS SKIN AREA; ADAPTING MECHANORECEPTORS; HUMAN HAND; REGENERATION AB Hypersensitivity to cold is a relatively frequent sequel of peripheral nerve injuries but its mechanism is not well understood. We suggested that incomplete recovery of diameter of regenerated fibers is one of the factors involved in cold intolerance after nerve damage. Conduction velocity is correlated to fiber diameter, and is slowed down by cold. In normal subjects, cold does not desynchronize the volleys of sensory impulses sufficiently to change the intelligibility:of the peripheral 'messages'. Sensory perceptions remain accurate although they acquire a characteristic numbness. On the other hand, post-traumatic reduction in fiber diameters causes a permanent distortion of the messages. We considered that when the distortion is severe, the resulting messages may be perceived by the centers as containing nociceptive components. We further hypothesized that, even in cases of moderate permanent distortion, cold acts by increasing the post-traumatic abnormalities of impulse synchronization. In winter, decompensation is observed when a threshold of desynchronization is reached. We constructed a model of peripheral nerve messages in an attempt to represent and quantitate the desynchronizations produced by cold and crush damage lesions in peripheral nerve messages. A number of parameters concerning fiber anatomy, exposure to cold, and type of nerve damage were taken into consideration. Four elementary types of desynchronization could be recognized by considering the times of arrival of pairs of impulses at the nervous centers. The difference between a normal and a distorted message could be expressed by eight variables. Thus, although our model was quite simple, a large amount of data was obtained and a preliminary statistical study was necessary in order to orient the final analysis. Then, we used factor analysis in an attempt to obtain a satisfactory interpretation of the data. The results indicated that peripheral desynchronization might explain, at least in part, the painful sensations experienced in winter by many patients after peripheral nerve injury. (C) 1997 Elsevier Science Ireland Ltd. C1 INST NATL POLYTECH LORRAINE,CTR RECH & AUTOMAT NANCY,LORRAINE,FRANCE. CHU NANCY BRABOIS,INST EUROPEEN BIOMAT & MICROCHIRURG,VANDOEUVRE NANCY,FRANCE. ECOLE SUPER SCI & TECHNOL INGN,CTR RECH AUTOMAT NANCY,NANCY,FRANCE. RP deMedinaceli, L (reprint author), NIMH,ST ELIZABETHS HOSP,WASHINGTON,DC 20032, USA. NR 27 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-2647 J9 BIOSYSTEMS JI Biosystems PY 1997 VL 43 IS 3 BP 145 EP 167 DI 10.1016/S0303-2647(97)01685-7 PG 23 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA XV793 UT WOS:A1997XV79300001 PM 9305546 ER PT J AU Richmond, BJ Gawne, TJ Jin, GX AF Richmond, BJ Gawne, TJ Jin, GX TI Neuronal codes: Reading them and learning how their structure influences network organization SO BIOSYSTEMS LA English DT Article; Proceedings Paper CT International Workshop on Neuronal Coding CY SEP 11-14, 1995 CL PRAGUE, CZECH REPUBLIC SP Charles Univ, Ctr Theoret Study, Acad Sci Czech Republic DE neuronal codes; network organisation; signal processing; interpretation ID TWO-DIMENSIONAL PATTERNS; INFERIOR TEMPORAL CORTEX; PRIMARY VISUAL-CORTEX; SINGLE UNITS; 2-DIMENSIONAL PATTERNS; RESPONSES AB Our investigations of the primate visual system show that neuronal responses carry information in a multi-dimensional code that is superimposed onto the response envelope in a slow time varying fashion. The precision of timing is 30 ms or more. In primary visual cortex response latency and response strength are largely independent, with latency more closely coding contrast or visibility and strength more closely coding stimulus orientation, or perhaps shape. Adjacent neurons in both V1 and inferior temporal cortex share only about 10% of their stimulus-related information, which we demonstrate to be consistent with the idea that cortical layers were organized to minimize information loss. RP Richmond, BJ (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 9,BETHESDA,MD 20892, USA. NR 21 TC 13 Z9 13 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-2647 J9 BIOSYSTEMS JI Biosystems PY 1997 VL 40 IS 1-2 BP 149 EP 157 DI 10.1016/0303-2647(96)01641-3 PG 9 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA VU215 UT WOS:A1997VU21500019 PM 8971207 ER PT J AU Apel, WS AF Apel, WS TI GelWorks 1D SO BIOTECHNOLOGY SOFTWARE & INTERNET JOURNAL LA English DT Software Review C1 NIH,BETHESDA,MD 20892. 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 1088-4270 J9 BIOTECHNOL SOFTW I J JI Biotechnol. Softw. Internet J. PD JAN-FEB PY 1997 VL 14 IS 1 BP 24 EP & PG 4 WC Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications SC Biotechnology & Applied Microbiology; Computer Science GA WH370 UT WOS:A1997WH37000005 ER PT J AU Ahern, K AF Ahern, K TI Kodak Digital Science(TM) Electrophoresis Documentation and Analysis System SO BIOTECHNOLOGY SOFTWARE & INTERNET JOURNAL LA English DT Software Review C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1088-4270 J9 BIOTECHNOL SOFTW I J JI Biotechnol. Softw. Internet J. PD JAN-FEB PY 1997 VL 14 IS 1 BP 27 EP 31 PG 5 WC Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications SC Biotechnology & Applied Microbiology; Computer Science GA WH370 UT WOS:A1997WH37000006 ER PT J AU Muller, JR Jones, GM Janz, S Potter, M AF Muller, JR Jones, GM Janz, S Potter, M TI Migration of cells with immunoglobulin/c-myc recombinations in lymphoid tissues of mice SO BLOOD LA English DT Article ID C-MYC; IDENTIFICATION; PLASMACYTOMA; INDUCTION; PATCHES AB Recombinations between c-myc and immunoglobulin (Ig) sequences that typically occur in pristane-induced mouse plasmacytomas were detected in secondary lymphoid tissues from normal mice, chiefly in the gut-associated lymphoid tissue. Based on the analysis of recombination sequences as clonotypic markers, migration of c-myc recombination-positive cells was observed between Peyer's patches and into the intestine. Treatment of plasmacytoma-susceptible BALB/cAn mice with pristane induced proliferation and migration of these cells into mesenteric lymph node, spleen, and oil granuloma within 7 days. Plasmacytoma-resistant strains of mice (DBA/2N, C3H/HeJ, C57BL/6) differed in that (1) they harbored fewer clones (Ig/c-myc recombinations were detected in 33% of resistant mice versus 91% of BALB/cAn mice after pristane treatment); (2) Ig/c-myc-positive cells were rarely detected in the oil granuloma, and (3) c-myc recombined predominantly with the Ig alpha locus in BALB/cAn mice (72%), but with the Ig mu locus in DBA/2N and in C57BL/6 (67%). The results demonstrate that normal mice generate a large number of lymphocytes with aberrant c-myc in intestinal tissues without developing tumors. RP Muller, JR (reprint author), NCI,GENET LAB,NIH,BLDG 37,ROOM 2B-09,37 CONVENT DR,BETHESDA,MD 20892, USA. NR 12 TC 29 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1997 VL 89 IS 1 BP 291 EP 296 PG 6 WC Hematology SC Hematology GA WA836 UT WOS:A1997WA83600033 PM 8978304 ER PT J AU Levin, MC Krichavsky, M Fox, RJ Lehky, T Jacobson, S Fox, C Kleghorn, F White, J Young, N Edwards, RJ Jack, NE Bartholomew, C AF Levin, MC Krichavsky, M Fox, RJ Lehky, T Jacobson, S Fox, C Kleghorn, F White, J Young, N Edwards, RJ Jack, NE Bartholomew, C TI Extensive latent retroviral infection in bone marrow of patients with HTLV-I-associated neurologic disease SO BLOOD LA English DT Letter ID TROPICAL SPASTIC PARAPARESIS; VIRUS TYPE-I; LYMPHOCYTES; PATHOGENESIS; ANTIBODIES; HIV C1 MOL HISTOL INC,GAITHERSBURG,MD. INST HUMAN VIROL,BALTIMORE,MD. NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. NHLDI,NIH,BETHESDA,MD. MED RES CTR,PORT OF SPAIN,TRINID & TOBAGO. RP Levin, MC (reprint author), NINCDS,VIRAL IMMUNOL SECT,NEUROIMMUNOL BRANCH,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 12 TC 14 Z9 14 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 JAN 1 PY 1997 VL 89 IS 1 BP 346 EP 348 PG 3 WC Hematology SC Hematology GA WA836 UT WOS:A1997WA83600041 PM 8978312 ER PT J AU Litvan, I Campbell, G Mangone, CA Verny, M McKee, A Chaudhuri, KR Jellinger, K Pearce, RKB DOlhaberriague, L AF Litvan, I Campbell, G Mangone, CA Verny, M McKee, A Chaudhuri, KR Jellinger, K Pearce, RKB DOlhaberriague, L TI Which clinical features differentiate progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) from related disorders? - A clinicopathological study SO BRAIN LA English DT Article DE progressive supranuclear palsy; statistical methods; diagnosis (parkinsonian disorders); classification and regression tree analysis ID MULTIPLE SYSTEM ATROPHY; LEWY BODY DISEASE; PARKINSONS-DISEASE; CORTICOBASAL DEGENERATION; COGNITIVE IMPAIRMENT; SUBCORTICAL GLIOSIS; ALZHEIMERS-DISEASE; SENILE DEMENTIA; PURE AKINESIA; GAZE PALSY AB The difficulty in differentiating progressive supranuclear palsy (PSP, also called Steele-Richardson-Olszewski syndrome) from other related disorders was the incentive for a study to determine the clinical features that best distinguish PSP Logistic regression and classification and regression tree analysis (CART) were used to analyse data obtained at the first visit from a sample of 83 patients with a clinical history of parkinsonism or dementia confirmed neuropathologically: including PSP (n = 24), corticobasal degeneration (n = II), Parkinson's disease (PD, n = II), diffuse Lewy body disease (n = 14), Pick's disease (n = 8) and multiple system atrophy (MSA, n = 15). Supranuclear vertical gaze palsy, moderate or severe postural instability and falls during the first year after onset of symptoms classified the sample with 9% error using logistic regression analysis. The CART identified similar features and was also helpful in identifying particular attributes that separate PSP from each of the other disorders. Unstable gait, absence of tremor-dominant disease and absence of a response to levodopa differentiated PSP from PD. Supranuclear vertical gaze palsy, gait instability and the absence of delusions distinguished PSP from diffuse Lewy body disease. Supranuclear vertical gaze palsy and increased age at symptom-onset distinguished PSP front MSA. Gait abnormality, severe upward gaze palsy, bilateral bradykinesia and absence of alien limb syndrome separated PSP from corticobasal degeneration. Postural instability successfully classified PSP from Pick's disease. The present study may help to minimize the difficulties neurologists experience when attempting to classify these disorders at early stages. C1 NINCDS,ANALYT BIOMETR SECT,BIOMETRY & FIELD STUDIES BRANCH,NIH,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. HOP LA PITIE SALPETRIERE,LAB NEUROPATHOL R ESCOUROLLE,F-75651 PARIS,FRANCE. LAINZ HOSP,LUDWIG BOLTZMANN INST CLIN NEUROBIOL,A-1130 VIENNA,AUSTRIA. INST PSYCHIAT,DEPT NEUROL,LONDON SE5 8AF,ENGLAND. INST NEUROL,PARKINSONS DIS SOC BRAIN TISSUE BANK,LONDON WC1N 3BG,ENGLAND. RP Litvan, I (reprint author), NINCDS,NEUROEPIDEMIOL BRANCH,NIH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 73 TC 109 Z9 111 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 1997 VL 120 BP 65 EP 74 DI 10.1093/brain/120.1.65 PN 1 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WJ826 UT WOS:A1997WJ82600006 PM 9055798 ER PT J AU VarghaKhadem, F Carr, LJ Isaacs, E Brett, E Adams, C Mishkin, M AF VarghaKhadem, F Carr, LJ Isaacs, E Brett, E Adams, C Mishkin, M TI Onset of speech after left hemispherectomy in a nine-year-old boy SO BRAIN LA English DT Review DE congenital aphasia; hemispherectomy; late speech onset; right hemisphere language; motor reorganization ID HEMIPLEGIC CEREBRAL-PALSY; MOTOR PATHWAYS; LANGUAGE; CHILDREN; ACQUISITION; MEMORY; EPILEPSY; REORGANIZATION; DISORDER; IQ AB Case Alex, with Sturge-Weber Syndrome affecting the left hemisphere, Sailed to develop speech throughout early boyhood, and his comprehension of single words and simple commands remained stagnant at an age equivalent of 3-4 years. But then, following left hemidecortication at age 8.5 years and withdrawal of anticonvulsants wizen he was more than 9 years old Alex suddenly began to acquire speech and language. He also showed an unusual degree of residual motor capacity on his right side. Alex's remarkable progress in learning speech and language, and the development of his other cognitive abilities, were measured periodically from the age of 9 to 15 years. His most recent scores on rests of receptive and expressive language place hint at an age equivalent of 8-10 years. Comparison with the level of function attained in these domains by nine other left hemispherectomized patients with early onset of disease and comparable IQ (range, 40-68) but with early development of speech and language, suggests that, surprisingly, Alex has suffered no permanent disadvantage fron his protracted period of mutism and severely limited comprehension Although the findings in Alex, as in other left-hemispherectomized patients, indicate definite limits to the cognitive and linguistic capacity of the isolated right hemisphere, Alex's achievements appear to challenge the widely held view that early childhood is a particularly critical period for acquisition of speech and language or any of their selective aspects, including phonology, grammar prosody and semantics. It is concluded that clearly articulated, well structured and appropriate language can be acquired for the first time as late as age 9 years with the right hemisphere alone. C1 INST CHILD HLTH, NEUROSCI UNIT, LONDON WC1N 2AP, ENGLAND. GREAT ORMOND ST HOSP CHILDREN, LONDON WC1N 3JH, ENGLAND. UCL, HUMAN NEUROPHYSIOL UNIT, DEPT PHYSIOL, LONDON, ENGLAND. RADCLIFFE INFIRM, DEPT NEUROSURG, OXFORD OX2 6HE, ENGLAND. NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. RP VarghaKhadem, F (reprint author), INST CHILD HLTH, COGNIT NEUROSCI UNIT, WOLFSON CTR, MECKLENBURGH SQ, LONDON WC1N 2AP, ENGLAND. RI Vargha-Khadem, Faraneh/C-2558-2008 NR 112 TC 134 Z9 138 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 1997 VL 120 BP 159 EP 182 DI 10.1093/brain/120.1.159 PN 1 PG 24 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WJ826 UT WOS:A1997WJ82600013 PM 9055805 ER PT B AU Karni, A AF Karni, A BE Ito, M TI The acquisition of perceptual and motor skills: a memory system in the adult human cortex SO BRAIN AND MIND: FOR BETTER UNDERSTANDING OF THE DYNAMIC FUNCTION OF MIND AND ITS SUPPORTING BRAIN MECHANISM LA English DT Proceedings Paper CT 9th TOYOTA Conference on Brain and Mind - For Better Understanding of the Dynamic Function of Mind and Its Supporting Brain Mechanism CY DEC 05-08, 1995 CL MIKKABI, JAPAN SP TOYOTA Motor Corp DE memory; cortex, human; plasticity; procedural learning RP Karni, A (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-82553-3 PY 1997 BP 73 EP 92 PG 20 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BJ92Z UT WOS:A1997BJ92Z00004 ER PT B AU Colby, CL Duhamel, JR AF Colby, CL Duhamel, JR BE Ito, M TI Spatial representations for action in parietal cortex SO BRAIN AND MIND: FOR BETTER UNDERSTANDING OF THE DYNAMIC FUNCTION OF MIND AND ITS SUPPORTING BRAIN MECHANISM LA English DT Proceedings Paper CT 9th TOYOTA Conference on Brain and Mind - For Better Understanding of the Dynamic Function of Mind and Its Supporting Brain Mechanism CY DEC 05-08, 1995 CL MIKKABI, JAPAN SP TOYOTA Motor Corp DE spatial perception; parietal cortex RP Colby, CL (reprint author), NEI,SENSORIMOTOR RES LAB,NIH,BLDG 49,ROOM 2A50,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-82553-3 PY 1997 BP 203 EP 220 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BJ92Z UT WOS:A1997BJ92Z00011 ER PT S AU Strasser, A Stanimirovic, D Kawai, N McCarron, RM Spatz, M AF Strasser, A Stanimirovic, D Kawai, N McCarron, RM Spatz, M BE James, HE Marshall, LF Reulen, HJ Baethmann, A Marmarou, A Ito, U Hoff, JT Kuroiwa, T Czernicki, Z TI Hypoxia modulates free radical formation in brain microvascular endothelium SO BRAIN EDEMA X SE ACTA NEUROCHIRURGICA SUPPLEMENTA LA English DT Proceedings Paper CT 10th International Symposium on Brain Edema CY OCT 20-23, 1996 CL SAN DIEGO, CA DE cerebral hypoxia; free radical formation; microvascular endothelium; blood-brain barrier AB Although free radical species (ROS; i.e., . O-2(-), . OH, H2O2) among other mediators, may be involved in altering the blood-brain barrier (BBB), little is known about the endogenous ability of cerebromicrovascular endothelium to generate ROS. This study examines the capacity of rat endothelial cells (RBEC) to produce ROS in normoxia and hypoxia/reoxygenation. Cultured RBEC were exposed to an oxygen-depleted atmosphere (containing 95% N2 and 5% CO2) for 4 hr at 37 degrees C and air (10 min) at room temperature to simulate "ischemia/reperfusion". Nitroblue tetrazolium (NET) reduction [formation of nitroblue formazan (NBF)] served as a marker for the production of ROS. The release of lactate dehydrogenase (LDH) and [H-3]arachidonic acid (AA) was used to assess cellular integrity. RBEC exposed to hypoxia/reoxygenation produced up to 59% greater NBF formation than controls without affecting the LDH or AA release. The production of ROS was calcium-dependent and not affected by AA or its metabolites. The findings indicate that the RBEC can produce superoxide dismutase (SOD)-inhibitable ROS which are augmented by hypoxia/reoxygenation. It is suggested that in vivo cerebromicrovascular endothelium may contribute to the formation of ROS and play a role in ischemic brain edema. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Spatz, M (reprint author), NINDS, Stroke Branch, NIH, 36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 0 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 3-211-82892-3 J9 ACT NEUR S JI Acta Neurochir. Suppl. PY 1997 VL 70 BP 8 EP 11 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA BK05T UT WOS:000071009100003 PM 9416263 ER PT S AU Kawai, N McCarron, RM Spatz, M AF Kawai, N McCarron, RM Spatz, M BE James, HE Marshall, LF Reulen, HJ Baethmann, A Marmarou, A Ito, U Hoff, JT Kuroiwa, T Czernicki, Z TI The effect of endothelins on ion transport systems in cultured rat brain capillary endothelial cells SO BRAIN EDEMA X SE ACTA NEUROCHIRURGICA SUPPLEMENTA LA English DT Proceedings Paper CT 10th International Symposium on Brain Edema CY OCT 20-23, 1996 CL SAN DIEGO, CA DE blood-brain barrier; capillary endothelium; ion transport; endothelins AB Brain capillary endothelial cells regulate the movement of ions and water across the blood-brain barrier via specific ion transport systems. Disturbances in these ion transport systems are involved in the formation of ischemic brain edema. This study describes the effects of endothelins (i.e., ET-1 and ET-3) on ion transport systems in cultured rat brain capillary endothelial cells using Rb-86(+) and Na-22(+) as markers for K+ and Na+, respectively. ET-1 stimulated K+ uptake and efflux with EC50 values of 0.6 nM and 0.5 nM, respectively. The potencies of ET-3 on these responses were considerably lower. Both ET-I and ET-3 stimulated Na+ uptake through a Na+/H+ exchange system with similar potencies (i.e., EC50 = 0.80 nM and 1.89 nM, respectively). ET-stimulated K+ uptake, KC efflux, and Na+ uptake activities were all inhibited by BQ123 (selective ETA receptor antagonist). ET-l-stimulated K+ uptake and efflux, in contrast to Na+ uptake, were also reduced by protein kinase C inhibitors and by an intracellular Ca2+ chelator. The results suggest that ETs can Effect the activities of ion and water transport at the blood-brain barrier through different signal transduction mechanisms. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Spatz, M (reprint author), NINDS, Stroke Branch, NIH, 36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 3-211-82892-3 J9 ACT NEUR S JI Acta Neurochir. Suppl. PY 1997 VL 70 BP 138 EP 140 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA BK05T UT WOS:000071009100042 PM 9416302 ER PT S AU Yasuma, Y Strasser, A Ruetzel, C McCarron, RM Spatz, M AF Yasuma, Y Strasser, A Ruetzel, C McCarron, RM Spatz, M BE James, HE Marshall, LF Reulen, HJ Baethmann, A Marmarou, A Ito, U Hoff, JT Kuroiwa, T Czernicki, Z TI The effect of nitric oxide inhibition on ischemic brain edema SO BRAIN EDEMA X SE ACTA NEUROCHIRURGICA SUPPLEMENTA LA English DT Proceedings Paper CT 10th International Symposium on Brain Edema CY OCT 20-23, 1996 CL SAN DIEGO, CA DE ischemic edema; nitric oxide; free radicals; cytotoxic edema AB The involvement of nitric oxide (NO) in the development of ischemic cytotoxic edema was investigated by inhibiting nitric oxide synthase (NOS) activity with N omega-nitro-L-arginine (NLA). Bilateral carotid artery occlusion (15 min) alone or with release (15 and 60 min) served as a model for edema induction. NLA, N omega-nitro-D-arginine methyl ester (D-NAME) or Ringer's solution were administered 4 hr prior to ischemia or sham operation. Treatment with a stable nitroxide radical, 4-hydroxy-2,2,6,6-tetramethylpiperidine-L-oxyl (TPL), was used to assess free radical involvement in edema. Accumulation of tissue water was evaluated by measuring specific gravity (SG) of brain cortex and histological examination. There was a greater reduction of cortical SG in early reperfusion (15 min) and a lesser decrease in SG(60 min later) in NLA- than in D-NAME- or Ringer's-treated gerbils. The NLA effect was confirmed by histological examination of the brain tissue. TPL treatment (pre-and postischemic) ameliorated the formation of edema to the same degree as NLA. The findings indicate a biphasic NLA modulation of cytotoxic edema most likely mediated through absence or presence of NO-derived free radicals. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Spatz, M (reprint author), NINDS, Stroke Branch, NIH, 36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 3-211-82892-3 J9 ACT NEUR S JI Acta Neurochir. Suppl. PY 1997 VL 70 BP 202 EP 205 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA BK05T UT WOS:000071009100062 PM 9416322 ER PT J AU Hainfellner, JA Liberski, PP Guiroy, DC Cervenakova, L Brown, P Gajdusek, DC Budka, H AF Hainfellner, JA Liberski, PP Guiroy, DC Cervenakova, L Brown, P Gajdusek, DC Budka, H TI Pathology and immunocytochemistry of a Kuru Brain SO BRAIN PATHOLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; PRION PROTEIN ACCUMULATION; AMYLOID PLAQUE; IMMUNOREACTIVITY; MICROGLIA; ISOFORM AB We report here results of modern staining techniques including anti-prion protein (PrP) immunocytochemistry to a set of archival brain specimens of a 16 year-old male who died from kuru in 1967. Brain suspensions transmitted disease to chimpanzees and New World monkeys. The PrP gene is homozygous for valine at the polymorphic codon 129. Histology shows neuronal loss, spongiform change, and astrogliosis. Lesions are maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, striatum, and thalamus, and are accentuated in middle and deep cerebral cortical layers. PrP accumulates as diffuse synaptic type deposits and mostly unicentric plaques. PrP deposition is maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, basal ganglia, and cerebellar cortex. Plaques are prominent in the striatum, thalamus, and granular layer of cerebellar cortex. Meticulous examination reveals only rare ''florid'' plaques with surrounding vacuolation. We conclude that 1) pathology including immunomorphology of PrP deposition in this kuru brain is within the lesion spectrum of Creutzfeldt-Jakob disease although plaques are unusually prominent and widespread; 2) kuru does not share the neuropathological hallmarks of the new Creutzfeldt-Jakob disease variant recently reported in the UK and France; 3) topographic prominence of PrP deposition parallels that of spongiform change and/or astrogliosis. C1 UNIV VIENNA,INST NEUROL,VIENNA,AUSTRIA. MED ACAD LODZ,DEPT ONCOL,ELECTRON MICROSCOP LAB,LODZ,POLAND. NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. OI Budka, Herbert/0000-0002-1933-1577 NR 30 TC 53 Z9 54 U1 2 U2 6 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 1997 VL 7 IS 1 BP 547 EP 553 DI 10.1111/j.1750-3639.1997.tb01072.x PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA WD341 UT WOS:A1997WD34100002 PM 9034563 ER PT J AU Liberski, PP Gajdusek, DC AF Liberski, PP Gajdusek, DC TI Kuru: Forty years later, a historical note SO BRAIN PATHOLOGY LA English DT Article C1 NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BETHESDA,MD 20892. RP Liberski, PP (reprint author), MED ACAD LODZ,DEPT ONCOL,LABS TUMOR BIOL,LAB ELECTRON MICROSCOPY & NEUROPATHOL,PADEREWSKI ST 4,PL-93509 LODZ,POLAND. NR 48 TC 24 Z9 25 U1 1 U2 2 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 1997 VL 7 IS 1 BP 555 EP 560 DI 10.1111/j.1750-3639.1997.tb01073.x PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA WD341 UT WOS:A1997WD34100003 PM 9034564 ER PT S AU Bronchti, G Corthesy, ME Welker, E AF Bronchti, G Corthesy, ME Welker, E BE Freund, HJ Sabel, BA Witte, OW TI Does nerve regeneration restore normal functional patterns in mouse barrel cortex? SO BRAIN PLASTICITY SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT Satellite Symposium on Brain Plasticity, to the XVIth International Symposium on Cerebral Blood Flow and Metabolism (BRAIN 95) CY JUL 03-07, 1995 CL COLOGNE, GERMANY ID SOMATOSENSORY CORTEX; DOMINANCE COLUMNS; VISUAL-CORTEX; ADULT MONKEYS; PLASTICITY; REORGANIZATION; ORGANIZATION; NEURONS; INJURY; HUMANS C1 NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. Univ Lausanne, Inst Anat, CH-1005 Lausanne, Switzerland. RP Bronchti, G (reprint author), NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 USA SN 0091-3952 BN 0-397-51760-2 J9 ADV NEUROL JI Adv.Neurol. PY 1997 VL 73 BP 91 EP 98 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BK90B UT WOS:000073835500007 PM 8959207 ER PT S AU Rauschecker, JP AF Rauschecker, JP BE Freund, HJ Sabel, BA Witte, OW TI Mechanisms of compensatory plasticity in the cerebral cortex SO BRAIN PLASTICITY SE ADVANCES IN NEUROLOGY LA English DT Article; Proceedings Paper CT Satellite Symposium on Brain Plasticity, to the XVIth International Symposium on Cerebral Blood Flow and Metabolism (BRAIN 95) CY JUL 03-07, 1995 CL COLOGNE, GERMANY ID PRIMARY AUDITORY-CORTEX; ANTERIOR ECTOSYLVIAN SULCUS; SUPERIOR COLLICULUS; LOCALIZATION BEHAVIOR; EARLY BLINDNESS; STRIATE CORTEX; DEPRIVED CATS; VISUAL-SYSTEM; ADULT CATS; MOTOR MAPS C1 Georgetown Univ, Med Ctr, Inst Cognit & Computat Sci, Washington, DC 20007 USA. NIH, Bethesda, MD 20892 USA. RP Rauschecker, JP (reprint author), Georgetown Univ, Med Ctr, Inst Cognit & Computat Sci, Washington, DC 20007 USA. RI Rauschecker, Josef/A-4120-2013 NR 58 TC 25 Z9 26 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA E WASHINGTON SQ, PHILADELPHIA, PA 19105 USA SN 0091-3952 BN 0-397-51760-2 J9 ADV NEUROL JI Adv.Neurol. PY 1997 VL 73 BP 137 EP 146 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BK90B UT WOS:000073835500011 PM 8959211 ER PT J AU Marini, AM Strauss, KI Jacobowitz, DM AF Marini, AM Strauss, KI Jacobowitz, DM TI Calretinin-containing neurons in rat cerebellar granule cell cultures SO BRAIN RESEARCH BULLETIN LA English DT Article DE calretinin; unipolar brush cell; Lugaro cell; calretinin mRNA; glutamate receptor agonists; excitotoxicity; AMPA/kainate glutamate receptor subtype (GluR(2)R(3)) ID METHYL-D-ASPARTATE; EXCITATORY AMINO-ACIDS; UNIPOLAR BRUSH CELL; IMMUNOHISTOCHEMICAL LOCALIZATION; IMMUNOCYTOCHEMICAL LOCALIZATION; RECEPTOR SUBTYPES; GLUTAMATE; IMMUNOREACTIVITY; ACTIVATION; PROTEIN AB Using an antiserum against calretinin, a calcium-binding protein, we discovered two distinct neuronal cell types that stain intensely in enriched cerebellar granule cells. One neuronal cell type resembles unipolar brush cells, whereas the other resembles Lugaro cells. During early culture times, these calretinin-positive neurons are most numerous but represent less than one percent of the total neuronal population. In cultured cells, calretinin mRNA levels peak at day three in vitro, followed by a rapid decline to undetectable levels by day six in vitro. However, calretinin-immunoreactive neurons are observed up to 29 days in vitro. Excitotoxic concentrations of glutamate receptor agonists failed to elicit an excitotoxic response on the intensely staining calretinin-positive neurons, whereas greater than 95% of the cerebellar granule cells were susceptible to the excitotoxic actions of the glutamate receptor agonists. To distinguish between the two possibilities that calretinin-positive neurons either do not express glutamate receptors or they are not susceptible to the excitotoxic effects of glutamate receptor agonists, we performed immunocytochemistry using glutamate receptor antibodies to detect the presence of receptor protein. We found that the AMPA/kainate glutamate receptor (GluR(2)R(3)) colocalized with calretinin, suggesting that calretinin-immunoreactive neurons express the AMPA/kainate receptor; cerebellar granule cells, which are known to express this receptor, were also immunoreactive for the GluR(2)R(3) receptor. Copyright (C) 1997 Elsevier Science Inc. C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP Marini, AM (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT NEUROL,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. NR 31 TC 19 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PY 1997 VL 42 IS 4 BP 279 EP 288 DI 10.1016/S0361-9230(96)00263-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA WH105 UT WOS:A1997WH10500004 PM 9043714 ER PT J AU Sterns, EE SenGupta, S Zee, B AF Sterns, EE SenGupta, S Zee, B TI Macromolecular interstitial clearance, tumour vascularity, other prognostic factors and breast cancer survival SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE angiogenesis; breast cancer; lymphatics; oncogenes; prognosis; vascularity ID PROTEIN EXPRESSION; CELL-PROLIFERATION; GROWTH-FACTOR; FOLLOW-UP; IN-SITU; P53; CARCINOMA; ANGIOGENESIS; C-ERBB-2; OVEREXPRESSION AB Background: Clearance of large molecules from the interstitial space is an important function of lymphatics and is affected by local pathologic changes. Objective: To determine if the clearance rate of interstitially injected albumin is correlated to tumour characteristics and outcome in women with invasive breast cancer. Method: In a consecutive series of women coming to biopsy for suspected breast cancer, technetium-tagged albumin was injected into the tissue adjacent to the palpable mass. The isotope disappearance rate was measured over two hours. Also assessed were the maximum vessel density (MVD - using Factor VIII polyclonal antisera), the proliferation rate (using Ki-67 antisera), node status: tumour size, histologic and nuclear grade, mitotic rate, and p53 and c-erbB-2 oncoproteins, All patients were followed until relapse and for a minimum of 10 years. Results: In multivariate analysis, an association between relapse-free survival and isotope clearance rate was suggested (p = 0.024). The best outcome was seen in patients with the least isotope clearance. Node status, size, histologic and nuclear grade, and mitotic rate correlated with survival, MVD did not correlate with survival and was inversely related to the isotope clearance rate, Tumour proliferation rate, and the c-erbB-2 and p53 oncoproteins did not relate to outcome. Conclusion: The role of lymphatics in breast cancer is difficult to study, Measurement of interstitial clearance may be a useful technique and could be a prognostic factor. C1 QUEENS UNIV,DEPT SURG,KINGSTON,ON K7L 2V7,CANADA. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 2V7,CANADA. KINGSTON GEN HOSP,KINGSTON,ON K7L 2V7,CANADA. QUEENS UNIV,NCI,CLIN TRIALS UNIT,KINGSTON,ON K7L 2V7,CANADA. OI Zee, Benny Chung-Ying/0000-0002-7238-845X NR 55 TC 4 Z9 4 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 1997 VL 42 IS 2 BP 113 EP 120 DI 10.1023/A:1005749825449 PG 8 WC Oncology SC Oncology GA WJ071 UT WOS:A1997WJ07100003 PM 9138600 ER PT J AU Zaloudik, J Basak, S Nesbit, M Speicher, DW Wunner, WH Miller, E ErnstGrotkowski, C Kennedy, R Bergsagel, LP Koido, T Herlyn, D AF Zaloudik, J Basak, S Nesbit, M Speicher, DW Wunner, WH Miller, E ErnstGrotkowski, C Kennedy, R Bergsagel, LP Koido, T Herlyn, D TI Expression of an antigen homologous to the human CO17-1A/GA733 colon cancer antigen in animal tissues SO BRITISH JOURNAL OF CANCER LA English DT Article DE colorectal carcinoma; CO17-1A/GA733 antigen homologue; murine epithelial glycoprotein; experimental animals ID CARCINOMA-ASSOCIATED ANTIGEN; IGG2A MONOCLONAL-ANTIBODIES; HUMAN-TUMOR GROWTH; COLORECTAL-CARCINOMA; EPITHELIAL GLYCOPROTEIN; ANTIIDIOTYPIC ANTIBODY; MOLECULAR-CLONING; CELL; CDNA; ADENOCARCINOMA AB The CO17-1A/GA733 antigen is associated with human carcinomas and some normal epithelial tissues. This antigen has shown promise as a target in approaches to passive and active immunotherapy of colorectal cancer. The relevance of animal models for studies of immunotherapy targeting this antigen in patients is dependent on the expression of the antigen on normal animal tissues. Immunohistoperoxidase staining with polyclonal rabbit antibodies to the human antigen revealed the human homologue on normal small intestine, colon and liver of mice, rats and non-human primates, whereas mouse monoclonal antibodies to the CO17-1A or GA733 epitopes on the human antigen did not detect the antigen. Polyclonal rabbit antibodies, elicited by the murine antigen homologue derived from recombinant baculovirus-infected insect cells, immunoprecipitated the antigen from mouse small intestine, colon, stomach, kidney and lung. The isolated recombinant murine protein bound polyclonal, but not monoclonal, antibodies to the human CO17-1A/GA733 antigen, and recombinant human antigen bound polyclonal antibodies elicited by the murine antigen homologue. Thus, the antigen homologue expressed by animal tissues is similar, but not identical, to the human antigen. These results have important implications for experimental active and passive immunotherapy targeting the CO17-1A/GA733 antigen. C1 WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. MED COLL PHILADELPHIA,PHILADELPHIA,PA 19129. UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK 73190. USN,MED ONCOL BRANCH,NCI,BETHESDA,MD 20814. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NCI NIH HHS [CA 10815, CA 43735, CA 605595] NR 34 TC 17 Z9 17 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PY 1997 VL 76 IS 7 BP 909 EP 916 DI 10.1038/bjc.1997.483 PG 8 WC Oncology SC Oncology GA XZ119 UT WOS:A1997XZ11900013 PM 9328151 ER PT J AU Petersen, I Langreck, H Wolf, G Schwendel, A Psille, R Vogt, P Reichel, MB Ried, T Diefel, M AF Petersen, I Langreck, H Wolf, G Schwendel, A Psille, R Vogt, P Reichel, MB Ried, T Diefel, M TI Small-cell lung cancer is characterized by a high incidence of deletions on chromosomes 3p, 4q, 5q, 10q, 13q and 17p SO BRITISH JOURNAL OF CANCER LA English DT Article DE small-cell lung cancer; lung cancer; comparative genomic hybridization; loss of heterozygosity; tumour genetics ID COMPARATIVE GENOMIC HYBRIDIZATION; RECEPTOR GENE AMPLIFICATION; TUMOR-SUPPRESSOR GENE; ALLELIC LOSS; APC GENE; DISTINCT REGIONS; POOR-PROGNOSIS; SOLID TUMORS; C-MYC; CARCINOMA AB The genetic mechanisms that define the malignant behaviour of small-cell lung cancer (SCLC) are poorly understood. We performed comparative genomic hybridization (CGH) on 22 autoptic SCLCs to screen the tumour genome for genomic imbalances. DNA loss of chromosome 3p was a basic alteration that occurred in all tumours. Additionally, deletions were observed on chromosome 10q in 94% of tumours and on chromosomes 4q, 5q, 13q and 17p in 86% of tumours. DNA loss was confirmed by loss of heterozygosity (LOH) analysis for chromosomes 3p, 5q and 10q. Simultaneous mutations of these six most abundant genetic changes were found in 12 cases. One single tumour carried at least five deletions. DNA under-representations were observed less frequently on chromosome 15q (55%) and chromosome 16q (45%). The prevalent imbalances were clearly indicated by the superposition of the 22 tumours to a CGH superkaryogram. In our view, the high incidence of chromosomal loss is an indication that SCLC is defined by a pattern of deletions and that the inactivation of multiple growth-inhibitory pathways contributes in particular to the aggressive phenotype of that type of tumour. C1 UNIV ZURICH HOSP,DEPT PATHOL,CH-8091 ZURICH,SWITZERLAND. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Petersen, I (reprint author), UNIV BERLIN,HOSP CHARITE,INST PATHOL,SCHUMANNSTR 20-21,D-10117 BERLIN,GERMANY. NR 63 TC 165 Z9 166 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PY 1997 VL 75 IS 1 BP 79 EP 86 DI 10.1038/bjc.1997.13 PG 8 WC Oncology SC Oncology GA WA344 UT WOS:A1997WA34400013 PM 9000602 ER PT J AU Ridge, SA Brown, O McMurrough, J FernandezSalguero, P Evans, WE Gonzalez, FJ McLeod, HL AF Ridge, SA Brown, O McMurrough, J FernandezSalguero, P Evans, WE Gonzalez, FJ McLeod, HL TI Mutations at codon 974 of the DPYD gene are a rare event SO BRITISH JOURNAL OF CANCER LA English DT Article DE dihydropyrimidine dehydrogenase; pyrimidine metabolism; 5-fluorouracil; thymine uraciluria ID DIHYDROPYRIMIDINE DEHYDROGENASE-DEFICIENCY; CHEMOTHERAPY; POPULATION; TOXICITY AB A mutation at codon 974 of the dihydropyrimidine dehydrogenase (DPD) gene was previously described in a cancer patient with undetectable DPD enzyme activity who experienced severe toxicity when treated with 5-fluorouracil. We have studied the frequency of this mutation in 29 Scottish subjects with low DPD enzyme activity and in 274 American subjects. We detected no mutations in the 606 alleles studied and conclude that mutations at codon 974 are a rare event. C1 NCI, MOL CARCINOGENESIS LAB, NIH, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DEPT PHARMACEUT, MEMPHIS, TN 38101 USA. RP Ridge, SA (reprint author), UNIV ABERDEEN, DEPT MED & THERAPEUT, POLWARTH BLDG, ABERDEEN AB9 2ZD, SCOTLAND. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 13 TC 8 Z9 9 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PY 1997 VL 75 IS 2 BP 178 EP 179 DI 10.1038/bjc.1997.29 PG 2 WC Oncology SC Oncology GA WC763 UT WOS:A1997WC76300004 PM 9010022 ER PT J AU Hyytinen, ER Thalmann, GN Zhau, HE Karhu, R Kallioniemi, OP Chung, LWK Visakorpi, T AF Hyytinen, ER Thalmann, GN Zhau, HE Karhu, R Kallioniemi, OP Chung, LWK Visakorpi, T TI Genetic changes associated with the acquisition of androgen-independent growth, tumorigenicity and metastatic potential in a prostate cancer model SO BRITISH JOURNAL OF CANCER LA English DT Article DE prostatic carcinoma; LNCaP cell line; genetic aberration; metastases; comparative genomic hybridization ID COMPARATIVE GENOMIC HYBRIDIZATION; CARCINOMA CELL-LINE; SOLID TUMORS; LNCAP MODEL; COPY NUMBER; HETEROZYGOSITY; CHROMOSOME-6; PROGRESSION; LOCI AB Genetic changes underlying the progression of human prostate cancer are incompletely understood. Recently, an experimental model system that resembles human prostate cancer progression was developed based on the serial passage of an androgen-responsive, non-tumorigenic LNCaP prostate cancer cell line into athymic castrated mice. Six different sublines, derived after one, two or three rounds of in vivo passage, sequentially acquired androgen independence and tumorigenicity as well as metastatic capacity. Here, we used comparative genomic hybridization (CGH) and locus-specific fluorescence in situ hybridization (FISH) analysis to search for genetic changes that may underlie the phenotypic progression events in this model system. Six genetic aberrations were seen by CGH in the parental LNCaP cell line. The derivative sublines shared virtually all these changes, indicating a common clonal origin, but also contained 3-7 additional genetic changes. Gain of the 13q12-913 chromosomal region as well as losses of 4, 6q24-qter, 20p and 21q were associated with androgen independence and tumorigenicity with additional changes correlating with metastasis. In conclusion, an accumulation of genetic changes correlates with tumour progression in this experimental in vivo model of prostate cancer progression. It is possible that the specific chromosomal aberrations involved in this model system may provide clues to the location of genes involved in human prostate cancer progression and metastasis. C1 UNIV TAMPERE,INST MED TECHNOL,CANC GENET LAB,FIN-33101 TAMPERE,FINLAND. TAMPERE UNIV HOSP,INST MED TECHNOL,CANC GENET LAB,FIN-33101 TAMPERE,FINLAND. UNIV HOSP BERN,DEPT UROL,CH-3010 BERN,SWITZERLAND. UNIV VIRGINIA,HLTH SCI CTR,DEPT UROL,CHARLOTTESVILLE,VA 22908. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT UROL,HOUSTON,TX 77030. NIH,CANC GENET LAB,NCHGR,BETHESDA,MD 20892. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 FU NCI NIH HHS [CA64863, CA57361]; NIDDK NIH HHS [DK47596] NR 26 TC 55 Z9 55 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PY 1997 VL 75 IS 2 BP 190 EP 195 DI 10.1038/bjc.1997.32 PG 6 WC Oncology SC Oncology GA WC763 UT WOS:A1997WC76300007 PM 9010025 ER PT J AU Enger, SM Longnecker, MP Lee, ER Frankl, HD Haile, RW AF Enger, SM Longnecker, MP Lee, ER Frankl, HD Haile, RW TI Resent and past physical activity and prevalence of colorectal adenomas SO BRITISH JOURNAL OF CANCER LA English DT Article DE colorectal adenoma; physical activity; case-control study ID SELF-DEFENSE OFFICIALS; COLON-CANCER; SERUM-CHOLESTEROL; SIGMOID COLON; POLYPS; RISK; EPIDEMIOLOGY; RECTUM; EXERCISE; DIET AB Epidemiological evidence has generally supported a protective association of physical activity with large-bowel adenomas, but whether the protective effects are restricted to recent or past activity is uncertain. We determined whether recent and past recreational or total daily activity was associated with prevalence of colorectal adenomas among male and female members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy (n = 488 matched pairs). Participants, aged 50-74 years, completed a 126-item semiquantitative food frequency questionnaire and were also interviewed regarding non-dietary risk factors in 1991-93, In the univariate analysis, all measures of recent recreational physical activity were associated with reduced prevalence of polyps. After adjustment for body mass index, smoking status, daily servings of fruit and vegetables, use of non-steroidal anti-inflammatory agents and intakes of calories, saturated fat and alcohol, the associations were weakened. For subjects engaging in high-intensity activities compared with subjects not engaging in vigorous activities, the multivariate odds ratio (OR) for recent recreational activity was 0.7 [95 % confidence interval (Cl) 0.4-1.1, trend P = 0.08]. Past recreational activity and past or recent total daily activity were not associated with prevalence of adenomas. These results support a modest association of recent recreational physical activity with prevalence of colorectal adenomas. C1 UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90095. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. BELLFLOWER MED CTR,DIV GASTROENTEROL,LOS ANGELES,CA 90027. SUNSET KAISER PERMANENTE MED CTR,DIV GASTROENTEROL,LOS ANGELES,CA 90027. RP Enger, SM (reprint author), UNIV SO CALIF,SCH MED,DEPT PREVENT MED,1420 SAN PABLO ST,PMB A202,LOS ANGELES,CA 90033, USA. FU NCI NIH HHS [CA-49565, 1-R01-CA51923] NR 44 TC 18 Z9 18 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PY 1997 VL 75 IS 5 BP 740 EP 745 DI 10.1038/bjc.1997.131 PG 6 WC Oncology SC Oncology GA WK066 UT WOS:A1997WK06600019 PM 9043034 ER PT J AU Sunaga, S Maki, K Lagasse, E Blanco, JCG Ozato, K Miyazaki, J Ikuta, K AF Sunaga, S Maki, K Lagasse, E Blanco, JCG Ozato, K Miyazaki, J Ikuta, K TI Myeloid differentiation is impaired in transgenic mice with targeted expression of a dominant negative form of retinoid X receptor beta SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE retinoid X receptor; dominant negative; retinoic acid; myeloid differentiation; transgenic mice ID ACUTE PROMYELOCYTIC LEUKEMIA; THYROID-HORMONE RECEPTOR; CALCIUM-BINDING PROTEINS; ACID RECEPTOR; CELL-LINE; SIGNALING PATHWAYS; MUTANT MICE; STEM-CELLS; V-ERBA; ALPHA AB To investigate the in vivo function of retinoid X receptor (RXR) on myelopoiesis, we generated transgenic (Tg) mice with targeted expression of a dominant negative form of RXR beta in myeloid cells. In these Tg mice the transgene is expected to suppress the function of heterodimeric receptors composed of RXR and its counterparts, such as retinoic acid receptor. Out of 12 mice analysed, one Tg mouse exhibited a severe maturation arrest at the promyelocytic stage. Three other Tg mice showed a mild inhibition of myeloid differentiation, which was further augmented when mice were treated with 5-fluorouracil (5-FU). Furthermore, four Tg mice showed impaired myeloid differentiation in response to the treatment by 5-FU or granulocyte-colony stimulating factor (G-CSF), although they exhibited apparently normal myelopoiesis in the untreated state. The phenotype of Tg mice observed after G-CSF treatment correlated with the expression level of the transgene, although the correlation was not found in untreated mice. These results indicated that myeloid differentiation is perturbed in the Tg mice by the dominant negative effect of the transgenic RXR, indicating that RXR plays a role in myelopoiesis. C1 UNIV TOKYO,FAC MED,DEPT DIS RELATED GENE REGULAT RES SANDOZ,BUNKYO KU,TOKYO 113,JAPAN. UNIV TOKYO,FAC MED,DEPT INTERNAL MED,BUNKYO KU,TOKYO 113,JAPAN. STANFORD UNIV,DEPT PATHOL,SCH MED,STANFORD,CA 94305. STANFORD UNIV,DEPT DEV BIOL,SCH MED,STANFORD,CA 94305. NIH,LAB MOL GROWTH REGULAT,NICHHD,BETHESDA,MD. TOHOKU UNIV,INST DEV AGING & CANC,SENDAI,MIYAGI 980,JAPAN. RI Miyazaki, Jun-ichi/N-1976-2015 OI Miyazaki, Jun-ichi/0000-0003-2475-589X NR 52 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 1997 VL 96 IS 1 BP 19 EP 30 DI 10.1046/j.1365-2141.1997.8692483.x PG 12 WC Hematology SC Hematology GA WD859 UT WOS:A1997WD85900004 PM 9012684 ER PT J AU Suomi, SJ AF Suomi, SJ TI Early determinants of behaviour: Evidence from primate studies SO BRITISH MEDICAL BULLETIN LA English DT Article ID RHESUS-MONKEYS; NONHUMAN-PRIMATES; SEPARATION; ATTACHMENT AB The idea that early experiences disproportionately influence adult behaviour has long been a Fixture of mainstream developmental theory. Although unambiguous empirical support for this view at the human level is surprisingly sparse, compelling evidence from animal studies abounds. Recent studies with rhesus monkeys have demonstrated dramatic short- and long-term effects of differential early social experiences on both behavioural and physiological functioning. Early social relationships with mothers or other caregivers appear to provide especially powerful determinants of behavioural propensities throughout the lifespan. RP Suomi, SJ (reprint author), NICHHD,COMPARAT ETHOL LAB,NIH,BLDG 31,ROOM B2B-15,BETHESDA,MD 20892, USA. NR 57 TC 237 Z9 238 U1 1 U2 27 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON, ENGLAND W1M 8AE SN 0007-1420 J9 BRIT MED BULL JI Br. Med. Bull. PD JAN PY 1997 VL 53 IS 1 BP 170 EP 184 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA WT294 UT WOS:A1997WT29400013 PM 9158292 ER PT J AU Gaver, DP Jacobs, PA Carpenter, RL Burkhart, JG AF Gaver, DP Jacobs, PA Carpenter, RL Burkhart, JG TI A mathematical model for intracellular effects of toxins on DNA adduction and repair SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; CELLS; ETHYLNITROSOUREA; DERIVATIVES; MUTATION; AGENTS AB The processes by which certain classes of toxic compounds or their metabolites may react with DNA to alter the genetic information contained in subsequent generations of cells or organisms are a major component of hazard associated with exposure to chemicals in the environment. Many classes of chemicals may form DNA adducts and there may or may not be a defined mechanism to remove a particular adduct from DNA independent of replication. Many compounds and metabolites that bind DNA also readily bind existing proteins; some classes of toxins and DNA adducts have the capacity to inactivate a repair enzyme and divert the repair process competitively. This paper formulates an intracellular dynamic model for one aspect of the action of toxins that form DNA adducts, recognizing a capacity for removal of those adducts by a repair enzyme combined with reaction of the toxin and/or the DNA adduct to inactivate the repair enzyme. This particular model illustrates the possible saturation of repair enzyme capacity by the toxin dosage and shows that bistable behavior can occur, with the potential to induce abrupt shifts away from steady-state equilibria. The model suggests that bistable behavior, dose and variation between individuals or tissues may combine under certain conditions to amplify the biological effect of dose observed as DNA adduction and its consequences as mutation. A model recognizing stochastic phenomena also indicates that variation in within-cell toxin concentration may promote jumps between stable equilibria. (C) 1997 Society for Mathematical Biology C1 NATL NAVAL MED CTR, DAYTON, OH 45433 USA. NATL NAVAL MED CTR, WRIGHT PATTERSON AFB, OH 45433 USA. NIEHS, ENVIRONM TOXICOL PROGRAM, RES TRIANGLE PK, NC 27709 USA. RP Gaver, DP (reprint author), USN, POSTGRAD SCH, DEPT OPERAT RES, MONTEREY, CA 93943 USA. NR 25 TC 5 Z9 5 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD JAN PY 1997 VL 59 IS 1 BP 89 EP 106 DI 10.1016/S0092-8240(96)00056-0 PG 18 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA VZ850 UT WOS:A1997VZ85000005 PM 8980304 ER PT J AU Robertson, SE Mayans, MV Horsfall, S Wright, PF Clemens, J Ivanoff, B Lambert, PH AF Robertson, SE Mayans, MV Horsfall, S Wright, PF Clemens, J Ivanoff, B Lambert, PH TI The WHO Global Programme for Vaccines and Immunization Vaccine Trial Registry SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article ID ORAL POLIOVIRUS VACCINE; DEVELOPING-COUNTRIES; EDMONSTON-ZAGREB; CLINICAL-TRIALS; MEASLES-VACCINE; IMMUNOGENICITY; EFFICACY; EPIDEMIOLOGY; INFANTS; HEALTH AB In 1995, the WHO Global Programme for Vaccines and Immunization established a Vaccine Trial Registry. As of September 1996, this registry included 50 WHO-supported vaccine trials, of which 25 (50%) were completed studies, The vaccines most frequently tested have been against measles (9 trials), poliovirus (8 trials), cholera (8 trials), enterotoxigenic Escherichia coli (4 trials), and pneumococcus (4 trials), Nearly 80% of these trials have been conducted in developing countries, with the largest number being in Africa. Among the 25 completed trials, outcomes measured were immune response (24 trials), adverse reactions (13 trials), morbidity (4 trials), and mortality (I trial). WHO's contributions to these studies include direct funding, assistance with study design, site visits, data analysis, vaccine procurement, and vaccine potency testing. C1 CTR EPIDEMIOL STUDIES AIDS CATALONIA,BADALONA,SPAIN. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37212. NICHHD,EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. RP Robertson, SE (reprint author), WHO,GLOBAL PROGRAMME VACCINES & IMMUNIZAT,VACCINE RES & DEV UNIT,CH-1211 GENEVA 27,SWITZERLAND. NR 39 TC 3 Z9 3 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 1997 VL 75 IS 4 BP 295 EP 305 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XZ713 UT WOS:A1997XZ71300001 PM 9342888 ER PT J AU Murphy, BR Collins, PL AF Murphy, BR Collins, PL TI Current status of respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) vaccine development: Memorandum from a Joint WHO/NIAID meeting SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article AB A Joint WHO/National Institute of Allergy and Infectious Diseases (NIAID) meeting on the current status of respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) vaccine development was held in Bethesda, MD, from 30 September to I October 1996. The meeting summarized the worldwide impact of RSV and PIV3; presented the current status of development of RSV and PIV3 vaccines; and examined the applications of recombinant DNA technology to the development and characterization of vaccines and to the understanding of viral pathogenesis. C1 NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892. NR 0 TC 28 Z9 28 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 1997 VL 75 IS 4 BP 307 EP 313 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XZ713 UT WOS:A1997XZ71300002 PM 9342889 ER PT S AU Potter, M Marcu, KB AF Potter, M Marcu, KB BE Potter, M Melchers, F TI The c-myc story: Where we've been, where we seem to be going SO C-MYC IN B-CELL NEOPLASIA: 14TH WORKSHOP ON MECHANISMS IN B-CELL NEOPLASIA SE Current Topics in Microbiology and Immunology LA English DT Review CT 14th Mechanisms in B-Cell Neoplasia Meeting CY OCT 21-23, 1996 CL BETHESDA, MD SP NCI, Cygnus Inc ID RNA-POLYMERASE-II; BURKITTS-LYMPHOMA CELLS; TRANSCRIPTION IN-VIVO; TATA-BINDING PROTEIN; ZINC-FINGER PROTEINS; NF-KAPPA-B; DNA-BINDING; IMMUNOGLOBULIN-KAPPA; NEOPLASTIC-CELLS; TRANSGENIC MICE C1 SUNY STONY BROOK, STONY BROOK, NY 11794 USA. RP Potter, M (reprint author), NCI, NIH, BETHESDA, MD 20892 USA. NR 106 TC 33 Z9 33 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-62892-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1997 VL 224 BP 1 EP 17 PG 17 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BJ51Q UT WOS:A1997BJ51Q00001 PM 9308224 ER PT S AU Levens, D Duncan, RC Tomonaga, T Michelotti, GA Collins, I DavisSmyth, T Zheng, T Michelotti, EF AF Levens, D Duncan, RC Tomonaga, T Michelotti, GA Collins, I DavisSmyth, T Zheng, T Michelotti, EF BE Potter, M Melchers, F TI DNA conformation, topology, and the regulation of c-myc expression SO C-MYC IN B-CELL NEOPLASIA: 14TH WORKSHOP ON MECHANISMS IN B-CELL NEOPLASIA SE Current Topics in Microbiology and Immunology LA English DT Review CT 14th Mechanisms in B-Cell Neoplasia Meeting CY OCT 21-23, 1996 CL BETHESDA, MD SP NCI, Cygnus Inc ID SINGLE-STRANDED-DNA; NUCLEAR RIBONUCLEOPROTEIN-K; ZINC-FINGER PROTEIN; CHROMATIN STRUCTURE; BINDING-PROTEIN; RNA-BINDING; IN-VIVO; TRANSCRIPTIONAL REPRESSOR; MOLECULAR-CLONING; GENE RP Levens, D (reprint author), NCI, PATHOL LAB, BLDG 10, BETHESDA, MD 20892 USA. RI Levens, David/C-9216-2009; Duncan, Robert/I-8168-2015 OI Levens, David/0000-0002-7616-922X; Duncan, Robert/0000-0001-8409-2501 NR 48 TC 27 Z9 27 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-62892-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1997 VL 224 BP 33 EP 46 PG 14 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BJ51Q UT WOS:A1997BJ51Q00003 PM 9308226 ER PT S AU Siwarski, D Muller, U Andersson, J Notario, V Melchers, F Rolink, A Huppi, K AF Siwarski, D Muller, U Andersson, J Notario, V Melchers, F Rolink, A Huppi, K BE Potter, M Melchers, F TI Structure and expression of the c-Myc Pvt 1 megagene locus SO C-MYC IN B-CELL NEOPLASIA: 14TH WORKSHOP ON MECHANISMS IN B-CELL NEOPLASIA SE Current Topics in Microbiology and Immunology LA English DT Review CT 14th Mechanisms in B-Cell Neoplasia Meeting CY OCT 21-23, 1996 CL BETHESDA, MD SP NCI, Cygnus Inc ID MURINE PLASMACYTOMAS; TRANSLOCATION; TRANSCRIPTS; ONCOGENE; BREAKPOINT; LYMPHOMA AB A chromosomal translocation (Tx) that interrupts the transcription of either c-Myc or Pvt 1 is the principal lesion in many B cell malignancies including Burkitt's Lymphoma (BL), AIDs-NHL, mouse plasmacytoma (Pet) and possibly multiple myeloma(MM). There is a restriction associated with this Tx such that only the immunoglobulin (Ig) heavy chain gene is found juxtaposed to c-Myc and only the Ig light chain gene is found juxtaposed to Pvt 1. Over the past several years, our laboratory has been instrumental in the elucidation of the structure of the mouse Pvt 1 locus as a means of understanding the relationship between these two divergent Txs which, nevertheless, produce indistinguishable disease phenotypes. In the mouse, we have identified a uniform Pvt1/Ig Ck fusion product which is consistently found in all tumors harboring Pvt 1 associated Txs. We have recently constructed transgenic mice harboring a translocated Pvt 1/Ck segment in order to determine whether 1). these mice produce the Pvt 1/Ck fusion product 2). these mice are immunocompromised and 3). these mice develop tumors of a B cell origin. C1 BASEL INST IMMUNOL, BASEL, SWITZERLAND. GEORGETOWN UNIV, MED CTR, DEPT RADIAT MED, WASHINGTON, DC 20007 USA. RP Siwarski, D (reprint author), NCI, GENET LAB, BLDG 37, BETHESDA, MD 20892 USA. NR 14 TC 9 Z9 9 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-62892-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1997 VL 224 BP 67 EP 72 PG 6 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BJ51Q UT WOS:A1997BJ51Q00006 PM 9308229 ER PT S AU Cultraro, CM Bino, T Segal, S AF Cultraro, CM Bino, T Segal, S BE Potter, M Melchers, F TI Regulated expression and function of the c-Myc antagonist, Mad1, during a molecular switch from proliferation to differentiation SO C-MYC IN B-CELL NEOPLASIA: 14TH WORKSHOP ON MECHANISMS IN B-CELL NEOPLASIA SE Current Topics in Microbiology and Immunology LA English DT Review CT 14th Mechanisms in B-Cell Neoplasia Meeting CY OCT 21-23, 1996 CL BETHESDA, MD SP NCI, Cygnus Inc ID MURINE ERYTHROLEUKEMIA-CELLS; POST-TRANSCRIPTIONAL REGULATION; REPRESSOR SIN3; MAX; MXI1; PROTEINS; TRANSFORMATION; GROWTH; TUMORIGENESIS; INHIBITION C1 UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20889 USA. RP Cultraro, CM (reprint author), NCI, NAVY MED ONCOL BRANCH, NIH, BETHESDA, MD 20889 USA. NR 37 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-62892-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1997 VL 224 BP 149 EP 158 PG 10 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BJ51Q UT WOS:A1997BJ51Q00015 PM 9308238 ER PT S AU Krylov, D Echlin, DR Taparowsky, EJ Vinson, C AF Krylov, D Echlin, DR Taparowsky, EJ Vinson, C BE Potter, M Melchers, F TI Design of dominant negatives to bHLHZip proteins that inhibit DNA binding SO C-MYC IN B-CELL NEOPLASIA: 14TH WORKSHOP ON MECHANISMS IN B-CELL NEOPLASIA SE Current Topics in Microbiology and Immunology LA English DT Review CT 14th Mechanisms in B-Cell Neoplasia Meeting CY OCT 21-23, 1996 CL BETHESDA, MD SP NCI, Cygnus Inc ID MYC PROTEINS; CELL-GROWTH; MAX; DIFFERENTIATION; MUTANT C1 PURDUE UNIV, DEPT BIOL SCI, W LAFAYETTE, IN 47907 USA. RP Krylov, D (reprint author), NCI, BIOCHEM LAB, NIH, BLDG 37, ROOM 4D06, BETHESDA, MD 20892 USA. NR 14 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-62892-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1997 VL 224 BP 169 EP 177 PG 9 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BJ51Q UT WOS:A1997BJ51Q00017 PM 9308240 ER PT S AU Janz, S Kovalchuk, AL Muller, JR Potter, M AF Janz, S Kovalchuk, AL Muller, JR Potter, M BE Potter, M Melchers, F TI Genetic recombinations between c-myc and Igh mu as precursors for recombinations between c-myc and Igh alpha in BALB/c plasmacytomas SO C-MYC IN B-CELL NEOPLASIA: 14TH WORKSHOP ON MECHANISMS IN B-CELL NEOPLASIA SE Current Topics in Microbiology and Immunology LA English DT Review CT 14th Mechanisms in B-Cell Neoplasia Meeting CY OCT 21-23, 1996 CL BETHESDA, MD SP NCI, Cygnus Inc ID HEAVY-CHAIN TRANSGENE; SWITCH REGION; CHROMOSOMAL TRANSLOCATIONS; ENHANCER ELEMENT; IMMUNOGLOBULIN; IDENTIFICATION; EXPRESSION; LOCUS; CELLS; BREAKPOINT AB In this paper we present evidence that primary plasmacytomas harboring a balanced chromosomal translocation t(12;15) may consist of a mosaic of neoplastic clones of tumor cells, in which some of the clones are derived from common progenitors by large additional deletions which alter or ''remodel'' the fine structure of the t(12;15) on the c-myc-deregulating chromosome. This finding is based on the molecular analysis of the t(12;15) in three plasmacytomas, TEPC 1194, PCT 4127 and PCT 4132, in which primary clones of tumor cells with recombinations between the Ig heavy-chain (Igh) mu locus (Igh mu) and c-myc were found to be related to secondary clones of tumor cells with recombinations between the Igh alpha locus (Igh alpha) and c-myc. Clonal relatedness was based on unique junction fragments between S mu and c-myc that were found to be identical in Igh mu/c-myc and Igh alpha/c-myc breakpoint regions. S mu/c-myc breakpoints with adjoining sequences can thus be used as clonotypic markers, providing molecular fingerprints for the evolution of precursor cells with Igh mu/c-myc recombinations into progenitor cells with Igh alpha/c-myc recombinations. We propose that aberrant isotype switch recombination or illegitimate rearrangement in switch regions converts Igh mu/c-myc rearrangements, which are found very rarely in established plasmacytomas, into Igh alpha/c-myc rearrangements, which are present in about 80% of plasmacytomas with t(12;15). Remodeling of the t(12;15) results in closer juxtaposition of c-myc to the 3'-C alpha locus control region and probably in enhanced transcription of c-myc. We suggest that remodeling of c-myc-deregulating rearrangements constitutes a novel progression mechanism in malignant B-cell development. RP Janz, S (reprint author), NCI, GENET LAB, DIV BASIC SCI, NIH, BLDG 37, BETHESDA, MD 20892 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-62892-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1997 VL 224 BP 241 EP 250 PG 10 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BJ51Q UT WOS:A1997BJ51Q00024 PM 9308247 ER PT S AU Muller, JR Mushinski, EB Jones, GM Williams, JA Janz, S Hausner, PF Potter, M AF Muller, JR Mushinski, EB Jones, GM Williams, JA Janz, S Hausner, PF Potter, M BE Potter, M Melchers, F TI Generation of immunoglobulin/c-myc recombinations in murine Peyer's patch follicles SO C-MYC IN B-CELL NEOPLASIA: 14TH WORKSHOP ON MECHANISMS IN B-CELL NEOPLASIA SE Current Topics in Microbiology and Immunology LA English DT Review CT 14th Mechanisms in B-Cell Neoplasia Meeting CY OCT 21-23, 1996 CL BETHESDA, MD SP NCI, Cygnus Inc ID C-MYC; CHROMOSOMAL TRANSLOCATIONS; PLASMACYTOMAS; MICE RP Muller, JR (reprint author), NCI, GENET LAB, NIH, BLDG 37, BETHESDA, MD 20892 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-62892-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1997 VL 224 BP 251 EP 255 PG 5 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BJ51Q UT WOS:A1997BJ51Q00025 PM 9308248 ER PT S AU Kuehl, WM Brents, LA Chesi, M Huppi, K Bergsagel, PL AF Kuehl, WM Brents, LA Chesi, M Huppi, K Bergsagel, PL BE Potter, M Melchers, F TI Dysregulation of c-myc in multiple myeloma SO C-MYC IN B-CELL NEOPLASIA: 14TH WORKSHOP ON MECHANISMS IN B-CELL NEOPLASIA SE Current Topics in Microbiology and Immunology LA English DT Review CT 14th Mechanisms in B-Cell Neoplasia Meeting CY OCT 21-23, 1996 CL BETHESDA, MD SP NCI, Cygnus Inc ID CELL-LINES; TRANSLOCATIONS; AMPLIFICATION; PROTOONCOGENE; EXPRESSION; VARIANT; REGION; MICE AB Translocation of c-myc to IgH switch regions, or less frequently to one of the IgL loci, is essentially an invariant event in murine plasmacytomas. This results in dysregulation of c-myc, manifested by selective expression of the translocated allele. Human multiple myeloma (MM) has a similarly high incidence of translocations involving IgH switch regions, but c-myc is infrequently involved as a partner in these translocations. However, in screening a panel of:20 MM cell lines, we identified six lines containing two genetically distinguishable c-myc alleles. For these six informative lines (and the corresponding tumor for one line) there is selective expression of one c-myc allele despite the apparent absence of translocation, DNA rearrangement, or amplification involving c-myc. This result suggests frequent tumor specific cis-dysregulation of c-myc in Mh I by a presently unknown mechanism. C1 NCI, GENET LAB, NEW YORK, NY 10021 USA. CORNELL UNIV, COLL MED, NEW YORK, NY 10021 USA. RP Kuehl, WM (reprint author), NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20889 USA. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 NR 19 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-62892-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1997 VL 224 BP 277 EP 282 PG 6 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BJ51Q UT WOS:A1997BJ51Q00029 PM 9308252 ER PT S AU Bergsagel, PL Nardini, E Brents, L Chesi, M Kuehl, WM AF Bergsagel, PL Nardini, E Brents, L Chesi, M Kuehl, WM BE Potter, M Melchers, F TI IgH translocations in multiple myeloma: A nearly universal event that rarely involves c-myc SO C-MYC IN B-CELL NEOPLASIA: 14TH WORKSHOP ON MECHANISMS IN B-CELL NEOPLASIA SE Current Topics in Microbiology and Immunology LA English DT Review CT 14th Mechanisms in B-Cell Neoplasia Meeting CY OCT 21-23, 1996 CL BETHESDA, MD SP NCI, Cygnus Inc ID CELL-LINES AB Dysregulation of c-myc by translocation to the switch. regions of the IgH locus occurs in most murine plasmacytomas. Translocations involving 14q32 have been reported in 20-40% of abnormal karyotypes from human multiple myeloma (MM), and involve a variety of loci. Using cytogenetics, FISH and a Southern blot assay, we analyzed 21 MM cell lines and one plasma cell leukemia and identified evidence of a 14q32 translocation in 20/22 samples. The partner loci involved are 11q13 in 6 (associated with cyclin D1 expression), 4p16 in 6 (associated with FGFR3 expression), unidentified in 3 and 1p13, 6, 8q24, 12q24, 16q23, and 21q22 once each. We conclude that conventional karyotypes underestimate the frequency of 14q32 translocations in MM, where they appear to be a nearly universal event. The translocations most frequently involve IgH switch regions, and include two recurrent partner loci (11q13 and 4p16) and a promiscuous array of ocher partner loci. Although c-myc appears to be cis-dysregulated frequently in MM, it is only rarely translocated to the IgH locus. C1 NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20889 USA. RP Bergsagel, PL (reprint author), CORNELL UNIV, COLL MED, NEW YORK, NY 10021 USA. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 NR 9 TC 32 Z9 32 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-62892-4 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1997 VL 224 BP 283 EP 287 PG 5 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BJ51Q UT WOS:A1997BJ51Q00030 PM 9308253 ER PT J AU Fisher, ER AF Fisher, ER TI Pathobiological considerations relating to the treatment of intraductal carcinoma (ductal carcinoma in situ) of the breast SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID FOLLOW-UP; IN-SITU; DEFINITIVE IRRADIATION; PATHOLOGIC FINDINGS; CYTOMETRIC ANALYSIS; PROJECT PROTOCOL-6; CONSERVING SURGERY; NODE METASTASES; INSITU; CANCER C1 NATL SURG ADJUVANT BREAST & BOWEL PROJECT,PITTSBURGH,PA. RP Fisher, ER (reprint author), SHADYSIDE HOSP,INST PATHOL,PITTSBURGH,PA 15232, USA. FU NCI NIH HHS [U10-CA-39086, U10-CA-37377, U10-CA-120270] NR 48 TC 14 Z9 15 U1 0 U2 0 PU AMER CANCER SOC PI NEW YORK PA C/O JB LIPPINCOTT CO 1180 AVE OF THE AMERICAS 6TH FLOOR, NEW YORK, NY 10036 SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JAN-FEB PY 1997 VL 47 IS 1 BP 52 EP 64 DI 10.3322/canjclin.47.1.52 PG 13 WC Oncology SC Oncology GA WL668 UT WOS:A1997WL66800004 PM 8996078 ER PT J AU Johnson, BE Damodaran, A Rushin, J Gross, A Le, PT Chen, HC Harris, RB AF Johnson, BE Damodaran, A Rushin, J Gross, A Le, PT Chen, HC Harris, RB TI Ectopic production and processing of atrial natriuretic peptide in a small cell lung carcinoma cell line and tumor from a patient with hyponatremia SO CANCER LA English DT Article DE lung neoplasm; hyponatremia; ectopic hormone syndromes; protein processing; posttranslational; syndrome of inappropriate antidiuretic hormone (SIADH) ID GRANULE SERINE PROTEINASE; ANTIDIURETIC-HORMONE; INAPPROPRIATE SECRETION; BRONCHOGENIC-CARCINOMA; CANCER; VASOPRESSIN; EXPRESSION; ENZYME; GROWTH; POLYPEPTIDE AB BACKGROUND. Tumors and tumor cell lines from two patients with small cell lung carcinoma (SCLC) (one with and one without hyponatremia) were studied. Ectopic production and prohormone processing of atrial natriuretic peptide (ANP) were investigated to determine if a biologically active peptide was produced in a tumor cell line from a patient with hyponatremia and no evidence of arginine vasopressin (AVP) production. METHODS. Ribonuclease (RNase) protection assays were performed on mRNA isolated from tumors and tumor cell lines established from two SCLC patients, one with and one without hyponatremia. Cellular extracts and conditioned media were studied using reversed-phase high performance Liquid chromatography (HPLC) to determine the immunoreactive form of ANP. Tumor cell line sonicates were studied for subcellular localization of enzymatic activity that cleaved pro-ANP peptide substrates. RESULTS. RNase protection assays showed a 200-base pair protected fragment in the mRNA isolated from the tumor and tumor cell line from the patient with hyponatremia (Patient 4). HPLC characterization of the cellular extract and conditioned medium from the tumor and tumor cell line ti om Patient 4 demonstrated ANP immunoreactivity in the same fraction as ANP-(S-99-Y-126). The tumor cell line extract that localizes to a subcellular fraction enriched for lysosomes and secretory organelles contains a 60-kilodalton molecular weight protein with enzyme activity that hydrolyzes synthetic pro-ANP substrates and catalyzes the formation of ANP-(S-99-Y-126). CONCLUSIONS. A tumor cell line from a patient with hyponatremia was able ectopically to produce, process, and secrete ANP in the same immunoreactive form as the biologically active molecule. Preliminary studies show that tumor cell line NCI-H1284 contains an enzyme that can cleave precursors at the same amino acid sequences needed to produce ANP-(S-99-Y-126) from pro-ANP. (C) 1997 American Cancer Society. C1 VIRGINIA COMMONWEALTH UNIV, DEPT BIOCHEM & MOL BIOPHYS, RICHMOND, VA 23298 USA. NATL NAVAL MED CTR, DEPT LAB, BETHESDA, MD USA. NICHHD, ENDOCRINOL & REPROD RES BRANCH, BETHESDA, MD 20892 USA. RP Johnson, BE (reprint author), NCI, NATL NAVAL MED CTR, NAVAL MED ONCOL BRANCH, BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. NR 37 TC 20 Z9 22 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 1997 VL 79 IS 1 BP 35 EP 44 PG 10 WC Oncology SC Oncology GA VZ232 UT WOS:A1997VZ23200006 PM 8988724 ER PT J AU Herold, AH Riker, AI Warner, EA Woodard, LJ Brownlee, HJ Pencev, D Oldenski, RJ Brady, PG AF Herold, AH Riker, AI Warner, EA Woodard, LJ Brownlee, HJ Pencev, D Oldenski, RJ Brady, PG TI Evidence of gender bias in patients undergoing flexible sigmoidoscopy SO CANCER DETECTION AND PREVENTION LA English DT Article DE gender bias; flexible sigmoidoscopy; colorectal cancer screening ID COLORECTAL-CANCER; WOMEN; MEN; SEX; TRANSPLANTATION; PHYSICIANS; TESTS; CARE; AGE AB Some studies have revealed gender bias against women in various aspects of medical care. There is no substantial evidence of gender bias in patients undergoing cancer evaluations, specifically colorectal cancer screening and diagnosis of colorectal complaints. This study was designed to examine the role of gender bias related to patients undergoing flexible sigmoidoscopy. At the University of South Florida, we conducted a retrospective study of 1910 patients at three distinct flexible sigmoidoscopy clinics over several years, through 1992. The proportions of male and female patients who underwent the procedure for indications of either screening for colorectal cancer or the diagnosis of colorectal complaints were determined. These proportions were compared with the respective male and female patient proportions from the total number of currently active patients at each site who were eligible to have the procedure for an appropriate indication. At all three sites, a significantly smaller proportion of women (p < 0.01) underwent the procedure than expected. This was true for both screening and diagnostic indications. Conversely, at all sites significantly more men (p < 0.01) underwent the procedure for both indications. The results of this study suggest gender bias against women for patients undergoing flexible sigmoidoscopy for both screening and diagnosis. This bias may adversely affect the lethality of colorectal cancer in women. It is important to determine if such biases are influenced by the physician's recommendation or mainly due to patient attitudes. C1 NCI,DEPT FAMILY MED,NIH,BETHESDA,MD 20892. NR 23 TC 34 Z9 34 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 1997 VL 21 IS 2 BP 141 EP 147 PG 7 WC Oncology SC Oncology GA WR523 UT WOS:A1997WR52300006 PM 9101075 ER PT J AU Sanford, KK Price, FM Brodeur, C Makrauer, FL Parshad, R AF Sanford, KK Price, FM Brodeur, C Makrauer, FL Parshad, R TI Deficient DNA repair in chronic ulcerative colitis SO CANCER DETECTION AND PREVENTION LA English DT Article DE chromatid breaks; G2 phase; ultraviolet irradiation; X-irradiation ID MICROSATELLITE INSTABILITY; CHROMATID DAMAGE; X-IRRADIATION; BREAST-CANCER; RADIOSENSITIVITY; FAMILY; CELLS; PREDISPOSITION; FIBROBLASTS; SENSITIVITY AB Carcinoma of the colon is a serious complication of chronic ulcerative colitis (CUC), a disease of unknown etiology. Peripheral blood lymphocytes from nine patients with CUC showed deficient repair of radiation-induced DNA damage compared with a group of healthy controls. DNA repair was measured indirectly by quantifying chromatid breaks after irradiation of cells with It-rays or ultraviolet during G2 phase of the cell cycle. Such breaks represent unrepaired DNA strand breaks that may arise directly from the damaging agent or indirectly during repair processes. Two types of deficiency were revealed. One was an abnormally high frequency of chromatid breaks after G2-phase X-irradiation. These may reflect deficient strand-break repair. The second deficiency was manifest as a low frequency of breaks not increased by addition of the DNA repair inhibitor araC. This low frequency apparently results from negligible incision activity. Deficient DNA repair in CUC may thus be a requisite predisposing factor for genomic instability and the potential development of colon carcinoma. RP Sanford, KK (reprint author), NCI,CELLULAR & MOL BIOL LAB,NIH,ROOM 1E24,BLDG 37,BETHESDA,MD 20892, USA. NR 26 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 1997 VL 21 IS 6 BP 540 EP 545 PG 6 WC Oncology SC Oncology GA YG489 UT WOS:A1997YG48900007 PM 9398994 ER PT J AU Patterson, BH Levander, OA AF Patterson, BH Levander, OA TI Naturally occurring selenium compounds in cancer chemoprevention trials: A workshop summary SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; SPONTANEOUS MAMMARY-TUMORS; SELENIFEROUS AREA; CHINA; SUPPLEMENTATION; MICE; LINXIAN; GENESIS; HEALTH AB Evidence from epidemiological studies and a human intervention trial indicates that selenium (Se) may have chemopreventive activity in humans, This report summarizes a workshop held by the National Cancer Institute to address the use of naturally occurring Se compounds in future cancer chemoprevention trials, Differences in the metabolism of inorganic and organic Se compounds can be seen both in the biochemical handling of these forms and in their kinetics in humans, Longterm supplementation could result in greater increases in muscle stores for organic rather than inorganic forms. Because of long half-lives, trials may have to be of long duration to assess efficacy and safety, The optimal size of dose for supplementation is controversial with respect to both efficacy and safety, In China, selenosis was observed in some individuals with a sustained intake of at least 750 mu g/day but was not observed among others with intakes exceeding 1 mg, These levels exceed the reference dose, a measure of the maximal safe intake, which is 350 mu g/day. A large-scale Se human intervention trial in the United States suggests no harm due to long-term Se intake of more than 200 mu g/day. Se deficiency has been shown to have deleterious effects on the immune system, allowing, for example, a benign form of the Coxsackievirus to become virulent in mice, These recent results may provide an explanation of earlier findings showing a protective effect of elevated Se intakes against a mouse mammary tumor virus, Additional studies on the use of Se as a chemopreventive agent in man seem warranted. C1 USDA,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. RP Patterson, BH (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EXECUT PLAZA N 344,BETHESDA,MD 20892, USA. NR 32 TC 55 Z9 58 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 1997 VL 6 IS 1 BP 63 EP 69 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WB772 UT WOS:A1997WB77200011 PM 8993799 ER PT J AU Sugimoto, Y Sato, S Tsukahara, S Suzuki, M Okochi, E Gottesman, MM Pastan, I Tsuruo, T AF Sugimoto, Y Sato, S Tsukahara, S Suzuki, M Okochi, E Gottesman, MM Pastan, I Tsuruo, T TI Coexpression of a multidrug resistance gene (MDR1) and herpes simplex virus thymidine kinase gene in a bicistronic retroviral vector Ha-MDR-IRES-TK allows selective killing of MDR1-transduced human tumors transplanted in nude mice SO CANCER GENE THERAPY LA English DT Article DE multidrug resistance gene; herpes simplex virus thymidine kinase; ganciclovir; bicistronic retrovirus vector; cancer chemotherapy; bone marrow transplantation ID HEMATOPOIETIC PRECURSOR CELLS; METASTATIC BREAST-CANCER; P-GLYCOPROTEIN GENE; BONE-MARROW; DRUG-RESISTANCE; TRANSGENIC MICE; MEDIATED TRANSFER; EXPRESSION; CDNA; THERAPY AB Ha-MDR-IRES-TK is a bicistronic vector that coexpresses the MDR1 gene and the herpes simplex virus thymidine kinase (HSV-TK) gene. In the present study we examined the effect of ganciclovir on MDR1-positive tumors that have been transduced with Ha-MDR-IRES-TK. To establish a human tumor xenograft model of MDR1-transduced recurrent tumors, human KB-3-1 carcinoma cells were transduced with HaMDR or Ha-MDR-IRES-TK, and one each of representative clones, termed KB/MDR and KB/MDR-TK, respectively, were isolated. KB/MDR and KB/MDR-TK showed similar levels of multidrug resistance in vitro. Vinblastine strongly inhibited the growth of the parental KB-3-1 tumors in nude mice but showed little or no effect against KB/MDR-TK tumors. Ganciclovir inhibited the in vivo growth of KB/MDR-TK tumors almost completely under conditions that did not affect the growth of KB-3-1 tumors. Coadministration of vinblastine and ganciclovir inhibited the in vivo growth of KB/MDR-TK premixed with KB-3-1 at any ratio. Long-term, high-level expression of human P-glycoprotein was observed in peripheral blood cells of mice transplanted with Ha-MDR-IRES-TK-transduced bone marrow cells. Ganciclovir eliminated the P-glycoprotein-positive normal blood eel Is. However, no systemic toxicity was observed. These results clearly demonstrate that it is possible to use ganciclovir to treat MDR1-positive tumors that have been unintentionally transduced with Ha-MDR-IRES-TK. This safety-modified vector should be useful for introducing the MDR1 gene into bone marrow cells to protect normal cells from the toxic effects of cancer chemotherapy. C1 HOECHST JAPAN LTD,KAWAGOE,SAITAMA 35011,JAPAN. NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV TOKYO,INST MOL & CELLULAR BIOSCI,TOKYO,JAPAN. RP Sugimoto, Y (reprint author), JAPANESE FDN CANC RES,CTR CANC CHEMOTHERAPY,TOSHIMA KU,1-37-1 KAMI IKEBUKURO,TOKYO 170,JAPAN. NR 32 TC 21 Z9 22 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JAN-FEB PY 1997 VL 4 IS 1 BP 51 EP 58 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA WE470 UT WOS:A1997WE47000007 PM 9012451 ER PT J AU Popescu, NC Zimonjic, DB AF Popescu, NC Zimonjic, DB TI Molecular cytogenetic characterization of cancer cell alterations SO CANCER GENETICS AND CYTOGENETICS LA English DT Review ID COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; FLUORESCENCE INSITU HYBRIDIZATION; HUMAN-BREAST-CANCER; AMPLIFIED DNA-SEQUENCES; SOLID TUMORS; PHILADELPHIA-CHROMOSOME; ONCOGENE AMPLIFICATION; CERVICAL-CARCINOMA; SYNTHESIS PRINS AB Chromosomal abnormalities are the hallmark of cancer cells. Recurring and highly consistent structural and numerical alterations have been identified in a large number of leukemias, lymphomas, and solid tumors. The identification of recurrent genetic alterations and the isolation of molecular markers have clinical applications in the diagnosis and prognosis of neoplasia and in the detection of minimal residual disease that ore essential for designing the mast effective therapeutic approach. Polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) are powerful techniques for detection of genomic alterations. The battery of FISH methods and DNA probes that are available can resolve virtually any chromosomal alterations regardless of their complexity. Combined chromosome banding, multifluor or spectral karyotype, and comparative genomic hybridization (CGH) allow identification of structural and numerical alterations on a global basis, mapping of the DNA copy number on the entire tumor genome, complete derivation of complex rearrangements, and localization of the breakpoints of translocations and deletions. Regions of recurrent alterations can be microdissected, amplified, microclone libraries constructed and probes localized on extended chromosomes or chromatin fibers for construction of high resolution physical maps that are critical for positional cloning and gene identification. In this review we attempted to cover the current trends in cancer molecular cytogenetics, and to outline the importance of molecular chromosome analysis in the understanding of oncogenesis and its clinical applications. Published by Elsevier Science Inc., 1997. RP Popescu, NC (reprint author), NCI,MOL CYTOGENET SECT,EXPT CARCINOGENESIS LAB,BLDG 37,ROOM 3C05,37 CONVENT DR,BETHESDA,MD 20892, USA. NR 109 TC 44 Z9 45 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JAN PY 1997 VL 93 IS 1 BP 10 EP 21 DI 10.1016/S0165-4608(96)00262-2 PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA WL245 UT WOS:A1997WL24500003 PM 9062575 ER PT J AU Meltzer, PS Guan, XY Su, YA Gracia, E Trent, JM AF Meltzer, PS Guan, XY Su, YA Gracia, E Trent, JM TI Identification of region specific genes by chromosome microdissection SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID MALIGNANT-MELANOMA; RAPID GENERATION; DNA; AMPLIFICATION; CLONING; PROBES; CLONES AB Chromosome microdissection is an extremely useful molecular cytogenetic tool for the characterization of chromosomal abnormalities in tumor cells. Although it has been used primarily in conjunction with fluorescence in situ hybridization (FISH), microdissection has also been useful for molecular analysis via microclone library construction. Recently, microdissection has been applied to the isolation of region specific cDNAs with sufficient success that gene discovery can now be added to the list of applications of this versatile molecular cytogenetic technique. (C) Elsevier Science Inc., 1997. RP Meltzer, PS (reprint author), NIH,CANC GENET LAB,NATL CTR HUMAN GENOME RES,9000 ROCKVILLE PIKE,BLDG 49,ROOM 4A22,BETHESDA,MD 20892, USA. