FN Thomson Reuters Web of Science™ VR 1.0 PT J AU CASSEDY, JH AF CASSEDY, JH TI DOCTORS, POLITICS AND SOCIETY - HISTORICAL ESSAYS - PORTER,D, PORTER,R SO SOCIAL HISTORY OF MEDICINE LA English DT Book Review RP CASSEDY, JH (reprint author), NATL LIB MED,BETHESDA,MD 20209, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0951-631X J9 SOC HIST MED JI Soc. Hist. Med. PD DEC PY 1994 VL 7 IS 3 BP 527 EP 528 DI 10.1093/shm/7.3.527 PG 2 WC History; History & Philosophy Of Science SC History; History & Philosophy of Science GA QG729 UT WOS:A1994QG72900016 ER PT J AU LOCKSHIN, MD AF LOCKSHIN, MD TI LUPUS PREGNANCIES AND NEONATAL LUPUS SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID CONGENITAL HEART-BLOCK; EXPERIMENTAL ANTIPHOSPHOLIPID SYNDROME; ALTERNATIVE COMPLEMENT PATHWAY; C1S-C1 INHIBITOR COMPLEX; SS-A ANTIBODIES; B LA ANTIBODIES; FETAL LOSS; ANTICARDIOLIPIN ANTIBODIES; DISEASE-ACTIVITY; INTRAUTERINE THERAPY RP LOCKSHIN, MD (reprint author), NIAMSD,BLDG 31,ROOM 4C-32,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 79 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD DEC PY 1994 VL 16 IS 2-3 BP 247 EP 259 PG 13 WC Immunology; Pathology SC Immunology; Pathology GA PZ769 UT WOS:A1994PZ76900008 PM 7716707 ER PT J AU GOURLEY, MF AF GOURLEY, MF TI SYSTEMIC LUPUS-ERYTHEMATOSUS - DISEASE MANAGEMENT SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; PULSE CYCLOPHOSPHAMIDE; MONOCLONAL-ANTIBODY; CONTROLLED TRIAL; EXTRACORPOREAL PHOTOCHEMOTHERAPY; INTRAVENOUS CYCLOPHOSPHAMIDE; AUTOIMMUNE THROMBOCYTOPENIA; ANTIPHOSPHOLIPID ANTIBODIES; IMMUNE THROMBOCYTOPENIA; FETAL DEATH RP GOURLEY, MF (reprint author), NIAMSD,BLDG 10,ROOM 9S210,BETHESDA,MD 20892, USA. NR 89 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD DEC PY 1994 VL 16 IS 2-3 BP 281 EP 294 PG 14 WC Immunology; Pathology SC Immunology; Pathology GA PZ769 UT WOS:A1994PZ76900010 PM 7716709 ER PT J AU ABBOTT, RD BEHRENS, GR SHARP, DS RODRIGUEZ, BL BURCHFIELD, CM ROSS, W YANO, K CURB, JD AF ABBOTT, RD BEHRENS, GR SHARP, DS RODRIGUEZ, BL BURCHFIELD, CM ROSS, W YANO, K CURB, JD TI BODY MASS INDEX AND THROMBOEMBOLIC STROKE IN NONSMOKING MEN IN OLDER MIDDLE-AGE - THE HONOLULU-HEART-PROGRAM SO STROKE LA English DT Article DE BODY MASS INDEX; CEREBROVASCULAR DISORDERS RISK FACTORS; THROMBOEMBOLISM ID RISK-FACTORS; PHYSICAL-ACTIVITY; JAPANESE MEN; FOLLOW-UP; CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; BLOOD-PRESSURE; MORTALITY; OBESITY; TRENDS AB Background and Purpose While evidence suggests that obesity has an independent relation to coronary artery disease, similar findings for stroke have not been established. The purpose of this study was to examine the relation between body mass index and the risk of thromboembolic stroke independently of other risk factors. Methods Since 1965, the Honolulu Heart Program has followed a cohort of men in a prospective study of cardiovascular disease. This article examines the relationship between the baseline measurement of body mass index and the risk of thromboembolic stroke in 1163 nonsmoking men in older middle age (55 to 68 years). Men who had an elevated risk of stroke due to hypertension, diabetes, and other risk factors were excluded from the analysis. Results After 22 years of follow-up, the rate of stroke increased significantly with increasing levels of body mass (P<.01). In the bottom tertile of the body mass index, the rate of thromboembolic stroke was 28.7 per 1000 (11/383). In the middle tertile, the rate was increased by 40% to 40.7 per 1000 (16/393), and in the top tertile, the rate of thromboembolic stroke was 55.4 per 1000 (21/387), a twofold excess compared with the bottom tertile. After adjustment for age and the residual effects of confounding risk factors, including systolic blood pressure and serum glucose, the estimated relative risk of stroke for the average body mass index in the top tertile (26.6 kg/m(2) compared with that in the bottom tertile (20.3 kg/m(2)) was 2.1 (95% confidence interval, 1.1 to 4.1). These findings were not affected by coronary events that occurred in the course of follow-up, nor did they appear to be influenced by deaths from other causes. Conclusions We conclude that elevated body mass is associated with an increased risk of thromboembolic stroke in nonsmoking men in older middle age who are free of commonly observed conditions related to cardiovascular disease. C1 HONOLULU HEART PROGRAM,HONOLULU,HI. NATL HEART LUNG & BLOOD INST,EPIDEMIOL & BIOMETRY PROGRAM,HONOLULU EPIDEMIOL RES SECT,HONOLULU,HI. UNIV HAWAII,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. US DEPT VET AFFAIRS,KUAKINI MED CTR,HONOLULU ASIA AGING STUDY,HONOLULU,HI. RP ABBOTT, RD (reprint author), UNIV VIRGINIA,SCH MED,DEPT MED,DIV BIOSTAT,BOX 432,CHARLOTTESVILLE,VA 22908, USA. FU NCRR NIH HHS [RR-00847]; NHLBI NIH HHS [N01-HC-05102] NR 45 TC 64 Z9 67 U1 1 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1994 VL 25 IS 12 BP 2370 EP 2376 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA PV675 UT WOS:A1994PV67500007 PM 7974575 ER PT J AU LI, RL DUNCAN, BB METCALF, PA CROUSE, JR SHARRETT, AR TYROLER, HA BARNES, R HEISS, G AF LI, RL DUNCAN, BB METCALF, PA CROUSE, JR SHARRETT, AR TYROLER, HA BARNES, R HEISS, G TI B-MODE-DETECTED CAROTID-ARTERY PLAQUE IN A GENERAL-POPULATION SO STROKE LA English DT Article DE ATHEROSCLEROSIS; CAROTID ARTERIES EPIDEMIOLOGY; RACIAL DIFFERENCES; ULTRASONICS ID TRANSIENT ISCHEMIC ATTACKS; RISK-FACTORS; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS; BLACK; ULTRASOUND; PREVALENCE; WOMEN AB Background and Purpose There is little information on the distribution of atherosclerotic lesions of the extracranial carotid artery wall in free-living populations. The purpose of the present study was to describe the prevalence from 1987 through 1989 of extracranial carotid artery plaque and plaque with acoustic attenuation (shadowing) lesions in a general population of white and black adults from four US communities. Methods B-mode ultrasound was used to characterize wall lesions in the common and internal carotid arteries and at the carotid artery bifurcation in 14 046 men and women 45 to 64 years old who participated in the Atherosclerosis Risk in Communities Study baseline survey. Results Thirty-four percent of participants had plaque and 6.4% had plaque with acoustic shadowing. The prevalence of plaque with acoustic shadowing increased steadily with age from 2.5% at ages 45 to 49 to 12.4% at ages 60 to 64. Overall, whites had more plaque with acoustic shadowing lesions than blacks (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.02 to 1.46), and men had more than women (OR, 1.42; 95% CI, 1.22 to 1.63). However, plaque lesions in the common carotid artery were less common among whites than among blacks, and no racial difference was observed in the prevalence of plaque with acoustic shadowing at this segment. Conclusions Although these prevalence rates are likely to be underestimated because of the emphasis on arterial boundary visualization of the scanning protocol, they show a large, mostly asymptomatic burden of atherosclerosis in these populations, especially among older individuals. Site-specific frequency rates of plaque varied between blacks and whites. Among those with plaque, however, whites had more lesions with acoustic shadowing attenuation. C1 UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,CHAPEL HILL,NC. UNIV FED RIO GRANDE SUL,SCH MED,DEPT SOCIAL MED,PORTO ALEGRE,RS,BRAZIL. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT MED,WINSTON SALEM,NC 27103. NHLBI,BETHESDA,MD 20892. ARIC,ULTRASOUND READING CTR,WINSTON SALEM,NC. FU NHLBI NIH HHS [N01-HC-55016, N01-HC-55018, N01-HC-55015] NR 26 TC 126 Z9 129 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1994 VL 25 IS 12 BP 2377 EP 2383 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA PV675 UT WOS:A1994PV67500008 PM 7974576 ER PT J AU MACFARLANE, MP FRAKER, DL SHAWKER, TH DOPPMAN, JL CHANG, RA SKARULIS, MC MARX, SJ SPIEGEL, AM ALEXANDER, HR AF MACFARLANE, MP FRAKER, DL SHAWKER, TH DOPPMAN, JL CHANG, RA SKARULIS, MC MARX, SJ SPIEGEL, AM ALEXANDER, HR TI USE OF PREOPERATIVE FINE-NEEDLE ASPIRATION IN PATIENTS UNDERGOING REOPERATION FOR PRIMARY HYPERPARATHYROIDISM SO SURGERY LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 17-19, 1994 CL DEARBORN, MI SP AMER ASSOC ENDOCRINE SURGEONS ID ENLARGED PARATHYROID-GLANDS; RECURRENT PRIMARY HYPERPARATHYROIDISM; HORMONE ASSAY; LOCALIZATION; PERSISTENT; GUIDANCE; BIOPSY; MANAGEMENT AB Background. Neck reexploration for primary hyperparathyroidism has a lower success rate and greater morbidity than initial exploration because of scarring and distortion of tissue planes and the possibility of a parathyroid neoplasm located in an ectopic or unusual position. Although the use of standard noninvasive imaging studies for reoperative parathyroid surgical procedure is well accepted, the use of invasive studies to localize parathyroid neoplasms, particularly percutaneous aspiration of potential lesions, is controversial. In this report we analyze the results and morbidity in patients undergoing fine-needle aspiration before neck reexploration. Methods. From 1982 to 1993, 255 patients underwent reexploration for persistent or recurrent hyperparathyroidism at the National Institutes of Health. Of these 255 patients 42 underwent 44 preoperative fine-needle aspirations by ultrasonography or computed tomography guidance in an attempt to localize a parathyroid neoplasm. The aspirated contents were then analyzed for parathyroid hormone content. Results. Of the 44 aspirations 26 (59%) were true positives with no false positives. Of 18 negative fine-needle aspirations, 11 (25%) were false negatives, and seven (16%) were true negatives. The specificity and sensitivity of percutaneous fine-needle aspiration were 100% and 70%, respectively. Conclusions. Percutaneous fine-needle aspiration for parathyroid hormone is a safe, well-tolerated technique that is highly specific and allows a directed surgical resection avoiding further invasive workup when the aspirate is positive. C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NIDDK,METAB DIS BRANCH,BETHESDA,MD. NIH,WARREN G MAGNUSON CLIN CTR,HENRY M JACKSON FDN,DEPT RADIOL,BETHESDA,MD. NR 25 TC 24 Z9 24 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1994 VL 116 IS 6 BP 959 EP 965 PG 7 WC Surgery SC Surgery GA PW090 UT WOS:A1994PW09000003 PM 7985103 ER PT J AU BILLINGSLEY, KG FRAKER, DL DOPPMAN, JL NORTON, JA SHAWKER, TH SKARULIS, MC MARX, SJ SPIEGEL, AM ALEXANDER, HR AF BILLINGSLEY, KG FRAKER, DL DOPPMAN, JL NORTON, JA SHAWKER, TH SKARULIS, MC MARX, SJ SPIEGEL, AM ALEXANDER, HR TI LOCALIZATION AND OPERATIVE MANAGEMENT OF UNDESCENDED PARATHYROID ADENOMAS IN PATIENTS WITH PERSISTENT PRIMARY HYPERPARATHYROIDISM SO SURGERY LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 17-19, 1994 CL DEARBORN, MI SP AMER ASSOC ENDOCRINE SURGEONS ID RECURRENT HYPERPARATHYROIDISM; HYPER-PARATHYROIDISM; REOPERATION; EXPLORATION; SURGERY AB Background. Between 5% and 10% of patients who undergo cervical exploration for primary hyperparathyroidism will have persistent or recurrent hyperparathyroidism. Many of these patients have parathyroid tumors in unusual locations. One such site of ectopic parathyroid tissue is an undescended parathyroid adenoma at or superior to the carotid bifurcation. We describe our experience with the preoperative localization and surgical management of undescended parathyroid adenomas. Methods. From 1982 to 1993 a consecutive series of 255 patients have undergone localization studies and surgical exploration for persistent or recurrent hyperparathyroidism at the Clinical Center of the National Institutes of Health. Operative strategy was determined by review of the patient's surgical history, disease reports, and data from localizing studies. Patients with an undescended parathyroid adenoma identified before the operation were examined with a direct approach high in the neck. Patients who did not have definitive preoperative localization were explored with the previous transverse cervical incision. Results. Seventeen undescended parathyroid adenomas were identified in 255 patients. Thirteen (76%) of 17 patients had an undescended parathyroid adenoma Precisely localized before the operation and were examined via a limited oblique incision high in the neck anterior to the sternocleidomastoid muscle. In the 13 patients who had undergone accurate localization before the operation, the median operative time was 75 minutes compared with 235 minutes for Sour patients who did not have an undescended parathyroid adenoma identified before the operation and were examined via a previous transverse cervical incision. All patients were cured of their hyperparathyroidism. Conclusions. Undescended parathyroid adenomas were the cause of failed cervical exploration in 17 (7%) of 255 patients. Accurate preoperative localization of these lesions is possible in most cases with a combination of noninvasive and invasive modalities. Successful preoperative localization can convert a prolonged exploration of the neck and mediastinum into a brief, curative procedure with minimal morbidity. C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NIDDK,METAB DIS BRANCH,BETHESDA,MD. NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DEPT SURG,ST LOUIS,MO 63110. NR 18 TC 36 Z9 36 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1994 VL 116 IS 6 BP 982 EP 990 PG 9 WC Surgery SC Surgery GA PW090 UT WOS:A1994PW09000006 PM 7985106 ER PT J AU SAJI, M LEVINE, MA ZEIGER, MA AF SAJI, M LEVINE, MA ZEIGER, MA TI AN IN-VITRO MODEL OF THYROID NEOPLASIA - PERMANENTLY TRANSFECTED FRTL-5 CELLS WITH THYROGLOBULIN PROMOTER CHOLERA-TOXIN A1 SUBUNIT MINIGENE SO SURGERY LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 17-19, 1994 CL DEARBORN, MI SP AMER ASSOC ENDOCRINE SURGEONS ID TYROSINE KINASE; MUTATIONS; CARCINOMAS; ONCOGENES; ADENOMAS; SEQUENCE; GENES; HYPERPLASIA; ACTIVATION; TRANSGENE AB Background. Activating mutations of protein G(s alpha) that stimulates adenylyl cyclase are present in a subset of thyroid adenomas. Cholera toxin A1 subunit (CT) mimics these mutations via adenosine diphosphate-ribosylation of G(s alpha). Methods. To test the role of activated G(s alpha) in thyroid neoplasia we developed an in vitro model. With molecular genetic techniques a transgene (TG-CT) in which the thyroglobulin gene (TG) promoter directs expression of CT was made. This transgene was transfected into rat thyroid follicular cells (FRTL-5). Integration of TG-CT transgene and its expression were examined. Results. Polymerase chain reaction of DNA from transfected FRTL-5 cells identified the TG-CT transgene in six cell lines. The TG-CT transfected clones exhibited up to a 65-fold (1.29 +/- 0.37 pmols cyclic adenosine monophosphate (cAMP)/mu gDNA) increase in cAMP over nontransfected FRTL-5 cells (0.02 +/- 0.001 pmols cAMP/mu g DNA). Insulin, a known stimulator of the TG promoter, further induced CT gene expression and led to a 209-fold (10.43 +/- 0.10 pmols cAMP/mu g DNA) increase in cAMP over nontransfected cells (0.05 +/- 0.00 pmols cAMP/mu g DNA). Conclusions. By mimicking a known mutation associated with thyroid neoplasms, these permanently transfected FRTL-5 cells lines will serve as a model to examine the long-term potential neoplastic effects of activated G(s alpha) on thyroid follicular cells. C1 JOHNS HOPKINS MED INST,DEPT MED,BALTIMORE,MD 21287. NIDDK,BETHESDA,MD. JOHNS HOPKINS MED INST,DEPT SURG,BALTIMORE,MD 21287. OI Levine, Michael/0000-0003-0036-7809 NR 24 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1994 VL 116 IS 6 BP 1048 EP 1053 PG 6 WC Surgery SC Surgery GA PW090 UT WOS:A1994PW09000016 PM 7985086 ER PT J AU ARNOLD, WS FRAKER, DL ALEXANDER, HR WEBER, HC NORTON, JA JENSEN, RT AF ARNOLD, WS FRAKER, DL ALEXANDER, HR WEBER, HC NORTON, JA JENSEN, RT TI APPARENT LYMPH-NODE PRIMARY GASTRINOMA SO SURGERY LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 17-19, 1994 CL DEARBORN, MI SP AMER ASSOC ENDOCRINE SURGEONS ID ZOLLINGER-ELLISON SYNDROME; CONSERVATIVE SURGERY; EXPERIENCE; RESECTION; VAGOTOMY; CHILDREN AB Background. The existence of lymph node (LN) primary gastrinoma as a cause of Zollinger-Ellison syndrome is controversial. We reviewed our experience with patients in whom gastrinomas were identified and excised only from LNs. Methods. From 1982 to 1992, 110 patients with ZES underwent exploration for gastrinoma and 21 (19%) had disease limited to one or more LNs. Standardized exploration included intraoperative ultrasonography, intraoperative endoscopy with transillumination, and exploratory duodenotomy in 86%, 67%, and 24% of patients, respectively. Each patient underwent yearly biochemical and radiologic follow-up. Results. Thirteen patients (62%) with a median follow-up period of 5.8 years had an initial biochemical cure, whereas eight patients (38%) with a median follow-up period of 3.6 years had persistent disease. Of the 13 patients whose condition initially returned to normal, four have had biochemical recurrence, with a median time to recurrence of 4.2 years and a median follow-up period of 7.4 years. Nine patients (43%) remain biochemically cured, with a median follow-up period of 5.3 years. Conclusions. Resection of apparent LN