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 20 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JAN PY 1997 VL 93 IS 1 BP 29 EP 32 DI 10.1016/S0165-4608(96)00269-5 PG 4 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA WL245 UT WOS:A1997WL24500005 PM 9062577 ER PT J AU Molldrem, J Wilson, WH AF Molldrem, J Wilson, WH TI Infusional chemotherapy for non-Hodgkin's lymphoma SO CANCER INVESTIGATION LA English DT Article ID CONTINUOUS INTRAVENOUS-INFUSION; LARGE-CELL LYMPHOMA; COMBINATION CHEMOTHERAPY; DRUG-RESISTANCE; MULTIDRUG-RESISTANCE; SCHEDULE DEPENDENCY; EPOCH CHEMOTHERAPY; PULMONARY TOXICITY; CLONOGENIC-ASSAY; RANDOMIZED TRIAL C1 NCI,MED BRANCH,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 65 TC 4 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1997 VL 15 IS 5 BP 465 EP 474 DI 10.3109/07357909709047586 PG 10 WC Oncology SC Oncology GA XX928 UT WOS:A1997XX92800009 PM 9316629 ER PT J AU Kobrin, CB Kwak, LW AF Kobrin, CB Kwak, LW TI Development of vaccine strategies for the treatment of B-cell malignancies SO CANCER INVESTIGATION LA English DT Article ID LYMPHOCYTE-T; TRANSPLANTATION RESISTANCE; CIRCUMSPOROZOITE PROTEIN; CYTOTOXIC LYMPHOCYTES; ANTITUMOR IMMUNITY; IMMUNIZATION; ANTIGEN; INDUCTION; ANTIBODY; TUMOR C1 NCI,DIV CLIN SCI,FREDERICK,MD 21702. RP Kobrin, CB (reprint author), SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,BLDG 567,ROOM 202,FREDERICK,MD 21702, USA. NR 64 TC 19 Z9 20 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1997 VL 15 IS 6 BP 577 EP 587 DI 10.3109/07357909709047600 PG 11 WC Oncology SC Oncology GA YK035 UT WOS:A1997YK03500010 PM 9412664 ER PT J AU Morris, AD Morris, RD Wilson, JF White, J Steinberg, S Okunieff, P Arriagada, R Le, MG BlichertToft, M vanDongen, JA AF Morris, AD Morris, RD Wilson, JF White, J Steinberg, S Okunieff, P Arriagada, R Le, MG BlichertToft, M vanDongen, JA TI Breast-conserving therapy vs mastectomy in early-stage breast cancer: A meta-analysis of 10-year survival SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE breast neoplasm; meta-analysis; breast-conserving therapy; mastectomy ID COMPARING TOTAL MASTECTOMY; CLINICAL-TRIAL; RANDOMIZED TRIAL; CONSERVATIVE TREATMENT; GEOGRAPHIC-VARIATION; AXILLARY DISSECTION; QUADRANTECTOMY; RADIOTHERAPY; IRRADIATION; LUMPECTOMY AB BACKGROUND The randomized trials comparing breast-conserving therapy (BCT), i.e., surgery and radiation to the breast, with mastectomy in early-stage breast cancer use a variety of protocols. Meta-analysis may assist in understanding the impact of these differences on survival. PURPOSE To evaluate the possible variations of the relative efficacy of BCT and mastectomy in terms of overall survival according to tumor size, nodal status, and use of adjuvant radiation therapy. METHODS The most recent published results and, where available, updated patient-level data from randomized controlled trials of BCT and mastectomy for early-stage breast cancer were combined in a meta-analysis using a random effects model. Pooled survival rates and odds ratios were generated according to subgroups of nodal status and tumor size. Five- and 10-year odds ratios were also determined according to adjuvant radiation protocol. RESULTS The pooled odds ratio comparing 10-year survival for BCT and mastectomy was 0.91. The odds ratios comparing the two treatment regimens were not significant after grouping according to tumor size and nodal status. When more than 50% of node-positive patients in both the mastectomy and BCT arms received adjuvant radiation, both arms had similar survival rates. When less than 50% of node-positive patients in both arms received adjuvant nodal radiation, the odds ratio was 0.69, and patients receiving BCT had a survival advantage. CONCLUSIONS Patients allocated to BCT have survival rates at least as high as patients allocated to mastectomy. When all protocols were combined, nodal status and tumor size did not significantly alter the relative survival rates, However, under some conditions, particularly for node-positive patients, BCT may confer a relative survival advantage over mastectomy. In particular, mastectomy without adjuvant radiation appears to be inferior to BCT for node-positive patients. C1 MED COLL WISCONSIN,DEPT RADIAT ONCOL,MILWAUKEE,WI 53226. NCI,BETHESDA,MD 20892. INST GUSTAVE ROUSSY,VILLEJUIF,FRANCE. RIGSHOSP,DK-2100 COPENHAGEN,DENMARK. NETHERLANDS CANC INST,AMSTERDAM,NETHERLANDS. MED COLL WISCONSIN,CTR ENVIRONM EPIDEMIOL,MILWAUKEE,WI 53226. RP Morris, AD (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,100 BLOSSUM ST COX LL,BOSTON,MA 02114, USA. RI White, Julia/J-6336-2014 NR 34 TC 103 Z9 108 U1 0 U2 3 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JAN-FEB PY 1997 VL 3 IS 1 BP 6 EP 12 PG 7 WC Oncology SC Oncology GA XC010 UT WOS:A1997XC01000003 PM 9072310 ER PT J AU Soldatenkov, VA Dritschilo, A Wang, FH Olah, Z Anderson, WB Kasid, U AF Soldatenkov, VA Dritschilo, A Wang, FH Olah, Z Anderson, WB Kasid, U TI Inhibition of Raf-1 protein kinase by antisense phosphorothioate oligodeoxyribonucleotide is associated with sensitization of human laryngeal squamous carcinoma cells to gamma radiation SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE Raf-1; antisense oligodeoxyribonucleotide; radiosensitizer; head and neck squamous cell carcinoma ID OLIGODEOXYNUCLEOTIDES; EXPRESSION; C-RAF-1; GENE; OLIGONUCLEOTIDES; RESISTANT; SEQUENCE AB BACKGROUND Previous studies suggest a central role for Raf-l protein kinase in mitogenic and radiation damage responsive signaling pathways. PURPOSE Here we report that the expression and enzymatic activity of Raf-1 protein are inhibited in SQ-20B cells exposed to raf antisense oligodeoxyribonucleotide (As-ODNs) directed against the translation initiation site of human C-raf-1 cDNA. In contrast, treatment of SQ-20B cells with an equimolar concentration of raf sense oligodeoxyribonucleotide (S-ODNs) had no effect on the expression and activity of Raf-l. RESULTS We have observed radiosensitization of raf As-ODNs-treated SQ-20B cells. The dose modifying factor of As-ODNs treatment was approximately 1.4. CONCLUSIONS These studies demonstrate that raf As-ODNs is a DNA sequence-specific radiosensitizer that may have potential for use in the radiation therapy of cancers. C1 GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,DEPT RADIAT MED,WASHINGTON,DC 20007. NCI,CELLULAR ONCOL LAB,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA58984, CA65012, CA46641] NR 29 TC 34 Z9 36 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JAN-FEB PY 1997 VL 3 IS 1 BP 13 EP 20 PG 8 WC Oncology SC Oncology GA XC010 UT WOS:A1997XC01000004 PM 9072302 ER PT J AU Cormier, JN Salgaller, ML Prevette, T Barracchini, KC Rivoltini, L Restifo, NP Rosenberg, SA Marincola, FM AF Cormier, JN Salgaller, ML Prevette, T Barracchini, KC Rivoltini, L Restifo, NP Rosenberg, SA Marincola, FM TI Enhancement of cellular immunity in melanoma patients immunized with a peptide from MART-1 Melan A SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE MART-1; melanoma; immunization ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; PERIPHERAL-BLOOD; SYNTHETIC PEPTIDE; HLA-A2 MELANOMAS; IN-VITRO; CELLS; RECOGNITION; IDENTIFICATION; VACCINATION AB PURPOSE In this study, we tested the effectiveness of a melanoma-associated antigen-derived peptide, MART-1(27-35), in eliciting cellular immune responses in vivo in the context of a phase I active immunization protocol. This peptide (AAGIGILTV) corresponds to residues 27-35 from the nonmutated melanoma-associated antigen MART-1/Melan A and is recognized by most melanoma-specific, HLA-A*0201-restricted, tumor-infiltrating lymphocytes. To test the in vivo induction of cytotoxic T lymphocyte (CTL) sensitization, we compared CTL reactivity in vitro from peripheral blood mononuclear cell (PBMC) pools obtained before and after vaccination. PATIENTS AND METHODS MART-1(27-35) was administered to HLA-A*0201 melanoma patients subcutaneously in an emulsification with incomplete Freund's adjuvant. A vaccination course included four inoculations of peptide at 3-week intervals. PBMC collected by leukapheresis and separated by Ficoll-Hypaque gradient before and after vaccination were analyzed in 18 patients by in vitro sensitization with MART-1(27-35). To induce MART-1(27-35)-specific CTL, PBMC were incubated with I mu M peptide (on day 0) and interleukin-2 (IL-2) (300 IU/mL, on days 1 and 4 after each stimulation). At weekly intervals, cells were harvested and an aliquot was cryopreserved for later analysis. The remaining cells were replated and restimulated using irradiated autologous PBMC pulsed with 1 mu M of relevant peptide After three restimulations, all samples from one patient were tested simultaneously for HLA-A*0201-restricted anti-MART-1(27-35) reactivity by microcytotoxicity and cytokine (IFN-gamma) release assays. RESULTS Toxicities were minimal and consisted oflocal irritation at the site of vaccine administration. None of the patients sustained a clinical response. The first eight patients were monitored by inducing CTL reactivity from PBMC obtained preimmunization and after two and four vaccinations. Only two prevaccination cultures were reactive to MART-I, compared with five and seven cultures from PBMC obtained after two and four vaccinations, respectively. Thus, an enhancement in cytotoxic activity could be detected in postvaccination CTL cultures, and serial vaccine administrations appeared to boost the detectability of cytotoxicity in vitro. For completeness, the analysis compared prevaccination with postvaccination PBMC cultures. Specific anti-MART1(27-35) cytotoxicity (greater than or equal to 10 lyric units) could be detected in two prevaccination and 12 postvaccination cultures after two in vitro stimulations. In 15 postvaccination CTL cultures, a more than threefold increase in specific release of IFN-gamma was noted, compared with prevaccination. DISCUSSION In vivo administration of a melanoma-associated antigen peptide, emulsified in incomplete Freund's adjuvant, could safely augment CTL reactivity against epitopes commonly expressed by melanoma cells. Although the enhancement of CTL reactivity did not achieve tumor regression, it is possible that the use of recombinant immunogens with increased immunomodulatory capabilities in future clinical trials could reach the threshold of CTL activation necessary for tumor regression. C1 NCI,SURG BRANCH,CLIN ONCOL PROGRAM,DIV CLIN SCI,BETHESDA,MD 20892. NIH,HLA LAB,DEPT TRANSFUS MED,CTR CLIN,BETHESDA,MD 20892. IST NAZL TUMORI,DEPT EXPT ONCOL D,I-20133 MILAN,ITALY. RI Restifo, Nicholas/A-5713-2008; Ain, Kenneth/A-5179-2012; OI Ain, Kenneth/0000-0002-2668-934X; Restifo, Nicholas P./0000-0003-4229-4580; Rivoltini, Licia/0000-0002-2409-6225 FU Intramural NIH HHS [NIH0010139353, Z01 BC010763-01, Z99 TW999999] NR 24 TC 260 Z9 267 U1 0 U2 2 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JAN-FEB PY 1997 VL 3 IS 1 BP 37 EP 44 PG 8 WC Oncology SC Oncology GA XC010 UT WOS:A1997XC01000007 PM 9072306 ER PT J AU Klauber, N Parangi, S Flynn, E Hamel, E DAmato, RJ AF Klauber, N Parangi, S Flynn, E Hamel, E DAmato, RJ TI Inhibition of angiogenesis and breast cancer in mice by the microtubule inhibitors 2-methoxyestradiol and taxol SO CANCER RESEARCH LA English DT Article ID ENDOGENOUS MAMMALIAN METABOLITE; TUBULIN POLYMERIZATION; TUMOR ANGIOGENESIS; CELLS; MICROSPHERES; GROWTH; MCF-7; SITE AB 2-Methoxyestradiol (2-ME), an endogenous estrogen metabolite which disrupts microtubule function, has been shown to inhibit proliferating cells in vitro and suppress certain murine tumors in vivo. In vitro screening has determined that breast cancer cell lines are most sensitive to inhibition by 2-ME. Additionally, 2-ME has been shown to inhibit angiogenesis in vitro. We tested whether 2-ME suppresses cytokine-induced angiogenesis in vivo and inhibits growth of a human breast carcinoma in severe combined immunodeficient mice. A model of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF)-induced corneal neovascularization in C57BL/6 mice was used to evaluate the antiangiogenic effects of 2-ME and other microtubule inhibitors such as Taxol, vincristine, and colchicine, 2-ME (150 mg/kg p.o., n = 20) inhibited bFGF and VEGF-induced neovascularization by 39% and 54%, respectively, Taxol (6 mg/kg i.p., n = 17) inhibited bFGF and VEGF-induced neovascularization by 45% and 37%, respectively. Vincristine (0.2 mg/kg i.p., n = 8) and colchicine (0.25 mg/kg i.p., n = 8) had no effect. Treatment with 2-ME (75 mg/kg p.o., n = 9) for 1 month suppressed the growth of a human breast carcinoma in mice by 60% without toxicity. Recognition of the antiangiogenic and antitumor properties of 2-ME and Taxol may be crucial in planning clinical applications to angiogenesis-dependent diseases. C1 CHILDRENS HOSP, DEPT SURG, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. BOSTON UNIV, SCH MED, DEPT SURG, BOSTON, MA 02118 USA. NCI, MOL PHARMACOL LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. NR 19 TC 439 Z9 450 U1 1 U2 17 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 JAN 1 PY 1997 VL 57 IS 1 BP 81 EP 86 PG 6 WC Oncology SC Oncology GA WA691 UT WOS:A1997WA69100018 PM 8988045 ER PT J AU Blagosklonny, MV Giannakakou, P ElDeiry, WS Kingston, DGI Higgs, PI Neckers, L Fojo, T AF Blagosklonny, MV Giannakakou, P ElDeiry, WS Kingston, DGI Higgs, PI Neckers, L Fojo, T TI Raf-1/bcl-2 phosphorylation: A step from microtubule damage to cell death SO CANCER RESEARCH LA English DT Article ID TAXOL-INDUCED APOPTOSIS; TYROSINE PHOSPHORYLATION; BCL-2 PROTEIN; ACTIVATION; MECHANISM; TUBULIN; AGENTS; P53; POLYMERIZATION; KINASES AB Recent studies have shown that paclitaxel leads to activation of Raf-l kinase and hare suggested that this activation is essential for bcl-2 phosphorylation and apoptosis, Ins the present study, we demonstrate that, in addition to paclitaxel, other agents that interact with tibulin and microtubules also induce Raf-1/bcl-2 phosphorylation, whereas DNA-damaging drugs, antimetabolites, and alkylating agents do not, Activation of Raf-l kinase by paclitaxel is linked to tubulin polymerization; the effect is blunted in paclitaxel-resistant cells, the tubulin of which does not polymerize following the addition of paclitaxel, In contrast. vincristine and vinblastine, drugs to which the paclitaxel-resisiant cells retain sensitivity were able to bring shout Raf-1 phosphorylation. The requirement for disruption of microtubules in this signaling cascade was strengthened further using paclitaxel analogues by demonstrating a correlation between tubulin polymerization, RaF-1/bcl-2 phosphorylation, and cytotoxicity. Inhibition of RNA or protein synthesis prevents Raf-l activation anti bcl-2 phosphorylation, suggesting that an intermediate protein(s) acts upstream of Raf-1 in this microtubule damage-activating pathway. A model is proposed that envisions a pathway of Raf-l activation and bcl-2 phosphorylation following disruption of microtubular architecture, serving a role similar to p53 induction following DNA damage. C1 NCI,MED BRANCH,NIH,BETHESDA,MD 20892. UNIV PENN,SCH MED,HOWARD HUGHES MED INST,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,CTR CANC,PHILADELPHIA,PA 19104. VIRGINIA POLYTECH INST & STATE UNIV,DEPT CHEM,BLACKSBURG,VA 24061. NCI,CLIN PHARMACOL BRANCH,NIH,BETHESDA,MD 20892. OI Kingston, David/0000-0001-8944-246X NR 40 TC 372 Z9 378 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1997 VL 57 IS 1 BP 130 EP 135 PG 6 WC Oncology SC Oncology GA WA691 UT WOS:A1997WA69100026 PM 8988053 ER PT J AU Knutsen, T AF Knutsen, T TI Cytogenetic mechanisms in the pathogenesis and progression of follicular lymphoma SO CANCER SURVEYS LA English DT Review ID NON-HODGKINS-LYMPHOMA; POLYMERASE CHAIN-REACTION; LARGE-CELL LYMPHOMA; T(14-18) CHROMOSOMAL TRANSLOCATION; BREAKPOINT-CLUSTER REGION; CONSECUTIVELY ASCERTAINED SPECIMENS; COMPARATIVE GENOMIC HYBRIDIZATION; BONE-MARROW TRANSPLANTATION; MALIGNANT-LYMPHOMA; CLINICAL CORRELATIONS RP Knutsen, T (reprint author), NCI,MED BRANCH,EXPT THERAPEUT SECT,CYTOGENET ONCOL LAB,NIH,BLDG 10,ROOM 12N-226,BETHESDA,MD 20892, USA. NR 104 TC 48 Z9 48 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0261-2429 J9 CANCER SURV JI Cancer Surv. PY 1997 VL 30 BP 163 EP 192 PG 30 WC Oncology SC Oncology GA XT528 UT WOS:A1997XT52800011 PM 9547992 ER PT J AU Jaffe, ES Wilson, WH AF Jaffe, ES Wilson, WH TI Lymphomatoid granulomatosis: Pathogenesis, pathology and clinical implications SO CANCER SURVEYS LA English DT Article ID EPSTEIN-BARR-VIRUS; CENTRAL NERVOUS-SYSTEM; POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDERS; ANGIOCENTRIC IMMUNOPROLIFERATIVE LESIONS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; T-CELL LYMPHOMA; HEMOPHAGOCYTIC SYNDROME; MALIGNANT-LYMPHOMA; B-LYMPHOCYTES; PULMONARY C1 NCI,DIV CLIN SCI,MED BRANCH,NIH,BETHESDA,MD 20892. RP Jaffe, ES (reprint author), NCI,DIV CLIN SCI,PATHOL LAB,NIH,BETHESDA,MD 20892, USA. NR 46 TC 104 Z9 109 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0261-2429 J9 CANCER SURV JI Cancer Surv. PY 1997 VL 30 BP 233 EP 248 PG 16 WC Oncology SC Oncology GA XT528 UT WOS:A1997XT52800014 PM 9547995 ER PT J AU OConnor, PM AF OConnor, PM TI Mammalian G(1) and G(2) phase checkpoints SO CANCER SURVEYS LA English DT Review ID P53 TUMOR-SUPPRESSOR; WILD-TYPE P53; DEPENDENT KINASE INHIBITOR; CELL-CYCLE CHECKPOINT; HAMSTER OVARY CELLS; NUCLEOTIDE EXCISION-REPAIR; DNA-DAMAGE; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; NITROGEN-MUSTARD RP OConnor, PM (reprint author), NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892, USA. NR 169 TC 174 Z9 181 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0261-2429 J9 CANCER SURV JI Cancer Surv. PY 1997 VL 29 BP 151 EP 182 PG 32 WC Oncology SC Oncology GA XE569 UT WOS:A1997XE56900009 PM 9338101 ER PT J AU Glaab, WE Tindall, KR AF Glaab, WE Tindall, KR TI Mutation rate at the hprt locus in human cancer cell lines with specific mismatch repair-gene defects SO CARCINOGENESIS LA English DT Article ID MICROSATELLITE INSTABILITY; COLON-CANCER; TUMOR-CELLS; BINDING; HETERODIMER; PHENOTYPES; DEFICIENCY; SEQUENCES; TOLERANCE; EXTRACTS AB Spontaneous mutation rates at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus were measured in human cancer cell lines defective in the mismatch repair (NMR) genes hMLH1, hPMS2, or GTBP, as well as in a cell line carrying mutations in both hMLH1 and hPMS2. The mutation rate was determined by quantitating mutant frequency increases within a single culture as a function of cell division, These MMR-deficient cell lines exhibited a 50- to 750-fold increase in mutation rate relative to a MMR-proficient cancer cell line, From lowest to highest, the spontaneous mutation rates relative to the MMR-gene defects studied here are as follows: hMLH1(-) < GTBP(-) < hPMS2(-) < hMLH1(-)/hPMS2(-). In addition, a cell line in which MMR was restored by chromosome transfer exhibited a mutation rate 12-fold below the MMR-deficient parental cell line. These data support the notion that MMR plays an important role in controlling the rate of spontaneous mutation and suggest that different MMR-gene defects may vary in their ability to repair different types of DNA mismatches, thus leading to measurable quantitative differences in spontaneous mutagenesis, Furthermore, a difference in mutation rates was observed between a hPMS2-defective cell line (3.1 x 10(-5) mutations/ cell/generation) and two hMLH1-defective cell lines (4.0 x 10(-6) and 7.3 x 10(-6) mutations/cell/generation). Assuming the hPMS2- and hMLH1-gene products only function in the proposed hMutL alpha heterodimer, then defects in either gene should yield comparable mutation rates, These data suggest that hPMS2 plays a critical role in MMR, while additional hMLH1 homologues or hPMS2 alone may function to partially complement defects in hMLH1. C1 UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. NIEHS,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,RES TRIANGLE PK,NC 27709. NR 41 TC 102 Z9 102 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 1997 VL 18 IS 1 BP 1 EP 8 DI 10.1093/carcin/18.1.1 PG 8 WC Oncology SC Oncology GA WJ978 UT WOS:A1997WJ97800001 PM 9054582 ER PT J AU Giurgiovich, AJ Diwan, BA Olivero, OA Anderson, LM Rice, JM Poirier, MC AF Giurgiovich, AJ Diwan, BA Olivero, OA Anderson, LM Rice, JM Poirier, MC TI Elevated mitochondrial cisplatin-DNA adduct levels in rat tissues after transplacental cisplatin exposure SO CARCINOGENESIS LA English DT Article ID CHINESE-HAMSTER OVARY; NUCLEAR-DNA; PREFERENTIAL BINDING; SKIN TUMORS; MOUSE; CELLS; CHEMOTHERAPY; DRUG; CARCINOGENICITY; RESISTANT AB Although there is evidence that the toxic effects of cis-diamminedichloroplatinum(II) (cisplatin) include morphologically abnormal mitochondria, direct demonstrations of mitochondrial DNA damage by this chemotherapeutic agent have rarely been reported, Here we show that, in rats exposed to a single dose of cisplatin during gestation, cisplatin-DNA binding levels in both maternal and fetal liver and brain mitochondrial DNA are higher than those observed in genomic DNA, Pregnant F344/NCr rats were injected i.p. with either 5 or 15 mg cisplatin/kg body wt at 18 days of gestation and killed 24 h later, Cisplatin-DNA adducts were determined by dissociation-enhanced lanthanide fluoroimmunoassay using a cisplatin-DNA standard modified in the same range as the biological samples, Values for genomic cisplatin-DNA adducts in multiple maternal and fetal tissues have been presented elsewhere, Here, genomic DNA adduct levels for liver, brain, kidney and placenta are reported again for comparison with mitochondrial DNA adduct levels in the same tissues, In maternal and fetal brain, mitochondrial DNA adduct levels were similar to 7- to 50-fold higher than genomic DNA adduct levels, and in fetal liver they were similar to 2- to 16-fold higher than genomic DNA adduct levels, These studies demonstrate extensive cisplatin-DNA adduct formation in brain and liver mitochondria of fetal rats exposed transplacentally and suggest that mitochondrial DNA in some organs may be a particular target for cisplatin genotoxicity. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BETHESDA,MD 20892. NCI,COMPARAT CARCINOGENESIS LAB,FCRDC,FREDERICK,MD 21701. SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. INT AGCY RES CANC,F-69372 LYON,FRANCE. NR 34 TC 32 Z9 32 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 1997 VL 18 IS 1 BP 93 EP 96 DI 10.1093/carcin/18.1.93 PG 4 WC Oncology SC Oncology GA WJ978 UT WOS:A1997WJ97800013 PM 9054594 ER PT J AU Tomatis, L Huff, J HertzPicciotto, I Sandler, DP Bucher, J Boffetta, P Axelson, O Blair, A Taylor, J Stayner, L Barrett, JC AF Tomatis, L Huff, J HertzPicciotto, I Sandler, DP Bucher, J Boffetta, P Axelson, O Blair, A Taylor, J Stayner, L Barrett, JC TI Avoided and avoidable risks of cancer SO CARCINOGENESIS LA English DT Article ID AIR-POLLUTION; UNITED-STATES; LUNG-CANCER; RESPIRATORY CANCER; DOSE-RESPONSE; ARSENIC EXPOSURE; FOLLOW-UP; MORTALITY; WORKERS; CARCINOGENESIS AB Despite the considerable efforts and funds devoted to cancer research over several decades, cancer still remains a mainly lethal disease, Cancer incidence and mortality have not declined at the same rate as other major causes of death, indicating that primary prevention remains a most valuable approach to decrease mortality, There is general agreement that environmental exposures are variously involved in the causation of the majority of cancer cases and that at least half of all cancers could be avoided by applying existing etiologic knowledge. There is disagreement, however, regarding the proportion of cancer risks. attributable to specific etiological factors, including diet, occupation and pollution, Estimates of attributable risks are largely based today on unverified assumptions and the calculation of attributable risks involves taking very unequal evidence of various types of factors and treating them equally, Effective primary prevention resulting in a reduction of cancer risk can be obtained by: (i) a reduction in the number of carcinogens to which humans are exposed; or (ii) a reduction of the exposure levels to carcinogens, Exposure levels that could be seen as sufficiently low when based on single agents, may actually not be safe in the context of the many other concomitant carcinogenic and mutagenic exposures, The list of human carcinogens and of their target organs might be quite different if: (i) epidemiological data were available for a larger proportion of human exposures for which there is experimental evidence of carcinogenicity; (ii) more attention was paid to epidemiological evidence that is suggestive of an exposure-cancer association, but is less than sufficient, particularly in identifying target organs; and (iii) experimental evidence of carcinogenicity, supported by mechanistic considerations, were more fully accepted as predictions of human risk. C1 NIEHS, RES TRIANGLE PK, NC 27709 USA. UNIV N CAROLINA, SCH PUBL HLTH, DIV EPIDEMIOL, CHAPEL HILL, NC USA. INT AGCY RES CANC, F-69372 LYON 08, FRANCE. LINKOPING UNIV, DEPT OCCUPAT HLTH, S-58183 LINKOPING, SWEDEN. NCI, ENVIRONM EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. NIOSH, CINCINNATI, OH 45226 USA. OI taylor, jack/0000-0001-5303-6398; Sandler, Dale/0000-0002-6776-0018 NR 91 TC 85 Z9 86 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 1997 VL 18 IS 1 BP 97 EP 105 DI 10.1093/carcin/18.1.97 PG 9 WC Oncology SC Oncology GA WJ978 UT WOS:A1997WJ97800014 PM 9054595 ER PT J AU Hussain, SP Kennedy, CH Amstad, P Lui, H Lechner, JF Harris, CC AF Hussain, SP Kennedy, CH Amstad, P Lui, H Lechner, JF Harris, CC TI Radon and lung carcinogenesis: Mutability of p53 codons 249 and 250 to Pu-238 alpha-particles in human bronchial epithelial cells SO CARCINOGENESIS LA English DT Article ID TUMOR-SUPPRESSOR GENE; HEPATOCELLULAR-CARCINOMA; INDUCED MUTAGENESIS; HOTSPOT CODON-248; MUTATION HOTSPOT; URANIUM MINERS; CANCER; RADIATION; LESIONS; RAS AB Radon-222, a decay product of uranium-238 and a source of high linear energy transfer (LET) alpha-particles, has been implicated in the increased risk of lung cancer in uranium miners as well as non-miners, p53 mutation spectrum studies of radon-associated lung cancer have failed to show any specific mutational hot spot with the exception of a single study in which 31% of squamous cell and large cell lung cancers from uranium miners showed a p53 codon 249 AGG(arg) --> ATG(met) mutation. Although the results of laboratory studies indicate that double-strand breaks and deletions are the principal genetic alterations caused by alpha-particles, uncertainty still prevails in the description of DNA damage in radon-associated human lung cancer. In the present study, we have evaluated the mutability of p53 codons 249 and 250 to alpha-particles in normal human bronchial epithelial (NHBE) cells using a highly sensitive genotypic mutation assay, Exposure of NHBE cells to a total dose of 4 Gy (equivalent to similar to 1460 working level months in uranium mining) of high LET alpha-radiation induced codon 249 AGG --> AAG transitions and codon 250 CCC --> ACC transversions with absolute mutation frequencies of 3.6 X 10(-7) and 3.8 x 10(-7) respectively. This mutation spectrum is consistent with our previous report of radon-associated human lung cancer. C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. LOVELACE BIOMED & ENVIRONM RES INST,INHALAT TOXICOL RES INST,ALBUQUERQUE,NM 87185. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. NR 34 TC 19 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 1997 VL 18 IS 1 BP 121 EP 125 DI 10.1093/carcin/18.1.121 PG 5 WC Oncology SC Oncology GA WJ978 UT WOS:A1997WJ97800017 PM 9054598 ER PT J AU Shou, MG Korzekwa, KR Brooks, EN Krausz, KW Gonzalez, FJ Gelboin, HV AF Shou, MG Korzekwa, KR Brooks, EN Krausz, KW Gonzalez, FJ Gelboin, HV TI Role of human hepatic cytochrome P450 1A2 and 3A4 in the metabolic activation of estrone SO CARCINOGENESIS LA English DT Article ID CDNA-DIRECTED EXPRESSION; HUMAN-LIVER-MICROSOMES; BREAST-CANCER-CELLS; SYRIAN-HAMSTERS; COVALENT BINDING; DNA-DAMAGE; ESTROGENS; HYDROXYLATION; CARCINOGENESIS; SEQUENCE AB The metabolic activation of estrone (E1), a potent estrogen was investigated using: recombinant human cytochrome P450 enzymes, 1A2, 2B6, 2C8, 2C9, 2C9(R144C), 2E1, 3A4, 3A5 and liver microsomes from 14 human organ donors, At least five products of E1 were detected and quantitated by HPLC and gas chromatography-mass spectrometry (GC-MS). Among these metabolites, 16 alpha-OH-E1, 2-OH-E1 and 4-OH-E1, which are believed to be associated with estrogen carcinogenesis in animals, were definitively identified. Of all P450s examined, 1A2 and 3A4 exhibited the highest activities with turnovers of 3.4 and 2.5 nmol/min/ nmol P450 for the total metabolism of E1, respectively, while 3A5, 2C9 and 2C9(R144C) showed moderate activities, 2B6, 2E1 and 2C8 did not produce any significant amount of products. 1A2 formed almost exclusively the 2-OH-E1 at a rate of 3.3 nmol/min/nmol but 3A4 preferentially formed the metabolite X1 (an unknown hydroxylation product) and 16 alpha-OH-E1. Kinetic characterization showed that the K-m values of 1A2, 3A4 and 3A5 were 14, 95 and 64 mu M and V-max were 5.43, 0.68 and 0.35 min(-1), respectively. All human liver microsomes were capable of metabolizing estrone and a 4-fold variation was seen between individuals. The relative amount of metabolites formed was generally 2-OH-E1 > metabolite X1 > 4-OH-E1 > 16 alpha-OH-E1 > metabolite X2, 3A4/5 enzyme complex was assessed by inhibitory monoclonal antibody specific for 3A4/5 to contribute 60-88% to the formation of individual metabolites in human liver except for 2-OH-E1 (3%). The formation of 2-OH-E1 and 16 alpha-OH-E1 by 14 human liver microsomes was significantly correlated with caffeine 3-demethylation supported by 1A2 (r(2) = 0.87) and with testosterone 6 beta-hydroxylation by 3A4 (r(2) = 0.66), respectively. Thus the metabolic patterns exhibited by human liver are likely due to the combined activities of the P450 1A2 and 3A4 enzymes. C1 UNIV PITTSBURGH, MED CTR, CTR CLIN PHARMACOL, PITTSBURGH, PA 15217 USA. CLARK ATLANTA UNIV, SCH BIOL, ATLANTA, GA 30314 USA. RP Shou, MG (reprint author), NCI, MOL CARCINOGENESIS LAB, NIH, BLDG 37, BETHESDA, MD 20892 USA. NR 61 TC 97 Z9 101 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 1997 VL 18 IS 1 BP 207 EP 214 DI 10.1093/carcin/18.1.207 PG 8 WC Oncology SC Oncology GA WJ978 UT WOS:A1997WJ97800027 PM 9054608 ER PT J AU Sipowicz, MA Weghorst, CM Shiao, YH Buzard, GS Calvert, RJ Anver, MR Anderson, LM Rice, JM AF Sipowicz, MA Weghorst, CM Shiao, YH Buzard, GS Calvert, RJ Anver, MR Anderson, LM Rice, JM TI Lack of p53 and ras mutations in Helicobacter hepaticus-induced liver tumors in A/JCr mice SO CARCINOGENESIS LA English DT Article ID CHRONIC ACTIVE HEPATITIS; MOUSE-LIVER; PROTOONCOGENE ACTIVATION; LUNG-TUMORS; GASTRIC-CANCER; B6C3F1 MOUSE; GENES; FREQUENCY; SPECTRA; PYLORI AB Helicobacter hepaticus is a recently discovered bacterium that invades mouse liver causing chronic active hepatitis followed by development of preneoplastic hepatocellular foci, hepatocellular adenomas and carcinomas. This establishes a unique animal model for study of the mechanisms of cancer development due to a chronic bacterial infection. A possible mechanism of bacteria-associated tumorigenesis is mutation of oncogenes or tumor suppressor genes. Since mutations in ras oncogenes have been widely detected in a variety of chemically induced and spontaneous mouse liver tumors and specific mutations in the p53 tumor suppressor gene have been associated with human bladder cancers attributed to chronic schistosomal infection, we studied exons 1 and 2 of the N-, K- and H-ras genes and exons 5-8 of the p53 gene for the presence of point mutations in 25 liver tumors from 10 naturally infected A/JCr mice, ranging in age from 16 to 24 months. The 20 adenomas and five carcinomas varied in size from 0.1 to 2.3 cm and arose in livers characterized by a wide assortment of pathological profiles, including hepatitis, inflammation, hyperplasia, hypertrophy, leukocyte infiltration, necrosis and focal phenotypic alteration. DNA samples extracted from formalin-fixed paraffin-embedded tissues were screened by PCR/SSCP analysis and showed no mutations in the analyzed genes. Complete absence of mutations in ras genes in 25 mouse liver tumors is unusual. Other genes may be targeted or H.hepaticus infection causes liver cancer through other pathways than direct damage to DNA. C1 SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. US FDA,OFF SPECIAL NUTR,CLIN RES & REVIEW STAFF,LAUREL,MD. RP Sipowicz, MA (reprint author), NCI,COMPARAT CARCINOGENESIS LAB,FCRDC,FREDERICK,MD 21702, USA. NR 32 TC 26 Z9 27 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 1997 VL 18 IS 1 BP 233 EP 236 DI 10.1093/carcin/18.1.233 PG 4 WC Oncology SC Oncology GA WJ978 UT WOS:A1997WJ97800031 PM 9054612 ER PT B AU Quarles, RH Farrer, RG Yim, SH AF Quarles, RH Farrer, RG Yim, SH BE Juurlink, BHJ Devon, RM Doucette, JR Nazarali, AJ Schreyer, DJ Verge, VMK TI Structure and function of myelin, an extended and biochemically modified cell surface membrane SO CELL BIOLOGY AND PATHOLOGY OF MYELIN: EVOLVING BIOLOGICAL CONCEPTS AND THERAPEUTIC APPROACHES SE ALTSCHUL SYMPOSIA SERIES LA English DT Proceedings Paper CT 4th International Altschul Symposium on Cell Biology and Pathology of Myelin - Evolving Biological Concepts and Therapeutic Approaches CY JUN 27-29, 1996 CL SASKATOON, CANADA SP Altschul Trust Fund RP Quarles, RH (reprint author), NINCDS,MYELIN & BRAIN DEV SECT,MOL & CELLULAR NEUROBIOL LAB,BLDG 49,RM 2A 10 NIH,BETHESDA,MD 20814, USA. NR 0 TC 8 Z9 8 U1 1 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45595-1 J9 ALTSCHUL SY PY 1997 VL 4 BP 1 EP 12 PG 12 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA BJ39H UT WOS:A1997BJ39H00001 ER PT S AU Bassett, DE Boguski, M Hieter, P AF Bassett, DE Boguski, M Hieter, P BE Dunphy, WG TI Identifying human homologs of cell cycle genes using dbEST and XREFdb SO CELL CYCLE CONTROL SE Methods in Enzymology LA English DT Review C1 NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, NIH, BETHESDA, MD 20894 USA. RP Bassett, DE (reprint author), JOHNS HOPKINS UNIV, SCH MED, DEPT MOL BIOL & GENET, BALTIMORE, MD 21205 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182184-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 283 BP 128 EP 140 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ41B UT WOS:A1997BJ41B00010 PM 9251016 ER PT S AU Murakami, MS VandeWoude, GF AF Murakami, MS VandeWoude, GF BE Dunphy, WG TI Mechanisms of Xenopus oocyte maturation SO CELL CYCLE CONTROL SE Methods in Enzymology LA English DT Review ID MOS PROTO-ONCOGENE; MAP KINASE KINASE; C-MOS; MEIOTIC MATURATION; CYTOPLASMIC POLYADENYLATION; CELL-CYCLE; M-PHASE; CATALYTIC SUBUNIT; DNA-REPLICATION; MESSENGER-RNAS RP Murakami, MS (reprint author), NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. NR 71 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182184-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 283 BP 584 EP 600 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ41B UT WOS:A1997BJ41B00044 PM 9251050 ER PT B AU Evans, GA Duhe, RJ Howard, OMZ Kirken, RA Da Silva, L Erwin, R Malabarba, MG Farrar, WL AF Evans, GA Duhe, RJ Howard, OMZ Kirken, RA Da Silva, L Erwin, R Malabarba, MG Farrar, WL BE Ruffolo, RR Poste, G Metcalf, BW TI Cytokine driven signal transmission SO CELL CYCLE REGULATION SE NEW HORIZONS IN THERAPEUTICS: SMITHKLINE BEECHAM PHARMACEUTICALS U.S. RESEARCH SYMPOSIA SERIES LA English DT Proceedings Paper CT 8th SmithKline-Beecham-Pharmaceuticals United-States Research Symposium on Cell Cycle Regulation CY NOV, 1995 CL KING OF PRUSSIA, PA SP SmithKline Beecham Pharm C1 NCI, BCDP, FCRDC, Frederick, MD 21702 USA. RP Evans, GA (reprint author), NCI, BCDP, FCRDC, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU HARWOOD ACADEMIC PUBL GMBH PI CHUR PA POSTSTRASSE 22, 7000 CHUR, SWITZERLAND BN 90-5702-204-4 J9 N HOR TH SK&B PH US PY 1997 VL 1 BP 91 EP 116 PG 26 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BK53R UT WOS:000072477200007 ER PT J AU Luo, G Zhang, JQ Nguyen, TP Herrera, AH Paterson, B Horowits, R AF Luo, G Zhang, JQ Nguyen, TP Herrera, AH Paterson, B Horowits, R TI Complete cDNA sequence and tissue localization of N-RAP, a novel nebulin-related protein of striated muscle SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE N-RAP; nebulin; mouse; skeletal muscle ID SKELETAL-MUSCLE; MONOCLONAL-ANTIBODIES; ACTIN-FILAMENTS; THIN-FILAMENTS; LIM DOMAIN; Z-LINE; SARCOMERE; VERTEBRATE; FRAGMENTS; CLONING AB We have cloned and sequenced the full-length cDNA of N-RAP, a novel nebulin-related protein, from mouse skeletal muscle. The N-RAP message is specifically expressed in skeletal and cardiac muscle, but is not detected by Northern blot in non-muscle tissues. The full-length N-RAP cDNA contains an open reading frame of 3,525 base pairs which is predicted to encode a protein of 133 kDa. A 587 amino acid region near the C-terminus is 45 % identical to the actin binding region of human nebulin, containing more than 2 complete 245 residue nebulin super repeats. The N-terminus contains the consensus sequence of a cysteine-rich LIM domain, which may function in mediating protein-protein interactions. These data suggest that the encoded protein may link actin filaments to some other proteins or structure. We expressed full-length N-RAP in Escherichia coli, as well as the nebulin-like super repeat region of N-RAP (N-RAP-SR) and the region between the LIM domain and N-RAP-SR (N-RAP-IB). An anti-N-RAP antibody raised against a 30 amino acid peptide corresponding to sequence from N-RAP-IB detected recombinant N-RAP and N-RAP-IB, but failed to detect N-RAP-SR. This antibody specifically identified a 185 kDa band as N-RAP on immunoblots of mouse skeletal and cardiac muscle proteins. In an assay of actin binding to electrophoresed and blotted proteins, we detected significant actin binding to expressed nebulin super repeats and N-RAP-SR, but only a trace amount of binding to N-RAP-IB. In immunofluorescence experiments, N-RAP was found to be localized at the myotendinous junction in mouse skeletal muscle and at the intercalated disc in cardiac muscle. Based on its domain organization, actin binding properties, and tissue localization, we propose that N-RAP play role in anchoring the terminal actin filaments in the myofibril to the membrane and may be important in transmitting tension from the myofibrils to the extracellular matrix. (C) 1997 Wiley-Liss, Inc. C1 NIAMSD, NIH, BETHESDA, MD 20892 USA. NCI, NIH, BETHESDA, MD 20892 USA. NR 42 TC 60 Z9 62 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PY 1997 VL 38 IS 1 BP 75 EP 90 PG 16 WC Cell Biology SC Cell Biology GA XU161 UT WOS:A1997XU16100007 PM 9295142 ER PT S AU Hallett, M Grafman, J AF Hallett, M Grafman, J BE Schmahmann, JD TI Executive function and motor skill learning SO CEREBELLUM AND COGNITION SE International Review of Neurobiology LA English DT Review ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; CEREBELLAR DEGENERATION; PREFRONTAL CORTEX; COGNITIVE-PROCESSES; PARKINSONS-DISEASE; FRONTAL-LOBE; ADAPTATION; IMPLICIT; LESIONS C1 NINCDS, COGNIT NEUROSCI SECT, MED NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Hallett, M (reprint author), NINCDS, HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH, BLDG 36, RM 4D04, BETHESDA, MD 20892 USA. NR 83 TC 42 Z9 43 U1 1 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 0-12-625660-8; 0-12-366841-7 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 1997 VL 41 BP 297 EP 323 PG 27 WC Neurosciences SC Neurosciences & Neurology GA BJ66A UT WOS:A1997BJ66A00013 PM 9378593 ER PT S AU Magrath, IT AF Magrath, IT BE Holmes, FF Kepes, JJ Vats, TS Schuler, D Nyary, I TI Non-Hodgkin's lymphomas: Epidemiology and treatment SO CHALLENGES AND OPPORTUNITIES IN PEDIATRIC ONCOLOGY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Challenges and Opportunities in Pediatric Oncology CY OCT 06-09, 1996 CL BUDAPEST, HUNGARY SP New York Acad Sci, Univ Kansas Med Ctr, Pediat Oncol Outreach Hungary Program, US Agcy Int Dev ID EPSTEIN-BARR-VIRUS; ACUTE LYMPHOBLASTIC-LEUKEMIA; COMBINED MODALITY TREATMENT; AMERICAN BURKITTS-LYMPHOMA; CHILDRENS CANCER GROUP; B-CELL LEUKEMIA; PEDIATRIC-ONCOLOGY; COMBINATION CHEMOTHERAPY; NUCLEAR ANTIGEN-1; RANDOMIZED TRIAL RP Magrath, IT (reprint author), NCI,LYMPHOMA BIOL SECT,PEDIAT BRANCH,NIH,10 CTR DR,MSC 1928,BLDG 10-13N240,BETHESDA,MD 20892, USA. NR 107 TC 8 Z9 9 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 1-57331-082-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 824 BP 91 EP 106 DI 10.1111/j.1749-6632.1997.tb46212.x PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BJ67W UT WOS:A1997BJ67W00008 PM 9382459 ER PT J AU Amouzadeh, HR Bourdi, M Martin, JL Martin, BM Pohl, LR AF Amouzadeh, HR Bourdi, M Martin, JL Martin, BM Pohl, LR TI UDP-glucose:glycoprotein glucosyltransferase associates with endoplasmic reticulum chaperones and its activity is decreased in vivo by the inhalation anesthetic halothane SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID PROTEIN DISULFIDE-ISOMERASE; RAT-LIVER; MOLECULAR CHAPERONES; HEPATITIS PATIENTS; SERUM ANTIBODIES; STRESS PROTEIN; IMMUNOGLOBULIN; BIP; CARBOXYLESTERASE; HEPATOCYTES AB Halothane causes an idiosyncratic hepatitis that is thought to result, in part, from immune reactions against one or more lumenal endoplasmic reticulum (ER) proteins that have been covalently modified by the trifluoroacetyl chloride metabolite of halothane. In this study, we have identified a 170 kDa protein target of halothane in the liver of rats. The 170 kDa protein was first detected when proteins in lysates of hepatocytes from halothane-treated rats were immunoprecipitated with antisera against several resident ER proteins. This 170 kDa protein was found to be associated with other protein targets of halothane, including protein disulfide isomerase, a protein disulfide isomerase isoform, a 59 kDa carboxylesterase, and 78 kDa glucose-regulated protein. Immunoblotting with antiserum directed against the trifluoroacetylated hapten indicated that the 170 kDa protein was trifluoroacetylated. Based upon its subcellular localization, molecular mass, N-terminal amino acid sequence, and antigenicity, the trifluoroacetylated 170 kDa protein was identified as UDP-glucose:glycoprotein glucosyltransferase (UGGT), a lumenal ER protein that is thought to have a role in the folding of N-linked glycoproteins. Moreover, treatment of rats with halothane caused a 44% decrease in the activity of liver microsomal UGGT, and at least 36% of the change in the activity of the enzyme could be due to a decrease in the level of the protein. The results suggest that the function of UGGT in folding of N-linked glycoproteins may be affected by other resident ER proteins or xenobiotics such as halothane. C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21287. NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. RP Amouzadeh, HR (reprint author), NHLBI,MOL & CELLULAR TOXICOL SECT,LAB MOL IMMUNOL,NIH,BLDG 10,ROOM 8N110,BETHESDA,MD 20892, USA. NR 30 TC 12 Z9 12 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 1997 VL 10 IS 1 BP 59 EP 63 DI 10.1021/tx9601364 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA WD805 UT WOS:A1997WD80500008 PM 9074803 ER PT J AU Pelkonen, P Lang, MA Negishi, M Wild, CP Juvonen, RO AF Pelkonen, P Lang, MA Negishi, M Wild, CP Juvonen, RO TI Interaction of aflatoxin B-1 with cytochrome P450 2A5 and its mutants: Correlation with metabolic activation and toxicity SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; HUMAN-LIVER; COUMARIN 7-HYDROXYLASE; AMINO-ACID; STEROID 15-ALPHA-HYDROXYLASE; II P-45015-ALPHA; CYP2A ENZYMES; MOUSE; EXPRESSION; CDNA AB Among members of the mouse cytochrome P450 2A family, P450 2A5 is the best catalyst-of anatoxin B-1 (AFB(1)) oxidation to its 8,9-epoxide (Pelkonen, P., Lang, M., Wild, C. P., Negishi, M., and Juvonen, R. O. (1994) fur. J. Pharmacol., Environ. Toxicol. Pharmacol. Sect. 292, 67-73). Here we studied the role of amino acid residues 209 and 365 of the P450 2A5 in the metabolism and toxicity of AFB(1) using recombinant yeasts. The two sites have previously been shown to be essential in the interaction of coumarin and steroids with the P450 2A5. Reducing the size of the amino acid at position 209 or introducing a negatively charged residue at this site increased the 8,9-epoxidation of AFB(1) compared to the wild type. In addition, replacing the hydrophobic amino acid at the 365 position with a positively charged lysine residue strongly decreased the metabolism of AFB(1). These mutations changed the KM values generally less than the V-max values. The changes in AFB(1) metabolism contrast with the changes in coumarin 7-hydroxylation caused by these amino acid substitutions, since reducing the size of the 209 residue strongly reduced coumarin metabolism and increased the KM values. On the other hand, the results with AFB(1) are similar to those obtained with steroid hydroxylation. This suggests that the size of the substrate is important when interacting with the residue 209 of the protein. The catalytic parameters of AFB(1) correlated generally with its toxicity to the recombinant yeasts expressing the activating enzyme and with the binding of AFB(1) to yeast DNA. Furthermore high affinity substrates and inhibitors (e.g., methoxsalen, metyrapone, coumarin 311, 7-methylcoumarin, coumarin, and pilocarpine) of P450 2A5 could efficiently block the toxicity of AFB(1). It is suggested that the recombinant yeasts expressing engineered P450 enzymes are a useful model to understand the substrate protein interactions, to study the relationship of metabolic parameters to toxicity, and to test potential inhibitors of metabolism based toxicity. C1 UNIV KUOPIO,DEPT PHARMACOL & TOXICOL,FIN-70211 KUOPIO,FINLAND. INT AGCY RES CANC,F-69372 LYON 08,FRANCE. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. UNIV LEEDS,RES SCH MED,MOL EPIDEMIOL UNIT,LEEDS LS16 6BG,W YORKSHIRE,ENGLAND. RI Lang, Matti/C-9948-2009 FU NIEHS NIH HHS [01ES06052] NR 33 TC 30 Z9 32 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 1997 VL 10 IS 1 BP 85 EP 90 DI 10.1021/tx960078m PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA WD805 UT WOS:A1997WD80500012 PM 9074807 ER PT B AU Milstien, S Bonner, TI AF Milstien, S Bonner, TI BE Pfleiderer, W Rokos, H TI Cloning of rat cDNA and the human gene for GTP cyclohydrolase I feedback regulatory protein, GFRP SO CHEMISTRY AND BIOLOGY OF PTERIDINES AND FOLATES 1997 LA English DT Proceedings Paper CT 11th International Symposium on Pteridines and Folates CY JUN 15-20, 1997 CL BERCHTESGADEN, GERMANY SP 10th Pterdine Symp 1993, Orange Beach, US, Seoul Natl Univ, Seoul, Korea, Swissair, Zurich, Switzerland, Eli Lilly Inc, Indianapolis, US, Schircks Labs, Jona, Switzerland, Hoffmann La Roche Ltd, Basel, Switzerland, BRAHNS Diagnost GmbH, Berlin, Germany, Int Soc Pteridinol, Graz, Austria, Novartis AG, Basel, Switzerland, Merrell Pharm Inc, Kansas City, US, Hoffmann LaRoche Ltd, Nutley, US, Hoechst Marion Roussell Inc, Cincinnati, US, Henning Berlin GmbH, Berlin, Germany, Milupa AG, Friedrichsdorf, Germany, Nigu Chemie GmbH, Waldkraiburg, Germany, Eprova AG, Schaffhausen, Switzerland, Cerbios Pharma S A, Lugano, Switzerland, Blackwell Wissensch Verlag GmbH, Berlin, Germany, Pfizer Inc, Groton, US, Dr Karl Thomae, Biberach, Germany, Byk Gulden Lomberg, Konstanz, Germany, Bayer Ag, Leverkusen, Germany, Grunenthal GmbH, Stolberg, Germany, Hoechst Marion Roussell, Frankfurt, Germany, Bristol Myers Squibb, Princeton, US, Merck AG, Darmstadt, Germany, Boehringer Mannheim, GmbH, Mannheim, Germany, Cyanamid Forsch, Schwabenheim, Germany RP Milstien, S (reprint author), NIMH,LAB CELLULAR & MOL REGULAT,NIH,BLDG 36,RM 3A-17,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL WISSENSCHAFTS-VERLAGGMBH PI BERLIN PA KURFURSTENDAMM 57, 10707 BERLIN, GERMANY BN 3-8263-3185-0 PY 1997 BP 547 EP 552 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA BJ89N UT WOS:A1997BJ89N00107 ER PT S AU Becerra, SP AF Becerra, SP BE Church, FC Cunningham, DD Ginsburg, D Hoffman, M Stone, SR Tollefsen, DM TI Structure-function studies on PEDF - A noninhibitory serpin with neurotrophic activity SO CHEMISTRY AND BIOLOGY OF SERPINS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Symposium on the Chemistry and Biology of Serpins CY APR 13-16, 1996 CL CHAPEL HILL, NORTH CAROLINA ID EPITHELIUM-DERIVED FACTOR; PIGMENT EPITHELIUM; INTERPHOTORECEPTOR MATRIX; ESCHERICHIA-COLI; HEPARIN-COFACTOR; CELL-SURVIVAL; RETINOBLASTOMA; DIFFERENTIATION; IDENTIFICATION; EXPRESSION C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Becerra, SP (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bldg 6,Room 308,6 Ctr Dr MSC 2740, Bethesda, MD 20892 USA. NR 28 TC 80 Z9 84 U1 0 U2 2 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45698-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 425 BP 223 EP 237 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BK17U UT WOS:000071428500021 PM 9433504 ER PT S AU Murphy, PM AF Murphy, PM BE Horuk, R TI Calcium flux assay of chemokine receptor expression in Xenopus oocytes SO CHEMOKINE RECEPTORS SE Methods in Enzymology LA English DT Review ID HUMAN INTERLEUKIN-8 RECEPTOR; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; MESSENGER-RNA; CDNA; TRANSLATION; PROTEIN; BETA RP Murphy, PM (reprint author), NIAID, LAB HOST DEF, NIH, BETHESDA, MD 20892 USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182189-7 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 288 BP 108 EP 117 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ78J UT WOS:A1997BJ78J00008 PM 9356990 ER PT J AU Taub, DD Key, ML Longo, DL Murphy, WJ AF Taub, DD Key, ML Longo, DL Murphy, WJ TI Chemokine-induced human lymphocyte infiltration and engraftment in huPBL-SCID mice SO CHEMOKINES SE METHODS IN ENZYMOLOGY LA English DT Review ID HUMAN T-LYMPHOCYTES; SEVERE COMBINED IMMUNODEFICIENCY; INTERFERON-INDUCIBLE PROTEIN-10; EXTRACELLULAR-MATRIX PROTEINS; COMBINED IMMUNE-DEFICIENCY; GROWTH-HORMONE; IN-VITRO; PERIPHERAL-TISSUES; ENDOTHELIAL-CELLS; MIGRATION C1 SAIC FREDERICK,FREDERICK,MD 21702. RP Taub, DD (reprint author), NIA,NIH,BALTIMORE,MD 21224, USA. NR 43 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 287 BP 265 EP 291 PG 27 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ75A UT WOS:A1997BJ75A00018 PM 9330328 ER PT J AU Vaaler, AK Forrester, JM Lesar, M Edison, M Venzon, D Johnson, BE AF Vaaler, AK Forrester, JM Lesar, M Edison, M Venzon, D Johnson, BE TI Obstructive atelectasis in patients with small cell lung cancer - Incidence and response to treatment SO CHEST LA English DT Article DE carcinoma, small cell; combination chemotherapy; lung neoplasm; radiation ID SUPERIOR VENA-CAVA; RADIATION-THERAPY; CHEMOTHERAPY; CARCINOMA; STAGE AB Study objectives: Define the incidence of obstructive atelectasis in patients Design: Retrospective review of clinical records and radiographic studies. Setting: Single federal government institution-the National Cancer Institute-Naval Medical Oncology Branch. Patients: One hundred seventy-two consecutive patients treated between 1983 and 1993. Interventions: Patients presenting with obstructive atelectasis were identified, The incidence of dyspnea, cough, and sputum production before starting treatment and 1, 3, and 6 months later was determined. Fiberoptic bronchoscopy and chest radiographs performed before starting treatment were compared with those obtained later in the patients' clinical course. Measurements ana results: Thirty-seven of 172 (22%) patients had obstructive atelectasis, Initial symptoms included cough in 25 (68%), dyspnea in 24 (65%), and productive cough in 10 (27%), The patients' symptoms of cough, dyspnea, and sputum production decreased to one third of the initial prevalence 1 month after the start of treatment. Fiberoptic bronchoscopy and chest radiographs performed 3 months after starting treatment demonstrated bronchial patency in 90%. Conclusions. Obstructive atelectasis occurs in approximately one fifth of patients presenting with small cell lung cancer. Chemotherapy and chemotherapy plus chest radiotherapy lead to symptomatic, bronchoscopic, and radiographic resolution in similar proportions of patients with obstructive atelectasis. C1 NATL NAVAL MED CTR, NCI, MED ONCOL BRANCH, BETHESDA, MD 20889 USA. NATL NAVAL MED CTR, DEPT INTERNAL MED, BETHESDA, MD 20889 USA. NATL NAVAL MED CTR, DEPT RADIOL, BETHESDA, MD 20889 USA. NCI, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 14 TC 17 Z9 18 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JAN PY 1997 VL 111 IS 1 BP 115 EP 120 DI 10.1378/chest.111.1.115 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA WC114 UT WOS:A1997WC11400026 PM 8996004 ER PT J AU Horowitz, LA Putnam, FW Noll, JG Trickett, PK AF Horowitz, LA Putnam, FW Noll, JG Trickett, PK TI Factors affecting utilization of treatment services by sexually abused girls SO CHILD ABUSE & NEGLECT LA English DT Article DE child sexual abuse; treatment; therapy dropout ID CHILD-PSYCHIATRY; FAMILIES; THERAPY; PSYCHOTHERAPY; SYMPTOMS AB This study describes the naturalistic therapy experiences of a sample of sexually abused girls and the relationship of these experiences to demographic factors, abuse experiences, psychopathology, and family functioning. The sample consisted of 81 sexually abused girls, aged 6 to 16, participating in a longitudinal study of the effects of sexual abuse. Results indicated strong effects for abuse experiences and child psychopathology on the total amount of therapy received. Patterns of treatment utilization were associated with ethnic minority status, but these differences are confounded by differing abuse experiences for racial groups in the sample. Other patterns of treatment utilization are discussed, as well as issues for further research and implications for treatment providers. 1996 Elsevier Science Ltd C1 UNIV SO CALIF,LOS ANGELES,CA. RP Horowitz, LA (reprint author), NIMH,UNIT DEV TRAUMATOL,15 N DR MSC 2668,BLDG 15K,BETHESDA,MD 20892, USA. NR 33 TC 22 Z9 23 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD JAN PY 1997 VL 21 IS 1 BP 35 EP 48 DI 10.1016/S0145-2134(96)00129-9 PG 14 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA VZ696 UT WOS:A1997VZ69600004 PM 9023021 ER PT J AU Lucey, DR Pinto, LA Bethke, FR Rusnak, J Melcher, GP Hashemi, FN Landay, AL Kessler, HA Paxton, RJ Grabstein, K Shearer, GM AF Lucey, DR Pinto, LA Bethke, FR Rusnak, J Melcher, GP Hashemi, FN Landay, AL Kessler, HA Paxton, RJ Grabstein, K Shearer, GM TI In vitro immunologic and virologic effects of interleukin 15 on peripheral blood mononuclear cells from normal donors and human immunodeficiency virus type 1-infected patients SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID ACTIVATED KILLER-CELLS; BETA-CHAIN; NK-CELLS; IN-VITRO; LYMPHOKINE; INFECTION; PROLIFERATION; INDIVIDUALS; INDUCTION; RECEPTOR AB Interleukin 15 (IL-15) is a cytokine that shares receptor subunits and functional activity, such as T-cell and B-cell stimulation, with IL-2. The effect of IL-2 on immune function and human immunodeficiency virus (HIV) viral load in HIV-infected patients is being actively studied. Thus, we examined how IL-15 compares with IL-2 in several in vitro immunologic and virologic assays in order to explore whether a rationale exists for pursuing initial clinical therapeutic trials With IL-15. The effects of IL-15 on induction of lymphokine-activated killer (Wt) cells, gamma interferon (IFN-gamma) production from HN-positive peripheral blood mononuclear cells (PBMCs), and HIV production from PBMCs were studied. Induction of Wt cells by IL-15 was found in eight of eight HIV positive donors. Incubation of PBMCs from some donors with IL-15 (1, 10, 50, and 100 ng/ml) induced production of IFN-gamma. The effect of IL-15 was compared with that of IL-2 on HIV replication in PBMCs from five HIV-positive patients and four HIV-negative donors whose PBMCs were infected in vitro with HIV. Levels of HIV p24 antigen were moderately lower in the presence of 10 ng of IL-15 per mi than with 10 ng of IL-2 per mi, but they were similar for 100 and 500 ng of each cytokine per mi. In summary, IL-15 can induce LAK cell activity in HIV-seropositive patients and can stimulate IFN-gamma production from PBMCs of some donors. IL 15 stimulates levels of HIV production from PBMCs which are similar to or moderately lower than those obtained with IL-2, depending on cytokine concentration. C1 NCI, EXPT IMMUNOL BRANCH, NIH, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC DYNCORP, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. WILFORD HALL USAF MED CTR, SAN ANTONIO, TX 78236 USA. RUSH MED COLL, CHICAGO, IL 60612 USA. IMMUNEX CORP, SEATTLE, WA USA. NR 28 TC 20 Z9 21 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JAN PY 1997 VL 4 IS 1 BP 43 EP 48 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WB629 UT WOS:A1997WB62900008 PM 9008279 ER PT J AU Jose, PA Drago, J Accili, D Eisner, GM Felder, RA AF Jose, PA Drago, J Accili, D Eisner, GM Felder, RA TI Transgenic mice to study the role of dopamine receptors in cardiovascular function SO CLINICAL AND EXPERIMENTAL HYPERTENSION LA English DT Article; Proceedings Paper CT 6th International Conference on Peripheral Dopamine CY JUN 28-JUL 01, 1996 CL UNIV CAMERINO, CAMERINO, ITALY HO UNIV CAMERINO DE dopamine receptor subtypes; hypertension; transgenic animals; sodium excretion ID SPONTANEOUSLY HYPERTENSIVE RATS; GLUTAMYL-L-DOPA; K+-ATPASE ACTIVITY; PROXIMAL TUBULE; ANGIOTENSIN-II; GENETIC-HYPERTENSION; SODIUM-EXCRETION; RENAL RESPONSE; ACTIVATION; RELEASE AB Dopamine, an intrarenal regulator of sodium transport, is important in the pathogenesis of hypertension. The transduction of D-1-like receptors in renal proximal tubules is defective in animal models of genetic hypertension. The defect is associated with an impaired regulation of proximal tubular sodium transport and cosegregates with hypertension in rats. Moreover, mice lacking one or both D-1A receptor alleles develop hypertension. Extrasynaptic D-3 receptors in renal tubules and juxtaglomerular cells may also regulate renal sodium transport and renin secretion while presynaptic D-3 receptors may act as autoreceptors to inhibit neural norepinephrine release. Mice lacking one or both D-3 alleles have elevated systolic blood pressure and developed diastolic hypertension. Although basal urine flow, sodium excretion, and glomerular filtration rate are similar, mice homozygous to the D-3 receptor have an impaired ability to excrete an acute saline load compared to heterozygous and wild type mice. These studies suggest that abnormalities in dopamine receptor genes or their regulation may lead to the development of hypertension via different pathogenetic mechanisms. C1 MONASH UNIV, DEPT ANAT, CLAYTON, VIC 3168, AUSTRALIA. NIDKD, DIABET BRANCH, BETHESDA, MD 20892 USA. GEORGETOWN UNIV, MED CTR, DEPT MED, WASHINGTON, DC 20007 USA. UNIV VIRGINIA, CTR HLTH SCI, DEPT PATHOL, CHARLOTTESVILLE, VA 22908 USA. RP Jose, PA (reprint author), GEORGETOWN UNIV, CHILDRENS MED CTR, WASHINGTON, DC 20007 USA. FU NHLBI NIH HHS [HL23081]; NIDDK NIH HHS [DK39308, DK44756] NR 61 TC 9 Z9 9 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1963 J9 CLIN EXP HYPERTENS JI Clin. Exp. Hypertens. PD JAN-FEB PY 1997 VL 19 IS 1-2 BP 15 EP 25 DI 10.3109/10641969709080801 PG 11 WC Pharmacology & Pharmacy; Peripheral Vascular Disease SC Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA WE938 UT WOS:A1997WE93800003 PM 9028632 ER PT J AU Goldstein, DS Holmes, C AF Goldstein, DS Holmes, C TI Metabolic fate of the sympathoneural imaging agent 6-[F-18]fluorodopamine in humans SO CLINICAL AND EXPERIMENTAL HYPERTENSION LA English DT Article; Proceedings Paper CT 6th International Conference on Peripheral Dopamine CY JUN 28-JUL 01, 1996 CL UNIV CAMERINO, CAMERINO, ITALY HO UNIV CAMERINO DE fluorodopamine; sympathetic nervous system; catecholamines; positron emission tomography ID CARDIAC SYMPATHETIC INNERVATION AB We examined the metabolism of 6-[F-18]fluorodopamine, by assaying arterial plasma concentrations of radioactivity, 6-[F-18]fluorodopamine, and 6-[F-18]fluorodopamine metabolites in untreated subjects or subjects given desipramine to block neuronal uptake of catecholamines or tyramine to displace vesicular amines. After the 3-min 6-[F-18]fluorodopamine infusion, plasma 6-[F-18]fluorodopamine levels declined precipitously, total radioactivity declining slowly. After 30 min, the main identified metabolite was 6-[F-18]fluorodopamine-sulfate. Desipramine attenuated the rapid increase in plasma 6-[F-18]fluorodihydroxyphenylacetic acid levels, and tyramine briefly increased 6-[F-18]fluorodopamine levels. Neither drug affected 6-[F-18]fluorodopamine-sulfate levels. The results indicate that soon after 6-[F-18]fluorodopamine infusion, plasma radioactivity corresponds mainly to 6-[F-18]fluorodopamine metabolites; that sympathetic nerves rapidly remove 6-[F-18]fluorodopamine, which then undergoes oxidative deamination in the neuronal cytoplasm and sequestration in sympathetic vesicles; and that sulfoconjugation of [F-18]fluorodopamine occurs extraneuronally. RP Goldstein, DS (reprint author), NINCDS,CLIN NEUROSCI BRANCH,NIH,BLDG 10,ROOM 6N252,10 CTR DR,MSC-1424,BETHESDA,MD 20892, USA. NR 4 TC 22 Z9 22 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1064-1963 J9 CLIN EXP HYPERTENS JI Clin. Exp. Hypertens. PD JAN-FEB PY 1997 VL 19 IS 1-2 BP 155 EP 161 DI 10.3109/10641969709080812 PG 7 WC Pharmacology & Pharmacy; Peripheral Vascular Disease SC Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA WE938 UT WOS:A1997WE93800014 PM 9028643 ER PT J AU Udey, MC AF Udey, MC TI Cadherins and Langerhans cell immunobiology SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT Symposium on New Frontiers in the Immunobiology of the Skin and Recent Advances in Cellular Reconstruction and Genetic Engineering CY MAR 29-30, 1996 CL SAN DIEGO, CA DE adhesion; cadherins; immunobiology; Langerhans cells; skin ID MOLECULE E-CADHERIN; DENDRITIC CELLS; ADHESION MOLECULE; CONTACT SENSITIVITY; PEMPHIGUS-VULGARIS; LEISHMANIA-MAJOR; PROTEIN ANTIGENS; LYMPH-NODES; T-CELLS; EXPRESSION AB Langerhans cells represent the epidermal contingent of a family of potent accessory cells termed 'dendritic cells'. Langerhans cells (and perhaps related cells in the dermis) are thought to be required for immune responses directed against foreign antigens and neoantigens that are encountered in skin. The 'life cycle' of the Langerhans cell is characterized by at least two distinct stages. Langerhans cells in epidermis (the 'sentinels') can ingest particulates and process antigens efficiently, but are weak stimulators of unprimed T cells. In contrast, Langerhans cells that have been induced to migrate to lymph nodes after contact with antigen in epidermis (the 'messengers') are not phagocytic and have limited antigen-processing capabilities, but are potent stimulators of naive T cells. If Langerhans cells are to fulfil both their 'sentinel' and 'messenger' roles, they must be able to persist in epidermis for considerable periods, and also be able to exit epidermis in a controlled fashion after exposure to antigen. Thus, regulation of Langerhans cell-keratinocyte adhesion represents a key control point in Langerhans cell trafficking and function. Langerhans cells express E-cadherin, a homophilic adhesion molecule that is prominently represented in epithelia. Keratinocytes also express this adhesion molecule, and E-cadherin clearly mediates adhesion of murine Langerhans cells to keratinocytes in vitro. We presume that E-cadherin is involved in the localization of Langerhans cells in epidermis. Murine thymocytes also express E-cadherin early in the course of their development, and it is likely that E-cadherin plays an as yet uncharacterized role in thymocyte-thymic epithelial cell adhesion and in T-cell development. Recently, it has also been demonstrated that some cutaneous T-cell lymphoma cell lines are E-cadherin(+), so E-cadherin may also mediate clinically important leucocyte-epithelial interactions in disease states. RP Udey, MC (reprint author), NCI, DERMATOL BRANCH, NIH, BLDG 10, ROOM 12N254, BETHESDA, MD 20892 USA. NR 32 TC 52 Z9 57 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 1997 VL 107 SU 1 BP 6 EP 8 PG 3 WC Immunology SC Immunology GA WE211 UT WOS:A1997WE21100004 PM 9020928 ER PT J AU Trent, JM Bittner, MH Zhang, J Wiltshire, R Ray, M Su, Y Gracia, E Meltzer, P DeRisi, J Penland, L Brown, P AF Trent, JM Bittner, MH Zhang, J Wiltshire, R Ray, M Su, Y Gracia, E Meltzer, P DeRisi, J Penland, L Brown, P TI Use of microgenomic technology for analysis of alterations in DNA copy number and gene expression in malignant melanoma SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT Symposium on New Frontiers in the Immunobiology of the Skin and Recent Advances in Cellular Reconstruction and Genetic Engineering CY MAR 29-30, 1996 CL SAN DIEGO, CA DE gene expression; genomics; melanoma ID COMPARATIVE GENOMIC HYBRIDIZATION; PRIMARY CUTANEOUS MELANOMA; TUMOR-SUPPRESSOR GENES; CHROMOSOME MICRODISSECTION; TUMORIGENICITY; PROGRESSION; CANCER; CELLS; HETEROZYGOSITY; IDENTIFICATION AB Chromosome abnormalities in human malignancies have identified the genomic location of several important growth-regulatory genes, including cellular oncogenes and tumour suppressor genes. Melanomas are characterized by recurring chromosome alterations, and it is important to identify those genes whose altered expression may be causally related to melanocytic transformation. This short report presents an overview of strategies used which combine the materials and technologies of the Human Genome Project with clinically directed studies of melanoma biology. The Human Genome Project combines various technologies, including cytogenetic, physical mapping, genetic mapping and DNA sequencing, in order to identify all of the human genes, but especially the 4000 estimated to contribute to human disease. This report focuses first on advances in genome technology that provide information on chromosome rearrangements and DNA copy number changes. This includes a discussion of chromosome microdissection as well as the microexcision of tissue specimens to gain insights into chromosome regions altered in association with melanocyte transformation. Next, there is a brief discussion of the generation and characterization of subtracted cDNA sublibraries which allow the identification of genes uniquely expressed in association with the transformed phenotype of human melanoma cells. Finally, we briefly discuss the feasibility of using a recently developed system for parallel examination of multiple genes based upon robotic printing of cDNAs on glass slides, and simultaneous two-colour fluorescence hybridization to study the expression patterns of cDNAs for their association with melanoma tumour suppression. The combination of these varied molecular technologies may provide insights into previously unrecognized genes involved causally in the pathobiology of this important neoplasm, and may provide new targets for clinical intervention. C1 STANFORD UNIV,MED CTR,DEPT BIOCHEM,STANFORD,CA 94305. RP Trent, JM (reprint author), NATL CTR HUMAN GENOME RES,CANC GENET LAB,NIH,49 CONVENT DR,MSC 4470,ROOM 4A22,BETHESDA,MD 20892, USA. NR 41 TC 17 Z9 17 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 1997 VL 107 SU 1 BP 33 EP 40 PG 8 WC Immunology SC Immunology GA WE211 UT WOS:A1997WE21100010 PM 9020934 ER PT J AU Morgan, RA AF Morgan, RA TI Gene therapy for HIV infection SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT Symposium on New Frontiers in the Immunobiology of the Skin and Recent Advances in Cellular Reconstruction and Genetic Engineering CY MAR 29-30, 1996 CL SAN DIEGO, CA DE AIDS; antisense RNA; retroviral vector; transdominant Rev ID AIDS; TYPE-1; EPIDEMIOLOGY; INHIBITION AB HIV-1 is the causative agent of acquired immune deficiency syndrome (AIDS) and is a major international health concern. The limited effectiveness of current antiviral therapies has led to the search for alternative treatments. One emerging field of medical treatment is termed human gene therapy. In principle, human gene therapy calls for the engineering of the cells from a medical patient with an agent that can potentially result in a therapeutic benefit to the patient. It has been suggested that gene therapy technology may be applied as an anti-HIV-1 agent. The term 'intracellular immunization' was suggested for strategies that work within a potential HIV-1 target cell to inhibit the productive infection of that cell by HIV-1. Various strategies based on this intracellular approach have been proposed and include the use of antisense, and transdominant HIV proteins. Both of these approaches can inhibit HIV-1 in vitro and a clinical trial has been proposed to test their effectiveness in vivo. RP Morgan, RA (reprint author), NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,NIH,BLDG 10,ROOM 10C103,BETHESDA,MD 20892, USA. NR 12 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 1997 VL 107 SU 1 BP 41 EP 44 PG 4 WC Immunology SC Immunology GA WE211 UT WOS:A1997WE21100011 PM 9020935 ER PT J AU Sosman, JA Aronson, FR Sznol, M Atkins, MB Dutcher, JP Weiss, GR Isaacs, RE Margolin, KA Fisher, RI Ernest, ML Mier, J Oleksowicz, L Eckhardt, JR Levitt, D Doroshow, JH AF Sosman, JA Aronson, FR Sznol, M Atkins, MB Dutcher, JP Weiss, GR Isaacs, RE Margolin, KA Fisher, RI Ernest, ML Mier, J Oleksowicz, L Eckhardt, JR Levitt, D Doroshow, JH TI Concurrent phase I trials of intravenous interleukin 6 in solid tumor patients: Reversible dose-limiting neurological toxicity SO CLINICAL CANCER RESEARCH LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-6; STIMULATORY FACTOR-II; RENAL-CELL CARCINOMA; MEGAKARYOCYTES INVITRO; CEREBROSPINAL-FLUID; ANTITUMOR-ACTIVITY; CANCER-PATIENTS; IL-6; INVIVO; ANEMIA AB Interleukin 6 (IL-6) has antitumor activity comparable to IL-2 in murine models with less toxicity, Because the biological effects of intermittent and continuous infusions may differ, we conducted two concurrent Phase I trials of daily x5, l-h, and continuous 120-h i,v, infusions to determine the toxicity, biological effects, and maximum tolerated dose of i,v, IL-6, Cohorts of six patients with advanced cancer received escalating doses (1, 3, 10, 30, 100, and 150 mu g/kg/day) of recombinant human IL-6 on days 1-5 and 8-12 of each 28-day course (l-h trial) or on days 1-5 of each 21-day course (120-h trial), Treatment was administered in regular inpatient wards and in outpatient clinics and was withheld in the event of grade 3 toxicity, Sixty-nine patients (l-h trial, n = 40; 120-h trial, It = 29) were enrolled, including 27 with renal cancer and 16 with melanoma, All were ambulatory, and 30 were asymptomatic, Fever (97%), anemia (78%), fatigue (56%), nausea or vomiting (49%), and elevated serum transaminase levels (42%) were the most frequent toxicities, Transient hypotension developed in 23 patients (33%), There were three deaths during the study due to progressive disease and/or infection, There were no objective responses, Dose-related increases in platelet counts and C-reactive protein levels were detected in most patients, Principal dose-limiting toxicities included atrial fibrillation (1 episode in the l-h trial and 4 episodes in the 120-h trial) and neurological toxicities (3 episodes in the l-h trial and 4 episodes in the 120-h trial), The neurological toxicities included confusion, slurred speech, blurred vision, proximal leg weakness, paraparesis, and ataxia, These effects were transient and reversed when IL-6 was discontinued, IL-6 can be given by i,v, infusion at biologically active doses with acceptable toxicity, Dose-limiting toxicities consisted mainly of a spectrum of severe but transient neurological toxicities and occasional episodes of atrial fibrillation, The maximum tolerated doses recommended for use with these i,v, schedules in Phase II trials are 100 mu g/kg/day by daily x5 l-h infusion and 30 mu g/kg/day by 120-h infusion, Phase II trials will be performed to determine the antitumor activity of IL-6 and better define its toxicity, Patients in these and other IL-6 studies should be monitored closely for neurological and cardiac effects. C1 LOYOLA UNIV,MED CTR,MAYWOOD,IL 60153. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NATL CANC INST,BETHESDA,MD 20852. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. ALBERT EINSTEIN CANC CTR,BRONX,NY 10461. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. SANDOZ CYTOKINE DEV UNIT,E HANOVER,NJ 07956. CITY HOPE NATL MED CTR,DUARTE,CA 91510. FU NCRR NIH HHS [MO1-RR00088] NR 36 TC 24 Z9 24 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 JAN PY 1997 VL 3 IS 1 BP 39 EP 46 PG 8 WC Oncology SC Oncology GA WY363 UT WOS:A1997WY36300006 PM 9815535 ER PT J AU Ramsbottom, D Scott, JM Molloy, A Weir, DG Kirke, PN Mills, JL Gallagher, PM Whitehead, AS AF Ramsbottom, D Scott, JM Molloy, A Weir, DG Kirke, PN Mills, JL Gallagher, PM Whitehead, AS TI Are common mutations of cystathionine beta-synthase involved in the aetiology of neural tube defects? SO CLINICAL GENETICS LA English DT Article DE cystathionine beta-synthase; genotyping; hyperhomocysteinemia; 5,10 methylenetetrahydrofolate reductase; neural tube defects ID METHYLENETETRAHYDROFOLATE REDUCTASE; RISK FACTOR; MOLECULAR-BASIS; HOMOCYSTINURIA; DEFICIENCY; DISEASE; GENE AB Mildly elevated maternal plasma homocysteine (Hcy) levels (hyperhomocysteinemia) have recently been observed in some neural tube defect (NTD) pregnancies. Plasma levels of Hey are governed by both genetic and nutritional factors and the aetiology of NTDs is also known to have both genetic and nutritional components. We therefore examined the frequency of relatively common mutations in the enzyme cystathionine beta-synthase (CBS), which is one of the main enzymes that controls Hey levels, in the NTD population. Neither the severely dysfunctional G307S CBS allele nor the recently reported 68 bp insertion/I278T CBS allele was observed at increased frequency in the cases relative to controls. We therefore conclude that loss of function CBS alleles do not account for a significant proportion of NTDs in Ireland. C1 TRINITY COLL DUBLIN,DEPT GENET,DUBLIN 2,IRELAND. TRINITY COLL DUBLIN,INST BIOTECHNOL,DUBLIN 2,IRELAND. TRINITY COLL DUBLIN,DEPT CLIN MED,DUBLIN 2,IRELAND. HLTH RES BOARD,DUBLIN,IRELAND. NICHHD,BETHESDA,MD 20892. NR 21 TC 71 Z9 74 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JAN PY 1997 VL 51 IS 1 BP 39 EP 42 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA WM688 UT WOS:A1997WM68800008 PM 9084933 ER PT J AU Rubin, GM Chang, HC Karim, F Laverty, T Michaud, NR Morrison, DK Rebay, I Tang, A Therrien, M Wassarman, DA AF Rubin, GM Chang, HC Karim, F Laverty, T Michaud, NR Morrison, DK Rebay, I Tang, A Therrien, M Wassarman, DA TI Signal transduction downstream from RAS in Drosophila SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposium on Quantitative Biology - Pattern Formation During Development CY 1997 CL PLAINVIEW, NEW YORK ID PROTEIN TYROSINE KINASE; ETS DOMAIN PROTEIN; KSR-1 GENE ENCODES; EYE DEVELOPMENT; ECTOPIC EXPRESSION; FATE DETERMINATION; FUSHI-TARAZU; MAP KINASE; CELL FATES; C-ELEGANS C1 Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Cell & Mol Biol, Berkeley, CA 94720 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Mechanisms Carcinogenesis Lab, Frederick, MD 21701 USA. RP Rubin, GM (reprint author), Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. OI Rubin, Gerald/0000-0001-8762-8703 NR 44 TC 23 Z9 23 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1997 VL 62 BP 347 EP 352 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA ZM731 UT WOS:000073570200040 PM 9598368 ER PT S AU Mitsuya, H AF Mitsuya, H BE Surbone, A Zwitter, M TI Telling the truth to cancer patients and patients with HIV-1 infection in Japan SO COMMUNICATION WITH THE CANCER PATIENT: INFORMATION AND TRUTH SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Communication with the Cancer Patient CY FEB 10-14, 1997 CL BLED, SLOVENIA SP Canc Ethics Fund, POP TV, Ljubljana ID INFORMED CONSENT; AIDS; CARE; ATTITUDES; RISK C1 NCI, Expt Retrovirol Sect, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Mitsuya, H (reprint author), NCI, Expt Retrovirol Sect, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. NR 33 TC 9 Z9 10 U1 2 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 0-89766-985-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 809 BP 279 EP 289 DI 10.1111/j.1749-6632.1997.tb48091.x PG 11 WC Oncology; Medical Ethics; Multidisciplinary Sciences SC Oncology; Medical Ethics; Science & Technology - Other Topics GA BR78Z UT WOS:000167539800029 PM 9103579 ER PT J AU Kulldorff, M AF Kulldorff, M TI A spatial scan statistic SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE point patterns; inhomogeneous Poisson process; Bernoulli process; clusters; clustering; confounders; sudden infant death syndrome ID INHOMOGENEOUS POPULATIONS; CLUSTERS; DISEASE; POWER AB The scan statistic is commonly used to test if a one dimensional point process is purely random, or if any clusters can be detected. Here it is simultaneously extended in three directions: (i) a spatial scan statistic for the detection of clusters in a multi-dimensional point process is proposed, (ii) the area of the scanning window is allowed to vary, and (iii) the baseline process may be any inhomogeneous Poisson process or Bernoulli process with intensity proportional to some known function. The main interest is in detecting clusters not explained by the baseline process. These methods are illustrated on an epidemiological data set, but there are other potential areas of application as well. C1 NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. UNIV UPPSALA,DEPT STAT,S-75120 UPPSALA,SWEDEN. RI Kulldorff, Martin/H-4282-2011; OI Kulldorff, Martin/0000-0002-5284-2993 NR 22 TC 1292 Z9 1344 U1 4 U2 69 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 1997 VL 26 IS 6 BP 1481 EP 1496 DI 10.1080/03610929708831995 PG 16 WC Statistics & Probability SC Mathematics GA XC912 UT WOS:A1997XC91200013 ER PT J AU Kloczkowski, A Jernigan, RL AF Kloczkowski, A Jernigan, RL TI Computer generation and enumeration of compact self-avoiding walks within simple geometries on lattices SO COMPUTATIONAL AND THEORETICAL POLYMER SCIENCE LA English DT Article DE self-avoiding walks; lattice; simple geometrics ID CONFORMATIONS; COPOLYMERS; SEQUENCE; PROTEINS AB We generated and enumerated all compact self-avoiding walks on the square and the cubic lattice within simple geometries. In two dimensions on the square lattice the self-avoiding walks are restricted to rectangles of size m x n, and in three dimensions on the cubic lattice the compact self-avoiding walks are restricted to parallelpipeds of size I x m x n. The enumerations are performed for all possible combinations of I, m, n. The enumerations were performed for walks (chains) up to 60 steps (bonds) in 2D, and up to 40 steps in 3D. We have reduced the number of possible conformations by eliminating conformations related by symmetries. In several cases we obtain interesting recursion relations between the number of conformations and the size of the rectangle (or parallelepiped). The calculations are performed both for walks (Hamiltonian paths) with two ends and for cyclic walks (chains), the so-called Hamiltonian circuits. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NCI, NIH, Mol Struct Sect, Lab Expt & Computat Biol, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012; Kloczkowski, Andrzej/B-9868-2012 NR 11 TC 22 Z9 22 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1089-3156 J9 COMPUT THEOR POLYM S JI Comput. Theor. Polym. Sci. PY 1997 VL 7 IS 3-4 BP 163 EP 173 DI 10.1016/S1089-3156(97)00022-6 PN 1 PG 11 WC Polymer Science SC Polymer Science GA ZZ274 UT WOS:000074713000007 ER PT B AU Crook, SM Ermentrout, GB AF Crook, SM Ermentrout, GB BE Bower, JM TI An analysis of the adaptive behavior of piriform cortex pyramidal cells SO COMPUTATIONAL NEUROSCIENCE: TRENDS IN RESEARCH, 1997 LA English DT Proceedings Paper CT 5th Annual Computational Neuroscience Meeting (CNS 96) CY JUL 14-17, 1996 CL BOSTON, MA SP NIMH, Natl Sci Fdn RP Crook, SM (reprint author), NIDDK,MATH RES BRANCH,NIH,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45699-0 PY 1997 BP 65 EP 70 PG 6 WC Mathematics, Applied; Neurosciences SC Mathematics; Neurosciences & Neurology GA BJ84S UT WOS:A1997BJ84S00011 ER PT B AU Tagamets, MA Horwitz, B AF Tagamets, MA Horwitz, B BE Bower, JM TI Modeling brain imaging data with neuronal assembly dynamics SO COMPUTATIONAL NEUROSCIENCE: TRENDS IN RESEARCH, 1997 LA English DT Proceedings Paper CT 5th Annual Computational Neuroscience Meeting (CNS 96) CY JUL 14-17, 1996 CL BOSTON, MA SP NIMH, Natl Sci Fdn RP Tagamets, MA (reprint author), NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20982, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45699-0 PY 1997 BP 949 EP 953 PG 5 WC Mathematics, Applied; Neurosciences SC Mathematics; Neurosciences & Neurology GA BJ84S UT WOS:A1997BJ84S00147 ER PT J AU Wootton, JC AF Wootton, JC TI Evaluating the effectiveness of sequence analysis algorithms using measures of relevant information SO COMPUTERS & CHEMISTRY LA English DT Article ID PROTEIN-SEQUENCE; ALIGNMENT; IDENTIFICATION; DATABASES; MOTIF; SECONDARY; FEATURES; PATTERNS AB Given vast quantities of molecular sequence data, and numerous different algorithms designed to discover, diagnose or model biologically interesting features in sequences, how is it possible to make objective evaluations of the diagnostic effectiveness of these algorithms and robust assessments of their relative strengths and limitations? An approach to this relatively neglected question is developed here, which is based on information measures of the diagnostic efficiency of different methods. From output lists of a procedure such as a database search, ''relevance weights'' are assigned that encode, for each sequence listed, the level of associated scientific evidence implicating that sequence as an example of a feature of interest. Relevance weights may be derived, following systematic protocols, from expert human judgement or, in principle, by automated information retrieval from electronic resources. Practical applications of this approach to algorithm assessment and development and parameter choice are demonstrated with examples of automated sequence motif modeling for the DNA-binding helix-turn-helix motif and the guanine exchange factor protein domain. The combined use of relevance weights and information measures appears to offer promising advantages over ROC analysis and may be generally applicable to diagnostic evaluation. Published by Elsevier Science Ltd. RP Wootton, JC (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BLDG 38A,ROOM 8N805,BETHESDA,MD 20894, USA. NR 39 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 0097-8485 J9 COMPUT CHEM JI Comput. Chem. PY 1997 VL 21 IS 4 BP 191 EP 202 DI 10.1016/S0097-8485(97)00001-6 PG 12 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA YL071 UT WOS:A1997YL07100002 PM 9415984 ER PT S AU Brigger, P Bacharach, SL Srinivasan, G Nour, KA Dilsizian, V Aldroubi, A Unser, M AF Brigger, P Bacharach, SL Srinivasan, G Nour, KA Dilsizian, V Aldroubi, A Unser, M GP IEEE IEEE TI Segmentation of gated Tl-SPECT images for automatic computation of myocardial volume and ejection fraction SO COMPUTERS IN CARDIOLOGY 1997, VOL 24 SE COMPUTERS IN CARDIOLOGY LA English DT Proceedings Paper CT 24th Annual Computers in Cardiology Conference CY SEP 07-10, 1997 CL LUND, SWEDEN SP IEEE AB We present an algorithm for automatic assessment of left ventricular ejection fraction (EF) and-absolute volume from gated Thallium-SPECT myocardial perfusion images. The system consists of two independent blocs for segmentation and computation of function. We introduce a novel formulation for computation of EF based on the epi-cardial contour. The algorithm was validated against manual border tracing from two physicians on different modalities, and gave consistent linear agreement. PET manual vs. automatic - avg. r = 0.91, Tl-SPECT manual vs. auto r = 0.79. The new epicardial method was compared to the endocardial method, showing the former's improved performance at high noise. Finally, preliminary comparison were made of EFs computed for PET, (TC)-T-99m- SPECT and Tl-201-SPECT to those obtained from planar gated blood pool imaging (GBP) yielding good results. The proposed scheme is specifically designed for Tl-201-SPECT, but may be used on other image modalities as well. It permits EF computation on relatively noisy images without the need for additional image acquisitions. C1 NIH, NCRR, BEIP, Bethesda, MD 20982 USA. RP Brigger, P (reprint author), NIH, NCRR, BEIP, 13 S DR MSC 5766, Bethesda, MD 20982 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0276-6574 BN 0-7803-4446-4 J9 COMPUT CARDIOL PY 1997 VL 24 BP 677 EP 680 DI 10.1109/CIC.1997.648141 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic SC Cardiovascular System & Cardiology; Computer Science; Engineering GA BK40E UT WOS:000072059000171 ER PT J AU Champoux, M Kriete, MF Eckhaus, MA Suomi, SJ AF Champoux, M Kriete, MF Eckhaus, MA Suomi, SJ TI Behavioral and physical concomitants of congenital hydrocephalus in a rhesus macaque (Macaca mulatta) neonate SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID SAIMIRI-SCIUREUS; BREEDING COLONY; MALFORMATIONS; MONKEYS AB A colony-born male rhesus monkey neonate was assigned to an ongoing protocol assessing behavioral and physiologic development in nursery-reared infants. It was sacrificed at day 20 because of poor weight gain, inability to self-feed, and generalized weakness. An asymmetric internal hydrocephalus was the only notable gross finding at necropsy. A retrospective analysis was performed comparing physical and behavioral measures for it with values for age-matched nursery-reared peers. Weight gain and formula intake lagged behind others in its cohort. The affected macaque spent more time in sleep and awake/quiet states and less time in an awake active state than did its peers. Behaviors during a neonatal temperament/reflex examination were indicative of high levels of irritability, poor muscular tone, nonexistent voluntary motor activity, and slower overall responding. In addition, asymmetric responses for some motor items were observed. However, vestibular/ocular reflexes appeared normal. The occasional observation of hydrocephalus in infants, as well as its prevalence throughout the primate order, indicates that hydrocephalus should be considered in the differential diagnosis for infants with feeding difficulties and motor dysfunction. C1 NEI,VET RES & RESOURCES SECT,BETHESDA,MD 20892. NCRR,VET RESOURCES PROGRAM,BETHESDA,MD 20892. RP Champoux, M (reprint author), NICHHD,COMPARAT ETHOL LAB,POOLESVILLE,MD 20837, USA. NR 28 TC 4 Z9 4 U1 1 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD JAN PY 1997 VL 36 IS 1 BP 56 EP 61 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA WG496 UT WOS:A1997WG49600003 PM 12456186 ER PT J AU Davis, JA Miller, GF Claire, MFS AF Davis, JA Miller, GF Claire, MFS TI Spontaneous rhabdomyosarcomas in (A/JxCBA/J)F1 mice SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID SPONTANEOUS NEOPLASMS; B6C3F1 MICE; DIFFERENTIATION; ACTIN AB Spontaneous rhahdomyosarcoma is rare in laboratory rodents. Incidence was estimated as 2.4/100,000 in BALB/c mice; incidence of < 0.5% for rodents is generally accepted. We describe spontaneous rhabdomyosarcoma in 2 aged, female ([A/J x CBA/J]F-1) mice. Part of a small breeding colony, these mice were experimentally naive; incidence was estimated as 12.5%. Tumors were located in the muscles of the thoracic wall and muscles of the dorsolumbar region. Cross-striations were detected, using phosphotungstic acid hematoxylin stain; presence of cross-striations within the neoplasm are diagnostic for rhabdomyosarcoma. C1 NCRR,VRP,PATHOL UNIT,NIH,BETHESDA,MD 20892. RP Davis, JA (reprint author), NINCDS,ANIM HLTH CARE SECT,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD JAN PY 1997 VL 36 IS 1 BP 87 EP 89 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA WG496 UT WOS:A1997WG49600010 PM 12456193 ER PT J AU Currey, KM Shapiro, BA AF Currey, KM Shapiro, BA TI Higher order structures of coxsackievirus B 5' nontranslated region RNA SO COXSACKIE B VIRUSES SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID SECONDARY STRUCTURE PREDICTION; COMPARATIVE SEQUENCE-ANALYSIS; RIBOSOME ENTRY SITE; POLIOVIRUS RNA; NONCODING REGION; INTERNAL INITIATION; ENERGY MINIMIZATION; TERTIARY STRUCTURE; GENETIC ALGORITHM; PICORNAVIRUS RNAS C1 NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,MATH BIOL LAB,FREDERICK,MD 21702. RP Currey, KM (reprint author), UNIV MARYLAND,DEPT PEDIAT,SIDS INST,22 S GREENE ST,BALTIMORE,MD 21201, USA. NR 67 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1997 VL 223 BP 169 EP 190 PG 22 WC Immunology; Microbiology SC Immunology; Microbiology GA BJ47L UT WOS:A1997BJ47L00008 PM 9294929 ER PT J AU Qasba, PK Kumar, S AF Qasba, PK Kumar, S TI Molecular divergence of lysozymes and alpha-lactalbumin SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE alpha-lactalbumin; lysozymes; galactosyltransferase; evolution; molecular divergence; lactose synthetase; protein-protein interactions; gene organizations; sequence similarity ID AMINO-ACID-SEQUENCE; EGG-WHITE LYSOZYME; TRANSFER RNA-SYNTHETASE; PROTEIN DISULFIDE-ISOMERASE; CALCIUM-BINDING LYSOZYMES; MULTIPLE CDNA SEQUENCES; METAL-ION BINDING; STOMACH LYSOZYMES; LACTOSE SYNTHETASE; CRYSTAL-STRUCTURE AB The vast number of proteins that sustain the currently living organisms have been generated from a relatively small number of ancestral genes that has involved a variety of processes. Lysozyme is an ancient protein whose origin goes back an estimated 400 to 600 million years. This protein was originally a bacteriolytic defensive agent and has been adapted to serve a digestive function on at least two occasions, separated by nearly 40 million years. The origins of the related goose type and T4 phage lysozyme that are distinct from the more common C type are obscure. They share no discernable amino acid sequence identity and yet they possess common secondary and tertiary structures. Lysozyme C gene also gave rise, after gene duplication 300 to 400 million years ago, to a gene that currently codes for alpha-lactalbumin, a protein expressed only in the lactating mammary gland of all but a few species of mammals. It is required for the synthesis of lactose, the sugar secreted in milk. alpha-lactalbumin shares only 40% identity in amino acid sequence with lysozyme C, but it has a closer spatial structure and gene organization. Although structurally similar, functionally they are quite distinct. Specific amino acid substitutions in alpha-lactalbumin account for the loss of the enzyme activity of lysozyme and the acquisition of the features necessary for its role in lactose synthesis. Evolutionary implications are as yet unclear but are being unraveled in many laboratories. C1 GEORGETOWN UNIV, DEPT CHEM, WASHINGTON, DC 20057 USA. RP NCI, STRUCT GLYCOBIOL SECT,LAB EXPT & COMPUTAT BIOL, NIH,POB B,BLDG 469, ROOM 221, FREDERICK, MD 21702 USA. NR 185 TC 95 Z9 102 U1 2 U2 12 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1040-9238 EI 1549-7798 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PY 1997 VL 32 IS 4 BP 255 EP + DI 10.3109/10409239709082574 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XU657 UT WOS:A1997XU65700001 PM 9307874 ER PT J AU Loftus, DJ AF Loftus, DJ TI Functional and structural issues related to epitope cross-recognition by T cells SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article; Proceedings Paper CT 9th International Symposium on the Immunobiology of Proteins and Peptides CY MAY 20-25, 1997 CL WHISTLER, CANADA SP Bristol Myers Squib, Amer Autoimmune Related Dis Assoc, Corixa, Cytel, Schering Plough Res Inst, Chiron Corp, Chiron Therapeut, Ciba Geigy, Genet Inst, NABI, Amgen, Pangaea Pharm, Anergen, StressGen Biotechnol, Medimmune, Bachem, Multiple Peptide Syst, Zeneca, Immune Response Corp, Peninsula Lab DE autoimmunity; crossreactivity; MHC; peptides; T cell receptors ID TUMOR-INFILTRATING LYMPHOCYTES; PEPTIDE-MHC COMPLEXES; MYELIN BASIC-PROTEIN; MOLECULAR MIMICRY; VIRAL PEPTIDES; POSITIVE SELECTION; SELF-PEPTIDE; RECEPTOR; ANTIGEN; IDENTIFICATION AB T cell epitope recognition is a pivotal process in the immune response. Structural and functional data obtained in recent years have contributed greatly to an understanding of how epitopes are formed by MHC/peptide complexes and how such epitopes are engaged by T cell receptors. Emerging as well from these studies is an appreciation of the tension that exists between epitope specificity and degeneracy, stemming from the highly flexible nature of ligand engagement by T cell receptors. The issues surrounding epitope cross-reactions are particularly germane to understanding the role played by epitope mimicry in contributing to autoreactive responses and autoimmune pathology. RP Loftus, DJ (reprint author), NCI,CELL BIOL LAB,NIH,BLDG 37,ROOM 1B03,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 45 TC 2 Z9 2 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 1997 VL 17 IS 5-6 BP 419 EP 426 PG 8 WC Immunology SC Immunology GA YK968 UT WOS:A1997YK96800005 PM 9419429 ER PT J AU Singer, DS Mozes, E Kirshner, S Kohn, LD AF Singer, DS Mozes, E Kirshner, S Kohn, LD TI Role of MHC class I molecules in autoimmune disease SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article; Proceedings Paper CT 9th International Symposium on the Immunobiology of Proteins and Peptides CY MAY 20-25, 1997 CL WHISTLER, CANADA SP Bristol Myers Squib, Amer Autoimmune Related Dis Assoc, Corixa, Cytel, Schering Plough Res Inst, Chiron Corp, Chiron Therapeut, Ciba Geigy, Genet Inst, NABI, Amgen, Pangaea Pharm, Anergen, StressGen Biotechnol, Medimmune, Bachem, Multiple Peptide Syst, Zeneca, Immune Response Corp, Peninsula Lab DE autoimmunity; MHC class I; transcription; regulation; cAMP ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTI-DNA IDIOTYPE; GENE-EXPRESSION; MICE; COMPLEX; CELLS; METHIMAZOLE; INTERFERON; MODULATION; INDUCTION AB The MHC class I molecules play a pivotal role in triggering cellular immune responses, binding and presenting intracellularly derived peptide antigens. Studies of MHC class I expression revealed a complex regulatory mechanism that integrates tissue-specific and hormonal modulation. Dynamic regulation occurs in the thyroid, in response to hormonal repression by TSH and stimulation by thyroid hormone. This dynamic cycle provides the basis for proposing the model that such regulation is important to maintain tolerance to self-antigens in tissues synthesizing large amounts of secretory proteins. Failure to appropriately regulate class I levels is predicted to result in autoimmunity. In support of this model, we found that class I-deficient mice are resistant to the experimentally induced autoimmune diseases, SLE, and blepharitis. Furthermore, pharmacological treatment with an agent that reduces class I expression also reduces the incidence and severity of both experimental and spontaneous autoimmune SLE. C1 NIDDK,BIOCHEM LAB,NIH,BETHESDA,MD 20892. WEIZMANN INST SCI,IL-76100 REHOVOT,ISRAEL. RP Singer, DS (reprint author), NCI,EXPT IMMUNOL BRANCH,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 13 TC 48 Z9 48 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 1997 VL 17 IS 5-6 BP 463 EP 468 PG 6 WC Immunology SC Immunology GA YK968 UT WOS:A1997YK96800009 PM 9419433 ER PT J AU Werner, H Le Roith, D AF Werner, H Le Roith, D TI The insulin-like growth factor-I receptor signaling pathways are important for tumorigenesis and inhibition of apoptosis SO CRITICAL REVIEWS IN ONCOGENESIS LA English DT Review DE tyrosine kinase; signal transduction; transcription; cell cycle; oncogene; tumor suppressors; p53; WT1 ID HUMAN-BREAST-CANCER; TUMOR-SUPPRESSOR WT1; ROUND-CELL TUMOR; MOUSE EMBRYO FIBROBLASTS; ZINC FINGER PROTEIN; DISTAL LONG ARM; WILMS-TUMOR; IGF-I; GENE-EXPRESSION; HEMATOPOIETIC-CELLS AB The biological actions of the insulin-like growth factors IGF-I and IGF-II are mediated by their activation of the IGF-IR, a transmembrane tyrosine kinase linked to the ras-raf-MAPK cascade. Functional IGF-IRs are required for the cell to progress through the cell cycle. Most importantly, cells lacking this receptor cannot be transformed by any of a number of dominant oncogenes, a finding that proves that the presence of the IGF-IR is important for the development of a malignant phenotype. Consistent with this role, the IGF-IR displays a potent antiapoptotic effect, both in vitro and in vivo. Because of its key role in the transformation process, the IGF-IR is actively studied as a potential therapeutic target in different types of neoplastic growth. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Fac Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. RP Le Roith, D (reprint author), NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NR 182 TC 113 Z9 116 U1 0 U2 3 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 0893-9675 J9 CRIT REV ONCOGENESIS JI Crit. Rev. Oncog. PY 1997 VL 8 IS 1 BP 71 EP 92 PG 22 WC Biochemistry & Molecular Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Oncology; Cell Biology GA YZ681 UT WOS:000072279700004 PM 9516087 ER PT J AU Rhim, JS Kung, HF AF Rhim, JS Kung, HF TI Human prostate carcinogenesis SO CRITICAL REVIEWS IN ONCOGENESIS LA English DT Review DE human prostate epithelial cells; immortalization; neoplastic transformation; ras oncogene; tumor suppressor genes; growth factors ID POLYMERASE CHAIN-REACTION; TUMOR-SUPPRESSOR GENE; EPITHELIAL-CELL LINE; HUMAN PAPILLOMAVIRUS DNA; FIBROBLAST GROWTH-FACTOR; HORMONE-RELATED PROTEIN; V-KI-RAS; ALLELIC LOSS; NEOPLASTIC TRANSFORMATION; HUMAN KERATINOCYTES AB Prostate cancer is a major medical problem that is expected to affect over 300,000 American men and cause over 40,000 deaths in 1997. Despite its widespread prevalence and because of the difficulties in clinical diagnosis and treatment of the disease, the etiological mechanism underlying prostate carcinogenesis remains poorly understood. Elucidation of the mechanism of prostate tumorigenesis has been slowed by a lack of tumor tissues and the limited number of human cell lines available for study. In vitro human cell models to study the molecular biology of prostate cancer progression an urgently needed. Normal human prostate cells require immortalization to provide a practical system for transformation studies. Neoplastic transformation of human prostate epithelial cells in culture has been achieved recently in a stepwise fashion-immortalization of primary cells in culture and conversion of the immortalized cells to a tumorigenic state. Reviewed here are the steps involved in the neoplastic transformation of human prostate cells. To provide an insight into the molecular and genetic mechanisms involved in the conversion of normal cells to a neoplastic state of growth, the authors have attempted to put into perspective the history of human prostate epithelial cell transformation by a combination of carcinogenic agents, and to discuss the current state-of-the-art in transformation of human prostate epithelial cells in culture. C1 NCI, Lab Biochem Physiol, Frederick, MD 21702 USA. RP Rhim, JS (reprint author), NCI, Lab Biochem Physiol, Bldg 567,Rm 152, Frederick, MD 21702 USA. NR 114 TC 14 Z9 14 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 0893-9675 J9 CRIT REV ONCOGENESIS JI Crit. Rev. Oncog. PY 1997 VL 8 IS 4 BP 305 EP 328 PG 24 WC Biochemistry & Molecular Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Oncology; Cell Biology GA ZP683 UT WOS:000073778000002 PM 9622052 ER PT B AU Korach, KS Lindzey, J AF Korach, KS Lindzey, J BE Waites, GMH Frick, J Baker, GWH TI Reproductive effects of estrogen receptor gene disruption in male mice SO CURRENT ADVANCES IN ANDROLOGY LA English DT Proceedings Paper CT VIth International Congress of Andrology - Current Advances in Andrology CY MAY 25-29, 1997 CL SALZBURG, AUSTRIA AB In male mice, ER disruption causes infertility due to deficiencies in both gametogenesis and sex behavior, An age dependent development of testicular dysmorphogenesis results in a progressive loss of germ cells. Circulating gonadotropins and testosterone are not appreciably higher in male ERKOs, indicating that testicular androgens can effectively exert feedback on gonadotropins in the absence of aromatization and activation of ER. Infertility in male ERKOs does not appear to be a result of compromised androgen action since the morphology of male reproductive tract organs is largely unaffected. Mounting behavior of ERKO males is normal whereas the ability to intromit and ejaculate is severely compromised. RP Korach, KS (reprint author), NIEHS,RECEPTOR BIOL SECT,LRDT,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MONDUZZI EDITORE PI 40128 BOLOGNA PA VIA FERRARESE 119/2, 40128 BOLOGNA, ITALY BN 88-323-0529-9 PY 1997 BP 45 EP 50 PG 6 WC Andrology SC Endocrinology & Metabolism GA BJ47P UT WOS:A1997BJ47P00006 ER PT J AU Moldovan, NI Milliken, EE Irani, K Chen, J Sohn, RH Finkel, T GoldschmidtClermont, PJ AF Moldovan, NI Milliken, EE Irani, K Chen, J Sohn, RH Finkel, T GoldschmidtClermont, PJ TI Regulation of endothelial cell adhesion by profilin SO CURRENT BIOLOGY LA English DT Article ID PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; ACTIN CYTOSKELETON; MAMMALIAN-CELLS; FOCAL ADHESION; PROFILACTIN; ADENOVIRUS; CLONING; GENE AB Background: Although profilin is believed to be an essential regulator of the actin cytoskeleton in most cells, its precise role in mammalian cells remains unknown. We have used replication-incompetent adenovirus carrying the human profilin I cDNA as a means rapidly to increase the concentration of profilin in human aortic endothelial cells 12-31-fold above baseline - levels never before achieved in mammalian cells. Results: The concentration of filamentous actin was not detectably affected by profilin overexpression. Actin stress fibers were, however, absent from areas of high profilin content in overexpressing cells, and the bulk of filaments was located at the periphery of the cells. We observed a gradient in the distribution of overexpressed profilin in migrating endothelial cells, with most profilin molecules concentrated near the advancing edge where focal contacts are being formed and focal adhesion proteins are located. Profilin overexpression resulted in increased recruitment of fibronectin receptors to the plasma membrane. Adhesion of endothelial cells to fibronectin was markedly and selectively increased by profilin overexpression, Conclusions: We conclude that an important role for profilin in mammalian cells may be its contribution to the formation of focal contacts, particularly those involving the fibronectin receptor. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT ANAT & CELL BIOL,BALTIMORE,MD 21287. NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NR 26 TC 32 Z9 34 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 1 PY 1997 VL 7 IS 1 BP 24 EP 30 DI 10.1016/S0960-9822(06)00024-8 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WE221 UT WOS:A1997WE22100023 PM 9024619 ER PT J AU Padlan, EA Margulies, DH AF Padlan, EA Margulies, DH TI T-cell receptors: Feeling out the complex SO CURRENT BIOLOGY LA English DT Article ID ANTIGEN RECEPTOR; CRYSTAL-STRUCTURE; RECOGNITION; LYMPHOCYTES; CHAIN AB Recent crystallographic studies show that the T-cell receptor has a largely immunoglobulin like structure and binds to MHC-peptide complexes through loops from paired V alpha and V beta domains that focus on the central amino acids of the MHC-bound peptide, and to bacterial superantigens via peripheral aspects of the V beta domain. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NIDDK,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013 NR 19 TC 2 Z9 2 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 JAN 1 PY 1997 VL 7 IS 1 BP R17 EP R20 DI 10.1016/S0960-9822(06)00010-8 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WE221 UT WOS:A1997WE22100008 PM 9072162 ER PT S AU Rouault, T Klausner, R AF Rouault, T Klausner, R BE Stadtman, ER Chock, PB TI Regulation of iron metabolism in eukaryotes SO CURRENT TOPICS IN CELLULAR REGULATION, VOL 35 SE CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID ELEMENT-BINDING-PROTEIN; FERRITIN MESSENGER-RNA; FE-S CLUSTER; ERYTHROID 5-AMINOLEVULINATE SYNTHASE; 5' UNTRANSLATED REGION; RESPONSIVE-ELEMENT; TRANSLATIONAL REGULATION; SULFUR CLUSTER; ACONITASE ACTIVITY; SUCCINATE-DEHYDROGENASE RP Rouault, T (reprint author), NICHHD, CELL BIOL & METAB BRANCH, NIH, BETHESDA, MD 20892 USA. NR 89 TC 185 Z9 188 U1 0 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2137 BN 0-12-152835-9 J9 CURR TOP CELL REGUL PY 1997 VL 35 BP 1 EP 19 DI 10.1016/S0070-2137(97)80001-5 PG 19 WC Cell Biology; Physiology SC Cell Biology; Physiology GA BJ03Y UT WOS:A1997BJ03Y00001 PM 9192174 ER PT S AU Warner, HR AF Warner, HR BE Stadtman, ER Chock, PB TI Aging and regulation of apoptosis SO CURRENT TOPICS IN CELLULAR REGULATION, VOL 35 SE CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID PROGRAMMED CELL-DEATH; AMYOTROPHIC-LATERAL-SCLEROSIS; CAENORHABDITIS-ELEGANS GENES; SENESCENT HUMAN-FIBROBLASTS; CENTRAL-NERVOUS-SYSTEM; C-MYC; SUPEROXIDE-DISMUTASE; LYMPHOPROLIFERATIVE SYNDROME; ENDONUCLEASE ACTIVATION; ALZHEIMERS-DISEASE RP Warner, HR (reprint author), NIA, BIOL AGING PROGRAM, NIH, BETHESDA, MD 20892 USA. NR 89 TC 51 Z9 52 U1 3 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2137 BN 0-12-152835-9 J9 CURR TOP CELL REGUL PY 1997 VL 35 BP 107 EP 121 DI 10.1016/S0070-2137(97)80004-0 PG 15 WC Cell Biology; Physiology SC Cell Biology; Physiology GA BJ03Y UT WOS:A1997BJ03Y00004 PM 9192177 ER PT S AU Rosner, JL Storz, G AF Rosner, JL Storz, G BE Stadtman, ER Chock, PB TI Regulation of bacterial responses to oxidative stress SO CURRENT TOPICS IN CELLULAR REGULATION, VOL 35 SE CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID MULTIPLE ANTIBIOTIC-RESISTANCE; POLYMERASE ALPHA-SUBUNIT; C-TERMINAL REGION; FACTOR KATF RPOS; PROTEIN H-NS; ESCHERICHIA-COLI; BACILLUS-SUBTILIS; SALMONELLA-TYPHIMURIUM; SIGMA-FACTOR; TRANSCRIPTIONAL ACTIVATION C1 NICHHD, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. RP Rosner, JL (reprint author), NIDDKD, MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. OI Storz, Gisela/0000-0001-6698-1241 NR 68 TC 32 Z9 33 U1 3 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2137 BN 0-12-152835-9 J9 CURR TOP CELL REGUL PY 1997 VL 35 BP 163 EP 177 DI 10.1016/S0070-2137(97)80007-6 PG 15 WC Cell Biology; Physiology SC Cell Biology; Physiology GA BJ03Y UT WOS:A1997BJ03Y00007 PM 9192180 ER PT J AU Hochgeschwender, U Gagneten, S Sauer, B Brennan, MB AF Hochgeschwender, U Gagneten, S Sauer, B Brennan, MB TI Functional mapping by Cre/lox mediated segmental duplications and deletions in the mouse SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 NIMH, Mol Genet Unit, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 79 IS 1-2 BP 48 EP 48 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA ZC293 UT WOS:000072562300051 ER PT J AU Robertson, GP Hufford, A Lugo, TG AF Robertson, GP Hufford, A Lugo, TG TI A panel of transferable fragments of human chromosome 11q SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; SOMATIC-CELL HYBRIDS; ATAXIA-TELANGIECTASIA; MALIGNANT-MELANOMA; OVARIAN-CANCER; BREAST-CANCER; HETEROZYGOSITY; REGION; MARKERS; TUMORIGENICITY AB Cytogenetic and molecular studies have implicated one or more tumor suppressor genes on the long arm of human chromosome 11 in the malignant progression of several human solid tumors, including malignant melanoma and carcinomas of the breast, cervix, ovary, and lung. Microcell-mediated chromosome transfer of an intact copy of chromosome 11 into tumor cell lines has provided additional evidence of tumor suppressor gene function in melanoma, breast cancer, and cervical cancer. However, sublocalization of the region(s) conferring the tumor suppressive effect has been difficult. To facilitate mapping of tumor suppressor gene(s) on chromosome 11, we have generated a panel of 25 mouse donor cell lines containing neo-tagged fragments of human chromosome 11q which can be transferred into cell lines to test for tumor suppressor activity. The chromosome fragments in these cell lines have been characterized by fluorescence in situ hybridization with probes to human DNA and to the centromere of chromosome 11, and also by analysis of microsatellite markers spanning chromosome 11. Finally, to demonstrate the usefulness of these cell lines as donors for microcell-mediated chromosome transfer, two fragments were transferred into the human melanoma cell line UACC 903. This panel of selectable subchromosomal fragments, derived from the long arm of human chromosome 11, will be useful for the regional localization of tumor suppressors and other genes by means of functional assays. C1 Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA. RP Lugo, TG (reprint author), NCI, Canc Diag Program, DCTDC, Execut Plaza N,Suite 700,6130 Execut Blvd, Rockville, MD 20892 USA. OI Robertson, Gavin P./0000-0003-0152-2997 FU NCI NIH HHS [R01-CA66021] NR 33 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 79 IS 1-2 BP 53 EP 59 DI 10.1159/000134682 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA ZC293 UT WOS:000072562300065 PM 9533012 ER PT J AU Cho, KW Satoh, H Youn, HY Watari, T Tsujimoto, H O'Brien, SJ Hasegawa, A AF Cho, KW Satoh, H Youn, HY Watari, T Tsujimoto, H O'Brien, SJ Hasegawa, A TI Assignment of the cat immunoglobulin heavy chain genes IGHM and IGHG to chromosome B3q26 and T cell receptor chain gene TCRG to A2q12 -> q13 by fluorescence in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID TRANSLOCATIONS; LOCALIZATION; FISH C1 Univ Tokyo, Inst Med Sci, Dept Pathol, Minato Ku, Tokyo 108, Japan. Univ Tokyo, Grad Sch Agr & Life Sci, Dept Vet Internal Med, Bunkyo Ku, Tokyo, Japan. Seoul Natl Univ, Coll Vet Med, Dept Vet Internal Med, Seoul, South Korea. Natl Canc Inst, Lab Genom Divers, Frederick, MD USA. RP Satoh, H (reprint author), Univ Tokyo, Inst Med Sci, Dept Pathol, Minato Ku, 4-6-1 Shirokanedai, Tokyo 108, Japan. NR 15 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 79 IS 1-2 BP 118 EP 120 DI 10.1159/000134696 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA ZC293 UT WOS:000072562300079 PM 9533026 ER PT J AU Pack, SD Tanigami, A Ledbetter, DH Sato, T Fukuda, MN AF Pack, SD Tanigami, A Ledbetter, DH Sato, T Fukuda, MN TI Assignment of trophoblast endometrial epithelium cell adhesion molecule trophinin gene TRO to human chromosome bands Xp11.22 -> p11.21 by in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID X-CHROMOSOME C1 Burnham Inst, La Jolla, CA 92037 USA. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. Natl Canc Ctr, Res Inst, Div Radiobiol, Tokyo 104, Japan. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Columbia Univ, Dept Pathol, Dept Otolaryngol Head & Neck Surg, New York, NY 10027 USA. RP Fukuda, MN (reprint author), Burnham Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Pack, Svetlana/C-2020-2014 FU NICHD NIH HHS [HD31671]; NIGMS NIH HHS [GM55147] NR 5 TC 18 Z9 19 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 79 IS 1-2 BP 123 EP 124 DI 10.1159/000134698 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA ZC293 UT WOS:000072562300081 PM 9533028 ER PT J AU Fowler, KJ Newson, AJ MacDonald, AC Kalitsis, P Lyu, MS Kozak, CA Choo, KHA AF Fowler, KJ Newson, AJ MacDonald, AC Kalitsis, P Lyu, MS Kozak, CA Choo, KHA TI Chromosomal localization of mouse Cenpa gene SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID HOMOLOG; MITOSIS; PROTEIN AB Using a previously isolated mouse centromere protein A (Cenpa) probe, we have localized the gene to the proximal region of mouse Chromosome 5, between the known Il6 and Yes1 loci near [Adra2C-D5H4S43-Hdh]. Comparison of this localization with that of human CENPA, which maps to chromosome 2, is consistent with the presence of a new region of conserved synteny between the two species. C1 Royal Childrens Hosp, Murdoch Inst Res Birth Defects, Parkville, Vic 3052, Australia. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Fowler, KJ (reprint author), Royal Childrens Hosp, Murdoch Inst Res Birth Defects, Flemington Rd, Parkville, Vic 3052, Australia. EM fowlerk@cryptic.rch.unimelb.edu.au RI Kalitsis, Paul/C-1916-2015 OI Kalitsis, Paul/0000-0001-5569-0609 NR 19 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 79 IS 3-4 BP 298 EP 301 DI 10.1159/000134748 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA ZM845 UT WOS:000073582100037 PM 9605877 ER PT J AU Papanicolaou, GJ Parsa, NZ Meltzer, PS Trent, JM AF Papanicolaou, GJ Parsa, NZ Meltzer, PS Trent, JM TI Assignment of interferon gamma receptor (IFNGR1) to human chromosome bands 6q24.1->q24.2 by in situ hybridization (vol 76, pg 181, 1997) SO CYTOGENETICS AND CELL GENETICS LA English DT Correction, Addition C1 NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. RP Papanicolaou, GJ (reprint author), UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 78 IS 2 BP 132 EP 132 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA YE373 UT WOS:A1997YE37300011 ER PT J AU Zullo, SJ Butler, L Zahorchak, RJ Macville, M Wilkes, C Merril, CR AF Zullo, SJ Butler, L Zahorchak, RJ Macville, M Wilkes, C Merril, CR TI Localization by fluorescence in situ hybridization (FISH) of human mitochondrial polymerase gamma (POLG) to human chromosome band 15q24 -> q26, and of mouse mitochondrial polymerase gamma (Polg) to mouse chromosome band 7E, with confirmation by direct sequence analysis of bacterial artificial chromosomes (BACs) SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID DNA-POLYMERASE; IDENTIFICATION; SUBUNIT; GENE AB Cloned cDNAs for the human mitochondrial DNA polymerase gamma (POLG) were identified by homology with the yeast mitochondrial DNA polymerase catalytic subunit (MIP). Fluorescence in situ hybridization (FISH) of human and mouse bacterial artificial chromosomes (BACs), hybridized by radioactively labeled POLG cDNAs, mapped to human chromosome band 15q24-->q26, as well as to mouse chromosome band 7E. Direct sequencing of the BAC DNA without subcloning confirmed the presence of both human POLG and mouse mitochondrial DNA polymerase gamma (Polg) in the respective BACs. C1 NIMH, Biochim Genet Lab, NIH, Bethesda, MD 20892 USA. Res Genet Inc, Huntsville, AL 35801 USA. Natl Human Genome Res Inst, Diagnost Dev Branch, NIH, Bethesda, MD USA. RP Zullo, SJ (reprint author), NIMH, Biochim Genet Lab, NIH, Bldg 10,Room 2D56, Bethesda, MD 20892 USA. EM zullo@helix.nih.gov NR 13 TC 12 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 78 IS 3-4 BP 281 EP 284 DI 10.1159/000134672 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA YW138 UT WOS:000071902100027 PM 9465903 ER PT J AU Gorodinsky, A Zimonjic, DB Popescu, NC Milbrandt, J AF Gorodinsky, A Zimonjic, DB Popescu, NC Milbrandt, J TI Assignment of the GDNF family receptor alpha-1 (GFRA1) to human chromosome band 10q26 by in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID TYROSINE KINASE; RET; PROTOONCOGENE C1 Washington Univ, Sch Med, Dept Pathol, Div Lab Med, St Louis, MO 63110 USA. NCI, Biol Lab, Bethesda, MD 20892 USA. RP Milbrandt, J (reprint author), Washington Univ, Sch Med, Dept Pathol, Div Lab Med, Campus Box 8118,660 S Euclid Ave, St Louis, MO 63110 USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 78 IS 3-4 BP 289 EP 290 DI 10.1159/000134674 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA YW138 UT WOS:000071902100029 PM 9465905 ER PT J AU Wienberg, J Stanyon, R Nash, WG OBrien, PCM Yang, F OBrien, SJ FergusonSmith, MA AF Wienberg, J Stanyon, R Nash, WG OBrien, PCM Yang, F OBrien, SJ FergusonSmith, MA TI Conservation of human vs. feline genome organization revealed by reciprocal chromosome painting SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID INSITU SUPPRESSION HYBRIDIZATION; CYTOGENETIC ANALYSIS; DNA LIBRARIES; FLUORESCENCE; MAMMALS; MAP; KARYOTYPES; PRIMATES; SEGMENTS; MOUSE AB We employed fluorescence in situ hybridization (FISH) with probes established by flow sorting metaphase chromosomes of the domestic cat (Felis cattus, 2n = 38) to ''paint'' homologous segments on human chromosomes and, reciprocally, using human chromosome paints on feline metaphase preparations. The results revealed, by direct microscopic observation, widespread conservation of genome organization between the two mammalian orders and confirmed 90% of the homologous genes mapped to both species. Fourteen of 23 human chomosomes were hybridized with single cat probes, and 9 of 19 cat chromosomes were entirely labeled by a single human probe. All other chromosomes were labeled with only two or, at most, three probes of the respective species. Y-chromosome probes gave no signals. Approximately 30 syntenic segments were identified, and the number of translocations could be estimated to be on the order of one new translocation per 10 million years in the phylogenetic lines leading to human and cat. Using the principle of maximum parsimony, the primitive vs. derived human chromosome segments were identified by comparison to the feline, cattle, and pig genomes, a first step in reconstructing the evolutionary heritage of the mammalian radiations. The results suggest that reciprocal chromosome painting will help reconstruct the history of genomic changes by determining the polarity of chromosomal rearrangements and establishing the ancestral karyotype for each principle branching point in mammalian evolution. C1 UNIV GENOA,DEPT ANTHROPOL SCI,GENOA,ITALY. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. RP Wienberg, J (reprint author), UNIV CAMBRIDGE,DEPT PATHOL,TENNIS COURT RD,CAMBRIDGE CB2 1QP,ENGLAND. OI Stanyon, Roscoe/0000-0002-7229-1092 NR 31 TC 102 Z9 102 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 77 IS 3-4 BP 211 EP 217 DI 10.1159/000134579 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA XQ680 UT WOS:A1997XQ68000015 PM 9284919 ER PT J AU Kallioniemi, O AF Kallioniemi, O TI DNA sequence copy number surveys in studies of tumor progression SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 NIH,NATL HUMAN GENOME RES INST,CANC GENET LAB,BETHESDA,MD 20852. TAMPERE UNIV HOSP,INST MED TECHNOL,TAMPERE,FINLAND. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 77 IS 1-2 BP L3 EP L3 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA XG385 UT WOS:A1997XG38500003 ER PT J AU Ried, T Macville, M Veldman, T PadillaNash, H Roschke, A Ning, Y duManoir, S BarAm, I Garini, Y Liyanage, M Schrock, E AF Ried, T Macville, M Veldman, T PadillaNash, H Roschke, A Ning, Y duManoir, S BarAm, I Garini, Y Liyanage, M Schrock, E TI Spectral karyotyping SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 NIH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. APPL SPECTRAL IMAGING,MIGDAL HAEMEQ,ISRAEL. NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 77 IS 1-2 BP L4 EP L4 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA XG385 UT WOS:A1997XG38500004 ER PT J AU Haas, OQ Schrock, E Ried, T AF Haas, OQ Schrock, E Ried, T TI Deciphering complex karyotypes of hematologic neoplasms with spectral karyotyping (SKY). SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 ST ANNA CHILDRENS HOSP,CHILDRENS CANC RES INST,A-1090 VIENNA,AUSTRIA. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 77 IS 1-2 BP W35 EP W35 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA XG385 UT WOS:A1997XG38500044 ER PT J AU Koi, M Lamb, PW Filatov, L Feinberg, AP Barrett, JC AF Koi, M Lamb, PW Filatov, L Feinberg, AP Barrett, JC TI Construction of chicken x human microcell hybrids for human gene targeting SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID MOUSE; CELLS; FUSION AB Human chromosomes 1, 2, 3, and 11 were tagged with pSV2 neo and transferred via microcell fusion from mouse A9 human monochromosomal hybrids to a chicken pre-B cell line, DT40, proficient for homologous recombination. Hybrids containing two copies of human chromosome 11 were transfected with targeting vectors containing a mammalian selectable gene with either the D11S16 or HRAS genomic sequences corresponding to two different chromosome 11 loci. Analysis of stable transfectants showed a high frequency (similar to 80%) of targeted integration of these constructs into each of the homologous loci of human chromosome 11 in DT40 hybrids. The results suggest that any human genomic sequences on human chromosomes transferred into DT40 cells could be targeted at high frequency, thereby allowing for subsequent modification of human genes and chromosomes. C1 NIEHS,MOL CARCINOGENESIS LAB,CANC & AGING GRP,NATL INST HLTH SCI,RES TRIANGLE PK,NC 27709. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. RP Koi, M (reprint author), NIEHS,MOL CARCINOGENESIS LAB,GENE MAPPING & CLONING GRP,NATL INST HLTH SCI,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Koi, Minoru/C-3489-2012; Koi, Minoru/G-9197-2014 FU NCI NIH HHS [CA54358] NR 13 TC 14 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 76 IS 1-2 BP 72 EP 76 DI 10.1159/000134519 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA WY176 UT WOS:A1997WY17600020 PM 9154132 ER PT J AU Pappanicolaou, GJ Parsa, NZ Meltzer, PS Trent, JM AF Pappanicolaou, GJ Parsa, NZ Meltzer, PS Trent, JM TI Assignment of interferon gamma receptor (IFNGR1) to human chromosome bands 6q24.1->q24.2 by in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article C1 NHGRI,CANC GENET LAB,NIH,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. NR 9 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 76 IS 3-4 BP 181 EP 182 DI 10.1159/000134542 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA XC053 UT WOS:A1997XC05300015 ER PT J AU Levanat, S Chidambaram, A Wicking, C BrayWard, P Pressman, C Toftgard, R Gailani, MR Myers, JC Wainwright, B Dean, M Bale, AE AF Levanat, S Chidambaram, A Wicking, C BrayWard, P Pressman, C Toftgard, R Gailani, MR Myers, JC Wainwright, B Dean, M Bale, AE TI Pulsed-field gel electrophoresis and FISH mapping of chromosome 9q22: Placement of a novel zinc finger gene within the NBCCS and ESS1 region SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID CELL-CARCINOMA-SYNDROME; HUMAN GENOME; INTERNATIONAL WORKSHOP; CONSTRUCTION; RESOLUTION; CLONING; CONTIG; ANEMIA; APRIL; MAP AB Chromosome 9q22 is a gene-rich region to which several human disease loci have been mapped. Pulsed field gel electrophoresis (PFGE) and FISH were used to determine the order of and distance between 12 chromosome 9q22 markers flanked by D9S196 and D9S180. D9S780 and XPA were within 190 kb of each other and hybridized to the same 460-kb NotI fragment as D9S180. ZNF169, a novel kruppel-type gene, and D9S280 shared several PFGE fragments indicating that they are not more than 300 kb apart. Interphase FISH showed that COL15A1 lies distal to the region bounded by D9S180 and D9S196 and that ZNF169 is adjacent to D9S196. Based on the restriction fragment lengths in this region and estimates from FISH, the distance from D9S180 to D9S196 is not less than 2 Mb. C1 YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06520. FREDERICK CANC RES & DEV CTR,SAIC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. UNIV QUEENSLAND,BRISBANE,QLD,AUSTRALIA. KAROLINSKA INST,CTR NUTR & TOXICOL,DEPT BIOSCI,HUDDINGE,SWEDEN. UNIV PENN,SCH MED,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Wicking, Carol/0000-0002-7225-3803 FU NCI NIH HHS [R01 CA57605, K11 CA 60199] NR 22 TC 8 Z9 8 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1997 VL 76 IS 3-4 BP 208 EP 213 DI 10.1159/000134551 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA XC053 UT WOS:A1997XC05300024 PM 9186526 ER PT J AU BenBaruch, A Bengali, K Tani, K Xu, LL Oppenheim, JJ Wang, JM AF BenBaruch, A Bengali, K Tani, K Xu, LL Oppenheim, JJ Wang, JM TI IL-8 and NAP-2 differ in their capacities to bind and chemoattract 293 cells transfected with either IL-8 receptor type A or type B SO CYTOKINE LA English DT Article DE IL-8; NAP-2; IL-8 receptors ID NEUTROPHIL-ACTIVATING PEPTIDE-2; HUMAN INTERLEUKIN-8 RECEPTOR; SIGNAL-TRANSDUCTION; AMINO TERMINUS; HIGH-AFFINITY; A RECEPTOR; GRO-ALPHA; RESIDUES; ANALOGS; BETA AB Two receptors for interleukin 8 (IL-8), IL-8rA and IL-8rB, have been cloned, Previous studies of neutrophils indicated that the two C-X-C chemokines; IL-8 and NAP-2, bind to IL-8rB with high affinity but that only IL-8 binds to IL-8rA with high affinity, In this study, human kidney embryonal 293 cells were transfected to express solely IL8rA or IL-8rB (the cells are designated IL-8rA/293 and IL-8rB/293, respectively), The authors show that NAP-2 bound both IL-8rA and IL-9rB specifically, While NAP-2 and IL-8 bound IL-8rB with comparable high affinity (2.9 +/- 0.5 and 2.8 +/- 0.8 nM, respectively), NAP-2 showed a lower binding affinity to IL-8rA (9 +/- 2 nM) compared with IL-8 (1.3 +/- 0.5 nM), A lower number of binding sites was detected for NAP-2 than for IL-8 on IL-8rA/293 cells as well on IL-8rB/293 cells, On both cell types (IL-8rA/293 and IL-8rb/293), NAP-2 and IL-8 could completely inhibit [I-125]NAP-2 binding, while unlabelled NAP-2 could only partially compete for [I-125]IL-8 binding. Functional assays revealed that although NAP-2 is chemotactic for both IL-8rA/293 and IL-8rB/293 cells, it is less potent than IL-8. While NAP-2 induced chemotaxis of IL-8rB/293 cells at the same optimal concentrations as IL-8 (10-100 ng/ml), the induction of optimal migratory response of IL-8rA/293 cells required much higher concentrations of NAP-2 than IL-8 (1000-3000 ng/ml and 10-100 ng/ml, respectively). The dose-response curve of the IL-8rB/293 cells to IL-8 was bell shaped, while the response to NAP-2 was sustained at a plateau level even at concentrations as high as 3000 ng/ml, It is likely that tertiary structural differences bet,peen NAP-2 and IL-8 account for their divergent abilities to bind and chemoattract 293 cells transfected with either IL-8 receptor type A or type B. (C) 1997 Academic Press Limited. C1 NCI,FREDERICK CANC RES & DEV CTR,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. NR 34 TC 34 Z9 34 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD JAN PY 1997 VL 9 IS 1 BP 37 EP 45 DI 10.1006/cyto.1996.0133 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA WL135 UT WOS:A1997WL13500005 PM 9067094 ER PT J AU Ding, I Wu, T Matsubara, H Magae, J Shou, M Cook, J Okunieff, P AF Ding, I Wu, T Matsubara, H Magae, J Shou, M Cook, J Okunieff, P TI Acidic fibroblast growth factor (FGF(1)) increases survival and haematopoietic recovery in total body irradiated C3H/HeNCr mice SO CYTOKINE LA English DT Article DE cell cycle; cytokines; radioprotection; radiation damage; heparin ID BONE-MARROW CELLS; ENDOTHELIAL-CELLS; SUPEROXIDE-DISMUTASE; PROGENITOR CELLS; IN-VIVO; MEGAKARYOCYTOPOIESIS; INTERLEUKIN-1; PROTEOGLYCAN; INDUCTION; COMPLEXES AB Basic fibroblast growth factor is known to stimulate the proliferation of bone marrow stem and/or progenitor cells in vitro and in vivo, We examined a similar cytokine, acidic fibroblast growth factor (FGF(1)), for its in vivo radiomodifying effects, Female C3H/HeNCr mice were given human recombinant FGF(1) intravenously at doses ranging from 1 to 24 pg. FGF(1) was delivered in two equal doses 24 and 4 h before or 24 h after otherwise lethal total body irradiation (TBI), In vivo FGF(1) radioprotection of C3H mice was maximized at a total dose of 12 mu g/mouse given before TBI. The radiomodification was 1.16 +/- 0.03 (+/- SD) with an increase of LD(50/30) from 736 +/- 9 to 854 +/- 16 cGy (P < 0.01), Some retroactive radiomodification was observed even when FGF(1) was given 24 h after irradiation (P < 0.05). FGF(1) radioprotected mice by improving the repopulation of haematopoietic progenitor cells of bone marrow, The radioprotection was not associated with an increase in S-phase fraction or detectable circulating IL-3, TNF-alpha or GM-CSF, suggesting that other mechanisms of protection were responsible, (C) 1997 Academic Press Limited. C1 NCI,RADIAT ONCOL BRANCH,NIH,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NCI,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20892. NR 32 TC 15 Z9 16 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD JAN PY 1997 VL 9 IS 1 BP 59 EP 65 DI 10.1006/cyto.1996.0136 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA WL135 UT WOS:A1997WL13500008 PM 9067097 ER PT B AU Kasprzak, KS AF Kasprzak, KS BE Hadjiliadis, ND TI The oxidative damage hypothesis of metal-induced genotoxicity and carcinogenesis SO CYTOTOXIC, MUTAGENIC AND CARCINOGENIC POTENTIAL OF HEAVY METALS RELATED TO HUMAN ENVIRONMENT SE NATO ADVANCED SCIENCE INSTITUTES SERIES, SER 2 LA English DT Proceedings Paper CT NATO Advanced Study Institute on Cytotoxic, Mutagenic and Carcinogenic Potential of Heavy Metals Related to Human Environment CY JUN 15-26, 1996 CL PRZESIEKA, POLAND SP NATO, Univ Ioannina, Univ Wroclaw AB This paper presents evidence that genotoxic and carcinogenic effects of certain transition metals are associated with oxidative damage to DNA and nuclear proteins. The metals, including Ni, Cr, and Co, are capable of causing promutagenic lesions, such as DNA base modifications, inter- and intra-molecular crosslinks of DNA and proteins, DNA strand breaks, rearrangements, and depurination. The underlying mechanisms involve generation of various kinds of active oxygen and other highly reactive species from metal-catalyzed redox reactions of O-2, H2O2, lipid peroxides, and other cellular substrates, and their attack on cell nucleus. Metal-mediated damage of other tissue and cellular components, resulting in inflammation, lipid peroxidation, suppression of cellular antioxidant defenses, and impairment of DNA repair, may also contribute to those mechanisms. Data revealing the oxidative character of metal-induced promutagenic DNA damage are particularly strong for two most powerful human metal carcinogens, nickel and chromium. However, without excluding various pathogenic effects caused by non-redox interactions, oxidative damage tends to take the leading role in explaining the mechanisms of carcinogenicity of cobalt and certain other metals as well. RP Kasprzak, KS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205,FREDERICK,MD 21702, USA. NR 0 TC 26 Z9 26 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4432-4 J9 NATO ASI 2 PY 1997 VL 26 BP 73 EP 92 PG 20 WC Chemistry, Multidisciplinary; Environmental Sciences SC Chemistry; Environmental Sciences & Ecology GA BH21Z UT WOS:A1997BH21Z00005 ER PT B AU Kasprzak, KS AF Kasprzak, KS BE Hadjiliadis, ND TI Effects of calcium, magnesium, zinc, and iron on nickel carcinogenesis: Inhibition versus enhancement SO CYTOTOXIC, MUTAGENIC AND CARCINOGENIC POTENTIAL OF HEAVY METALS RELATED TO HUMAN ENVIRONMENT SE NATO ADVANCED SCIENCE INSTITUTES SERIES, SER 2 LA English DT Proceedings Paper CT NATO Advanced Study Institute on Cytotoxic, Mutagenic and Carcinogenic Potential of Heavy Metals Related to Human Environment CY JUN 15-26, 1996 CL PRZESIEKA, POLAND SP NATO, Univ Ioannina, Univ Wroclaw AB This paper reviews the investigations on interactions between nickel and calcium, magnesium, zinc, or iron, aimed at elucidation of the mechanisms of nickel carcinogenesis and its prevention. Depending on the animal species, target tissues, particular metal compounds, and routes of administration, the divalent metals magnesium, calcium, or zinc, inhibit or have no effect on nickel carcinogenesis, whereas trivalent iron can either inhibit or enhance it. The molecular mechanisms involved in the observed effects are likely to include interactions at the tissue and cellular metal transport levels. They may, as well, depend on binding competition among metal ions at chromatin (e.g., DNA, histones, transcription factors, DNA repair enzymes) and other regulatory molecules in both the target cells, which give rise to tumors, and immune cells, which ale responsible for controlling tumor growth. RP Kasprzak, KS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205,FREDERICK,MD 21702, USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4432-4 J9 NATO ASI 2 PY 1997 VL 26 BP 93 EP 106 PG 14 WC Chemistry, Multidisciplinary; Environmental Sciences SC Chemistry; Environmental Sciences & Ecology GA BH21Z UT WOS:A1997BH21Z00006 ER PT B AU Bal, W Kasprzak, KS AF Bal, W Kasprzak, KS BE Hadjiliadis, ND TI Modeling the metal binding sites in core histones: Interactions of carcinogenic Ni(II) with the -CAIH- motif of histone H3. SO CYTOTOXIC, MUTAGENIC AND CARCINOGENIC POTENTIAL OF HEAVY METALS RELATED TO HUMAN ENVIRONMENT SE NATO ADVANCED SCIENCE INSTITUTES SERIES, SER 2 LA English DT Proceedings Paper CT NATO Advanced Study Institute on Cytotoxic, Mutagenic and Carcinogenic Potential of Heavy Metals Related to Human Environment CY JUN 15-26, 1996 CL PRZESIEKA, POLAND SP NATO, Univ Ioannina, Univ Wroclaw AB This paper presents results of studies on interactions of carcinogenic nickel with -CAIH-, a potential metal binding motif in nuclear chromatin. Structural and mechanistic results are discussed in the perspective of various concepts in nickel carcinogenesis. Evidence is presented for a major role of oxidative mechanism of damage caused by Ni(II) binding and reactivity on both genotoxic (DNA) and epigenetic (core histones) levels. Preliminary results of a study of (H3-H4)(2) histone tetramer supporting the validity of CAIH model are also shown. RP Bal, W (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205,FREDERICK,MD 21702, USA. NR 0 TC 17 Z9 17 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4432-4 J9 NATO ASI 2 PY 1997 VL 26 BP 107 EP 121 PG 15 WC Chemistry, Multidisciplinary; Environmental Sciences SC Chemistry; Environmental Sciences & Ecology GA BH21Z UT WOS:A1997BH21Z00007 ER PT B AU Sipowicz, MA Diwan, BA Ramljak, D Buzard, GS Yu, W Waalkes, MP Rice, JM Kasprzak, KS Anderson, LM AF Sipowicz, MA Diwan, BA Ramljak, D Buzard, GS Yu, W Waalkes, MP Rice, JM Kasprzak, KS Anderson, LM BE Hadjiliadis, ND TI Perinatal effects of metals and cancer in offspring SO CYTOTOXIC, MUTAGENIC AND CARCINOGENIC POTENTIAL OF HEAVY METALS RELATED TO HUMAN ENVIRONMENT SE NATO ADVANCED SCIENCE INSTITUTES SERIES, SER 2 LA English DT Proceedings Paper CT NATO Advanced Study Institute on Cytotoxic, Mutagenic and Carcinogenic Potential of Heavy Metals Related to Human Environment CY JUN 15-26, 1996 CL PRZESIEKA, POLAND SP NATO, Univ Ioannina, Univ Wroclaw RP Sipowicz, MA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,DIV BASIC SCI,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4432-4 J9 NATO ASI 2 PY 1997 VL 26 BP 123 EP 138 PG 16 WC Chemistry, Multidisciplinary; Environmental Sciences SC Chemistry; Environmental Sciences & Ecology GA BH21Z UT WOS:A1997BH21Z00008 ER PT B AU Tombran-Tink, J Chader, G Koenekoop, R AF Tombran-Tink, J Chader, G Koenekoop, R BE LaVail, MM Hollyfield, JG Anderson, RE TI Molecular analysis of the human PEDF gene, a candidate gene for retinal degeneration: Localization to 17p13.3 SO DEGENERATIVE RETINAL DISEASES LA English DT Proceedings Paper CT VII International Symposium on Retinal Degeneration CY OCT 05-09, 1996 CL SENDAI, JAPAN C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tombran-Tink, J (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-45701-6 PY 1997 BP 245 EP 254 PG 10 WC Ophthalmology SC Ophthalmology GA BK07H UT WOS:000071070800027 ER PT S AU Borkowski, TA Letterio, JJ Mackall, CL Saitoh, A Farr, AG Wang, XJ Roop, DR Gress, RE Udey, MC AF Borkowski, TA Letterio, JJ Mackall, CL Saitoh, A Farr, AG Wang, XJ Roop, DR Gress, RE Udey, MC BE RicciardiCastagnoli, P TI Langerhans cells in the TGF beta 1 null mouse SO DENDRITIC CELLS IN FUNDAMENTAL AND CLINICAL IMMUNOLOGY, VOL 3 SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 4th International Conference on Dendritic Cells in Fundamental and Clinical Immunology CY OCT 05-10, 1996 CL LIDO, ITALY ID GROWTH-FACTOR-BETA; DENDRITIC CELLS; EXPRESSION; MICE RP Borkowski, TA (reprint author), NCI, DERMATOL BRANCH, NIH, BLDG 10, BETHESDA, MD 20892 USA. NR 17 TC 18 Z9 19 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45592-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 417 BP 307 EP 310 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BJ40F UT WOS:A1997BJ40F00050 PM 9286378 ER PT S AU Bender, A Sapp, M Feldman, M Reddy, A Seder, R Schuler, G Steinman, RM Bhardwaj, N AF Bender, A Sapp, M Feldman, M Reddy, A Seder, R Schuler, G Steinman, RM Bhardwaj, N BE RicciardiCastagnoli, P TI Dendritic cells as immunogens for human CTL responses SO DENDRITIC CELLS IN FUNDAMENTAL AND CLINICAL IMMUNOLOGY, VOL 3 SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 4th International Conference on Dendritic Cells in Fundamental and Clinical Immunology CY OCT 05-10, 1996 CL LIDO, ITALY ID STIMULATORY FACTOR; T-CELLS; IMMUNOREGULATORY FUNCTIONS; INTERFERON-GAMMA; INFLUENZA-VIRUS; HUMAN BLOOD; INTERLEUKIN-12; GENERATION; CYTOKINE; IL-12 AB The cellular requirements for generating potent human CD8+ CTLs to influenza A virus in vitro have been defined. Furthermore, we have developed improved methods for generating large numbers of DCs from non-proliferating progenitors. These developments have enabled the design of new strategies to elicit CTLs in vivo. For example, together with IL-12, antigen-pulsed DCs may be a useful approach for boosting CTL responses against infectious agents and malignancies. Our results also reopen the potential use of inactivated virus preparations as immunogens for CTL responses. C1 ROCKEFELLER UNIV, NEW YORK, NY 10021 USA. NIH, BETHESDA, MD 20892 USA. RP Bender, A (reprint author), UNIV ERLANGEN NURNBERG, D-8520 ERLANGEN, GERMANY. RI Steinman, Ralph/F-7729-2012 NR 18 TC 8 Z9 8 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45592-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 417 BP 383 EP 387 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BJ40F UT WOS:A1997BJ40F00062 PM 9286390 ER PT S AU Weissman, D Rubbert, A Combadiere, C Murphy, PM Fauci, AS AF Weissman, D Rubbert, A Combadiere, C Murphy, PM Fauci, AS BE RicciardiCastagnoli, P TI Dendritic cells express and use multiple HIV coreceptors SO DENDRITIC CELLS IN FUNDAMENTAL AND CLINICAL IMMUNOLOGY, VOL 3 SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 4th International Conference on Dendritic Cells in Fundamental and Clinical Immunology CY OCT 05-10, 1996 CL LIDO, ITALY ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELLS; RECEPTOR; INFECTION; CHEMOKINE; ENTRY; 7-TRANSMEMBRANE; IDENTIFICATION; COFACTOR; CLONING C1 NIAID, HOST DEF LAB, NIH, BETHESDA, MD 20892 USA. RP Weissman, D (reprint author), NIAID, IMMUNOREGULAT LAB, NIH, BLDG 10, BETHESDA, MD 20892 USA. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 15 TC 10 Z9 10 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45592-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 417 BP 401 EP 406 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BJ40F UT WOS:A1997BJ40F00065 PM 9286393 ER PT S AU Slavkin, HC Diekwisch, TGH AF Slavkin, HC Diekwisch, TGH BE Chadwick, DJ Cardew, G TI Molecular strategies of tooth enamel formation are highly conserved during vertebrate evolution SO DENTAL ENAMEL SE CIBA FOUNDATION SYMPOSIA LA English DT Article; Proceedings Paper CT Symposium on Dental Enamel CY APR 23-25, 1996 CL CIBA FDN, LONDON, ENGLAND SP Ciba Fdn HO CIBA FDN ID IMMUNOHISTOCHEMICAL LOCALIZATION; AMELOGENIN; GENES; TEETH; CHROMOSOMES; TRANSCRIPT; PROTEINS AB The vertebrate body plan is determined by a variety of morphoregulatory genes that are highly conserved throughout evolution. This review presents a phylogenetic analysis of selected molecular and morphological features in vertebrates with particular emphasis upon the phylogeny of tooth morphogenesis and enamel formation. Three lines of evidence support our hypothesis that the agnathans (e.g. hagfishes) are the most primitive extant vertebrates and that enamel gene products are highly conserved during vertebrate evolution. First, an antibody raised against the polypeptide produced by exon 4 of the mouse amelogenin gene recognizes proteins in hagfish, sharks, reptiles and mammals. Second, electron photomicrographic evidence suggests heterochronic shifts in the relative time and rate of enamel formation during vertebrate tooth evolution. Third, mRNA phenotyping suggests significant homology between amelogenin transcripts expressed in species of various vertebrate phyla including agnathans and mammals. These three lines of evidence indicate that amelogenin gene products are expressed in agnathan, reptilian and mammalian teeth. C1 BAYLOR COLL DENT, DEPT BIOMED SCI, DALLAS, TX 75266 USA. RP Slavkin, HC (reprint author), NIDR, NIH, BLDG 31, ROOM 2C39, BETHESDA, MD 20892 USA. FU NIDCR NIH HHS [DE-02848, DE-09165, DE-06425] NR 35 TC 18 Z9 18 U1 0 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND SN 0300-5208 BN 0-471-96872-2 J9 CIBA F SYMP PY 1997 VL 205 BP 73 EP 84 PG 12 WC Dentistry, Oral Surgery & Medicine; Medicine, General & Internal SC Dentistry, Oral Surgery & Medicine; General & Internal Medicine GA BH80W UT WOS:A1997BH80W00005 PM 9189618 ER PT S AU Deutsch, D Dafni, L Palmon, A Hekmati, M Young, MF Fisher, LW AF Deutsch, D Dafni, L Palmon, A Hekmati, M Young, MF Fisher, LW BE Chadwick, DJ Cardew, G TI Tuftelin: Enamel mineralization and amelogenesis imperfecta SO DENTAL ENAMEL SE CIBA FOUNDATION SYMPOSIA LA English DT Article; Proceedings Paper CT Symposium on Dental Enamel CY APR 23-25, 1996 CL CIBA FDN, LONDON, ENGLAND SP Ciba Fdn HO CIBA FDN ID RAT INCISOR; PROTEINS; GENE; FETAL; BIOSYNTHESIS; MUTATION; ALBUMIN; AIH1 AB Tuftelin is a novel acidic enamel protein thought to play a major role in enamel mineralization. Its identity and localization has been confirmed by amino acid composition, enzyme-linked immunosorbant assay, Western blots, indirect immunohistochemistry and high resolution protein-A gold immunocytochemistry. The deduced tuftelin protein (pI 5.2) contains 389 amino acids and has a calculated peptide molecular mass of 43 814 Da. Immunological studies suggest conservation of tuftelin structure between species throughout vertebrate evolution. The cDNA sequence encodes for several putative pose-translation sites including one N-glycosylation consensus site, seven O-glycosylation sites and seven phosphorylation sites, as well as an EF-hand calcium-binding domain (with mismatch), localized towards the N-terminal region. At the C-terminal region (residues 252-345) tuftelin contains structurally relevant determinants for self assembly. We recently cloned and partially sequenced the human tuftelin gene (four exons have now been sequenced). These sequences include exon 1 and over 1000 bases of the putative promoter region. Employing fluorescent in situ hybridization, we mapped the human tuftelin gene to chromosome Iq 21-31. Localization of the human tuftelin gene to a well-defined cytogenetic region may be important in understanding the aetiology of autosomally inherited amelogenesis imperfecta, the most common enamel hereditary disease. C1 NIDR, BONE RES BRANCH, NIH, BETHESDA, MD 20892 USA. RP Deutsch, D (reprint author), HEBREW UNIV JERUSALEM, HADASSAH MED SCH, FAC MED DENT, DENT RES UNIT, POB 1172, IL-91010 JERUSALEM, ISRAEL. NR 46 TC 13 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND SN 0300-5208 BN 0-471-96872-2 J9 CIBA F SYMP PY 1997 VL 205 BP 135 EP 155 PG 21 WC Dentistry, Oral Surgery & Medicine; Medicine, General & Internal SC Dentistry, Oral Surgery & Medicine; General & Internal Medicine GA BH80W UT WOS:A1997BH80W00009 PM 9189622 ER PT B AU Lebowitz, BD AF Lebowitz, BD BE Rubinstein, RL Lawton, MP TI Depression in the nursing home: Developments and prospects SO DEPRESSION IN LONG TERM AND RESIDENTIAL CARE: ADVANCES IN RESEARCH AND TREATMENT LA English DT Proceedings Paper CT Conference on Shades of Gray - Depression Among the Old and Frail - A Multidisciplinary Symposium CY APR 11-12, 1994 CL PHILADELPHIA, PA ID CARE C1 NIMH, Mental Disorders Aging Res Branch, Rockville, MD 20857 USA. RP Lebowitz, BD (reprint author), NIMH, Mental Disorders Aging Res Branch, Rockville, MD 20857 USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PUBLISHING CO PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 0-8261-9550-4 PY 1997 BP 223 EP 233 PG 11 WC Psychology, Clinical; Geriatrics & Gerontology; Nursing; Psychiatry; Psychology; Social Work SC Psychology; Geriatrics & Gerontology; Nursing; Psychiatry; Social Work GA BN28E UT WOS:000081417600011 ER PT J AU Knezevic, V DeSanto, R Mackem, S AF Knezevic, V DeSanto, R Mackem, S TI Two novel chick T-box genes related to mouse Brachyury are expressed in different, non-overlapping mesodermal domains during gastrulation SO DEVELOPMENT LA English DT Article DE gastrulation; notochord; primitive streak; somitogenesis; T-box; Brachyury; chick embryo; activin; FGF; retinoic acid ID PRIMITIVE STREAK FORMATION; RETINOIC ACID; HOMEOBOX GENE; ZEBRAFISH HOMOLOG; DNA-BINDING; EMBRYO; PROTEIN; NOTOCHORD; INDUCTION; PATTERN AB The mouse Brachyury (T) gene plays critical roles in the genesis of normal mesoderm during gastrulation and in the maintenance of a functioning notochord. Abrogation of Brachyury (T) expression within the chordamesoderm of homozygous null mutants nevertheless spares anterior axis formation. An intriguing possibility to explain the preservation of anterior axis formation in these mutants would be the existence of other genes compensating for the loss of Brachyury. This compensation and the recent demonstration that Brachyury is the prototype for an evolutionarily conserved family, prompted a search for other T-box genes participating in axis formation. The chick Brachyury orthologue and two related chick T-box genes that are expressed at the onset of gastrulation have been isolated. One of these novel genes (Ch-TbxT) becomes restricted to the axial mesoderm lineage and is a potential candidate for complementing or extending Brachyury function in the anterior axis (formation of the head process, prechordal plate). The other gene (Ch-Tbx6L), together with chick T, appears to mark primitive streak progenitors before gastrulation. As cells leave the primitive streak, Ch-Tbx6L becomes restricted to the early paraxial mesoderm lineage and could play a role in regulating somitogenesis. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 69 TC 97 Z9 100 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN PY 1997 VL 124 IS 2 BP 411 EP 419 PG 9 WC Developmental Biology SC Developmental Biology GA WH004 UT WOS:A1997WH00400015 PM 9053317 ER PT J AU Mori, C Nakamura, N Dix, DJ Fujioka, M Nakagawa, S Shiota, K Eddy, EM AF Mori, C Nakamura, N Dix, DJ Fujioka, M Nakagawa, S Shiota, K Eddy, EM TI Morphological analysis of germ cell apoptosis during postnatal testis development in normal and hsp 70-2 knockout mice SO DEVELOPMENTAL DYNAMICS LA English DT Article DE testis; spermatogenesis; apoptosis; mouse; TUNEL; HSP70-2 ID DNA FRAGMENTATION; SERTOLI CELLS; ADULT-RATS; SEMINIFEROUS EPITHELIUM; SPERMATOGENIC CELLS; HORMONAL-CONTROL; DEATH; MOUSE; IDENTIFICATION; DEGENERATION AB The present study examined the occurrence of apoptotic cell death in the testis of wild-type mice from postnatal days 3 to 28 and in juvenile Hsp70-2 knockout mice. Adult Hsp70-2 knockout males are infertile and lack spermatids and spermatozoa (Dir et al. [1996a] Proc. Natl. Acad. Sci. U.S.A. 93:3264-3268). To identify the cell types undergoing apoptosis, we also examined the relationship between the occurrence of apoptotic cell death and the expression pattern of the Hsp70-2 gene product (heat-shock protein 70-2 [Hsp70-2]; marker for spermatocytes and spermatids), germ cell nuclear antigen 1 (GCNA1; marker for spermatogonia and spermatocytes), and vimentin (marker for Sertoli cells). This study shows that during postnatal development of the wildtype mouse testis (1) the percentage of apoptotic cell death detected by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method is higher in mice from days 8 to 22 than in younger or older mice, (2) the majority of apoptotic cells are spermatogonia and less frequently are spermatocytes, and (3) the degenerative cell death of spermatogonia and primary spermatocytes involves apoptosis with fragmentation of DNA. The analysis of apoptotic cell death in the testes of juvenile Hsp70-2 knockout mice showed an additional increased level of apoptosis at day 17, during the first wave of spermatogenesis, in pachytene spermatocytes. (C) 1997 Wiley-Liss, Inc. C1 KYOTO UNIV,FAC MED,CENT LAB ELECTRON MICROSCOPY,KYOTO,JAPAN. NIEHS,GAMETE BIOL SECT,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. US EPA,REPROD TOXICOL DIV,NATL HLTH & ENVIRONM EFFECTS RES LAB,RES TRIANGLE PK,NC 27711. RP Mori, C (reprint author), KYOTO UNIV,FAC MED,DEPT ANAT & DEV BIOL,SAKYO KU,KYOTO 60601,JAPAN. NR 55 TC 105 Z9 114 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JAN PY 1997 VL 208 IS 1 BP 125 EP 136 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA WA756 UT WOS:A1997WA75600012 PM 8989527 ER PT J AU Leco, KJ Harvey, MB Hogan, A Copeland, NG Gilbert, DJ Jenkins, NA Edwards, DR Schultz, GA AF Leco, KJ Harvey, MB Hogan, A Copeland, NG Gilbert, DJ Jenkins, NA Edwards, DR Schultz, GA TI Matrix metalloproteinase-9 maps to the distal end of chromosome 2 in the mouse SO DEVELOPMENTAL GENETICS LA English DT Article DE parthenogenetic embryos; trophoblast; imprinting ID IV COLLAGENASE; GROWTH-FACTOR; EMBRYO IMPLANTATION; EXPRESSION; INHIBITOR; GENE AB The activity and expression of matrix metalloproteinase-9/gelatinase B(MMP-9), an enzyme implicated in the implantation process in mice, was investigated in normal and parthenogenetic blastocyst outgrowths. Conditioned media from parthenogenetic blastocysts after 4 days of culture had reduced levels of MMP-9 activity compared to conditioned medium from normal outgrowths, levels of MMP-9 mRNA assayed by reverse transcription-polymerase chain reaction methods were also reduced in parthenogenetic blastocysts compared io normal outgrowths. Geneiic mapping studies showed that Mmp9 maps to the distal end of chromosome 2 near the proxima boundary of a region affected by genomic imprinting. Both parental alleles of Mmp9, however, are expressed in 11.5-day embryos derived from interspecific crosses of Mus musculus and Mus spretus. Thus, loss of MMP-9 activity in parthenogenetic blastocysts does not appear to be due to imprinting but, rather, due io a defect of trophoblast giant cell proliferation and differentiation. (C) 1997 Wiley-iiss, Inc. C1 UNIV CALGARY, DEPT MED BIOCHEM, CALGARY, AB T2N 4N1, CANADA. PRINCESS MARGARET HOSP, ONTARIO CANC INST, TORONTO, ON M4X 1K9, CANADA. QUEENSLAND UNIV TECHNOL, SCH LIFE SCI, BRISBANE, QLD, AUSTRALIA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MAMMALIAN GENET LAB, FREDERICK, MD 21701 USA. RI Edwards, Dylan/B-4734-2009 OI Edwards, Dylan/0000-0002-3292-2064 NR 26 TC 4 Z9 4 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0192-253X J9 DEV GENET JI Dev. Genet. PY 1997 VL 21 IS 1 BP 55 EP 60 DI 10.1002/(SICI)1520-6408(1997)21:1<55::AID-DVG6>3.0.CO;2-7 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA XU917 UT WOS:A1997XU91700006 PM 9291580 ER PT J AU Stewart, CL Cullinan, EB AF Stewart, CL Cullinan, EB TI Preimplantation development of the Mammalian embryo and its regulation by growth factors SO DEVELOPMENTAL GENETICS LA English DT Review DE preimplantation development; growth factors; leukemia inhibitory factor ID LEUKEMIA INHIBITORY FACTOR; TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; PERIIMPLANTATION MOUSE UTERUS; UTERINE EPITHELIAL-CELLS; DEVELOPMENT IN-VITRO; MICE LACKING; FACTOR-ALPHA; HUMAN ENDOMETRIUM AB Preimplantation development in mammals involves both the development of the embryo and the preparation of the uterus in anticipation of blastocyst implantation. Preparation of the uterus for implantation is primarily under the control of the ovarian sex steroids, estrogen and progesterone. Increasing evidence is revealing that their effects on cell proliferation and differentiation in the uterus are mediated by locally produced growth factors and cytokines. In contrast, preimplantation development of the embryo to the blastocyst stage appears to be independent of exogenous growth factors. implantation, the point at which the blastocyst forms a more intimate association with the maternal tissues, is regulated by the uterine expression of leukemia inhibitory factor (LIF), LIF is required both io promote embryo attachment and for decidualization of the uterus. In the absence of LIF, neither of these events occur. Uterine expression of LIF al the time of implantation has been described in many species, suggesting that LIF may be of general significance in regulating embryo implantation in mammals. (C) 1997 Wiley-Liss, Inc. C1 CHILDRENS HOSP PHILADELPHIA,DEPT PEDIAT,PHILADELPHIA,PA 19104. HOFFMANN LA ROCHE INC,INFLAMMAT AUTOIMMUNE DIS,NUTLEY,NJ 07110. RP Stewart, CL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,LAB CANC & DEV BIOL,FREDERICK,MD 21702, USA. NR 124 TC 107 Z9 113 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-253X J9 DEV GENET JI Dev. Genet. PY 1997 VL 21 IS 1 BP 91 EP 101 DI 10.1002/(SICI)1520-6408(1997)21:1<91::AID-DVG11>3.0.CO;2-D PG 11 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA XU917 UT WOS:A1997XU91700011 PM 9291585 ER PT J AU IshizuyaOka, A Stolow, MA Ueda, S Shi, YB AF IshizuyaOka, A Stolow, MA Ueda, S Shi, YB TI Temporal and spatial expression of an intestinal Na+/PO43- cotransporter correlates with epithelial transformation during thyroid hormone-dependent frog metamorphosis SO DEVELOPMENTAL GENETICS LA English DT Article DE intestine; tadpole; thyroid hormone ID BINDING PROTEIN GENE; AMPHIBIAN METAMORPHOSIS; XENOPUS-LAEVIS; CELL-DEATH; CLONING; INVITRO; CORTEX; SYSTEM; CDNA AB The amphibian intestine has two morphologically distinct structures during development. Early embryogenesis generates a simple, tubelike intestine in the tadpole whereas after thyroid hormone (T-3)-dependent metamorphosis a newly remodeled adult intestine is formed similar to that of higher vertebrates. This change requires a drastic transformation of the epithelial layer. We have isolated a Na+/PO43- cotransporter gene that may contribute to this transformation. The deduced amino acid sequence of this gene shows a high degree of homology to the mammalian renal Na+/PO43- cotransporters, which have little or no expression in organs other than the kidney. The frog gene is highly expressed and regulated by T-3 in the intestine with lithe expression and/or regulation by T-3 in most other organs. Its mRNA is restricted to the differentiated epithelial cells both in tadpoles and postmetamorphic frogs. Interestingly, its expression is low in premetamorphic tadpoles, but up-regulated when metamorphosis is initiated by endogenous T-3. As the larval epithelium undergoes programmed cell death (apoptosis), the mRNA level drops to a minimum. Subsequently the gene is reactivated at the tip region of the newly formed adult intestinal folds and a crest-trough polarity of expression is established by the end of metamorphosis. This temporal regulation profile is also reproduced when premetamorphic tadpoles are treated with T-3 to induce precocious intestinal remodeling. These results suggest a possible role of the Na+/PO43- cotransporter during metamorphosis and demonstrate that the adult epithelial cell differentiation pattern is established in the direction of crest-to-trough of the intestinal fold, concurrent with the epithelial morphogenic process. (C) 1997 Wiley-Liss, Inc. C1 NICHHD,MOL EMBRYOL LAB,BETHESDA,MD 20892. DOKKYO UNIV,SCH MED,DEPT ANAT,MIBU,TOCHIGI 32102,JAPAN. NR 42 TC 20 Z9 20 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 0192-253X J9 DEV GENET JI Dev. Genet. PY 1997 VL 20 IS 1 BP 53 EP 66 DI 10.1002/(SICI)1520-6408(1997)20:1<53::AID-DVG7>3.0.CO;2-8 PG 14 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA WQ636 UT WOS:A1997WQ63600007 PM 9094212 ER PT J AU Li, X Cvekl, A Bassnett, S Piatigorsky, J AF Li, X Cvekl, A Bassnett, S Piatigorsky, J TI Lens-preferred activity of chicken delta 1- and delta 2-crystallin enhancers in transgenic mice and evidence for retinoic acid-responsive regulation of the delta 1-crystallin gene SO DEVELOPMENTAL GENETICS LA English DT Article DE delta-crystallin; lens; gene expression; enhancers; transgenic mice; retinoic acid ID A-CRYSTALLIN PROMOTER; ARGININOSUCCINATE LYASE; INTERGENIC SPACER; NONLENS TISSUES; MAMMALIAN LENS; DUCK LENS; EXPRESSION; PROTEINS; CELLS; RECEPTORS AB There are two tandemly linked delta-crystallin genes (5' delta 1-delta 2 3') in the chicken, with the delta 1-crystallin gene being expressed much more highly (50-100-fold) in the embryonic lens than the delta 2-crystallin gene. Previous transfection experiments have shown that a lens-preferred enhancer exists in the third intron of each chicken delta-crystallin gene. In the present investigation we have used transgenic mice to establish that both the chicken delta 1- and delta 2-crystallin enhancers are preferentially active in the mouse lens in combination with their homologous promoter and the chloramphenicol acetyltransferase (CAT) reporter gene. The promoter/CAT constructs lacking the enhancers were inactive in the transgenic mice. In one case, a truncated delta 2-crystallin promoter (-308/+24) in combination with the enhancer was also active in the Purkinje cells of the cerebellum of the transgenic mice, which could prove useful in future experiments. Finally, retinoic acid receptors (RAR beta) activated the delta 1-crystallin, but not the delta 2-crystallin enhancer in the recombinant plasmids in cotransfected embryonic chicken lens epithelial cells treated with retinoic acid. This activation did not occur when using the core enhancer (fragment B4) lacking surrounding flanking sequences (fragment B3 and B5) of the enhancer. Together these experiments show that the chicken delta-crystallin enhancers show lens-preference in transgenic mice despite the absence of delta-crystallin in this species and add retinoic acid nuclear receptors to the growing list of transcription factors (including Pax-6, Sox-2, and delta EF3) that directly or indirectly contribute to the high expression of the delta 1-crystallin gene in the lens. (C) 1997 Wiley-Liss, Inc.(dagger) C1 NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,ST LOUIS,MO 63110. RI Cvekl, Ales/B-2427-2013 NR 44 TC 15 Z9 15 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 0192-253X J9 DEV GENET JI Dev. Genet. PY 1997 VL 20 IS 3 BP 258 EP 266 PG 9 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA XJ155 UT WOS:A1997XJ15500008 PM 9216065 ER PT J AU Gao, CY Zakeri, Z Zhu, Y He, HY Zelenka, PS AF Gao, CY Zakeri, Z Zhu, Y He, HY Zelenka, PS TI Expression of Cdk5, p35, and Cdk5-associated kinase activity in the developing rat lens SO DEVELOPMENTAL GENETICS LA English DT Article DE cyctin-dependent kinase; Cdk5; differentiation; rat lens; development; H1K ID CYCLIN-DEPENDENT KINASE-5; DIRECTED PROTEIN-KINASE; INTERMEDIATE FILAMENT PROTEINS; FIBER CELL-DIFFERENTIATION; NEURONAL CDC2-LIKE KINASE; TAU-PROTEIN; ALPHA-CRYSTALLINS; BOVINE BRAIN; KDA SUBUNIT; ACTIVATOR AB We have investigated the expression of Cdk5 and its regulatory subunit, p35, in the developing rat lens from embryonic day 16 (E16) to postnatal day 8 (P8). Reverse transcription and polymerase chain reaction (RT/PCR) detected Cdk5 and p35 mRNA expression in lens epithelial cells and in differentiating lens Fibers throughout this developmental period. Subsequent sequencing of the RT/PCR products confirmed their identities. In situ hybridization with Cdk5 and p35 riboprobes showed especially high expression of both mRNAs in the newly formed lens fiber cells in the bow region of the lens. Immunocytochemistry at E18 showed that Cdk5 was present in the cytoplasm df lens epithelial cells and fiber cells, with especially strong immunostaining at the anterior ends of the fibers. Fiber cells in the final stages of maturation, immediately prior to nuclear degeneration, showed positive staining for Cdk5 in the nucleus. Immunoprecipitation of proteins with Cdk5 antibody followed by immunoblotting with either N-terminal specific or C-terminal specific p35 antibodies demonstrated that p35 is complexed with Cdk5 in lens epithelial cells and lens fibers. Immunoprecipitates of Cdk5 from epithelial and fibers showed kinase activity in vitro using histone H1 as a substrate. These findings demonstrate that p35/Cdk5 activity is not restricted to neurons and raise the possibility that this kinase may play a role in lens fiber cell differentiation. (C) 1997 Wiley-Liss, Inc.