primary gastrinoma is warranted, because 43% of those who underwent resection had no evidence of disease, with a median follow-up period of 5.3 years. C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NIDDKD,BETHESDA,MD 20892. NR 25 TC 43 Z9 43 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1994 VL 116 IS 6 BP 1123 EP 1130 PG 8 WC Surgery SC Surgery GA PW090 UT WOS:A1994PW09000027 PM 7985097 ER PT J AU LEXOW, N JOYCE, JN KIM, SJ PHILLIPS, J CASANOVA, MF BIRD, ED KLEINMAN, JE WINOKUR, A AF LEXOW, N JOYCE, JN KIM, SJ PHILLIPS, J CASANOVA, MF BIRD, ED KLEINMAN, JE WINOKUR, A TI ALTERATIONS IN TRH RECEPTORS IN TEMPORAL-LOBE OF SCHIZOPHRENICS - A QUANTITATIVE AUTORADIOGRAPHIC STUDY SO SYNAPSE LA English DT Article DE THYROTROPIN-RELEASING HORMONE; HUNTINGTONS DISEASE; ALZHEIMERS DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; AMYGDALA; HIPPOCAMPUS ID THYROTROPIN-RELEASING-HORMONE; MESOLIMBIC DOPAMINE SYSTEM; HUMAN-BRAIN; ALZHEIMERS-DISEASE; HIPPOCAMPAL-FORMATION; AMYGDALOID COMPLEX; HUNTINGTONS-DISEASE; MEMORY IMPAIRMENT; SUBSTANTIA NIGRA; CENTRAL NUCLEUS AB We utilized quantitative autoradiography to determine the distribution of receptors for thyrotropin-releasing hormone (TRH) throughout the human temporal lobe and to examine the distribution of these receptors in discrete subregions of the temporal lobe from patients diagnosed premortem with schizophrenia. When compared to non-neurologic controls, schizophrenic patients demonstrated an increase of 51% in the concentration of TRH receptors in the molecular layer of the dentate gyrus. Within nuclei of the schizophrenic amygdala, marked decreases were found in the central (44%), medial (38%), cortical (36%), accessory cortical (52%), lateral (54%), and medial basal (22%) nuclei. We also examined postmortem brain samples from patients with Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease for alterations in the distribution of TRH receptors. No significant differences from non-neuropsychiatric controls were noted within the hippocampus in any of these disease states; however, slight alterations were noted in the central and medial basal amygdala in Huntington's disease and in the cortical amygdala in Alzheimer's disease. These disease-specific findings suggest that TRH may play a role in the neurochemical dysfunction of schizophrenia. (C) 1994 Wiley-Liss, Inc. C1 UNIV PENN,DEPT PHARMACOL,PHILADELPHIA,PA 19104. NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,CTR NEUROSCI,NEUROPATHOL SECT,WASHINGTON,DC 20032. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02114. RP LEXOW, N (reprint author), UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104, USA. FU NCRR NIH HHS [2-S07-RR-05415-26]; NIMH NIH HHS [MH00044]; NINDS NIH HHS [R01 NS19597] NR 90 TC 8 Z9 8 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD DEC PY 1994 VL 18 IS 4 BP 315 EP 327 DI 10.1002/syn.890180407 PG 13 WC Neurosciences SC Neurosciences & Neurology GA QH899 UT WOS:A1994QH89900006 PM 7886624 ER PT J AU WURTH, YA REINDERS, JMC RALL, WF KRUIP, TAM AF WURTH, YA REINDERS, JMC RALL, WF KRUIP, TAM TI DEVELOPMENTAL POTENTIAL OF IN-VITRO PRODUCED BOVINE EMBRYOS FOLLOWING CRYOPRESERVATION AND SINGLE-EMBRYO TRANSFER SO THERIOGENOLOGY LA English DT Article DE BOVINE; IN VITRO; CRYOPRESERVATION; SINGLE-EMBRYO TRANSFER ID FERTILIZED INVITRO; BLASTOCYST STAGE; CATTLE EMBRYOS; CUMULUS CELLS; CO-CULTURE; OOCYTES; BIRTH; CALVES AB Information on the developmental potential of in vitro-produced, cryopreserved bovine embryos following single-embryo transfer to synchronized recipients is limited. The aim of this study was to compare the pregnancy rates of vitrified, conventionally cryopreserved, and control (unfrozen) in vitro embryos. The embryos were cryopreserved either by Vitrification in Solution 3a (VS3a) or by conventional slow freezing in 10% glycerol. Forty-two percent (n=121) of the recipients established pregnancy when in vitro produced morulae to expanded blastocyst stage embryos were transferred immediately following culture. Significantly more morulae on Day 7 and 8 of culture established pregnancy (11/14) than blastocysts on Days 7 to 9 of culture (40/107; P<0.05). Significantly fewer biastocysts on Day 9 of culture established pregnancy (12/35) than those on Days 7 and 8 of culture (39/86; P<0.05). Cryopreserved embryos yielded significantly fewer pregnancy rates than freshly transferred embryos (P<0.05). Twenty-three percent (n=85) of vitrified embryos and 14% (n=35) of conventially frozen embryos established pregnancies. When cryopreservation methods were compared in terms of embryo stage, vitrification did not yield significantly better results than the conventional freezing method, but this might be due to the low number of conventionally frozen embryos transferred. These data indicate that in vitro produced embryos yield high pregnancy rates when transferred immediately following in vitro culture for 7 or 8 d to the morula and blastocyst stages. Cryopreservation of in vitro produced embryos either by vitrification or conventional freezing reduced their ability to establish pregnancy. Vitrification was found to be the more practicable method; therefore, when transfer of fresh embryos is not possible, vitrification should be preferred to conventional freezing methods. C1 INST ANIM SCI & HLTH,8219 PH LELYSTAD,NETHERLANDS. KI OOST,DEPT ET,HELLENDOORN,NETHERLANDS. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NR 25 TC 40 Z9 42 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0093-691X J9 THERIOGENOLOGY JI Theriogenology PD DEC PY 1994 VL 42 IS 8 BP 1275 EP 1284 DI 10.1016/0093-691X(94)90247-G PG 10 WC Reproductive Biology; Veterinary Sciences SC Reproductive Biology; Veterinary Sciences GA PV519 UT WOS:A1994PV51900005 ER PT J AU HIDAKA, A BAN, T PANESAR, NS MINEGISHI, T KOHN, LD TAHARA, K AF HIDAKA, A BAN, T PANESAR, NS MINEGISHI, T KOHN, LD TAHARA, K TI THYROTROPIN STIMULATION OF THE LUTROPIN/CHORIOGONADOTROPIN RECEPTOR - DIFFERENT SITES MEDIATE AGONIST ACTIVITY AND HIGH-AFFINITY BINDING SO THYROID LA English DT Article ID CHORIONIC-GONADOTROPIN RECEPTOR; AUTOIMMUNE THYROID-DISEASE; INOSITOL PHOSPHATE LEVELS; 3RD CYTOPLASMIC LOOP; N-TERMINAL REGION; TSH-RECEPTOR; EXTRACELLULAR DOMAIN; IDIOPATHIC MYXEDEMA; CYCLIC-AMP; CHORIOGONADOTROPIN RECEPTOR AB Surprisingly, thyrotropin (TSH) can increase cAMP and inositol phosphate (IP) levels in Cos-7 cells transfected with the hutropin (LH)/choriogonadotropin (CG) receptor (LH/CGR) as well as LH or CG, as evidenced by similar EC(50) and maximal stimulation values. Additionally surprising, TSH activation is evident, despite markedly reduced levels of high affinity TSH binding by comparison to CG (Hidaka A, et al. 1993 Biochem Biophys Res Commun 196:187-195). In this report, we questioned whether the unusual TSH activity, as well as the discrepancy between TSH activity and binding, might reflect the existence of distinct agonist and binding sites on the LH/CGR extracellular domain and the ability of TSH to interact with the former despite a minimal interaction with the latter. We evaluated this possibility by using two chimeras spanning the extracellular domain of the TSHR and the LH/CGR: Mc1 + 2, where residues 8-165 of the TSHR are substituted, and Mc2 + 3 + 4, where residues 90-370 are replaced with the corresponding peptide segment from the LH/CGR. After transfection in Cos-7 cells, Mc2 + 3 + 4 exhibits higher affinity for CG than wild-type LH/CGR, but has no CG agonist response in assays measuring cAMP or inositol phosphate (IP) levels. Conversely, the Mc1 + 2 chimera exhibits significantly decreased affinity for CG, but CG agonist activity Is comparable to wild-type LH/CGR in cAMP and IP assays. These data show that the extracellular domain of the LH/CGR does have distinct sites for CG binding and agonist activity: the C-terminus in Mc2 + 3 + 4 is important for high affinity CG binding, whereas the N-terminus in Mc1 + 2 is able to exhibit a CG agonist response, despite low affinity binding. When evaluated using TSH, Mc1 + 2,with the C-terminus of the TSHR present, exhibits high affinity TSH binding comparable to wild-type TSHR. Unexpectedly, Mc1 + 2, with the substitution of the N-terminus of the extracellular domain of the LH/CGR, exhibits even better TSH agonist activity than wild-type TSHR, not a loss of activity. Thus, the N-terminus of the extracellular domain of the LH/CGR can couple TSH binding to signal transduction events even better than the N-terminus of the TSHR. This may, in part, explain why TSH has an unusual agonist activity in cells transfected with LH/CGR, despite relatively low affinity binding. Although distinct agonist and binding sites exist in the linear sequence of the extracellular domain, the activity of the two sites is interdependent. Thus, Mc1 + 2 retains the linear epitopes for reactivity with blocking TSHR autoantibodies; however, the ability of these antibodies to inhibit TSH-increased cAMP levels is reduced by comparison to wild-type TSHR. Three of the four blocking TSHR IgGs were, in addition able to inhibit hCG increased cAMP levels in Mc1 + 2-transfected cells better than inhibition of TSH-stimulated cAMP levels in the same cells. There is, therefore, an altered interaction between the N- and C-terminus in Mc1 + 2; as a result, high affinity TSH binding overcomes the blocking TSHRAb inhibition, whereas low affinity hCG binding does not and inhibition persists. C1 NIDDKD,BIOCHEM & METAB LAB,CELL REGULAT SECT,BETHESDA,MD 20892. CHIBA UNIV,SCH MED,DEPT INTERNAL MED 2,CHIBA 280,JAPAN. GUNMA UNIV,SCH MED,DEPT OBSTET & GYNECOL,MAEBASHI,GUMMA 371,JAPAN. NR 56 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD WIN PY 1994 VL 4 IS 4 BP 447 EP 457 DI 10.1089/thy.1994.4.447 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QB897 UT WOS:A1994QB89700010 PM 7711510 ER PT J AU KELLNERCOUSIN, K MIALHE, E MATHIEU, M AF KELLNERCOUSIN, K MIALHE, E MATHIEU, M TI IDENTIFICATION OF INSULIN-LIKE PEPTIDES IN CEREBRAL GANGLIA NEUROSECRETORY-CELLS OF THE MUSSEL MYTILUS-EDULIS SO TISSUE & CELL LA English DT Article DE INSULIN-LIKE; NEUROSECRETORY CELLS; MYTILUS EDULIS; IMMUNOCYTOCHEMISTRY; ELISA; GROWTH CONTROL ID CENTRAL-NERVOUS-SYSTEM; LOBSTER HOMARUS-AMERICANUS; BIOLOGICAL-ACTIVITY; LYMNAEA-STAGNALIS; MESSENGER-RNA; GROWTH; SEQUENCE; SNAIL; PREPROINSULIN; EXPRESSION AB The immunostaining patterns of cerebral ganglia sections from the mussel Mytilus edulis with monoclonal antibodies raised against cerebral ganglia (CG) extracts were compared to those obtained with various polyclonal anti-insulin-like antibodies. One of the monoclonal antibodies (MAB 46) revealed clusters of positive cells in localization comparable to those revealed by the polyclonal antibodies. The nature of the antigen recognized by MAB 46 and the polyclonal antibodies was compared by gel filtration-HPLC of a cerebral ganglia extract. Similar peaks were revealed by the monoclonal and polyclonal antibodies. MAB 46 significantly inhibited the cerebral ganglia induced stimulation of amino-acid incorporation by mantle edge cell suspensions, suggesting that the antigen recognized by MAB 46 is involved in the control of growth. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. RP KELLNERCOUSIN, K (reprint author), IBBA,BIOL & BIOTECHNOL MARINES LAB,IFREMER,UMR 14,EQUIPE RECH MARINE,ESPLANADE PAIX,F-14032 CAEN,FRANCE. NR 45 TC 12 Z9 14 U1 1 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0040-8166 J9 TISSUE CELL JI Tissue Cell PD DEC PY 1994 VL 26 IS 6 BP 891 EP 899 DI 10.1016/0040-8166(94)90038-8 PG 9 WC Anatomy & Morphology; Cell Biology SC Anatomy & Morphology; Cell Biology GA PZ489 UT WOS:A1994PZ48900008 PM 7886675 ER PT J AU KU, WW CHAPIN, RE AF KU, WW CHAPIN, RE TI SPERMATOCYTE TOXICITY OF 2-METHOXYETHANOL IN-VIVO AND IN-VITRO - REQUIREMENT FOR AN INTACT SEMINIFEROUS TUBULE STRUCTURE FOR GERM-CELL DEGENERATION SO TOXICOLOGY IN VITRO LA English DT Article ID ETHYLENE-GLYCOL MONOMETHYL; SPERMATOGENIC CELLS; TESTICULAR TOXICITY; RAT; INVITRO; ETHER; METABOLISM; CULTURES; INVIVO; MOUSE AB Cultures of isolated testicular cells are widely used for evaluating mechanisms of action of direct-acting testicular toxicants. However, for testicular cells, the expression of toxicity in vitro is frequently different from that found in vivo. 2-Methoxyethanol (ME) produces testicular lesions in rats which are characterized by pachytene spermatocyte degeneration 24 hr after dosing. As part of a study to evaluate mechanisms of male germ cell toxicants, we compared the morphological aspects of spermatocyte toxicity after in vivo exposure to ME with those found in various testicular cell culture systems after in vitro exposure to the active ME metabolite, 2-methoxyacetic acid (MAA). Immature rats were used because they respond to in vivo ME treatment in the same way as adults, but their testes are relatively enriched in pachytene spermatocytes. 24-day-old rats were given a single dose of 250 mg ME/kg body weight by gavage and the testes were evaluated 24 hr after dosing. In vitro, cultured seminiferous tubules, Sertoli-germ cell co-cultures, and enriched mixed germ cells, all prepared from 24-day-old rats, were evaluated after 24-hr in vitro exposure to 5 mM MAA (a level of MAA found after ME exposure in vivo). Testes from ME-exposed rats showed the expected pachytene spermatocyte degeneration 24 hr after dosing. Similar changes were observed in cultured seminiferous tubules after 24 hr of exposure to MAA in vitro. However, without the intact seminiferous tubule structure in vitro, the expression of MAA spermatocyte toxicity was different. In conventional Sertoli-germ cell co-cultures, spermatocyte detach ment from the Sertoli cell monolayer occurred as expected, although no significant morphological degeneration was observed in these detached germ cells. Similarly, no increase in degenerating spermatocytes was noted in isolated enriched mixed germ cells after in vitro MAA exposure. Instead, toxicity in these germ cell fractions was expressed only by increased uptake of trypan blue dye, revealing an increase in plasma membrane permeability. In summary, this in vivo/in vitro comparison of the spermatocyte toxicity of ME/MAA showed that the expression of toxicity is different in the different culture architectures and that an intact seminiferous tubule structure is required for full expression of the morphological degeneration produced by ME/MAA, and suggests the usefulness of culture seminiferous tubules in future mechanistic studies. C1 NIEHS,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. OI Chapin, Robert/0000-0002-5997-1261 NR 24 TC 17 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD DEC PY 1994 VL 8 IS 6 BP 1191 EP & DI 10.1016/0887-2333(94)90109-0 PG 0 WC Toxicology SC Toxicology GA PW463 UT WOS:A1994PW46300006 PM 20693088 ER PT J AU TSUTSUI, T MATSUDO, Y TANAKA, Y ROKUKAWA, A SATO, H OMORI, N BARRETT, JC AF TSUTSUI, T MATSUDO, Y TANAKA, Y ROKUKAWA, A SATO, H OMORI, N BARRETT, JC TI QUANTITATIVE COMPARISON OF CYTOTOXICITY OF DENTAL ANTISEPTICS TO NORMAL HUMAN ORAL KERATINOCYTES IN-VITRO SO TOXICOLOGY IN VITRO LA English DT Article ID NEUTRAL RED AB The cytotoxicities of antiseptics used in dentistry were examined with normal human keratinocytes from the oral cavity by the uptake of neutral red (NR assay). The NR assay is a quantitative in vitro assay that distinguishes between viable, damaged or dead cells. Cultures from different individuals were established, and secondary cultures in serum-free medium were used. The amount of NR extracted from cells after a 3-hr uptake of the dye was linearly proportional to the number of cells exposed to the dye. The cytotoxicity of antiseptics used on mucous membranes in the oral cavity was determined from the dose-response curves of inhibition of NR uptake in cells treated with antiseptics for 2 days. As a quantitative measure of cytotoxicity, NR(50) (i.e. the concentration of antiseptics that resulted in a 50% decrease in NR uptake relative to untreated controls) was extrapolated from dose-response curves. The rank-order of cytotoxicities (NR(50)) was Hyamine (10% benzethonium chloride solution) > Hibitane (5% chlorhexidine gluconate solution) > acrinol (0.2% acrinol solution) > Iodine Carbol (liquefied phenol with 3% iodine) > iodine glycerin (glycerin with 10% iodine) > dilute iodine tincture (3% iodine solution) approximate to iodine tincture (6% iodine solution) approximate to Isodine (10% povidone-iodine solution) > Oxydol (3% hydrogen peroxide solution). These results provide useful estimates of relative toxicities of antiseptics to human cells, which can be compared with antimicro-organism activity to maximize therapeutic benefit with minimal toxicity. C1 NIEHS,MOLEC CARCINOGENESIS LAB,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. RP TSUTSUI, T (reprint author), NIPPON DENT UNIV TOKYO,SCH DENT,DEPT PHARMACOL,CHIYODA KU,1-9-20 FUJIMI,TOKYO 102,JAPAN. NR 14 TC 1 Z9 1 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD DEC PY 1994 VL 8 IS 6 BP 1253 EP 1258 DI 10.1016/0887-2333(94)90117-1 PG 6 WC Toxicology SC Toxicology GA PW463 UT WOS:A1994PW46300014 PM 20693096 ER PT J AU RAYMER, JH SLAUTER, RW VELEZ, GR GAUDETTE, N AF RAYMER, JH SLAUTER, RW VELEZ, GR GAUDETTE, N TI A NONREBREATHING BREATH COLLECTION SYSTEM