(dagger) C1 NEI, MOL & DEV BIOL LAB, NIH, BETHESDA, MD 20892 USA. CUNY QUEENS COLL, DEPT BIOL, FLUSHING, NY 11367 USA. CUNY QUEENS COLL, GRAD CTR, FLUSHING, NY 11367 USA. FU PHS HHS [KO4 RO1-10101] NR 54 TC 67 Z9 69 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0192-253X J9 DEV GENET JI Dev. Genet. PY 1997 VL 20 IS 3 BP 267 EP 275 PG 9 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA XJ155 UT WOS:A1997XJ15500009 PM 9216066 ER PT J AU IshizuyaOka, A Ueda, S Shi, YB AF IshizuyaOka, A Ueda, S Shi, YB TI Temporal and spatial regulation of a putative transcriptional repressor implicates it as playing a role in thyroid hormone-dependent organ transformation SO DEVELOPMENTAL GENETICS LA English DT Article DE thyroid hormone; metamorphosis; transcriptional repressor; apoptosis; cell proliferation; morphogenesis ID BINDING PROTEIN GENE; AMPHIBIAN METAMORPHOSIS; XENOPUS-LAEVIS; BETA GENE; EXPRESSION; APOPTOSIS; LARVAL; DEATH; MYC AB Thyroid hormone (T-3) induces both larval cell death and adult cell proliferation and differentiation during amphibian metamorphosis. We have previously isolated a bZip transcription factor (TH/bZip) as a T-3 response gene in the metamorphosing Xenopus intestine. We demonstrate that the Xenopus TH/bZip gene is a direct T-3-response gene and ubiquitously regulated by T-3 in tadpoles. Developmental in situ hybridization analyses have shown that TH/bZip gene is regulated in a cell-type-specific manner that correlates with tissue transformation. In particular, it is found to be expressed in the larval intestinal epithelial ce Is prior to their apoptotic degeneration and in the proliferating adult cell types. However, the gene is repressed again upon adult cell differentiation. This regulation pattern mimics that of the thyroid hormone receptor (TR)beta genes. Since the TH/bZip gene is a direct T-3-response gene, such a correlation suggests that TR beta may be involved in the regulation of the TH/bZip gene. More importantly, in situ hybridization reveals a strong spatiotemporal correlation of TH/bZip expression with the tissue-specific remodeling in the intestine, suggesting that TH/bZip gene may participate, depending on the cell types, in both inducing apoptosis and stimulating cell proliferation. A similar role has been reported For the proto-oncogene c-myc, another leucine-zipper-containing transcription factor, in tissue culture cell systems. (C) 1997 Wiley-Liss, Inc. C1 NICHHD,MOL EMBRYOL LAB,BETHESDA,MD 20892. RP IshizuyaOka, A (reprint author), DOKKYO UNIV,SCH MED,DEPT ANAT,MIBU,TOCHIGI 32102,JAPAN. NR 41 TC 25 Z9 25 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 0192-253X J9 DEV GENET JI Dev. Genet. PY 1997 VL 20 IS 4 BP 329 EP 337 DI 10.1002/(SICI)1520-6408(1997)20:4<329::AID-DVG4>3.0.CO;2-9 PG 9 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA XP319 UT WOS:A1997XP31900004 PM 9254907 ER PT J AU Romans, SM Roeltgen, DP Kushner, H Ross, JL AF Romans, SM Roeltgen, DP Kushner, H Ross, JL TI Executive function in girls with Turner's syndrome SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID FRONTAL-LOBE; NEUROPSYCHOLOGICAL ASPECTS; LEARNING-DISABILITIES; X-MONOSOMY; CHILDREN; PERFORMANCE; IMPAIRMENT; PHENOTYPE; DEFICITS AB Turner's syndrome (TS), a genetic disorder affecting girls, has a well-described neurocognitive profile including difficulty with visuospatial processing and attention skills. The goal of this study was to investigate executive function and attention abilities in girls with TS. Executive skills include the ability to plan, organize, monitor, and execute multistep problem-solving processes. Measures of attention and executive function were analyzed from 105 girls with TS and from 153 female controls matched for age, IQ, and socioeconomic status. Three age groups were evaluated in order to assess developmental patterns in executive skills. The TS group (all ages) performed significantly less well than did controls on measures of attention, including the Freedom From Distractibility factor of the Wechsler Intelligence Scale for Children-Revised and the Test of Variables of Attention. In the executive function domain, girls with TS performed at levels comparable to controls on the Wisconsin Card Sort Test and on measures of semantic clustering, but they exhibited significant deficits on the Rey-Osterrieth organizational component and the Tower of Hanoi. In summary, girls with TS showed evidence of increased impulsivity at all ages studied. Their performance on tests of executive function with complex spatial demands showed similar impairment at all ages studied. Further exploration of the contribution of multimodal factors and the resulting neurocognitive profile in individuals with TS is warranted. C1 THOMAS JEFFERSON UNIV, JEFFERSON MED COLL, DEPT PEDIAT, PHILADELPHIA, PA 19107 USA. MED COLL PENN & HAHNEMANN UNIV, WILLIAMSPORT HOSP, WILLIAMSPORT, PA USA. MED COLL PENN & HAHNEMANN UNIV, DEPT BIOSTAT, WILLIAMSPORT, PA USA. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD USA. NR 44 TC 27 Z9 27 U1 1 U2 7 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 1997 VL 13 IS 1 BP 23 EP 40 PG 18 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA WH292 UT WOS:A1997WH29200002 ER PT J AU Casey, BJ Trainor, R Giedd, J Vauss, Y Vaituzis, CK Hamburger, S Kozuch, P Rapoport, JL AF Casey, BJ Trainor, R Giedd, J Vauss, Y Vaituzis, CK Hamburger, S Kozuch, P Rapoport, JL TI The role of the anterior cingulate in automatic and controlled processes: A developmental neuroanatomical study SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE cingulate; development; attention ID POSITRON EMISSION TOMOGRAPHY; HUMAN-BRAIN; SENSORY STIMULATION; CORTEX; CHILDREN; SPEED; MORPHOLOGY; ATTENTION; MRI; AGE AB This study examines the role of the anterior cingulate in the development of attention. Task performance relying predominantly on either automatic or controlled processes was correlated with magnetic resonance imaging based measures of the anterior cingulate in 26 normal children ages 5 to 16 years. Attentional measures were assessed with a visual discrimination paradigm. Parasagittal slices from a 3-D, T1-weighted volume data set were used to obtain area measurements of the anterior cingulate. Response latencies decreased with age for both tasks. There were significant correlations between attentional performance and right, but not left, anterior cingulate measures. Performance was faster and more accurate during trials requiring predominantly controlled processes for those children with larger right anterior cingulate measures. The results are consistent with adult neuroimaging findings of activation in the right anterior cingulate during attention tasks and with lesion studies implicating greater right hemisphere involvement in attentional processes. (C) 1997 John Wiley & Sons, Inc. C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. RP Casey, BJ (reprint author), UNIV PITTSBURGH,MED CTR,WESTERN PSYCHIAT INST & CLIN,ROOM E-519,3811 OHARA ST,PITTSBURGH,PA 15213, USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; kozuch, patricia/0000-0002-7465-9671 NR 43 TC 160 Z9 162 U1 2 U2 10 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD JAN PY 1997 VL 30 IS 1 BP 61 EP 69 DI 10.1002/(SICI)1098-2302(199701)30:1<61::AID-DEV6>3.0.CO;2-T PG 9 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA WA748 UT WOS:A1997WA74800006 PM 8989533 ER PT J AU Broberg, AG Wessels, H Lamb, ME Hwang, CP AF Broberg, AG Wessels, H Lamb, ME Hwang, CP TI Effects of day care on the development of cognitive abilities in 8-year-olds: A longitudinal study SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID CHILD-CARE; SCHOOL; PREDICTION; PRESCHOOL; HOME; INTELLIGENCE; ACHIEVEMENT; EXPERIENCE; AGE AB In Goteborg, Sweden, 146 children (72 girls) were enrolled in a longitudinal study when they averaged 16 months of age. None of the children had experienced regular out-of-home care yet, but within 3 months, 54 entered center care and 33 entered family day care. Quality of home and out-of-home care environments, child temperament, and the development of verbal abilities were assessed regularly during preschool years. When they were 8 years old (2nd grade), cognitive ability tests were administered to the 123 children (65 girls) still in the study. Tested ability was related to the number of months children had spent in center-based day care before 3.5 years of age. Child care quality predicted cognitive abilities among children who had spent at least 36 months in out-of-home care during their preschool years. Both tested and rated cognitive abilities in 2nd grade were related to earlier measures of verbal ability and to paternal involvement during preschool years. C1 NICHHD,SECT SOCIAL & EMOT DEV,BETHESDA,MD 20814. RP Broberg, AG (reprint author), GOTHENBURG UNIV,DEPT PSYCHOL,HARALDSGATAN 1,S-41314 GOTHENBURG,SWEDEN. NR 66 TC 74 Z9 75 U1 6 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD JAN PY 1997 VL 33 IS 1 BP 62 EP 69 DI 10.1037/0012-1649.33.1.62 PG 8 WC Psychology, Developmental SC Psychology GA WB791 UT WOS:A1997WB79100008 PM 9050391 ER PT J AU Zhang, BW Lan, MS Notkins, AL AF Zhang, BW Lan, MS Notkins, AL TI Autoantibodies to IA-2 in IDDM - Location of major antigenic determinants SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; GLUTAMIC-ACID DECARBOXYLASE; ISLET-CELL ANTIGEN-512; TRYPTIC FRAGMENTS; ANTIBODIES; AUTOANTIGEN; IDENTIFICATION AB Thirty-three IDDM sera that immunoprecipitated full-length IA-2 were tested for reactivity with different fragments of the IA-2 molecule, The fragments were prepared by PCR amplification of IA-2 cDNA and by expression in a rabbit reticulocyte transcription/translation system, Whereas all 33 sera reacted with the intracellular domain (amino acid 604 to 979), none of the sera reacted with the extracellular domain of IA-2 (amino acid 31 to 577). Analysis of the reactivity of IDDM sera with the different regions of the intracellular domain showed that 94% (31 of the 33) reacted with the COOH-terminus (amino acid 771 to 979), 40% reacted with the NH2-terminus (amino acid 604 to 776), and 40% reacted with the middle portion (amino, acid 692 to 875). Of the 31 sera that reacted with the COOH-terminus, 14 of these reacted only with the COOH-terminus and with no other region, Of the 13 sera that reacted with the NH2-terminus, only one reacted exclusively with the NH2-terminus. Treatment of the different domains of IA-2 with trypsin showed that only the COOH-terminus was resistant to trypsin, arguing that it is from this region of the IA-2 molecule that the 40-kDa tryptic fragment from insulinoma cells is derived, From these experiments, it is concluded that the major antigenic determinant of IA-2 is located at the COOH-terminus and that minor antigenic determinants are located at the NH2-terminus and middle portion of the intracellular domain. C1 NIDR, ORAL MED LAB, NIH, BETHESDA, MD 20892 USA. NR 15 TC 48 Z9 50 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 1997 VL 46 IS 1 BP 40 EP 43 DI 10.2337/diabetes.46.1.40 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VY995 UT WOS:A1997VY99500008 PM 8971079 ER PT J AU Haffner, SM Howard, G Mayer, E Bergman, RN Savage, PJ Rewers, M Mykkanen, L Karter, AJ Hamman, R Saad, MF AF Haffner, SM Howard, G Mayer, E Bergman, RN Savage, PJ Rewers, M Mykkanen, L Karter, AJ Hamman, R Saad, MF TI Insulin sensitivity and acute insulin response in African-Americans, non-Hispanic Whites, and Hispanics with NIDDM - The insulin resistance atherosclerosis study SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; BODY-FAT DISTRIBUTION; GLUCOSE-TOLERANCE TEST; MEXICAN-AMERICANS; MINIMAL MODEL; ADIPOSE-TISSUE; BLACK; OBESITY; RISK; KETOACIDOSIS AB NIDDM is usually characterized by beta-cell failure and decreased insulin sensitivity, It has been reported that a high proportion of African-American NIDDM subjects are insulin sensitive, To examine this issue, we determined insulin sensitivity (S-1) in 479 NIDDM subjects by minimal model analyses of frequently sampled intravenous glucose tolerance (FSIGT) from the Insulin Resistance Atherosclerosis Study (IRAS), a large multicenter study of insulin sensitivity and cardiovascular risk in African-Americans, Hispanics, and non-Hispanic whites, The African-Americans and non-Hispanic whites were sampled in Los Angeles and Oakland, California, The non-Hispanic whites and Hispanics were sampled in San Antonio, Texas, and San Luis Valley, Colorado, We defined the proportion of insulin-sensitive (S-1) subjects as greater than or equal to 1.61 min(-1) . pU(-1) . ml(-1), which is above the median for nondiabetic subjects of all ethnic groups in the IRAS, Using this definition, the proportion of insulin-sensitive diabetic subjects was very low in all ethnic groups (non-Hispanic whites [14.3%] vs, African-Americans [6.5%], P = 0.039 in Los Angeles and Oakland; non-Hispanic whites [6.8%] vs, Hispanics [4.9%], P = 0.737 in San Luis Valley and San Antonio). These results were also similar in newly diagnosed mildly hyperglycemic diabetic subjects. In addition, these results were not affected by the adjustment for differences in obesity, body fat distribution, and severity of hyperglycemia. Even in nonobese subjects (with BMI <30 kg/m(2)), the proportion of insulin-sensitive subjects (S-1 greater than or equal to 1.61 min(-1) . mu U-1 . ml(-1)) was low (3.6-9.7%). The acute insulin response (AIR) was significantly higher in African-Americans than in non-Hispanic whites; there were no ethnic differences in AIR between Hispanics and non-Hispanic whites, There were no significant ethnic differences for non-insulin-mediated glucose disposal (S-G). We conclude that the number of insulin-sensitive NIDDM subjects is low and similar among non-Hispanic whites, Hispanics, and African-Americans in the U.S. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV SO CALIF,SCH MED,DEPT PHYSIOL & BIOPHYS,LOS ANGELES,CA 90033. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,NIH,BETHESDA,MD 20892. UNIV COLORADO,SCH MED,DEPT PREVENT MED & BIOMETR,DENVER,CO. UNIV KUOPIO,DEPT MED,FIN-70211 KUOPIO,FINLAND. KAISER PERMANENTE,DIV RES,OAKLAND,CA. UNIV SO CALIF,SCH MED,DEPT MED,LOS ANGELES,CA 90033. RP Haffner, SM (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,7703 FLOUD CURL DR,SAN ANTONIO,TX 78284, USA. FU NHLBI NIH HHS [HL47889, HL47887, HL47890] NR 34 TC 142 Z9 143 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 1997 VL 46 IS 1 BP 63 EP 69 DI 10.2337/diabetes.46.1.63 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VY995 UT WOS:A1997VY99500012 PM 8971083 ER PT J AU Tataranni, PA Pratley, R Shuldiner, A Ravussin, E AF Tataranni, PA Pratley, R Shuldiner, A Ravussin, E TI beta(3)-Adrenergic receptor gene variant and lipid metabolism in Pima Indians SO DIABETOLOGIA LA English DT Letter ID DEPENDENT DIABETES-MELLITUS RP Tataranni, PA (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 6 TC 18 Z9 18 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 1997 VL 40 IS 1 BP 123 EP 124 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WD931 UT WOS:A1997WD93100022 PM 9028730 ER PT S AU Gonzalez, FJ AF Gonzalez, FJ BE Back, N Cohen, IR Kritchevsky, D Lajtha, A Paoletti, R TI The role of peroxisome proliferator activated receptor alpha in peroxisome proliferation, physiological homeostasis, and chemical carcinogenesis SO DIETARY FAT AND CANCER: GENETIC AND MOLECULAR INTERACTIONS SE Advances in Experimental Medicine and Biology LA English DT Review CT American-Institute-for-Cancer-Research 7th Annual Conference on Dietary Fat and Cancer - Genetic and Molecular Interactions CY AUG 28-30, 1996 CL WASHINGTON, D.C. SP Amer Inst Canc Res ID RETINOID-X-RECEPTOR; ACID-BINDING-PROTEIN; ACYL-COA OXIDASE; UNSCHEDULED DNA-SYNTHESIS; TISSUE-SELECTIVE MANNER; ENZYME GENE-EXPRESSION; HAMSTER EMBRYO CELLS; LONG-TERM EXPOSURE; NUCLEAR FACTOR-IV; MALE F344 RATS RP Gonzalez, FJ (reprint author), NCI, METAB LAB,DIV BASIC SCI,NIH,BLDG 37, ROOM 3E-24, BETHESDA, MD 20892 USA. NR 109 TC 17 Z9 18 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45683-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 422 BP 109 EP 125 PG 17 WC Oncology; Medicine, Research & Experimental; Nutrition & Dietetics SC Oncology; Research & Experimental Medicine; Nutrition & Dietetics GA BJ93Z UT WOS:A1997BJ93Z00009 PM 9361819 ER PT J AU Jensen, RT AF Jensen, RT TI Use of peptide receptor agonists and antagonists for diagnosis and treatment SO DIGESTION LA English DT Article; Proceedings Paper CT International Conference on Future Perspectives in Gastroenterology CY JUN 06-08, 1996 CL LEIPZIG, GERMANY DE peptide receptors; agonist; antagonist; octreotide; endothelin; cholecystokinin; bradykinin; gastrin-releasing peptide ID ENDOTHELINS; DISEASE; CCK C1 NIDDKD,NIH,DIGEST DIS BRANCH,BETHESDA,MD. NR 26 TC 1 Z9 1 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0012-2823 J9 DIGESTION JI Digestion PY 1997 VL 58 SU 1 BP 86 EP 93 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XJ357 UT WOS:A1997XJ35700024 PM 9225102 ER PT J AU Takagi, H Fukusato, T Kawaharada, U Kuboyama, SI Merlino, G Tsutsumi, Y AF Takagi, H Fukusato, T Kawaharada, U Kuboyama, SI Merlino, G Tsutsumi, Y TI Histochemical analysis of hyperplastic stomach of TGF-alpha transgenic mice SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE transforming growth factor-alpha; transgenic mouse; mucin histochemistry; immunohistochemistry ID GROWTH-FACTOR-ALPHA; MENETRIERS DISEASE; GASTRIC-MUCOSA; SECRETION; PANCREAS; DIFFERENTIATION; RECEPTOR; CELLS; GLAND; ACID AB Hypertrophic gastric mucosa in transgenic mice overexpressing transforming growth factor (TGF)-alpha showed mucosal cellular hyperplasia with dysplasia, suppression of gastric acid secretion, and chief and parietal cell depletion. In order to clarify the effects of TGF-alpha on the gastric mucose, we analyzed the stomach of TGF-alpha transgenic mice by mucin histochemical staining and immunohistochemical analysis of TGF-alpha. In transgenic mice, especially those older than 3 months, the fundic gland was notably atrophic but the total mucosa was thickened. The mucous neck cells were hypersecretory and associated with abnormal sulfation. Mucosal hyperplasia was caused by proliferation of surface epithelial cells, associated with formation of intracytoplasmic lumina. The hyperplastic foveolar cells revealed production of a high amount of sialomucin. In addition, the involved stomach regionally revealed collagenous fibrosis in the submucosal layer. The wide distribution of TGF-alpha in the hyperplastic foveolar cells was in sharp contrast to negative expression in the foveolar cells in the control mice. These findings demonstrated the various regulatory functions of TGF-alpha in mucin production, fibrogenesis, and neck cell proliferation in the stomach. C1 GUNMA UNIV,COLL MED CARE & TECHNOL,DEPT PATHOL,MAEBASHI,GUMMA 371,JAPAN. GUNMA UNIV,COLL MED CARE & TECHNOL,DEPT MED TECHNOL,MAEBASHI,GUMMA 371,JAPAN. KURUME UNIV,SCH MED,DEPT INTERNAL MED 2,KURUME,FUKUOKA 830,JAPAN. NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. TOKAI UNIV,SCH MED,DEPT PATHOL,ISEHARA,KANAGAWA 25911,JAPAN. RP Takagi, H (reprint author), GUNMA UNIV,COLL MED CARE & TECHNOL,SCH MED,DEPT INTERNAL MED 1,SHOWAMACHI 3-39,MAEBASHI,GUMMA 371,JAPAN. NR 33 TC 9 Z9 10 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 1997 VL 42 IS 1 BP 91 EP 98 DI 10.1023/A:1018837121947 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WE663 UT WOS:A1997WE66300014 PM 9009121 ER PT J AU Zhang, ZJ Zimonjic, DB Popescu, NC Wang, N Gerhard, DS Stone, EM Arbour, NC DeVries, HG Scheffer, H Gerritsen, J Collee, JM TenKate, LP Mukherjee, AB AF Zhang, ZJ Zimonjic, DB Popescu, NC Wang, N Gerhard, DS Stone, EM Arbour, NC DeVries, HG Scheffer, H Gerritsen, J Collee, JM TenKate, LP Mukherjee, AB TI Human uteroglobin gene: Structure, subchromosomal localization, and polymorphism SO DNA AND CELL BIOLOGY LA English DT Article ID IN-SITU HYBRIDIZATION; ANTIINFLAMMATORY PEPTIDES ANTIFLAMMINS; PLATELET-ACTIVATING-FACTOR; TISSUE-SPECIFIC EXPRESSION; BASOPHILIC LEUKEMIA-CELLS; RABBIT UTEROGLOBIN; PHOSPHOLIPASE-A2 ACTIVITY; MOLECULAR-CLONING; 10-KD PROTEIN; LIPOCORTIN-I AB Human uteroglobin (hUG) or Clara cell 10-kD protein (cc10 kDa) is a steroid-dependent, immunomodulatory, cytokine-like protein, It is secreted by mucosal epithelial cells of all vertebrates studied, The cDNA encoding hUG and the 5' promoter region of the gene have been characterized previously, Here, we report that the structure of the entire hUG gene is virtually identical to those of rabbit, rat, and mouse, It is localized on human chromosome 11q12.3-13.1, a region in which several important candidate disease genes have been mapped by linkage analyses, Our data indicate that candidate genes for atopic (allergic) asthma and Best's vitelliform macular dystrophy are in closest proximity to the hUG gene, To determine whether hUG gene mutation may be involved in the pathogenesis of these diseases, we studied two isolated groups of patients, each afflicted with either atopy or Best's disease, respectively, We detected a single base-pair change in the hUG gene in Best's disease patients and normal controls but no such change was detected in atopy patients, This alteration in hUG gene-sequence in Best disease family appears to be a polymorphism, Although the results of our investigation did not uncover mutations in hUG gene that could be causally related to the pathogenesis of either of these diseases, its conservation throughout vertebrate phyla implies that this gene is of physiological importance, Moreover, the close proximity of this gene to several candidate disease genes makes it an important chromosomal marker in cloning and characterization of those genes. C1 NICHHD, SECT DEV GENET, HERITABLE DISORDERS BRANCH, NIH, BETHESDA, MD 20892 USA. NCI, EXPT CARCINOGENESIS LAB, NIH, BETHESDA, MD 20892 USA. WASHINGTON UNIV, SCH MED, DEPT GENET, ST LOUIS, MO 63110 USA. WASHINGTON UNIV, SCH MED, DEPT PSYCHIAT, ST LOUIS, MO 63110 USA. UNIV IOWA, COLL MED, DEPT OPHTHALMOL, IOWA CITY, IA 52242 USA. UNIV GRONINGEN, DEPT MED GENET, GRONINGEN, NETHERLANDS. UNIV GRONINGEN HOSP, BEATRIX CHILDS HOSP, GRONINGEN, NETHERLANDS. FREE UNIV AMSTERDAM, DEPT HUMAN GENET, AMSTERDAM, NETHERLANDS. RI Scheffer, Hans/E-4644-2012 OI Scheffer, Hans/0000-0002-2986-0915 NR 91 TC 44 Z9 45 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JAN PY 1997 VL 16 IS 1 BP 73 EP 83 DI 10.1089/dna.1997.16.73 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA WH003 UT WOS:A1997WH00300008 PM 9022046 ER PT J AU Haynes, SR AF Haynes, SR TI Primary structure of Drosophila ribosomal protein L14 and identification of conserved protein motifs SO DNA SEQUENCE LA English DT Article DE Drosophila; homology; L14; ribosomal protein; ribosome ID GENE AB Determination of the primary structure of individual ribosomal proteins is important for understanding their functions and organization within the ribosome. I have sequenced a cDNA that encodes a Drosophila homolog of the rat ribosomal protein L14. The cDNA sequence was 601 nucleotides long, with an open reading frame encoding a protein of 166 amino acids. Homology searches revealed 34-38% sequence identity to the rat and yeast L14 ribosomal proteins. There were also extensive homologies to sequences in the EST database, which are likely to encode portions of L14. Analysis of sequence comparisons revealed several highly conserved regions, one of which is related to a portion of ribosomal protein L27. The sizes of the L14 proteins vary between different species, with most of the variability confined to the C-terminal region. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Haynes, SR (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-5179 J9 DNA SEQUENCE JI DNA Seq. PY 1997 VL 8 IS 1-2 BP 105 EP 108 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YZ461 UT WOS:000072256400015 PM 9522130 ER PT J AU Tan, DP AF Tan, DP TI Cloning and sequence analysis of a cDNA encoding bovine ribosomal protein P2: Predicted alpha-helices and potential phosphorylation sites SO DNA SEQUENCE LA English DT Article DE alpha helix; autoimmune disease; evolution; peptide elongation; phosphorylation site ID NUCLEOTIDE-SEQUENCE; GENES; EXPRESSION; PHOSPHOPROTEIN-P2; FAMILY AB A cDNA corresponding to bovine acidic ribosomal P2 was cloned and sequenced. It encodes a polypeptide 115 amino acids long. The secondary structure prediction shows that bovine P2 contains a large part of the protein domain as alpha helices. Alignment and analysis of 16 eukaryotic P2 proteins of 12 species reveal that there are three predicted alpha-helical regions conserved in almost all P2 proteins; helix 1 and helix 2 may be part of a helix-turn-helix structure. Sequence analysis indicates that there are seven serine residues in bovine P2 protein which are potential phosphorylation sites for a variety of Ser/Thr kinases. A few such sites appear at similar positions in many P2 proteins. The antigenic region is predicted to be located in the stretch of acidic amino acids in the vicinity of the C-terminus of P2. The predicted alpha-helical structures, potential phosphorylation sites and antigenic regions of the P2 protein provide some insights into the structure of P2 protein and deserve further experimental study. RP Tan, DP (reprint author), NHLBI,BIOCHIM GENET LAB,NIH,BLDG 36,RM 1C06,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 1 Z9 2 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-5179 J9 DNA SEQUENCE JI DNA Seq. PY 1997 VL 7 IS 3-4 BP 203 EP 208 DI 10.3109/10425179709034036 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XN560 UT WOS:A1997XN56000008 PM 9254014 ER PT B AU Cone, EJ Goldberger, BA AF Cone, EJ Goldberger, BA BE Nahas, GG Burks, TF TI Pharmacokinetics and tissue distribution of opiates SO DRUG ABUSE IN THE DECADE OF THE BRAIN LA English DT Proceedings Paper CT International Symposium on Drug Abuse in the Decade of the Brain CY SEP 22-23, 1995 CL HOUSTON, TX SP Univ Texas, Houston Hlth Sci Ctr, Houstons Drug Free Business Initiat AB Until recently, toxicologic investigations of heroin-related deaths had been limited to the identification and measurement of morphine and conjugated morphine in postmortem blood, urine and tissue. Identification of heroin, and its specific metabolite, 6-acetylmorphine, was not practical. With recent advances in extraction and detection technology, testing for heroin and 6-acetylmorphine can now be readily performed. Blood and urine specimens were collected from twenty-one cases of death due to acute narcotic intoxication. Analyses were conducted with blood and urine. The mode of death was categorized as rapid, delayed or undetermined. The data indicated that compared to delayed deaths, rapid deaths were characterized by the following trends: higher mean concentrations of 6-acetylmorphine, free morphine and total morphine in blood; higher ratio of free morphine to total morphine concentration in blood; lower mean concentrations of 6-acetylmorphine and morphine in urine; greater likelihood to detect 6-acetylmorphine in blood; and lesser likelihood to detect heroin in urine. In a detailed study, multiple tissue specimens from two subjects who died of heroin intoxication were collected. Heroin was identified in urine and injection site tissue. Concentrations of 6-acetylmorphine in cerebrospinal fluid, brain and spleen were substantially higher than in blood, liver, kidney and lung. All specimens were positive for morphine. These studies demonstrated that measurement of heroin and metabolites provides useful information for the differential diagnosis of heroin-related deaths. RP Cone, EJ (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU I O S PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS BN 90-5199-305-6 PY 1997 BP 71 EP 77 PG 7 WC Substance Abuse SC Substance Abuse GA BH38Z UT WOS:A1997BH38Z00010 ER PT B AU London, ED Cascella, NG Wong, DF Phillips, RL Dannals, RF Links, JM Herning, R Grayson, R Jaffe, JH Wagner, HN AF London, ED Cascella, NG Wong, DF Phillips, RL Dannals, RF Links, JM Herning, R Grayson, R Jaffe, JH Wagner, HN BE Nahas, GG Burks, TF TI Cocaine induced reduction of glucose utilization in human brain - A study using positron emission tomography and [fluorine 18]-fluorodeoxyglucose SO DRUG ABUSE IN THE DECADE OF THE BRAIN LA English DT Proceedings Paper CT International Symposium on Drug Abuse in the Decade of the Brain CY SEP 22-23, 1995 CL HOUSTON, TX SP Univ Texas, Houston Hlth Sci Ctr, Houstons Drug Free Business Initiat RP London, ED (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU I O S PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS BN 90-5199-305-6 PY 1997 BP 191 EP 206 PG 16 WC Substance Abuse SC Substance Abuse GA BH38Z UT WOS:A1997BH38Z00023 ER PT B AU Kuhar, MJ AF Kuhar, MJ BE Nahas, GG Burks, TF TI Cocaine and the dopamine transporter SO DRUG ABUSE IN THE DECADE OF THE BRAIN LA English DT Proceedings Paper CT International Symposium on Drug Abuse in the Decade of the Brain CY SEP 22-23, 1995 CL HOUSTON, TX SP Univ Texas, Houston Hlth Sci Ctr, Houstons Drug Free Business Initiat RP Kuhar, MJ (reprint author), NIDA,DIV INTRAMURAL RES,NEUROSCI BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS BN 90-5199-305-6 PY 1997 BP 207 EP 212 PG 6 WC Substance Abuse SC Substance Abuse GA BH38Z UT WOS:A1997BH38Z00024 ER PT J AU Masuko, Y Tazawa, K Sato, H Viroonchatapan, E Takemori, S Shimizu, T Ohkami, H Nagae, H Fujimaki, M Horikoshi, I Weinstein, JN AF Masuko, Y Tazawa, K Sato, H Viroonchatapan, E Takemori, S Shimizu, T Ohkami, H Nagae, H Fujimaki, M Horikoshi, I Weinstein, JN TI Antitumor activity of selective hyperthermia in tumour-bearing rats using thermosensitive magnetoliposomes as a new hyperthermic material SO DRUG DELIVERY LA English DT Article DE dextran magnetite; inductive heating; selective hyperthermia; thermosensitive magnetoliposomes ID LOCALIZED HYPERTHERMIA; FERROMAGNETIC IMPLANTS; LIPOSOMES; METHOTREXATE; SYSTEM AB The antitumor activity of dextran magnetite (DM)-incorporating thermosensitive liposomes, namely thermosensitive magnetoliposomes (TMs), as a new hyperthermic material was examined in rats bearing AH60C tumors. TMs were injected at an iron concentration of 15 mg per cm(3) tumor into AH60C tumors placed subcutaneously in the backs of Donryu rats. After injection, the whole body of the rat (treated group) was exposed to a 500-kHz electromagnetic held generated by inductive heating. The treated group was further divided into once-and twice-treated groups in order to examine whether repetitive hyperthermia is possible after a single TM injection, A control group also received a TM injection but was not treated with hyperthermia. In the heated groups, there was a marked temperature rise inside the tumor up to 42 degrees C within 7 min, but surrounding tissues were not heated. The inhibition of the growth of AH60C tumor in the treated groups was significantly greater than in the control group (P <.01). Histological examination indicated that the tumor cells in the treated and surviving rats disappeared completely after hyperthermia and that TMs remained in the necrotic tissues. Moreover, the survival rate was significantly higher in the treated groups than in the control group (P <.01); the twice-treated group showed even better results (100% complete recovery). Thus, selective hyperthermia with TMs may prove useful in the treatment of localized tumors. C1 TOYAMA MED & PHARMACEUT UNIV,DEPT HOSP PHARM,TOYAMA 93001,JAPAN. MEITO SANGYO CORP,NAGOYA RES,NAGOYA,AICHI,JAPAN. NCI,MOL PHARMACOL LAB,NIH,BETHESDA,MD 20892. RP Masuko, Y (reprint author), TOYAMA MED & PHARMACEUT UNIV,DEPT SURG 2,2630 SUGITANI,TOYAMA 93001,JAPAN. NR 22 TC 13 Z9 13 U1 0 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 1071-7544 J9 DRUG DELIV JI Drug Deliv. PD JAN-MAR PY 1997 VL 4 IS 1 BP 37 EP 42 DI 10.3109/10717549709033186 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YJ342 UT WOS:A1997YJ34200006 ER PT J AU Honkakoski, P Negishi, M AF Honkakoski, P Negishi, M TI The structure, function, and regulation of cytochrome P450 2A enzymes SO DRUG METABOLISM REVIEWS LA English DT Review ID HUMAN LIVER-MICROSOMES; STEROID 15-ALPHA-HYDROXYLASE GENE; COUMARIN 7-HYDROXYLASE ACTIVITY; MESSENGER-RNA STABILIZATION; RABBIT NASAL MICROSOMES; PLASMA GROWTH-HORMONE; MOUSE-LIVER; HYDROXYLASE-ACTIVITY; RAT-LIVER; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE NNK C1 NIEHS,PHARMACOGENET SECT,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. OI Honkakoski, Paavo/0000-0002-4332-3577 NR 93 TC 58 Z9 61 U1 0 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 1997 VL 29 IS 4 BP 977 EP 996 DI 10.3109/03602539709002240 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YK823 UT WOS:A1997YK82300006 PM 9421682 ER PT J AU Domanski, MJ Follmann, D Mirsky, I AF Domanski, MJ Follmann, D Mirsky, I TI A new approach to assessing regional and global myocardial contractility SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE myocardial contractility; 2-D echocardiography; carotid pulse tracing ID FIBER SHORTENING RELATION; WALL STRESS-VELOCITY; INDEX AB A number of studies that assessed myocardial contractility by noninvasive means have been conducted in the past. However, many of these studies are limited because they assessed the velocity of fiber shortening-afterload relationship at only a single location. in. the ventricle, thus assuming uniform contractility throughout the ventricle. This is often. not the case, particularly in patients with coronary disease. The present study provides a new approach to assessing regional and global function that will be applicable to patients with nonuniform contractile function and makes use of entirely noninvasively obtained data. In addition, the method proposed will permit the question of linearity or nonlinearity of shortening rate-afterload relationship to be addressed in a more detailed, quantitative manner. RP Domanski, MJ (reprint author), NHLBI,CLIN TRIALS GRP,BETHESDA,MD 20892, USA. NR 13 TC 1 Z9 1 U1 0 U2 1 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD JAN PY 1997 VL 14 IS 1 BP 1 EP 7 DI 10.1111/j.1540-8175.1997.tb00683.x PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WF703 UT WOS:A1997WF70300002 ER PT S AU Kitzler, J Hardman, R Hill, E Reddy, N Philpot, R Eling, TE AF Kitzler, J Hardman, R Hill, E Reddy, N Philpot, R Eling, TE BE Honn, KV Nigam, S Marnett, LJ TI Cloning and sequencing of Prostaglandin H synthetase from rat tracheal epithelial cells: Structural evidence that a TPA regulated mRNA codes for the rat ortholog of murine PHS-1 SO EICOSANOIDS AND OTHER BIOACTIVE LIPIDS IN CANCER, INFLAMMATION, AND RADIATION INJURY 2, PTS A AND B SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury CY OCT 13-16, 1993 CL GEORGETOWN UNIV CONF CTR, WASHINGTON, D.C. SP Armed Forced Radiobiol Res Inst, Bethesda, Everlight Chem Ind Corp, Henri Beaufour Inc, Radiat Oncol Res & Dev Ctr, Detroit, Schering AG, Berlin, Adv Magnet, Bayer AG, Biomol, Cayman Chem, Ciba Geigy Pharm Div, Free Univ Berlin, Berlin, Georgetown Univ, Washington, DC, Henry Beaufour Inst, Lombardi Comprehens Canc Ctr, Merck Res Labs & Mreck Frosst Ctr Therapeut Res, Miles Inc, Monsanto, Oxford Biomed, Ross Labs, Sphinx Pharm Corp, Syntex Res, Upjon Co, Wayne State Univ, Detroit HO GEORGETOWN UNIV CONF CTR ID EXPRESSION; GENE C1 NIEHS, Eicosanoid Res Grp, Mol Biophys Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Kitzler, J (reprint author), NIEHS, Eicosanoid Res Grp, Mol Biophys Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45360-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 400 BP 65 EP 70 PN A&B PG 6 WC Oncology; Medicine, Research & Experimental; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Radiology, Nuclear Medicine & Medical Imaging GA BK61T UT WOS:000072752200009 PM 9547538 ER PT S AU Eling, TE Hill, EM Glasgow, WC AF Eling, TE Hill, EM Glasgow, WC BE Honn, KV Nigam, S Marnett, LJ TI Role of archidonic acid and linoleic acid metabolism in epidermal growth factor initiated proliferation of Syrian hamster embryo fibroblasts SO EICOSANOIDS AND OTHER BIOACTIVE LIPIDS IN CANCER, INFLAMMATION, AND RADIATION INJURY 2, PTS A AND B SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury CY OCT 13-16, 1993 CL GEORGETOWN UNIV CONF CTR, WASHINGTON, D.C. SP Armed Forced Radiobiol Res Inst, Bethesda, Everlight Chem Ind Corp, Henri Beaufour Inc, Radiat Oncol Res & Dev Ctr, Detroit, Schering AG, Berlin, Adv Magnet, Bayer AG, Biomol, Cayman Chem, Ciba Geigy Pharm Div, Free Univ Berlin, Berlin, Georgetown Univ, Washington, DC, Henry Beaufour Inst, Lombardi Comprehens Canc Ctr, Merck Res Labs & Mreck Frosst Ctr Therapeut Res, Miles Inc, Monsanto, Oxford Biomed, Ross Labs, Sphinx Pharm Corp, Syntex Res, Upjon Co, Wayne State Univ, Detroit HO GEORGETOWN UNIV CONF CTR ID ARACHIDONIC-ACID; MITOGENIC RESPONSE; MODULATION; CELLS; EXPRESSION; GENE C1 NIEHS, Mol Biophys Lab, Eicosanoid Biochem Sect, Res Triangle Pk, NC 27709 USA. RP Eling, TE (reprint author), NIEHS, Mol Biophys Lab, Eicosanoid Biochem Sect, POB 12233, Res Triangle Pk, NC 27709 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45360-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 400 BP 495 EP 500 PN A&B PG 6 WC Oncology; Medicine, Research & Experimental; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Radiology, Nuclear Medicine & Medical Imaging GA BK61T UT WOS:000072752200066 PM 9547595 ER PT S AU Samid, D Hudgins, WR Shack, S Liu, L Prasanna, P Myers, CE AF Samid, D Hudgins, WR Shack, S Liu, L Prasanna, P Myers, CE BE Honn, KV Nigam, S Marnett, LJ TI Phenylacetate and phenylbutyrate as novel, nontoxic differentiation inducers SO EICOSANOIDS AND OTHER BIOACTIVE LIPIDS IN CANCER, INFLAMMATION, AND RADIATION INJURY 2, PTS A AND B SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury CY OCT 13-16, 1993 CL GEORGETOWN UNIV CONF CTR, WASHINGTON, D.C. SP Armed Forced Radiobiol Res Inst, Bethesda, Everlight Chem Ind Corp, Henri Beaufour Inc, Radiat Oncol Res & Dev Ctr, Detroit, Schering AG, Berlin, Adv Magnet, Bayer AG, Biomol, Cayman Chem, Ciba Geigy Pharm Div, Free Univ Berlin, Berlin, Georgetown Univ, Washington, DC, Henry Beaufour Inst, Lombardi Comprehens Canc Ctr, Merck Res Labs & Mreck Frosst Ctr Therapeut Res, Miles Inc, Monsanto, Oxford Biomed, Ross Labs, Sphinx Pharm Corp, Syntex Res, Upjon Co, Wayne State Univ, Detroit HO GEORGETOWN UNIV CONF CTR ID FETAL HEMOGLOBIN PRODUCTION; ACID; 4-PHENYLBUTYRATE C1 NCI, Clin Pharmacol Branch, Bethesda, MD 20892 USA. RP Samid, D (reprint author), NCI, Clin Pharmacol Branch, Bethesda, MD 20892 USA. NR 17 TC 56 Z9 64 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45360-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 400 BP 501 EP 505 PN A&B PG 5 WC Oncology; Medicine, Research & Experimental; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Radiology, Nuclear Medicine & Medical Imaging GA BK61T UT WOS:000072752200067 PM 9547596 ER PT S AU Glasgow, WC Eling, TE AF Glasgow, WC Eling, TE BE Honn, KV Nigam, S Marnett, LJ TI Structural requirements for enhancement of EGF-dependent DNA synthesis by oxygenated metabolites of linoleic acid SO EICOSANOIDS AND OTHER BIOACTIVE LIPIDS IN CANCER, INFLAMMATION, AND RADIATION INJURY 2, PTS A AND B SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury CY OCT 13-16, 1993 CL GEORGETOWN UNIV CONF CTR, WASHINGTON, D.C. SP Armed Forced Radiobiol Res Inst, Bethesda, Everlight Chem Ind Corp, Henri Beaufour Inc, Radiat Oncol Res & Dev Ctr, Detroit, Schering AG, Berlin, Adv Magnet, Bayer AG, Biomol, Cayman Chem, Ciba Geigy Pharm Div, Free Univ Berlin, Berlin, Georgetown Univ, Washington, DC, Henry Beaufour Inst, Lombardi Comprehens Canc Ctr, Merck Res Labs & Mreck Frosst Ctr Therapeut Res, Miles Inc, Monsanto, Oxford Biomed, Ross Labs, Sphinx Pharm Corp, Syntex Res, Upjon Co, Wayne State Univ, Detroit HO GEORGETOWN UNIV CONF CTR ID FATTY-ACIDS; 13-HYDROXYOCTADECADIENOIC ACID; ARACHIDONIC-ACID; GROWTH; STIMULATION; CANCER; BREAST; CELLS; HYDROPEROXIDES; AUTOXIDATION C1 NIEHS, Mol Biophys Lab, Eicosanoid Res Grp, Res Triangle Pk, NC 27709 USA. RP Glasgow, WC (reprint author), NIEHS, Mol Biophys Lab, Eicosanoid Res Grp, POB 12233, Res Triangle Pk, NC 27709 USA. NR 20 TC 1 Z9 1 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45360-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 400 BP 507 EP 512 PN A&B PG 6 WC Oncology; Medicine, Research & Experimental; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Radiology, Nuclear Medicine & Medical Imaging GA BK61T UT WOS:000072752200068 PM 9547597 ER PT S AU Aota, SI Yamada, KM AF Aota, SI Yamada, KM BE Honn, KV Nigam, S Marnett, LJ TI Integrin functions and signal transduction SO EICOSANOIDS AND OTHER BIOACTIVE LIPIDS IN CANCER, INFLAMMATION, AND RADIATION INJURY 2, PTS A AND B SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury CY OCT 13-16, 1993 CL GEORGETOWN UNIV CONF CTR, WASHINGTON, D.C. SP Armed Forced Radiobiol Res Inst, Bethesda, Everlight Chem Ind Corp, Henri Beaufour Inc, Radiat Oncol Res & Dev Ctr, Detroit, Schering AG, Berlin, Adv Magnet, Bayer AG, Biomol, Cayman Chem, Ciba Geigy Pharm Div, Free Univ Berlin, Berlin, Georgetown Univ, Washington, DC, Henry Beaufour Inst, Lombardi Comprehens Canc Ctr, Merck Res Labs & Mreck Frosst Ctr Therapeut Res, Miles Inc, Monsanto, Oxford Biomed, Ross Labs, Sphinx Pharm Corp, Syntex Res, Upjon Co, Wayne State Univ, Detroit HO GEORGETOWN UNIV CONF CTR ID PROTEIN-KINASE-C; CELL-SUBSTRATUM ADHESION; FIBRONECTIN RECEPTOR; EXTRACELLULAR-MATRIX; TYROSINE PHOSPHORYLATION; LIPOXYGENASE METABOLITE; ENDOTHELIAL-CELLS; MONOCLONAL-ANTIBODY; MELANOMA-CELLS; BINDING DOMAIN C1 NIDR, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Aota, SI (reprint author), NIDR, Dev Biol Lab, NIH, Bldg 30, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 62 TC 19 Z9 19 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45360-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 400 BP 669 EP 682 PN A&B PG 14 WC Oncology; Medicine, Research & Experimental; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Radiology, Nuclear Medicine & Medical Imaging GA BK61T UT WOS:000072752200089 PM 9547618 ER PT S AU Eling, TE Everhart, AL AngermanStewart, J Hui, RT Glasgow, WC AF Eling, TE Everhart, AL AngermanStewart, J Hui, RT Glasgow, WC BE Honn, KV Marnett, LJ Nigam, S Jones, RL Wong, PYK TI Modulation of epidermal growth factor signal transduction by linoleic acid metabolites SO EICOSANOIDS AND OTHER BIOACTIVE LIPIDS IN CANCER, INFLAMMATION, AND RADIATION INJURY 3 SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury CY OCT 04-07, 1995 CL HONG KONG, HONG KONG SP ONO Pharm, Harper Hosp, Henri Beaufour Inst, Univ Med & Dent New Jersey, Sch Osteopath Med, LNT Corp Inc, Hong Kong, Mr M H Lee, BIOMIDE Corp, Cayman Chem Co, Chinese Univ Hong Kong, Ciba Geigy, Taiwan, Everlight Chem Ind Corp, Jujisawa Pharm Co, Fukumi Res Inst, Genetech, Glaxo Wellcome Inc, Kissei Pharm Co, Merck Fosst Canada Ina, Mochida Pharm Co Japan, Nippon Suisan Kaisha Ltd, Otsuka Pharm Co, Oxford Biomed Res, Searle Res & Dev, Schering AG, Shionogi Pharm, Osaka, Syntex, US, Takeda Chem Ind, Upjoin Co, Unitech Sci Inc, Wayne State Univ, Dept Radiat Oncol ID ARACHIDONIC-ACID; MITOGENIC RESPONSE; FIBROBLASTS; CELLS RP Eling, TE (reprint author), NIEHS, MOL BIOPHYS LAB, NIH, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 8 TC 6 Z9 6 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45487-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 407 BP 319 EP 322 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA BJ63C UT WOS:A1997BJ63C00047 PM 9321970 ER PT S AU Glasgow, WC Everhart, AL AF Glasgow, WC Everhart, AL BE Honn, KV Marnett, LJ Nigam, S Jones, RL Wong, PYK TI The role of linoleic acid metabolism in the proliferative response of cells overexpressing the erbB-2/HER2 oncogene SO EICOSANOIDS AND OTHER BIOACTIVE LIPIDS IN CANCER, INFLAMMATION, AND RADIATION INJURY 3 SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury CY OCT 04-07, 1995 CL HONG KONG, HONG KONG SP ONO Pharm, Harper Hosp, Henri Beaufour Inst, Univ Med & Dent New Jersey, Sch Osteopath Med, LNT Corp Inc, Hong Kong, Mr M H Lee, BIOMIDE Corp, Cayman Chem Co, Chinese Univ Hong Kong, Ciba Geigy, Taiwan, Everlight Chem Ind Corp, Jujisawa Pharm Co, Fukumi Res Inst, Genetech, Glaxo Wellcome Inc, Kissei Pharm Co, Merck Fosst Canada Ina, Mochida Pharm Co Japan, Nippon Suisan Kaisha Ltd, Otsuka Pharm Co, Oxford Biomed Res, Searle Res & Dev, Schering AG, Shionogi Pharm, Osaka, Syntex, US, Takeda Chem Ind, Upjoin Co, Unitech Sci Inc, Wayne State Univ, Dept Radiat Oncol ID HUMAN-BREAST-CANCER; TUMOR-SUPPRESSOR GENE; GROWTH RP Glasgow, WC (reprint author), NIEHS, MOL BIOPHYS LAB, NIH, RES TRIANGLE PK, NC 27709 USA. NR 12 TC 6 Z9 6 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-45487-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 407 BP 393 EP 397 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA BJ63C UT WOS:A1997BJ63C00059 PM 9321982 ER PT J AU Kornyshev, AA Leikin, S Sutmann, G AF Kornyshev, AA Leikin, S Sutmann, G TI ''Overscreening'' in a polar liquid as a result of coupling between polarization and density fluctuations SO ELECTROCHIMICA ACTA LA English DT Article; Proceedings Paper CT 6th International Frumkins Symposium Dedicated to Alexander Naumovich Frunkins Centenary CY AUG 21-25, 1995 CL MOSCOW, RUSSIA DE nonlocal dielectric function; polarization fluctuations; electrolyte solutions; interionic interaction ID STATIC DIELECTRIC-PROPERTIES; MICROSCOPIC EXPRESSION; COMPUTER-SIMULATION; HYDRATION FORCE; CHARGED FLUIDS; WATER; MODEL; SEMICONDUCTOR; WAVELENGTH; TRANSITION AB Static nonlocal dielectric response of a polar liquid with linearly coupled polarization and density fluctuations is studied. We use a simple quadratic Landau-Ginzburg Hamiltonian to show that the symmetry of interaction between density and vectorial polarization might lead to a striking enhancement of the polarizability at a certain finite wavelength. A similar effect in water has been obtained in recent computer simulations in accordance with neutron diffraction data and predicted by molecular theories. Here, we suggest that the coupling between density and polarization fluctuations might be one of the sources of this behaviour and discuss the conditions for its realization. A closed-form expression is derived for the wave-vector (k-) dependent response function and compared with computer simulation and diffraction data. The expression may be used as a simple analytical framework for describing dielectric screening in polar liquids. Implications of the resonance shape of the response function in k-space are studied for the interionic mean force potential and for the reorganization energy of electron exchange reactions between two ions. Copyright (C) 1996 Elsevier Science Ltd. C1 NIH, STRUCT BIOL LAB, DIV COMP RES & TECHNOL, BETHESDA, MD 20892 USA. RUSSIAN ACAD SCI, AN FRUMKIN ELECTROCHEM INST, MOSCOW 117071, RUSSIA. RP Kornyshev, AA (reprint author), FORSCHUNGSZENTRUM JULICH, FORSCHUNGSZENTRUM, INST ENERGIEVERFAHRENSTECHN, POSTFACH 1913, D-52425 JULICH, GERMANY. RI Leikin, Sergey/A-5518-2008; Kornyshev, Alexei/C-3404-2008 OI Leikin, Sergey/0000-0001-7095-0739; NR 40 TC 33 Z9 33 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0013-4686 J9 ELECTROCHIM ACTA JI Electrochim. Acta PY 1997 VL 42 IS 5 BP 849 EP 865 DI 10.1016/S0013-4686(96)00330-1 PG 17 WC Electrochemistry SC Electrochemistry GA WB636 UT WOS:A1997WB63600015 ER PT J AU Dobi, A Mahan, MA VonAgoston, D AF Dobi, A Mahan, MA VonAgoston, D TI Detection of conformation bias between the complementary strands of deoxynucleotide repeat (TG/AC)(n) SO ELECTROPHORESIS LA English DT Article DE DNA-repeat; nucleic acid conformation; polyacrylamide gel electrophoresis; DNA ID GEL-ELECTROPHORESIS; MICROSATELLITE INSTABILITY; DNA FRAGMENTS; CANCER; GENE; MARKERS; LOCUS; POLYMORPHISMS; SEQUENCE; LINKAGE AB Antiparallel complementary strands of DNA contribute symmetrically to the helical structure and its stability; rough conformational differences between complementary strands would interfere with this symmetric contribution and the stability. To detect conformational differences between complementary strands, we challenged the complementary strands to different ''pore size'' of acrylamide gels and measured differences in migration during electrophoretic mobility analysis. Changes in migration differences revealed a significant structural bias between the complementary strands of the dinucleotide repeat deoxy-(TG/AC)(n). C1 NIH,NICHD,LDN,UNIT MOL CONTROL NEURODIFFERENTIAT,BETHESDA,MD 20892. PRINCETON UNIV,UNDERGRAD PROGRAM,PRINCETON,NJ 08544. NR 32 TC 6 Z9 6 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JAN PY 1997 VL 18 IS 1 BP 12 EP 16 DI 10.1002/elps.1150180104 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WH231 UT WOS:A1997WH23100003 PM 9059814 ER PT J AU Baseman, JB Tully, JG AF Baseman, JB Tully, JG TI Mycoplasmas: Sophisticated, reemerging, and burdened by their notoriety SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HUMAN UROGENITAL TRACT; II MHC PROTEINS; NONGONOCOCCAL URETHRITIS; CYTADHESIN-P1 GENE; MULTIPLE COPIES; PNEUMONIAE; GENITALIUM; INFECTION; SEQUENCE; ASSOCIATION AB Mycoplasmas are most unusual self-replicating bacteria, possessing very small genomes, lacking cell wall components, requiring cholesterol for membrane function and growth, using UGA codon for tryptophan, passing through ''bacterial-retaining'' filters, and displaying genetic economy that requires a strict dependence on the host for nutrients and refuge. In addition, many of the mycoplasmas pathogenic for humans and animals possess extraordinary specialized tip organelles that mediate their intimate interaction with eucaryotic cells. This host-adapted survival is achieved through surface parasitism of target cells, acquisition of essential biosynthetic precursors, and in some cases, subsequent entry and survival intracellularly. Misconceptions concerning the role of mycoplasmas in disease pathogenesis can be directly attributed to their biological subtleties and to fundamental deficits in understanding their virulence capabilities. In this review, we highlight the biology and pathogenesis of these procaryotes and provide new evidence that may lead to increased appreciation of their role as human pathogens. C1 NIAID,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. RP Baseman, JB (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MICROBIOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIAID NIH HHS [AI 27873, AI 32829, AI 41010] NR 79 TC 174 Z9 192 U1 2 U2 11 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN-MAR PY 1997 VL 3 IS 1 BP 21 EP 32 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WQ421 UT WOS:A1997WQ42100003 PM 9126441 ER PT J AU Tajima, T Mikami, A Fukushi, M Nakae, J Kikuchi, Y Fujieda, K AF Tajima, T Mikami, A Fukushi, M Nakae, J Kikuchi, Y Fujieda, K TI Conventional molecular diagnosis of steroid 21-hydroxylase deficiency using mismatched primers and polymerase chain reaction SO ENDOCRINE RESEARCH LA English DT Article ID GENETIC DIAGNOSIS; CYP21B GENES; MUTATIONS; GENOTYPE; PHENOTYPE AB We tested a conventional method based on polymerase chain reaction (PCR) and specific primers with one mismatched base at the 3' end to introduce restriction enzyme sites in order to detect mutations of the CYP21 gene without radioisotope. Using this method, the intron 2 mutation causing aberrant splicing of mRNA (In2G) and the exon 4 mutation (Ile->Asn, Ex4) in the CYP21 gene were analyzed. The nonsense mutation in exon 8 (Ex8NON) of the CYP21 gene was also investigated by PCR and subsequent restriction enzyme digestion. The mismatched primers successfully amplified the CYP21 gene containing the In2G and the Ex4 mutation sites, and the presence of these two mutations could be determined by restriction enzyme digestion after PCR. We used this new method to study 33 patients. Twenty-five of these patients were found to have at least one mutation (In2G and/or Ex4 mutation). By enzyme digestion after PCR, the Ex8NON mutation was also identified (7 out of 33 patients). In conclusion, we have developed a new method to detect point mutations in the CYP21 gene. This method was proved to be sensitive and rapid for the detection of the mutations studied. Therefore, this method is suitable for clinical genetic diagnosis. C1 HOKKAIDO UNIV,SCH MED,DEPT PEDIAT,KITA KU,SAPPORO,HOKKAIDO 060,JAPAN. SAPPORO CITY INST PUBL HLTH,SAPPORO,HOKKAIDO,JAPAN. RP Tajima, T (reprint author), NICHHD,DEB,SECT DEV ENDOCRINOL,NIH,BETHESDA,MD 20892, USA. RI Toshihiro, Tajima/A-5720-2012 NR 13 TC 2 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0743-5800 J9 ENDOCR RES JI Endocr. Res. PY 1997 VL 23 IS 3 BP 231 EP 244 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XX664 UT WOS:A1997XX66400008 PM 9378109 ER PT J AU Li, QL Feng, P Satoh, T Shi, ZX Wang, R Weintraub, BD Wilber, JF AF Li, QL Feng, P Satoh, T Shi, ZX Wang, R Weintraub, BD Wilber, JF TI Regulation of the human TRH (hTRH) gene by human thyroid hormone receptor beta 1 (hTR beta 1) mutants SO ENDOCRINE RESEARCH LA English DT Article ID GENERALIZED RESISTANCE; PITUITARY RESISTANCE; LIGAND-BINDING; TRANSCRIPTION; DIMERIZATION; MUTATIONS; KINDREDS AB TRH is negatively regulated by T3 both in the hypothalamic paraventricular nucleus and transient transfection models. Mutations in hTR beta 1 genes are associated with the syndrome of generalized resistance to thyroid hormone. To investigate potential effects of mutant TRs on T3 regulation of the hTRH gene, transient gene expression assays were performed in human neuroblastoma (HTB-11) cells with an hTRH promoter-luciferase construct, wild type (WT) hTR beta 1, and three qualitatively distinct hTR beta 1 mutant forms (ED, OK and PV). In the presence of T3 (10(-9) M), liganded WT-hTR beta 1 inhibited hTRH promoter activity significantly (40%). Co-transfection of each of the two mutants (ED and OK) achieved similar levels of inhibition only at 10 to 100 fold increased T3 concentrations. Of interest, a 10x excess of mutant ED or OK could also exert dominant negative effects upon WT hTR beta 1-T3 mediated inhibitory actions on the hTRH promoter. In contrast, mutant TR-PV exerted neither inhibitory nor dominant negative effects at even higher concentrations of T3. Moreover, all three unliganded mutant forms stimulated TRH promoter activity significantly in the absence of T3, despite their different mutations in the ligand-binding domain (LBD). These data demonstrate that thyroid hormone resistance at the level of TRH gene regulation, due to reduced inhibitory actions of mutant TR-T3 complexes, as well as dominant negative effects upon WT hTR beta 1 mediated inhibition, likely contribute to elevated TSH values observed in the syndrome of thyroid hormone resistance. C1 Univ Maryland, Sch Med, Dept Med, Div Endocrinol, Baltimore, MD 21201 USA. NIDDK, Mol & Cellular Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Ctr Med Biotechnol, Inst Human Virol, Div Endocrinol, Baltimore, MD 21201 USA. Univ Maryland, Ctr Med Biotechnol, Inst Human Virol, Lab Glycoprot Hormones, Baltimore, MD 21201 USA. RP Li, QL (reprint author), Univ Maryland, Sch Med, Dept Med, Div Endocrinol, Baltimore, MD 21201 USA. NR 21 TC 6 Z9 7 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0743-5800 J9 ENDOCR RES JI Endocr. Res. PY 1997 VL 23 IS 4 BP 297 EP 309 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YM049 UT WOS:000071022800003 PM 9430820 ER PT J AU Cutler, GB AF Cutler, GB TI Corticotropin-releasing hormone (CRH): Clinical studies and use SO ENDOCRINOLOGIST LA English DT Article ID DIFFERENTIAL-DIAGNOSIS; CUSHINGS-SYNDROME; STIMULATION TEST; HYPERCORTISOLISM AB Clinical studies have suggested two areas in which corticotropin releasing hormone (CRH) may be useful in the differential diagnosis of Cushing's syndrome. First, for patients with adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome in whom radiologic studies have failed to localize the source, CRH is useful in differentiating pituitary from ectopic sources of ACTH. Second, in patients with mild to moderate hypercortisolism, defined as urinary free cortisol excretion of 90-360 mu g/day, the dexamethasone-CRH test is useful in differentiating pituitary Cushing's disease from pseudo-Cushing states. The rationale for using CRH to distinguish ectopic from pituitary sources of ACTH is that ectopic ACTH-secreting tumors, unlike pituitary ACTH-secreting tumors, do not, as a rule, express CRH receptors or respond to CRH. A simple procedure has been developed in which CRH (1 mu g/kg) is given intravenously between 8 and 9 a.m. The increase in ACTH after 15 and 30 minutes is expressed as a percentage of the mean basal level, which is the average of samples taken 5 minutes and 1 minute before administration. An increase >35% in ACTH level indicates Cushing's disease. This test has a sensitivity of about 90%. The rationale for using CRH to diagnose a pseudo-Cushing state is that CRH responsiveness in these patients is blunted compared with patients with Cushing's disease. The latter hyperrespond to CRH because their endogenous CRH is suppressed and their tumors are less subject to feedback inhibition from elevated cortisol levels. By combining the low-dose dexamethasone and CRH test, a higher diagnostic accuracy can be achieved. RP Cutler, GB (reprint author), NICHHD,DEPT HLTH & HUMAN SERV,NIH,BLDG 10,ROOM 10N262,10 CTR DR MSC 1862,BETHESDA,MD 20892, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD JAN-FEB PY 1997 VL 7 IS 1 SU S BP S10 EP S16 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WL572 UT WOS:A1997WL57200004 ER PT J AU Doppman, JL AF Doppman, JL TI Petrosal sinus sampling and corticotropin-releasing hormone in Cushing's syndrome SO ENDOCRINOLOGIST LA English DT Article ID DISEASE AB Approximately 5% of patients with proven Cushing's disease have nondiagnostic inferior petrosal sinus (IPS) samples before corticotropin-releasing hormone (CRH) stimulation, presumably due to the cyclic function of the corticotropin adenoma. Because this 5% cannot be predicted, CRH stimulation is essential in all patients undergoing petrosal sinus sampling. Studies on the efficacy of CRH stimulation in lateralization show that, aside from the 5% of patients who require CRH stimulation to produce a positive study result, CRH stimulation has little influence on the accuracy of lateralization. To offset the unavailability of CRH before synthetic CRH was approved for clinical use, cavernous sinus (CS) sampling has been proposed as an alternative to IPS sampling. The results of our studies comparing the accuracy of CS sampling with IPS sampling show that with the availability of CRH stimulation there is no advantage to CS sampling. In fact, it increases costs. Preliminary results with internal jugular vein sampling are presented. This is a less invasive procedure than IPS sampling and requires CRH stimulation for reliable results. RP Doppman, JL (reprint author), NIH,DEPT DIAGNOST RADIOL,CTR CLIN,BLDG 10,ROOM 1C660,BETHESDA,MD 20892, USA. NR 15 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD JAN-FEB PY 1997 VL 7 IS 1 SU S BP S24 EP S29 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WL572 UT WOS:A1997WL57200006 ER PT J AU Ma, YJ BergvonderEmde, K Rage, F Wetsel, WC Ojeda, SR AF Ma, YJ BergvonderEmde, K Rage, F Wetsel, WC Ojeda, SR TI Hypothalamic astrocytes respond to transforming growth factor-alpha with the secretion of neuroactive substances that stimulate the release of luteinizing hormone-releasing hormone SO ENDOCRINOLOGY LA English DT Article ID GENE-EXPRESSION; FEMALE PUBERTY; SYNAPTIC INPUT; CELL-LINE; FACTOR-I; NEURONS; INSULIN AB Previous studies demonstrated the involvement of transforming growth factor-alpha (TGF alpha), a member of the epidermal growth factor (EGF) family, in the developmental regulation of hypothalamic LHRH release. Although both TGF alpha and EGF stimulate LHRH release, they do not appear to act directly on LHRH neurons, as no EGF/TGF alpha receptors are detected on these cells in vivo. Instead, the stimulatory effect of TGF alpha on LHRH release seems to require a glial intermediacy. The present study identifies one of the glial molecules involved in this process. In vitro exposure of purified hypothalamic astrocytes to TGF alpha or EGF in a defined medium led to activation of the cyclooxygenase-mediated pathway of arachidonic acid metabolism, as indicated by an increase in PGE, release, but failed to affect lipooxygenase-mediated metabolism, as assessed by the lack of increase in leukotriene C4 production; addition of TCF alpha- (T-CM) or EGF-conditioned medium to cultures of LHRH-producing GT1-1 cells stimulated LHRH release. In contrast, direct exposure of GT1-1 cells to the growth factors was ineffective. Incubation of the cells in medium conditioned by untreated astrocytes (CM) was also ineffective. Blockade of either EGF receptor signal transduction or cyclooxygenase activity in the astrocytic cultures prevented both TGF alpha-induced PGE, formation in astrocytes and the stimulatory effect of T-CM on LHRH release. Immunoneutralization of PGE(2) actions or selective removal of the PG from T-CM also prevented T-CM-induced LHRH release. Addition of exogenous PGE(2) restored the effect. Thus, PGE, is one of the glial molecules involved in mediating the stimulatory effect of TGF alpha on LHRH release. The effectiveness of PGE(2) in eliciting LHRH release was, however, greatly reduced when PG was delivered to GT1-1 cells in astrocyte-defined medium instead of CM. Thus, astrocytes appear to produce a yet to be identified substance(s) that facilitates the stimulatory effect of PGE(2) on LHRH output. We postulate that the ability of TGF alpha to enhance LHRH release depends on the potentiating interaction of PGE(2) with these additional glial-derived molecules. C1 OREGON HLTH SCI UNIV, OREGON REG PRIMATE RES CTR, DIV NEUROSCI, BEAVERTON, OR 97006 USA. NATL INST ENVIRONM & HLTH SCI, LAB CELL & MOL PHARMACOL, RES TRIANGLE PK, NC 27709 USA. RI Rage, Florence/F-4828-2016 NR 38 TC 116 Z9 118 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 1997 VL 138 IS 1 BP 19 EP 25 DI 10.1210/en.138.1.19 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VZ824 UT WOS:A1997VZ82400005 PM 8977380 ER PT J AU Grossmann, M Wong, R Teh, NG TRopea, JE EastPalmer, J Weintraub, BD Szkudlinski, MW AF Grossmann, M Wong, R Teh, NG TRopea, JE EastPalmer, J Weintraub, BD Szkudlinski, MW TI Expression of biologically active human thyrotropin (hTSH) in a baculovirus system: Effect of insect cell glycosylation on hTSH activity in vitro and in vivo SO ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 10th International Congress of Endocrinology CY JUN 12-15, 1996 CL SAN FRANCISCO, CA ID RECOMBINANT HUMAN THYROTROPIN; HUMAN CHORIONIC-GONADOTROPIN; THYROID-STIMULATING HORMONE; HAMSTER OVARY CELLS; BETA-SUBUNIT; HUMAN CHORIOGONADOTROPIN; ALPHA-SUBUNIT; GLYCOPROTEIN HORMONES; CARBOHYDRATE VARIANT; METABOLIC-CLEARANCE AB To obtain large amounts of hTSH and to study the role of the N-linked oligosaccharides for its biological activity, hTSH was produced using recombinant baculovirus containing the human alpha-subunit and a hTSH beta-minigene, respectively, both under the control of the polyhedrin promoter. Expression in insect cells was 800-1000 ng/ml, 30-fold higher than in our optimized mammalian transient transfection system using Chinese hamster ovary (CHO) cells (20-50 ng/ml). The in vitro activity of insect-cell expressed hTSH (IC-hTSH) was increased 5-fold compared with CHO-hTSH, judged by the ability to induce cAMP production in CHO cells stably transfected with the hTSH receptor (JP09) and the rat thryoid cell line FRTL-5, as well as growth promotion in FRTL-5 cells. Lectin binding and enzymatic desialylation studies suggested that in contrast to CHO-hTSH, IC-hTSH lacked complex-type oligosaccharides terminating with sialic acid but contained predominantly high mannose-type oligosaccharides. The in vitro activity of CHO-hTSH also increased 5- to 6-fold upon treatment of the hTSH-producing cells with the oligosaccharide processing inhibitors swainsonine and castanospermine, which inhibit formation of complex, terminally sialylated oligosaccharides, and upon enzymatic desialylation. In contrast, insect cell-expression or treatment with processing inhibitors did not affect TSH receptor binding. Despite the higher in vitro activity, IC-hTSH had a much lower in vivo activity, IC-hTSH had a much lower in vivo activity than CHO-hTSH, due to rapid clearance from the circulation. In summary, this study shows for the first time that relatively high levels of recombinant hTSH with high in vitro bioactivity can be produced in a baculovirus system. Cell-dependent glycosylation is a major factor that determines the final in vivo biopotency of recombinant glycoproteins, a finding that should be of general relevance for all insect cell-produced glycosylated proteins. Although not suitable for clinical use, highly bioactive recombinants hTSH derived from high expression in insect cells should be useful in defining structure-function relations of hormone analogs. C1 CTR MED BIOTECHNOL, INST HUMAN VIROL, MOL ENDOCRINOL LAB, BALTIMORE, MD 21201 USA. UNIV MARYLAND, SCH MED, DEPT MED, DIV ENDOCRINOL, BALTIMORE, MD 21201 USA. NIDDK, MOL & CELLULAR ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 49 TC 38 Z9 39 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 1997 VL 138 IS 1 BP 92 EP 100 DI 10.1210/en.138.1.92 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VZ824 UT WOS:A1997VZ82400015 PM 8977390 ER PT J AU Montuenga, LM Martinez, A Miller, MJ Unsworth, EJ Cuttitta, F AF Montuenga, LM Martinez, A Miller, MJ Unsworth, EJ Cuttitta, F TI Expression of adrenomedullin and its receptor during embryogenesis suggests autocrine or paracrine modes of action SO ENDOCRINOLOGY LA English DT Article ID IMMUNOREACTIVE ADRENOMEDULLIN; HYPOTENSIVE PEPTIDE; PORCINE TISSUE; GROWTH-FACTORS; CELLS; RAT; PHEOCHROMOCYTOMA; IDENTIFICATION AB The present study reports the developmental patterns of expression of adrenomedullin (AM) in rat and mouse embryos. AM is a novel multifunctional peptide recently isolated from a human pheochromocytoma, which has been shown to promote growth in a variety of mammalian cell Lines. We have applied several techniques to investigate the localization of both tile AM peptide and its receptor throughout development. Immunocytochemical detection has been performed using different specific antibodies against AM and its gene-related peptide pro-AM N-terminal 20 peptide. In situ hybridization showed the localization of the messenger RNAs for AM and its receptor. Western blot analysis together with reverse transcription-PCR gave further support to the localization of AM and ita receptor in a variety of embryonic tissues. The localization of the receptor paralleled that of AM itself, suggesting an autocrine or paracrine mode of action. The spatio-temporal pattern of expression of AM in cardiovascular, neural, Rad skeletal-forming tissues as well as in the main embryonic internal organs is described. The primitive placenta, especially the giant trophoblastic dells, shows high levels of AM and AM receptor. The heart is the first organ that expresses AM during development. Tho kidney, lung, and developing tooth, in which epithelial-mesenchymal interactions are taking place, show specific patterns of AM expression. In several regions of the embryo, the patterns of AM expression correspond to the degree of differentiation. The possible involvement of AM in the control of embryonic invasion, proliferation and differentiation is discussed. C1 UNIV NAVARRA, DEPT HIST & PATHOL, E-31080 PAMPLONA, SPAIN. US FDA, CTR BIOL EVALUAT & RES, BETHESDA, MD 20892 USA. RP Montuenga, LM (reprint author), NATL CANC INST, BIOMARKERS & PREVENT RES BRANCH, 9610 MED CTR DR, ROCKVILLE, MD 20850 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 33 TC 156 Z9 158 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 1997 VL 138 IS 1 BP 440 EP 451 DI 10.1210/en.138.1.440 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VZ824 UT WOS:A1997VZ82400059 PM 8977434 ER PT J AU Rissman, EF Early, AH Taylor, JA Korach, KS Lubahn, DB AF Rissman, EF Early, AH Taylor, JA Korach, KS Lubahn, DB TI Estrogen receptors are essential for female sexual receptivity SO ENDOCRINOLOGY LA English DT Article ID MOUSE; EXPRESSION; DISRUPTION; GENE AB One of the most important, robust and evolutionarily conserved functions for neural estrogen receptor (ER) is as a mediator of female sexual behavior. Using homozygotic ER knockout (ERKO) mice we tested the hypothesis that ER controls female receptivity. Females with either two normal copies of the ER gene (wild-types), or an insertational disruption (knockouts) of the ER were ovariectomized. Each female was treated with 17 beta-estradiol (EB) alone, and with EB in combination with progesterone, prior to tests for behavioral receptivity. Under both hormonal conditions female ERKO mice did not display sexual receptivity whereas wild-type litter-mates were receptive to males. Male behavior indicated that females of both genotypes were equally attractive. Brain tissues were examined with immunocytochemical methods showed that ERKOs had greatly reduced levels of ER immunoreactivity in hypothalamus. In sum, the data show that ER is required for the display of sexual receptivity, but is not essential for female attractivity. C1 UNIV MISSOURI, DEPT BIOCHEM, COLUMBIA, MO 65211 USA. UNIV MISSOURI, DEPT CHILD HLTH, COLUMBIA, MO 65211 USA. NIEHS, NIH, REPROD & DEV TOXICOL LAB, RES TRIANGLE PK, NC 27709 USA. RP Rissman, EF (reprint author), UNIV VIRGINIA, DEPT BIOL, GILMER HALL, CHARLOTTESVILLE, VA 22903 USA. OI Korach, Kenneth/0000-0002-7765-418X FU NIMH NIH HHS [K02 MH01349] NR 15 TC 116 Z9 117 U1 0 U2 4 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 JAN PY 1997 VL 138 IS 1 BP 507 EP 510 DI 10.1210/en.138.1.507 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VZ824 UT WOS:A1997VZ82400066 PM 8977441 ER PT J AU deBoer, JG Erfle, H Walsh, D Holcroft, J Provost, JS Rogers, B Tindall, KR Glickman, BW AF deBoer, JG Erfle, H Walsh, D Holcroft, J Provost, JS Rogers, B Tindall, KR Glickman, BW TI Spectrum of spontaneous mutations in liver tissue of lacI transgenic mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE Big Blue(R) mice; mutational spectra; DNA sequencing; tissues; spontaneous mutation ID INDUCED POINT MUTATIONS; ESCHERICHIA-COLI; SHUTTLE VECTOR; ENVIRONMENTAL CARCINOGENS; SPONTANEOUS MUTAGENESIS; MOLECULAR ANALYSIS; DNA-SYNTHESIS; BONE-MARROW; HUMAN-CELLS; HPRT GENE AB The advent of transgenic technology has greatly facilitated the study of mutation in animals in vivo. The Big Blue(R) mouse system, transgenic for the loci gene, permits not only the quantification of mutations in different tissues but also provides for the generation of in vivo-derived mutational spectra. This report details the sequence alterations of 348 spontaneous mutations recovered From the liver of 6-8-week-old male Big Blue(R) mice. The spectra recovered from two strains of mice, C57B1/6 and B6C3F1, were compared and found to be very similar. The predominant mutations are G:C --> A:T transitions, with 75% of these occurring at 5'-CpG-3' sequences. This mutational bias is consistent with deamination-directed mutation at methylated cytosine bases. The second most common class of mutations is G:C --> T:A transversions. A significant clonal expansion of mutants was found in several animals, and this was used to make an approximate correction of the mutant frequency such that the most conservative estimate of mutation frequency is presented. The establishment of this substantial data-base of spontaneous mutations in the liver of Big Blue(R) mice is intended to serve as a reference against which mutations recovered after treatment can be compared. (C) 1997 Wiley-Liss, Inc. C1 TACONICS,GERMANTOWN,NY. STRATAGENE INC,LA JOLLA,CA. NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC. RP deBoer, JG (reprint author), UNIV VICTORIA,DEPT BIOL,CTR ENVIRONM HLTH,POB 1700,VICTORIA,BC V8W 2Y2,CANADA. FU NIEHS NIH HHS [N01-ES-35365] NR 59 TC 55 Z9 55 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1997 VL 30 IS 3 BP 273 EP 286 PG 14 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA YE792 UT WOS:A1997YE79200005 PM 9366905 ER PT J AU Marchetti, F Lowe, X Bishop, J Wyrobek, AJ AF Marchetti, F Lowe, X Bishop, J Wyrobek, AJ TI Induction of chromosomal aberrations in mouse zygotes by acrylamide treatment of male germ cells and their correlation with dominant lethality and heritable translocations SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE chromosome aberrations; in vivo; fluorescence in situ hybridization; spermatogenesis ID MALE-MICE; LOCUS MUTATIONS; DAMAGE; SPERMATOGENESIS; SPERMATIDS; BINDING; OOCYTES; INVITRO; MMS; DNA AB The objectives of this research were: 1) to investigate the time course of the cytogenetic defects induced by acryclamide (AA) treatment (5 x 50 mg/kg) of male germ cells in first-cleavage zygote metaphases using PAINT/DAPI analysis, and 2) to characterize the correlation between chromosomal aberrations at first cleavage, dominant lethality, and heritable translocations. PAINT/DAPI analysis employs multicolor fluorescence in situ hybridization painting plus DAPI staining to detect both stable and unstable chromosomal aberrations at first-cleavage metaphase of the zygote. High levels of chromosomally defective zygotes were detected after mating at all postmeiotic stages (20-190-fold, P < 0.001). Early spermatozoa (6.5 d post-treatment) were the most sensitive, with 76% of the zygotes carrying cytogenetic defects. A significant 10-fold increase was also detected 27.5 d post-treatment, indicating that AA had a cytogenetic effect on meiotic stages. PAINT/DAPI analysis revealed that. 1) AA-induced chromosomal breaks occurred at random, and 2) the frequencies of symmetrical and asymmetrical exchanges were similar at all mating days, except 9.5 d after AA treatment, where significantly (P < 0.02) more asymmetrical aberrations were found. Furthermore, the proportions of zygotes carrying unstable and stable chromosomal aberrations followed a similar post-treatment time course as the proportions of dominant lethality among embryos and heritable translocations among offspring. These findings indicate that PAINT/DAPI analysis of zygotic metaphases is a promising method for detecting male germ cell mutagens capable of inducing chromosomal aberrations and for evaluating the associated risks for embryonic loss and balanced translocations at birth. (C) 1997 Wiley-Liss, Inc. C1 Univ Calif Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94550 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Marchetti, F (reprint author), Univ Calif Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, L-452,POB 808, Livermore, CA 94550 USA. OI Marchetti, Francesco/0000-0002-9435-4867 FU NIEHS NIH HHS [Y01-ES-10203-00] NR 33 TC 30 Z9 31 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1997 VL 30 IS 4 BP 410 EP 417 DI 10.1002/(SICI)1098-2280(1997)30:4<410::AID-EM6>3.0.CO;2-M PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA YP963 UT WOS:000071333600006 PM 9435882 ER PT J AU Galloway, SM Sofuni, T Shelby, MD Thilagar, A Kumaroo, V Kaur, P Gulati, D Putman, DL Murli, H Marshall, R Tanaka, N Anderson, B Zeiger, E Ishidate, M AF Galloway, SM Sofuni, T Shelby, MD Thilagar, A Kumaroo, V Kaur, P Gulati, D Putman, DL Murli, H Marshall, R Tanaka, N Anderson, B Zeiger, E Ishidate, M TI Multilaboratory comparison of in vitro tests for chromosome aberrations in CHO and CHL cells tested under the same protocols SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE chromosome aberrations; test protocols; CHO and CHL cells ID HAMSTER OVARY CELLS; CHROMATID EXCHANGE TESTS; GENOTOXICITY TEST PROCEDURES; INTERNATIONAL WORKSHOP; CHINESE; CHEMICALS; INVITRO; TIME; STANDARDIZATION; INDUCTION AB Different test results have been reported for the some chemicals in two in vitro chromosome aberration test systems, CHL cells tested by a Japanese protocol and CHO cells tested by the US Notional Toxicology Program [Sofuni et al., Mutat Res 241:173-213,1990]. Here, laboratories in Japan, the US and the UK tested 9 such chemicals in CHL and CHO cells using the same protocols and found all 9 positive in both cell types; differences in earlier conclusions with these chemicals were due mainly to test protocol, not to different sensitivities of the cells. The most important protocol difference is sampling time. Chemicals that were negative in the NTP series using a sampling time of 10 to 13 hours often produced positive results when retested here with a 20- to 24-hour sampling time. While positive results were obtained in both cell types, CHL cells sometimes had higher aberration levels and survived at higher doses than CHO cells would tolerate. This may reflect some intrinsic difference in sensitivity but may also be affected by factors such as cell cycle length and culture media (e.g., oxygen scavenging capacity). The collaboration reported here also contributed to a better understanding of scoring aberrations, especially ''gaps''; there was good agreement on what types of aberrations should be included in the totals when scoring criteria were clearly defined, for example, many changes classified as ''gaps'' by the Japanese system were classified as ''breaks'' in the scoring systems used in the United States and the United Kingdom, and were appropriately included in total aberration counts. (C) 1997 Wiley-Liss, Inc. C1 NATL INST HLTH SCI,SETAGAYA KU,TOKYO 158,JAPAN. FDSC,HATANO RES INST,HADANO,KANAGAWA,JAPAN. OLYMPUS OPT CO LTD,HACHIOJI,TOKYO,JAPAN. NIEHS,RES TRIANGLE PK,NC 27709. SITEK,RES LABS,ROCKVILLE,MD. MICROBIOL ASSOCIATES INC,ROCKVILLE,MD. NOVEL PHARMACEUT INC,LEXINGTON,KY. HAZLETON WASHINGTON INC,VIENNA,VA. HAZLETON EUROPE,HARROGATE,ENGLAND. RP Galloway, SM (reprint author), MERCK RES LABS,W 45-304,W POINT,PA 19486, USA. NR 19 TC 16 Z9 16 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1997 VL 29 IS 2 BP 189 EP 207 PG 19 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA WQ848 UT WOS:A1997WQ84800010 PM 9118971 ER PT J AU Tice, RR NylanderFrench, LA French, JE AF Tice, RR NylanderFrench, LA French, JE TI Absence of systemic in vivo genotoxicity after dermal exposure to ethyl acrylate and tripropylene glycol diacrylate in Tg.AC (v-Ha-ras) mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE monofunctional acrylates; multifunctional acrylates; skin; genotoxicity; transgenic mouse; alkaline single cell gel electrophoresis; micronuclei; DNA damage ID PERIPHERAL-BLOOD ERYTHROCYTES; MOUSE LYMPHOMA-CELLS; BONE-MARROW DAMAGE; MULTIFUNCTIONAL ACRYLATES; ONCOGENICITY BIOASSAYS; 2-ETHYLHEXYL ACRYLATE; MICRONUCLEUS TEST; METHYL ACRYLATE; B6C3F1 MICE; DNA DAMAGE AB Acrylates may be polymerized to stable surface coatings (paints, lacquers, inks, etc.) by alkylation via the Michaelis-type addition reaction. Thus, acrylates have an inherent potential as electrophiles to be genotoxic, limited in their biological activity by their physicochemical properties. To evaluate their systemic genotoxicity, ethyl acrylate (EA), tripropylene glycol diacrylate (TPGDA), or Lacquer A, on ultraviolet radiation curable lacquer containing TPGDA as the active ingredient, were applied dermally to Tg.AC mice (3 times a week for 20 weeks). Peripheral blood leukocytes were evaluated for DNA damage (single-strand breaks, alkali labile sites, DNA crosslinking) at weeks 4, 8, 12, 16, and 20 by using the alkaline (pH > 13) single cell gel (SCG) assay. Peripheral blood polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were evaluated For the presence of micronuclei at week 20. The extent of DNA migration in leukocytes and the frequency of micronucleated erythrocytes was not significantly altered by treatment with TPGDA when administered alone or in Lacquer A or with EA, at doses that induced cell proliferation in keratinocytes. The absence of genotoxicity in these two cell populations suggests that these acrylates are not genotoxic or that they are not absorbed systemically when applied dermally. However, a significant, dose-dependent increase in the percentage of PCE relative to the vehicle control was present in mice treated with TPGDA, while a dose-dependent, but nonsignificant, increase in the percentage of PCE was observed in mice treated with lacquer A. This observed increase in the rate of erythropoiesis may reflect bone marrow/blood toxicity, a homeostatic mechanism in response to the treatment-induced tumor burden, and/or a hematopoietic response to epidermal keratinocyte cytokines induced by tissue injury. (C) 1997 Wiley-Liss, Inc. C1 NATL INST OCCUPAT HLTH,S-17184 SOLNA,SWEDEN. NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC. RP Tice, RR (reprint author), INTEGRATED SYST LAB,POB 13501,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-15321] NR 50 TC 8 Z9 8 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1997 VL 29 IS 3 BP 240 EP 249 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA WX069 UT WOS:A1997WX06900003 PM 9142166 ER PT J AU Fetterman, BA Kim, BS Margolin, BH Schildcrout, JS Smith, MG Wagner, SM Zeiger, E AF Fetterman, BA Kim, BS Margolin, BH Schildcrout, JS Smith, MG Wagner, SM Zeiger, E TI Predicting rodent carcinogenicity from mutagenic potency measured in the Ames Salmonella assay SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE statistics; National Toxicology Program; carcinogenic potency; mutagenic potency; Salmonella ID GENETIC TOXICITY ASSAYS; STATISTICAL-ANALYSIS; MICROSOME TEST; CHEMICALS AB Many in vitro tests have been developed to identify chemicals that can damage cellular DNA or cause mutations, and secondarily to identify potential carcinogens. The test receiving by far the most use and attention has been the Salmonella (SAL) mutagenesis test developed by Ames and colleagues [(1973). Proc Natl Acad Sci USA 70:2281-2285; (1975): Mutat Res 31:347-364], because of its initial promise of high qualitative (YES/NO) predictivity for cancer in rodents and, by extension, in humans. In addition to the initial reports of high qualitative predictivity, there was also an early report by Meselson and Russell [in Hiatt HH et al. (1977): ''Origins of Human Cancer, Book C: Human Risk Assessment,'' pp 1473-1481] of a quantitative relationship between mutagenic potency measured in SAL and carcinogenic potency measured in rodents, for a small number of chemicals. However, other reports using larger numbers of chemicals have found only very weak correlations. The primary purpose of this study was to determine whether mutagenic potency, as measured in a number of different ways, could be used to improve predictivity of carcinogenicity, either qualitatively or quantitatively. To this end, eight measures of SAI mutagenic potency were used. This study firmly establishes that the predictive relationship between mutagenic potency in SAL and rodent carcinogenicity is, at best, weak. When predicting qualitative carcinogenicity, only qualitative mutagenicity is useful, none of the quantitative measures of potency considered improves the carcinogenicity prediction. In fact, when qualitative mutagenicity is forced out of the model, the quantitative measures are still not predictive of carcinogenicity. When predicting quantitative carcinogenicity, several possible methods were considered for summarizing potency over all experiments; however, in all cases, the relationship between mutagenic potency predictors and quantitative carcinogenicity is very weak. (C) 1997 Wiley-Liss, Inc. C1 UNIV N CAROLINA, DEPT BIOSTAT, CHAPEL HILL, NC 27599 USA. YONSEI UNIV, DEPT APPL STAT, SEOUL 120749, SOUTH KOREA. NATL INST ENVIRONM HLTH SCI, ENVIRONM TOXICOL PROGRAM, RES TRIANGLE PK, NC USA. FU PHS HHS [273-90-1-0005] NR 23 TC 37 Z9 37 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1997 VL 29 IS 3 BP 312 EP 322 DI 10.1002/(SICI)1098-2280(1997)29:3<312::AID-EM12>3.0.CO;2-H PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA WX069 UT WOS:A1997WX06900012 PM 9142175 ER PT J AU Chan, PC Huff, J AF Chan, PC Huff, J TI Arsenic carcinogenesis in animals and in humans: Mechanistic, experimental, and epidemiological evidence SO ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS-PART C OF JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH LA English DT Review ID DNA-STRAND BREAKS; NATIONAL TOXICOLOGY PROGRAM; FETAL LUNG FIBROBLASTS; CHROMATID EXCHANGE SCE; CHINESE-HAMSTER CELLS; MEDIUM-TERM BIOASSAY; PROTEIN CROSS-LINKS; DIMETHYLARSINIC ACID; INORGANIC ARSENICS; DRINKING-WATER C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Chan, PC (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 209 TC 77 Z9 77 U1 1 U2 6 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1059-0501 J9 ENVIRON CARCIN ECO R JI Environ. Carcinog. Ecotoxical. Rev.