FOR THE STUDY OF EXOGENOUS AND ENDOGENOUS COMPOUNDS IN THE FISHER-344 RAT SO TOXICOLOGY METHODS LA English DT Article DE NONREBREATHING BREATH COLLECTION; VOLATILE ORGANIC COMPOUNDS; THERMAL DESORPTION GAS CHROMATOGRAPHY; FISHER-344 RAT; CARBON TETRACHLORIDE ADMINISTRATION ID ELECTROPHILIC CHLORINE; CARBON-TETRACHLORIDE; LIPID-PEROXIDATION; CYTOCHROME-P-450; PRODUCTS; ACETONE; GAS AB A nose-only, nonrebreathing breath collection system for use with Fisher-344 rats was developed and characterized. The system is open in design and relies on mass now controllers to regulate both the introduction of clean, humidified air and the withdrawal of exhaled breath in a balanced fashion, The system accommodates simultaneous collection from three rats held in Battelle-type restrainers modified to include an auxiliary nitrogen purge to minimize the infiltration of volatile organic compounds (VOCs) from the room and excreta into the collected breath, The VOCs in breath were collected onto Tenax or multisorbent cartridges and analyzed by thermal desorption/gas chromatography with flame ionization or mass spectrometric detection, Recoveries through the collection and analysis system for a mixture of chemically diverse standard compounds at 4-10 ng/L each averaged 98%. The administration of carbon tetrachloride dramatically increased the number and amount of VOCs in breath, Increases were measured for hydrocarbons, aldehydes, ketones, and chlorinated species. The composition of these VOCs in breath was observed to be time dependent. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP RAYMER, JH (reprint author), RES TRIANGLE INST,3040 CORNWALLIS RD,RES TRIANGLE PK,NC 27709, USA. NR 21 TC 4 Z9 4 U1 1 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 1051-7235 J9 TOXICOL METHOD JI Toxicol. Method. PD DEC PY 1994 VL 4 IS 4 BP 243 EP 258 DI 10.3109/15376519409068450 PG 16 WC Toxicology SC Toxicology GA PY546 UT WOS:A1994PY54600004 ER PT J AU DEHESADAVILA, M MARTIN, BM NOBILE, M PRESTIPINO, G POSSANI, LD AF DEHESADAVILA, M MARTIN, BM NOBILE, M PRESTIPINO, G POSSANI, LD TI ISOLATION OF A TOXIN FROM CENTRUROIDES INFAMATUS INFAMATUS KOCH SCORPION-VENOM THAT MODIFIES NA+ PERMEABILITY ON CHICK DORSAL-ROOT GANGLION-CELLS SO TOXICON LA English DT Article ID SENSORY NEURONS; CURRENTS; HOFFMANN AB A novel toxin was isolated and characterized from the venom of the Mexican scorpion Centruroides infamatus infamatus. It has an apparent mol. wt of 7600, compatible with the presence of 66 amino acid residues per molecule. The N-terminal amino acid sequence was determined (up to residue 48) and showed approximately 95% similarity with toxins from other Mexican scorpions of the genus Centruroides. Experiments conducted with chick dorsal root ganglion cells showed that toxin 1 is a Na+ channel effector, causing a decrease in the peak Na+ permeability, similar to decreases observed for typical beta-scorpion toxins. C1 UNIV NACL AUTONOMA MEXICO,INST BIOTECHNOL,DEPT BIOQUIM,CUERNAVACA 62271,MORELOS,MEXICO. NIMH,MOLEC NEUROGENET SECT,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. CNR,IST CIBERNET & BIOFIS,I-16146 GENOA,ITALY. RI Possani, Lourival/J-2397-2013 NR 17 TC 5 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0041-0101 J9 TOXICON JI Toxicon PD DEC PY 1994 VL 32 IS 12 BP 1487 EP 1493 DI 10.1016/0041-0101(94)90307-7 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QB416 UT WOS:A1994QB41600001 PM 7725317 ER PT J AU MARTI, GE BAUER, S PURI, RK NOGUCHI, PD AF MARTI, GE BAUER, S PURI, RK NOGUCHI, PD TI REGULATORY REVIEW OF CELLULAR AND GENE THERAPIES - AN OVERVIEW OF THE PROCESS SO TRANSFUSION SCIENCE LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the European-Society-for-Haemapheresis CY SEP 12-15, 1993 CL ABERDEEN, SCOTLAND SP EUROPEAN SOC HAEMAPHERESIS AB Cell and gene therapies, using several different approaches, have been proposed for a variety of genetic diseases, cancer and AIDS. The major regulatory review process in the US consists of an institutional review board, the recombinant DNA advisory committee (RAC) and the Food and Drug Administration (FDA). Within the Center for Biologics Evaluation and Research, the Division of Cellular and Gene Therapies has been formed to primarily review investigational new drug applications (INDs) for cellular and gene therapies. Several appropriate ''points to consider'' documents have been prepared and the RAC has approved over 40 clinical protocols. Advances in biotechnology and the scientific basis for these advances are changing rapidly. Although a flexible, case-by-case approach is necessitated by these rapid changes, regulatory concerns common to all biologicals administered to human subjects remain unchanged. These include safety, efficacy, purity, potency, quality control and assessment, and reproducibility of individual lots. The goal of the review process is a prompt, complete and meticulous review. The emphasis of a pre-IND meeting is toward a working relationship between the sponsor and the FDA prior to the phase I, II and III clinical trials. A timely and ongoing evaluation of pre-clinical testing cannot be overemphasized in this rapidly growing and changing field. The development of a working relationship at this stage will ensure a seamless integration of the IND process with the product and establishment license applications. Because replication-competent retrovirus (RCR) represents a potential for pathogenicity, the FDA is recommending a conservative approach to RCR testing. RP MARTI, GE (reprint author), NIH,FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,OFF THERAPEUT RES & REVIEW,ROCKVILLE,MD 20892, USA. OI Bauer, Steven/0000-0003-2831-846X 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 0955-3886 J9 TRANSFUS SCI JI Transfus. Sci. PD DEC PY 1994 VL 15 IS 4 BP 323 EP 329 DI 10.1016/0955-3886(94)90163-5 PG 7 WC Hematology SC Hematology GA PQ801 UT WOS:A1994PQ80100002 PM 10155549 ER PT J AU OMMAYA, AK ATWATER, I COONROD, BA BOSHERO, AC SZPAKGLASMAN, M LUBENSKY, I BACHER, J AF OMMAYA, AK ATWATER, I COONROD, BA BOSHERO, AC SZPAKGLASMAN, M LUBENSKY, I BACHER, J TI NOVEL TRANSPLANTATION APPROACH - ISLET-CELL GRAFTS IN CEREBRAL SPINAL-FLUID SHUNTS IN DOGS SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress of the Cell-Transplant-Society CY MAY 01-04, 1994 CL MINNEAPOLIS, MN SP Cell Transplant Soc C1 NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,SURG RADIOL & PHARM SECT,BETHESDA,MD 20892. NR 0 TC 3 Z9 4 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD DEC PY 1994 VL 26 IS 6 BP 3340 EP 3342 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PW987 UT WOS:A1994PW98700107 PM 7998164 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - GLOWING BLUE GELS AND NUKED NUCLEASES SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Note ID DNA AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses some unidentified blue fluorescence observed emanating from agarose gels, and the use of microwave ovens for DNA restriction digests. For details on how to partake in the newsgroup, see the accompanying box. RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 1994 VL 19 IS 12 BP 556 EP 557 DI 10.1016/0968-0004(94)90061-2 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX385 UT WOS:A1994PX38500014 PM 7846770 ER PT J AU BRISTOL, JA RHEE, SG AF BRISTOL, JA RHEE, SG TI REGULATION OF PHOSPHOLIPASE C-BETA ISOZYMES BY G-PROTEINS SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID PHOSPHATIDYLINOSITOL-TRANSFER PROTEIN; GAMMA-SUBUNITS; ALPHA-SUBUNITS; BINDING PROTEIN; GTP-BINDING; ACTIVATION; PURIFICATION; RECONSTITUTION; RECEPTORS; DIVERSITY AB Phospholipase C (PLC) isozymes ave known to be regulated in part, by heterotrimeric GTP-binding protein (G-protein) subunits, including G alpha subunits of the G(q) family and G beta gamma subunits. New data show that PLC can also be regulated by a high molecular weight G-protein that doubles as a cellular transglutaminase. Furthermore, a soluble phosphatidylinositol transfer protein (PITP) has been implicated in sustaining the activity of PLC by delivering substrate to the plasma membrane. Such diverse regulatory mechanisms imply that the PLC isozymes are precisely controlled and have specific roles in generating second messengers in response to various external stimuli. RP BRISTOL, JA (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,BETHESDA,MD 20892, USA. NR 37 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD DEC PY 1994 VL 5 IS 10 BP 402 EP 406 DI 10.1016/1043-2760(95)92522-K PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PY361 UT WOS:A1994PY36100002 PM 18407236 ER PT J AU NAZAROV, V HILBERT, D WOLFF, L AF NAZAROV, V HILBERT, D WOLFF, L TI SUSCEPTIBILITY AND RESISTANCE TO MOLONEY MURINE LEUKEMIA VIRUS-INDUCED PROMONOCYTIC LEUKEMIA SO VIROLOGY LA English DT Article ID HOST IMMUNE-RESPONSE; C-MYB ACTIVATION; GENETIC-CONTROL; MESSENGER-RNA; BALB/C MICE; FRIEND; TUMORS; INDUCTION; SEQUENCE; RECOVERY AB Moloney murine leukemia virus (M-MuLV) induces promonocytic leukemias, called MML, in pristane-treated adult mice. These tumors invariably express fused gag-myb mRNA as a consequence of virus integration and activation of the c-myb locus. In the present study it was determined that while BALB/c and DBA/2N mice are highly susceptible, C57BL/6, C3H/He, STS/A, NFS, NIH/Swiss, SJL/J, and NZB mice are strongly resistant to tumor induction. Although C57BL/6 mice were resistant because they were unable to support early virus replication in hematopoietic tissue, NFS and C3H/He mice supported replication and were shown, using RT-PCR, to have cells in the bone marrow and spleen that expressed the aberrant, leukemia-related gag-myb mRNA. This provided evidence that early stages of leukemia were permitted to develop in these mice, but preneoplastic cells were unable to progress to the acute phase. Experiments in which MML was induced by M-MuLV plus pristane treatment in immunodeficient C3H/He nu/nu and sublethally irradiated C3H/He mice suggested that the immune response may play a role in eliminating preleukemic cells in immunocompetent C3H/He. Tumors from these mice had rearrangements at the c-myb locus and expressed gag-myb RNA. It was concluded that, at least in the case of C3H/He mice, resistance is not due to an inability of virus to activate c-myb or to a lack of other tumor promoting events. Rather, leukemia development appears to be restricted by an immune response, presumably T-cell mediated. Evidence is provided that non-H-2 MHC genes are required for resistance in both C57BL/6 and C3H/He mice and that resistance is dominant. This provides an animal model for the study of tumor progression as it relates to the immune response (C) 1994 Academic Press, Inc C1 NCI,GENET LAB,BETHESDA,MD 20892. NR 28 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 1994 VL 205 IS 2 BP 479 EP 485 DI 10.1006/viro.1994.1668 PG 7 WC Virology SC Virology GA PU592 UT WOS:A1994PU59200010 PM 7975249 ER PT J AU KENNEDY, PGE MAJOR, EO WILLIAMS, RK STRAUS, SE AF KENNEDY, PGE MAJOR, EO WILLIAMS, RK STRAUS, SE TI DOWN-REGULATION OF GLIAL FIBRILLARY ACIDIC PROTEIN EXPRESSION DURING ACUTE LYTIC VARICELLA-ZOSTER VIRUS-INFECTION OF CULTURED HUMAN ASTROCYTES SO VIROLOGY LA English DT Note ID CELLS; NEURONS AB The effects of the varicella-zoster virus (VZV) OKA vaccine strain in producing morphologic and antigenic changes in dissociated cultures of human fetal brain was investigated. Cultures containing 80% glial acidic fibriliary protein (GFAP), GFAP(+) (positive) astrocytes and 20% GFAP(-) (negative) fibroblastic-like cells were infected with cell-free VZV OKA at a multiplicity of infection of 0.1 plaque-forming units per cell. Cytopathic effects and significant viral antigen labeling with antibodies against VZV gpl and immediate-early (IE) protein 62 were first detected 6 to 7 days postinfection. Several observations indicated that astrocyte GFAP expression was altered and diminished as a result of VZV infection itself, thereby raising doubts about the utility of combining cell markers and viral antigenic labeling in assessing the susceptibility of neural cell types to viral infection. The down-regulation of GFAP expression by VZV appears to be mediated by early rather than late events in the viral replication cycle and may not be the result of virally induced global shut-off of host cell protein synthesis. Similar observations were made using VZV Ellen, a multipassaged, nonvaccine strain. These observations have potential in vivo implications related to histologic analysis of VZV-infected tissues and disease pathogenesis. (C) 1994 Academic Press, Inc. C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892. NINCDS,MOLEC MED & NEUROSCI LAB,BETHESDA,MD 20892. NR 16 TC 15 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 1994 VL 205 IS 2 BP 558 EP 562 DI 10.1006/viro.1994.1679 PG 5 WC Virology SC Virology GA PU592 UT WOS:A1994PU59200021 PM 7975257 ER PT J AU OTT, DE KELLER, J REIN, A AF OTT, DE KELLER, J REIN, A TI 10A1 MULV INDUCES A MURINE LEUKEMIA THAT EXPRESSES HEMATOPOIETIC STEM-CELL MARKERS BY A MECHANISM THAT INCLUDES FLI-1 INTEGRATION SO VIROLOGY LA English DT Note ID C-KIT RECEPTOR; NON-T-CELL; LYMPHOCYTE-B PRECURSORS; ERYTHROPOIETIN RECEPTOR; PROGENITOR CELLS; SURFACE-MARKERS; GROWTH-FACTOR; IDENTIFICATION; VIRUSES; FRIEND AB The 10A1 murine leukemia virus induces tumors that lack lineage-specific markers found on myeloid, T-cell, and B-cell lineages. Either erythroid or multipotent stem cells can have this phenotype; therefore we have used fluorescence-activated cell sorter analysis with either multipotent stem cell markers or markers found on lineage-restricted precursors to differentiate between these two possibilities. The results showed that tumors induced by 10A1 expressed multipotent stem cell markers as well as some lineage-restricted precursor markers. To further study the tumor phenotype, we analyzed total RNAs from 1OA1-induced tumors by Northern blotting for c-kit, erythropoietin receptor, and T-cell gamma receptor mRNAs. Most of the tumors contained these mRNAs, which are characteristic of early hematopoietic cells. These results are consistent with the hypothesis that 1OA1-induced tumor cells are early multipotent hematopoietic stem cells. Southern blot analysis revealed that 14 of 14 1OA1-induced tumor cell DNAs examined contained MuLV integrations into the fli-1 gene. The results strongly suggested that promoter insertion into fli-1 is required for tumor formation. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP OTT, DE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENSIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 49 TC 23 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 1994 VL 205 IS 2 BP 563 EP 568 DI 10.1006/viro.1994.1680 PG 6 WC Virology SC Virology GA PU592 UT WOS:A1994PU59200022 PM 7975258 ER PT J AU BROKAW, JL YEE, CL MUNGER, K AF BROKAW, JL YEE, CL MUNGER, K TI A MUTATIONAL ANALYSIS OF THE AMINO-TERMINAL DOMAIN OF THE HUMAN PAPILLOMAVIRUS TYPE-16 E7 ONCOPROTEIN SO VIROLOGY LA English DT Note ID HUMAN KERATINOCYTES; ADENOVIRUS E1A; RETINOBLASTOMA PROTEIN; GENE-PRODUCT; T-ANTIGEN; ASSOCIATION; BIND; E6; IMMORTALIZATION; TRANSFORMATION AB The human papillomavirus type 16 (HPV-16) E7 oncoprotein shares structural and functional similarity with the adenovirus (Ad) E1A protein and the SV40 large tumor antigen (TAg), Like these other DNA tumor virus oncoproteins, HPV-16 E7 interacts with the ''pocket proteins,'' a family of host cellular proteins that include the retinoblastoma tumor suppressor protein and can cooperate with the ras oncogene to transform primary rodent cells. Mutational analyses have indicated that amino acid sequences outside of the pRB binding region are also important for the cellular transformation property oi HPV-16 E7. These sequences include an amino terminal domain of the E7 protein that is similar to a portion of conserved region 1 of Ad E1A. In this study it is shown that the homologous amino acid sequences in Ad E1A and SV40 TAg are functionally interchangeable with the amino terminal HPV-16 E7 domain in transformation assays. Deletion analysis across the amino terminus of HPV-16 E7 indicated that the overall integrity of the entire CR1 homology domain is important for the biological activity oi the HPV E7 oncoprotein. (C) 1994 Academic Press, Inc. C1 NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. OI Munger, Karl/0000-0003-3288-9935 NR 27 TC 30 Z9 31 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 1994 VL 205 IS 2 BP 603 EP 607 DI 10.1006/viro.1994.1688 PG 5 WC Virology SC Virology GA PU592 UT WOS:A1994PU59200030 PM 7975265 ER PT J AU KANG, MH WON, SM PARK, SS KIM, SG NOVAK, RF KIM, ND AF KANG, MH WON, SM PARK, SS KIM, SG NOVAK, RF KIM, ND TI PIPERINE EFFECTS ON THE EXPRESSION OF P4502E1, P4502B AND P4501A IN RAT SO XENOBIOTICA LA English DT Article ID INDUCTION; METABOLISM; MICE AB 1. Treatment of rat with piperine (PIP) (1 . 4 mmol/kg, 3 days ip injections) resulted in an approximate two-fold increase in total liver microsomal P450 content relative to that in uninduced animals. 2. 4-Nitrophenol and aniline hyroxylase activities in the hepatic microsomes prepared from rat treated with PIP decreased by 30 and 28% respectively as compared with control. Immunoblot analyses also revealed decreased P4502E1 levels in hepatic microsomes from PIP-treated animals. 