-Pt. C J. Env. Sci. Health PY 1997 VL 15 IS 2 BP 83 EP 122 PG 40 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA YM751 UT WOS:000071097200001 ER PT J AU Jirles, B Thigpen, J Forsythe, D AF Jirles, B Thigpen, J Forsythe, D TI Lead in drinking water: A preventive solution SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter RP Jirles, B (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 1997 VL 105 IS 1 BP 15 EP 15 DI 10.2307/3433045 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WM698 UT WOS:A1997WM69800005 PM 9074865 ER PT J AU Foran, JA Allaben, WT Ashby, J Bass, R Wharf, C Bucher, JR Burnam, W Bus, JS Butterworth, BE Carakostas, M Emerson, J Cardona, RA Cohen, SM DeGeorge, J FennerCrisp, P Gaylor, D Gee, JF Goodman, JI Grant, DL Hattan, DG Hayashi, Y Henderson, RF Herrman, JL Koeter, HBWM LeBoeuf, RA Lorentzen, RJ McConnell, EE Mitsumori, K Olin, SS Parker, JC Renwick, A Stevens, JT Swenberg, JA Taylor, AS VanGemert, M Vu, V Walker, R Watson, M Yielding, KL AF Foran, JA Allaben, WT Ashby, J Bass, R Wharf, C Bucher, JR Burnam, W Bus, JS Butterworth, BE Carakostas, M Emerson, J Cardona, RA Cohen, SM DeGeorge, J FennerCrisp, P Gaylor, D Gee, JF Goodman, JI Grant, DL Hattan, DG Hayashi, Y Henderson, RF Herrman, JL Koeter, HBWM LeBoeuf, RA Lorentzen, RJ McConnell, EE Mitsumori, K Olin, SS Parker, JC Renwick, A Stevens, JT Swenberg, JA Taylor, AS VanGemert, M Vu, V Walker, R Watson, M Yielding, KL TI Principles for the selection of doses in chronic rodent bioassays SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID CARCINOGENICITY AB Dose selection in chronic rodent bioassays has been one of the most debated issues in risk assessment. The Committee on Risk Assessment Methods of the National Research Council attempted but failed, in 1993 to reach consensus on how to select doses for chronic rodent bioassays. However, a more recent effort conducted by the ILSI Risk Science Institute has resulted in a consensus set of principles for dose selection, including selection of the highest dose for chronic rodent bioassays. The principles encourage a move away from sole reliance on a maximum tolerated dose (MTD), as it has been traditionally defined (primarily by body weight and histopathology), and toward the use of sound scientific and toxicologic principles for the selection of all doses in the chronic bioassay. Specifically, the principles recommend that dose selection for chronic studies must be based on sound toxicologic principles; dose selection should consider human exposure; dose selection should be based on a variety of endpoints and effects derived from prechronic studies; and dose selection should consider physicochemical and other factors. Implementation of the principles internationally will have two important benefits: improvement in the quality and consistency of the rodent bioassay and international harmonization of dose selection procedures. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. ZENECA LTD,ALDERLEY PARK,CHESHIRE,ENGLAND. NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. US EPA,OFF PESTICIDE PROGRAMS,WASHINGTON,DC 20460. DOW CHEM CO USA,MIDLAND,MI 48674. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. COCA COLA CO,ATLANTA,GA. UNIROYAL CHEM CO,BETHANY,CT. UNIV NEBRASKA,MED CTR,OMAHA,NE. US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. CALIF ENVIRONM PROTECT AGCY,DEPT PESTICIDE REGULAT,SACRAMENTO,CA. MICHIGAN STATE UNIV,DEPT PHARMACOL & TOXICOL,E LANSING,MI 48824. HLTH CANADA,PEST MANAGEMENT REGULATORY AGCY,OTTAWA,ON K1A 0L2,CANADA. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NATL INST HLTH SCI,DIV RISK ASSESSMENT,TOKYO,JAPAN. LOVELACE BIOMED & ENVIRONM RES INST,INHALAT TOXICOL RES INST,ALBUQUERQUE,NM 87185. WHO,INT PROGRAMME CHEM SAFETY,CH-1211 GENEVA,SWITZERLAND. ORG ECON COOPERAT & DEV,ENVIRONM DIRECTORATE,PARIS,FRANCE. PROCTER & GAMBLE CO,CINCINNATI,OH. US FDA,OFF PLANNING & STRATEG INITIAT,WASHINGTON,DC 20204. NATL INST HLTH SCI,BIOL SAFETY RES CTR,TOKYO 158,JAPAN. US EPA,OFF RES & DEV,WASHINGTON,DC 20460. UNIV SOUTHAMPTON,CLIN PHARMACOL GRP,SOUTHAMPTON,HANTS,ENGLAND. CIBA GEIGY LTD,BASEL,SWITZERLAND. UNIV N CAROLINA,CHAPEL HILL,NC. BRI INT,SAN DIEGO,CA. US EPA,OFF POLLUT PREVENT & TOX,WASHINGTON,DC 20460. UNIV SURREY,SCH BIOL SCI,GUILDFORD GU2 5XH,SURREY,ENGLAND. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. CHARLES CONN & VAN GEMERT,CHARLOTTE HALL,MD. RP Foran, JA (reprint author), ILSI RISK SCI INST,1126 16TH ST NW,WASHINGTON,DC 20036, USA. NR 13 TC 12 Z9 13 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 1997 VL 105 IS 1 BP 18 EP 20 DI 10.2307/3433048 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WM698 UT WOS:A1997WM69800008 PM 9074868 ER PT J AU Wine, RN Li, LH Barnes, LH Gulati, DK Chapin, RE AF Wine, RN Li, LH Barnes, LH Gulati, DK Chapin, RE TI Reproductive toxicity of di-n-butylphthalate in a continuous breeding protocol in Sprague-Dawley rats SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE continuous breeding; developmental defects; di-n-butylphthalate; rat; reproductive toxicity ID PHTHALIC-ACID ESTERS; BUTYL PHTHALATE; TESTICULAR ATROPHY; DIBUTYL PHTHALATE; DEVELOPMENTAL TOXICITY; PENTYL PHTHALATE; BONE-MARROW; DOSE LEVELS; IN-VITRO; MECHANISM AB The phthalate ester di-n-butylphthalate (DBP) is used extensively in the manufacture of plastics; its reproductive toxicity was tested in rats by the National Toxicology Program's Reproductive Assessment by Continuous Breeding protocol. Levels of 0.1, 0.5, and 1.0% DBP in the diet were selected, and this dosing design yielded average daily DBP intakes of 52, 256, and 509 mg/kg for males and 80, 385, and 794 mg/kg for females, respectively. DBP consumption by F-0 rats reduced the total number of live pups per litter in all treated groups by 8-17% and live pup weights in the 0.5% and 1.0% dose groups by <13%. In rests to determine the affected sex, the number of offspring was unchanged, but the weights of pups from treated females were significantly decreased and offspring from treated males were unchanged. At necropsy, high-dose F-0 females had a 14% reduction in body weight, and both sexes had similar or equal to 10-15% increased kidney and liver to body weight ratios compared to controls. Sperm parameters and estrous cyclicity were not affected. In the F-1 mating trial, indices of mating pregnancy, and fertility in the 1.0% dose group were all sharply decreased (one live litter was delivered cut of 20 cohabited pairs), concomitant with a 13% decrease in dam body weight. Live F-2 pup weights were 6-8% lower in all dose groups. F-1 necropsy results revealed that epididymal sperm counts and testicular spermatid head counts were significantly decreased in the 1.0% dose group. Histopathologic investigation showed that 8 of 10 F-1 males consuming 1.0% DBP had degenerated seminiferous tubules and 5 of 10 had underdeveloped or otherwise defective epididymides. No ovarian or uterine lesions were observed. In conclusion, this study showed that DBP is a reproductive/developmental toxicant in Sprague-Dawley rats exposed both as adults and during development; it also indicates that the adverse reproductive/developmental effects of DBP on the second generation were greater than on the first generation. C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. ENVIRONM HLTH RES & TESTING INC,LEXINGTON,KY 40503. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [N01-ES-45060, N01-ES-45061, N01-ES-65142] NR 44 TC 149 Z9 154 U1 0 U2 5 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 1997 VL 105 IS 1 BP 102 EP 107 DI 10.1289/ehp.97105102 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WM698 UT WOS:A1997WM69800029 PM 9074889 ER PT J AU Fawell, J Robinson, D Bull, R Birnbaum, L Butterworth, B Daniel, P GalalGorchev, H Hauchman, F Julkunen, P Klaassen, C Krasner, S OrmeZavaleta, J Tardiff, T AF Fawell, J Robinson, D Bull, R Birnbaum, L Butterworth, B Daniel, P GalalGorchev, H Hauchman, F Julkunen, P Klaassen, C Krasner, S OrmeZavaleta, J Tardiff, T TI Disinfection by-products in drinking water: Critical issues in health effects research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 INT LIFE SCI INST, WASHINGTON, DC 20036 USA. CTR WATER RES, MEDMENHAM, BUCKS, ENGLAND. PACIFIC NW LAB, RICHLAND, WA 99352 USA. US EPA, NATL HLTH & ENVIRONM EFFECTS RES LAB, RES TRIANGLE PK, NC 27711 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. CHEM IND INST TOXICOL, RES TRIANGLE PK, NC 27709 USA. CAMP DRESSER & MCKEE INC, WALNUT CREEK, CA 94596 USA. WHO, INT PROGRAMME CHEM SAFETY, GENEVA, SWITZERLAND. COCA COLA CO, ATLANTA, GA 30301 USA. UNIV KANSAS, MED CTR, KANSAS CITY, KS 66103 USA. METROPOLITAN WATER DIST SO CALIF, LA VERNE, CA 91750 USA. COLORADO STATE UNIV, FT COLLINS, CO 80523 USA. EA ENGN SCI & TECHNOL INC, SILVER SPRING, MD 20910 USA. NR 0 TC 18 Z9 18 U1 2 U2 7 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 1997 VL 105 IS 1 BP 108 EP 109 DI 10.1289/ehp.97105108 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA WM698 UT WOS:A1997WM69800030 PM 9074890 ER PT S AU Sato, S Sugiyama, K Carper, D AF Sato, S Sugiyama, K Carper, D BE Weiner, H Lindahl, R Crabb, DW Flynn, TG TI Aldose reductase as dihydrodiol dehydrogenase: Naphthoquinone formation by rat lens aldose reductase SO ENZYMOLOGY AND MOLECULAR BIOLOGY OF CARBONYL METABOLISM 6 SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 8th International Workshop on Enzymology and Molecular Biology of Carbonyl Metabolism CY JUN 29-JUL 03, 1996 CL DEADWOOD, SD SP Nutrasweet Co, Univ South Dakota Sch Med, Univ Physicians ID NAPHTHALENE CATARACT; INVITRO C1 NEI,LAB MECHANISMS OCULAR DIS,NIH,BETHESDA,MD 20892. RP Sato, S (reprint author), NEI,LAB OCULAR THERAPEUT,NIH,BETHESDA,MD 20892, USA. NR 14 TC 2 Z9 2 U1 0 U2 2 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45509-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 414 BP 499 EP 505 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BH33M UT WOS:A1997BH33M00056 PM 9059655 ER PT S AU Iwata, T Minucci, S McGowan, M Carper, D AF Iwata, T Minucci, S McGowan, M Carper, D BE Weiner, H Lindahl, R Crabb, DW Flynn, TG TI Gene regulation of aldose reductase under osmotic stress SO ENZYMOLOGY AND MOLECULAR BIOLOGY OF CARBONYL METABOLISM 6 SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 8th International Workshop on Enzymology and Molecular Biology of Carbonyl Metabolism CY JUN 29-JUL 03, 1996 CL DEADWOOD, SD SP Nutrasweet Co, Univ South Dakota Sch Med, Univ Physicians ID CELLS; EXPRESSION; PROMOTER; RAT C1 NEI,LAB MOL GROWTH REGULAT,NICHHD,BETHESDA,MD 20892. RP Iwata, T (reprint author), NEI,LAB MECHANISMS OCULAR DIS,NIH,BETHESDA,MD 20892, USA. RI Minucci, Saverio/J-9669-2012 NR 12 TC 0 Z9 0 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45509-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 414 BP 507 EP 514 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BH33M UT WOS:A1997BH33M00057 PM 9059656 ER PT S AU Mizoguchi, T Ogura, T Yagi, K Kador, PF AF Mizoguchi, T Ogura, T Yagi, K Kador, PF BE Weiner, H Lindahl, R Crabb, DW Flynn, TG TI D-fructose-mediated stimulation of bovine lens aldose reductase activation by UV-irradiation SO ENZYMOLOGY AND MOLECULAR BIOLOGY OF CARBONYL METABOLISM 6 SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 8th International Workshop on Enzymology and Molecular Biology of Carbonyl Metabolism CY JUN 29-JUL 03, 1996 CL DEADWOOD, SD SP Nutrasweet Co, Univ South Dakota Sch Med, Univ Physicians ID GLYCATION; INACTIVATION; RADIATION; IDENTIFICATION; CELLS C1 NEI,NIH,BETHESDA,MD 20892. RP Mizoguchi, T (reprint author), OSAKA UNIV,FAC PHARMACEUT SCI,1-6 YAMADA OKA,SUITA,OSAKA 565,JAPAN. NR 26 TC 0 Z9 0 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45509-9 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1997 VL 414 BP 529 EP 535 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BH33M UT WOS:A1997BH33M00060 PM 9059659 ER PT J AU Zhang, J Zeisler, J Hatch, MC Berkowitz, G AF Zhang, J Zeisler, J Hatch, MC Berkowitz, G TI Epidemiology of pregnancy-induced hypertension SO EPIDEMIOLOGIC REVIEWS LA English DT Review ID LOW-DOSE ASPIRIN; FETAL GROWTH-RETARDATION; GLUTATHIONE-PEROXIDASE ACTIVITY; RANDOMIZED CONTROLLED TRIALS; BLOOD-PRESSURE MEASUREMENT; EARLY-ONSET PREECLAMPSIA; PRE-ECLAMPSIA; ANTIPHOSPHOLIPID ANTIBODIES; RISK-FACTORS; LIPID-PEROXIDATION C1 Mt Sinai Sch Med, Dept Community Med, New York, NY USA. Mt Sinai Sch Med, Dept Obstet Gynecol & Reprod Sci, New York, NY USA. RP Zhang, J (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. NR 149 TC 103 Z9 108 U1 2 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 1997 VL 19 IS 2 BP 218 EP 232 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YX478 UT WOS:000072044000003 PM 9494784 ER PT J AU Schairer, C Adami, HO Hoover, R Persson, I AF Schairer, C Adami, HO Hoover, R Persson, I TI Cause specific mortality in women receiving hormone replacement therapy SO EPIDEMIOLOGY LA English DT Article DE all-cause and specific cause mortality; hormone replacement therapy; cohort study ID POPULATION-BASED COHORT; FOLLOW-UP; POSTMENOPAUSAL ESTROGEN; CARDIOVASCULAR-DISEASE; BREAST-CANCER; ENDOMETRIAL CANCER; SWEDISH POPULATION; RISK; STROKE AB To assess the risks and benefits of menopausal hormone replacement therapy, we followed a 23,246-member, population-based cohort of Swedish women who were prescribed menopausal estrogens for an average of 8.6 years for mortality. Compared with the general population, the standardized mortality ratio for all cause mortality in this cohort was 0.77 (95% confidence limits = 0.73, 0.81). Deaths in each of the 12 major categories of causes of death except for injuries occurred 12% to 86% less frequently than expected. We examined in detail four specific causes of death according to the type of hormone prescribed, namely weak estrogens (primarily estriol), more potent estrogens (primarily estradiol and conjugated estrogens) in combination with a progestin, and more potent estrogens without a progestin. Mortality from endometrial cancer was not related to the prescription of weak estrogens or an estrogen progestin combination, but mortality was 40% higher in women prescribed more potent estrogens without a progestin. Women prescribed weak estrogens, more potent estrogens, and the combined estrogen-progestin regimen were at reduced risk of death from ischemic heart disease (standardized mortality ratios of 0.7, 0.6, and 0.4, respectively). The more potent estrogens and the estrogen-progestin combination were associated with a marked reduction in risk of intracerebral hemorrhage (standardized mortality ratios of 0.4 and 0.6, respectively) and ''other'' cerebrovascular disease, but not other types of stroke. The concern that use of progestins would lead to psychic disorders related to suicide received no support from our results. Breast cancer results are described elsewhere. These data provide little evidence of an adverse effect of the combined estrogen-progestin regimen as compared with estrogens alone on mortality. They do indicate, however, that both selection factors and biology may contribute to the almost across-the-board reduction in mortality associated with hormone replacement therapy. RP Schairer, C (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPN ROOM 443,6130 EXECUT BLVD,MSC 7374,BETHESDA,MD 20892, USA. NR 37 TC 77 Z9 77 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 1997 VL 8 IS 1 BP 59 EP 65 DI 10.1097/00001648-199701000-00010 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VZ663 UT WOS:A1997VZ66300013 PM 9116097 ER PT J AU Troisi, R Schairer, C Chow, WH Schatzkin, A Brinton, LA Fraumeni, JF AF Troisi, R Schairer, C Chow, WH Schatzkin, A Brinton, LA Fraumeni, JF TI Reproductive factors, oral contraceptive use, and risk of colorectal cancer SO EPIDEMIOLOGY LA English DT Article DE colorectal cancer; oral contraceptive use; reproductive factors; parity; menopause; menarche; cohort studies ID EXOGENOUS FEMALE HORMONES; LARGE-BOWEL-CANCER; COLON-CANCER; UNITED-STATES; WOMEN; AGE; PARITY; HISTORY; COHORT; BIRTH AB Multiparity and use of oral contraceptives are hypothesized to reduce risk of colorectal cancer. Among 57,529 women, 31-90 years of age, who volunteered for a nationwide breast cancer screening program from 1973 to 1980, we observed 154 pathologically confirmed cases of colon cancer and 49 cases of rectal cancer in up to 10 years of follow up (388,555 person-years). Parity was not associated with risk of colorectal cancer [age-adjusted rate ratio for greater than or equal to 4 children us no children = 1.0; 95% confidence interval (CI) = 0.72-1.5], although decreases in proximal colon cancer and increases in distal colon cancer were observed among parous women. The effect of parity did not vary by age at diagnosis. We found no strong or consistent association for age at menarche, age at first birth, or age at natural menopause. In addition, oral contraceptive use, reflecting mainly past use, was unrelated to risk of colorectal cancer (rate ratio = 1.0; 95% CI = 0.75-1.4). These findings do not corroborate the hypothesis that reproductive events or oral contraceptives influence the development of colorectal cancer. RP Troisi, R (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N,ROOM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 32 TC 38 Z9 38 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 1997 VL 8 IS 1 BP 75 EP 79 DI 10.1097/00001648-199701000-00012 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VZ663 UT WOS:A1997VZ66300015 PM 9116100 ER PT J AU Little, RE Gladen, BC Ataniyazova, OA Monaghan, SC Tabacova, S Zadorozhnaja, TD Mendel, NA AF Little, RE Gladen, BC Ataniyazova, OA Monaghan, SC Tabacova, S Zadorozhnaja, TD Mendel, NA TI Bridges between East and West SO EPIDEMIOLOGY LA English DT Article ID LIPID PEROXIDES; GLUTATHIONE RP Little, RE (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 1997 VL 8 IS 1 BP 107 EP 109 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VZ663 UT WOS:A1997VZ66300021 ER PT J AU Theodore, WH Sato, S Kufta, CV Gaillard, WD Kelley, K AF Theodore, WH Sato, S Kufta, CV Gaillard, WD Kelley, K TI FDG-positron emission tomography and invasive EEG, seizure focus detection and surgical outcome SO EPILEPSIA LA English DT Article DE [F-18]2-deoxyglucose positron emission tomography; video-electroencephalography; invasive EEG; seizure focus determination ID TEMPORAL-LOBE EPILEPSY; CEREBRAL BLOOD-FLOW; DEPTH-ELECTRODE; PRESURGICAL EVALUATION; LOBECTOMY; MRI; PET; RECORDINGS; METABOLISM; HYPOMETABOLISM AB Purpose: To study the value of [F-18]2-deoxyglucose (FDG)-positron emission tomography when surface ictal EEG is nonlocalizing. Methods: FDG-PET scans were performed in 46 patients with complex partial seizures (CPS) not localized by ictal surface-sphenoidal video-EEG (VEEG) telemetry. Interictal PET was performed with continuous EEG monitoring, and images were analyzed with a standard template. Forty patients subsequently had subdural and 6 had depth electrodes (invasive EEG, IEEG); 22 had bilateral implants. A focus was detected in 40, and 35 had temporal lobectomy based on IEEG localization. Results: There was a close association between IEEG and PET localization (p < 0.01): 26 patients had relative unilateral temporal FDG-PET hypometabolism, all had congruent IEEG, and 18 of 23 were seizure-free after temporal lobectomy. Five patients had unilateral frontotemporal hypometabolism (3 of 5 were seizure-free), 1 had frontal hypometabolism, and 14 had no lateralized PET abnormality (4 of 7 were seizure-free). Patients who became seizure-free had significantly higher lateral temporal asymmetry index (Al). PET showed greater than or equal to 15% relative temporal hypometabolism (Al) in 12 of 22 patients with nonlateralized surface ictal VEEG and was capable of distinguishing between frontal and temporal foci in 16 of 24 patients with lateralized, but not localized, surface ictal video-EEG. Conclusions: FDG-PET provides valuable data in patients with unlocalized surface ictal EEG and can reduce the number of patients who require IEEG studies. Quantitation is necessary for optimal PET interpretation. RP Theodore, WH (reprint author), NINCDS,CLIN EPILEPSY SECT,EPILEPSY RES BRANCH,SURG NEUROL BRANCH,NIH,BLDG 10,ROOM 5C-205,BETHESDA,MD 20892, USA. NR 34 TC 81 Z9 82 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JAN PY 1997 VL 38 IS 1 BP 81 EP 86 DI 10.1111/j.1528-1157.1997.tb01081.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA WF699 UT WOS:A1997WF69900010 PM 9024188 ER PT S AU Lancaster, JM Wiseman, RW AF Lancaster, JM Wiseman, RW BE Aldaz, CM Gould, MN McLachlan, J Slaga, TJ TI Recent advances in the molecular genetics of hereditary breast and ovarian cancer SO ETIOLOGY OF BREAST AND GYNECOLOGICAL CANCERS SE PROGRESS IN CLINICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT 9th International Conference on Carcinogenesis and Risk Assessment CY NOV 29-DEC 02, 1995 CL AUSTIN, TEXAS ID NONPOLYPOSIS COLORECTAL-CANCER; MISMATCH REPAIR DEFICIENCY; PROTEIN TRUNCATION TEST; TUMOR-SUPPRESSOR GENE; POLYPOSIS-COLI GENE; SUSCEPTIBILITY GENE; FAMILIAL BREAST; BRCA1 MUTATIONS; GERMLINE MUTATIONS; RAPID DETECTION C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Lancaster, JM (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 112 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS, INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-7742 BN 0-471-16901-3 J9 PROG CLIN BIOL RES JI Prog.Clin.Biol.Res. PY 1997 VL 396 BP 31 EP 51 PG 21 WC Biology; Oncology; Public, Environmental & Occupational Health; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Oncology; Public, Environmental & Occupational Health; Research & Experimental Medicine GA BK06D UT WOS:000071016800003 PM 9108588 ER PT S AU Brown, KD Tagle, DA AF Brown, KD Tagle, DA BE Aldaz, CM Gould, MN McLachlan, J Slaga, TJ TI Molecular perspectives on cancer, the cell cycle and the inherited disorder Ataxia-Telangiectasia SO ETIOLOGY OF BREAST AND GYNECOLOGICAL CANCERS SE PROGRESS IN CLINICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT 9th International Conference on Carcinogenesis and Risk Assessment CY NOV 29-DEC 02, 1995 CL AUSTIN, TEXAS ID DEPENDENT PROTEIN-KINASE; X-LINKED MUTANTS; RNA-POLYMERASE-I; P70 S6 KINASE; IONIZING-RADIATION; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; DNA-SYNTHESIS; SCHIZOSACCHAROMYCES-POMBE; V(D)J RECOMBINATION AB Ataxia-Telangiectasia (A-T) is an autosomal recessive disorder which presents a wide array of clinical symptoms including enhanced cancer predisposition and progressive cerebellar degeneration leading to general neuromotor dysfunction. The A-T cellular phenotype consists of higher levels of chromosome breakage, increased sensitivity to ionizing radiation and radiomimetic drugs, and defective cell cycle checkpoints in response to genome damage. Positional-cloning of the gene mutated in A-T, designated ATM, identified a 13 kb transcript encoding a 3056 amino acid protein which possesses a carboxy-terminal domain with distinct homology to phosphatidylinositol-3 kinase. Furthermore, ATM related proteins have been identified in yeast, Drosophila and other mammalian species which are involved in cell cycle control and cellular responses to DNA damage. Development of cellular and animal models for A-T can serve to better dissect the role and involvement of ATM in cell cycle regulation, cancer development, neuronal cell death and other hallmark symptoms of this disorder. C1 NIH, Natl Ctr Human Genome Res, Lab Gene Transfer, Bethesda, MD 20892 USA. RP Brown, KD (reprint author), NIH, Natl Ctr Human Genome Res, Lab Gene Transfer, Bethesda, MD 20892 USA. NR 85 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS, INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-7742 BN 0-471-16901-3 J9 PROG CLIN BIOL RES JI Prog.Clin.Biol.Res. PY 1997 VL 396 BP 101 EP 113 PG 13 WC Biology; Oncology; Public, Environmental & Occupational Health; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Oncology; Public, Environmental & Occupational Health; Research & Experimental Medicine GA BK06D UT WOS:000071016800007 PM 9108592 ER PT S AU Land, CE AF Land, CE BE Aldaz, CM Gould, MN McLachlan, J Slaga, TJ TI Radiation and breast cancer risk SO ETIOLOGY OF BREAST AND GYNECOLOGICAL CANCERS SE PROGRESS IN CLINICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT 9th International Conference on Carcinogenesis and Risk Assessment CY NOV 29-DEC 02, 1995 CL AUSTIN, TEXAS ID CASE-CONTROL INTERVIEW; ATOMIC-BOMB SURVIVORS; BRCA1; WOMEN; IRRADIATION; MORTALITY; MUTATION; THERAPY; JEWISH C1 NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. RP Land, CE (reprint author), NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. NR 27 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS, INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-7742 BN 0-471-16901-3 J9 PROG CLIN BIOL RES JI Prog.Clin.Biol.Res. PY 1997 VL 396 BP 115 EP 124 PG 10 WC Biology; Oncology; Public, Environmental & Occupational Health; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Oncology; Public, Environmental & Occupational Health; Research & Experimental Medicine GA BK06D UT WOS:000071016800008 PM 9108593 ER PT S AU Kelloff, GJ Boone, CW Crowell, JA Nayfield, SG Hawk, ET Steele, VE Lubet, RA Sigman, CC AF Kelloff, GJ Boone, CW Crowell, JA Nayfield, SG Hawk, ET Steele, VE Lubet, RA Sigman, CC BE Aldaz, CM Gould, MN McLachlan, J Slaga, TJ TI Perspectives and progress in development of breast cancer chemopreventive drugs SO ETIOLOGY OF BREAST AND GYNECOLOGICAL CANCERS SE PROGRESS IN CLINICAL AND BIOLOGICAL RESEARCH LA English DT Review CT 9th International Conference on Carcinogenesis and Risk Assessment CY NOV 29-DEC 02, 1995 CL AUSTIN, TX ID DUCTAL CARCINOMA INSITU; PLASMA DEHYDROEPIANDROSTERONE SULFATE; MONOTERPENE PERILLYL ALCOHOL; COLONIC ADENOCARCINOMA CELLS; INDUCED MAMMARY-TUMORS; SPRAGUE-DAWLEY RATS; OVARIAN-CANCER; DIETARY-FAT; AROMATASE INHIBITOR; ENDOMETRIAL CANCER C1 NCI, Chemoprevent Branch, Div Canc Prevent & Control, NIH, Bethesda, MD 20892 USA. RP Kelloff, GJ (reprint author), NCI, Chemoprevent Branch, Div Canc Prevent & Control, NIH, Bethesda, MD 20892 USA. NR 155 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS, INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-7742 BN 0-471-16901-3 J9 PROG CLIN BIOL RES JI Prog.Clin.Biol.Res. PY 1997 VL 396 BP 159 EP 183 PG 25 WC Biology; Oncology; Public, Environmental & Occupational Health; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Oncology; Public, Environmental & Occupational Health; Research & Experimental Medicine GA BK06D UT WOS:000071016800012 PM 9108597 ER PT S AU Ford, LG Johnson, KA AF Ford, LG Johnson, KA BE Aldaz, CM Gould, MN McLachlan, J Slaga, TJ TI Tamoxifen breast cancer prevention trial - An update SO ETIOLOGY OF BREAST AND GYNECOLOGICAL CANCERS SE PROGRESS IN CLINICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT 9th International Conference on Carcinogenesis and Risk Assessment CY NOV 29-DEC 02, 1995 CL AUSTIN, TEXAS ID SURGICAL ADJUVANT BREAST; POSTMENOPAUSAL WOMEN; ENDOMETRIAL CANCER; RANDOMIZED TRIAL; THERAPY; RATS; BONE; MORBIDITY; OVARIAN; DAMAGE C1 NCI, Community Oncol & Rehabil Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Ford, LG (reprint author), NCI, Community Oncol & Rehabil Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. NR 39 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS, INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-7742 BN 0-471-16901-3 J9 PROG CLIN BIOL RES JI Prog.Clin.Biol.Res. PY 1997 VL 396 BP 271 EP 282 PG 12 WC Biology; Oncology; Public, Environmental & Occupational Health; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Oncology; Public, Environmental & Occupational Health; Research & Experimental Medicine GA BK06D UT WOS:000071016800019 PM 9108604 ER PT J AU Bezrukov, SM Kasianowicz, JJ AF Bezrukov, SM Kasianowicz, JJ TI The charge state of an ion channel controls neutral polymer entry into its pore SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE ion channel; transport; polymers; hydration; water structure; alpha hemolysin; poly(ethylene glycol) ID PHOSPHOLIPID SURFACE-CHARGE; PROTON-TRANSFER; OSMOTIC-STRESS; K+ CHANNEL; WATER; CONDUCTANCE; DYNAMICS; GRAMICIDIN; MEMBRANES; SELECTIVITY AB Electrostatic potentials created by fixed or induced charges regulate many cellular phenomena including the rate of ion transport through proteinaceous ion channels. Nanometer-scale pores of these channels also play a critical role in the transport of charged and neutral macromolecules. We demonstrate here that, surprisingly, changing the charge state of a channel markedly alters the ability of non-electrolyte polymers to enter the channel's pore. Specifically, we show that the partitioning of differently-sized linear nonelectrolyte polymers of ethylene glycol into the Staphylococcus aureus alpha-hemolysin channel is altered by the solution pH. Protonating some of the channel side chains decreases the characteristic polymer size (molecular weight) that can enter the pore by similar to 25% but increases the ionic current by similar to 15%. Thus, the ''steric'' and ''electric'' size of the channel change in opposite directions. The results suggest that effects due to polymer and channel hydration are crucial for polymer transport through such pores. C1 LENINGRAD NUCL PHYS INST,GATCHINA 188350,RUSSIA. NIST,DIV BIOTECHNOL,BIOMOL MAT GRP,GAITHERSBURG,MD 20899. RP Bezrukov, SM (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. NR 42 TC 76 Z9 76 U1 1 U2 12 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PY 1997 VL 26 IS 6 BP 471 EP 476 DI 10.1007/s002490050101 PG 6 WC Biophysics SC Biophysics GA YH599 UT WOS:A1997YH59900006 PM 9404007 ER PT J AU Keown, MB Ghirlando, R Mackay, GA Sutton, BJ Gould, HJ AF Keown, MB Ghirlando, R Mackay, GA Sutton, BJ Gould, HJ TI Basis of the 1:1 stoichiometry of the high affinity receptor Fc epsilon RI-IgE complex SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article; Proceedings Paper CT 4th United-Kingdom-Analytical-Ultracentrifuge-Users-Group Meeting CY MAR 25-26, 1996 CL UNIV LEICESTER, LEICESTER, ENGLAND SP UK Analyt Ultracentrifuge Users Grp, Natl Ctr Macromolec Hydrodynam HO UNIV LEICESTER DE IgE; Fc epsilon RI; stoichiometry; analytical centrifugation ID NEUTRON-SCATTERING; IMMUNOGLOBULIN-E; ALPHA-CHAIN; FRAGMENT; PROTEINS AB A soluble fragment of the high-affinity IgE receptor Fc epsilon RI alpha-chain (sFc epsilon RI alpha) binds to the Fc fragment of IgE (IgE-Fc) as a 1:1 complex. IgE-Fc consists of a dimer of the C epsilon 2, C epsilon 3 and C epsilon 4 domains of the epsilon-heavy chain of IgE. This region of IgE has been modelled on the crystal structure of the Fc region of IgG(1), which exhibits twofold rotational symmetry. This implies that IgE should be divalent with respect to its ligands. X-ray scattering studies reveal however that the twofold rotational symmetry of IgE-Fc is perturbed by a bend in the linker region between the C epsilon 2 and C epsilon 3 domains. The 1:1 stoichiometry could then arise from the conformational asymmetry or from steric occlusion of one of the sites by the overhanging C epsilon 2 domains. To test this hypothesis we have expressed a recombinant epsilon-chain fragment containing C epsilon 3 and C epsilon 4. This product, Fc epsilon 3-4, is secreted from cells as a disulphide linked dimer and binds with higher affinity than either IgE or IgE-Fc to cell surface Fc epsilon RI. Titration experiments, together with molecular mass measurements of the Fc epsilon 3-4/sFc epsilon RI alpha complex, reveal that Fc epsilon 3-4 binds only a single receptor molecule. This excludes the possibility that steric hindrance by C epsilon 2 accounts for the unexpected stoichiometry. C1 UNIV LONDON KINGS COLL,RANDALL INST,LONDON WC2B 5RL,ENGLAND. NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Ghirlando, Rodolfo/A-8880-2009 NR 20 TC 28 Z9 28 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PY 1997 VL 25 IS 5-6 BP 471 EP 476 DI 10.1007/s002490050062 PG 6 WC Biophysics SC Biophysics GA XB528 UT WOS:A1997XB52800021 PM 9188170 ER PT J AU Hatfill, S Fitzgerald, W Glushakova, S Grivel, JC Baibakov, B Sylwester, A Zimmerberg, J Margolis, L AF Hatfill, S Fitzgerald, W Glushakova, S Grivel, JC Baibakov, B Sylwester, A Zimmerberg, J Margolis, L TI Pathogenesis in human tissue histoculture SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract C1 NICHHD,LAB CELLULAR & MOL BIOPHYS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PY 1997 VL 74 SU 47 BP 66 EP 66 PG 1 WC Cell Biology SC Cell Biology GA YG407 UT WOS:A1997YG40700066 ER PT J AU Ruhl, S Sandberg, AL Cisar, JO AF Ruhl, S Sandberg, AL Cisar, JO TI Lectin-mediated binding of Streptococci and Actinomyces to leukosialin and leukocyte common antigen on granulocytes SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract C1 UNIV REGENSBURG,DEPT OPERAT DENT & PERIODONTOL,D-8400 REGENSBURG,GERMANY. NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PY 1997 VL 74 SU 46 BP 84 EP 84 PG 1 WC Cell Biology SC Cell Biology GA YA741 UT WOS:A1997YA74100084 ER PT J AU Cavenagh, M Dasso, M AF Cavenagh, M Dasso, M TI RanBP2 associates with UBC9/hus5 and a modified form of RanGAP1. SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PY 1997 VL 72 SU 44 BP 32 EP 32 PG 1 WC Cell Biology SC Cell Biology GA WU212 UT WOS:A1997WU21200032 ER PT J AU Michieli, P Comoglio, P Givol, D Pierce, J AF Michieli, P Comoglio, P Givol, D Pierce, J TI Opposing effects of oncogene products on the p21Waf1 promoter: Relevance to oncogenic transformation and cell cycle progression. SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract C1 UNIV TURIN,SCH MED,INST CANC RES,CANDIOLO,TORINO,ITALY. WEIZMANN INST SCI,DEPT MOL CELL BIOL,IL-76100 REHOVOT,ISRAEL. NCI,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PY 1997 VL 72 SU 44 BP 94 EP 94 PG 1 WC Cell Biology SC Cell Biology GA WU212 UT WOS:A1997WU21200094 ER PT J AU Neyroz, P Menna, C Masotti, L Knutson, JR AF Neyroz, P Menna, C Masotti, L Knutson, JR TI Characterization of the zinc-induced structural transition of p13(suc1) by extrinsic fluorescence methods SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PY 1997 VL 72 SU 44 BP 99 EP 99 PG 1 WC Cell Biology SC Cell Biology GA WU212 UT WOS:A1997WU21200099 ER PT J AU Schonherr, E Kresse, H OConnell, B Fisher, JW Young, MF AF Schonherr, E Kresse, H OConnell, B Fisher, JW Young, MF TI Expression of decorin in endothelial cells undergoing angiogenesis. SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract C1 UNIV MUNSTER,INST PHYSIOL CHEM & PATHOBIOCHEM,D-48129 MUNSTER,GERMANY. NIDR,NIH,BETHESDA,MD 20892. UNIV BERN,INST ANAT,CH-3000 BERN 9,SWITZERLAND. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PY 1997 VL 72 SU 43 BP 160 EP 160 PG 1 WC Cell Biology SC Cell Biology GA WN584 UT WOS:A1997WN58400159 ER PT J AU Walsh, TJ Giri, N AF Walsh, TJ Giri, N TI Pradimicins: A novel class of broad-spectrum antifungal compounds SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Trends in Invasive Fungal Infections 3 Meeting CY SEP, 1995 CL BRUSSELS, BELGIUM ID BIOLOGICAL-ACTIVITIES; D-MANNOPYRANOSIDE; ANTIBIOTICS; DERIVATIVES; BMS-181184; TAXONOMY; INVITRO; AGENTS; BIOSYNTHESIS; BMY-28864 AB Pradimicins are a new class of antifungal compounds currently undergoing preclinical and early phase I clinical trials. The pradimicin structure is characterized by an aglycone of dihydrobenzo (alpha) napthacenequinone with substitutions by a D-amino acid and hexose sugar. Pradimicins possess a novel mechanism of action consisting of a specific binding recognition to terminal D-mannosides of the cell wall of Candida albicans, resulting in the formation of a ternary complex consisting of D-mannoside, pradimicin, and calcium that leads to disruption of the integrity of the fungal cell membrane. Pradimicin in the form of BMS-181184 has broad-spectrum in vitro antifungal activity against Candida spp., Cryptococcus neoformans, Aspergillus spp., dematiaceous molds, and the Zygomycetes. Fusarium spp. are comparatively resistant to high concentrations of pradimicin. Initial in vivo studies indicate that pradimicins have antifungal activity against experimental murine disseminated candidiasis and disseminated aspergillosis. Early studies indicate an excellent therapeutic index with no major end-organ toxicity. Pradimicins warrant further investigation for treatment of opportunistic mycoses in immuno-compromised hosts. RP Walsh, TJ (reprint author), NCI,PEDIAT BRANCH,IMMUNOCOMPROMISED HOST SECT,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 27 TC 34 Z9 36 U1 1 U2 2 PU MMW MEDIZIN VERLAG GMBH PI MUNICH PA MUNCHEN, SUBSCRIPTION DEPT, D-81664 MUNICH, GERMANY SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD JAN PY 1997 VL 16 IS 1 BP 93 EP 97 DI 10.1007/BF01575126 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA WL372 UT WOS:A1997WL37200017 PM 9063679 ER PT J AU Fuse, E Nishiie, H Kobayashi, H Ikeda, S Saito, H Covey, J Kobayashi, S AF Fuse, E Nishiie, H Kobayashi, H Ikeda, S Saito, H Covey, J Kobayashi, S TI Disposition of DX-52-1, a novel anticancer agent, after intravenous administration to mice and dogs SO EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS LA English DT Article DE quinocarmycin; anti-cancer drugs; blood; distribution; excretion ID ANTITUMOR-ACTIVITY; CELL-LINES; KW2152; QUINOCARCIN; DC-52 AB DX-52-1 is a new derivative of a quinocarmycin analogue. The disposition of [H-3]-DX-52-1 was investigated in mice and dogs after intravenous administration (4 and 0.15 mg/kg, respectively). The plasma concentration of non-volatile radioactivity was 7.4 mu g eq./ml 3 min after administration to mice, then declined biphasically until 2 h. The distribution of non-volatile radioactivity into blood cells was 20% 3 min after administration, being maintained until 30 min. The plasma concentration of unchanged drug was almost equal to that of the radioactivity 3 min after administration and the unchanged drug ratio decreased rapidly. High radioactivity was found in the gall bladder, kidney, liver, and lung 15 min after administration. No radioactivity was detected in most tissues 24 h post-administration. The cumulative excretion of total radioactivity into urine and feces after administration was 68 and 28% within 96 h, respectively. The plasma concentration of non-volatile radioactivity was 0.65 mu g eq./ml 3 min after administration to dogs. The distribution of non-volatile radioactivity into blood cells was about 20% 3 min after administration and this level tended to increase with time. The cumulative excretion of total radioactivity into urine and feces after administration was 62 and 24%, respectively. C1 NATL CANC INST,BETHESDA,MD. RP Fuse, E (reprint author), KYOWA HAKKO KOGYO CO LTD,PHARMACEUT RES LABS,1188 SHIMOTOGARI,NAGAIZUMI,SHIZUOKA 411,JAPAN. NR 12 TC 4 Z9 4 U1 0 U2 0 PU MEDECINE ET HYGIENE PI GENEVA 4 PA 78 AVE ROSERALE, 1211 GENEVA 4, SWITZERLAND SN 0378-7966 J9 EUR J DRUG METAB PH JI Eur. J. Drug Metabol. Pharmacokinet. PD JAN-MAR PY 1997 VL 22 IS 1 BP 53 EP 63 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XB146 UT WOS:A1997XB14600007 PM 9179561 ER PT J AU LeRoith, D Blakesley, VA AF LeRoith, D Blakesley, VA TI The yin and the yang of the IGF system: Immunological manifestations of GH resistance SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Editorial Material ID GROWTH-FACTOR-I; RECEPTOR; SERUM RP LeRoith, D (reprint author), NIDDK, DIABET BRANCH, NIH, BETHESDA, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JAN PY 1997 VL 136 IS 1 BP 33 EP 34 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WL971 UT WOS:A1997WL97100006 PM 9037121 ER PT J AU Blesa, R Mohr, E Miletich, RS Randolph, C Hildebrand, K Sampson, M Chase, TN AF Blesa, R Mohr, E Miletich, RS Randolph, C Hildebrand, K Sampson, M Chase, TN TI Changes in cerebral glucose metabolism with normal aging SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE cerebral glucose metabolism; normal aging; PET scanning ID POSITRON EMISSION TOMOGRAPHY; ALZHEIMERS-DISEASE; HUNTINGTONS-DISEASE; RISK-FACTORS; HUMAN-BRAIN; ATROPHY; DEMENTIA; PET; AMNESIA; AGE AB The pattern of changes in cerebral glucose metabolism occurring with normal aging has been unclear. Advances in imaging technology, such as improved resolution and anatomical referencing, allow for more precise regional measurement than previously possible. This study explored cerebral glucose metabolism in 17 normal controls ranging in age from 20 to 74 years. High resolution PET scanning, with MRT-based regions of interest correcting for partial volume and atrophy effects, revealed a linear association between advancing age and declining cerebral glucose metabolism. The decline averaged 8% per decade for the whole brain. Changes were most pronounced in limbic structures, and could be implicated in age-associated memory loss. C1 UNIV OTTAWA,FAC MED NEUROL,OTTAWA CIVIC HOSP,OTTAWA,ON,CANADA. UNIV OTTAWA,ELISABETH BRUYERE HLTH CTR,OTTAWA,ON,CANADA. SUNY BUFFALO,MILLARD FILLMORE HOSP,DENT NEUROL INST,BUFFALO,NY 14260. NINCDS,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. RP Blesa, R (reprint author), UNIV BARCELONA,SERV NEUROL,HOSP CLIN & PROV,VILLARROEL 170,BARCELONA 08036,SPAIN. RI Sampson, Margaret/A-9128-2011; OI Sampson, Margaret/0000-0003-2550-9893 NR 52 TC 15 Z9 15 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD JAN PY 1997 VL 4 IS 1 BP 8 EP 14 DI 10.1111/j.1468-1331.1997.tb00294.x PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WN505 UT WOS:A1997WN50500003 PM 24283817 ER PT J AU Palmberg, C Koivisto, P Hyytinen, E Isola, J Visakorpi, T Kallioniemi, OP Tammela, T AF Palmberg, C Koivisto, P Hyytinen, E Isola, J Visakorpi, T Kallioniemi, OP Tammela, T TI Androgen receptor gene amplification in a recurrent prostate cancer after monotherapy with the nonsteroidal potent antiandrogen Casodex (bicalutamide) with a subsequent favorable response to maximal androgen blockade SO EUROPEAN UROLOGY LA English DT Article DE androgen receptor; gene amplification; prostate cancer, recurrent ID CARCINOMA; ICI-176,334; CASTRATION; FLUTAMIDE; THERAPY; TRIAL AB Objective: We recently found amplification of the androgen receptor (AR) gene in similar to 30% of locally recurrent prostate carcinomas from patients treated by conventional androgen deprivation (castration) therapy, whereas none of the untreated primary prostate tumors showed this amplification, This suggests that AR gene amplification was selected during androgen deprivation therapy, The present case study represents our initial approach to evaluate the role that AR amplification may play in therapy resistance after other forms of endocrine therapy, Material and Methods: Specimens from both a primary and a subsequent locally recurrent tumor were studied for amplification of the AR gene by fluorescence in situ hybridization from a prostate cancer patient who experienced tumor progression after monotherapy with the potent antiandrogen bicalutamide (Casodex, a trade mark, the property of Zeneca Ltd), Results and Conclusions: High-level amplification of the AR gene was found in the recurrent tumor, whereas no evidence of amplification was found in the primary tumor, After recurrence, the patient first received chemotherapy (ifosfamide) for 15 weeks with no response, followed by maximal androgen blockade (MAB), The latter therapy resulted in a favorable short-term response, This case study has the following implications which warrant further research: (1) AR amplification may be selected not only by. castration but also by therapy with a competitive peripheral androgen-receptor-blocking agent, and (2) recurrent tumors with AR amplification may be particularly likely to benefit from MAB as a second-line therapy. C1 TAMPERE UNIV HOSP,CANC GENET LAB,FIN-33521 TAMPERE,FINLAND. INST MED TECHNOL,TAMPERE,FINLAND. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. RP Palmberg, C (reprint author), TAMPERE UNIV HOSP,DIV UROL,POB 2000,FIN-33521 TAMPERE,FINLAND. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 18 TC 41 Z9 41 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-2838 J9 EUR UROL JI Eur. Urol. PY 1997 VL 31 IS 2 BP 216 EP 219 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA WL378 UT WOS:A1997WL37800016 PM 9076469 ER PT J AU Baskar, PV Nagel, JE Narayan, O McClure, HM Adler, WH Hildreth, JEK AF Baskar, PV Nagel, JE Narayan, O McClure, HM Adler, WH Hildreth, JEK TI Antibody to human MHC class I inhibits SIV(smm)PBj1.9-induced proliferation of pigtailed macaque lymphocytes SO EXPERIMENTAL AND CLINICAL IMMUNOGENETICS LA English DT Article DE simian immunodeficiency virus; lymphocytes, pigtailed macaque; MHC class I; Staphylococcus enterotoxin A; toxin shock syndrome toxin-1; Staphylococcus enterotoxin E ID SIMIAN IMMUNODEFICIENCY VIRUS; MONOCLONAL-ANTIBODIES; ADHESION RECEPTORS; RHESUS-MONKEYS; CELL-ADHESION; T-CELLS; ANTIGEN; IDENTIFICATION; EXPRESSION; ACTIVATION AB Previously we have shown that the simian immunodeficiency virus SIV(smm)PBj1.9, a molecular clone of SIV(smm)PBj14, induces proliferation of human peripheral blood mononuclear cells (PBMC). We have extended this observation to show that SIV(smm)PBj1.9 induces proliferation of PBMC from pigtailed macaques. This proliferative response was markedly inhibited by mAbs against human class I MHC, class II MHC and CD4 antigens, and partially inhibited by mAbs against integrin beta(2) subunit (CD18) and LFA-1 (CD11a). However, these antibodies differed in their ability to inhibit in vitro viral infectivity of PBMC. While anti-CD4, MHC class II, and LFA-1 strongly inhibited viral infectivity, antibodies to MHC class I demonstrated little effect on viral infectivity. A control antibody (PLM2) against porcine CD18 inhibited neither virus-induced proliferation nor viral infectivity. Based on these results, we suggest that SIV(smm)PBj1.9-induced proliferation requires the participation of class I MHC, class II MHC and CD4 molecules. In addition, the observation that anti-class I MHC Ab inhibited proliferation of macaque PBMC induced by mitogen (PHA) and bacterial superantigens, such as Staphylococcus enterotoxin A and toxin shock syndrome toxin-l, suggests that SIV(smm)PBj1.9 also contains a viral superantigen similar to that previously demonstrated in SIV(smm)PBj14. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOL SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT COMPARAT MED,BALTIMORE,MD. EMORY UNIV,DEPT PATHOL,ATLANTA,GA 30322. EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. RP Baskar, PV (reprint author), NIA,GERONTOL RES CTR,NIH,4940 EASTERN AVE,BOX 21,BALTIMORE,MD 21224, USA. FU NIAID NIH HHS [AI07394, AI29382, AI31806] NR 39 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-9670 J9 EXP CLIN IMMUNOGENET JI Exp. Clin. Immunogenet. PY 1997 VL 14 IS 2 BP 141 EP 148 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology SC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology GA YG606 UT WOS:A1997YG60600005 PM 9395890 ER PT J AU Edberg, JC Wainstein, E Wu, JM Csernok, E Sneller, MC Hoffman, GS Keystone, EC Gross, WL Kimberly, RP AF Edberg, JC Wainstein, E Wu, JM Csernok, E Sneller, MC Hoffman, GS Keystone, EC Gross, WL Kimberly, RP TI Analysis of Fc gamma RII gene polymorphisms in Wegener's granulomatosis SO EXPERIMENTAL AND CLINICAL IMMUNOGENETICS LA English DT Article DE ANCA Fc gamma receptors; neutrophils; monocyte/macrophages; mononuclear phagocytes; vasculitis ID NATURAL-KILLER-CELLS; RECEPTOR-III CD16; CYTOPLASMIC ANTIBODIES ANCA; PROTEIN-TYROSINE KINASE; LUPUS-ERYTHEMATOSUS SLE; HUMAN NEUTROPHILS; IMMUNOGLOBULIN-G; EPSILON-RI; SIGNAL-TRANSDUCTION; CD32 POLYMORPHISM AB Fc gamma receptors (Fc gamma Rs) are potent initiators of proinflammatory reactions and tissue injury programs through the oxidative burst, degranulation and the production of a variety of proinflammatory cytokines, Direct experimental evidence indicates that translocation of ANCA target from intracellular granules to the neutrophil membrane and subsequent binding of ANCA enables Fc gamma R-mediated neutrophil activation, In the presence of ANCA, these data provide a framework from which to understand the importance of ANCA class, subclass, and titer in Wegener's granulomatosis and other ANCA-positive vasculitides. The well-characterized and functionally important alleles of neutrophil Fc gamma R (Fc gamma RIIa-H131/R131 and Fc gamma RIIIb-NA1/NA2) are possible inheritable genetic elements that may alter disease severity and/or phenotype. C1 Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Hosp Salvador, Secc Reumatol, Dept Med, Santiago, Chile. Univ Lubeck, Rheumaklin Bad Bramstedt, D-2400 Lubeck, Germany. Univ Lubeck, Poliklin Rheumatol, D-2400 Lubeck, Germany. NIAID, Immunol Dis Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Rheumat & Immunol Dis, Cleveland, OH 44195 USA. Univ Toronto, Wellesley Hosp, Div Adv Therapeut Studies Rheumat Dis, Toronto, ON M4Y 1J3, Canada. RP Kimberly, RP (reprint author), Univ Alabama, Div Clin Immunol & Rheumatol, 429 Tinsley Harrison Tower,1900 Univ Blvd, Birmingham, AL 35294 USA. RI Gross, Wolfgang Ludwig/C-8733-2011 NR 74 TC 50 Z9 53 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-9670 J9 EXP CLIN IMMUNOGENET JI Exp. Clin. Immunogenet. PY 1997 VL 14 IS 3 BP 183 EP 195 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology SC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology GA YU841 UT WOS:000071761400002 PM 9493787 ER PT J AU Grill, SE Hallett, M McShane, LM AF Grill, SE Hallett, M McShane, LM TI Timing of onset of afferent responses and of use of kinesthetic information for control of movement in normal and cerebellar-impaired subjects SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE kinesthesia; coordination; cerebellum; muscle spindles; cutaneous mechanoreceptors; human ID ALIGNED PURKINJE-CELLS; VOLUNTARY MOVEMENT; POSITION SENSE; INTERPHALANGEAL JOINT; PERTURBED LOCOMOTION; PASSIVE MOVEMENTS; MUSCLE AFFERENTS; DECEREBRATE CAT; MOTOR FUNCTION; FINGER AB A coordinated triggering task requiring use of kinesthetic information was employed to assess the timing of use of kinesthetic information in normal subjects and patients with cerebellar dysfunction. Passive movements of varying velocity were imposed in the flexor direction about the metacarpophalangeal joint of the right index finger, Subjects attempted to depress a switch with their left thumb when the index finger moved past a specified angle that was learned during a training session. The velocities ranged from 10 degrees/s to 88 degrees/s in 2 degrees/s increments. After 200 trials, subjects were then instructed instead to react as quickly as possible (reaction-time task) to the onset of movement for an additional 200 trials. For the same movements, the timing of onset of responses of muscle spindle afferents and cutaneous mechanoreceptors was determined by recording the responses of these afferents using microneurography. For slow velocities, patients were able to perform similarly to normals but at faster velocities patients triggered too late compared with normals. Patients required more time to use kinesthetic information than did normal subjects. An estimate of kinesthetic processing was not longer in patients. The chief explanation for the prolonged time required to use kinesthetic information in patients was that their reaction times were prolonged by 93 ms. In addition, the movement time was also prolonged, but this accounted for only 23 ms. Impaired motor performance in tasks requiring the use of kinesthetic information in cerebellar patients can be explained largely by their prolonged reaction times. Muscle spindle afferents responded on average much sooner than cutaneous mechanoreceptors. Because of the limited time available to perform the kinesthetic triggering task, the role for cutaneous mechanoreceptors to provide signals for on-line coordination of movement appears limited compared with muscle spindle afferents. C1 NCI,BIOMETRY BRANCH DCPC,NIH,BETHESDA,MD 20892. RP Grill, SE (reprint author), NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,10 CTR DR MSC 1430,BLDG 10 RM 5N234,BETHESDA,MD 20892, USA. NR 63 TC 18 Z9 18 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 1997 VL 113 IS 1 BP 33 EP 47 PG 15 WC Neurosciences SC Neurosciences & Neurology GA WE157 UT WOS:A1997WE15700005 PM 9028773 ER PT J AU Sprott, RL AF Sprott, RL TI Proceedings of the second international conference on animal models for aging research - Preface SO EXPERIMENTAL GERONTOLOGY LA English DT Editorial Material RP Sprott, RL (reprint author), NIA,NIH,BIOL AGING PROGRAM,7201 WISCONSIN AVE,SUITE 2C231,BETHESDA,MD 20892, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JAN-APR PY 1997 VL 32 IS 1-2 BP 1 EP 2 DI 10.1016/S0531-5565(96)00077-0 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA WN275 UT WOS:A1997WN27500001 ER PT J AU Sprott, RL AF Sprott, RL TI Mouse and rat genotype choices SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT Proceedings of the 2nd International Conference on Animal Models for Aging Research CY MAY 12-19, 1995 CL KYOTO, JAPAN SP Natl Inst on Aging DE models; genetic; mice; rats ID STRAINS; MODEL AB There are advantages and disadvantages to all animal models for aging research. Investigators need to understand these issues, as well as the nature of each relevant model, to choose the best model for their research. There is no ''best'' or ''worst'' model for aging research. Five genetically defined rodent models of potential utility in aging research are: (1) inbred strains and Fl hybrid mice and rats, (2) single gene mutations and other single locus effects, (3) congenic lines, (4) recombinant Inbred (RI) strains, and (5) genetically selected strains and stocks. Animals of each of these types are available for research, but only inbred and Fl hybrid mice and rats are commercially available as aged animals. A general understanding of the need for careful genetic definition and for the best available barrier-breeding facilities has improved the quality of aging research significantly in the last two decades. Copyright (C) 1997 Elsevier Science Inc. RP Sprott, RL (reprint author), NIA,NIH,BIOL AGING PROGRAM,7201 WISCONSIN AVE,GATEWAY BLDG,RM 2C231,BETHESDA,MD 20892, USA. NR 15 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JAN-APR PY 1997 VL 32 IS 1-2 BP 79 EP 86 DI 10.1016/S0531-5565(96)00035-6 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA WN275 UT WOS:A1997WN27500009 PM 9088904 ER PT J AU Sprott, RL AF Sprott, RL TI Diet and calorie restriction SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT Proceedings of the 2nd International Conference on Animal Models for Aging Research CY MAY 12-19, 1995 CL KYOTO, JAPAN SP Natl Inst on Aging DE caloric restriction; mice; rats; life span ID FISCHER-344 AB Current data suggest that the life spans of commonly held rodent species have decreased and the occurrence of tumors occurs earlier in the lifespan of ad libitum-fed animals. The most likely cause of this change in the life span of barrier-reared genetically defined animals is increased body weight. The effects of caloric restriction on a variety of functional measures and on age-dependent tumors and lesions are the focus of this presentation. Recommendations for caloric restriction, or at least ''dietary control,'' will be discussed. Copyright (C) 1997 Elsevier Science Inc. RP Sprott, RL (reprint author), NIA,NIH,BIOL AGING PROGRAM,7201 WISCONSIN AVE,GATEWAY BLDG,SUITE 2C231,BETHESDA,MD 20892, USA. NR 7 TC 43 Z9 44 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JAN-APR PY 1997 VL 32 IS 1-2 BP 205 EP 214 DI 10.1016/S0531-5565(96)00065-4 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA WN275 UT WOS:A1997WN27500022 PM 9088917 ER PT J AU Wanidworanun, C Levy, DD Shear, HL AF Wanidworanun, C Levy, DD Shear, HL TI Plasmodium chabaudi: cDNA of Pc96, a protective antigen associated with the erythrocyte membrane of infected erythrocytes SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Plasmodium chabaudi; Pc96; cDNA; protective immune response; erythrocytes ID FALCIPARUM; PARASITE; ANTIBODIES; RECOGNIZE; SERA C1 ALBERT EINSTEIN COLL MED,BRONX,NY 10467. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RP Wanidworanun, C (reprint author), MONTEFIORE MED CTR,DEPT MED,DIV HEMATOL,BRONX,NY 10467, USA. FU NIAID NIH HHS [AI34064, AI15235] NR 14 TC 3 Z9 3 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JAN PY 1997 VL 85 IS 1 BP 92 EP 98 DI 10.1006/expr.1996.4122 PG 7 WC Parasitology SC Parasitology GA WF956 UT WOS:A1997WF95600012 PM 9024207 ER PT J AU Whitcup, SM AF Whitcup, SM TI The initiating stimuli for uveitis SO EYE LA English DT Article ID ENDOTOXIN-INDUCED UVEITIS; EXPERIMENTAL AUTOIMMUNE UVEITIS; SYMPATHETIC OPHTHALMIA; HUMAN-DISEASE; NEUTROPHILS; ANTIGEN; LIPOPOLYSACCHARIDE; CYTOKINE; KINETICS; MODEL RP Whitcup, SM (reprint author), NEI,10 CTR DR,BETHESDA,MD 20892, USA. NR 28 TC 7 Z9 7 U1 0 U2 0 PU ROYAL COLL OPHTHALMOLOGISTS PI LONDON PA 17 CORNWALL TERRACE, LONDON, ENGLAND NW1 4QW SN 0950-222X J9 EYE JI Eye PY 1997 VL 11 BP 167 EP 170 PN 2 PG 4 WC Ophthalmology SC Ophthalmology GA XA346 UT WOS:A1997XA34600005 PM 9349407 ER PT J AU Prasad, SA Gregerson, DS AF Prasad, SA Gregerson, DS TI Antigen presentation in uveitis SO EYE LA English DT Article DE antigen presentation; autoantigens; immune tolerance; retinitis; T lymphocytes ID T-CELL HYBRIDOMAS; MYELIN BASIC-PROTEIN; B-CELLS; IL-2 PRODUCTION; LYMPHOCYTE-B; S-ANTIGEN; RECEPTOR; INDUCTION; RESPONSES; UNRESPONSIVENESS AB Experimental autoimmune uveoretinitis (EAU) is not only a valuable model for human inflammatory eye diseases, it is also a useful system for studying many aspects of immunobiology. One such aspect is self/non-self discrimination, the ability of the immune system to tolerate self molecules while responding aggressively to foreign antigens. Our laboratory has used EAU to investigate the mechanisms of T cell tolerance to retinal S-antigen (S-Ag). Several mechanisms have been proposed to maintain T cell tolerance to autoantigens, including clonal deletion and clonal anergy. As immunisation with S-Ag or pathogenic peptides activates uveitogenic T cells, tolerance to this autoantigen cannot be due to clonal deletion. Nevertheless, tolerance acts to keep these existing autoreactive T cells in a naive, or innocuous state. Here me suggest a novel mechanism - low-affinity occupancy of the autoantigen-specific T cell receptor (TCR) by self-antigen - that may act in concert with the well-known,ia mechanisms to maintain tolerance to S-Ag in the LEW rat. This model differs from clonal energy in that the missing antigen-presenting cell (APC) activity is not a co-stimulatory function but a TCR co-ligand that increases the avidity of the interaction between the TCR and its peptide-major histocompatibility complex (MHC) ligand. In the absence of this co-ligand only partial signals are generated through the TCR, leading to incomplete T cell activation. This model was deduced from experiments with T cell lines and hybridomas specific for S-Ag, which showed that: (1) autoreactive T cells required a novel APC function, (2) this novel function was necessary to provide complete TCR engagement, and (3) activation of autoreactive T cells was restricted to specific APC. C1 UNIV MINNESOTA,DEPT OPHTHALMOL,MINNEAPOLIS,MN 55455. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. NR 30 TC 2 Z9 2 U1 0 U2 0 PU ROYAL COLL OPHTHALMOLOGISTS PI LONDON PA 17 CORNWALL TERRACE, LONDON, ENGLAND NW1 4QW SN 0950-222X J9 EYE JI Eye PY 1997 VL 11 BP 176 EP 182 PN 2 PG 7 WC Ophthalmology SC Ophthalmology GA XA346 UT WOS:A1997XA34600007 PM 9349409 ER PT J AU Caspi, RR Sun, B Agarwal, RK Silver, PB Rizzo, LV Chan, CC Wiggert, B Wilder, RL AF Caspi, RR Sun, B Agarwal, RK Silver, PB Rizzo, LV Chan, CC Wiggert, B Wilder, RL TI T cell mechanisms in experimental autoimmune uveoretinitis: Susceptibility is a function of the cytokine response profile SO EYE LA English DT Article DE T lymphocytes; autoimmunity; cytokines; experimental autoimmune uveoretinitis; uveitis ID RETINOID-BINDING PROTEIN; INTERPHOTORECEPTOR AB This study addresses the question whether susceptibility versus resistance to experimental autoimmune uveoretinitis (EAU) is connected to a Th1-type (interferon-gamma high, interleukin-4 low), versus a Th2-type (IFN-gamma low, IL-4 high) response. Primed lymph node cells of susceptible Lewis rats produced IFN-gamma in response to antigen in culture and transferred EAU to syngeneic recipients, whereas lymph node cells of resistant F344 rats made no IFN-gamma and did not transfer disease. Reversal of the disease pattern, by treatment of F344 rats,vith B. pertussis toxin and immunisation of Lewis rats with antigen in incomplete Freund's adjuvant, resulted in a parallel reversal of these response patterns. Neither strain produced significant IL-4 responses. A study of the response patterns in mice confirmed that high Th1 responders were susceptible, whereas low Th1 responders and Th2 responders were resistant. We conclude that susceptibility to EAU is connected with a Th1-dominant response, but resistance can involve either a 'null', F344-like response (Th1-low/Th2-low) or a Th2-dominant response. C1 NEI,RETINAL CELL & MOL BIOL LAB,BETHESDA,MD 20892. NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. RP Caspi, RR (reprint author), NEI,IMMUNOL LAB,NIH,BLDG 10,ROOM 10N222,10 CTR DR,MSC 1858,BETHESDA,MD 20892, USA. RI Rizzo, Luiz Vicente/B-4458-2009 NR 11 TC 66 Z9 67 U1 0 U2 1 PU ROYAL COLL OPHTHALMOLOGISTS PI LONDON PA 17 CORNWALL TERRACE, LONDON, ENGLAND NW1 4QW SN 0950-222X J9 EYE JI Eye PY 1997 VL 11 BP 209 EP 212 PN 2 PG 4 WC Ophthalmology SC Ophthalmology GA XA346 UT WOS:A1997XA34600012 PM 9349414 ER PT J AU Nussenblatt, RB Csaky, K AF Nussenblatt, RB Csaky, K TI Perspectives on gene therapy in the treatment of ocular inflammation SO EYE LA English DT Article DE ocular disease; gene therapy; uveitis; autoimmune disease ID TRANSGENIC MICE; RETINA; EXPRESSION; LENS AB Gene therapy may become a powerful therapeutic strategy. However, the application of this method in the treatment of ocular disease presents us with interesting and unique questions. Gene therapy for ocular inflammatory disease has the potential for both therapeutic interventions and a method for studying mechanisms of disease. An evolving philosophy on this subject would support the use of somatic gene therapy for ocular inflammatory disease, even if not life threatening. Major technical questions remain, including the use of the appropriate vector, the best methodology for the stable insertion into the genome, and the duration and intensity of expression of the transgene. Various transgenes encoding a wide variety of proteins can be envisaged for the insertion of genes. The study of gyrate atrophy, an hereditary ocular disorder and an excellent candidate for gene therapy, has given us enormous information in the development of practical therapeutic strategies, as have in vitro studies of gene insertion. Future concerns will need to concentrate on the use of better methods for gene insertion and homologous recombination techniques for the development of animal models and later as a strategy for gene therapy. The use of gene therapy as a drug delivery system must also be considered. In addition, the elucidation of the various events controlling transcription for the expression of transgenes in various resident ocular cells is necessary. RP Nussenblatt, RB (reprint author), NEI,10 CTR DR,MSC 1858,BLDG 10,ROOM 10N202,BETHESDA,MD 20892, USA. NR 17 TC 7 Z9 7 U1 0 U2 0 PU ROYAL COLL OPHTHALMOLOGISTS PI LONDON PA 17 CORNWALL TERRACE, LONDON, ENGLAND NW1 4QW SN 0950-222X J9 EYE JI Eye PY 1997 VL 11 BP 217 EP 221 PN 2 PG 5 WC Ophthalmology SC Ophthalmology GA XA346 UT WOS:A1997XA34600014 PM 9349416 ER PT J AU Roy, MS Rodgers, GP AF Roy, MS Rodgers, GP TI Letters to the editor SO EYE LA English DT Letter ID SICKLE-CELL DISEASE; HETEROGENEITY C1 NIDDK, BIOL CHEM LAB, NIH, BETHESDA, MD 20892 USA. RP Roy, MS (reprint author), UNIV MED & DENT NEW JERSEY, NEW JERSEY MED SCH, 90 BERGEN ST, NEWARK, NJ 07103 USA. NR 6 TC 1 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X EI 1476-5454 J9 EYE JI Eye PY 1997 VL 11 BP 432 EP 433 PN 3 PG 2 WC Ophthalmology SC Ophthalmology GA XJ744 UT WOS:A1997XJ74400048 PM 9373505 ER PT J AU Bork, P Hofmann, K Bucher, P Neuwald, AF Altschul, SF Koonin, EV AF Bork, P Hofmann, K Bucher, P Neuwald, AF Altschul, SF Koonin, EV TI A superfamily of conserved domains in DNA damage responsive cell cycle checkpoint proteins SO FASEB JOURNAL LA English DT Article DE BRCT domain; database search; PARP; profile; motif ID REPLICATION FACTOR-C; SACCHAROMYCES-CEREVISIAE; POLY(ADP-RIBOSE) POLYMERASE; FISSION YEAST; TRANSCRIPTIONAL ACTIVATION; RETINOBLASTOMA PROTEIN; SEQUENCE SIMILARITY; SECONDARY STRUCTURE; MULTIPLE ALIGNMENT; FEEDBACK CONTROLS AB Computer analysis of a conserved domain, BRCT, first described at the carboxyl terminus of the breast cancer protein BRCA1, a p53 binding protein (53BP1), and the yeast cell cycle checkpoint protein RAD9 revealed a large superfamily of domains that occur predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage. The BRCT domain consists of similar to 95 amino acid residues and occurs as a tandem repeat at the carboxyl terminus of numerous proteins, but has been observed also as a tandem repeat at the amino terminus or as a single copy. The BRCT superfamily presently includes similar to 40 nonorthologous proteins, namely, BRCA1, 53BP1, and RAD9; a protein family that consists of the fission yeast replication checkpoint protein Rad4, the oncoprotein ECT2, the DNA repair protein XRCC1, and yeast DNA polymerase subunit DPB11; DNA binding enzymes such as terminal deoxynucleotidyltransferases, deoxycytidyl transferase involved in DNA repair, and DNA-ligases III and IV; yeast multifunctional transcription factor RAP1; and several uncharacterized gene products. Another previously described domain that is shared by bacterial NAD-dependent DNA-ligases, the large subunits of eukaryotic replication factor C, and poly(ADP-ribose) polymerases appears to be a distinct version of the BRCT domain. The retinoblastoma protein (a universal tumor suppressor) and related proteins may contain a distant relative of the BRCT domain. Despite the functional diversity of all these proteins, participation in DNA damage-responsive checkpoints appears to be a unifying theme. Thus, the BRCT domain is likely to perform critical, yet uncharacterized, functions in the cell cycle control of organisms from bacteria to humans. The carboxyterminal BRCT domain of BRCA1 corresponds precisely to the recently identified minimal transcription activation domain of this protein, indicating one such, function. C1 EUROPEAN MOL BIOL LAB,D-69012 HEIDELBERG,GERMANY. MAX DELBRUCK CTR MOL MED,BERLIN,GERMANY. SWISS INST EXPT CANC RES,CH-1066 EPALINGES,SWITZERLAND. RP Bork, P (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894, USA. RI Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 95 TC 586 Z9 600 U1 4 U2 13 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 1997 VL 11 IS 1 BP 68 EP 76 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA WK147 UT WOS:A1997WK14700010 PM 9034168 ER PT J AU Hock, DL Huhn, RD Kemmann, E AF Hock, DL Huhn, RD Kemmann, E TI Stimulation of granulocyte colony stimulating factor (G-CSF) and leukocytosis in women receiving menotropin therapy. SO FERTILITY AND STERILITY LA English DT Meeting Abstract C1 UMDNJ,ROBERT WOOD JOHNSON MED SCH,DEPT OB GYN & REPROD SCI,NEW BRUNSWICK,NJ. NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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. PY 1997 SU S BP P298 EP P298 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA XY160 UT WOS:A1997XY16000479 ER PT J AU Leondires, MP Miller, BT Escalpes, M Rogers, BJ Segars, JH Gehlbach, DL Scott, RT AF Leondires, MP Miller, BT Escalpes, M Rogers, BJ Segars, JH Gehlbach, DL Scott, RT TI Clinical efficacy and cost effectiveness of a microdose GnRH-a protocol compared to a luteal phase GnRH-a protocol for controlled ovarian hyperstimulation. SO FERTILITY AND STERILITY LA English DT Meeting Abstract C1 NIH, BETHESDA, MD 20892 USA. WALTER REED REPROD SCI CTR, BETHESDA, MD USA. NATL NAVAL MED CTR, BETHESDA, MD USA. NR 0 TC 0 Z9 0 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. PY 1997 SU S BP P259 EP P259 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA XY160 UT WOS:A1997XY16000440 ER PT S AU Ross, JBA Szabo, AG Hogue, CWV AF Ross, JBA Szabo, AG Hogue, CWV BE Brand, L Johnson, ML TI Enhancement of protein spectra with tryptophan analogs: Fluorescence spectroscopy of protein-protein and protein-nucleic acid interactions SO FLUORESCENCE SPECTROSCOPY SE Methods in Enzymology LA English DT Review ID TIME-RESOLVED FLUORESCENCE; SITE-SPECIFIC INCORPORATION; UNNATURAL AMINO-ACIDS; LAMBDA CI-REPRESSOR; TRANSCRIPTION TRANSLATION SYSTEM; TRANSFER RNA-SYNTHETASE; ESCHERICHIA-COLI; EXCITED-STATE; BACILLUS-SUBTILIS; BIOSYNTHETIC INCORPORATION C1 UNIV WINDSOR, DEPT CHEM & BIOCHEM, WINDSOR, ON N9B 3P4, CANADA. NIH, NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. RP Ross, JBA (reprint author), MT SINAI SCH MED, DEPT BIOCHEM, NEW YORK, NY 10029 USA. RI Hogue, Christopher/B-6726-2008 FU NHLBI NIH HHS [HL-29017]; NIGMS NIH HHS [GM-39750] NR 113 TC 98 Z9 98 U1 0 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182179-X J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 278 BP 151 EP 190 PG 40 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ03V UT WOS:A1997BJ03V00008 PM 9170313 ER PT S AU Gryczynski, Z Lubkowski, J Bucci, E AF Gryczynski, Z Lubkowski, J Bucci, E BE Brand, L Johnson, ML TI Intrinsic fluorescence of hemoglobins and myoglobins SO FLUORESCENCE SPECTROSCOPY SE Methods in Enzymology LA English DT Review ID TIME-RESOLVED FLUORESCENCE; ENERGY-TRANSFER; LINEAR DICHROISM; TRANSITION MOMENTS; CIRCULAR-DICHROISM; DISORDERED HEMES; SPERM WHALE; RESOLUTION; PICOSECOND; TRYPTOPHANS C1 NCI, FREDERICK CANC RES & DEV CTR, MACROMOL STRUCT LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. RP Gryczynski, Z (reprint author), UNIV MARYLAND, SCH MED, DEPT BIOCHEM, BALTIMORE, MD 21201 USA. NR 63 TC 33 Z9 33 U1 2 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182179-X J9 METHOD ENZYMOL JI Methods Enzymol. PY 1997 VL 278 BP 538 EP 569 PG 32 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJ03V UT WOS:A1997BJ03V00028 PM 9170333 ER PT J AU delaCruz, XF Mahoney, MW Lee, B AF delaCruz, XF Mahoney, MW Lee, B TI Discrete representations of the protein C-alpha chain SO FOLDING & DESIGN LA English DT Article DE alpha carbon chain; discrete representation; virtual angle ID RELATE 2 SETS; SECONDARY STRUCTURE; PREDICTION; ACCURACY; ROTATION; VECTORS AB Background: When a large number of protein conformations are generated and screened, as in protein structure prediction studies, it is often advantageous to change the conformation in units of four consecutive residues at a time. The internal geometry of a chain of four consecutive C-alpha atoms is completely described by means of the three angles theta 1, pi, and theta 2, where tau is the virtual torsion angle defined by the four atoms and theta 1 and theta 2 are the virtual bond angles flanking the torsion angle on either side. In this paper, we examine the quality of the protein structures that can be obtained when they are represented by means of a set of discrete values for these angles (discrete states). Results: Different models were produced by selecting various different discrete states. The performance of these models was tested by rebuilding the C-alpha chains of 139 high-resolution nonhomologous protein structures using the build-up procedure of Park and Levitt. We find that the discrete state models introduce distortions at three levers, which can be measured by means of the 'context-free', 'in-context', and the overall root-mean-square deviation of the C-alpha coordinates (crms), respectively, and we find that these different levels of distortions are interrelated. As found by Park and Levitt, the overall crms decreases smoothly for most models with the complexity of the model. However, the decrease is significantly faster with our models than observed by Park and Levitt with their models. We also find that it is possible to choose models that perform considerably worse than expected from this smooth dependence on complexity. Conclusions: Of our models, the most suitable for use in initial protein folding studies appears to be model S8, in which the effective number of states available for a given residue quartet is 6.5. This model builds helices, beta-strands, and coil/loop structures with approximately equal quality and gives the overall crms Value of 1.9 Angstrom on average with relatively little variation among the different proteins tried. C1 NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 20 TC 6 Z9 6 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 1359-0278 J9 FOLD DES JI Fold. Des. PY 1997 VL 2 IS 4 BP 223 EP 234 DI 10.1016/S1359-0278(97)00031-X PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XR103 UT WOS:A1997XR10300004 PM 9269563 ER PT J AU Liberski, PP Brown, P Gajdusek, CD AF Liberski, PP Brown, P Gajdusek, CD TI The evolution of views on the nosological position of transmissible spongiform encephalopathies SO FOLIA NEUROPATHOLOGICA LA English DT Article; Proceedings Paper CT Annual Conference of Polish-Association-of-Neuropathologists on Degenerative Disorders of the Central Nervous System CY MAY 24, 1997 CL WARSAW, POLAND SP Polish Assoc Neuropathologists DE scrapie; Creutzfeldt-Jakob disease; Gerstmann-Straussler-Scheinker disease; prions; PrP ID CREUTZFELDT-JAKOB-DISEASE; PRION PROTEIN GENE; STRAUSSLER-SCHEINKER DISEASE; FATAL FAMILIAL INSOMNIA; AMYLOID PRECURSOR GENE; POINT MUTATION; NEUROFIBRILLARY TANGLES; CODON-129 POLYMORPHISM; MISSENSE VARIANT; DNA POLYMORPHISM AB We report here on the evolution of view on the nature of transmissible spongiform encephalopathies or prion disease. While the nosological position of these diseases is well understood, the nature of the agent is still a matter of dispute. There is no doubt, however, that the gene for PrP plays a major role in the whole group of neurodegenerations. C1 Sch Med, Dept Oncol, Labs Tumor Biol, Lodz, Poland. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. NR 111 TC 1 Z9 1 U1 0 U2 1 PU SEVERUS PUBLISHING HOUSE PI WARSAW PA UL CONRADA 4/146, 01-922 WARSAW, POLAND SN 0028-3894 J9 FOLIA NEUROPATHOL JI Folia Neuropathol. PY 1997 VL 35 IS 4 BP 214 EP 225 PG 12 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA YU989 UT WOS:000071777300003 PM 9833398 ER PT J AU Walis, A Liberski, PP Brown, P Gajdusek, DC AF Walis, A Liberski, PP Brown, P Gajdusek, DC TI Electron microscopic studies of the optic nerve in experimental scrapie and the panencephalopathic type of Creutzfeldt-Jakob disease SO FOLIA NEUROPATHOLOGICA LA English DT Article; Proceedings Paper CT Annual Conference of Polish-Association-of-Neuropathologists on Degenerative Disorders of the Central Nervous System CY MAY 24, 1997 CL WARSAW, POLAND SP Polish Assoc Neuropathologists DE scrapie; Creutzfeldt-Jakob disease; optic nerves; ultrastructure ID PATHOLOGY AB We report the optic nerve ultrastructural pathology in experimental scrapie and Creutzfeldt-Jakob disease. Vacuoles developed within myelinated axons contained typical secondary vacuoles and curled membranes. These were seen either within the axoplasm or within the myelin sheath which split either at the major dense line or at the intraperiod line. Spongiform changes were accompanied by an exuberant cellular reaction consisting of macrophages and hypertrophic astrocytes. Occasionally, vesicular myelin degeneration and coated vesicles in a close proximity to the myelin were observed. C1 Sch Med, Dept Oncol, Labs Tumor Biol, Lodz, Poland. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. NR 7 TC 13 Z9 13 U1 2 U2 2 PU SEVERUS PUBLISHING HOUSE PI WARSAW PA UL CONRADA 4/146, 01-922 WARSAW, POLAND SN 0028-3894 J9 FOLIA NEUROPATHOL JI Folia Neuropathol. PY 1997 VL 35 IS 4 BP 255 EP 258 PG 4 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA YU989 UT WOS:000071777300011 PM 9833406 ER PT J AU Matuszak, Z Reszka, KJ Chignell, CF AF Matuszak, Z Reszka, KJ Chignell, CF TI Reaction of melatonin and related indoles with hydroxyl radicals: EPR and spin trapping investigations SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE DMPO; EPR; Fenton; hydroxyl radicals; 6-hydroxymelatonin; melatonin; serotonin; spin trapping ID RATE CONSTANTS; SEROTONIN AB It has been suggested that the indole hormone melatonin (N-acetyl-5-methoxytryptamine, MLT) is an important natural antioxidant and free radical scavenger [J. Pineal Res., 14:51; 1993]. In the present work we determined the rate constants, k(r), for scavenging (OH)-O-. radicals by melatonin, 5-methoxytryptamine (5-MeO-T), 5-hydroxytryptamine (serotonin, 5-OH-T), 6-chloromelatonin (6-Cl-MLT), 6-hydroxymelatonin (6-OH-MLT), and kynurenine (KN) in aqueous solutions. Hydroxyl radicals were generated using a Fenton reaction in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), which competed with the indoles for the radicals. It was found that MLT reacts with (OH)-O-. with k(r) = 2.7 x 10(10) M-1 s(-1). Other indoles and KN reacted with (OH)-O-. radicals with similarly high rates (k(r) > 10(10) M-1 s(-1)). In contrast to nonhydroxylated indoles (MLT, 6-Cl-MLT, and 5-MeO-T), hydroxylated indoles (5-OH-T and 6-OH-MLT) may function both as (OH)-O-. promoters and (OH)-O-. scavengers. The melatonin precursor serotonin promoted the generation of (OH)-O-. radicals in the presence of ferric iron and H2O2, and the melatonin metabolite 6-hydroxymelatonin generated large quantities of (OH)-O-. radicals in aerated solutions containing Fe3+ ion, even in the absence of externally added hydrogen peroxide. These reactions may be relevant to the biological action of these physiologically important indolic compounds. Published by Elsevier Science Inc. C1 NIEHS,MOL BIOPHYS LAB,NIH,RES TRIANGLE PK,NC 27709. NR 28 TC 228 Z9 229 U1 2 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1997 VL 23 IS 3 BP 367 EP 372 DI 10.1016/S0891-5849(96)00614-4 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA XG674 UT WOS:A1997XG67400003 PM 9214572 ER PT J AU Hahn, SM Mitchell, JB Shacter, E AF Hahn, SM Mitchell, JB Shacter, E TI Tempol inhibits neutrophil and hydrogen peroxide-mediated DNA damage SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE oxidative stress; nitroxides; DNA damage; inflammation; protection; anti-oxidant; inflammation; neutrophil; free radicals ID TUMOR PROMOTION; POLYMORPHONUCLEAR LEUKOCYTES; MAMMALIAN-CELLS; OXYGEN; RADICALS; PHAGOCYTES; INDUCTION; BASES; TRANSFORMATION; PLASMACYTOMAS AB Inflammatory conditions characterized by neutrophil activation are associated with a variety of chronic diseases, Reactive oxygen species are produced by activated neutrophils and produce DNA damage which may lead to tissue damage. Previous studies have shown that activated murine neutrophils induce DNA strand breaks in a target plasmacytoma cell, RIMPC 2394. We studied the effect of a water soluble nitroxide anti-oxidant, Tempol, on murine neutrophil induction of DNA strand breaks in this system. Murine neutrophils were isolated from the peritoneal cavity of BALB/cAn mice after an IP injection of pristane oil. Neutrophils were activated by the phorbol esther PMA and co-incubated with RIMPC 2394 cells. Control alkaline elution studies revealed progressive DNA strand breaks in RIMPC cells with time. The addition of Tempol to the incubation mixture prevented DNA damage in a dose dependent fashion. Five mM Tempol provided complete protection. Tempol protection against DNA strand breaks was similar for both stimulated neutrophils and exogenously added hydrogen peroxide. Measurement of hydrogen peroxide produced by stimulated neutrophils demonstrated that Tempol did not decrease hydrogen peroxide concentration. Oxidation of reduced metals, thereby interfering with the production of hydroxyl radical, is the most Likely mechanism of nitroxide protection, although superoxide dismutase (SOD)-like activity and scavenging of carbon-based free radicals may also account for a portion of the observed protection. The anti-oxidant activity of Tempol inhibited DNA damage by activated neutrophils. The nitroxides as a class of compounds may have a role in the investigation and modification of inflammatory conditions. Published by Elsevier Science Inc. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NCI,DIV CLIN SCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NR 51 TC 37 Z9 37 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1997 VL 23 IS 6 BP 879 EP 884 DI 10.1016/S0891-5849(97)00079-8 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA XW761 UT WOS:A1997XW76100010 PM 9378367 ER PT J AU Poole, LB Chae, HZ Flores, BM Reed, SL Rhee, SG Torian, BE AF Poole, LB Chae, HZ Flores, BM Reed, SL Rhee, SG Torian, BE TI Peroxidase activity of a TSA-like antioxidant protein from a pathogenic amoeba SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE amoebic dysentery; enteric pathogens; thiol-specific antioxidant; alkyl hydroperoxide reductase; peroxidase; thioredoxin; thioredoxin reductase ID THIOL-SPECIFIC ANTIOXIDANT; ALKYL HYDROPEROXIDE REDUCTASE; PERIPHERAL MEMBRANE-PROTEIN; AMEBIC LIVER-ABSCESS; ENTAMOEBA-HISTOLYTICA; SALMONELLA-TYPHIMURIUM; OXIDATIVE DAMAGE; SPONTANEOUS MUTAGENESIS; THIOREDOXIN REDUCTASE; HYDROGEN-PEROXIDE AB The 29 kDa surface protein of Entamoeba histolytica is an abundant antigenic protein expressed by pathogenic strains of this organism. The protein is a member of a widely-dispersed group of homologues which includes at least two cysteinyl peroxidases, Salmonella typhimurium alkyl hydroperoxidase C-22 protein (AhpC) and Saccharomyces cerevisiae thiol-specific antioxidant protein (TSA). Here, for the first time in a pathogenic eukaryote, we have demonstrated that the amoebic protein also possesses peroxidatic and antioxidant activities in the presence of reductants such as dithiothreitol or thioredoxin reductase plus thioredoxin. Although the S. typhimurium AhpF flavoprotein was not an effective reductant of the amoebic TSA protein, one inhibitory monoclonal antibody directed toward amoebic TSA was also partially inhibitory toward reduced but not oxidized bacterial AhpC. These antioxidant proteins are likely to be important not only in general cell protection, but also in the promotion of infection and invasion by these pathogenic organisms through protection against oxidative attack by activated host phagocytic cells. (C) 1997 Elsevier Science Inc. C1 NHLBI,LAB CELL SIGNALLING,NIH,BETHESDA,MD 20892. IDAHO STATE UNIV,DEPT PHARMACEUT SCI,POCATELLO,ID 83209. UNIV CALIF SAN DIEGO,DIV INFECT DIS,SAN DIEGO,CA 92103. RP Poole, LB (reprint author), WAKE FOREST UNIV,MED CTR,DEPT BIOCHEM,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. FU NIAID NIH HHS [AI28188]; NIGMS NIH HHS [GM50389, R01 GM050389] NR 27 TC 36 Z9 36 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1997 VL 23 IS 6 BP 955 EP 959 DI 10.1016/S0891-5849(97)00066-X PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA XW761 UT WOS:A1997XW76100018 PM 9378375 ER PT J AU Carini, R Leonarduzzi, G Camandola, S Musso, T Varesio, L Baeuerle, PA Poli, G AF Carini, R Leonarduzzi, G Camandola, S Musso, T Varesio, L Baeuerle, PA Poli, G TI Activation of human immunodeficiency virus long terminal repeat by arachidonic acid SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE HIV-1 LTR; AIDS; PGE 2; 5-HETE; eicosapentenoic acid; arachidonate oxidative metabolism; free radicals ID NECROSIS FACTOR-ALPHA; PROTEIN-KINASE-C; NF-KAPPA-B; SIGNAL TRANSDUCTION; EXPRESSION; CELLS; REPLICATION; FOS AB Arachidonic acid is the precursor of highly reactive mediators, including prostaglandins and leukotrienes, and the most abundant n-6 polyunsaturated fatty acid in mammalian cell membranes. It is released from phospholipids upon many inflammatory stimuli. In this study, a chloramphenicol acyltransferase reporter gene, under control of the human immunodeficiency virus-1 long terminal repeat, was strongly induced upon treating human promonocytes with arachidonic acid. The n-3 fatty acid eicosapentenoic, found in abundance in fish oil, had no effect. HIV-1 long terminal repeat activation by arachidonic acid was suppressed by inhibitors of both lipoxygenase and cyclooxygenase pathways, suggesting that metabolites, rather than arachidonic acid itself, mediated the stimulatory effect. This is the first report linking HIV-1 expression to the metabolism of arachidonic acid. Copyright (C) 1996 Elsevier Science Inc. C1 UNIV TURIN,DIPARTIMENTO MED & ONCOL SPERIMENTALE,SEZ PATOL GEN,I-10125 TURIN,ITALY. NCI,FREDERICK CANC RES & DEV CTR,EXPT IMMUNOL LAB,BMRP,FREDERICK,MD 21702. UNIV FREIBURG,INST BIOCHEM,D-79104 FREIBURG,GERMANY. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 NR 25 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1997 VL 22 IS 1-2 BP 195 EP 199 DI 10.1016/S0891-5849(96)00291-2 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA VU758 UT WOS:A1997VU75800021 PM 8958144 ER PT J AU Raynaud, F EvainBrion, D Gerbaud, P Marciano, D Gorin, I Liapi, C Anderson, WB AF Raynaud, F EvainBrion, D Gerbaud, P Marciano, D Gorin, I Liapi, C Anderson, WB TI Oxidative modulation of cyclic AMP-dependent protein kinase in human fibroblasts: Possible role in psoriasis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE cAMP-dependent protein kinase; oxidative modulation; hydrogen peroxide; fibroblasts; psoriasis ID MANGANESE SUPEROXIDE-DISMUTASE; TUMOR NECROSIS FACTOR; CULTURED HUMAN KERATINOCYTES; LIPID-PEROXIDATION; REGULATORY SUBUNIT; RECEPTOR PROTEINS; ENDOTHELIAL-CELLS; MESSENGER-RNA; CAMP; BINDING AB Previous studies have established that cyclic AMP-dependent protein kinase (PKA) activity, as well as 8-azido-[P-32]-cAMP binding to the RI and RII regulatory subunits, are decreased in cells from psoriatic patients compared to cells from normal patients. Here we show that the exposure of normal human dermal fibroblasts in culture to hydrogen peroxide and to oxygen free-radical generating systems decreased PKA activity, as well as cyclic AMP binding to the RI and RII regulatory subunits, to levels similar to those observed with psoriatic fibroblasts. Likewise, treatment of normal cytosolic preparations of PKA, as well as purified bovine PKA II, in vitro with free radical generating systems also resulted in decreased PKA activity and 8-azido [P-32]-cAMP binding to the RI and RII regulatory subunits. Further, treatment of psoriatic fibroblasts with free radical scavenging agents such as vitamins E and C, and mannitol, and also with superoxide dismutase, restored the ability of RI and RII to bind 8-azido-[P-32]-cAMP toward normal levels. Western blot analysis showed that the protein levels of the RI and RII subunits are similar in normal and psoriatic fibroblasts, and that the amounts of RI and RII are not altered by treatment of the cells with free radical-generating systems. These results suggest that oxidative modification may serve as a mechanism to alter PKA activity in human cells, and that an altered oxidative state may be involved in mediating the decrease in PKA activity and cyclic AMP binding noted in cells from psoriatic patients. Copyright (C) 1997 Elsevier Science Inc. C1 NCI,CELLULAR ONCOL LAB,NIH,BETHESDA,MD 20892. HOP TARNIER,DERMATOL SERV,F-75005 PARIS,FRANCE. UNIV PARIS 05,FAC SCI PHARMACEUT & BIOL,UNITE INSERM 427,F-75006 PARIS,FRANCE. NR 68 TC 27 Z9 27 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1997 VL 22 IS 4 BP 623 EP 632 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA WC167 UT WOS:A1997WC16700006 PM 9013125 ER PT J AU Lloyd, RV Hanna, PM Mason, RP AF Lloyd, RV Hanna, PM Mason, RP TI The origin of the hydroxyl radical oxygen in the Fenton reaction SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE hydroxyl radical; Fenton reaction; spin trapping; electron spin resonance; electron paramagnetic resonance; free radicals ID HYDROGEN-PEROXIDE; OXIDATION; ADDUCTS; IRON; IONS AB There is an ongoing discussion in the chemical literature regarding the nature of the highly reactive hydroxyl radical formed from the reaction between ferrous iron and hydrogen peroxide (the Fenton reaction). However, the fundamental experiment of directly determining the source of the hydroxyl radicals formed in the reaction has not yet been carried out. In this study, we have used both hydrogen peroxide and water labeled with O-17, together with ESR spin trapping, to detect the hydroxyl radicals formed in the reaction. ESR experiments were run in phosphate buffer with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trap, and either H2O2 or H2O labeled with O-17. The hydroxyl radical was generated by addition of Fe2+ ion to H2O2, or as a control, by photolysis of H2O2 in the ESR cavity. Observed ESR spectra were the sum of DMPO/(OH)-O-. 16 and DMPO/(OH)-O-. 17 radical adduct spectra. Within experimental accuracy, the percentage of O-17-labeled hydroxyl radical trapped by the DMPO was the same as in the original hydrogen peroxide, for either method of hydroxyl radical generation, indicating that the trapped hydroxyl radical was derived exclusively from hydrogen peroxide and that there was no exchange of oxygen atoms between H2O2 and solvent water. Likewise, the complementary reaction with ordinary H2O2 and O-17-labeled water also showed that none of the hydroxyl radical was derived from water. Our results do not preclude the ferryl intermediate, [Fe=O](2+) reacting with DMPO to form DMPO/(OH)-O-. if the ferryl oxygen is derived from H2O2, rather than from a water ligand. Copyright (C) 1997 Elsevier Science Inc. C1 UNIV MEMPHIS,DEPT CHEM,MEMPHIS,TN 38152. NIEHS,NIH,RES TRIANGLE PK,NC 27709. NR 16 TC 194 Z9 201 U1 10 U2 45 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1997 VL 22 IS 5 BP 885 EP 888 DI 10.1016/S0891-5849(96)00432-7 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA WD842 UT WOS:A1997WD84200016 PM 9119257 ER PT J AU Twomey, P Taira, J DeGraff, W Mitchell, JB Russo, A Krishna, MC Hankovszky, OH Frank, L Hideg, K AF Twomey, P Taira, J DeGraff, W Mitchell, JB Russo, A Krishna, MC Hankovszky, OH Frank, L Hideg, K TI Direct evidence for in vivo nitroxide free radical production from a new antiarrhythmic drug by EPR spectroscopy SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE cardiac arrhythmias; EPR spectroscopy; free radicals ID SPIN LABELS; OXYGEN; DAMAGE; SUPEROXIDE; CELLS; METABOLISM; INHIBITION; TEMPOL; MICE AB The new Class I anti-arrhythmic agent, 2,2,5,5-tetramethyl-3-pyrroline-1-carboxamide derivative, is currently being evaluated in clinical trials in patients with a high risk for cardiac arrhythmias. In this study we show that this antiarrhythmic drug can be chemically converted to the nitroxide free radical analog. Further, using an in vivo Electron Paramagnetic Resonance (EPR) spectroscopy model by detecting free radicals in the distal portion of the tail of an anesthetized mouse, we demonstrate that the drug is oxidized to the corresponding nitroxide. In vitro studies using Chinese hamster V79 cells suggest that the oxidation products of the drug, namely, the hydroxylamine and the nitroxide protect against oxidative damage induced by hydrogen peroxide (H2O2) Taken together, our results suggest that, in addition to the antiarrhythmic effects of the parent drug, sufficient levels of nitroxides may accumulate from the parent drug in vivo to provide antioxidant defense to cardiac tissue that may be subject to ischemia and oxidation-driven injury. Copyright (C) 1997 Elsevier Science Inc. C1 NCI,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20892. UNIV PECS,CENT RES LAB,H-7643 PECS,HUNGARY. ALKALOIDA CO LTD,TISZAVASVARI,HUNGARY. NR 31 TC 37 Z9 37 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1997 VL 22 IS 5 BP 909 EP 916 DI 10.1016/S0891-5849(96)00477-7 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA WD842 UT WOS:A1997WD84200020 PM 9119261 ER PT J AU Hahn, SM Sullivan, FJ DeLuca, AM Krishna, CM Wersto, N Venzon, D Russo, A Mitchell, JB AF Hahn, SM Sullivan, FJ DeLuca, AM Krishna, CM Wersto, N Venzon, D Russo, A Mitchell, JB TI Evaluation of tempol radioprotection in a murine tumor model SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE radioprotection; nitroxides; tumor regrowth; tumor control; bioreduction; free radicals ID MALIGNANT TISSUES; RADIATION; NITROXIDES; AGENTS; CHEMOTHERAPY; WR-2721; OXYGEN; DAMAGE; CELLS; MOUSE AB Tempol, a stable nitroxide free radical compound, is an in vitro and in vivo radioprotector. Previous studies have shown that Tempol protects C3H mice against whole-body radiation-induced bone marrow failure. In this study, the radioprotection of tumor tissue was evaluated. RIF-1 tumor cells were implanted in female C3H mice 10 d prior to radiation. Groups of mice were injected intraperitoneally with Tempol (275 mg/kg) or PBS followed 10 min later by a single dose of radiation to the tumor bed. Tumor growth curves generated after 10 and 33.3 Gy doses of radiation showed no difference in growth between the Tempol- and PBS-treated animals. A full radiation dose-response experiment revealed a tumor control dose in 50% of the animals in 30 d (TCD50/30) value of 36.7 Gy for Tempol-treated mice and 41.8 Gy for saline-treated mice suggesting no protection of the RIF-1 tumor by Tempol. Tumor pharmacokinetics were done to determine why Tempol differentially protected bone marrow and not tumor cells. Differential reduction of Tempol in the RIF-1 tumor and bone marrow was evaluated with EPR spectroscopy 10, 20, and 30 min after injection. Bioreduction of Tempol to its corresponding hydroxylamine (which is not a radioprotector) occurred to a greater extent in RIF-1 tumor cells compared to bone marrow. We conclude that the differences in radioprotection may result from enhanced intratumor bioreduction of Tempol to its nonradioprotective hydroxylamine analogue. The nitroxides as a class of compounds may provide a means to exploit the redox differences between normal tissues and tumors. (C) 1997 Elsevier Science Inc. C1 NCI,RADIAT BIOL BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 30 TC 62 Z9 65 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1997 VL 22 IS 7 BP 1211 EP 1216 DI 10.1016/S0891-5849(96)00556-4 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA WT377 UT WOS:A1997WT37700011 PM 9098095 ER PT J AU Ciolino, HP Levine, RL AF Ciolino, HP Levine, RL TI Modification of proteins in endothelial cell death during oxidative stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE oxidative stress; oxidative modification of proteins; endothelial cells; in vitro study ID HYDROGEN-PEROXIDE; FREE-RADICALS; INJURY; IRON; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; PHOSPHORYLATION; INACTIVATION; NEUTROPHILS; MECHANISMS; ASCORBATE AB Exposure of bovine aortic endothelial cells in vitro to oxidative stress causes a cascade of changes in cell function, culminating in cell death if the stress is sufficiently severe. Oxidative modification of proteins, as measured by the reaction of 2,4-dinitrophenylhydrazine with carbonyl groups of oxidized proteins, increased three- to fourfold in endothelial cells exposed to hydrogen peroxide or to a xanthine/xanthine oxidase system. The increase in oxidative modification of protein occurred rapidly, preceding loss of cellular ATP and eventual cell death. Oxidative modification of protein was paralleled by loss of activity of the key metabolic enzymes, glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The finding that oxidative modification of protein is an early event following oxidative stress suggests that oxidative modification of protein is not only a marker for oxidative damage but also a causal factor in oxidative injury. C1 NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. RI Levine, Rodney/D-9885-2011 NR 29 TC 71 Z9 71 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1997 VL 22 IS 7 BP 1277 EP 1282 DI 10.1016/S0891-5849(96)00495-9 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA WT377 UT WOS:A1997WT37700018 PM 9098102 ER PT B AU Mason, RP AF Mason, RP BE Minisci, F TI Electron spin resonance investigations of free radical toxicology SO FREE RADICALS IN BIOLOGY AND ENVIRONMENT SE NATO ADVANCED SCIENCE INSTITUTE SERIES, SUB-SERIES 3, HIGH TECHNOLOGY LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Free Radicals in Biology and Environment CY JUN 21-26, 1996 CL BARDOLINO, ITALY SP NATO, Sci Affairs Div, Politecn Milano, Glaxo Wellcome S p A RP Mason, RP (reprint author), NIEHS,LAB PHARMACOL & CHEM,NIH,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4502-9 J9 NATO ASI 3 HIGH TECH PY 1997 VL 27 BP 1 EP 27 PG 27 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BH53Y UT WOS:A1997BH53Y00001 ER PT S AU Levin, MC Jacobson, S AF Levin, MC Jacobson, S BE Reis, DJ Posner, JB TI Cellular and humoral immune responses associated with HTLV-I associated myelopathy tropical spastic paraparesis. SO FRONTIERS OF NEUROLOGY: A SYMPOSIUM IN HONOR OF FRED PLUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Frontiers of Neurology - A Symposium in Honor of Fred Plum CY OCT 05, 1996 CL CORNELL UNIV MED COLL, NEW YORK, NEW YORK SP CHARLES A DANA FDN HO CORNELL UNIV MED COLL ID CENTRAL-NERVOUS-SYSTEM; VIRUS TYPE-I; CYTOTOXIC LYMPHOCYTES-T; SPINAL-CORD LESIONS; CEREBROSPINAL-FLUID; PROVIRAL DNA; NEUROLOGICAL DISEASE; ANTIBODIES; INFECTION; PATHOGENESIS C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Levin, MC (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Link Bldg 415,855 Monroe Ave, Memphis, TN 38163 USA. NR 41 TC 7 Z9 7 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-096-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 835 BP 142 EP 152 DI 10.1111/j.1749-6632.1997.tb48625.x PG 11 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BK36C UT WOS:000071899600013 PM 9616769 ER PT J AU Crowell, JA Page, JG Rodman, LE Heath, JE Goldenthal, EI Hall, LB Kelloff, GJ AF Crowell, JA Page, JG Rodman, LE Heath, JE Goldenthal, EI Hall, LB Kelloff, GJ TI Chronic toxicity studies of 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione, a potential chemopreventive agent SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; SCHISTOSOMA-MANSONI; DNA DAMAGE; F344 RATS; OLTIPRAZ; INDUCTION; CANCER; MICE; COMBINATION; PROTECTION AB The synthetic compound Oltipraz, 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione, is related to the 1,2-dithiolthiones naturally found in cruciferous vegetables, the consumption of which has been epidemiologically associated with reduced frequency of colorectal cancers. Oltipraz has shown chemopreventive efficacy in numerous laboratory epithelial cancer models and is a potential chemopreventive, antimutagenic compound that specifically induces Phase II enzymes. Thirteen-week and 1-year toxicity studies in rats and dogs were performed to characterize the toxicities of the compound at high dosages and to support potential further development as a chemopreventive agent in clinical trials. Administration to rats by gavage for 13 weeks at dosages of 5 and 50 mg/kg/day and for 52 weeks at dosages of 10, 30, and 60 mg/kg/ day produced effects on the liver and on clinical chemistry and hematology parameters. Absolute and relative liver weight increases correlated with diffuse hypertrophy in the mid- and high-dose males and centrilobular hypertrophy in the high-dose females. Granularity of hepatocyte cytoplasm was also observed. These anatomical findings were associated with dose-associated slight increases in albumin, total protein, and cholesterol in the males and a moderate increase in cholesterol only in the females. In addition, slight decreases in erythrocyte count, hemoglobin, and hematocrit and reticulocyte elevations occurred. The no effect dose was considered 10 mg/kg/day. Administration by capsule to dogs at dosages of 10 and 100 mg/kg/day for 13 weeks and of 5, 15, and 60 mg/kg/day for 52 weeks also produced effects on the same endpoints noted in the rodent studies. in the 13-week study, precipitate was observed in the bile canaliculi, and gonadal atrophy and increased pituitary weights occurred in the males. Cholesterol and alkaline phosphatase activity were slightly elevated in both studies. Decreased hematology parameters in the 13-week study also occurred. The no effect dose was considered to be 5 mg/kg/day. Oltipraz is being carefully evaluated in clinical trials as a potential antimutagenic compound. (C) 1997 Society of Toxicology. C1 NCI,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. SO RES INST,BIRMINGHAM,AL 35205. MPI RES,MATTAWAN,MI 49701. HOFFMAN LAROCHE,NUTLEY,NJ 07003. FU NCI NIH HHS [N01-CN-95169-03, N01-CN-95170-03] NR 39 TC 78 Z9 78 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JAN PY 1997 VL 35 IS 1 BP 9 EP 21 DI 10.1006/faat.1996.2256 PG 13 WC Toxicology SC Toxicology GA WE862 UT WOS:A1997WE86200002 PM 9024669 ER PT J AU Boorman, GA Gauger, JR Johnson, TR Tomlinson, MJ Findlay, JC Travlos, GS McCormick, DL AF Boorman, GA Gauger, JR Johnson, TR Tomlinson, MJ Findlay, JC Travlos, GS McCormick, DL TI Eight-week toxicity study of 60 Hz magnetic fields in F344 rats and B6C3F1 mice SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID 60-HZ ELECTRIC-FIELDS; CHILDHOOD-CANCER; PINEAL-GLAND; LIVER FOCI; MOUSE-SKIN; EXPOSURE; 50-HZ; PROMOTION; PLASMA AB Toxicity studies were performed by exposing F344/N rats and B6C3F1 mice (10 animals per sex per species per group) to transient-free, linearly polarized 60 Hz magnetic fields for 8 weeks. Targeted magnetic fields strengths used were 0 gauss (G; sham control fields did not exceed 0.001 G), 0.02 G, 2 G, and 10 G. Exposure was whole-body and continuous for 18.5 hr per day, 7 days per week. An additional group of rats and mice was exposed intermittently (1 hr on/1 hr off) to 10 G fields for the same period of time. Endpoints evaluated included morbidity, mortality, gross pathology, histopathology, body/organ weights, clinical chemistry (rats only), and hematology (rats only). All mice and all male rats survived until the end of the study. One female rat (2-G exposure group) died during Week 7 of the study; the death was not attributed to magnetic field exposure. In both studies, the mean body weight gains of exposed animals were similar to those of the respective controls. There were no gross, histological, hematological, or biochemical lesions attributed to magnetic field exposure. Statistically significant increases in liver weight and liver to body weight ratio occurred in female rats of all exposure groups but only at the termination. These data suggest that, for the variables evaluated in these studies, an g-week exposure to linear-polarized, transient-free 60 Hz magnetic fields at field intensities of up to 10 G is not associated with significant toxicity in F344/N rats and B6C3F1 mice. Furthermore, there was no toxicity observed in animals receiving intermittent (1 hr on/1 hr off) exposures to 10-G fields. A 2-year study in F344/N rats and B6C3F1 mice is nearing completion of the in-life phase without overt toxicity in any exposed group. It is premature, however, to make any prediction concerning the possible influence of exposure to 60 Hz magnetic fields on cancer rates. (C) 1997 Society of Toxicology. C1 IIT, RES INST, CHICAGO, IL 60616 USA. PATHOL ASSOCIATES INC, CHICAGO, IL 60616 USA. RP Boorman, GA (reprint author), NIEHS, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 29 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JAN PY 1997 VL 35 IS 1 BP 55 EP 63 DI 10.1006/faat.1996.2257 PG 9 WC Toxicology SC Toxicology GA WE862 UT WOS:A1997WE86200006 PM 9024673 ER PT J AU Weber, HC Venzon, DJ Jensen, RT Metz, DC AF Weber, HC Venzon, DJ Jensen, RT Metz, DC TI Studies on the interrelation between Zollinger-Ellison syndrome, Helicobacter pylori, and proton pump inhibitor therapy SO GASTROENTEROLOGY LA English DT Article ID GASTRIC-ACID SECRETION; MULTIPLE ENDOCRINE NEOPLASIA; ANTIINFLAMMATORY DRUG-USE; LONG-TERM; CAMPYLOBACTER-PYLORI; DUODENAL-ULCER; INFECTION; RESECTION; MANAGEMENT; LOCALIZATION AB Background & Aims: The interrelation between Helicobacter pylori infection and proton pump inhibitor therapy in patients with Zollinger-Ellison syndrome is unknown. The aim of this study was to evaluate the influence of these factors on parameters of Zollinger-Ellison syndrome, Methods: Prevalence of H. pylori was determined by biopsy and antibody testing in 84 patients. The influence of H. pylori status on clinical and laboratory parameters of Zollinger-Ellison syndrome was evaluated, Seroconversion after surgery was assessed retrospectively in infected patients, Results: The prevalence of H. pylori exposure was 23% (10% with active infection). Acid output was higher in H. pylori-negative patients, but other clinical and biochemical parameters did not differ, Parameters were also similar for patients determined to be H. pylori positive by histology or antibody testing alone. Seroconversion rates did not differ between those rendered or not rendered disease free despite a significant reduction in acid output, Conclusions: H. pylori infection is not a risk factor for peptic ulceration in patients with Zollinger-Ellison syndrome. The prevalence is lower than in the general population and muck lower than for patients with idiopathic peptic ulcer disease, Long-term omeprazole therapy in H. pylori-positive patients with Zollinger-Ellison syndrome may lead to a reduction in parietal cell mass. C1 NIDDK,DIGEST DIS BRANCH,NIH,BETHESDA,MD. NCI,NIH,BETHESDA,MD 20892. HOSP UNIV PENN,GI PHYSIOL LAB,DIV GASTROENTEROL,PHILADELPHIA,PA 19104. RI Venzon, David/B-3078-2008 NR 51 TC 26 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 1997 VL 112 IS 1 BP 84 EP 91 DI 10.1016/S0016-5085(97)70222-1 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WA905 UT WOS:A1997WA90500014 PM 8978346 ER PT J AU Williams, SC Angerer, ND Johnson, PF AF Williams, SC Angerer, ND Johnson, PF TI C/EBP proteins contain nuclear localization signals imbedded in their basic regions SO GENE EXPRESSION LA English DT Article DE C/EBP proteins; CRP1 (C/EBP epsilon); C/EBP beta; nuclear localization signals; basic region; bZIP ID ENHANCER-BINDING-PROTEIN; DNA-BINDING; TRANSCRIPTION FACTOR; LEUCINE ZIPPER; TARGETING SEQUENCE; NF-M; GENE-EXPRESSION; T-ANTIGEN; DOMAIN; BIPARTITE AB The C/EBP-related proteins (C/EBP alpha, CRP1, C/EBP beta, and C/EBP delta) form a subfamily of bZIP (basic region/leucine zipper) transcription factors that display sequence homology within the bZIP domain. The conserved basic region contains two motifs that exhibit significant homology to the bipartite nuclear localization Signal (NLS) first described in nucleoplasmin. CRP1 and C/EBP beta proteins bearing deletions of the basic region accumulate in the cytoplasm, in contrast to their normal nuclear location. Analysis of chimeric proteins consisting of CRP1 basic region sequences fused to beta-galactosidase revealed that the CRP1 basic region contains a single NLS that differs from conventional bipartite signals in two ways. First, mutation of a pair of arginine residues at the N-terminus of the proposed NLS does not disrupt its function. Second, the CRP1 NLS requires additional nonbasic residues at its C-terminus. A basic residue within the CRP1 NLS that is not conserved within the C/EBP family is occupied instead by an uncharged residue in C/EBP alpha, and C/EBP beta. When this nonconserved arginine residue was changed to alanine the CRP1 NLS behaved as a classical bipartite signal, suggesting that bipartite NLSs are present in all family members but that NLSs of the individual members differ slightly. Additionally, mutation of critical NLS residues in the intact CRP1 and C/EBP beta proteins showed that these elements exhibit more bipartite-like characteristics when present in their normal sequence context. Finally, we observed that a C/EBP beta protein lacking its NLS can be localized to the nucleus when coexpressed with C/EBP alpha, indicating that a single NLS is sufficient to promote nuclear transport of a bZIP dimer. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, Lubbock, TX 79430 USA. RP Johnson, PF (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 59 TC 48 Z9 48 U1 0 U2 2 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 1052-2166 J9 GENE EXPRESSION JI Gene Expr. PY 1997 VL 6 IS 6 BP 371 EP 385 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YX379 UT WOS:000072034300004 PM 9495318 ER PT J AU Bedell, MA Jenkins, NA Copeland, NG AF Bedell, MA Jenkins, NA Copeland, NG TI Mouse models of human disease .1. Techniques and resources for genetic analysis in mice SO GENES & DEVELOPMENT LA English DT Review ID EMBRYONIC STEM-CELLS; X-LINKED AGAMMAGLOBULINEMIA; TRANSGENIC MICE; TARGETED DISRUPTION; TYROSINE KINASE; LOCUS ANALYSIS; MUTATION; STRAINS; EXPRESSION; PROTEIN C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 66 TC 93 Z9 97 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 1997 VL 11 IS 1 BP 1 EP 10 DI 10.1101/gad.11.1.1 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA WC922 UT WOS:A1997WC92200001 PM 9000047 ER PT J AU Bedell, MA Largaespada, DA Jenkins, NA Copeland, NG AF Bedell, MA Largaespada, DA Jenkins, NA Copeland, NG TI Mouse models of human disease .2. Recent progress and future directions SO GENES & DEVELOPMENT LA English DT Review ID MUCOPOLYSACCHARIDOSIS TYPE-VII; AMYLOID PRECURSOR PROTEIN; NONPOLYPOSIS COLORECTAL-CANCER; ANDROGEN RECEPTOR GENE; ENDOTHELIN-B RECEPTOR; MICE EXPRESSING HUMAN; SICKLE-CELL DISEASE; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; NEONATAL SEVERE HYPERPARATHYROIDISM; SPHINGOMYELINASE-DEFICIENT MICE C1 NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. RI Largaespada, David/C-9832-2014 NR 352 TC 112 Z9 116 U1 0 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 1997 VL 11 IS 1 BP 11 EP 43 DI 10.1101/gad.11.1.11 PG 33 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA WC922 UT WOS:A1997WC92200002 PM 9000048 ER PT J AU Mizuuchi, K AF Mizuuchi, K TI Polynucleotidyl transfer reactions in site-specific DNA recombination SO GENES TO CELLS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; GAMMA-DELTA-RESOLVASE; CATALYZED PHOSPHORYL TRANSFER; MU-TRANSPOSASE TETRAMER; P-ELEMENT TRANSPOSITION; INTEGRASE PROTEIN; STRAND TRANSFER; V(D)J RECOMBINATION; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI AB Site-specific DNA rearrangement reactions are widespread among organisms. They are used, for example, by vertebrates to boost immune response diversity, and in turn by parasitic organisms to evade the host immune system by surface antigen switching. Parasitic genetic elements ubiquitous to most organisms invade new host genomic sites by a variety of types of site-specific recombination. Polynucleotidyl transfer reactions are central to these DNA recombination reactions. The recombinase of each reaction system that 'catalyses' such chemical reactions at specific DNA sites are apparently designed to accomplish unique DNA geometrical specificity, or delicate control over the extent or direction of the reaction, with the sacrifice of protein turnover. Here we discuss our current understanding of several issues that relate to the polynucleotidyl transfer steps in several of the better studied site-specific recombination reactions. C1 NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 80 TC 74 Z9 74 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 1356-9597 J9 GENES CELLS JI Genes Cells PD JAN PY 1997 VL 2 IS 1 BP 1 EP 12 DI 10.1046/j.1365-2443.1997.970297.x PG 12 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA WR948 UT WOS:A1997WR94800001 PM 9112436 ER PT J AU Goldin, LR Bailey-Wilson, JE Borecki, IB Falk, CT Goldstein, AM Suarez, BK MacCluer, JW AF Goldin, LR Bailey-Wilson, JE Borecki, IB Falk, CT Goldstein, AM Suarez, BK MacCluer, JW TI Detection of genes for complex traits - Preface SO GENETIC EPIDEMIOLOGY LA English DT Editorial Material C1 NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. NIH, Natl Human Genome Res Inst, Triad Technol Ctr, Baltimore, MD 21224 USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. Washington Univ, Dept Psychiat, St Louis, MO 63110 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. RP Goldin, LR (reprint author), NIMH, Clin Neurosci Branch, 10 Ctr Dr,MSC 1274,Bldg 10,Room 3N218, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP XXV EP XXVI PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800001 ER PT J AU Goldin, LR Gershon, ES Berrettini, WH Stine, OC DePaulo, R McMahon, F Meyers, D Nothen, M Propping, P Cichon, S Fimmers, R Baur, M Albus, M Franzek, E Kreiner, R Maier, W Rietschel, M Baron, M Knowles, J Gilliam, C Endicott, J Gurling, H Curtis, D Smyth, C Kelsoe, J AF Goldin, LR Gershon, ES Berrettini, WH Stine, OC DePaulo, R McMahon, F Meyers, D Nothen, M Propping, P Cichon, S Fimmers, R Baur, M Albus, M Franzek, E Kreiner, R Maier, W Rietschel, M Baron, M Knowles, J Gilliam, C Endicott, J Gurling, H Curtis, D Smyth, C Kelsoe, J TI Description of the genetic analysis workshop 10 bipolar disorder linkage data sets SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 10 (GAW10) CY OCT 26-29, 1996 CL WATSONVILLE, CA DE bipolar disorder; chromosome 18; chromosome 5; linkage analysis ID CHROMOSOME-18; LOCUS C1 NIMH, Clin Neurogenet Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. Mental State Hosp, Inst Med Stat, Haar, Germany. Mental State Hosp, Inst Human Genet, Haar, Germany. Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. Univ Wurzburg, Wurzburg, Germany. Univ Dresden, Dept Psychiat, Dresden, Germany. Columbia Univ, New York State Psychiat Inst, Dept Med Genet, New York, NY USA. UCL, Sch Med, Dept Psychiat, London, England. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. RP Goldin, LR (reprint author), NIMH, Clin Neurogenet Branch, NIH, 10 Ctr Dr,MSC 1274,Bldg 10 3N218, Bethesda, MD 20892 USA. RI McMahon, Francis/A-7290-2009; Gurling, Hugh/A-5029-2010; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; McMahon, Francis/0000-0002-9469-305X NR 13 TC 13 Z9 13 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP 563 EP 568 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800003 PM 9433543 ER PT J AU Badner, JA Goldin, LR AF Badner, JA Goldin, LR TI Bipolar disorder and chromosome 18: An analysis of multiple data sets SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 10 (GAW10) CY OCT 26-29, 1996 CL WATSONVILLE, CALIFORNIA DE linkage; linkage disequilibrium; manic-depression ID LINKAGE AB There have been conflicting reports of linkage between bipolar disorder and chromosome 18. We have analyzed five separate data sets using the two-point affected sib-pair method and family based association methods. We have found evidence of linkage in multiple data sets and differences in maternal and paternal allele sharing. Suggestive, though nonsignificant, evidence of linkage disequilibrium of two tightly linked markers has also been demonstrated in multiple data sets. (C) 1997 Wiley-Liss, Inc. C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Badner, JA (reprint author), NIMH, NIH, 10-3N218, Bethesda, MD 20892 USA. FU NCRR NIH HHS [RR03655] NR 10 TC 2 Z9 2 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP 569 EP 574 DI 10.1002/(SICI)1098-2272(1997)14:6<569::AID-GEPI3>3.0.CO;2-V PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800004 PM 9433544 ER PT J AU Dorr, DA Rice, JP Armstrong, C Reich, T Blehar, M AF Dorr, DA Rice, JP Armstrong, C Reich, T Blehar, M TI A meta-analysis of chromosome 18 linkage data for bipolar illness SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 10 (GAW10) CY OCT 26-29, 1996 CL WATSONVILLE, CALIFORNIA DE bipolar illness; linkage analysis; meta-analysis ID COMPLEX TRAITS; DISORDER; GENE AB We find a meta-data set(715 families, up to 1,124 sib pairs) for bipolar illness to have a strong signal in a 10 cM region around D18S40, and excess paternal sharing on the q arm near marker D18S64. We describe a method for metaanalysis of microsatellite marker data using affected sib-pair (ASP) methodology. Inherent difficulties in such analysis include heterogeneity of allele frequencies and protocol design, measurement errors in genotyping, and map construction. Using identity-by-descent (IBD) allele sharing as the dependent variable, a logistic regression to test for heterogeneity finds only mild heterogeneity, and a limited parent-of-origin effect. (C) 1997 Wiley-Liss, Inc. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. NIMH, Rockville, MD 20857 USA. RP Dorr, DA (reprint author), Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. FU NIMH NIH HHS [MH37685, MH31302] NR 6 TC 20 Z9 20 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP 617 EP 622 DI 10.1002/(SICI)1098-2272(1997)14:6<617::AID-GEPI11>3.0.CO;2-T PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800012 PM 9433552 ER PT J AU Lin, JP Bale, SJ AF Lin, JP Bale, SJ TI Parental transmission and D18S37 allele sharing in bipolar affective disorder SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 10 (GAW10) CY OCT 26-29, 1996 CL WATSONVILLE, CALIFORNIA DE allele sharing; bipolar affected disorders; parental transmission ID LINKAGE; CHROMOSOME-18 AB We combined the five chromosome 18 bipolar affective disorder data sets provided by GAW10, totaling 185 families with 3,394 individuals, and performed analysis of differential parental transmission and chromosome 18 marker allele sharing in families with transmission through fathers vs those through mothers. Results indicated a significant excess of maternal transmission of bipolar disorder. All pedigrees were then broken into nuclear families and affected sib-pair linkage analyses performed on the marker, D18S37. There was significant linkage in the data overall, as well as in each subgroup of paternal, maternal and unknown parental transmission nuclear families. There were no significant differences in identical-by-descent (IBD) scores among the three transmission subgroups. These findings support an excess of maternal transmission, and linkage between bipolar disorder and marker D18S37. However, our results do not support the previous suggestion that there are differences in chromosome 18 marker allele sharing depending on the transmitting parent. (C) 1997 Wiley-Liss, Inc. C1 NIAMSD, Genet Studies Sect, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lin, JP (reprint author), NIAMSD, Genet Studies Sect, Skin Biol Lab, NIH, Bldg 6,Room 429,6 Ctr Dr MSC 2757, Bethesda, MD 20892 USA. NR 9 TC 25 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP 665 EP 668 DI 10.1002/(SICI)1098-2272(1997)14:6<665::AID-GEPI19>3.0.CO;2-O PG 4 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800020 PM 9433560 ER PT J AU Simonsen, KL Kaplan, NL Martin, ER AF Simonsen, KL Kaplan, NL Martin, ER TI A Monte Carlo permutation approach to choosing an affection status model for bipolar affective disorder SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 10 (GAW10) CY OCT 26-29, 1996 CL WATSONVILLE, CALIFORNIA DE affection status model; bipolar illness; permutation test; phenotypic variation ID OLD-ORDER AMISH; LINKAGE; MARKERS AB A permutation test is proposed for assessing affection status models. The test uses marker data from regions with prior evidence of linkage to susceptibility genes, and three different test statistics are examined. We applied the test to the GAW10 data and found no evidence on chromosome 18 to reject the affection status model that groups individuals diagnosed with either bipolar I, bipolar II or unipolar. The chromosome 5 data gave similar results, and further suggested that individuals diagnosed with unipolar-single episode not be included as affected. A preliminary power study suggested that one of the proposed statistics, S, is to be preferred in certain circumstances. (C) 1997 Wiley-Liss, Inc. C1 N Carolina State Univ, Dept Stat, Program Stat Genet, Raleigh, NC 27695 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Simonsen, KL (reprint author), N Carolina State Univ, Dept Stat, Program Stat Genet, Raleigh, NC 27695 USA. RI Simonsen, Katy/A-4193-2012 FU NIGMS NIH HHS [GM45344] NR 8 TC 0 Z9 1 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP 681 EP 686 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800023 PM 9433563 ER PT J AU Wyszynski, DF Doetsch, JP Pugh, EW Bailey-Wilson, JE AF Wyszynski, DF Doetsch, JP Pugh, EW Bailey-Wilson, JE TI Comparison of selected methods used to analyze bipolar disorder SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 10 (GAW10) CY OCT 26-29, 1996 CL WATSONVILLE, CALIFORNIA DE associations; genetics; linkage; linkage disequilibrium; pleiotropy ID LINKAGE; CHROMOSOME-18 AB Susceptibility genes on chromosome 18, and a parent-of-origin effect, have been suggested for bipolar disorder. We analyzed BP data sets provided by the National Institutes of Mental Health and Johns Hopkins University to the Genetic Analysis Workshop 10. Numerous statistical methods were applied to detect association, linkage, and parent-of-origin effects, under alternative diagnostic models. The methods were subsequently compared. Our results suggest that the evidence of linkage of BP to chromosome 18 markers tends to increase, often substantially, as the classification of "affected" individuals broadens. Additionally, a parent-of-origin effect was detected in some of the families. (C) 1997 Wiley-Liss, Inc. C1 Natl Human Genome Res Inst, Ctr Inherited Dis Res, NIH, Baltimore, MD 21224 USA. Western Maryland Coll, Westminster, MD 21157 USA. RP Wyszynski, DF (reprint author), Natl Human Genome Res Inst, Ctr Inherited Dis Res, NIH, 333 Cassell Dr,Suite 2000, Baltimore, MD 21224 USA. OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCRR NIH HHS [RR03655] NR 13 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP 705 EP 710 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800027 PM 9433567 ER PT J AU Goldin, LR Chase, GA AF Goldin, LR Chase, GA TI Improvement of the power to detect complex disease genes by regional inference procedures SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 10 (GAW10) CY OCT 26-29, 1996 CL WATSONVILLE, CALIFORNIA DE error rates; genome screening; regional inference; sib-pair tests ID LINKAGE; TRAITS AB Theoretical studies and simulations suggest that "true" linkage peaks are longer than "false" peaks of the same significance level. Our goal for this study was to improve the power oflinkage detection by using a regional criterion for linkage; that is, requiring more than one p-value in a given region to pass a threshold. We tested this method by determining the power and type I error for finding the underlying loci on chromosomes 5 and 8 that contribute to the variability of Q1 (after adjusting Q1 for covariates). We used the Haseman-Elston sib-pair statistic to test for linkage of all 367 markers to the adjusted Q1 trait in 100 replicates. We compared the regional inference procedure to that of the Lander and Kruglyak (LK) criteria for significant and suggestive linkage. For example, the power to detect the chromosome 5 locus was 48% for the LK criterion for significant linkage (p less than or equal to 0.0001) and 63% when we required two p-values out of five consecutive ones to be less than or equal to 0.001. The type I error was not more than 5% for either method (2% for the LK and 5% for our criterion). This suggests that using a criterion based on length may improve the power oflinkage detection for complex traits. (C) 1997 Wiley-Liss, Inc. C1 NIMH, Clin Neurogenet Branch, Bethesda, MD 20814 USA. Georgetown Univ, Med Ctr, Dept Biomath & Biostat, Washington, DC 20007 USA. RP Goldin, LR (reprint author), NIMH, Clin Neurogenet Branch, Bldg 10,Rm 3N218,10 Ctr Dr,MSC 1274, Bethesda, MD 20814 USA. FU NCRR NIH HHS [RR03655] NR 6 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP 785 EP 789 DI 10.1002/(SICI)1098-2272(1997)14:6<785::AID-GEPI37>3.3.CO;2-8 PG 5 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800038 PM 9433578 ER PT J AU Korczak, JF Goldstein, AM AF Korczak, JF Goldstein, AM TI Sib-pair linkage analyses of nuclear family data: Quantitative versus dichotomous disease classification SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 10 (GAW10) CY OCT 26-29, 1996 CL WATSONVILLE, CALIFORNIA DE complex traits; genome scanning; nonparametric linkage analysis; oligogenic traits ID MARKER AB Model-free sib-pair linkage analysis was used to screen 367 highly polymorphic markers for evidence of linkage to a disease, defined either quantitatively (Q1) or dichotomously (AF). Five individual replicates, plus a case family data set containing all families in these replicates with at least one individual with AF, were analyzed. Sib-pair linkage results for Q1 and AF varied considerably among the five replicates and did not consistently detect any of the three underlying major loci, MG1, MG2, and MG3. For the pooled case families, linkage analyses of Q1, but not AF, detected the flanking markers for MG1 and MG2 at the 0.05 and 0.01 levels, respectively. Overall, type 1 error rates were not elevated. The ability to analyze the disease quantitatively (Q1) and construct a data set more appropriate for linkage analysis (case families) enhanced the power to detect at least some of the major loci underlying the disease. (C) 1997 Wiley-Liss, Inc. C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. RP Korczak, JF (reprint author), NCI, Genet Epidemiol Branch, Execut Plaza N,Room 400,6130 xecut Blvd,MSC 7360, Bethesda, MD 20892 USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP 827 EP 832 DI 10.1002/(SICI)1098-2272(1997)14:6<827::AID-GEPI44>3.0.CO;2-P PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800045 PM 9433585 ER PT J AU Pugh, EW Jaquish, CE Sorant, AJM Doetsch, JP Bailey-Wilson, JE Wilson, AF AF Pugh, EW Jaquish, CE Sorant, AJM Doetsch, JP Bailey-Wilson, JE Wilson, AF TI Comparison of sib-pair and variance-components methods for genomic screening SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 10 (GAW10) CY OCT 26-29, 1996 CL WATSONVILLE, CALIFORNIA DE linkage; sib-pair method; statistical power; type I error; variance-components method ID LINKAGE AB The statistical properties of sib-pair and variance-components linkage methods were compared using the nuclear family data from Problem 2. Overall, the power to detect linkage was not high for either method. The variance-components method had better power for detection of linkage, particularly when covariates were included in the model. Type I error rates were similar to nominal error rates for both methods. (C) 1997 Wiley-Liss, Inc. C1 Natl Human Genome Res Inst, NIH, Baltimore, MD 21224 USA. Western Maryland Coll, Westminster, MD 21157 USA. RP Wilson, AF (reprint author), Natl Human Genome Res Inst, NIH, 333 Cassell Dr,Suite 2000, Baltimore, MD 21224 USA. RI Wilson, Alexander/C-2320-2009; OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCRR NIH HHS [RR03655]; NHLBI NIH HHS [HL28972]; NIGMS NIH HHS [GM31575] NR 8 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP 867 EP 872 DI 10.1002/(SICI)1098-2272(1997)14:6<867::AID-GEPI51>3.0.CO;2-K PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800052 PM 9433592 ER PT J AU Mitchell, BD Ghosh, S Schneider, JL Birznieks, G Blangero, J AF Mitchell, BD Ghosh, S Schneider, JL Birznieks, G Blangero, J TI Power of variance component linkage analysis to detect epistasis SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 10 (GAW10) CY OCT 26-29, 1996 CL WATSONVILLE, CALIFORNIA DE epistasis; linkage; power; simulation ID PEDIGREES AB Variance component methods are now being used in linkage analysis to detect genes influencing complex diseases. These methods are easily extended to allow for simultaneous estimation of both the additive effects of multiple loci on phenotypic variation (conditional oligogenic analysis) and the additive interaction (epistatic) effects among loci. We performed linkage analyses on 200 of the simulated replicates in order to evaluate the power to detect the main effects of MG1 and MG2 on Q1 as well as their interaction effects. The power to detect the main effect of MG1 was moderately good, although the power to detect MG2 and the MG1xMG2 interaction was poor. (C) 1997 Wiley-Liss, Inc. C1 SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. RP Mitchell, BD (reprint author), SW Fdn Biomed Res, Dept Genet, POB 760549, San Antonio, TX 78245 USA. OI Mitchell, Braxton/0000-0003-4920-4744 FU NHLBI NIH HHS [HL28972, P01-HL45522]; NIDDK NIH HHS [DK44297] NR 8 TC 36 Z9 40 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP 1017 EP 1022 DI 10.1002/(SICI)1098-2272(1997)14:6<1017::AID-GEPI76>3.0.CO;2-L PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800077 PM 9433617 ER PT J AU Moldin, SO AF Moldin, SO TI Detection and replication of linkage to a complex human disease SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 10 (GAW10) CY OCT 26-29, 1996 CL WATSONVILLE, CALIFORNIA DE extreme discordant sib pairs; multivariate genetic analysis; sampling ID QUANTITATIVE TRAIT LOCI; GUIDELINES; PAIRS AB Efforts to map susceptibility loci for complex human diseases frequently result in weak evidence for linkage, followed by failures to convincingly replicate. If a disease locus influences both affection status (AF) and a quantitative trait, a variant of the extreme discordant sib pair (EDSP) strategy may be used to judiciously sample families for a replication study. This approach was evaluated by conducting joint segregation and linkage analysis of four bivariate phenotypes, each comprising AF and one quantitative trait (Q2, Q3, Q4, Q5), and undertaking a genomic scan of the GAW10 Problem 2B data set. Suggestive evidence was found for linkage of AF/Q2 to marker D8G26 (lod = 1.63, chi(2) = 7.52, p = 3.05 x 10(-3). Sets of 23 EDSP families were selected based on Q2 values that demarcated the bottom 1%, 2%, 5%, 10%, or 20% of the distribution. Highly significant evidence for linkage was found when the 1% or 2% cutoffs were used (lod > 4, chi(2) > 20, p < 4 x 10(-6)), but more than 1,000 families had to be screened. Significant evidence for linkage (lod = 3.24, chi(2) = 14.91, p = 5.63 x 10(-5)) was found in the EDSP sample obtained using a 5% cutoff; about 300 families had to be screened. Only suggestive evidence for linkage (lod = 1.65, chi(2) = 7.59, p = 2.93 x 10(-3)) was found in non-EDSP families. Use of EDSP sampling variants can permit convincing replications not otherwise obtainable in the genetic analysis of complex diseases. (C) 1997 Wiley-Liss, Inc. C1 NIMH, Genet Res Branch, NIH, Rockville, MD 20857 USA. RP Moldin, SO (reprint author), NIMH, Genet Res Branch, NIH, Room 10C-26,5600 Fishers Lane, Rockville, MD 20857 USA. NR 8 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP 1023 EP 1028 DI 10.1002/(SICI)1098-2272(1997)14:6<1023::AID-GEPI77>3.0.CO;2-K PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800078 PM 9433618 ER PT J AU Goldstein, AM Falk, RT Korczak, JF Lubin, JH AF Goldstein, AM Falk, RT Korczak, JF Lubin, JH TI Detecting gene-environment interactions using a case-control design SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Genetic Analysis Workshop 10 (GAW10) CY OCT 26-29, 1996 CL WATSONVILLE, CALIFORNIA DE case-control studies; environmental exposures; genes; interactions ID SAMPLE-SIZE; JEWISH AB We assessed the sample size required for detecting gene-environment (G x E) interactions in a case-control study of complex diseases. The results suggest that large numbers of cases and controls will be required to detect G x E interaction for some odds ratio and exposure frequency combinations. These and other results suggest that alternative study designs may be needed to detect G x E interaction particularly with rare genes or uncommon environmental exposures. (C) 1997 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Goldstein, AM (reprint author), Genet Epidemiol Branch, EPN 439, 6130 Execut Blvd, Bethesda, MD 20892 USA. NR 10 TC 21 Z9 22 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1997 VL 14 IS 6 BP 1085 EP 1089 DI 10.1002/(SICI)1098-2272(1997)14:6<1085::AID-GEPI87>3.0.CO;2-D PG 5 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA YM987 UT WOS:000071121800088 PM 9433628 ER PT J AU Abbaszadegan, MR Struewing, JP Brown, KM Snider, JV Goodsaid, F Gore-Langton, R Hughes, MR AF Abbaszadegan, MR Struewing, JP Brown, KM Snider, JV Goodsaid, F Gore-Langton, R Hughes, MR TI Automated detection of prevalent mutations in BRCA1 and BRCA2 genes, using a fluorogenic PCR allelic discrimination assay SO GENETIC TESTING LA English DT Article ID CANCER SUSCEPTIBILITY GENE; WHOLE-GENOME AMPLIFICATION; POLYMERASE CHAIN-REACTION; OVARIAN-CANCER; BREAST-CANCER; SINGLE-CELL; PRODUCT; RISK AB Mutations in the genes BRCA1 and BRCA2 account for 5%-10% of familial early onset breast cancer. Identification of these mutations allows molecular diagnosis for breast cancer susceptibility. A high through-put automated PCR allelic discrimination assay (ADA) was developed to detect the prevalent mutations in these genes. Two allele specific oligonucleotides (ASO) are directly used in the PCR reaction, in both of which the fluorescent reporter and quencher dyes are attached to the 5' and 3' ends, respectively. During PCR, fluorescence is generated after cleavage of the annealed ASO by the 5' nuclease activity of Tag polymerase. The wild-type BRCA sequence is distinguished from the mutant sequence by the differential fluorescence emission of two different reporter dyes. The sensitivity of ADA is at the level of a single cell following a nested PCR, Eighty-six patient samples can be analyzed for each mutation in 15-min post-PCR without the need for radioactivity, gel electrophoresis, or membrane blotting/hybridization. C1 Georgetown Univ, Med Ctr, Inst Mol & Human Genet, Washington, DC 20007 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. Perkin Elmer Corp, Appl Biosyst Div, Foster City, CA 94404 USA. RP Abbaszadegan, MR (reprint author), Georgetown Univ, Med Ctr, Inst Mol & Human Genet, 3800 Reservoir Rd NW,M4000, Washington, DC 20007 USA. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 18 TC 10 Z9 10 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PY 1997 VL 1 IS 3 BP 171 EP 180 DI 10.1089/gte.1997.1.171 PG 10 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 161UV UT WOS:000078308800004 PM 10464643 ER PT J AU Westmoreland, J Porter, G Radman, M Resnick, MA AF Westmoreland, J Porter, G Radman, M Resnick, MA TI Highly mismatched molecules resembling recombination intermediates efficiently transform mismatch repair proficient Escherichia coli SO GENETICS LA English DT Article ID XENOPUS-LAEVIS OOCYTES; HOMEOLOGOUS RECOMBINATION; SACCHAROMYCES-CEREVISIAE; COMPLEX HETERODUPLEXES; DIVERGED DNAS; GENE; SYSTEM; CELLS; SEQUENCES; BARRIER AB The ability of related DNAs to undergo recombination decreases with increased sequence divergence. Mismatch repair has been proposed to be a key factor in preventing homeologous recombination; however, the contribution of mismatch repair is not universal. Although mismatch repair has been proposed to act by preventing strand exchange and/or inactivating multiply mismatched heteroduplexes, there has been no systematic study to determine at what step(s) in recombination mismatch repair acts in vivo. Since heteroduplex is a commonly proposed intermediate in many models of recombination, we have investigated the consequences of mismatch repair on plasmids that are multiply mismatched in heteroduplex structures that are similar to those that might arise during recombination. Plasmids containing multiply mismatched regions were transformed into wild-type and Mut(-) Escherichia coli mutants. There was only a 30-40% reduction in transformation of Mut(+) as compared to mutS and mutL strains for DNAs containing an 18% mismatched heteroduplex. The products obtained from mutS hosts differed from those obtained from Mut(+) hosts in that there were many more colonies containing mixtures of two plasmids, due to survival of both strands of the heteroduplex. There were nearly 10 times more recombinants obtained from the mutS as compared to the wild-type host. Based on these results and those from other studies with E. coli and yeast, we propose that the prevention of recombination between highly diverged DNAs may be al a step earlier than heteroduplex formation. C1 NIEHS,MOL GENET LAB,NATL INST HLTH,RES TRIANGLE PK,NC 27709. INST JACQUES MONOD,F-75251 PARIS 05,FRANCE. NR 26 TC 27 Z9 27 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 1997 VL 145 IS 1 BP 29 EP 38 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA WC868 UT WOS:A1997WC86800006 PM 9017387 ER PT J AU Bouffard, GG Iyer, LM Idol, JR Braden, VV Cunningham, AF Weintraub, LA MohrTidwell, RM Peluso, DC Fulton, RS Leckie, MP Green, ED AF Bouffard, GG Iyer, LM Idol, JR Braden, VV Cunningham, AF Weintraub, LA MohrTidwell, RM Peluso, DC Fulton, RS Leckie, MP Green, ED TI A collection of 1814 human chromosome 7-specific STSs SO GENOME RESEARCH LA English DT Article ID SEQUENCE-TAGGED-SITES; YEAST ARTIFICIAL CHROMOSOMES; HUMAN Y-CHROMOSOME; YAC CONTIG MAP; HUMAN GENOME; GENETIC MAPS; LINKAGE MAP; CLONES; LOCALIZATION; MARKERS AB An established goal of the ongoing Human Genome Project is the development. and mapping of sequence-tagged sites (STSs) every 100 kb, on average, across all human chromosomes. En route to constructing such a physical map of human chromosome 7, we have generated 1814 chromosome 7-specific STSs. The corresponding PCR assays were designed by the use of DNA sequence determined in our laboratory (79%) or generated elsewhere (21%) and were demonstrated to be suitable for screening yeast artificial chromosome (YAC) libraries. This collection provides the requisite landmarks for constructing a physical map of chromosome 7 at <100-kb average spacing of STSs. C1 NIH,NATL CTR HUMAN GENOME RES,GENOME TECHNOL BRANCH,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63110. NR 52 TC 17 Z9 17 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD JAN PY 1997 VL 7 IS 1 BP 59 EP 64 DI 10.1101/gr.7.1.59 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WG092 UT WOS:A1997WG09200007 PM 9037602 ER PT B AU Wolfe, AP AF Wolfe, AP BE Nicolini, C TI Transcriptional regulation in a chromatin environment SO GENOME STRUCTURE AND FUNCTION: FROM CHROMOSOMES CHARACTERIZATION TO GENES TECHNOLOGY SE NATO ADVANCED SCIENCE INSTITUTE SERIES, SUB-SERIES 3, HIGH TECHNOLOGY LA English DT Proceedings Paper CT NATO Advanced Study Institute on Genome Structure and Function CY JUN 13-23, 1996 CL MARCIANA MARINA, ITALY SP NATO, El B A Fdn RP Wolfe, AP (reprint author), NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4565-7 J9 NATO ASI 3 HIGH TECH PY 1997 VL 31 BP 83 EP 109 PG 27 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology; Genetics & Heredity GA BJ67U UT WOS:A1997BJ67U00004 ER PT J AU Grgurevich, S Linnekin, D Musso, T Zhang, XY Modi, W Varesio, L Ruscetti, FW Ortaldo, JR McVicar, DW AF Grgurevich, S Linnekin, D Musso, T Zhang, XY Modi, W Varesio, L Ruscetti, FW Ortaldo, JR McVicar, DW TI The Csk-like proteins Lsk, Hyl, and Matk represent the same Csk homologous kinase (Chk) and are regulated by stem cell factor in the megakaryoblastic cell line MO7e SO GROWTH FACTORS LA English DT Article DE kinase; stem cell growth factor; src kinase ID P50(CSK) TYROSINE KINASE; HUMAN MONOCYTES; MOLECULAR-CLONING; GROWTH-FACTOR; C-KIT; GENE; SRC; IDENTIFICATION; PHOSPHORYLATES; ENCODES AB Recently, the cDNAs for Lsk, Matk and Hyl, three Csk-related protein tyrosine kinases, have been cloned, We have examined the relationship of Lsk, Matk and Hyl, and found that the gene for each of these proteins is localized to the same region of human chromosome 19, Further, the proteins encoded by Lsk and Matk cDNAs are immunologically similar, These data strongly suggest that Lsk, Hyl and Matk are the same gene product, Previous reports demonstrating expression of Hyl and Matk in hematopoietic lineages led us to investigate the regulation of Lsk expression in response to stem cell factor (SCF) and granulocyte-macrophage colony stimulating factor (GIC I-CSF) in M07e, a human leukemic cell Line, Induction of Lsk/Hyl/Matk protein and mRNA was observed after treatment with SCF but not with GM-CSF. GM-CSF and IL-3, potent mitogens, had no effect on Lsk/Hyl/Matk expression, In contrast, PR-IA induced Lsk/Hyl/Matk but did not stimulate proliferation, Therefore, induction of Lsk/Hyl/Matk does not correlate,vith the capacity to stimulate proliferation, None of the stimuli examined increased Csk protein or mRNA expression, These data demonstrate differential regulation of Csk family members by cytokines and suggest a role for Lsk/Hyl/Matk in responses mediated by SCF and PMA, Further, our data demonstrate that, as has been seen in blood monocytes, cytokine driven translational control of Lsk/Hyl/Matk is likely a critical mode of regulation, Lastly, since our studies strongly suggest that the Lsk, Hyl and Matk kinases are related and regulated distinctly from Csk, me and several of the original authors have agreed to rename this kinase the Csk homologous kinase (Chk). C1 NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,EXPT IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,LAB LEUKOCYTE BIOL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI McVicar, Daniel/G-1970-2015; varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 NR 31 TC 17 Z9 17 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0897-7194 J9 GROWTH FACTORS JI Growth Factors PY 1997 VL 14 IS 2-3 BP 103 EP 115 DI 10.3109/08977199709021514 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA XL885 UT WOS:A1997XL88500002 PM 9255603 ER PT J AU Jakowlew, SB Mariano, JM You, L AF Jakowlew, SB Mariano, JM You, L TI Effects of transforming growth factor-beta 1 and phorbol ester on PAI-1 and PA genes in human lung cells SO GROWTH FACTORS LA English DT Article DE TGF-beta; plasminogen activator; plasminogen activator inhibitor; extracellular matrix; lung; protein kinase ID PLASMINOGEN-ACTIVATOR INHIBITOR; PROTEIN-KINASE-C; ACCOMPANIES VIRAL TRANSFORMATION; FACTOR-BETA; TGF-BETA; MESSENGER-RNAS; RESPONSIVE ELEMENT; EXPRESSION CLONING; CARCINOMA-CELLS; II RECEPTOR AB Transforming growth factor-beta (TGF-beta) mediates the production of extracellular matrix proteins, proteases and protease inhibitors in epithelial cells. Both TGF-beta and phorbol-L2-myristate-13-acetate (PMA) exert both positive and negative effects on mitogenesis in these as well as other cell types. Phorbol esters act through stimulation of protein kinase C (PKC) and are among the most potent tumor promoters known. The present study was conducted to determine whether the effect of TGF-beta in human non-small cell lung cancer (NSCLC) and normal human bronchial epithelial (NHBE) cells parallels that of the phorbol esters and whether this effect of TGF-beta involves PKC. TGF-beta 1 and PMA increased expression of TGF-beta 1 mRNA 24 hr after their addition to both NSCLC and NHBE cells. The effects of these agents on expression of the mRNAs for TGF-beta 2 and TGF-beta 3 were more complex; while TGF-beta 2 and TGF-beta 3 mRNAs increased transiently in response to TGF-beta 1 in NHBE cells and TGF-beta 3 mRNA increased transiently in some NSCLC tells, expression of these mRNAs decreased in most of these cells in response to PMA with the exception of the carcinoid NCI-H727 where TGF-beta 2 mRNA increased dramatically. TGF-beta 1 and PMA both caused a persistent increase in expression of the mRNAs for both plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator (PA) up to 24 hr in most NSCLC cells, with the increase in PAI-1 mRNA beginning several hours before that of PA mRNA. In contrast, while TGF-beta 1 also increased expression of PAI-1 mRNA in NHBE cells, the expression of PA mRNA decreased simultaneously. The effect of PMA on PAI-1 and PA mRNAs was opposite of TGF-beta 1 in these cells, with expression of PAI-1 mRNA decreasing and PA mRNA increasing after addition of PR IA. These data show that there is parallel regulation of the genes for TGF-beta 1, PAI-1 and PA by TGF-beta 1 and PMA in NSCLC, but differential regulation of the genes for PAI-1 and PA by these agents in NHBE cells. The responses of the mRNAs and proteins of TGF-beta 1, PAI-1 and PA to TGF-beta 1 and PMA were inhibited by the serine/threonine kinase inhibitor H7 in NSCLC cells. Treatment of NSCLC cells with TGF-beta 1 and PMA resulted in a persistent increase in the expression of fibronectin mRNA and protein. This response was blocked by the addition of H7. Inhibition of these effects by H7 in NSCLC cells suggests that H7 blocks TGF-beta responses hy inhibiting a protein serine/threonine kinase(s), Because the effects of TGF-beta and PMA on the different TGF-beta isoforms, PA, PAI and fibronectin in NHBE and NSCLC cells are complex, our data suggest that there are distinct mechanisms for controlling the different TSF-beta isoforms, PA, PAI and extracellular matrix proteins in normal lung and lung cancer cells. RP Jakowlew, SB (reprint author), NCI, BIOMARKERS & PREVENT RES BRANCH, 9610 MED CTR DR, SUITE C300 ROCKVILLE, ROCKVILLE, MD 20850 USA. NR 74 TC 7 Z9 7 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0897-7194 J9 GROWTH FACTORS JI Growth Factors PY 1997 VL 14 IS 2-3 BP 177 EP 197 DI 10.3109/08977199709021519 PG 21 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA XL885 UT WOS:A1997XL88500007 PM 9255608 ER PT J AU Creighton, WM Taylor, AJ Dichek, DA Dong, G Roberts, AB Schulick, AH Mannam, P Virmani, R AF Creighton, WM Taylor, AJ Dichek, DA Dong, G Roberts, AB Schulick, AH Mannam, P Virmani, R TI Regional variability in the time course of TGF-beta 1 expression, cellular proliferation and extracellular matrix expansion following arterial injury SO GROWTH FACTORS LA English DT Article DE transforming growth factor-beta 1; cellular proliferation; extracellular matrix; arterial neointima; arterial media ID SMOOTH-MUSCLE CELLS; TRANSFORMING GROWTH-FACTOR; FACTOR TYPE-BETA; TGF-BETA; ANGIOTENSIN-II; FACTOR-BETA-1; ADULT; GROWTH-FACTOR-BETA-1; ACTIVATION; INHIBITION AB Transforming growth factor-beta 1 (TGF-beta 1) has been variably associated with the regulation of cellular proliferation and extracellular matrix expansion after arterial injury, We tested these associations in vivo in the rat carotid injury model, At 0, 3, 7, 14 and 28 days following arterial balloon injury, regional expression of TGF-beta 1 mRNA was assessed using in situ hybridization and the results compared to measures of cellular proliferation and extracellular matrix expansion, Both the TGF-beta 1 concentration measured in culture media of explanted carotid arteries and the quantitative in situ hybridization signal for TGF-beta 1 in arterial media and neointima were maximal at 14 days after balloon injury, However, medial cellular proliferation was maximal at 3 days whereas neointimal proliferation was maximal at 14 days and significantly greater than medial proliferation. Neointimal cell density declined significantly between 7 and 14 days, indicating the expansion of extracellular matrix; however, medial cell density was unchanged between 3 and 28 days after balloon injury, Thus, differences in the regional arterial wall relationships between the time course of cellular proliferation, extracellular matrix expansion and the level of TGF-beta 1 expression demonstrate in vivo variability in the response to TGF-beta 1. C1 UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,SAN FRANCISCO,CA 94141. NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. NHLBI,MOL HEMATOL BRANCH,NIH,BETHESDA,MD 20892. RP Creighton, WM (reprint author), ARMED FORCES INST PATHOL,DIV CARDIOVASC,WASHINGTON,DC 20306, USA. NR 43 TC 14 Z9 18 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0897-7194 J9 GROWTH FACTORS JI Growth Factors PY 1997 VL 14 IS 4 BP 297 EP 306 DI 10.3109/08977199709021527 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA YA892 UT WOS:A1997YA89200007 PM 9386993 ER PT B AU Bottaro, DP Cioce, V Chan, AML Adams, DH Rubin, JS AF Bottaro, DP Cioce, V Chan, AML Adams, DH Rubin, JS BE Ziegler, TR Pierce, GF Herndon, DN TI Hepatocyte growth factor SO GROWTH FACTORS AND WOUND HEALING: BASIC SCIENCE AND POTENTIAL CLINICAL APPLICATIONS SE SERONO SYMPOSIA, USA LA English DT Proceedings Paper CT International Symposium on Growth Factors and Wound Healing - Basic Science and Potential Clinical Applications CY SEP 28-OCT 01, 1995 CL BOSTON, MA RP Bottaro, DP (reprint author), NCI,CELLULAR & MOL BIOL LAB,NIH,BLDG 37,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 BN 0-387-94968-2 J9 SERONO SYMP PY 1997 BP 304 EP 316 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA BJ63T UT WOS:A1997BJ63T00018 ER PT J AU Le Roith, D AF Le Roith, D TI Growth Regulation in the 21st century: on track with an online approach SO GROWTH REGULATION LA English DT Editorial Material C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Le Roith, D (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 10,Room 8S235A,10 Ctr Dr,NSC 1770, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0956-523X J9 GROWTH REGULAT JI Growth Regul. PY 1997 VL 7 IS 1 BP 1 EP 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 101BG UT WOS:000074849300001 ER PT J AU Glied, S Hoven, CW Moore, RE Garrett, AB Regier, DA AF Glied, S Hoven, CW Moore, RE Garrett, AB Regier, DA TI Children's access to mental health care: Does insurance matter? SO HEALTH AFFAIRS LA English DT Article ID ADOLESCENTS AB Using data from a 1992 community survey of children and their parents (or guardians), we found major gaps in mental health insurance coverage. Interestingly, private insurance had no statistically significant effect on use of mental health services. Youth without insurance coverage and those with public insurance had higher rates of serious emotional disorder than did those with private insurance. The analysis is based on the National Institute of Mental Health's Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) study, conducted in three mainland U.S. sites and in Puerto Rico. C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD. RP Glied, S (reprint author), COLUMBIA UNIV,NEW YORK STATE PSYCHIAT INST,NEW YORK,NY 10027, USA. FU NIMH NIH HHS [MH30906, R01 MH52698-01] NR 12 TC 39 Z9 39 U1 3 U2 3 PU PROJECT HOPE-HEALTH AFFAIRS PI SYRACUSE PA PO BOX 8015, SYRACUSE, NY 13217 SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JAN-FEB PY 1997 VL 16 IS 1 BP 167 EP 174 DI 10.1377/hlthaff.16.1.167 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA WD594 UT WOS:A1997WD59400017 PM 9018954 ER PT B AU Colaianni, LA AF Colaianni, LA BE Bakker, S TI Professional development & management strategy: Keeping up-to-date on changes in resources SO HEALTH INFORMATION MANAGEMENT: WHAT STRATEGIES? LA English DT Proceedings Paper CT 5th European Conference of Medical and Health Libraries - Health Information Management: What Strategies CY SEP 18-21, 1996 CL COIMBRA, PORTUGAL SP European Assoc Hlth Informat & Libs C1 NATL LIB MED,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4546-0 PY 1997 BP 13 EP 17 PG 5 WC Information Science & Library Science SC Information Science & Library Science GA BH83K UT WOS:A1997BH83K00003 ER PT J AU Lerman, C Gold, K Audrain, J Lin, TH Boyd, NR Orleans, CT Wilfond, B Louben, G Caporaso, N AF Lerman, C Gold, K Audrain, J Lin, TH Boyd, NR Orleans, CT Wilfond, B Louben, G Caporaso, N TI Incorporating biomarkers of exposure and genetic susceptibility into smoking cessation treatment: Effects on smoking-related cognitions, emotions, and behavior change SO HEALTH PSYCHOLOGY LA English DT Article DE smoking; genetics; risk notification; counseling ID LUNG-CANCER RISK; RANDOMIZED TRIAL; CARBON-MONOXIDE; HEAVY SMOKERS; HEALTH; CONTEMPLATION; INTERVENTIONS; POLYMORPHISM; POPULATION; OXIDATION AB In this article the authors report on the short-term impact of incorporating biomarker feedback about exposure and genetic susceptibility into minimal-contact quit-smoking counseling (QSC). Four hundred and twenty-seven smokers were randomized to 1 of 3 treatments: (a) QSC, (b) QSC + exposure biomarker feedback (EBF) about carbon monoxide in exhaled breath, or (b) QSC + EBF + biomarker feedback about genetic susceptibility to lung cancer (SBF). We observed significant immediate positive effects of SEE compared with EBF and QSC, on perceived risk, perceived quitting benefits, and fear arousal. However, at the 2-month follow-up, there were no group differences; in quit rates. SBF did lead to significant reductions in the number of cigarettes smoked for smokers who were in the preparation stage. Smokers in the EBF and QSC conditions showed reductions in depressive symptoms by 2 months, but smokers in the SBF condition did not. In the context of QSC, genetic feedback may heighten vulnerability and possibly promote distress, but may not immediately enhance quitting in most smokers. C1 FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. ROBERT WOOD JOHNSON FDN,PRINCETON,NJ 08540. UNIV ARIZONA,CTR HLTH SCI,TUCSON,AZ 85721. NATL CANC INST,ROCKVILLE,MD. RP Lerman, C (reprint author), GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007, USA. FU NCI NIH HHS [R01 CA63562] NR 50 TC 114 Z9 114 U1 2 U2 6 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 JAN PY 1997 VL 16 IS 1 BP 87 EP 99 DI 10.1037/0278-6133.16.1.87 PG 13 WC Psychology, Clinical; Psychology SC Psychology GA WF187 UT WOS:A1997WF18700008 PM 9028818 ER PT J AU Merritt, D Jones, RT Head, C Thibodeau, SN Fairbanks, VF Steinberg, MH Coleman, MB Rodgers, GP AF Merritt, D Jones, RT Head, C Thibodeau, SN Fairbanks, VF Steinberg, MH Coleman, MB Rodgers, GP TI HB seal rock [(alpha 2)142 term->Glu, codon 142 (T)under-barAA->(G)under-barAA]: An extended alpha chain variant associated with anemia, microcytosis, and alpha-thalassemia-2 (-3.7 KB) SO HEMOGLOBIN LA English DT Article ID TERMINATION MUTANT; GLOBIN CHAINS; IDENTIFICATION; DISEASE; MUTATION; GENE AB Hb Seal Rock was first reported in a young African-American woman and her 2-year-old daughter (1). It is an extended cc chain variant which, like Hb Constant Spring, is present in small quantity and is expressed as an alpha-thalassemia. The mutation, TAA-->GAA affects codon 142 of the alpha 2 gene. In this family, the index case was a compound heterozygote for Hb Seal Rock trait and for alpha-thalassemia trait (-3.7 kb). Her hematologic expression was similar to mild Hb H disease, presumably because the Seal Rock mutation affects the alpha 2 gene that is normally responsible for approximately 70% of alpha-globin synthesis. Her daughter had only Hb Seal Rock trait, but was phenotypically alpha-thalassemia-2 trait due to the expression of the Seal Rock mutation on one of her alpha 2-globin genes, the other three alpha-globin genes being unaffected. C1 OREGON HLTH SCI UNIV,DEPT BIOCHEM,PORTLAND,OR 97201. MAYO CLIN & MAYO FDN,DEPT LAB MED & PATHOL,ROCHESTER,MN 55905. VET ADM MED CTR,DEPT MED,JACKSON,MS 39216. NIH,MOL HEMATOL UNIT,BIOL CHEM LAB,BETHESDA,MD 20892. RP Merritt, D (reprint author), ST LOUIS UNIV,SCH MED,DEPT OBSTET & GYNECOL,ST LOUIS,MO 63110, USA. FU NHLBI NIH HHS [HL20142] NR 27 TC 9 Z9 9 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0363-0269 J9 HEMOGLOBIN JI Hemoglobin PY 1997 VL 21 IS 4 BP 331 EP 344 DI 10.3109/03630269709000666 PG 14 WC Biochemistry & Molecular Biology; Hematology SC Biochemistry & Molecular Biology; Hematology GA XM421 UT WOS:A1997XM42100003 PM 9255612 ER PT J AU Bruccoleri, A Gallucci, R Germolec, DR Blackshear, P Simeonova, P Thurman, RG Luster, MI AF Bruccoleri, A Gallucci, R Germolec, DR Blackshear, P Simeonova, P Thurman, RG Luster, MI TI Induction of early-immediate genes by tumor necrosis factor alpha contribute to liver repair following chemical-induced hepatotoxicity SO HEPATOLOGY LA English DT Article ID CARBON-TETRACHLORIDE; C-FOS; PROTOONCOGENE EXPRESSION; ALCOHOLIC HEPATITIS; NUCLEAR ANTIGEN; RAT; JUN; REGENERATION; MITOGEN; CELLS AB We and others have shown that tumor necrosis factor alpha (TNF-alpha) expression is increased in the livers of experimental animals following exposure to the chemical hepatotoxin, carbon tetrachloride (CCl4). Because TNF-alpha is involved in mediating inflammatory responses, its elevated expression is presumed to be associated with potentiating hepatotoxicity and/or aiding in liver repair processes, To study the role of TNF-alpha in chemical-induced hepatotoxicity, mice were administered neutralizing antibodies to TNF-alpha before administration of low, but hepatotoxic, doses of CCl4. Antibody treatment prevented CCl4-mediated increases in early-immediate gene expression associated with liver regeneration, including expression of c-jun and c-fos proto-oncogenes, as well as DNA binding of the activator protein-1 (AP-1) nuclear transcription factor, Hepatocyte proliferation following CCl4 treatment was also reduced in anti-TNF-alpha antibody-treated mice, as evidenced by a lack of proliferating cell nuclear antigen (PCNA) staining. Antibody treatment slightly delayed liver repair processes, as evidenced by extending the period in which plasma liver enzyme levels were increased and hepatocellular necrosis could be observed. Consistent with the above observations, injection of recombinant TNF-alpha into control mice induced rapid expression of c-jun and c-fos protooncogenes, Taken together, these results indicate that TNF-alpha positively modulates liver recovery following CCl4 exposure presumably by stimulating early-immediate genes involved in hepatic mitogenesis, a phenomenon also observed following partial hepatectomy. C1 NIOSH,TOXICOL & MOL BIOL BRANCH,MORGANTOWN,WV 26505. NIEHS,RES TRIANGLE PK,NC 27709. UNIV MILAN,INST PHARMACOL SCI,CTR COSMET TOXICOL,MILAN,ITALY. NR 45 TC 122 Z9 126 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 1997 VL 25 IS 1 BP 133 EP 141 DI 10.1002/hep.510250125 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WA902 UT WOS:A1997WA90200025 PM 8985279 ER PT S AU Martino, RL Yap, TK Suh, EB AF Martino, RL Yap, TK Suh, EB BE Hertzberger, B Sloot, P TI Parallel algorithms in molecular biology SO HIGH-PERFORMANCE COMPUTING AND NETWORKING SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT High Performance Computing and Networking Europe 1997 Conference CY APR 28-30, 1997 CL VIENNA, AUSTRIA ID PROTEIN AB Scalable parallel computer architectures provide the computational performance needed for advanced computing problems in molecular biology. Many scientific challenges in molecular biology have associated with them a computational requirement that must be solved before scientific progress can be made. We have developed a number of parallel algorithms and techniques useful in determining biological structure and function. Two example applications are the alignment of multiple DNA and protein sequences using speculative computation and the calculation of the solvent accessible surface area of proteins used to predict the three-dimensional conformation of these molecules from their primary structure. Timing results demonstrate substantial performance improvements with parallel implementations compared with conventional sequential systems. As the developed methods allow molecular biologists to perform computational tasks that would not otherwise be possible, we continue to develop parallel algorithms useful to this important scientific field. C1 Natl Inst Hlth, Div Comp Res & Technol, Computat Biosci & Engn Lab, Bethesda, MD 20892 USA. RP Martino, RL (reprint author), Natl Inst Hlth, Div Comp Res & Technol, Computat Biosci & Engn Lab, Bldg 12A Room 2033,12 S Dr MSC 5624, Bethesda, MD 20892 USA. EM martino@alw.nih.