3. In contrast with P4502E1 suppression, hepatic 2B1 and 2B2 levels were significantly increased in PIP-induced animals, as evidenced by both metabolic activity and immunoblot analysis of the liver microsomal fractions. The rate of hexobarbital hydroxylase activity in microsomes from PIP-treated animals was markedly elevated and was inhibited by approximately 62% in the presence of monoclonal anti-P4502B IgG. Immunoblot analyses demonstrated that P4502B1 and 2B2 levels in hepatic microsomes from PIP-treated animals were comparable with those from phenobarbital-treated animals. 4. 7-Ethoxycoumarin deethylase activity was elevated approximately two-fold in PIP-induced animals and was 17% of that derived from 3-methylcholanthrene-induced animals. 7-ethoxycoumarin deethylase activity in PIP-induced hepatic microsomes was inhibited 63% in the presence of monoclonal anti-P4501A antibody. Immunoblot analysis confirmed the increase in P4501A levels by PIP, which was 15% of that in hepatic microsomes from 3-methylcholanthrene-induced animals. 5. PIP treatment failed to affect microsomal epoxide hydrolase (mEH) and glutathione S-transferases (GST) expression, as indicated by immunoblot analyses using polyclonal antibodies toward mEH and GST subunits Ya, Yb1, Yb2 and Yc. 6. These results demonstrate that PIP treatment suppressed P4502E1 expression and enhanced 2B and 1A expression, whereas this agent failed to affect hepatic mEH and GST expression. C1 SEOUL NATL UNIV,COLL PHARM,SEOUL,SOUTH KOREA. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. DUKSUNG WOMENS UNIV,COLL PHARM,SEOUL,SOUTH KOREA. WAYNE STATE UNIV,INST CHEM TOXICOL,DETROIT,MI 48201. NR 19 TC 11 Z9 13 U1 0 U2 3 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD DEC PY 1994 VL 24 IS 12 BP 1195 EP 1204 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QL106 UT WOS:A1994QL10600003 PM 7771106 ER PT J AU PARK, CS PARDHASARADHI, K GIANOTTI, C VILLEGAS, E KRISHNA, G AF PARK, CS PARDHASARADHI, K GIANOTTI, C VILLEGAS, E KRISHNA, G TI HUMAN RETINA EXPRESSES BOTH CONSTITUTIVE AND INDUCIBLE ISOFORMS OF NITRIC-OXIDE SYNTHASE MESSENGER-RNA SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PIGMENTED EPITHELIAL-CELLS; MOLECULAR-CLONING AB The present study provided evidence for the presence of two forms of nitric oxide synthase(NOS) gene in the human retina. Expression of retinal constitutive type(rbNOS) and inducible type(riNOS) of NOS was detected in human retinal poly A(+)RNA by reverse transcriptase polymerase chain reaction(RT-PCR) method. The deduced amino acid sequence of the human retinal rbNOS showed more than 99% homology with human brain bNOS and that of riNOS was identical to the chondrocytes inducible iNOS with the exception for one amino acid. These differences in amino acid sequences of rbNOS and riNOS,with their counterparts in human brain and human chondrocytes sequences,were only in the non-cofactor binding sites. Northern blot analysis of the human retinal poly Af RNA and total RNA, using the PCR-amplified riNOS probe revealed the existence of riNOS message with the appearance of the band with the expected size of 4.4kb, while the message for rbNOS was not detectable. This was the first report of the deduced nucleotide sequence identification of two NOS genes from a human tissue, while there had been earlier reports from culture cells. (C) 1994 Academic Press, Inc. C1 NHLBI,MOLEC IMMUNOL LAB,CHEM PHARMACOL SECT,BETHESDA,MD 20892. RI Villegas, Eric/A-7373-2015 OI Villegas, Eric/0000-0002-8059-8588 NR 23 TC 35 Z9 40 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 30 PY 1994 VL 205 IS 1 BP 85 EP 91 DI 10.1006/bbrc.1994.2633 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PW785 UT WOS:A1994PW78500014 PM 7528017 ER PT J AU SHI, XL MAO, Y AF SHI, XL MAO, Y TI 8-HYDROXY-2'-DEOXYGUANOSINE FORMATION AND DNA-DAMAGE INDUCED BY SULFUR-TRIOXIDE ANION-RADICALS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SULFITE; OXIDATION; DIOXIDE AB The 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation and DNA damage by sulfur trioxide anion radicals (SO3.-) were investigated using ESR spin trapping, HPLC, and electrophoretic assays. Sulfite (SO32-) autoxidation generated both hydroxyl ((OH)-O-.) and SO3.-) radicals. Oxidation of SO32- by chromium(VI) generated only SO3.- with much enhanced yield. deoxyguanosine (dG) with SO32- generated 8-OHdG albeit at low yield. Chromium(VI) enhanced the yield four-fold. Electrophoretic assays showed that SO3.- radicals generated by chromium(VI) oxidation of SO32- caused DNA double strand breaks. The results demonstrate that SO3.- radicals are capable of causing dG hydroxylation and DNA double strand breaks. (C) 1994 Academic Press, Inc. RP SHI, XL (reprint author), NCI,EXPTL PATHOL LAB,BLDG 41,ROOM C301,BETHESDA,MD 20892, USA. RI Shi, Xianglin/B-8588-2012 NR 21 TC 63 Z9 66 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 30 PY 1994 VL 205 IS 1 BP 141 EP 147 DI 10.1006/bbrc.1994.2641 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PW785 UT WOS:A1994PW78500022 PM 7999014 ER PT J AU TATEISHI, K ARAKAWA, F MISUMI, Y TRESTON, AM VOS, M MATSUOKA, Y AF TATEISHI, K ARAKAWA, F MISUMI, Y TRESTON, AM VOS, M MATSUOKA, Y TI ISOLATION AND FUNCTIONAL EXPRESSION OF HUMAN PANCREATIC PEPTIDYLGLYCINE ALPHA-AMIDATING MONOOXYGENASE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MESSENGER-RNA; ENZYMES PAM; PANCREASTATIN; LOCALIZATION; CELLS; PEPTIDE; SECRETION; CLONING; FORMS; CDNA AB Pancreastatin (PST) is processed from chromogranin A and the C-terminal amide of the peptide is an absolute requirement for biological activities. Human pancreatic carcinoma cells QGP-1 which produce both chromogranin A and PST were used to isolate cDNAs encoding two forms of peptidylglycine alpha-amidating monooxygenase (PAM). The two forms are a full length bifunctional enzyme and a variant lacking the transmembrane domain-coding region. When the cDNAs of these two forms were expressed in COS-7 cells, cells transfected with the predicted soluble form released into the culture medium a very much higher amidating activity which converts human chromogranin A-(273-302) to PST-29. The optimal pH for amidating activity was 5.4 and Cu2+, ascorbate and catalase were required as cofactors for the both forms of PAM. Km values for the membrane-bound and the soluble forms of PAM were 15.7 +/- 3.1 mu M and 12.4 +/- 1.6 mu M, respectively. These results demonstrate that both forms of PAM can function in the posttranslational processing of chromogranin A to PST in the environment of a secretory vesicle. (C) 1994 Academic Press, Inc. C1 FUKUOKA UNIV,SCH MED,DEPT BIOCHEM 2,FUKUOKA 81480,JAPAN. NCI,DIV CANC PREVENT & CONTROL,BIOMAKERS & PREVENT RES BRANCH,BETHESDA,MD 20892. RP TATEISHI, K (reprint author), FUKUOKA UNIV,SCH MED,DEPT BIOCHEM 1,FUKUOKA 81480,JAPAN. NR 21 TC 14 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 30 PY 1994 VL 205 IS 1 BP 282 EP 290 DI 10.1006/bbrc.1994.2662 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PW785 UT WOS:A1994PW78500043 PM 7999037 ER PT J AU KOBAYASHI, J INADERA, H FUJITA, Y TALLEY, G MORISAKI, N YOSHIDA, S SAITO, Y FOJO, SS BREWER, HB AF KOBAYASHI, J INADERA, H FUJITA, Y TALLEY, G MORISAKI, N YOSHIDA, S SAITO, Y FOJO, SS BREWER, HB TI A NATURALLY-OCCURRING MUTATION AT THE 2ND BASE OF CODON ASPARAGINE-43 IN THE PROPOSED N-LINKED GLYCOSYLATION SITE OF HUMAN LIPOPROTEIN-LIPASE - IN-VIVO EVIDENCE THAT ASPARAGINE-43 IS ESSENTIAL FOR CATALYSIS AND SECRETION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MISSENSE MUTATION; FAMILIAL CHYLOMICRONEMIA; ENZYME-ACTIVITY; HEPATIC LIPASE; GENE; DEFICIENCY; EXPRESSION; CELLS; DNA; IDENTIFICATION AB The patient was a 20-year-old male. His fasting plasma triglyceride and cholesterol levels were 1258 mg/dl and 138 mg/dl, respectively. The lipoprotein lipase(LPL) activity and mass from postheparin plasma of the patient were 0.00 mu mol/ml/h (normal range: 5.51+/-1.12) and 23 ng/ml (normal range: 220+/-42), respectively. DNA sequence analysis of the LPL gene from the patient revealed a homozymous nucleotide change: a A --> G transition at nucleotide position 383, resulting in an amino acid substitution of Ser for Asn(43), which is believed to be an N-linked glycosylation site of the LPL mature protein. Expression studies of this mutant LPL cDNA produced an inactive LPL protein which was not secreted into the media. (C) 1994 academic Press, Inc. C1 CHIBA UNIV,DEPT INTERNAL MED 2,CHIBA,JAPAN. YAMAGATA UNIV,SCH MED,DEPT LAB MED,YAMAGATA 99023,JAPAN. TOKYO WOMENS MED COLL,HOSP 2ND,DEPT