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0302-9743 BN 3-540-62898-3 J9 LECT NOTES COMPUT SC PY 1997 VL 1225 BP 232 EP 240 PG 9 WC Computer Science, Information Systems; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA BK98Z UT WOS:000074015300023 ER PT J AU Martin, A Wiggs, CL Weisberg, J AF Martin, A Wiggs, CL Weisberg, J TI Modulation of human medial temporal lobe activity by form, meaning, and experience SO HIPPOCAMPUS LA English DT Article DE positron emission tomography; PET; memory; cognition; hippocampus; encoding ID POSITRON EMISSION TOMOGRAPHY; HIPPOCAMPAL-FORMATION; EPISODIC MEMORY; HUMAN BRAIN; NOVELTY; RECOGNITION; FAMILIARITY; RETRIEVAL; PICTURES; OBJECT AB Clinically the hallmark of the human amnesic syndrome is an impaired ability to consciously recollect or remember daily events. If the medial region of the temporal lobes, including the hippocampus and related structures, is critical for establishing these new memories, then this brain region should be active whenever events are experienced, regardless of whether subjects are asked explicitly to learn and remember. Here we show that the medial temporal region is active during encoding and that the hemisphere activated and the amount of activation depend on the type of stimulus presented (objects or words), whether the stimulus can be encoded for meaning (real objects and words versus nonsense objects and words), and task experience (first versus the second time a task is performed). These findings demonstrate that the medial temporal lobe memory system is engaged automatically when we attend to a perceptual event and that the location and amount of activation depend on stimulus characteristics (physical form, meaning) and experience. (C) 1997 Wiley-Liss, Inc.dagger C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Martin, A (reprint author), NIMH, Lab Brain & Cognit, Bldg 10 Room 4C-104,10 Ctr Dr MSC 1366, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 31 TC 111 Z9 112 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 1997 VL 7 IS 6 BP 587 EP 593 DI 10.1002/(SICI)1098-1063(1997)7:6<587::AID-HIPO1>3.0.CO;2-C PG 7 WC Neurosciences SC Neurosciences & Neurology GA YP536 UT WOS:000071287700002 PM 9443055 ER PT J AU Vinores, SA Youssri, AI Luna, JD Chen, YS Bhargave, S Vinores, MA Schoenfeld, CL Peng, B Chan, CC LaRochelle, W Green, WR Campochiaro, PA AF Vinores, SA Youssri, AI Luna, JD Chen, YS Bhargave, S Vinores, MA Schoenfeld, CL Peng, B Chan, CC LaRochelle, W Green, WR Campochiaro, PA TI Upregulation of vascular endothelial growth factor in ischemic and non-ischemic human and experimental retinal disease SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Article DE blood-retinal barrier; ischemia; vascular endothelial growth factor; experimental autoimmune uveoretinitis; macular edema ID PROLIFERATIVE DIABETIC-RETINOPATHY; PIGMENT EPITHELIAL-CELLS; CENTRAL-NERVOUS-SYSTEM; FACTOR MESSENGER-RNA; PERMEABILITY FACTOR; BARRIER BREAKDOWN; FACTOR VEGF; FACTOR EXPRESSION; IMMUNOHISTOCHEMICAL LOCALIZATION; TUMOR ANGIOGENESIS AB Vascular endothelial growth factor (VEGF) is induced by hypoxia and it has been implicated in the development of iris and retinal neovascularization (NV) in ischemic retinopathies in which it has been suggested that Muller cells are responsible for increased VEGF production. VEGF, however, is also known to be a potent mediator of vascular permeability in other tissues and may perform this function in retina. Immunohistochemical staining for VEGF was performed on a variety of human and experimental ischemic and non-ischemic ocular disorders in which blood retinal barrier (BRB) breakdown is known to occur to determine if there is an upregulation of VEGF in these conditions. We found increased VEGF immunoreactivity in ganglion cells of rats with oxygen-induced ischemic retinopathy and in ganglion cells, the inner plexiform layer, and some cells in the inner nuclear layer of rats with experimental autoimmune uveoretinitis (EAU), in which there was no identifiable ischemia or NV. In rats with EAU, VEGF staining intensity increased from 8 to 11 days after immunization, coincident with BRB failure. These results were confirmed using two distinct anti-VEGF antibodies and by immunoblot and the immunohistochemical staining was eliminated by pre-incubating the antibodies with VEGF peptide. VEGF staining was also increased in the retina and iris of patients with ischemic retinopathies, such as diabetic retinopathy and retinal vascular occlusive disease, and in patients with disorders in which retinal ischemia does not play a major role, such as aphakic/pseudophakic cystoid macular edema, retinoblastoma, ocular inflammatory disease or infection, and choroidal melanoma. VEGF was primarily localized within retinal neurons and retinal pigmented epithelial cells in these cases. In addition or in association with its role of inducing NV, VEGF may contribute to BRB breakdown of in a variety of ocular disorders and blockage of VEGF signaling may help to reduce some types of macular edema. C1 NEI,NIH,BETHESDA,MD 20892. NCI,NIH,BETHESDA,MD 20892. RP Vinores, SA (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT OPHTHALMOL,WILMER OPTHALMOL INST,600 N WOLFE ST,BALTIMORE,MD 21287, USA. FU NEI NIH HHS [EY05951, EY10017] NR 67 TC 158 Z9 168 U1 1 U2 2 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JAN PY 1997 VL 12 IS 1 BP 99 EP 109 PG 11 WC Cell Biology; Pathology SC Cell Biology; Pathology GA WJ847 UT WOS:A1997WJ84700012 PM 9046048 ER PT J AU Sunila, I Vaccarezza, M Pantaleo, G Fauci, AS Orenstein, JM AF Sunila, I Vaccarezza, M Pantaleo, G Fauci, AS Orenstein, JM TI Activated cytotoxic lymphocytes in lymph nodes from human immunodeficiency virus (HIV) 1-infected patients: A light and electronmicroscopic study SO HISTOPATHOLOGY LA English DT Article DE human immunodeficiency virus (HIV) type 1; lymph nodes; cytotoxic lymphocytes; perforin; TIA-1 ID FOLLICULAR DENDRITIC CELLS; AIDS-RELATED LYMPHADENOPATHY; CD8+ LYMPHOCYTES; PERSISTENT LYMPHADENOPATHY; INFECTED PATIENTS; COMPLEX ARC; TYPE-1; GRANULES; PERFORIN; EXPRESSION AB Persistent generalized lymphadenopathy often develops during HIV-infection. It is characterized by follicular hyperplasia which progresses over time to follicular involution and finally lymphocyte depletion. To determine whether activated cytotoxic T cells (CD8+) are present in the hyperplastic germinal centres, light and electronmicroscopic immunogold labelling with monoclonal antibodies were used to localize two cytotoxic molecules, perforin and TIA-1, Perforin and TIA-1-positive cells were detected in the follicles and paracortex of lymph nodes from HIV-infected patients, whereas labelling was seen only in cells of the paracortex in the hyperplastic lymph nodes from HIV-negative patients. Cytotoxic granules, staining positive for perforin and TIA-1, were identified by transmission electronmicroscopy, often in proximity to follicular dendritic cells within the hyperplastic germinal centres of only HIV-positive patients. These cytotoxic cells may play a role in the follicular dendritic cell loss and concomitant follicular involution that occur during the evolution of HIV disease. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. RP Sunila, I (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,2300 EYE ST NW,WASHINGTON,DC 20037, USA. RI Pantaleo, Giuseppe/K-6163-2016; OI VACCAREZZA, Mauro/0000-0003-3060-318X NR 32 TC 3 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD JAN PY 1997 VL 30 IS 1 BP 31 EP 40 DI 10.1046/j.1365-2559.1996.d01-559.x PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA WE322 UT WOS:A1997WE32200006 PM 9023555 ER PT S AU Germain, RN Bikoff, EK Bonifacino, JS Castellino, F Han, R Marks, MS Romagnoli, P Zhong, GM AF Germain, RN Bikoff, EK Bonifacino, JS Castellino, F Han, R Marks, MS Romagnoli, P Zhong, GM BE Svejgaard, A Buus, S Fugger, L TI Invariant chain regulation of MHC class II function in the secretory and endocytic pathways SO HLA AND DISEASE - THE MOLECULAR BASIS SE ALFRED BENZON SYMPOSIUM SERIES LA English DT Proceedings Paper CT 40th Symposium of the Alfred-Benzon-Foundation on HLA and Disease - the Molecular Basis CY AUG 04-08, 1996 CL ROYAL DANISH ACAD SCI & LETT, COPENHAGEN, DENMARK SP Alfred Benzon Fdn HO ROYAL DANISH ACAD SCI & LETT RP Germain, RN (reprint author), NIAID,NIH,10 CTR DR,MSC 1892,BETHESDA,MD 20892, USA. RI Romagnoli, Paola/K-2237-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MUNKSGAARD PI COPENHAGEN K PA 35 NORRE SOGADE POSTBOX 2148, DK-1016 COPENHAGEN K, DENMARK SN 0105-3639 BN 87-16-11942-8 J9 ALFRED BENZON SYMP S PY 1997 VL 40 BP 114 EP 129 PG 16 WC Immunology SC Immunology GA BJ08M UT WOS:A1997BJ08M00009 ER PT B AU Mudd, SH AF Mudd, SH BE Graham, I Refsum, H Rosenberg, IH Ueland, PM Shuman, JM TI Cystathionine beta-synthase deficiency: Metabolic aspects SO HOMOCYSTEINE METABOLISM: FROM BASIC SCIENCE TO CLINICAL MEDICINE SE DEVELOPMENTS IN CARDIOVASCULAR MEDICINE LA English DT Proceedings Paper CT International Conference on Homocysteine Metabolism CY JUL 02-06, 1995 CL DROMOLAND CASTLE, IRELAND SP Medice Co C1 NIMH, Bethesda, MD 20892 USA. RP Mudd, SH (reprint author), NIMH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC PUBLISHERS PI NORWELL PA 101 PHILIP DRIVE, ASSINIPPI PARK, NORWELL, MA 02061 USA BN 0-7923-9983-8 J9 DEV CARDIOVASC MED PY 1997 BP 77 EP 82 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Physiology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Physiology GA BL45Y UT WOS:000075570600011 ER PT J AU Oberfield, SE Nirenberg, A Allen, JC Cohen, H Donahue, B Prasad, V Schiff, R Pang, SY Ghavimi, F David, R Chrousos, G Sklar, C AF Oberfield, SE Nirenberg, A Allen, JC Cohen, H Donahue, B Prasad, V Schiff, R Pang, SY Ghavimi, F David, R Chrousos, G Sklar, C TI Hypothalamic-pituitary-adrenal function following cranial irradiation SO HORMONE RESEARCH LA English DT Article DE hypothalamic-pituitary-adrenal function; cranial irradiation; childhood ID TOTAL-BODY IRRADIATION; RADIATION; ADRENOCORTICOTROPIN; CORTICOTROPIN; CORTISOL; RADIOIMMUNOASSAY; HYPOPITUITARISM; DYSFUNCTION; DEFICIENCY; SEQUELAE AB We assessed the effect of cranial irradiation on hypothalamic-pituitary (HP)adrenal function in 17 patients (12 females, 5 males) treated with cranial/ craniospinal irradiation for acute leukemia (2 patients) or tumors distant from the hypothalamus and pituitary (8 medulloblastoma, 3 astrocytoma, 3 rhabdomyosarcoma, 1 ependymoma), Estimated doses of radiation (RT) to the HP region ranged from 18 to 72 Gy. Thirteen of seventeen patients were also treated with chemotherapy. Patients were a median of 3.75 years of age (1.5-19 years) at diagnosis and were studied at a median of 5 years (0.1-20 pears) after RT, Patients received corticotropin-releasing factor (oCRF, 1 mu g/kg i.v.), and sampling for cortisol and ACTH levels was performed at -15, 0, 15, 30, 60, 90 and 120 min. The -15- and 0-min levels were combined for a standardized baseline value (Base), Cortisol levels at 0, Base, 30 and 120 min, as well as the peak cortisol response, were significantly lower in the patients. Twelve of seventeen patients' peak cortisol levels fell below the normal range. The patients' mean integrated values for cortisol (area under the curve) were not, however, different from controls. The ACTH responses to oCRF did not differ between patients and controls. No relationship was observed between ACTH or cortisol responses and the time elapsed from treatment or dose of HP RT, Further, in 10 of 12 patients, 0-min dehydroepiandrosterone sulfate levels were lower than the expected normal mean levels for age, sex and pubertal status, and in 4 of these 10 patients the values were below the normal range. These data suggest that some patients treated with HP RT may be at risk for adrenal insufficiency. C1 NYU,MED CTR,DEPT NEUROL,NEW YORK,NY 10016. NYU,MED CTR,DEPT EPIDEMIOL & BIOSTAT,NEW YORK,NY 10016. NYU,MED CTR,DEPT RADIAT ONCOL,NEW YORK,NY 10016. UNIV ILLINOIS,DEPT PEDIAT,CHICAGO,IL. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NICHHD,BETHESDA,MD. RP Oberfield, SE (reprint author), NYU,MED CTR,DEPT PEDIAT,550 FIRST AVE,NEW YORK,NY 10016, USA. FU NCRR NIH HHS [MO1RR00096] NR 32 TC 22 Z9 23 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PD JAN PY 1997 VL 47 IS 1 BP 9 EP 16 DI 10.1159/000185357 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WB467 UT WOS:A1997WB46700002 PM 9010712 ER PT B AU Bennett, J AF Bennett, J BE VandenBossche, H Stevens, DA Odds, FC TI Melanin production in Cryptococcus neoformans SO HOST-FUNGUS INTERPLAY LA English DT Proceedings Paper CT 5th Symposium on Topics in Mycology - Host-Fungus Interplay CY JUN 27-30, 1995 CL STANFORD UNIV, STANFORD, CA SP Janssen Res Fdn, Int Soc Human & Anim Mycol, Stanford Univ Med Sch, Dept Med, Div Infectious Dis HO STANFORD UNIV RP Bennett, J (reprint author), NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATIONAL FOUNDATION INFECTIOUSDISEASES PI BETHESDA PA 4733 BETHESDA AVE SUITE 750, BETHESDA, MD 20814-5228 BN 0-9614520-2-1 PY 1997 BP 95 EP 97 PG 3 WC Infectious Diseases; Mycology SC Infectious Diseases; Mycology GA BJ03B UT WOS:A1997BJ03B00011 ER PT B AU Parta, M Washburn, RG KwonChung, KJ AF Parta, M Washburn, RG KwonChung, KJ BE VandenBossche, H Stevens, DA Odds, FC TI The role of hydrophobic surface protein layers of filamentous fungi in host-pathogen interactions SO HOST-FUNGUS INTERPLAY LA English DT Proceedings Paper CT 5th Symposium on Topics in Mycology - Host-Fungus Interplay CY JUN 27-30, 1995 CL STANFORD UNIV, STANFORD, CA SP Janssen Res Fdn, Int Soc Human & Anim Mycol, Stanford Univ Med Sch, Dept Med, Div Infectious Dis HO STANFORD UNIV AB The determinants of fungal pathogenicity are intimately associated with characteristics adapted to survival and dispersal. Hydrophobins, cell surface proteins present in many genera, may contribute to spore dispersability. Ln addition, the hydrophobins present on spore surfaces may provide a significant barrier to adverse environmental factors and host defenses. Known to be involved in insect and plant pathogenesis, the hydrophobins have as of yet no defined role in human infections with filamentous fungi. The recent cloning of genes that encode the rodlet layers of Aspergillus conidia (rodA and dewA in A. nidulans, HYP1 in A. fumigatus) have provided further incentive to study conida-host interactions. We have studied the role in host defense of the spore coat protein of A. fumigatus, a major pathogen in immunocompromised humans, and in A. nidulans, an organism for which there is a more substantial molecular and genetic background. The gene for the rodlet layer in A. fumigatus, HYP1, restores the rodlet layer in A. nidulans deleted for its homologue, RodA. Fibrinogen binding is slightly impaired in an A. nidulans rodA deletant and significantly impaired in an A. nidulans double deletant for rodA and dewA, and preincubation of wild-type Aspergillus nidulans with fibrinogen decreased subsequent opsonization with complement. Current knowledge regarding the importance of fungal hydrophobins in plant pathogens such as Magnaporthe grisea, and entomopathogenic fungi (Metarhizium anisopliae) will also be summarized. RP Parta, M (reprint author), NIAID,CLIN MYCOL SECT,CLIN INVEST LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATIONAL FOUNDATION INFECTIOUSDISEASES PI BETHESDA PA 4733 BETHESDA AVE SUITE 750, BETHESDA, MD 20814-5228 BN 0-9614520-2-1 PY 1997 BP 237 EP 245 PG 9 WC Infectious Diseases; Mycology SC Infectious Diseases; Mycology GA BJ03B UT WOS:A1997BJ03B00026 ER PT B AU Walsh, TJ Roilides, E Lyman, CA Pizzo, PA AF Walsh, TJ Roilides, E Lyman, CA Pizzo, PA BE VandenBossche, H Stevens, DA Odds, FC TI Augmentation of pulmonary host defenses against invasive aspergillosis SO HOST-FUNGUS INTERPLAY LA English DT Proceedings Paper CT 5th Symposium on Topics in Mycology - Host-Fungus Interplay CY JUN 27-30, 1995 CL STANFORD UNIV, STANFORD, CA SP Janssen Res Fdn, Int Soc Human & Anim Mycol, Stanford Univ Med Sch, Dept Med, Div Infectious Dis HO STANFORD UNIV DE aspergillosis; neutrophils; monocytes; macrophages; G-CSF; GM-CSF; interferon-gamma; cytokines; methylprednisolone; cyclosporin A AB Invasive pulmonary aspergillosis is an important cause of morbidity and mortality in immunocompromised patients, particularly those with persistent and profound neutropenia, recipients of bone marrow and solid organ transplantation, HIV-infected patients, and children with neutrophil defects such as chronic granulomatous disease.(1-3) The impact of invasive aspergillosis is underscored in a recent study by Pannuti et al(3) who found that Aspergillus species were the cause of 36% (20 of 55) of cases of proven nosocomial pneumonia. The crude mortality for patients with Aspergillus pneumonia was 95%. Further analysis indicated that elimination of 90% of cases of invasive aspergillosis would reduce the overall associated crude mortality to 43%. RP Walsh, TJ (reprint author), NCI,MYCOL UNIT,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATIONAL FOUNDATION INFECTIOUSDISEASES PI BETHESDA PA 4733 BETHESDA AVE SUITE 750, BETHESDA, MD 20814-5228 BN 0-9614520-2-1 PY 1997 BP 297 EP 305 PG 9 WC Infectious Diseases; Mycology SC Infectious Diseases; Mycology GA BJ03B UT WOS:A1997BJ03B00031 ER PT J AU Jons, PH Ernst, M Hankerson, J Hardy, K Zametkin, AJ AF Jons, PH Ernst, M Hankerson, J Hardy, K Zametkin, AJ TI Follow-up of radial arterial catheterization for positron emission tomography studies SO HUMAN BRAIN MAPPING LA English DT Article DE arterial line; radial artery; PET; risk factors; catheterization ID CANNULATION AB Radial arterial catheterization is needed for repeated arterial blood samples to construct tracer input curves of positron emission tomography (PET) scans (Herscovitch [1993]: Rheum Dis Clin North Am 19:765-794). Complications resulting from such short-term catheterizations are rare. Sixteen investigators followed 106 subjects who had arterial lines placed in the context of a PET study. Abnormalities were reported in 8 of 106 (7.5%) cases. Of these eight cases, three (37.5%) were inpatients diagnosed with anorexia nervosa, a condition that may represent a risk factor. All abnormalities were benign, did not affect motor function, and did not require medical intervention. (C) 1997 Wiley-Liss, Inc. C1 NIMH,CEREBRAL METAB LAB,NIH,BETHESDA,MD 20892. NIH,DEPT ANESTHESIA,CTR CLIN,BETHESDA,MD 20892. OI Hardy, Kristina/0000-0002-5479-5043 NR 14 TC 7 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1997 VL 5 IS 2 BP 119 EP 123 DI 10.1002/(SICI)1097-0193(1997)5:2<119::AID-HBM5>3.0.CO;2-6 PG 5 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA XC645 UT WOS:A1997XC64500005 PM 10096416 ER PT J AU Momenan, R Hommer, D Rawlings, R Ruttimann, U Kerich, M Rio, D AF Momenan, R Hommer, D Rawlings, R Ruttimann, U Kerich, M Rio, D TI Intensity-adaptive segmentation of single-echo T-1-weighted magnetic resonance images SO HUMAN BRAIN MAPPING LA English DT Article DE brain volume; gray matter; white matter; ventricle; clustering; region growing ID WHITE-MATTER; GRAY-MATTER; HUMAN BRAIN; MR-IMAGES AB A procedure for segmentation of intracranial tissues, including cerebrospinal fluid surrounding the brain, cortical and subcortical gray matter, and white matter, in a T-1-weighted magnetic resonance image of the brain, has been developed. The proposed method utilizes information from the histogram of pixel intensities of the intracranial image. Based on this information, an unsupervised K-means clustering procedure separates various tissue regions. Information about the approximate location of anatomical regions within the intracranial space is used to detect ventricles and the caudate nuclei. First a description and justification for the procedure is presented. Then the performance of the procedure is evaluated by analysis of variance. In conclusion, the results of applying this procedure to 31 healthy subjects are presented and future improvements are discussed. (C) 1997 Wiley-Liss, Inc. C1 MEDDATA RES, VIENNA, VA 22182 USA. RP Momenan, R (reprint author), NIAAA, CLIN STUDIES LAB,DIV INTRAMURAL CLIN & BIOL RES, NIH,10-3C112, 10 CTR DR, MSC 1256, BETHESDA, MD 20892 USA. NR 20 TC 26 Z9 26 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 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1997 VL 5 IS 3 BP 194 EP 205 DI 10.1002/(SICI)1097-0193(1997)5:3<194::AID-HBM4>3.0.CO;2-Z PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA XP161 UT WOS:A1997XP16100004 PM 20408215 ER PT J AU Clark, VP Parasuraman, R Keil, K Kulansky, R Fannon, S Maisog, JM Ungerleider, LG Haxby, JV AF Clark, VP Parasuraman, R Keil, K Kulansky, R Fannon, S Maisog, JM Ungerleider, LG Haxby, JV TI Selective attention to face identity and color studied with fMRI SO HUMAN BRAIN MAPPING LA English DT Article; Proceedings Paper CT BrainMap 96 Workshop - Methods for Mapping and Modeling the Human Brain CY DEC, 1996 CL SAN ANTONIO, TX DE brain mapping; color perception; face recognition; selective attention; extrastriate cortex; visual cortex; visual pathways; magnetic resonance imaging ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; HUMAN VISUAL-CORTEX; MRI AB Cortical areas associated with selective attention to the color and identity of faces were located using functional magnetic resonance imaging (fMRI). Six subjects performed tasks which required selective attention to face identity or color similarity using the same color-washed face stimuli. Performance of the color attention task but not the face attention task was associated with a region of activity in the collateral sulcus and nearby regions of the lingual and fusiform gyri. Performance of both tasks was associated with a region of activity in ventral occipitotemporal cortex that was lateral to the color responsive area and had a greater spatial extent. These fMRI results converge with results obtained from PET and ERP studies to demonstrate similar anatomical locations of functional areas for face and color processing across studies. (C) 1997 Wiley-Liss, Inc. C1 CATHOLIC UNIV AMER,WASHINGTON,DC 20064. RP Clark, VP (reprint author), NIMH,LBC,NIH,PSYCHOL & PSYCHOPATHOL LAB,10-4C104,10 CTR DR,MSC-1366,BETHESDA,MD 20892, USA. RI Clark, Vincent/B-3343-2010 OI Clark, Vincent/0000-0002-9151-2102 NR 12 TC 64 Z9 65 U1 2 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1997 VL 5 IS 4 BP 293 EP 297 PG 5 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA XU258 UT WOS:A1997XU25800015 PM 20408231 ER PT J AU Chmielowska, J Maisog, JM Hallett, M AF Chmielowska, J Maisog, JM Hallett, M TI Analysis of single-subject data sets with a low number of PET scans SO HUMAN BRAIN MAPPING LA English DT Article DE PET; motor; statistical parametric maps; single subject ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; PRIMARY MOTOR CORTEX; AUTOMATED ALGORITHM; ACTIVATION; IMAGES; BRAIN; MOVEMENTS; AREAS; TASK AB We present a procedure for the statistical analysis of single-subject PET data sets with a low number of scans (six total, two scans for each of three conditions) and describe the results of applying this method of analysis on the PET data of 10 normal subjects, performing a motor task, with six scans per subject. Development of this procedure, which combines well-established methods of statistical analysis in functional neuroimaging (a pooled estimate of variance and spatial-extent-based analysis), was motivated by the need for a statistical, individual analysis of PET data sets with a low number of scans from stroke patients in which the location and extent of an infarct varied from subject-to-subject. The results of this spatial-extent-based, single-subject analysis of PET data (including coregistration of significant. PET activation to every individual's MRI image and transformation into Talairach space) showed activation in all major cortical motor areas, while no activation was detected in small structures such as the putamen and thalamus. Individual variability in the pattern of statistically significant regions of activation across 10 normal subjects, performing the same motor task, was observed. The results obtained in this study from individual analysis of a low number of PET scans of normal subjects are consistent with previous results of group PET analysis of normal subjects performing similar motor tasks, and these current results indicate that this procedure can help in the examination of PET data sets demanding a single-subject analysis (e.g., involving stroke). (C) 1997 Wiley-Liss, Inc. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. NIMH,SECT FUNCT BRAIN IMAGING,PSYCHOL & PSYCHOPATHOL LAB,NIH,BETHESDA,MD 20892. NR 29 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1997 VL 5 IS 6 BP 445 EP 453 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA YJ337 UT WOS:A1997YJ33700005 PM 20408247 ER PT J AU Huang, B Crolla, JA Christian, SL WolfLedbetter, ME Macha, ME Papenhausen, PN Ledbetter, DH AF Huang, B Crolla, JA Christian, SL WolfLedbetter, ME Macha, ME Papenhausen, PN Ledbetter, DH TI Refined molecular characterization of the breakpoints in small inv dup(15) chromosomes SO HUMAN GENETICS LA English DT Article ID PRADER-WILLI-SYNDROME; STRUCTURALLY ABNORMAL CHROMOSOMES; ANGELMAN-SYNDROME; INSITU HYBRIDIZATION; SITU HYBRIDIZATION; SYNDROME REGION; HUMAN GENOME; FLUORESCENCE; PROBANDS; DELETION AB Inv dup(15) is the most common supernumerary marker chromosome in humans. To investigate the mechanism responsible for this frequent chromosome rearrangement, we characterized the breakpoints in 18 individuals with small inv dup(15) chromosomes [i.e., negative for the Prader-Willi (PWS)/Angelman syndrome (AS) critical region]. Since two proximal breakpoint regions (''hotspots'') for PWS/AS deletions have been previously identified with the most proximal 15q markers D15S541/S542 and S543, we hypothesized that formation of the small inv dup(15) chromosomes may involve one or both of these breakpoint hotspots. By analysis with S542, both breakpoint regions were found to be involved in approximately equal frequencies. In ten cases, the inv dup(15) was negative for S542 (Class I), indicating the breakpoint is between the centromere and the most proximal marker on chromosome 15. For the other eight cases, S542 was positive by fluorescence in situ hybridization (5/5) and/or microsatellite analysis (7/7), but S543 was negative (Class II). These two breakpoint regions appear to be the same as the two proximal breakpoints reported in the common PWS/AS deletions. To initiate cloning and sequencing of the Class II breakpoint, the gap in the yeast artificial chromosome (YAC) contig between S541/S542 and S543 was filled by screening the CEPH YAC and me,oa-YAC libraries. YACs 705C2 and 368H3 were found to bridge this gap, and therefore contain the more distal breakpoint region. The finding of consistent breakpoints in small inv dup(15), like that: found in PWS/AS deletions, provides strong evidence for hotspots for chromosome breakage in this region. In addition, our results show that two extra copies (tetrasomy) of the region from 15cen to the euchromatic region containing S542 are present in individuals with Class II breakpoints. Since most individuals carrying a small inv dup(15) are phenotypically normal, the euchromatin region included in the small inv dup(15) chromosomes does not appear to contain genes with clinically significant dosage effects. C1 UNIV CHICAGO,CTR MED GENET,CHICAGO,IL 60637. NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. WESSEX REG GENET LAB,SALISBURY,WILTS,ENGLAND. LAB CORP AMER,RES TRIANGLE PK,NC. NR 28 TC 82 Z9 83 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 1997 VL 99 IS 1 BP 11 EP 17 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA VY641 UT WOS:A1997VY64100003 PM 9003485 ER PT J AU Wyszynski, DF Maestri, N McIntosh, I Smith, EA Lewanda, AF GarciaDelgado, C VinagerasGuarneros, E Wulfsberg, E Beaty, TH AF Wyszynski, DF Maestri, N McIntosh, I Smith, EA Lewanda, AF GarciaDelgado, C VinagerasGuarneros, E Wulfsberg, E Beaty, TH TI Evidence for an association between markers on chromosome 19q and non-syndromic cleft lip with or without deft palate in two groups of multiplex families SO HUMAN GENETICS LA English DT Article ID MULTILOCUS LINKAGE ANALYSIS; GROWTH FACTOR-ALPHA; GENE; DNA AB It has been reported that BCL3 on chromosome 19q, or a nearby gene, may play a role in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in some families. We tested 30 USA and 11 Mexican multiplex NSCL/P families for four markers on chromosome 19q: D19S178, APOC2/AC1, APOC2/007, and BCL3. While likelihood-based linkage analysis failed to show significant evidence of linkage, the transmission disequilibrium test indicated highly significant deviation from independent assortment of allele 3 at the BCL3 marker in both data sets (USA:P = 0.001; Mexican: P = 0.018: both combined: P < 0.001) and for allele 13 of the D19S178 marker in the Mexican data set (P = 0.004). These results support an association, possibly due to linkage disequilibrium, between chromosome 19 markers and a putative NSCL/P locus. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT MED GENET,WASHINGTON,DC 20010. HOSP INFANTIL MEXICO DR FEDERICO GOMEZ,DEPT MED GENET,MEXICO CITY,DF,MEXICO. HOSP INFANTIL MEXICO DR FEDERICO GOMEZ,DEPT PLAST & RECONSTRUCT SURG,MEXICO CITY,DF,MEXICO. UNIV MARYLAND,DIV HUMAN GENET,BALTIMORE,MD 21201. RP Wyszynski, DF (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NIDCR NIH HHS [R01-DE10293] NR 20 TC 49 Z9 53 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 1997 VL 99 IS 1 BP 22 EP 26 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA VY641 UT WOS:A1997VY64100005 PM 9003487 ER PT J AU Kim, CJ Lee, KH Roden, MM Marincola, FM AF Kim, CJ Lee, KH Roden, MM Marincola, FM TI Functional characterization of anti-MART(27-35) CD8+ cytolytic T lymphocyte clones generated by endogenous presentation of the antigen. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,CC,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1997 VL 55 SU 1 BP 10 EP 10 PG 1 WC Immunology SC Immunology GA YA772 UT WOS:A1997YA77200014 ER PT J AU Hoyer, RJ Hahn, AB Carrington, M Hurley, CK AF Hoyer, RJ Hahn, AB Carrington, M Hurley, CK TI Identification of a null HLA-B allele in a Caucasian family. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. MED UNIV S CAROLINA,CHARLESTON,SC 29425. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1997 VL 55 SU 1 BP 35 EP 35 PG 1 WC Immunology SC Immunology GA YA772 UT WOS:A1997YA77200061 ER PT J AU Han, M Currier, J Kehn, P Robinson, MA AF Han, M Currier, J Kehn, P Robinson, MA TI Distinctive patterns of TCRA CDR3 diversity in CD4-8- T cells from healthy individuals SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1997 VL 55 SU 1 BP 43 EP 43 PG 1 WC Immunology SC Immunology GA YA772 UT WOS:A1997YA77200078 ER PT J AU Kehn, PJ Robinson, MA AF Kehn, PJ Robinson, MA TI Frequency of TCRBV13S2 positive T cells in PBMC correlates with the number of BV13S2 genes. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID,IMMUNOGENET LAB,NIH,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1997 VL 55 SU 1 BP 43 EP 43 PG 1 WC Immunology SC Immunology GA YA772 UT WOS:A1997YA77200077 ER PT J AU Lee, KH Kim, CJ Zimmerman, PA Marincola, FM AF Lee, KH Kim, CJ Zimmerman, PA Marincola, FM TI A new high resolution TCR V beta screening using RT-PCR and heteroduplex analysis: Identification and monitoring of epitope-specific CTL. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NIAID,HELMINTH IMMUNOL SECT,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1997 VL 55 SU 1 BP 44 EP 44 PG 1 WC Immunology SC Immunology GA YA772 UT WOS:A1997YA77200079 ER PT J AU Barcellos, LF Thomson, G Carrington, M Schafer, J Begovich, AB Lin, P Xu, XH Min, BQ Marti, D Klitz, W AF Barcellos, LF Thomson, G Carrington, M Schafer, J Begovich, AB Lin, P Xu, XH Min, BQ Marti, D Klitz, W TI Multiple sclerosis candidate locus association study uncovers chromosome 19q13.2 susceptibility in Caucasian and Northern Chinese populations. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 UNIV CALIF BERKELEY,ROCHE MOL SYST,DEPT HUMAN GENET,DEPT INTEGRAT BIOL,ALAMEDA,CA. NCI,FREDERICK,MD 21701. UNIV CALIF DAVIS,DEPT NEUROL,DAVIS,CA. BEIJING HOSP,BEIJING,PEOPLES R CHINA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1997 VL 55 SU 1 BP 60 EP 60 PG 1 WC Immunology SC Immunology GA YA772 UT WOS:A1997YA77200112 ER PT J AU McConnachie, PR Wortsman, J Kohn, LD OConnor, TP AF McConnachie, PR Wortsman, J Kohn, LD OConnor, TP TI The occurrence of Graves' disease in a renal transplant recipient. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 SO ILLINOIS UNIV,SCH MED,MEM MED CTR,IMMUNOTRANSPLANT LAB,SPRINGFIELD,IL. SO ILLINOIS UNIV,SCH MED,DIV ENDOCRINOL,SPRINGFIELD,IL. SO ILLINOIS UNIV,SCH MED,DEPT SURG,SPRINGFIELD,IL 62794. NIDDK,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1997 VL 55 SU 1 BP 79 EP 79 PG 1 WC Immunology SC Immunology GA YA772 UT WOS:A1997YA77200150 ER PT J AU Simonis, TB Barracchini, KC Hackett, JA Marincola, FM AF Simonis, TB Barracchini, KC Hackett, JA Marincola, FM TI HLA-A*02 allele frequencies of different ethnic groups. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NIH,HLA LAB,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1997 VL 55 SU 1 BP 99 EP 99 PG 1 WC Immunology SC Immunology GA YA772 UT WOS:A1997YA77200189 ER PT J AU Bettinotti, MP Barracchini, K Lee, KH Kicklighter, EJ Marincola, FM AF Bettinotti, MP Barracchini, K Lee, KH Kicklighter, EJ Marincola, FM TI A strategy for HLA-C allele identification combining PCR-SSP, heteroduplex analysis and sequencing. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NCI,DEPT TRANSFUS MED,CC,NIH,BETHESDA,MD. NCI,SURG BRANCH,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1997 VL 55 SU 1 BP 101 EP 101 PG 1 WC Immunology SC Immunology GA YA772 UT WOS:A1997YA77200192 ER PT J AU Bettinotti, MP Hackett, J Roden, MM Kim, CJ Stroncek, D Marincola, FM AF Bettinotti, MP Hackett, J Roden, MM Kim, CJ Stroncek, D Marincola, FM TI A new HLA-A*0201 variant with one amino acid change (V->E) at position 152. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NCI,SURG BRANCH,NIH,BETHESDA,MD. NCI,DEPT TRANSFUS MED,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1997 VL 55 SU 1 BP 122 EP 122 PG 1 WC Immunology SC Immunology GA YA772 UT WOS:A1997YA77200235 ER PT J AU Kicklighter, EJ Lee, KH Zimmerman, PA Marincola, FM AF Kicklighter, EJ Lee, KH Zimmerman, PA Marincola, FM TI High resolution HLA A2 subtyping using directed heteroduplex analysis. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID,DEPT TRANSFUS MED,CC,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1997 VL 55 SU 1 BP 138 EP 138 PG 1 WC Immunology SC Immunology GA YA772 UT WOS:A1997YA77200266 ER PT J AU McGinnis, MD Brown, CL Chadwick, RB Krausa, P Kronick, MN Harding, A Carrington, M AF McGinnis, MD Brown, CL Chadwick, RB Krausa, P Kronick, MN Harding, A Carrington, M TI Modified Taq polymerase: Invisible hot start PCR improves HLA typing methods. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 PE APPL BIOSYST,FOSTER CITY,CA. NCI,FCRDC,SAIC,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 1997 VL 55 SU 1 BP 146 EP 146 PG 1 WC Immunology SC Immunology GA YA772 UT WOS:A1997YA77200283 ER PT J AU Mogayzel, PJ Henning, KA Bittner, ML Novotny, EA Schwiebert, EM Guggino, WB Jiang, Y Rosenfeld, MA AF Mogayzel, PJ Henning, KA Bittner, ML Novotny, EA Schwiebert, EM Guggino, WB Jiang, Y Rosenfeld, MA TI Functional human CFTR produced by stable Chinese hamster ovary cell lines derived using yeast artificial chromosomes SO HUMAN MOLECULAR GENETICS LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS GENE; DNA FIBER-FISH; MAMMALIAN-CELLS; CHLORIDE CHANNELS; EPITHELIAL-CELLS; PROMOTER REGION; TRANSGENIC MICE; MOUSE CELLS; EXPRESSION AB The cystic fibrosis transmembrane conductance regulator gene (CFTR) encodes a transmembrane protein (CFTR) which functions in part as a cyclic adenosine monophosphate (cAMP)-regulated chloride channel, CFTR expression is controlled temporally and cell specifically by mechanisms that are poorly understood, Insight into CFTR regulation could be facilitated by the successful introduction of the entire 230 kb human CFTR and adjacent sequences into mammalian cells, To this end, we have introduced two different CFTR-containing yeast artificial chromosomes (YACs) (320 and 620 kb) into Chinese hamster ovary-K1 (CHO) cells. Clonal cell lines containing human CFTR were identified by PCR, and the genetic and functional analyses of one clone containing each YAC are described, Integration of the human CFTR-containing YACs into the CHO genome at a unique site in each cell line was demonstrated by fluorescence in situ hybridization (FISH). Southern blot analysis suggested that on the order of one copy of human CFTR was integrated per CHO cell genome, Fiber-FISH and restriction analysis suggested that CFTR remained grossly intact. Northern analysis showed full-length, human CFTR mRNA. Immunoprecipitation followed by phosphorylation with protein kinase demonstrated mature, glycosylated CFTR. Finally, chloride secretion in response to cAMP indicated the functional nature of the human CFTR, This study provides several novel results including: (i) functional human CFTR can be expressed from these YACs; (ii) CHO cells are a permissive environment for expression of human CFTR; (iii) the level of human CFTR expression in CHO cells is unexpectedly high given the lack of endogenous CFTR production; and (iv) the suggestion by Fiber-FISH of CFTR integrity correlates with functional gene expression. These YACs and the cell lines derived from them should be useful tools for the study of CFTR expression. C1 NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,DEPT PEDIAT,BALTIMORE,MD 21287. JOHNS HOPKINS MED INST,DEPT ANESTHESIA & CRIT CARE MED,BALTIMORE,MD 21287. JOHNS HOPKINS MED INST,DEPT PHYSIOL,BALTIMORE,MD 21287. FU NHLBI NIH HHS [HL 47122]; NIDDK NIH HHS [DK 48977] NR 50 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN PY 1997 VL 6 IS 1 BP 59 EP 68 DI 10.1093/hmg/6.1.59 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA WD349 UT WOS:A1997WD34900009 PM 9002671 ER PT J AU Nussbaum, RL Polymeropoulos, MH AF Nussbaum, RL Polymeropoulos, MH TI Genetics of Parkinson's disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID AUTOSOMAL-DOMINANT PARKINSONISM; POSITRON EMISSION TOMOGRAPHY; ONSET ALZHEIMERS-DISEASE; LEWY-BODY PARKINSONISM; A-BETA COMPONENT; CLINICAL-DIAGNOSIS; MONOAMINE-OXIDASE; SKELETAL-MUSCLE; RISK; ANTICIPATION AB For the past 40 years, research into Parkinson's disease (PD) has been predominantly the province of epidemiologists interested in pursuing the connection between the disease and environmental factors such as viral infection or neurotoxins, Hereditary influences were actually discounted because of a high monozygotic twin discordance rate found in studies that were later shown to be inadequate and inconclusive, There has recently been a resurgence of interest in investigating hereditary factors in PD when it became more and more apparent that a positive family history was a major risk factor for the disease. Meanwhile, it also became increasingly apparent from neuropathological studies that the common, idiopathic form of Parkinson's disease had, in fact, a pathological correlate, i.e., the existence of Lewy bodies, an eosinophilic cytoplasmic inclusion body, distributed diffusely throughout the substnatia nigra, hypothalamus, hippocampus, autonomic ganglia and olfactory tracts. Although candidate gene approaches to linkage in PD families have not been rewarding, a genome wide scan mapped PD to 4q21-23 in one large family with PD with diffuse Lewy bodies, where a candidate gene, alpha-synuclein, resides, This gene encodes a presynaptic protein of which a peptide fragment is known to be a constituent of Alzheimer's disease plaques, The identification of a missense mutation in the alpha-synuclein gene in four independent PD families suggests that at least some fraction of familial PD with diffuse Lewy bodies is the result of an abnormal protein that interferes with normal protein degradation leading to the development of inclusions and ultimately neuronal cell death. There may be common pathogenetic mechanisms involved in alpha-synuclein mutations in PD and beta-amyloid and presenilin gene mutations in Alzheimer's disease. RP Nussbaum, RL (reprint author), NATL HUMAN GENOME RES INST,LAB GENET DIS RES,BETHESDA,MD 20892, USA. NR 70 TC 96 Z9 104 U1 4 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PY 1997 VL 6 IS 10 BP 1687 EP 1691 DI 10.1093/hmg/6.10.1687 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA XV039 UT WOS:A1997XV03900009 PM 9300660 ER PT J AU Adams, EM Becker, JA Griffith, L Segal, A Plotz, PH Raben, N AF Adams, EM Becker, JA Griffith, L Segal, A Plotz, PH Raben, N TI Glycogenosis Type II: A juvenile-specific mutation with an unusual splicing pattern and a shared mutation in African Americans SO HUMAN MUTATION LA English DT Article DE acid maltase deficiency; glycogen storage disease; splicing mutation; intron retention; exon skip ID LYSOSOMAL ALPHA-GLUCOSIDASE; DISEASE TYPE-II; PRE-MESSENGER-RNA; ACID MALTASE DEFICIENCY; MISSENSE MUTATION; DNA FRAGMENTS; GC-CLAMP; ONSET; GENE; TRANSPORT AB The recessively inherited deficiency of acid alpha-glucosidase (GAA) called Glycogenosis Type II is expressed as three different phenotypes: infantile, juvenile, and adult. At the molecular level, infantile and adult forms of the disease have been extensively studied, but little is known regarding the genetic defects associated with the juvenile form. We describe a novel mutation that defines the intermediate juvenile phenotype in a compound heterozygous patient. A transversion of t to g in intron 6 at position -22 creates a cryptic acceptor site and results in unusual splicing abnormality: insertion of 21 nucleotides of the intronic sequence into mRNA and removal of exon 6 without disruption of the reading frame. The second mutation, Arg854Stop in exon 18, had been previously identified in another African-American patient (Hermans et al., 1993a). Family study indicates that a silent allele harboring the Arg854Stop mutation in our patient is inherited from the patient's father who is also African American, thus suggesting a common mutation in this population. (C) 1997 Wiley-Liss, Inc.(dagger). C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT CARDIOL,WASHINGTON,DC 20010. NR 34 TC 22 Z9 23 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1997 VL 10 IS 2 BP 128 EP 134 DI 10.1002/(SICI)1098-1004(1997)10:2<128::AID-HUMU5>3.0.CO;2-G PG 7 WC Genetics & Heredity SC Genetics & Heredity GA XN177 UT WOS:A1997XN17700005 PM 9259196 ER PT J AU Narkis, G Adam, A Jaber, L Pennybacker, M Proia, RL Navon, R AF Narkis, G Adam, A Jaber, L Pennybacker, M Proia, RL Navon, R TI Molecular basis of heat labile hexosaminidase B among Jews and Arabs SO HUMAN MUTATION LA English DT Article DE HEXB mutations; heat-labile Hex B; Tay-Sachs disease; Sandhoff disease ID HUMAN BETA-HEXOSAMINIDASE; INFANTILE SANDHOFF DISEASE; HEXB GENE; 50-KB DELETION; MESSENGER-RNA; ADULT FORM; MUTATION; CHAIN; EXPRESSION; SUBUNIT AB Genotyping individuals for Tay-Sachs disease (TSD) is mainly based on the heat lability of beta-hexosaminidase (Hex) A (alpha beta) and the heat stability of Hex B (beta beta). Mutations in the HEXB gene encoding the beta-subunits of Hex that result in heat-labile Hex B thus may lead to erroneous enzymatic genotyping regarding TSD. Utilizing single strand conformation polymorphism (SSCP) analysis for all 14 exons of HEXB followed by direct sequencing of aberrant fragments, we screened individuals whose Hex B was heat labile. A novel heat labile mutation, previously concluded to exist in the HEXB gene, was identified among Jews and Arabs as 1627 G-->A. One individual with heat labile Hex B (HLB) was negative for this novel mutation and for the known 1514 G-->A HLB mutation, proving that there exists at least one other unidentified HLB mutation. Based on these results, it is advisable to perform DNA tests for 1627 G-->A mutation in suspected HLB individuals. (C) 1997 Wiley-Liss, Inc. C1 SAPIR MED CTR,MOL GENET LAB,IL-44281 KEFAR SAVA,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN GENET,TEL AVIV,ISRAEL. OPEN UNIV ISRAEL,TEL AVIV,ISRAEL. SCHNEIDER CHILDREN HOSP,TAIBE BRIDGE PEACE PEDIAT CTR & COMMUNITY UNIT,PETAH TIQWA,ISRAEL. NIDDKD,BIOCHEM GENET SECT,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. RI Proia, Richard/A-7908-2012 NR 28 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1997 VL 10 IS 6 BP 424 EP 429 DI 10.1002/(SICI)1098-1004(1997)10:6<424::AID-HUMU2>3.0.CO;2-D PG 6 WC Genetics & Heredity SC Genetics & Heredity GA YH817 UT WOS:A1997YH81700002 PM 9401004 ER PT J AU Drucker, L Golan, A Boles, DJ ElBedour, K Proia, RL Navon, R AF Drucker, L Golan, A Boles, DJ ElBedour, K Proia, RL Navon, R TI Novel HEXA mutation in a Bedouin Tay-Sachs patient associated with exon skipping and reduced transcript level SO HUMAN MUTATION LA English DT Article DE Tay-Sachs disease; hexosaminidase A; exon skipping; mRNA quantitation ID RNA SPLICE JUNCTIONS; DISEASE; SELECTION; SEQUENCE; GENE AB An Israeli-Bedouin infant from a consanguineous family was diagnosed with Tay Sachs disease (TSD), The patient was found to carry the novel + 3tIVS4 mutation in homozygosity, Direct sequencing of the cDNA showed that the + 3tIVS4 mutation caused complete skipping of exon 4 resulting in a stop codon 17bp downstream. We postulate that the insertion disrupts base pairing between the consensus sequence and U1 snRNA causing exon skipping. The resultant transcript contains a premature termination codon and is severely reduced in amount. An extended nucleotide portion of the 5' end of IVS4 was sequenced. (C) 1997 Wiley-Liss, Inc. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN GENET,TEL AVIV,ISRAEL. SAPIR MED CTR,KEFAR SAVA,ISRAEL. SOROKA MED CTR,DEPT NEONATOL,NEONATAL INTENS CARE UNIT,IL-84101 BEER SHEVA,ISRAEL. NIDDKD,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20824. RI Proia, Richard/A-7908-2012 NR 11 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1997 VL 9 IS 3 BP 260 EP 264 DI 10.1002/(SICI)1098-1004(1997)9:3<260::AID-HUMU7>3.0.CO;2-B PG 5 WC Genetics & Heredity SC Genetics & Heredity GA WP910 UT WOS:A1997WP91000007 PM 9090529 ER PT J AU Highsmith, WE Burch, LH Zhou, ZQ Olsen, JC Strong, TV Smith, T Friedman, KJ Silverman, LM Boucher, RC Collins, FS Knowles, MR AF Highsmith, WE Burch, LH Zhou, ZQ Olsen, JC Strong, TV Smith, T Friedman, KJ Silverman, LM Boucher, RC Collins, FS Knowles, MR TI Identification of a splice site mutation (2789+5 G>A) associated with small amounts of normal CFTR mRNA and mild cystic fibrosis SO HUMAN MUTATION LA English DT Article DE exon 14b; pancreatic sufficiency; quantitative CFTR mRNA ID MESSENGER-RNA TRANSCRIPTS; BETA-THALASSEMIA; GENE; REGULATOR; EXPRESSION; JUNCTIONS; GENOTYPE; CHANNELS; SPECTRUM; MARKERS AB A splicing mutation was identified at the 1-5 position of the splice donor site of exon 14b of CFTR in CF patients in a consanguineous family that is remarkable for unusually mild disease. Quantitative studies of nasal epithelial mRNA revealed that homozygotes for the spice site mutation produced approximately 4% of the normal amount of normally-spliced CFTR. We propose that this small amount of normally spliced mRNA is associated with synthesis of some normal CFTR protein, and accounts for the mild phenotype, Further characterization of epithelial function and clinical phenotype in patients bearing this form of mutation, termed a type V mutation, will be useful in determining the level of CFTR associated with amelioration of lung disease. (C) 1997 Wiley-Liss, Inc. C1 UNIV N CAROLINA,SCH MED,CYST FIBROSIS PULM RES & TREATMENT CTR,CHAPEL HILL,NC 27599. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. UNIV ALABAMA,GENE THERAPY PROGRAM,BIRMINGHAM,AL 35294. UNIV COLL,NALT DIAGNOST CTR,GALWAY,IRELAND. UNC HOSP,CHAPEL HILL,NC 27599. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RI Highsmith, William/B-6175-2008; OI Smith, Terry/0000-0002-4956-3299 FU NCRR NIH HHS [RR000046]; NHLBI NIH HHS [HL34322] NR 27 TC 51 Z9 52 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1997 VL 9 IS 4 BP 332 EP 338 DI 10.1002/(SICI)1098-1004(1997)9:4<332::AID-HUMU5>3.0.CO;2-7 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA WQ432 UT WOS:A1997WQ43200005 PM 9101293 ER PT J AU Shastry, BS Hejtmancik, JF Trese, MT AF Shastry, BS Hejtmancik, JF Trese, MT TI Identification of novel missense mutations in Norrie disease gene associated with one X-linked and four sporadic cases of familial exudative vitreoretinopathy SO HUMAN MUTATION LA English DT Article DE mutation; Norrie disease; vitreoretinopathy; sporadic; X-linked; autosomal ID POLYMORPHISMS; LINKAGE; MOTIF AB X-linked Familial Exudative Vitreoretinopathy (XLFEVR) is a hereditary eye disorder that affects both the retina and the vitreous body. It is characterized by an abnormal vascularization of the peripheral retina, It has been previously shown by linkage and candidate gene analysis that XLFEVR and Norrie disease are allelic. In this report we describe four novel mutations (R41K, H42R, K58N, and Y120C) in the Norrie disease gene associated with one X-linked and four sporadic cases of FEVR. One mutation (H42R) was found to be segregating with the disease in three generations (X-linked family), and the others are sporadic. These sequence alterations changed the encoded amino acids in the Norrie disease protein and were not found in 17 unaffected family members or in 36 randomly selected normal individuals. This study provides additional evidence that mutations in the same gene fan result in FEVR and Norrie disease. It also demonstrates that it may be beneficial for clinical diagnosis to screen for mutations in the Norrie disease gene in sporadic FEVR cases. (C) 1997 Wiley-Liss, Inc. C1 NEI,BETHESDA,MD 20892. WILLIAM BEAUMONT HOSP,DEPT OPHTHALMOL,ROYAL OAK,MI 48073. RP Shastry, BS (reprint author), OAKLAND UNIV,EYE RES INST,ROCHESTER,MI 48309, USA. FU NEI NIH HHS [EY05230]; PHS HHS [GA95002] NR 26 TC 55 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1997 VL 9 IS 5 BP 396 EP 401 DI 10.1002/(SICI)1098-1004(1997)9:5<396::AID-HUMU3>3.0.CO;2-2 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA WW877 UT WOS:A1997WW87700003 PM 9143917 ER PT S AU Gazzinelli, RT Camargo, MM Almeida, IC Morita, YS Giraldo, M AcostaSerrano, A Hieny, S Englund, PT Ferguson, MAJ Travassos, LR Sher, A AF Gazzinelli, RT Camargo, MM Almeida, IC Morita, YS Giraldo, M AcostaSerrano, A Hieny, S Englund, PT Ferguson, MAJ Travassos, LR Sher, A BE Adorini, L TI Identification and characterization of protozoan products that trigger the synthesis of IL-12 by inflammatory macrophages SO IL-12 SE CHEMICAL IMMUNOLOGY LA English DT Review ID NECROSIS-FACTOR-ALPHA; PROTEIN-KINASE-C; LEISHMANIA-DONOVANI LIPOPHOSPHOGLYCAN; NATURAL-KILLER-CELLS; VASCULAR ENDOTHELIAL-CELLS; BLOOD MONONUCLEAR-CELLS; CD4(+) T-CELLS; TOXOPLASMA-GONDII; TRYPANOSOMA-CRUZI; IFN-GAMMA C1 UFMG, BIOCHEM & IMMUNOL DEPT, BELO HORIZONTE, MG, BRAZIL. UNIFESP, DISCIPLINE CELLULAR BIOL, SAO PAULO, BRAZIL. NIAID, PARASIT DIS LAB, NIH, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, DEPT BIOL CHEM, BALTIMORE, MD USA. UNIV DUNDEE, DEPT BIOCHEM, DUNDEE DD1 4HN, SCOTLAND. RP Gazzinelli, RT (reprint author), FDN OSWALDO CRUZ, LAB CHAGAS DIS, CPQRR, AV AUGUSTO DE LIMA 1715, BR-30190002 BELO HORIZONTE, MG, BRAZIL. RI Ferguson, Michael/F-7829-2010; Camargo, Maristela/G-8584-2011; Travassos, Luiz/J-3631-2012; Acosta-Serrano, Alvaro/L-5503-2015; OI Camargo, Maristela/0000-0003-2815-125X; Acosta-Serrano, Alvaro/0000-0002-2576-7959; Ferguson, Michael/0000-0003-1321-8714 FU NIAID NIH HHS [AI27608] NR 67 TC 20 Z9 20 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1015-0145 BN 3-8055-6526-7 J9 CHEM IMMUNOL JI Chem.Immunol. PY 1997 VL 68 BP 136 EP 152 PG 17 WC Immunology SC Immunology GA BJ75C UT WOS:A1997BJ75C00008 PM 9329220 ER PT B AU Kempner, KM Chow, D Choyke, P Cox, JR Elson, JE Johnson, CA Okunieff, P Ostrow, H Pfeifer, JC Martino, RL AF Kempner, KM Chow, D Choyke, P Cox, JR Elson, JE Johnson, CA Okunieff, P Ostrow, H Pfeifer, JC Martino, RL BE Kim, YM TI The development of an ATM-based Radiology Consultation WorkStation for radiotherapy treatment planning SO IMAGE DISPLAY - MEDICAL IMAGING 1997 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Image Display - Medical Imaging 1997 CY FEB 23-25, 1997 CL NEWPORT BEACH, CA SP Soc Photo Opt Instrumentat Engineers, Amer Assoc Physicists Med, Amer Physiol Soc, US FDA, Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Informat Syst Consortium, Radiol Soc N Amer, Soc Comp Applicat Radiol DE telemedicine; multimedia system; ATM network; medical consultation; medical Imaging AB The Radiology Consultation WorkStation (RCWS) is a multimedia, medical imaging workstation being developed for use in an electronic radiology environment, utilizing a prototype Asynchronous Transfer Mode (ATM) telemedicine network, in support of radiotherapy treatment planning. A radiation oncologist in the Radiation Oncology Department, and a radiologist in the Diagnostic Radiology Department, will be able to consult, utilizing high-quality audio/video channels and high-resolution medical image displays, prior to the design of a treatment plan. Organ and lesion contouring is performed via a shared-cursor feature, in a consultation mode, allowing medical specialists to fully interact during the identification and delineation of lesions and other features. RP Kempner, KM (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2442-0 J9 P SOC PHOTO-OPT INS PY 1997 VL 3031 BP 500 EP 511 DI 10.1117/12.273928 PG 12 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BH93H UT WOS:A1997BH93H00049 ER PT S AU Appel, NM AF Appel, NM BE Lester, DS Felder, CC Lewis, EN TI Classical and contemporary histochemical approaches for evaluating central nervous system microanatomy SO IMAGING BRAIN STRUCTURE AND FUNCTION: EMERGING TECHNOLOGIES IN THE NEUROSCIENCES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Current and Emerging Techniques in Monitoring Brain Structure and Function CY MAR 28-29, 1996 CL BETHESDA, MD SP US FDA, Ctr Drug Evaluat & Res, NIMH ID INTERMEDIOLATERAL CELL COLUMN; COEXISTING NEUROTRANSMITTERS; PREGANGLIONIC NEURONS; SPINAL-CORD; TRANSPORT; FIBERS; BRAIN; VIRUS C1 NIA, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. RP Appel, NM (reprint author), US FDA, MOD 1 LAB FACIL, DIV APPL PHARMACOL RES, OFF TESTING & RES, CTR DRUG EVALUAT & RES, LAUREL, MD 20708 USA. NR 49 TC 3 Z9 3 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-069-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 820 BP 14 EP 28 DI 10.1111/j.1749-6632.1997.tb46186.x PG 15 WC Multidisciplinary Sciences; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BJ18E UT WOS:A1997BJ18E00002 PM 9237446 ER PT S AU Vocci, FJ London, ED AF Vocci, FJ London, ED BE Lester, DS Felder, CC Lewis, EN TI Assessment of neurotoxicity from potential medications for drug abuse: Ibogaine testing and brain imaging SO IMAGING BRAIN STRUCTURE AND FUNCTION: EMERGING TECHNOLOGIES IN THE NEUROSCIENCES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Current and Emerging Techniques in Monitoring Brain Structure and Function CY MAR 28-29, 1996 CL BETHESDA, MD SP US FDA, Ctr Drug Evaluat & Res, NIMH ID EXTRACELLULAR DOPAMINE LEVELS; POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-UTILIZATION; MEDIAL PREFRONTAL CORTEX; INVIVO MICRODIALYSIS; PURKINJE-CELLS; PARASAGITTAL ZONES; NUCLEUS-ACCUMBENS; MOTOR BEHAVIOR; D-AMPHETAMINE C1 NIDA, BRAIN IMAGING SECT, INTRAMURAL RES PROGRAM, BALTIMORE, MD 21224 USA. RP Vocci, FJ (reprint author), NIDA, MEDICAT DEV DIV, ROOM 11A55, 5600 FISHERS LANE, ROCKVILLE, MD 20857 USA. NR 41 TC 1 Z9 1 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-069-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 820 BP 29 EP 40 DI 10.1111/j.1749-6632.1997.tb46187.x PG 12 WC Multidisciplinary Sciences; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BJ18E UT WOS:A1997BJ18E00003 PM 9237447 ER PT S AU Rapoport, SI Purdon, D Shetty, HU Grange, E Smith, Q Jones, C Chang, MCJ AF Rapoport, SI Purdon, D Shetty, HU Grange, E Smith, Q Jones, C Chang, MCJ BE Lester, DS Felder, CC Lewis, EN TI In vivo imaging of fatty acid incorporation into brain to examine signal transduction and neuroplasticity involving phospholipids SO IMAGING BRAIN STRUCTURE AND FUNCTION: EMERGING TECHNOLOGIES IN THE NEUROSCIENCES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Current and Emerging Techniques in Monitoring Brain Structure and Function CY MAR 28-29, 1996 CL BETHESDA, MD SP US FDA, Ctr Drug Evaluat & Res, NIMH ID ARACHIDONIC-ACID; UNANESTHETIZED RATS; ALZHEIMERS-DISEASE; AWAKE RATS; METABOLISM; PALMITATE; STIMULATION; ACTIVATION; LIPIDS; PET RP Rapoport, SI (reprint author), NIA, NEUROSCI LAB, NIH, BLDG 10, RM 6C-103, BETHESDA, MD 20892 USA. NR 35 TC 32 Z9 32 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-069-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 820 BP 56 EP 74 DI 10.1111/j.1749-6632.1997.tb46189.x PG 19 WC Multidisciplinary Sciences; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BJ18E UT WOS:A1997BJ18E00005 PM 9237449 ER PT S AU Basser, PJ AF Basser, PJ BE Lester, DS Felder, CC Lewis, EN TI New histological and physiological stains derived from diffusion-tensor MR images SO IMAGING BRAIN STRUCTURE AND FUNCTION: EMERGING TECHNOLOGIES IN THE NEUROSCIENCES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Current and Emerging Techniques in Monitoring Brain Structure and Function CY MAR 28-29, 1996 CL BETHESDA, MD SP US FDA, Ctr Drug Evaluat & Res, NIMH ID SELF-DIFFUSION; WATER DIFFUSION; NERVOUS-SYSTEM; WHITE MATTER; ANISOTROPY; SPECTROSCOPY; RAT; AXONOGRAPHY; INVIVO; MUSCLE RP Basser, PJ (reprint author), NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13, ROOM 3N-17, 13 SOUTH DR, BETHESDA, MD 20892 USA. RI Basser, Peter/H-5477-2011 NR 44 TC 82 Z9 85 U1 0 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-069-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 820 BP 123 EP 138 DI 10.1111/j.1749-6632.1997.tb46192.x PG 16 WC Multidisciplinary Sciences; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BJ18E UT WOS:A1997BJ18E00008 PM 9237452 ER PT S AU Lewis, EN Kidder, LH Levin, IW Kalasinsky, VF Hanig, JP Lester, DS AF Lewis, EN Kidder, LH Levin, IW Kalasinsky, VF Hanig, JP Lester, DS BE Lester, DS Felder, CC Lewis, EN TI Applications of Fourier transform infrared imaging microscopy in neurotoxicity SO IMAGING BRAIN STRUCTURE AND FUNCTION: EMERGING TECHNOLOGIES IN THE NEUROSCIENCES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Current and Emerging Techniques in Monitoring Brain Structure and Function CY MAR 28-29, 1996 CL BETHESDA, MD SP US FDA, Ctr Drug Evaluat & Res, NIMH C1 ARMED FORCES INST PATHOL, DEPT ENVIRONM & TOXICOL PATHOL, WASHINGTON, DC 20306 USA. US FDA, CTR DRUG EVALUAT & RES, LAUREL, MD 20708 USA. RP Lewis, EN (reprint author), NIDDKD, CHEM PHYS LAB, NIH, BLDG 2, BETHESDA, MD 20892 USA. NR 26 TC 14 Z9 14 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-069-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 820 BP 234 EP 247 DI 10.1111/j.1749-6632.1997.tb46199.x PG 14 WC Multidisciplinary Sciences; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BJ18E UT WOS:A1997BJ18E00015 PM 9237459 ER PT S AU Hanig, JP Sobotka, T Contrera, J Rapoport, S Munzner, R Slikker, W Johannessen, J Wilcox, B Vocci, F OCallaghan, JP Lester, D AF Hanig, JP Sobotka, T Contrera, J Rapoport, S Munzner, R Slikker, W Johannessen, J Wilcox, B Vocci, F OCallaghan, JP Lester, D BE Lester, DS Felder, CC Lewis, EN TI Future directions for neurotoxicity testing: Towards a unified approach - Panel Discussion SO IMAGING BRAIN STRUCTURE AND FUNCTION: EMERGING TECHNOLOGIES IN THE NEUROSCIENCES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Current and Emerging Techniques in Monitoring Brain Structure and Function CY MAR 28-29, 1996 CL BETHESDA, MD SP US FDA, Ctr Drug Evaluat & Res, NIMH C1 US FDA, CTR FOOD SAFETY & APPL NUTR, LAUREL, MD USA. NIA, NIH, BETHESDA, MD 20892 USA. US FDA, NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. US FDA, CTR BIOL EVALUAT & RES, BETHESDA, MD 20014 USA. NIDA, NIH, ROCKVILLE, MD USA. US EPA, RES TRIANGLE PK, NC 27711 USA. RP Hanig, JP (reprint author), US FDA, CTR DRUG EVALUAT & RES, LAUREL, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-069-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 820 BP 300 EP 313 DI 10.1111/j.1749-6632.1997.tb46203.x PG 14 WC Multidisciplinary Sciences; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BJ18E UT WOS:A1997BJ18E00019 ER PT J AU Zhan, SX Kozak, CA Zhan, SL Chanock, SJ AF Zhan, SX Kozak, CA Zhan, SL Chanock, SJ TI Cloning and chromosomal localization of Ncf4, the mouse homologue of p40-phox SO IMMUNOGENETICS LA English DT Article ID NADPH OXIDASE; COMPLEX; P40(PHOX); P47(PHOX); RECEPTOR; DOMAINS; SYSTEM C1 NCI,PEDIAT BRANCH,IMMUNOCOMPROMISED HOST SECT,NIH,BETHESDA,MD 20892. NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. NR 16 TC 4 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PY 1997 VL 45 IS 3 BP 217 EP 219 DI 10.1007/s002510050192 PG 3 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA WE190 UT WOS:A1997WE19000008 PM 8995189 ER PT J AU Kondo, A Sidney, J Southwood, S delGuercio, MF Appella, E Sakamoto, H Grey, HM Celis, E Chesnut, RW Kubo, RT Sette, A AF Kondo, A Sidney, J Southwood, S delGuercio, MF Appella, E Sakamoto, H Grey, HM Celis, E Chesnut, RW Kubo, RT Sette, A TI Two distinct HLA-A*0101-specific submotifs illustrate alternative peptide binding modes SO IMMUNOGENETICS LA English DT Article ID SECONDARY ANCHOR RESIDUES; CLASS-I MOLECULES; MHC COMPLEXES; HLA; MOTIFS; ALLELES; EPITOPES AB Previous studies have defined two different peptide binding motifs specific for HLA-A*0101. These motifs are characterized by the presence of tyrosine (Y) at the C-termini of 9-mer and 10-mer peptides, and either a small polar or hydrophobic (S, T, M) residue in position 2, or a negatively charged (D or E) residue in position 3. In this study, the structural requirements for peptide binding to A*0101 have been further analyzed by examining the binding capacity of large sets of peptides corresponding to naturally occurring sequences which bore one or the other of these two A*0101-specific motifs. By correlating the presence of specific residue types at each position along the peptide sequence with increased (or decreased) binding affinity, the prominent influence of secondary anchor residues was revealed. In most cases, the two anchors in positions 2 and 3 appear to act synergistically. With the exception of the DE(3) submotif in 9-mer peptides, a positive role for aromatic residues in position 1 and the center of the peptide (positions 4 or 5 of 9- or 10-mer peptides, respectively), and proline at C-3, were also consistently detected. However, secondary anchor residues also appear to differ significantly between the two different submotifs, demonstrating that A*0101 can utilize alternative modes in binding its peptide ligands. According to these analyses, specific refined submotifs were also established, and their merit verified by independent sets of potential A*0101 binding peptides. Besides providing useful insight into the nature of the interaction of the A*0101 allele with its peptide ligands, such refined motifs should also facilitate accurate prediction of potential A*0101-restricted peptide epitopes. C1 CYTEL CORP,SAN DIEGO,CA 92121. TAKARA SHUZO CO LTD,BIOTECHNOL RES LABS,OTSU,SHIGA 52021,JAPAN. NCI,CELL BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. LA JOLLA INST ALLERGY & IMMUNOL,SAN DIEGO,CA 92121. RI Sakamoto, Hiroshi/A-3181-2011 NR 24 TC 24 Z9 24 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PY 1997 VL 45 IS 4 BP 249 EP 258 DI 10.1007/s002510050200 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA WJ493 UT WOS:A1997WJ49300003 PM 9002445 ER PT J AU Kawakami, Y Rosenberg, SA AF Kawakami, Y Rosenberg, SA TI Human tumor antigens recognized by T-cells SO IMMUNOLOGIC RESEARCH LA English DT Review DE tumor antigens; T-cells; tolerance; immunotherapy ID HUMAN-MELANOMA ANTIGENS; ESTABLISHED PULMONARY METASTASES; PAPILLOMAVIRUS TYPE-16 E6; CYTOLYTIC LYMPHOCYTES-T; HUMAN GENE MAGE-3; INFILTRATING LYMPHOCYTES; IN-VIVO; HLA-A2 MELANOMAS; DENDRITIC CELLS; BREAST-CANCER AB T-cells play an important role in in vivo tumor rejection in many animal tumor models and in human melanoma. Many human tumor antigens recognized by autologous T-cells have now been identified. These are found to be nonmutated and mutated peptides derived from various self proteins as well as viral proteins. A variety of mechanisms involved in generating these T-cell epitopes on growing cancers have also been identified. However, the role of these identified antigens remains to be evaluated. Passive or active immunotherapies using these identified tumor antigens are being conducted in many institutions. The results obtained from these clinical trials may give us better insight into the role of T-cell responses to each antigen in tumor rejection as well as the development of new antigen-specific immunotherapies for patients with cancer. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Kawakami, Y (reprint author), NCI, Surg Branch, NIH, Bldg 10,Rm 2B-42,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 135 TC 110 Z9 114 U1 2 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 1997 VL 16 IS 4 BP 313 EP 339 DI 10.1007/BF02786397 PG 27 WC Immunology SC Immunology GA YM727 UT WOS:000071094800001 PM 9439758 ER PT J AU Fujihara, K Goldman, B Oseroff, AR Glenister, N Jaffe, ES Bisaccia, E Pincus, S Greenberg, SJ AF Fujihara, K Goldman, B Oseroff, AR Glenister, N Jaffe, ES Bisaccia, E Pincus, S Greenberg, SJ TI HTLV-associated diseases: Human retroviral infection and cutaneous T-cell lymphomas SO IMMUNOLOGICAL INVESTIGATIONS LA English DT Article; Proceedings Paper CT Proceedings of the 13th International Convocation on Immunology - Immunological and Molecular Diagnosis of Infectious Disease CY JUN 01-05, 1996 CL BUFFALO, NY SP SUNY, Ernest Witebsky Ctr Immunol DE retrovirus; HTLV-I; HTLV-II; HIV; lymphoma, T-cell, cutaneous; PCR ID VIRUS TYPE-I; POLYMERASE CHAIN-REACTION; MYCOSIS-FUNGOIDES; LEUKEMIA-LYMPHOMA; DNA; BLOOD; REGION AB An array of neurologic, oncologic, and autoimmune disorders are associated with infection with the human pathogenic retroviruses human T-cell leukemia virus types I and II (HTLV-I, II), as well as the human immunodeficiency viruses (HIV). The cutaneous T-cell lymphomas, mycosis fungoides (MF) and its hematogenous variant Sezary Syndrome (SS), share similar clinical and pathological features to HTLV-I-associated adult T-cell leukemia (ATL) and speculation of a retroviral link to MF and SS, especially in areas non-endemic for ATL, has lead to an intensified search for HTLV- and HIV-like agents in these diseases. To further explore a potential role for human retroviruses in MF and SS, skin biopsy-derived or peripheral blood mononuclear cell-derived DNA from 17 patients (MF, n=7; erythrodermic MF (EMF), n=5; SS, n=5) from the North Eastern United States were screened using gene amplification by PCR and a liquid hybridization detection assay. Previously published primers and probes for HTLV-I (LTR, gag, pol, env, and pX), and our own primers and probes for HTLV-I (gag, pol, and env), HTLV-II (pol and env) and HIV-I (gag and pol) were employed. Serum antibodies to HTLV-I were negative in all but one EMF patient. The single HTLV-I seropositive patient carrying a diagnosis of EMF generated positive amplified signals for all of the eight HTLV-I regions tested. Ultimately, this individual evolved to exhibit clinical manifestations indistinguishable from ATL. The other 16 patients were negative for all 12 HTLV and HIV retroviral regions. Our findings suggest that none of the known prototypic human retroviruses are associated with seronegative MF and SS. The uniformly positive results for HTLV-I in the seropositive patient suggests that this patient initially presented with a smoldering form of ATL and illustrates the difficulty that sometimes may be encountered in the differential diagnosis of MF, SS, and ATL based solely on clinical and histopathological criteria. C1 ROSWELL PK CANC INST,DEPT NEUROL,LAB NEUROIMMUNOL & NEUROVIROL,BUFFALO,NY 14263. ROSWELL PK CANC INST,DEPT DERMATOL,BUFFALO,NY 14263. SUNY BUFFALO,BUFFALO,NY 14263. NCI,NIH,BETHESDA,MD 20892. MORRISTOWN MEM HOSP,DEPT DERMATOL,MORRISTOWN,NJ 07960. NR 27 TC 5 Z9 5 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0882-0139 J9 IMMUNOL INVEST JI Immunol. Invest. PY 1997 VL 26 IS 1-2 BP 231 EP 242 DI 10.3109/08820139709048929 PG 12 WC Immunology SC Immunology GA WG293 UT WOS:A1997WG29300021 PM 9037626 ER PT J AU Bloch, EF Knight, EM Carmon, T McDonaldPinkett, S Carter, J Boomer, A Ogunfusika, M Petersen, M Famakin, B Aniagolu, J Walker, J Gant, R Walters, CS Gaither, TA AF Bloch, EF Knight, EM Carmon, T McDonaldPinkett, S Carter, J Boomer, A Ogunfusika, M Petersen, M Famakin, B Aniagolu, J Walker, J Gant, R Walters, CS Gaither, TA TI C5b-7 and C5b-8 precursors of the membrane attack complex (C5b-9) are effective killers of E-coli J5 during serum incubation SO IMMUNOLOGICAL INVESTIGATIONS LA English DT Article ID ESCHERICHIA-COLI; INHIBITION; C9 AB The finding that C9-deficient sera (C9D) can kill serum sensitive strains of Gram-negative bacteria by us and other investigators, questions the role of C9 in the membrane attack complex as necessary for cell death. In these studies we have demonstrated that C5b-8 complexes generated on E. coli J5 during incubation in C9-depleted and C9-neutralized sera are effective in killing Gram-negative bacteria. In the same study, we extended our investigations to show that the deposition of C5b-7 complexes (from C8-deficient [C8D], C8 depleted and C8-neutralized sera) is also effective in killing Gram-negative bacteria. In all cases, these studies demonstrated that when E. coli J5 was incubated with C8D, C9D and pooled normal human serum [PNHS], deposited C5b-9 complexes from PNHS produced more killing than C5b-7 or C5b-8 complexes alone. These experiments clearly demonstrated that C5b-7 and C5b-8 complexes are bactericidal and that multimeric C9 within C5b-9 is not an absolute requirement for inner membrane damage and cell death of Gram-negative bacteria. C1 NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. RP Bloch, EF (reprint author), HOWARD UNIV,COLL MED,DEPT MICROBIOL,WASHINGTON,DC 20059, USA. NR 14 TC 6 Z9 6 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0882-0139 J9 IMMUNOL INVEST JI Immunol. Invest. PY 1997 VL 26 IS 4 BP 409 EP 419 DI 10.3109/08820139709022698 PG 11 WC Immunology SC Immunology GA XL596 UT WOS:A1997XL59600002 PM 9246562 ER PT J AU Han, RC AF Han, RC TI Impact of a truncated invariant chain on in vitro assembly of class II MHC molecules depends on the affinity of invariant chain for a given alpha beta dimer SO IMMUNOLOGICAL INVESTIGATIONS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CELL-SURFACE EXPRESSION; HLA-DR; PEPTIDE BINDING; INTRACELLULAR-TRANSPORT; ALLELIC POLYMORPHISM; MICE LACKING; CLIP; ANTIGENS; COMPARTMENTS AB The assembly of major histocompatibility complex (MHC) class II alpha and beta chains occurs in the endoplasmic reticulum (ER) with the involvement of MHC class II-associated invariant chain (Ii). The present study investigated the impact of Ii on the assembly of both I-A haplotype-matched and -mismatched alpha and beta chains using an in vitro translation system. The alpha and beta chains of I-A(b), I-A(d) and I-A(k) were cotranslated in vitro in different combinations with or without cotranslation of a truncated murine Ii (mIi 1-131). The translated products were sequentially immunoprecipitated, first with conformation-dependent monoclonal antibodies, then with conformation-independent antibodies. The results show: (1), Ii did not associate with free A alpha and free A beta chains; (2), mIi 1-131 significantly augmented the amount of properly assembled A alpha(b)A beta(b), A alpha(b)A beta(d), A alpha A beta(k) and A alpha(k)A beta(b) dimers, but had little affect on the assembly of A alpha(d)A beta(d), A alpha(k)A beta(k), A alpha(d)A beta(b), A alpha(k)A beta(d) and A alpha(d)A beta(k); (3), All A alpha A beta dimers whose assembly could be significantly facilitated by mIi 1-131 could be coimmunoprecipitated along with substantial amounts of mIi 1-131. This finding is consistent with prior observations that the impact of Ii on class II molecule assembly is allele specific. Furthermore, these results suggest that the efficient assembly of alpha and beta chains is primarily determined by the affinity between alpha and beta chains and that the high affinity of mIi for A alpha A beta dimers is required for mIi 1-131 to assist proper A alpha A beta assembly, most probably through a mechanism in which Ii stabilizes properly assembled A alpha A beta dimers or promotes folding of associated alpha and beta chains to help achieve a stable dimer state. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 56 TC 3 Z9 3 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0882-0139 J9 IMMUNOL INVEST JI Immunol. Invest. PY 1997 VL 26 IS 4 BP 421 EP 437 DI 10.3109/08820139709022699 PG 17 WC Immunology SC Immunology GA XL596 UT WOS:A1997XL59600003 PM 9246563 ER PT J AU Heeney, JL Bruck, C Goudsmit, J Montagnier, L Schultz, A Tyrrell, D ZollaPazner, S AF Heeney, JL Bruck, C Goudsmit, J Montagnier, L Schultz, A Tyrrell, D ZollaPazner, S TI Immune correlates of protection from HIV infection and AIDS SO IMMUNOLOGY TODAY LA English DT Article ID VACCINE PROTECTION; VIRUS LOAD; T-CELLS; SUPPRESSION; COMPLEX AB At an international workshop*, the immune responses observed in cases of protection from HIV infection or disease progression were discussed. An understanding of the immunological mechanisms associated with protection from lentivirus infection and disease is likely to have an important impact on vaccine design and new therapeutic strategies. C1 SMITHKLINE BEECHAM BIOL,B-1330 RIXENSART,BELGIUM. UNIV AMSTERDAM,ACAD MED CTR,HUMAN RETROVIRUS LAB,DEPT VIROL,NL-1105 AZ AMSTERDAM,NETHERLANDS. INST PASTEUR,UNITE ONCOL VIRALE,DEPT SIDA & RETROVIRUS,F-75015 PARIS 15,FRANCE. NIH,NIAID,PRECLIN DEV BRANCH,BETHESDA,MD 20892. PUBL HLTH LAB SERV,CTR APPL MICROBIOL & RES,SALISBURY SP4 0JG,WILTS,ENGLAND. NYU,MED CTR,VA MED CTR,NEW YORK,NY 10010. RP Heeney, JL (reprint author), BIOMED PRIMATE RES CTR,DEPT VIROL,LANGE KLEIWEG 157,NL-2288 GJ RIJSWIJK,NETHERLANDS. OI Heeney, Jonathan/0000-0003-2702-1621 NR 30 TC 24 Z9 24 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 JAN PY 1997 VL 18 IS 1 BP 4 EP 8 DI 10.1016/S0167-5699(97)80005-9 PG 5 WC Immunology SC Immunology GA WE197 UT WOS:A1997WE19700004 PM 9018965 ER PT S AU Cheever, AW Yap, GS AF Cheever, AW Yap, GS BE Freedman, DO TI Immunologic basis of disease and disease regulation in schistosomiasis SO IMMUNOPATHOGENETIC ASPECTS OF DISEASE INDUCED BY HELMINTH PARASITES SE CHEMICAL IMMUNOLOGY LA English DT Review ID MANSONI-INFECTED MICE; T-CELL CLONES; EXPERIMENTAL MURINE SCHISTOSOMIASIS; INTERCELLULAR-ADHESION MOLECULE-1; DIFFERENT CLINICAL FORMS; LIVER COLLAGEN-SYNTHESIS; EGG GRANULOMA-FORMATION; IMMUNE-RESPONSES; HEPATIC-FIBROSIS; IN-VIVO C1 BIOMED RES INST, ROCKVILLE, MD 20852 USA. RP Cheever, AW (reprint author), NIAID, PARASIT DIS LAB, IMMUNOBIOL SECT, BLDG 4, ROOM 126, BETHESDA, MD 20892 USA. NR 106 TC 14 Z9 14 U1 1 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1015-0145 BN 3-8055-6400-7 J9 CHEM IMMUNOL JI Chem.Immunol. PY 1997 VL 66 BP 159 EP 176 PG 18 WC Immunology SC Immunology GA BH53H UT WOS:A1997BH53H00007 PM 9103669 ER PT B AU Ron, E AF Ron, E BE Boice, JD TI Cancer risk following radioactive iodine-131 exposures in medicine SO IMPLICATIONS OF NEW DATA ON RADIATION CANCER RISK SE PROCEEDINGS OF THE NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS LA English DT Proceedings Paper CT 32nd Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements on Implications of New Data on Radiation Cancer Risk CY APR 03-04, 1996 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements RP Ron, E (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL COUNCIL RADIATION PROTECTION MEASUREMENTS PI BETHESDA PA 7910 WOODMONT AVE, SUITE 1016, BETHESDA, MD 20814 BN 0-929600-55-X J9 P NAT C RAD PY 1997 IS 18 BP 65 EP 77 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BH87C UT WOS:A1997BH87C00005 ER PT B AU Curtis, RE AF Curtis, RE BE Boice, JD TI Second cancers following radiotherapy for cancer SO IMPLICATIONS OF NEW DATA ON RADIATION CANCER RISK SE PROCEEDINGS OF THE NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS LA English DT Proceedings Paper CT 32nd Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements on Implications of New Data on Radiation Cancer Risk CY APR 03-04, 1996 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements RP Curtis, RE (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATL COUNCIL RADIATION PROTECTION MEASUREMENTS PI BETHESDA PA 7910 WOODMONT AVE, SUITE 1016, BETHESDA, MD 20814 BN 0-929600-55-X J9 P NAT C RAD PY 1997 IS 18 BP 79 EP 94 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BH87C UT WOS:A1997BH87C00006 ER PT B AU Gilbert, ES AF Gilbert, ES BE Boice, JD TI Combined analysis of studies of nuclear workers SO IMPLICATIONS OF NEW DATA ON RADIATION CANCER RISK SE PROCEEDINGS OF THE NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS LA English DT Proceedings Paper CT 32nd Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements on Implications of New Data on Radiation Cancer Risk CY APR 03-04, 1996 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements C1 BATTELLE MEM INST,PACIFIC NW LABS,RICHLAND,WA 99352. RP Gilbert, ES (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATL COUNCIL RADIATION PROTECTION MEASUREMENTS PI BETHESDA PA 7910 WOODMONT AVE, SUITE 1016, BETHESDA, MD 20814 BN 0-929600-55-X J9 P NAT C RAD PY 1997 IS 18 BP 97 EP 111 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BH87C UT WOS:A1997BH87C00007 ER PT B AU Inskip, PD Tekkel, M Rahu, M Veidebaum, T Hakulinen, T Auvinen, A Rytomaa, T Servomaa, K Obrams, GI Stengrevics, A Kesminiene, AZ Kurtinaitis, J Hartshorne, MF Littlefield, LG Salomaa, S Tucker, JD Bigbee, WL Jensen, RH Moloney, WC Boice, JD AF Inskip, PD Tekkel, M Rahu, M Veidebaum, T Hakulinen, T Auvinen, A Rytomaa, T Servomaa, K Obrams, GI Stengrevics, A Kesminiene, AZ Kurtinaitis, J Hartshorne, MF Littlefield, LG Salomaa, S Tucker, JD Bigbee, WL Jensen, RH Moloney, WC Boice, JD BE Boice, JD TI Studies of leukemia and thyroid disease among Chernobyl clean-up workers from the Baltics SO IMPLICATIONS OF NEW DATA ON RADIATION CANCER RISK SE PROCEEDINGS OF THE NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS LA English DT Proceedings Paper CT 32nd Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements on Implications of New Data on Radiation Cancer Risk CY APR 03-04, 1996 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements AB Following the reactor accident at Chernobyl (Ukraine) in late April of 1986, hundreds of thousands of men from throughout the former Soviet Union were sent to Chernobyl to entomb the damaged reactor, remove radioactive debris, and help decontaminate the local environment. They remained for an average of three months and were allowed to accumulate up to 25 cGy of radiation before being sent home. Doses for some workers may have exceeded the allowable limit. The experience of Chernobyl cleanup workers is potentially informative about cancer risks associated with protracted exposure to low levels of radiation. Cohorts of clean-up workers from the Baltic Republics were assembled for study, based on military records and other lists. The study population includes 4,833 men from Estonia, 5,709 from Latvia and at least 5,446 from Liahuania, where a pilot study is underway. They are being monitored for cancer incidence through linkages with the corresponding national cancer registries. Biodosimetric assays, including fluorescent in situ hybridization (FISH) for chromosome translocation analysis and the glycophorin A (GPA) somatic cell mutation assay, are being used to supplement information about radiation doses from worker records and questionnaires. Thyroid screening examinations, including palpation, ultrasound and, selectively, fine-needle aspiration biopsies were performed on nearly 2,000 workers in the Estonian cohort (mean age, 40 y) during the spring of 1995, nine years after the reactor accident. The study is still in progress. Work began first in Estonia, and results presented here pertain to this subgroup except as otherwise noted. The average age at the time of arrival at Chernobyl was 31 years. 62% were sent in 1986. The mean documented dose based on military or other records was 11 cGy. Results of FISH and GPA analyses do not indicate that the mean dose for the population was markedly higher than the average documented dose, but neither biomarker correlated well with documented dose for individual workers. Linkage with the Estonian Cancer Registry for the years 1986-93 identified zero cases of leukemia versus 1 expected, based on incidence rates for the general population. Two hundred and one of 1,979 cleanup workers examined by ultrasound (10.2%) had one or more thyroid nodules. Two of 77 biopsied nodules proved to be cancerous. Nodularity was significantly associated with age but not with documented dose, dates, duration or type of duty at Chernobyl. A nonsignificant positive association was observed between nodularity and the frequency of lymphocytes with chromosome translocations (p((1)) = 0.10). Possible reasons for the apparent absence or rarity of radiation-induced thyroid nodules include low and protracted doses, low susceptibility among men exposed as adults, and insufficient passage of time since the accident. C1 NCI,DIV CANC EPIDEMIOL & GENET,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD. RP Inskip, PD (reprint author), TEXAS A&M UNIV,COLL VET MED,DEPT VET ANAT & PUBL HLTH,COLLEGE STN,TX 77843, USA. RI Rahu, Mati/A-9981-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATL COUNCIL RADIATION PROTECTION MEASUREMENTS PI BETHESDA PA 7910 WOODMONT AVE, SUITE 1016, BETHESDA, MD 20814 BN 0-929600-55-X J9 P NAT C RAD PY 1997 IS 18 BP 123 EP 141 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BH87C UT WOS:A1997BH87C00009 ER PT B AU Lubin, JH AF Lubin, JH BE Boice, JD TI Studies of indoor radon and lung cancer risk SO IMPLICATIONS OF NEW DATA ON RADIATION CANCER RISK SE PROCEEDINGS OF THE NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS LA English DT Proceedings Paper CT 32nd Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements on Implications of New Data on Radiation Cancer Risk CY APR 03-04, 1996 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements RP Lubin, JH (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL COUNCIL RADIATION PROTECTION MEASUREMENTS PI BETHESDA PA 7910 WOODMONT AVE, SUITE 1016, BETHESDA, MD 20814 BN 0-929600-55-X J9 P NAT C RAD PY 1997 IS 18 BP 177 EP 194 PG 18 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BH87C UT WOS:A1997BH87C00012 ER PT B AU Bennett, WP AF Bennett, WP BE Boice, JD TI Does radiation cause molecular signatures? SO IMPLICATIONS OF NEW DATA ON RADIATION CANCER RISK SE PROCEEDINGS OF THE NATIONAL COUNCIL ON RADIATION PROTECTION AND MEASUREMENTS LA English DT Proceedings Paper CT 32nd Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements on Implications of New Data on Radiation Cancer Risk CY APR 03-04, 1996 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements RP Bennett, WP (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL COUNCIL RADIATION PROTECTION MEASUREMENTS PI BETHESDA PA 7910 WOODMONT AVE, SUITE 1016, BETHESDA, MD 20814 BN 0-929600-55-X J9 P NAT C RAD PY 1997 IS 18 BP 223 EP 227 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BH87C UT WOS:A1997BH87C00015 ER PT J AU Liao, XB Tang, Y Chattopadhyay, SK Hartley, JW Morse, HC AF Liao, XB Tang, Y Chattopadhyay, SK Hartley, JW Morse, HC TI Upregulation of Gfi-1, a gene involved in IL-2-independent growth of T cells, in a murine retrovirus-induced immunodeficiency syndrome SO IN VIVO LA English DT Article DE Gfi-1; lymphoma; MAIDS; protooncogenes; retroviral integration; transcriptional activation ID C57BL/6 MICE; B-CELLS; MAIDS; PROGRESSION; INFECTION; VIRUS; MOUSE; AIDS; INTERLEUKIN-2; ACTIVATION AB Background. A prominent feature of retrovirus-induced immunodeficiency in mice (MAIDS) is early polyclonal activation of CD4(+) T cells followed by the appearance of monoclonal lymphomas marked by clonal proviral integrations. These events appear to occur independent of interleukin-2 (IL-2), suggesting the activity of an alternative growth-promoting pathway. We studied the possible contributions to T cell expansion of a gene, Gfi-1, previously shown to confer IL-2 independence to rat T cell lymphomas. Materials. Results. Conclusions. We studied 17 mice with MAIDS that had clonal populations of T cells. Proviral integrations at Gfi-1 were detected in two animals. These integrations were associated with enhanced transcription of Gfi-1. Unexpectedly, elevated levels of Gfi-1 transcripts were also observed in four T cell lymphomas without detectable integrations at this locus. This suggests that IL-2-independent T cell growth in MAIDS may be driven by transcriptional activation of Gfi-1 by proviral insertion or transactivation. C1 NIAID, IMMUNOPATHOL LAB, NIH, BETHESDA, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 24 TC 6 Z9 6 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD JAN-FEB PY 1997 VL 11 IS 1 BP 9 EP 12 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WK185 UT WOS:A1997WK18500002 PM 9067766 ER PT J AU Ahmed, SF Oswald, IP Caspar, P Hieny, S Keefer, L Sher, A James, SL AF Ahmed, SF Oswald, IP Caspar, P Hieny, S Keefer, L Sher, A James, SL TI Developmental differences determine larval susceptibility to nitric oxide-mediated killing in a murine model of vaccination against Schistosoma mansoni SO INFECTION AND IMMUNITY LA English DT Article ID LUNG-STAGE; PROTECTIVE IMMUNITY; GLUCOSE-METABOLISM; CYTO-TOXICITY; IN-VITRO; MICE; MACROPHAGES; HELMINTHS; MIGRATION; PHASE AB A persistent paradox in our understanding of protective immunity against Schistosoma mansoni infection in animals vaccinated with attenuated parasites has been that attrition of challenge parasites occurs during migration through the lungs in vivo, although parasites recovered from the lungs appear to be relatively resistant to cytotoxic effector mechanisms in vitro. We have compared the susceptibilities of different stages of larvae to killing by nitric oxide (NO), which was previously shown to be involved in the larvicidal function of cytokine-activated cytotoxic effector cells, Lung-stage larvae obtained 1 week after infection were not killed in vitro by NO generated either by a chemical NO donor or by activated cells, In contrast, parasites obtained from the portal system of control mice or from the lungs of vaccinated mice 2.5 weeks following challenge infection were killed by NO. As previously shown for mammalian cell targets, the effects of NO in susceptible larval stages may involve enzymes required for aerobic energy metabolism, since similar cytotoxicity was demonstrated by chemical inhibitors of the citric acid cycle or mitochondrial respiration, Taken together with previous observations of enhanced Th1 activity and expression of NO synthase in the lungs of vaccinated mice at 2.5 weeks after challenge infection, these observations elucidate the immune mechanism of vaccine-induced resistance to S, mansoni infection, Moreover, they suggest that conversion to a less metabolically active state may allow pathogens to escape the effects of the important effector molecule NO. C1 NIAID,PARASITOL & INT PROGRAMS BRANCH,NIH,IMMUNOBIOL SECT,LAB PARASIT DIS,BETHESDA,MD 20892. NCI,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RI OSWALD, Isabelle/A-8497-2013; OI OSWALD, Isabelle/0000-0001-9918-277X NR 35 TC 42 Z9 45 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 JAN PY 1997 VL 65 IS 1 BP 219 EP 226 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WA609 UT WOS:A1997WA60900031 PM 8975915 ER PT S AU Buvat, I Bartlett, ML Kitsiou, AN Carson, JM Srinivasan, G Nour, KA Chen, CC Dilsizian, V Bacharach, SL AF Buvat, I Bartlett, ML Kitsiou, AN Carson, JM Srinivasan, G Nour, KA Chen, CC Dilsizian, V Bacharach, SL BE Duncan, J Gindi, G TI Using spatial-temporal images for analysis of gated cardiac tomographic data: The "M-mode" revisited SO INFORMATION PROCESSING IN MEDICAL IMAGING SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 15th International Conference on Information Processing in Medical Imaging CY JUN 09-13, 1997 CL GREEN MT COLL, POULTNEY, VERMONT HO GREEN MT COLL ID LEFT-VENTRICULAR FUNCTION; EMISSION TOMOGRAPHY; VALIDATION; PARAMETER AB Recent advances in SPECT and PET technology permit ECG gating of tomographic cardiac images, allowing simultaneous measurement of 3D cardiac ventricular function with perfusion/metabolism. Extracting indices of regional function from these 4D data sets (3D space + time) remains a challenge. All approaches currently used to quantitate gated tomographic sequences deal separately with the spatial and temporal data. As functional information is based on close coupling between spatial and temporal changes, it could be beneficial to produce an image combining spatial and temporal information. In this paper we describe a method for producing such spatial-temporal images and, using gated FDG PET data, test the ability of these images to improve visual and quantitative assessment of cardiac function. Other potential schemes to make use of the space-time nature of this new representation are also discussed. C1 CHU Pitie Salpetriere, U66 INSERM, CNRS, F-75634 Paris 13, France. NIH, Bethesda, MD 20892 USA. RP Buvat, I (reprint author), CHU Pitie Salpetriere, U66 INSERM, CNRS, 91 Bd Hop, F-75634 Paris 13, France. NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0302-9743 BN 3-540-63046-5 J9 LECT NOTES COMPUT SC PY 1997 VL 1230 BP 85 EP 98 PG 14 WC Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BK96M UT WOS:000073946600007 ER PT S AU Xu, CY Pham, DL Prince, JL AF Xu, CY Pham, DL Prince, JL BE Duncan, J Gindi, G TI Finding the brain cortex using fuzzy segmentation, isosurfaces, and deformable surface models SO INFORMATION PROCESSING IN MEDICAL IMAGING SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT 15th International Conference on Information Processing in Medical Imaging CY JUN 09-13, 1997 CL GREEN MT COLL, POULTNEY, VT HO GREEN MT COLL AB A method for finding the cortical surface of the brain from magnetic resonance images using a combination of fuzzy segmentation, isosurface extraction, and a deformable surface is presented. After MR images are acquired and preprocessed to remove extracranial tissue, fuzzy membership functions for gray matter, white matter, and cerebrospinal fluid are computed. An iterative procedure using isosurfaces of filtered white matter membership functions is then used to obtain a topologically correct estimate of the cortical surface. This estimate forms the initialization of a deformable surface, which is then allowed to converge to peaks of the gray matter membership function. We demonstrate the results of each step and show the final parameterized map of the medial layer of the cortex. C1 Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. NIA, GRC, LPC, NIH, Baltimore, MD 21224 USA. RP Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 NR 12 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-63046-5 J9 LECT NOTES COMPUT SC PY 1997 VL 1230 BP 399 EP 404 PG 6 WC Computer Science, Theory & Methods; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BK96M UT WOS:000073946600033 ER PT S AU Carter, CS Altemus, M AF Carter, CS Altemus, M BE Carter, CS Lederhendler, II Kirkpatrick, B TI Integrative functions of lactational hormones in social behavior and stress management SO INTEGRATIVE NEUROBIOLOGY OF AFFILIATION SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference of the New-York-Academy-of-Sciences on the Integrative Neurobiology of Affiliation CY MAR 14-17, 1996 CL WASHINGTON, D.C. SP New York Acad Sci, NIMH, MICHHD, Natl Sci Fdn ID CORTICOTROPIN-RELEASING-FACTOR; MATERNAL-BEHAVIOR; MALE-RATS; OXYTOCIN INCREASES; SEXUAL-BEHAVIOR; PLASMA OXYTOCIN; VASOPRESSIN; STIMULATION; SECRETION; PROLACTIN C1 NIMH, CLIN SCI LAB, NIH, BETHESDA, MD 20892 USA. RP Carter, CS (reprint author), UNIV MARYLAND, DEPT ZOOL, COLLEGE PK, MD 20742 USA. FU NICHD NIH HHS [HD 16679]; NIMH NIH HHS [MH 45836] NR 78 TC 123 Z9 124 U1 2 U2 14 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-059-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 807 BP 164 EP 174 DI 10.1111/j.1749-6632.1997.tb51918.x PG 11 WC Behavioral Sciences; Multidisciplinary Sciences SC Behavioral Sciences; Science & Technology - Other Topics GA BJ17S UT WOS:A1997BJ17S00009 PM 9071349 ER PT S AU Witt, DM AF Witt, DM BE Carter, CS Lederhendler, II Kirkpatrick, B TI Regulatory mechanisms of oxytocin-mediated sociosexual behavior SO INTEGRATIVE NEUROBIOLOGY OF AFFILIATION SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference of the New-York-Academy-of-Sciences on the Integrative Neurobiology of Affiliation CY MAR 14-17, 1996 CL WASHINGTON, D.C. SP New York Acad Sci, NIMH, MICHHD, Natl Sci Fdn ID VENTROMEDIAL HYPOTHALAMIC NUCLEUS; FEMALE PRAIRIE VOLES; SEXUAL-BEHAVIOR; MICROTUS-OCHROGASTER; MALE-RATS; C-FOS; RECEPTOR-BINDING; PREOPTIC AREA; MESSENGER-RNA; PARAVENTRICULAR NUCLEUS C1 NINCDS, NEUROCHEM LAB, NIH, BETHESDA, MD 20892 USA. NR 80 TC 33 Z9 33 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-059-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 807 BP 287 EP 301 DI 10.1111/j.1749-6632.1997.tb51927.x PG 15 WC Behavioral Sciences; Multidisciplinary Sciences SC Behavioral Sciences; Science & Technology - Other Topics GA BJ17S UT WOS:A1997BJ17S00018 PM 9071358 ER PT S AU Malkova, L Mishkin, M Suomi, SJ Bachevalier, J AF Malkova, L Mishkin, M Suomi, SJ Bachevalier, J BE Carter, CS Lederhendler, II Kirkpatrick, B TI Socioemotional behavior in adult rhesus monkeys after early versus late lesions of the medial temporal lobe SO INTEGRATIVE NEUROBIOLOGY OF AFFILIATION SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference of the New-York-Academy-of-Sciences on the Integrative Neurobiology of Affiliation CY MAR 14-17, 1996 CL WASHINGTON, D.C. SP New York Acad Sci, NIMH, MICHHD, Natl Sci Fdn ID MEMORY C1 NICHHD, COMPARAT ETHOL LAB, BETHESDA, MD 20892 USA. UNIV TEXAS, SCH MED, DEPT ANAT & NEUROBIOL, HOUSTON, TX 77030 USA. RP Malkova, L (reprint author), NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20982 USA. NR 5 TC 25 Z9 25 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-059-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 807 BP 538 EP 540 DI 10.1111/j.1749-6632.1997.tb51961.x PG 3 WC Behavioral Sciences; Multidisciplinary Sciences SC Behavioral Sciences; Science & Technology - Other Topics GA BJ17S UT WOS:A1997BJ17S00052 PM 9071392 ER PT S AU Newman, JD Bernhards, DE AF Newman, JD Bernhards, DE BE Carter, CS Lederhendler, II Kirkpatrick, B TI The affiliative vocal subsystem of squirrel monkeys SO INTEGRATIVE NEUROBIOLOGY OF AFFILIATION SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference of the New-York-Academy-of-Sciences on the Integrative Neurobiology of Affiliation CY MAR 14-17, 1996 CL WASHINGTON, D.C. SP New York Acad Sci, NIMH, MICHHD, Natl Sci Fdn ID SAIMIRI-SCIUREUS RP Newman, JD (reprint author), NICHHD, COMPARAT ETHOL LAB, NIH, POOLESVILLE, MD 20837 USA. NR 7 TC 2 Z9 2 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-059-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 807 BP 546 EP 548 DI 10.1111/j.1749-6632.1997.tb51964.x PG 3 WC Behavioral Sciences; Multidisciplinary Sciences SC Behavioral Sciences; Science & Technology - Other Topics GA BJ17S UT WOS:A1997BJ17S00055 PM 9071395 ER PT S AU Pieper, JO Forester, DC Elmer, GI AF Pieper, JO Forester, DC Elmer, GI BE Carter, CS Lederhendler, II Kirkpatrick, B TI Mice show strain differences in social affiliation - Implications for open field behavior SO INTEGRATIVE NEUROBIOLOGY OF AFFILIATION SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference of the New-York-Academy-of-Sciences on the Integrative Neurobiology of Affiliation CY MAR 14-17, 1996 CL WASHINGTON, D.C. SP New York Acad Sci, NIMH, MICHHD, Natl Sci Fdn ID INBRED STRAINS C1 TOWSON STATE UNIV, DEPT BIOL, TOWSON, MD 21204 USA. RP Pieper, JO (reprint author), NIDA, ADDICT RES CTR, BEHAV PHARMACOL & GENET SECT, POB 5180, BALTIMORE, MD 21224 USA. NR 4 TC 3 Z9 3 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-059-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1997 VL 807 BP 552 EP 555 DI 10.1111/j.1749-6632.1997.tb51966.x PG 4 WC Behavioral Sciences; Multidisciplinary Sciences SC Behavioral Sciences; Science & Technology - Other Topics GA BJ17S UT WOS:A1997BJ17S00057 PM 9071396 ER PT S AU Rhee, SG Bae, YS AF Rhee, SG Bae, YS BE Heilmeyer, L TI Regulation of phospholipase C isozymes SO INTERACTING PROTEIN DOMAINS: THEIR ROLE IN SIGNAL AND ENERGY TRANSDUCTION SE NATO ADVANCED SCIENCE INSTITUTES SERIES, SERIES H, CELL BIOLOGY LA English DT Proceedings Paper CT NATO Advanced Study Institute on Structure and Function of Interacting Protein Domains in Signal and Energy Transduction CY SEP 10-19, 1996 CL MARATEA, ITALY SP NATO Adv Study Inst C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1010-8793 BN 3-540-63124-0 J9 NATO ADV SCI I H-CEL PY 1997 VL 102 BP 87 EP 92 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BL41T UT WOS:000075441300014 ER PT J AU Seder, RA Prussin, C AF Seder, RA Prussin, C TI Are differentiated human T helper cells reversible? SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Allergy-A Disease of Modern Society Meeting CY SEP 06-11, 1996 CL SALZBURG, AUSTRIA DE CD4+; T cell differentiation; IL-4; IL-12; Th1 cells; Th2 cells ID TH2 AB Cytokines and cytokine antagonists have important roles in controlling the type of immune response generated. These mediators have the most profound effects if used at the initiation of an immune response. For example, IL-4 and IL-12 are important determinants in the generation of Th1 and Th2 cells, respectively, in both murine and human systems. One critical question that relates to human pathogenesis is whether Th1- and Th2-type cells can be altered after disease is initiated. Data will be presented showing how cytokines can change the types of cytokines produced from established Th1 and Th2 cells. Moreover, intracellular staining of cytokines was done to more accurately define whether cytokine production was altered on a single cell basis. These studies may have implications for immune manipulation for established allergic or autoimmune diseases. C1 NIAID,LAB ALLERGY DIS,NIH,BETHESDA,MD 20892. RP Seder, RA (reprint author), NIAID,CLIN INVEST LAB,LYMPHOKINE REGULAT UNIT,NIH,BLDG 10,ROOM 11C215,BETHESDA,MD 20892, USA. OI Prussin, Calman/0000-0002-3917-3326 NR 5 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 1997 VL 113 IS 1-3 BP 163 EP 166 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA WV647 UT WOS:A1997WV64700041 PM 9130511 ER PT J AU Nagata, H Okada, T Worobec, AS Semere, T Metcalfe, DD AF Nagata, H Okada, T Worobec, AS Semere, T Metcalfe, DD TI c-kit mutation in a population of patients with mastocytosis SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Allergy-A Disease of Modern Society Meeting CY SEP 06-11, 1996 CL SALZBURG, AUSTRIA DE mast cells; mastocytosis; stem cell factor; c-kit ID PERIPHERAL-BLOOD; POINT MUTATION; MAST-CELLS; LINE AB The c-kil Asp816Val activating mutation is found in all patients with mastocytosis with an associated hematologic disorder, and at least in a subset of patients with indolent mastocytosis. The case of an 11-month-old child is presented who was categorized as having indolent mastocytosis, and where the Asp816Val mutation was identified in lesional skin, but not in bone marrow or in peripheral blood mononuclear cell populations. The significance of these findings is discussed. C1 NIAID,LAB ALLERG DIS,NIH,BETHESDA,MD 20892. CHIBA UNIV,SCH MED,DEPT OTOLARYNGOL,CHIBA 260,JAPAN. AICHI MED UNIV,DEPT PHYSIOL,AICHI,JAPAN. NR 7 TC 62 Z9 62 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PY 1997 VL 113 IS 1-3 BP 184 EP 186 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA WV647 UT WOS:A1997WV64700047 PM 9130517 ER PT B AU Brigger, P Bacharach, S Aldroubi, A Unser, M AF Brigger, P Bacharach, S Aldroubi, A Unser, M GP IEEE SIGNAL PROC SOC TI Segmentation of gated SPECT images for automatic computation of myocardial volume and ejection fraction SO INTERNATIONAL CONFERENCE ON IMAGE PROCESSING - PROCEEDINGS, VOL II LA English DT Proceedings Paper CT International Conference on Image Processing CY OCT 26-29, 1997 CL SANTA BARBARA, CA SP IEEE Signal Proc Soc AB We describe an image processing system for the automatic assessment of ejection fraction (EF)from noisy SPECT left ventricular myocardial perfusion images. A segmentation scheme consisting of an elliptical coordinate transformation, matched filtering and dynamic contour tracking detects the endo- and epicardia boundaries. Computation of EF is performed based on the epi-rather than the endo-cardial boundary, which proves to be more robust for images with low signal-to-noise ratios. The computation incorporates anatomical constraints of constant myocardial mass and smooth cardiac variation. The algorithm was tested on different image modalities and shows good linear agreement with EFs obtained from conventional approaches based on planar gated blood pool imaging (PET: y=8.7+1.07x, r=0.84, Technetium-99m MIBI SPECT: y=5.0+0.80x, r=0.90, Thallium-201 SPECT: y=23.5+0.82x, r=0.77, RMS error = 10.0). The proposed scheme may be an alternative for EF computation without the need for additional image acquisitions. RP Brigger, P (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3W13,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU I E E E, COMPUTER SOC PRESS PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, LOS ALAMITOS, CA 90720 BN 0-8186-8183-7 PY 1997 BP 113 EP 116 DI 10.1109/ICIP.1997.638686 PG 4 WC Computer Science, Information Systems; Computer Science, Theory & Methods; Engineering, Electrical & Electronic; Optics SC Computer Science; Engineering; Optics GA BJ90B UT WOS:A1997BJ90B00029 ER PT J AU Fukushima, A Lai, JC Chanaud, NP Shiloach, J Whitcup, SM Nussenblatt, RB Gery, I AF Fukushima, A Lai, JC Chanaud, NP Shiloach, J Whitcup, SM Nussenblatt, RB Gery, I TI Permissive recognition of immunodominant determinants of the retinal S-antigen in different rat strains, primates and humans SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE antigenic peptides; autoimmunity; experimental autoimmune uveoretinitis; immunopathogenic antigens; intraocular inflammation (uveitis); lymphocyte proliferation; MHC polymorphism ID MYELIN BASIC-PROTEIN; T-CELL EPITOPE; MAJOR HISTOCOMPATIBILITY COMPLEX; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS PATIENTS; CLASS-II MOLECULES; MHC CLASS-II; IMMUNE RESPONSIVENESS; IMMUNOGENIC PEPTIDES; UVEITIS PATIENTS AB The majority of antigenic peptides exhibit restriction in their interaction with the MHC molecules on antigen-presenting cells of different haplotypes, Certain peptides, however, are 'permissive': they bind strongly to different MHC molecules and are selected as the immunodominant epitopes by animals using these MHC gene products, Here we show for the first time that several peptides from four regions of the sequence of human S-antigen (H-SAS), a retinal-specific protein, demonstrate high levels of permissiveness, Each of these peptides was found to be immunodominant in at least some of four inbred rat strains and five cynomolgus monkeys, immunized with whole H-SAg, Moreover, some of these peptides were recognized by lymphocytes from four normal controls and four patients with uveitis who responded against the H-SAg molecule. On the other hand, the permissive peptides stimulated marginal or no response in cultures of Lewis rats injected with adjuvant alone, or rat and human cell lines specific to other antigens, thus demonstrating that these peptides do not carry any non-specific mitogenic activity, One peptide, 29, which was found immunodominant in the monkeys, the uveitis patients and Lewis rats, is highly immunopathogenic in this rat strain, No good correlation between immunodominance and immunopathogenicity was found with other H-SAg peptides, The finding of cross-species permissiveness among peptides of H-SAg and similar observations with myelin proteins suggest that permissiveness could be quite prevalent among peptides of immunopathogenic antigens. C1 NEI,NIH,BETHESDA,MD 20892. KOCHI MED SCH,DEPT OPHTHALMOL,NANKOKU,KOCHI 783,JAPAN. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20814. NIDDKD,NIH,BETHESDA,MD 20892. NR 46 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JAN PY 1997 VL 9 IS 1 BP 169 EP 177 DI 10.1093/intimm/9.1.169 PG 9 WC Immunology SC Immunology GA WH028 UT WOS:A1997WH02800017 PM 9043958 ER PT J AU Pennington, JAT Schoen, SA AF Pennington, JAT Schoen, SA TI Total diet study: Estimated dietary intakes of nutritional elements, 1982-1991 (vol, 66, pg 350, 1996) SO INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH LA English DT Correction, Addition RP Pennington, JAT (reprint author), NIDDK,DIV NUTR RES COORDINAT,NIH,NATCHER BLDG,ROOM 5AN32A,45 CTR DR,MSC 6600,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU VERLAG HANS HUBER PI BERN 9 PA LANGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND SN 0300-9831 J9 INT J VITAM NUTR RES JI Int. J. Vitam. Nutr. Res. PY 1997 VL 67 IS 3 BP 207 EP 207 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XD621 UT WOS:A1997XD62100013 ER PT J AU Pennington, JAT Schoen, SA AF Pennington, JAT Schoen, SA TI Contributions of food groups to estimated intakes of nutritional elements: Results from the FDA total diet studies, 1982-1991 (vol 66, pg 342, 1996) SO INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH LA English DT Correction, Addition DE food groups; dietary Intakes; US Food and Drug Administration; Nutrients, Na, K, I; Ca, Mg, Mn, Fe; Zn, Cu, Se, P RP Pennington, JAT (reprint author), NIDDK,DIV NUTR RES COORDINAT,NIH,NATCHER BLDG,ROOM 5AN32A,45 CTR DR,MSC 6600,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU VERLAG HANS HUBER PI BERN 9 PA LANGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND SN 0300-9831 J9 INT J VITAM NUTR RES JI Int. J. Vitam. Nutr. Res. PY 1997 VL 67 IS 3 BP 207 EP 207 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XD621 UT WOS:A1997XD62100012 ER PT J AU Buto, S Ghirelli, C Aiello, P Tagliabue, E Ardini, E Magnifico, A Montuori, N Sobel, ME Colnaghi, MI Menard, S AF Buto, S Ghirelli, C Aiello, P Tagliabue, E Ardini, E Magnifico, A Montuori, N Sobel, ME Colnaghi, MI Menard, S TI Production and characterization of monoclonal antibodies directed against the laminin receptor precursor SO INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS LA English DT Article DE 67-kDa laminin receptor; 67LR 37-kDa precursor of the laminin receptor; 37LRP monoclonal antibodies; MAbs ID BINDING PROTEIN; MESSENGER-RNA; EXPRESSION; CARCINOMAS; CELLS AB The 67-kDa laminin receptor (67LR) is an important tumor marker whose molecular structure has not yet been fully elucidated. To shed new light on this molecule, we raised a series of eight new monoclonal antibodies, designated MPLR1 to 8, directed against the 37-kDa recombinant laminin receptor precursor (37LRP). Cross-competition experiments demonstrated that the epitopes recognized by MPLR2, 4 and 5 partially overlap, since MPLR4 and 5 compete with labelled MPLR2 for the binding to recombinant 37LRP. These three antibodies belong to the IgG1 class, whereas the other ones are all IgM. Presumably due to the fact that they are directed against partially unfolded antigenic determinants expressed on the recombinant protein, MPLRs did not recognize the native protein. Indeed, they showed no reactivity at the membrane level in cytofluorimetric analysis and they did not work in immunoprecipitation experiments. In contrast, these reagents are valuable tools in immunoblotting, since they clearly identify a 67-kDa protein (the mature laminin receptor) in addition to the 37-kDa precursor form. MPLRs are thus a new powerful tool which could help in the characterization of the still enigmatic 67LR molecule. C1 IST NAZL STUDIO & CURA TUMORI,DIV EXPT ONCOL E,I-20133 MILAN,ITALY. NCI,PATHOL LAB,MOL PATHOL SECT,BETHESDA,MD 20892. RI Montuori, Nunzia/J-8542-2013; Tagliabue, Elda/B-9377-2017; OI Tagliabue, Elda/0000-0001-9877-2903; Montuori, Nunzia/0000-0001-8697-986X NR 12 TC 12 Z9 12 U1 0 U2 1 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0393-6155 J9 INT J BIOL MARKER JI Int. J. Biol. Markers PD JAN-MAR PY 1997 VL 12 IS 1 BP 1 EP 5 PG 5 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA XB852 UT WOS:A1997XB85200001 PM 9176710 ER PT J AU Petersen, E Potter, K Butler, J Fishbein, KW Horton, W Spencer, RGS McFarland, EW AF Petersen, E Potter, K Butler, J Fishbein, KW Horton, W Spencer, RGS McFarland, EW TI Bioreactor and probe system for magnetic resonance microimaging and spectroscopy of chondrocytes and neocartilage SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY LA English DT Article ID CARTILAGE; DESIGN AB We have developed a nuclear magnetic resonance (NMR)-compatible hollow fiber chondrocyte bioreactor (HFBR), permitting the noninvasive study of neocartilage under conditions optimized for cell growth and matrix expression. The system was used to investigate the properties of neocartilage which developed from embryonic chick chondrocytes. Histologic studies performed 30 days after inoculation of the HFBR with chondrocytes showed cartilage growth units demarcated by stromal layers surrounding each fiber, the tissue itself was highly cellular with abundant proteoglycan content. Spin-density, spin-lattice, and spin-spin relaxation and magnetization transfer contrast images revealed heterogeneous tissue with NMR properties that correlated well with histologic data. It was found that the apparent free water content of the neocartilage was greater than that seen in mature cartilage, even in regions of relatively low cell density. The bioenergetic profile of the cells in culture was monitored with P-31-NMR spectroscopy, and the presence of phosphocreatine was clearly demonstrated. Overall metabolic stability was confirmed between days 10 and 17 after inoculation. A significant decrease in intracellular pH with time was observed during early development of the chondrocyte system. (C) 1997 John Wiley & Sons, Inc. C1 UNIV CALIF SANTA BARBARA,DEPT CHEM ENGN,SANTA BARBARA,CA 93106. NIA,NUCL MAGNET RESONANCE UNIT,NIH,BALTIMORE,MD 21224. NIA,BIOL CHEM LAB,NIH,BALTIMORE,MD 21224. RI McFarland, Eric/G-1763-2014; OI Fishbein, Kenneth/0000-0002-6353-4603 NR 19 TC 17 Z9 18 U1 0 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-9457 J9 INT J IMAG SYST TECH JI Int. J. Imaging Syst. Technol. PY 1997 VL 8 IS 3 BP 285 EP 292 DI 10.1002/(SICI)1098-1098(1997)8:3<285::AID-IMA6>3.0.CO;2-6 PG 8 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA XE661 UT WOS:A1997XE66100006 ER PT J AU Shkarin, P Spencer, RGS AF Shkarin, P Spencer, RGS TI Time domain simulation of Fourier imaging by summation of isochromats SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY LA English DT Article ID SPIN ECHOES AB We have developed a time-domain simulation of two-dimensional Fourier imaging in which the signal is represented by a finite Fourier series. Each term corresponds to a spin isochromat and has a coefficient that evolves in response to radiofrequency and gradient pulses, and periods of free precession. An explicit calculation is performed to derive the number of isochromats required to achieve a specified degree of precision, permitting accurate results to be obtained in an efficient fashion. With this, the time-domain signal throughout the entire experiment is calculated. The resulting time domain data is combined into the standard k-space matrix and yields an image after two-dimensional Fourier transformation. Multiple-shot sequences such as spin warp and single-shot experiments such as Burst are simulated in the same fashion. Our procedure makes no assumptions about transverse dephasing between pulses, so that complicated sequences of direct and stimulated echoes are correctly modeled. The influence of spin-spin and spin-lattice relaxation is included in a natural way. A number of artifacts can be quantitatively reproduced. (C) 1997 John Wiley & Sons, Inc. C1 NIA, NIH, GRC 4D08, BALTIMORE, MD 21224 USA. NR 12 TC 14 Z9 14 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-9457 J9 INT J IMAG SYST TECH JI Int. J. Imaging Syst. Technol. PY 1997 VL 8 IS 5 BP 419 EP 426 DI 10.1002/(SICI)1098-1098(1997)8:5<419::AID-IMA1>3.0.CO;2-D PG 8 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA XW388 UT WOS:A1997XW38800001 ER PT J AU Hahn, SM Sullivan, FJ DeLuca, AM Sprague, M Hampshire, VA Krishna, MC Russo, A Mitchell, JB AF Hahn, SM Sullivan, FJ DeLuca, AM Sprague, M Hampshire, VA Krishna, MC Russo, A Mitchell, JB TI Protection of mitomycin C induced skin extravasation with the nitroxide, 3-carbamoyl-PROXYL (3-CP) SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE nitroxide; mitomycin-C; extravasation; skin; swine; 3-CP ID DIMETHYL-SULFOXIDE; CYTOTOXICITY; PREVENTION; INJURIES; NECROSIS; ULCERS; OXYGEN; DAMAGE; TEMPOL; DMSO AB Extravasation tissue injury from chemotherapeutic drugs is a serious clinical problem. A swine model has been useful for studying skin extravasation and evaluating potential antidotes. Mitomycin C (MMC) skin extravasation was studied. Nitroxides, a class of compounds which are protective against a variety of oxidative stresses in vitro, including MMC, were tested as antidotes. Miniature swine were anesthetized and given intradermal (ID) injections of MMC. MMC alone caused skin necrosis and ulceration. Several nitroxides were screened as protectors of MMC induced skin necrosis. 3-carbamoyl-PROXYL (3-CP) was the lone nitroxide which protected if given 5 min after extravasation. Administration of 3-CP 10 min after MMC injection was not protective. In vitro studies with monolayered V79 cells showed that 3-CP had a direct protective effect against MMC cytotoxicity in a concentration-dependent fashion. Therefore, in the swine model doses of 3-CP ranging from 25-100 mM were tested and found to protect against MMC skin necrosis 90 days after injection. Histologic sections of the 3-CP- and MMC-treated pig skin showed a marked reduction in the degree of acute inflammation and the absence of deep dermal scarring when compared to MMC alone. C1 NCI,RADIAT BIOL BRANCH,DIV CLIN SCI,BETHESDA,MD 20892. TRIPLER ARMY MED CTR,DEPT RADIAT ONCOL,HONOLULU,HI 96859. NIH,VET RESOURCES PROGRAM,NATL CTR RES RESOURCES,BETHESDA,MD 20892. NR 34 TC 6 Z9 6 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JAN PY 1997 VL 10 IS 1 BP 119 EP 123 PG 5 WC Oncology SC Oncology GA WA196 UT WOS:A1997WA19600018 PM 21533354 ER PT J AU Simon, A Nagel, D Kitchen, BJ Bode, U AF Simon, A Nagel, D Kitchen, BJ Bode, U TI Clinical relevance of etoposide (VP-16) pharmacokinetics in children and adults SO INTERNATIONAL JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY LA English DT Review DE etoposide; pharmacokinetics; children ID HIGH-DOSE ETOPOSIDE; BONE-MARROW TRANSPLANTATION; CELL LUNG-CANCER; CONTINUOUS-INFUSION ETOPOSIDE; REFRACTORY SOLID TUMORS; PHASE-I TRIAL; TOTAL-BODY IRRADIATION; ORAL ETOPOSIDE; ANTICANCER DRUGS; UNBOUND ETOPOSIDE AB A review of etoposide (VP-16) pharmacokinetics (PK) was undertaken to summarize the published data for pediatric patients in particular. While the PK of VP-16 in children has been studied only after intravenous (TV) administration, data from adults have been collected after IV, intraperitoneal, intrapleural, intraarterial and oral administration of the drug. As broad information about VP-16 PK in adults is available, the established pharmacokinetic profile is presented. The knowledge of VP-16 PK in children is scanty, although some studies include pediatric patients. While available results suggest that VP-16 distribution and elimination are independent of dose and schedule of administration, data detailing the influence of age on these parameters are still lacking. Moreover, studies of the degree of protein binding of VP-16 in children have not been published yet, although a recent study suggested a correlation between patient's age and the degree of plasma protein binding. A significant delay of elimination or increase in systemic toxicity after the administration of standard doses to patients with impaired renal function has not been documented yet, although renal clearance accounts for more than 35% of total body clearance in most studies. Recommendations for dose reductions in patients with impaired renal function are preliminary and should be the focus of,further investigations in all age groups. According to studies in adults, hepatobiliary clearance of VP-16 is of minor importance. Thus, recommendations to reduce the VP-16 dose in patients with liver dysfunction are not supported by changes in PK but by the genuine hepa totoxicity of the drug. Recent studies confirm that the liver cytochrome P450-3A4 is the dominant enzyme pathway of VP-16 metabolism. Four metabolites of VP-16 have been identified in vivo, two of which are cytotoxic in vitro. Pharmacokinetic data for these metabolites are not available. The interaction of VP-16 with other plasma components is of clinical importance. Studies in adults show an increased free fraction of VP-16 in patients with concomitant hyperbilirubinemia or hypoalbuminemia. In children and adults VP-16 elimination is accelerated following treatment with anticonvulsants. As the use of the commercially available preparation may cause dose-independent hyper sensitivity reactions secondary to its solvents, recent efforts have resulted in a hydrophilic derivative, VP-16 phosphate. First studies demonstrate unchanged PK and a lower incidence of hypersensitivity reactions than the parent compound. A first glance of the reviewed data describing VP-16 PK does not suggest major differences between juvenile and adult patients. Further studies on the issues mentioned should confirm these assumptions. These results could also contribute to the concept of drug monitoring as a suggested optimization of VP-16 tumoricidal efficacy. C1 UNIV BONN,DEPT PEDIAT HEMATOL ONCOL,D-53113 BONN,GERMANY. NCI,NIH,BETHESDA,MD 20892. NR 134 TC 1 Z9 1 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1070-2903 J9 INT J PEDIAT HEM ONC JI Int. J. Pediatr. Hematol-Oncol. PY 1997 VL 4 IS 4 BP 401 EP 414 PG 14 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA YE853 UT WOS:A1997YE85300011 ER PT J AU Chanock, SJ AF Chanock, SJ TI A review of antibacterial and antifungal therapy in the febrile child with neutropenia induced by antineoplastic therapy SO INTERNATIONAL JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY LA English DT Article; Proceedings Paper CT 15th Congress of the European-Society-for-Paediatric-Haematology-and-Immunology CY AUG 23-26, 1995 CL BINGEN, GERMANY SP European Soc Paediat Haematol & Immunol DE antibacterial therapy; antifungal therapy; fever; neutropenia ID GRANULOCYTOPENIC CANCER-PATIENTS; EMPIRIC ANTIBIOTIC-THERAPY; PATIENTS RECEIVING CIPROFLOXACIN; ANTI-MICROBIAL MODULATION; AMPHOTERICIN-B; ACUTE-LEUKEMIA; DOUBLE-BLIND; TRIMETHOPRIM-SULFAMETHOXAZOLE; FUNGAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS AB The rational use of antibiotic therapy in children at risk for a severe, life-threatening infection represents one of the major advances in the supportive care of children undergoing antineoplastic therapy. in particular, this success is apparent in the approach toward the child with fever and neutropenia, induced by myelosuppressive therapy. This review discusses the empirical use of antibacterial and antifungal therapy and addresses the basis of modifications in therapy. The ability to support patients through periods of high risk, such as profound neutropenia, has led to an increase in the number of patients treated. Consequently, this increase in the population at risk requires a familiarity with the subtleties of the decisions when to start, modify and terminate therapy. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Pediat Oncol Branch, NIH, 10-13N240, Bethesda, MD 20892 USA. NR 96 TC 0 Z9 0 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1070-2903 J9 INT J PEDIAT HEM ONC JI Int. J. Pediatr. Hematol-Oncol. PY 1997 VL 4 IS 5 BP 459 EP 472 PG 14 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA YQ954 UT WOS:000071441900004 ER PT J AU Adamson, PC Poplack, DG AF Adamson, PC Poplack, DG TI Pharmacokinetic variability and apparent drug resistance SO INTERNATIONAL JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY LA English DT Article DE pharmacokinetics; drug resistance ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; MERCAPTOPURINE METABOLISM; CHILDHOOD LEUKEMIA; MENINGEAL LEUKEMIA; THIOPURINE METHYLTRANSFERASE; SYSTEMIC EXPOSURE; DOSE INTENSITY; PHASE-I; 6-MERCAPTOPURINE C1 NCI, Pharmacol & Expt Therapeut Sect, Pediat Branch, Bethesda, MD 20892 USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. RP Adamson, PC (reprint author), NCI, Pharmacol & Expt Therapeut Sect, Pediat Branch, Bldg 10,Room 13N240,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 49 TC 0 Z9 0 U1 1 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1070-2903 J9 INT J PEDIAT HEM ONC JI Int. J. Pediatr. Hematol-Oncol. PY 1997 VL 4 IS 6 BP 525 EP 530 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA ZB137 UT WOS:000072440100002 ER PT J AU Martinez, RA AF Martinez, RA TI Addressing Murphy's law in health care policy: A responsibility for physicians SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Editorial Material RP Martinez, RA (reprint author), NIMH,5600 FISHERS LANE,PARKLAWN 18-101,ROCKVILLE,MD 20857, USA. NR 4 TC 2 Z9 2 U1 1 U2 1 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 1997 VL 27 IS 3 BP 293 EP 296 PG 4 WC Psychiatry SC Psychiatry GA YG579 UT WOS:A1997YG57900009 PM 9565730 ER PT J AU Fitzek, M Thornton, A Rabenow, J Lev, M Pardo, F Bussiere, M Braun, I Finklestein, D Hochberg, F Cosgrove, GR Okunieff, P Munzenrider, J Liebsch, N Harsh, G AF Fitzek, M Thornton, A Rabenow, J Lev, M Pardo, F Bussiere, M Braun, I Finklestein, D Hochberg, F Cosgrove, GR Okunieff, P Munzenrider, J Liebsch, N Harsh, G TI Results of 90 Gy proton/photon radiation therapy for glioblastoma multiforme SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT DIAGNOST RADIOL,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT BIOSTAT,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA. NATL CANC INST,RADIAT ONCOL BRANCH,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 1997 VL 39 IS 2 SU S BP 139 EP 139 DI 10.1016/S0360-3016(97)80566-4 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XW280 UT WOS:A1997XW28000092 ER PT J AU Kim, CY Tsai, MH Osmanian, C Calkins, DP Graeber, TG Greenspan, DL Kennedy, AS Rinker, LH Varia, MA DiPaolo, JA Peehl, DM Raleigh, JA Giaccia, AJ AF Kim, CY Tsai, MH Osmanian, C Calkins, DP Graeber, TG Greenspan, DL Kennedy, AS Rinker, LH Varia, MA DiPaolo, JA Peehl, DM Raleigh, JA Giaccia, AJ TI The role of hypoxia, p53, and apoptosis in human cervical carcinoma pathogenesis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract C1 STANFORD UNIV,SCH MED,DEPT RADIAT ONCOL,STANFORD,CA 94305. STANFORD UNIV,SCH MED,DEPT UROL,STANFORD,CA 94305. UNIV N CAROLINA,SCH MED,DEPT RADIAT ONCOL,CHAPEL HILL,NC 27599. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. NCI,BIOL LAB,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 1997 VL 39 IS 2 SU S BP 206 EP 206 DI 10.1016/S0360-3016(97)80701-8 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XW280 UT WOS:A1997XW28000224 ER PT J AU Tao, ML Weiss, RE Guo, MD Byrne, J Mills, JL Robison, LL Zeltzer, LK AF Tao, ML Weiss, RE Guo, MD Byrne, J Mills, JL Robison, LL Zeltzer, LK TI The relationship between CNS prophylactic treatment and smoking behavior in adult survivors of childhood leukemia: A National Cancer Institute and Childrens Cancer Group (NCI/CCG) study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. NCI,BETHESDA,MD 20892. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 1997 VL 39 IS 2 SU S BP 233 EP 233 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XW280 UT WOS:A1997XW28000278 ER PT J AU Meredith, R Alvarez, R Partridge, E Khazaeli, MB Grizzle, W Schlom, J LoBuglio, A AF Meredith, R Alvarez, R Partridge, E Khazaeli, MB Grizzle, W Schlom, J LoBuglio, A TI Enhanced intraperitoneal radioimmunotherapy with adjuvant interferon and taxol SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract C1 UNIV ALABAMA,CTR COMPREHENS CANC,TUSCALOOSA,AL 35487. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 1997 VL 39 IS 2 SU S BP 303 EP 303 DI 10.1016/S0360-3016(97)80892-9 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XW280 UT WOS:A1997XW28000416 ER PT J AU Carle, P Whitcomb, RF Hackett, KJ Tully, JG Rose, DL Bove, JM Henegar, RB Konai, M Williamson, DL AF Carle, P Whitcomb, RF Hackett, KJ Tully, JG Rose, DL Bove, JM Henegar, RB Konai, M Williamson, DL TI Spiroplasma diabroticae sp nov, from the Southern Corn Rootworm Beetle, Diabrotica undecimpunctata (Coleoptera: Chrysomelidae) SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID GENUS SPIROPLASMA; CLASS MOLLICUTES; CLASSIFICATION; MYCOPLASMAS; DEFORMATION AB Spiroplasma strain DU-1(T) (T = type strain), which was isolated from hemolymph of the corn rootworm Diabrotica undecimpunctata (Coleoptera: Chrysomelidae), was serologically distinct from other spiroplasma species, groups, and subgroups, Cells of strain DU-1(T) were shown by light microscopy to be helical motile filaments, Electron microscopy revealed cells bounded by a single cytoplasmic membrane, with no evidence of a cell wall, The organism was not sensitive to 500 U of penicillin per ml. Strain DU-1(T) grew well in SM-1, M1D, and SP-4 liquid media, in broth supplemented with 1% bovine serum fraction or conventional horse serum, and under both aerobic and anaerobic conditions, This organism did not appear to have a sterol requirement for growth, as has been reported for several other Spiroplasma species or strains, Optimal growth occurred at 32 degrees C, with a doubling time of 0.9 h; strain DU-1(T) multiplied at 10 to 41 degrees C but failed to grow at 5 or 43 degrees C, It produced acid from glucose but hydrolyzed neither arginine nor urea, The results of reciprocal serologic tests in which antigens or antisera to established Spiroplasma species, groups, subgroups, and putative groups were used indicated that strain DU-1(T) was serologically distinct, This organism has a DNA guanine-plus-cytosine content of 25 +/- 1 mol% and a genome size of 1,350 kbp, Strain DU-1(T) is a member of a cluster of fast-growing insect-associated spiroplasmas, as determined by sequence analysis of 16S rRNA, On the basis of the results of this study and previously published data, strain DU-1 (= ATCC 43210) is designated the type strain of a new species, Spiroplasma diabroticae. C1 USDA ARS,BELTSVILLE AGR RES CTR,VEGETABLE LAB,BELTSVILLE,MD 20705. USDA ARS,BELTSVILLE AGR RES CTR,INSECT BIOCONTROL LAB,BELTSVILLE,MD 20705. UNIV BORDEAUX 2,F-33883 VILLENAVE DORNON,FRANCE. INRA,BIOL CELLULAIRE & MOL LAB,F-33883 VILLENAVE DORNON,FRANCE. NIAID,MYCOPLASMA SECT,MOL MICROBIOL LAB,FREDERICK CANC RES FACIL,FREDERICK,MD 21702. SUNY STONY BROOK,DEPT ANAT SCI,STONY BROOK,NY 11794. NR 25 TC 4 Z9 5 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JAN PY 1997 VL 47 IS 1 BP 78 EP 80 PG 3 WC Microbiology SC Microbiology GA WC106 UT WOS:A1997WC10600013 PM 8995806 ER PT J AU Secchiero, P Berneman, ZN Sun, D Nicholas, J Rietz, MS AF Secchiero, P Berneman, ZN Sun, D Nicholas, J Rietz, MS TI Identification of envelope glycoproteins H and B homologues of human herpesvirus 7 SO INTERVIROLOGY LA English DT Article DE HHV-7; gB; gH; sequence ID VARICELLA-ZOSTER VIRUS; EPSTEIN-BARR VIRUS; SIMPLEX VIRUS; HUMAN CYTOMEGALOVIRUS; MONOCLONAL-ANTIBODIES; INFECTED-CELLS; EXANTHEM-SUBITUM; SEQUENCE; EXPRESSION; GH AB The genes encoding the envelope glycoprotein H (gH) and gB homologues were identified by sequencing genomic clones of human herpesvirus-7 (HHV-7), strain JI. A gB cDNA clone from HHV-7 strain AL was also identified, The deduced primary translation products of the gH and gB genes are a protein of 690 amino acids, with a predicted mass of 80.4 kD, and a protein of 822 amino acids, with a predicted mass of 93.3 kD, respectively. Both the predicted proteins have the characteristics of transmembrane glycoproteins, containing signal and transmembrane sequence motifs and characterized by the presence of 10 (gH) and 11 (gB) potential motifs for N-glycosylation, Comparison of amino acid sequence of HHV-7 gH and gB with the homologous sequences of the other human herpesviruses reveals closest homology with HHV-6 (38.8% identity for gH, 56.2% identity for the gB), In addition, significant sequence similarity was also observed between the gH and gB of HHV-7 and the homologs encoded by human cytomegalovirus (21.6% identity for gH, 37.6% identity for gB). No significant differences existed between the gB sequence of the two different HHV-7 strains analyzed. The products of the HHV-7 gH and gB expressed transiently in eukaryotic cells were specifically recognized by an HHV-7-reactive human serum in immunofluorescence assays. C1 UNIV MARYLAND,CTR MED BIOTECHNOL,INST HUMAN VIROL,BALTIMORE,MD 21201. UNIV ANTWERP HOSP,EDEGEM,BELGIUM. NIH,TUMOR CELL BIOL LAB,BETHESDA,MD. JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21205. RI secchiero, paola/G-9689-2015 OI secchiero, paola/0000-0003-4101-7987 NR 47 TC 10 Z9 10 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0300-5526 J9 INTERVIROLOGY JI Intervirology PD JAN-FEB PY 1997 VL 40 IS 1 BP 22 EP 32 PG 11 WC Virology SC Virology GA XQ431 UT WOS:A1997XQ43100004 PM 9268767 ER PT S AU Johnstone, PAS Rohde, DC Saunders, EL Mitchell, JB AF Johnstone, PAS Rohde, DC Saunders, EL Mitchell, JB BE Vaeth, JM TI Combining intraoperative and conventional external radiotherapy doses: A biology-based approach SO INTRAOPERATIVE RADIATION THERAPY IN THE TREATMENT OF CANCER SE Frontiers of Radiation Therapy and Oncology LA English DT Article; Proceedings Paper CT 6th International IORT Symposium / 31st San Francisco Cancer Symposium CY SEP 22-25, 1996 CL SAN FRANCISCO, CA C1 UNIV CALIF SAN DIEGO, LA JOLLA, CA 92093 USA. NCI, RADIAT BIOL BRANCH, BETHESDA, MD 20892 USA. RP USN, MED CTR, DIV RADIAT ONCOL, SAN DIEGO, CA 92134 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0071-9676 BN 3-8055-6456-2 J9 FRONT RADIAT THER ON JI Front.Radiat.Ther.Oncol. PY 1997 VL 31 BP 18 EP 21 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BJ32X UT WOS:A1997BJ32X00005 PM 9263780 ER PT J AU Eckhardt, SG Pluda, JM AF Eckhardt, SG Pluda, JM TI Development of angiogenesis inhibitors for cancer therapy SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE angiogenesis; angiogenesis inhibitors ID TUMOR ANGIOGENESIS; METASTASIS; CARCINOMA AB Abundant literature exists demonstrating that tumors are dependent on angiogenesis for both tumor growth and invasion. The extent of angiogenesis in primary tumors has been demonstrated to be associated with a negative prognosis in several tumors including non-small cell lung carcinoma, prostate cancer, and in node-negative breast cancer, where angiogenesis is an independent negative prognostic factor. These data demonstrate the significance of angiogenesis in tumor biology and indicate that it can be utilized as a target for novel therapeutic strategies. The recent expansion of knowledge into the specific pathways of tumor angiogenesis has provided reagents which can now be utilized to provide markers of efficacy of antiangiogenic agents in cancer patients. A critical part of the development of angiogenesis inhibitors for cancer therapy is the clinical trial strategy. Since these agents are primarily thought to be cytostatic, carefully designed trials must be conducted which focus on appropriate endpoints and integrate relevant biologic markers to support efficacy. C1 NCI,INVEST DRUG BRANCH,CTEP,DCT,ROCKVILLE,MD 20852. RP Eckhardt, SG (reprint author), CANC THERAPY & RES CTR S TEXAS,INST DRUG DEV,4450 MED DR,SAN ANTONIO,TX 78229, USA. NR 10 TC 30 Z9 30 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PY 1997 VL 15 IS 1 BP 1 EP 3 DI 10.1023/A:1005710426406 PG 3 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA XD971 UT WOS:A1997XD97100001 PM 9195284 ER PT J AU Peng, B Li, Q Roberge, FG Chan, CC AF Peng, B Li, Q Roberge, FG Chan, CC TI Effect of transforming growth factor beta-1 in endotoxin-induced uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE cytokine; endotoxin-induced uveitis (EIU); interleukin-6; ocular inflammation; transforming growth factor beta-1 (TGF beta-1) ID RAT AB Purpose. Transforming growth factor beta-1 (TGF beta-1) can modulate inflammation. Endotoxin-induced uveitis (EIU) is characterized by acute ocular inflammation related to the release of cytokines, including interleukin (1L)-6. The authors investigated the effect of TGF beta-1 on EIU in mice. Methods. Three independent experiments were performed. Endotoxin-induced uveitis was induced in C3H/HeN mice by an injection of 200 mu g of lipopolysaccharide (LPS). Two micrograms of TGF beta-1 in 0.1 mi phosphate-buffered saline (PBS) or 0.1 mi PBS alone was administered intraperitoneally at 8 hours after LPS injection. Twenty-four hours after LPS injection, the aqueous humor of the right eyes was collected for leukocyte count, protein concentration, and IL-6 assay. Left eyes were processed for routine histology. Results. TGF beta-1-treated mice showed less ocular inflammation histologically than to the animals that were given PBS. This was confirmed by decreases in leukocyte count, protein concentration, and IL-6 level in the aqueous humor. Conclusions. TGF beta-1 inhibits the development of EIU. TGF beta-1 may be useful for the modulation of uveitis in humans. C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 10 TC 6 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 1997 VL 38 IS 1 BP 257 EP 260 PG 4 WC Ophthalmology SC Ophthalmology GA WC897 UT WOS:A1997WC89700028 PM 9008650 ER PT B AU Rosenthal, JP AF Rosenthal, JP GP ORG ECON COOPERAT & DEV TI Equitable sharing of biodiversity benefits: Agreements on genetic resources SO INVESTING IN BIOLOGICAL DIVERSITY: THE CAIRNS CONFERENCE SE OECD PROCEEDINGS LA English DT Proceedings Paper CT OECD International Conference on Incentive Measures for the Conservation and the Sustainable Use of Biological Diversity CY MAR 25-28, 1996 CL CAIRNS, AUSTRALIA SP Org Econ Cooperat & Dev C1 NIH, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ORGANIZATION ECONOMIC COOPERATION & DEVELOPMENT PI PARIS PA 2, RUE ANDRE PASCAL, CEDEX 16, 75775 PARIS, FRANCE BN 92-64-15502-3 J9 OECD PROC PY 1997 BP 253 EP 274 PG 22 WC Environmental Studies; Planning & Development SC Environmental Sciences & Ecology; Public Administration GA BL28P UT WOS:000075162600013 ER PT B AU Walker, FL Thoma, GR AF Walker, FL Thoma, GR BE Cibbarelli, PR Nixon, C TI Internet document delivery: An end user survey SO IOLS '97: INTEGRATED ONLINE LIBRARY SYSTEMS, PROCEEDINGS - 1997: EXPANDING EXPECTATIONS LA English DT Proceedings Paper CT 12th Integrated Online Library Systems Meeting on Expanding Expectations (IOLS 97) CY MAY 14-15, 1997 CL NEW YORK, NY SP Informat Today Inc DE Internet; DocView; survey; document delivery; TIFF; GEDI; MIME; Ariel; Raosoft AB The Internet is serving as an increasingly useful vehicle for electronic document delivery. Many libraries and information providers are now using the Internet for delivering electronically scanned versions of printed documents to patrons who have tools for receiving and using them. An example of such a tool is DocView, a Windows-based software application developed at an R&D division of the National Library of Medicine. DocView facilitates Internet document delivery by enabling a library patron to receive bitmapped images of documents sent by a library's Ariel system. The Ariel system sends the documents rapidly and directly to the patron's desktop personal computer running DocView. The DocView software also facilitates two other means of Internet document delivery, by serving as a TIFF viewer for scanned documents received through Internet client software such as World Wide Web browsers and MIME email. After a number of sites had beta tested DocView for several months, they received a beta version that included an electronic survey. The survey questions were automatically presented to the tester after 45 days of use, then the tester's responses were electronically forwarded over the Internet to the developers at NLM. The survey solicited opinions from users, many of whom were receiving library documents electronically for the first time, instead of photocopies. The survey identified which features of DocView were useful, and revealed what users thought of Internet document delivery. This paper describes and analyzes the results of the survey. C1 NATL LIB MED,NATL CTR BIOMED COMMUN,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMATION TODAY INC PI MEDFORD PA 143 OLD MARLTON PIKE, MEDFORD, NJ 08055 BN 1-57387-042-0 PY 1997 BP 145 EP 153 PG 9 WC Information Science & Library Science SC Information Science & Library Science GA BJ41Y UT WOS:A1997BJ41Y00018 ER PT B AU Di Francesco, V McQueen, P Garnier, J Munson, PJ AF Di Francesco, V McQueen, P Garnier, J Munson, PJ BE Gaasterland, T Karp, P Karplus, K Ouzounis, C Sander, C Valencia, A TI Incorporating global information into secondary structure prediction with hidden Markov models of protein folds SO ISMB-97 - FIFTH INTERNATIONAL CONFERENCE ON INTELLIGENT SYSTEMS FOR MOLECULAR BIOLOGY, PROCEEDINGS LA English DT Proceedings Paper CT 5th International Conference on Intelligent Systems for Molecular Biology (ISMB-97) CY JUN 21-25, 1997 CL HALKIDIKI, GREECE SP Cultural Capital Europe 1997, Thessaloniki, GlaxoWellcome PLC, Int Soc Computat Biol, SmithKline Beecham Corp, Silicon Graph, Sun Microsyst, US DOE, US NIH, US Natl Sci Fdn, Univ Patras, Greece DE protein structure prediction; hidden Markov models; fold recognition; secondary structure AB Here we propose an approach to include global structural information in the secondary structure prediction procedure based on hidden Markov models (HMMs) of protein folds. We first identify the correct fold or 'topology' of a protein by means of the HMMs of topology families of proteins. Then the most likely structural model for that protein is used to modify the sequence of secondary structure states previously obtained with a prediction algorithm. Our goal is to investigate the effect on the prediction accuracy of including global structural information in the secondary structure prediction scheme, by means of the HMMs. We find that when the HMM of the predicted topology of a protein is used to adjust the secondary structure sequence, predicted originally with the Quadratic-Logistic method, the cross-validated prediction accuracy (Q3) improves by 3%. The topology is correctly predicted in 68% of the cases. We conclude that this HMM based approach is a promising tool for effectively incorporating global structural information in the secondary structure prediction scheme. C1 NIH, Bethesda, MD 20892 USA. RP Di Francesco, V (reprint author), NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ARTIFICIAL INTELLIGENCE PI MENLO PK PA 445 BURGESS DR, MENLO PK, CA 94025 USA BN 1-57735-022-7 PY 1997 BP 100 EP 103 PG 4 WC Biochemistry & Molecular Biology; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics SC Biochemistry & Molecular Biology; Computer Science; Medical Informatics GA BK49D UT WOS:000072320000014 ER PT B AU Hunter, L Zeeberg, B AF Hunter, L Zeeberg, B BE Gaasterland, T Karp, P Karplus, K Ouzounis, C Sander, C Valencia, A TI Identifying chimerism in proteins using hidden Markov models of codon usage SO ISMB-97 - FIFTH INTERNATIONAL CONFERENCE ON INTELLIGENT SYSTEMS FOR MOLECULAR BIOLOGY, PROCEEDINGS LA English DT Proceedings Paper CT 5th International Conference on Intelligent Systems for Molecular Biology (ISMB-97) CY JUN 21-25, 1997 CL HALKIDIKI, GREECE SP Cultural Capital Europe 1997, Thessaloniki, GlaxoWellcome PLC, Int Soc Computat Biol, SmithKline Beecham Corp, Silicon Graph, Sun Microsyst, US DOE, US NIH, US Natl Sci Fdn, Univ Patras, Greece AB Protein chimerism is a phenomenon involving the combination of multiple ancestral sequences into a single, multi-domain protein through evolution. We propose a novel method for detecting chimeric proteins by analyzing their nucleotide sequence. The method tests for differences in the distributions of synonymous (isoaccepting) codons in different regions of the protein. The test involves the comparison of the ability of varying size hidden Markov models (HMMs) of codon usage to fit the natural sequence, relative to a set of randomized controls. We demonstrate the method on the families of yeast nuclear and mitochondrial amino-acyl tRNA synthetases. The method is potentially useful for the automated screening of entire genomes or large databases. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Hunter, L (reprint author), Natl Lib Med, Bldg 38A,9th Floor, Bethesda, MD 20894 USA. OI Hunter, Lawrence/0000-0003-1455-3370 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ARTIFICIAL INTELLIGENCE PI MENLO PK PA 445 BURGESS DR, MENLO PK, CA 94025 USA BN 1-57735-022-7 PY 1997 BP 153 EP 156 PG 4 WC Biochemistry & Molecular Biology; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics SC Biochemistry & Molecular Biology; Computer Science; Medical Informatics GA BK49D UT WOS:000072320000022 ER PT B AU Munson, PJ Singh, RK AF Munson, PJ Singh, RK BE Gaasterland, T Karp, P Karplus, K Ouzounis, C Sander, C Valencia, A TI Multi-body interactions within the graph of protein structure SO ISMB-97 - FIFTH INTERNATIONAL CONFERENCE ON INTELLIGENT SYSTEMS FOR MOLECULAR BIOLOGY, PROCEEDINGS LA English DT Proceedings Paper CT 5th International Conference on Intelligent Systems for Molecular Biology (ISMB-97) CY JUN 21-25, 1997 CL HALKIDIKI, GREECE SP Cultural Capital Europe 1997, Thessaloniki, GlaxoWellcome PLC, Int Soc Computat Biol, SmithKline Beecham Corp, Silicon Graph, Sun Microsyst, US DOE, US NIH, US Natl Sci Fdn, Univ Patras, Greece AB We construct a graphical representation of protein structure based on the 3D C-alpha carbon point set, using the Delaunay tessellation to define interacting quadruples of amino acid residues. The tessellation is filtered by two criteria: interaction distance less than 9.5 angstroms and circumsphere radius less than 8.0 angstroms using dataset of 608 protein structures of low mutual sequence identity and a likelihood ratio test, we show that 3-body and 4-body interactions are indeed significant. We identify particular significant three-body interactions by first reducing the dataset to interacting triples, and classifying amino acid residues in a reduced alphabet. Although cystein was previously shown to be a dominant source of S-body interactions, we now identify additional significant 3-body interactions of charged, hydrophobic and small residues. C1 NIH, Analyt Biostat Sect, LSB, DCRT, Bethesda, MD 20892 USA. RP Munson, PJ (reprint author), NIH, Analyt Biostat Sect, LSB, DCRT, Bldg 12A,Room 2041, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ARTIFICIAL INTELLIGENCE PI MENLO PK PA 445 BURGESS DR, MENLO PK, CA 94025 USA BN 1-57735-022-7 PY 1997 BP 198 EP 201 PG 4 WC Biochemistry & Molecular Biology; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Medical Informatics SC Biochemistry & Molecular Biology; Computer Science; Medical Informatics GA BK49D UT WOS:000072320000028 ER PT J AU Benjamin, J Ebstein, RP Belmaker, RH AF Benjamin, J Ebstein, RP Belmaker, RH TI Personality genetics SO ISRAEL JOURNAL OF PSYCHIATRY AND RELATED SCIENCES LA English DT Article ID BIPOLAR AFFECTIVE-DISORDER; DOPAMINE-RECEPTOR GENE; TWINS REARED APART; NOVELTY SEEKING; SUSCEPTIBILITY GENE; MAJOR DEPRESSION; HUMAN-BEHAVIOR; X-CHROMOSOME; DNA MARKERS; SCHIZOPHRENIA AB Although 30-60% of the variance in many personality traits is inherited, until recently little was known about the responsible genes. Preliminary studies of family history in bipolar disorder and of X-linkage of personality traits in color-blindness suggested a ''quantitative trait locus'' (QTL) approach to the genetics of normal personality. Ln methodically similar but independent studies of 124 Israeli and 315 American normal volunteers we showed an association between the dopamine D4 receptor gene (D4DR) and the personality trait of novelty seeking. In the Israeli sample we also found an interaction between the D4DR gene and the serotonin 2C receptor gene (5-HT2C) with a marked effect on the trait of reward dependence. Further investigation of genes for personality traits may suggest Links between normal personality and psychiatric illness. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. BEN GURION UNIV NEGEV,IL-84105 BEER SHEVA,ISRAEL. S HERZOG MEM HOSP,RES LAB,JERUSALEM,ISRAEL. MINIST HLTH,BEERSHEBA MENTAL HLTH CTR,BEER SHEVA,ISRAEL. RP Benjamin, J (reprint author), SOROKA MED CTR,DEPT PSYCHIAT,POB 151,IL-84101 BEER SHEVA,ISRAEL. OI Ebstein, Richard/0000-0002-3626-541X NR 59 TC 20 Z9 21 U1 1 U2 5 PU GEFEN PUBL HOUSE LTD PI JERUSALEM PA PO BOX 6056, JERUSALEM 91060, ISRAEL SN 0333-7308 J9 ISRAEL J PSYCHIAT JI Isr. J. Psychiatr. Relat. Sci. PY 1997 VL 34 IS 4 BP 270 EP 280 PG 11 WC Psychiatry SC Psychiatry GA YJ110 UT WOS:A1997YJ11000005 PM 9409084 ER PT B AU Kun, LG AF Kun, LG BE Eck, V Krekule, I TI Performance computers and communications and telemedicine: From home care to privacy and security of health care data SO ITAB '97 - INFORMATION TECHNOLOGY APPLICATIONS IN BIOMEDICINE, PROCEEDINGS LA English DT Proceedings Paper CT IEEE Engineering-in-Medicine-and-Biology-Society Region-8 International Conference on Information Technology Applications in Biomedicine (ITAB 97) CY SEP 07-09, 1997 CL PRAGUE, CZECH REPUBLIC SP IEEE Engn Med & Biol Soc, Reg 8, Czech Soc Biomed Engn & Med Informat, Czech Tech Univ, Prague, Charles Univ, 1st Fac Med, Prague, Acad Sci Czech Republic, Inst Physiol, Prague, Minist Hlth Czech Republic, Prague AB We are living in an information age and the 21st century will be the Age of Information. Implementation and support of the NII/GII strategic plan will occur through the utilization of High Performance Computing and Communications [HPCC]. HPCC technology provides a potentially huge payoff in health care. From teleconsultations to availability of health-related databases, the effect of using high performance computing and communications will enhance patient care, improve drug design, and broaden access to medical information. Geographic distance, time to accomplish tasks, separation of people from resources, and outdated organizational structures are impediments that inhibit the ultimate achievement of all these goals. Information technology has a pervasive: and unprecedented ability to remove these barriers to progress. As part of the strategic planning process, three broad classes of user-driven applications have been identified:(1) high performance applications: (2) high confidence applications-improving integration, privacy, security, and reliability of information flows within and across enterprises; and (3) high capability applications for the individual-empowering individuals with universal, easy-to-use access information, and providing customization and support of their information space. C1 AHCPR, CIT, Rockville, MD USA. RP Kun, LG (reprint author), AHCPR, CIT, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-4318-2 PY 1997 BP 21 EP 22 DI 10.1109/ITAB.1997.649390 PG 2 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA BK48S UT WOS:000072315700006 ER PT B AU Ackerman, MJ AF Ackerman, MJ BE Eck, V Krekule, I TI The Visible Human Project (TM): A resource for anatomical visualization SO ITAB '97 - INFORMATION TECHNOLOGY APPLICATIONS IN BIOMEDICINE, PROCEEDINGS LA English DT Proceedings Paper CT IEEE Engineering-in-Medicine-and-Biology-Society Region-8 International Conference on Information Technology Applications in Biomedicine (ITAB 97) CY SEP 07-09, 1997 CL PRAGUE, CZECH REPUBLIC SP IEEE Engn Med & Biol Soc, Reg 8, Czech Soc Biomed Engn & Med Informat, Czech Tech Univ, Prague, Charles Univ, 1st Fac Med, Prague, Acad Sci Czech Republic, Inst Physiol, Prague, Minist Hlth Czech Republic, Prague AB The National Library of Medicine (NLM) has long been a world leader in the archiving and distribution of the print-based images of biology and medicine. NLM has also been a pioneer in the use of computer systems to encode and distribute textual knowledge of the life sciences. NLM's :Long Range Planning effort of 1985-86 foresaw a coming era where NLM's Bibliographic and factual database services would be complemented by libraries of digital images, distributed over high speed computer networks and by high capacity physical media. The NLM Planning Panel on Electronic Imaging recommended that NLM should undertake the building a digital image library consisting of computerized tomography (CT) and magnetic resonance (MR) images, and, cryosection images of a representative, carefully selected and prepared male and female cadaver-the "Visible Human Project(TM)." The male and female Visible Human data sets are now being made available through a license agreement with the NLM. The data sets are supporting a wide range of educational, diagnostic, treatment planning, and commercial uses. The value of this national resource in the public domain increases through its application. Its utility will continue to grow as related databases are attached to it, and as more attributes are given to its image elements. C1 Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. RP Ackerman, MJ (reprint author), Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-4318-2 PY 1997 BP 29 EP 31 DI 10.1109/ITAB.1997.649392 PG 3 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA BK48S UT WOS:000072315700008 ER PT J AU OBrien, TR Rosenberg, PS Goedert, JJ Kroner, BL Eyster, E AF OBrien, TR Rosenberg, PS Goedert, JJ Kroner, BL Eyster, E TI Dose of non-heat-treated factor VIII concentrate and HIV-1 RNA levels - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 RES TRIANGLE INST,ROCKVILLE,MD. MILTON S HERSHEY MED CTR,HERSHEY,PA. RP OBrien, TR (reprint author), NCI,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 1 PY 1997 VL 277 IS 1 BP 20 EP 21 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VZ767 UT WOS:A1997VZ76700016 ER PT J AU McNutt, SW Hu, YR Schreiber, GB Crawford, PB Obarzanek, E Mellin, L AF McNutt, SW Hu, YR Schreiber, GB Crawford, PB Obarzanek, E Mellin, L TI A longitudinal study of the dietary practices of black and white girls 9 and 10 years old at enrollment: The NHLBI growth and health study SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE adolescent females; dietary intake; eating practices; obesity; socioeconomic status; racial differences ID NUTRITION EXAMINATION SURVEYS; WEIGHT-LOSS; BEHAVIOR-MODIFICATION; NATIONAL-HEALTH; WOMEN; CHILDREN; OBESITY; PREVALENCE; OVERWEIGHT; ADULTS AB Purpose: To determine whether there are racial differences in the frequency with which black and white girls engaged in eating practices commonly targeted for modification in weight reduction programs. Methods: This is part of the NHLBI Growth and Health Study, a longitudinal study of preadolescent girls designed to examine the factors associated with development of obesity, and its later effects on cardiovascular risk factors. Black and white girls ages 9-10 years at entry (n = 2,379) were recruited at three clinical sites. Racial differences were examined in 11 ''weight-related'' eating practices such as eating with TV, eating while doing homework, and skipping meals. Multiple logistic regression analyses were then conducted for each of the dependent variables. Results: Black girls were more than twice as Likely as white girls to frequently engage in the targeted weight-related eating practices. The odds of a study girl frequently engaging in most of these eating practices decreased with an increase in parents' income and education level. However, even when controlling for socioeconomic and demographic effects, black girls remained more likely to engage in these eating practices than white girls. For most of the behaviors, girls who frequently practiced a behavior had higher energy intakes compared to those who practiced it infrequently. Conclusions: The finding that black girls at an early age more frequently engage in eating practices associated with weight gain may have significant implications for obesity development. For both young black and white girls, early education efforts may be necessary in helping develop good eating habits. Since it appears that black girls have a higher risk of developing adverse weight-related eating practices, culturally appropriate education materials may be required. (C) Society for Adolescent Medicine, 1997 C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. NHLBI,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,CTR ADOLESCENT OBES,SAN FRANCISCO,CA 94143. RP McNutt, SW (reprint author), WESTAT CORP,1650 RES BLVD,WB 376,ROCKVILLE,MD 20850, USA. FU NHLBI NIH HHS [HC-55025, HC-55024, HC-55023] NR 36 TC 50 Z9 50 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD JAN PY 1997 VL 20 IS 1 BP 27 EP 37 DI 10.1016/S1054-139X(96)00176-0 PG 11 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA WC301 UT WOS:A1997WC30100007 PM 9007656 ER PT J AU Kauffman, RD Sforzo, GS Frost, B Todd, MK AF Kauffman, RD Sforzo, GS Frost, B Todd, MK TI The effects of exercise training on resting prostacyclin and thromboxane A(2) in older adults SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Article DE exercise training; prostacyclin; thromboxane A(2) ID PLATELET-FUNCTION; ARACHIDONIC-ACID; HEALTHY-MEN; PLASMA; BLOOD; AGE; BIOSYNTHESIS; ACTIVATION; CELLS; RATS AB Ten adult volunteers participated in 16 weeks of cardiovascular exercise training (EG) to determine the effects of training on resting prostacyclin (PGI(2)) and thromboxane A(2) (TXA(2)). Six volunteers of similar age served as sedentary controls (CG). Blood was collected in tubes after training and eicosanoids were measured by standard I-125 RIA methods. Over the 16 weeks of the study, PGI(2) decreased 48% for EG and 33% for CG. There were no between-group differences for PGI(2) values. No significant within-group changes in TXA(2) were found, whereas between-group pretraining TXA(2) values were significantly different. A time main effect for PGI(2) may indicate a seasonal shift in this eicosanoid; however, the additional 15% decrease in PGI(2) for EG may be due to a training-induced reduction in PGI(2) substrate and/or endothelial sensitivity to agonists. The lack of within-group changes in TXA(2) may be due to a combination of high platelet turnover and a training stimulus inadequate to alter platelet function. C1 DEPT EXERCISE SCI,ITHACA,NY 14850. W CHESTER UNIV,DEPT CHEM,W CHESTER,PA 19383. LONGWOOD COLL,DEPT HPERD,FARMVILLE,VA 23909. RP Kauffman, RD (reprint author), NATL INST HLTH,NHLBI,MOL DIS BRANCH,5 RES COURT,ROCKVILLE,MD 20850, USA. NR 30 TC 0 Z9 0 U1 0 U2 1 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, CHAMPAIGN, IL 61820-2200 SN 1063-8652 J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD JAN PY 1997 VL 5 IS 1 BP 59 EP 70 PG 12 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA VZ774 UT WOS:A1997VZ77400006 ER PT J AU Ryan, JJ AF Ryan, JJ TI Interleukin-4 and its receptor: Essential mediators of the allergic response SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review RP Ryan, JJ (reprint author), NIAID,IMMUNOL LAB,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 8 TC 86 Z9 89 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 BP 1 EP 5 PN 1 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA WD061 UT WOS:A1997WD06100001 PM 9003204 ER PT J AU Polakova, K Plaksin, D Mage, MG Margulies, DH AF Polakova, K Plaksin, D Mage, MG Margulies, DH TI Rigidification of the alpha 2 helix by a valine to proline mutation in position 162 of an MHC class 1 molecule does not prevent peptide specific antigen presentation. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NIAID,LI,MOL BIOL SECT,NIH,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 35 EP 35 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200035 ER PT J AU Nagaraju, K Kirk, K Raben, N Plotz, P AF Nagaraju, K Kirk, K Raben, N Plotz, P TI Cytokine- and chemokine-induced expression of MHC class I, MHC class II, and ICAM I on normal human skeletal myoblasts. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAMS,ARB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 63 EP 63 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200063 ER PT J AU Rosenthal, LA Yarboro, CH Finbloom, DS AF Rosenthal, LA Yarboro, CH Finbloom, DS TI Formation of atypical interferon-stimulated response element (ISRE) binding complexes in peripheral blood mononuclear cells (PBMC) from systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 81 EP 81 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200081 ER PT J AU Marth, T Neurath, M Cuccherini, B Schneider, T Holland, S Zeitz, M Strober, W AF Marth, T Neurath, M Cuccherini, B Schneider, T Holland, S Zeitz, M Strober, W TI Defects of monocyte IL-12 production and humoral immunity in Whipple's disease. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIH,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. UNIV SAARLAND,D-6650 HOMBURG,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 111 EP 111 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200110 ER PT J AU BergmannLeitner, ES Schlom, J Abrams, SI AF BergmannLeitner, ES Schlom, J Abrams, SI TI Production of peptide derived human CD8+ cytotoxic T cells which lyse tumor cells expressing the endogenous ras oncogene. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 182 EP 182 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200181 ER PT J AU Bristol, JA Schlom, J Abrams, SI AF Bristol, JA Schlom, J Abrams, SI TI Modification of a murine mutant ras CD8(+) CTL peptide antigen with increased immunogenicity for an oncoprotein-specific immune response. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 183 EP 183 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200182 ER PT J AU Guptill, VA Zaremba, S Schlom, J Kantor, JA AF Guptill, VA Zaremba, S Schlom, J Kantor, JA TI Recombinant vaccinia virus (rV) expression of a CTL epitope from carcinoembryonic antigen (CEA). SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 186 EP 186 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200185 ER PT J AU Yang, G Pu, RL DSouza, P Vyas, GN AF Yang, G Pu, RL DSouza, P Vyas, GN TI Neutralizing antibodies against HIV determined by amplification of viral LTR-sequences from the cells infected in vitro by non-neutralized virions. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NIAID,DIV AIDS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 192 EP 192 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200191 ER PT J AU Plotz, P Nagaraju, K Kirk, K Raben, N AF Plotz, P Nagaraju, K Kirk, K Raben, N TI Human skeletal muscle myoblasts express a variety of cytokines and chemokines under the influence of proinflammatory stimuli. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAMS,ARB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 215 EP 215 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200214 ER PT J AU Amichay, D Farber, JM AF Amichay, D Farber, JM TI Expression of chemokines differ during mouse embryogenesis. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 226 EP 226 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200225 ER PT J AU Cho, J Vliagoftis, H Song, C Tsai, PB Zin, A Metcalfe, DD Oh, CK AF Cho, J Vliagoftis, H Song, C Tsai, PB Zin, A Metcalfe, DD Oh, CK TI Identification of novel inducible mast cell genes by subtraction library. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 HARBOR UCLA MED CTR,TORRANCE,CA 90509. NIH,BETHESDA,MD 20892. RI Vliagoftis, Harissios/C-6480-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 367 EP 367 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200366 ER PT J AU Whittlesey, K Dastych, J Metcalfe, DD AF Whittlesey, K Dastych, J Metcalfe, DD TI Expression of hyaluronan-recogizing isoform of CD44 by human and murine mast cells. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 376 EP 376 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200375 ER PT J AU Zhang, J Swaim, WD Berenstein, EH Siraganian, RP AF Zhang, J Swaim, WD Berenstein, EH Siraganian, RP TI Syk protein tyrosine kinase is essential for the high affinity IgE receptor-induced morphological changes in mast cells. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 379 EP 379 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200378 ER PT J AU Adachi, S Metcalfe, DD AF Adachi, S Metcalfe, DD TI Attachment of murine mast cells to endothelium. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID,LAB ALLERG DIS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 380 EP 380 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200379 ER PT J AU Tsai, PB Cho, J Song, C Rumsaeng, V Zin, A Metcalfe, DD Oh, CK AF Tsai, PB Cho, J Song, C Rumsaeng, V Zin, A Metcalfe, DD Oh, CK TI Induction of serglycin gene in mast cells following aggregation of Fc epsilon RI. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. HARBOR UCLA MED CTR,TORRANCE,CA 90509. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 388 EP 388 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200387 ER PT J AU Myers, LA Riester, DE Schiff, RI Schiff, SE Williams, LW Roberts, JL Puck, JM Buckley, RH AF Myers, LA Riester, DE Schiff, RI Schiff, SE Williams, LW Roberts, JL Puck, JM Buckley, RH TI Bone marrow transplantation for SCID in the neonatal period. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. DUKE UNIV,DURHAM,NC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 411 EP 411 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200409 ER PT J AU Xia, HZ Irani, AA Klisch, G NobenTrauth, N Kochan, JP Huff, T Schwartz, LB AF Xia, HZ Irani, AA Klisch, G NobenTrauth, N Kochan, JP Huff, T Schwartz, LB TI Recombinant human (rh) IL-4 induces Fc epsilon eRI on RhSCF-dependent fetal liver-derived human mast cells. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. NIH,BETHESDA,MD 20892. VIRGINIA COMMONWEALTH UNIV,RICHMOND,VA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 423 EP 423 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200421 ER PT J AU Lempicki, RA Pavlick, MV Donoghue, ET Kovacs, J Adelesberger, J Baseler, M Lane, HC AF Lempicki, RA Pavlick, MV Donoghue, ET Kovacs, J Adelesberger, J Baseler, M Lane, HC TI IL-2 relieves G(1) cell cycle arrest in CD8+ T-cells from HIV+ individuals. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID,NIH,BETHESDA,MD 20892. SAIC,FREDERICK,MD. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1997 VL 99 IS 1 SU S BP 432 EP 432 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA WH142 UT WOS:A1997WH14200430 ER EF