PEDIAT,TOKYO 162,JAPAN. RP KOBAYASHI, J (reprint author), NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892, USA. NR 32 TC 8 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 30 PY 1994 VL 205 IS 1 BP 506 EP 515 DI 10.1006/bbrc.1994.2694 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PW785 UT WOS:A1994PW78500075 PM 7999071 ER PT J AU TSOI, SCM LI, SSL AF TSOI, SCM LI, SSL TI THE NUCLEOTIDE AND DEDUCED AMINO-ACID-SEQUENCES OF A CDNA-ENCODING LACTATE-DEHYDROGENASE FROM CAENORHABDITIS-ELEGANS - THE EVOLUTIONARY RELATIONSHIPS OF LACTATE-DEHYDROGENASES FROM MAMMALS, BIRDS, AMPHIBIAN, FISH, NEMATODE, PLANTS, BACTERIA, MYCOPLASMA, AND PLASMODIUM SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GENE; TESTIS; MUSCLE; HEART AB The nucleotide and deduced amino-acid sequences of a cDNA encoding L-lactate dehydrogenase (LDH) from nematode, Caenorhabditis elegans, were reported. This first invertebrate LDH sequence of 333 amino acids, including the initiation methionine, exhibits 63% identity with that of the most primitive vertebrate lamprey. The evolutionary relationships among 36 LDH isozymes from mammals, birds, amphibian, fish, nematode, plants, bacteria, mycoplasma and plasmodium were analyzed. The invertebrate nematode LDH is evolutionarily positioned between plant LDH and mammalian testicular LDH-C isozymes. The mammalian LDH-C isozyme appears to have arisen after the invertebrate LDH, but prior to the divergence of vertebrate LDH-A (muscle) and LDH-B (heart) isozymes as described previously. (C) 1994 Academic Press, Inc. C1 NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709. NR 15 TC 18 Z9 20 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 30 PY 1994 VL 205 IS 1 BP 558 EP 564 DI 10.1006/bbrc.1994.2701 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PW785 UT WOS:A1994PW78500082 PM 7999079 ER PT J AU SALONPAA, P PELKONEN, O KOJO, A PASANEN, M NEGISHI, M RAUNIO, H AF SALONPAA, P PELKONEN, O KOJO, A PASANEN, M NEGISHI, M RAUNIO, H TI CYTOCHROME P4502A5 EXPRESSION AND INDUCIBILITY BY PHENOBARBITAL IS MODULATED BY CAMP IN MOUSE PRIMARY HEPATOCYTES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID STEROID 15-ALPHA-HYDROXYLASE GENE; COUMARIN 7-HYDROXYLASE; II P-45015-ALPHA; INDUCTION; PYRAZOLE; ENZYMES; FAMILY; LIVER AB Factors involved in CYP2A5 expression were studied in mouse liver primary hepatocytes in culture. CYP2A5-mediated coumarin 7-hydroxylase (COH) activity was retained in simple culture conditions for at least 96 hours and the activity was inducible up to 33-fold by phenobarbital (PB). The constitutive activity and inducibility of COH was totally blocked by treatment of hepatocytes with actinomycin D, and short initial treatment with cycloheximide caused superinducibility when coadministered with PB. Treatment of hepatocytes with inhibitors of protein kinase C, tyrosine kinases and a generator of nitric oxide did not affect COH basal activity or inducibility. Administration of dibutyryl cAMP, forskolin, and 3-isobutyl-1-methyl-xanthine (IBMX) enhanced both basal and PB-induced COH activities and CYP2A5 mRNA levels, indicating that cAMP plays a major role in CYP2A5 expression. (C) 1994 Academic Press, Inc. C1 UNIV OULU,DEPT PHARMACOL & TOXICOL,SF-90220 OULU,FINLAND. UNIV KUOPIO,DEPT PHARMACOL & TOXICOL,KUOPIO,FINLAND. NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,RES TRIANGLE PK,NC. NR 15 TC 40 Z9 40 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 30 PY 1994 VL 205 IS 1 BP 631 EP 637 DI 10.1006/bbrc.1994.2712 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PW785 UT WOS:A1994PW78500093 PM 7528014 ER PT J AU RODRIGUEZ, ER TAN, CD ONWUTA, US YU, ZX FERRANS, VJ PARRILLO, JE AF RODRIGUEZ, ER TAN, CD ONWUTA, US YU, ZX FERRANS, VJ PARRILLO, JE TI 3,5,3'-TRIIODO-L-THYRONINE INDUCES CARDIAC MYOCYTE DIFFERENTIATION BUT NOT NEURONAL DIFFERENTIATION IN P19 TERATOCARCINOMA CELLS IN A DOSE-DEPENDENT MANNER SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID THYROID-HORMONE RECEPTOR; RETINOIC ACID; MYOSIN; HEART; GENE; TRANSCRIPTION; PROTEIN AB P19 teratocarcinoma cells differentiate into neurons or muscle when treated with varying doses of retinoic acid, dimethylsulfoxide, thioguanine or butyrate. We induced cardiac differentiation in P19 cells by treating them with 3,5,3'-Triiodo-L-Thyronine (T-3). P19 cells received doses of T-3 ranging from 30 pM to 300 nM. The beating colonies were counted, and a dose response curve showed that the optimal concentration of T-3 was 30 nM. The colonies beat rhythmically for 4-6 weeks, and the cardiac myocytes showed clearly evident cardiac-specific organelles such as nexuses and atrial granules. No evidence of neuronal or skeletal muscle differentiation was seen with any of the concentrations of T-3 used. Reverse transcription-polymerase chain reaction showed these cells to express the cardiac ventricular specific marker myosin light chain 2V. T-3 is capable of inducing P19 cells to differentiate, in a dose related manner, into spontaneously beating cardiac myocytes identified as such on the basis of ultrastructural criteria. The induction of differentiation is accompanied by expression of cardiao-specific genes. These findings suggest that perhaps genes bearing thyroid response elements in their promoter regions play an important role in the cardiac differentiation induced by T-3 in P19 teratocarcinoma cells, (C) 1994 Academic Press, Inc. C1 RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT PATHOL,CHICAGO,IL 60612. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP RODRIGUEZ, ER (reprint author), RUSH PRESBYTERIAN ST LUKES MED CTR,CARDIOL SECT,1653 W CONGRESS PKWY,CHICAGO,IL 60612, USA. NR 26 TC 17 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 30 PY 1994 VL 205 IS 1 BP 652 EP 658 DI 10.1006/bbrc.1994.2715 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PW785 UT WOS:A1994PW78500096 PM 7999094 ER PT J AU LIU, ZQ BARRETT, EJ DALKIN, AC ZWART, AD CHOU, JY AF LIU, ZQ BARRETT, EJ DALKIN, AC ZWART, AD CHOU, JY TI EFFECT OF ACUTE DIABETES ON RAT HEPATIC GLUCOSE-6-PHOSPHATASE ACTIVITY AND ITS MESSENGER-RNA LEVEL SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID STORAGE-DISEASE TYPE-1A; MICROSOMAL GLUCOSE-6-PHOSPHATASE; GLUCONEOGENESIS; HEPATOCYTES; INSULIN; GENE AB Glucose-6-phosphatase catalyzes the final step of glucose production by liver and kidney. Though its strategic position has sparked interest in its regulation, difficulty with isolating a pure, stable enzyme has slowed progress. Virtually all previous work examining the physiologic regulation of this enzyme has relied on estimates of glucose-6-phosphatase activity in crude microsome preparations. The recent cloning of human and murine glucose-6-phosphatase cDNAs has now allowed study of its mRNA expression. We studied the effect of acute, streptozotocin-induced diabetes on hepatic microsomal glucose-6-phosphatase activity and mRNA expression in young (89+/-3 g), juvenile (304+/-4 g) and adult (512+/-10 g) rats. In control rats, mRNA expression and enzyme activity was similar among the three age groups. Streptozotocin-induced diabetes significantly increased the enzyme activities in both intact and triton-treated microsomes in all groups of rats (p<0.001). Glucose-6-phosphatase mRNA expression was increased in the diabetic rats as well (p<0.0001). Blood glucose concentrations correlated significantly with glucose-6-phosphatase mRNA level (p<0.005) and both intact (p<0.002) and triton-treated (p<0.001) microsomal glucose-6-phosphatase activity. Both intact and triton-treated microsomal glucose-6-phosphatase activity correlated with mRNA level (p<0.001, for each). We conclude that acute streptozotocin-diabetes increases expression of glucose-6-phosphatase mRNA and this contributes to the increased glucose-6-phosphatase activity seen with diabetes mellitus. (C) 1994 Academic Press, Inc. C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. RP LIU, ZQ (reprint author), UNIV VIRGINIA,HLTH SCI CTR,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22908, USA. FU NIDDK NIH HHS [5 T32 DK07320, 5 T32 DK07646-03] NR 21 TC 86 Z9 87 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 30 PY 1994 VL 205 IS 1 BP 680 EP 686 DI 10.1006/bbrc.1994.2719 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PW785 UT WOS:A1994PW78500100 PM 7999098 ER PT J AU ALBERT, JM DEMETS, BL AF ALBERT, JM DEMETS, BL TI ON A MODEL-BASED APPROACH TO ESTIMATING EFFICACY IN CLINICAL-TRIALS SO STATISTICS IN MEDICINE LA English DT Article AB Treatment efficacy is of primary importance in phase III clinical trials. Determining the true size of the treatment effect is often complicated by patient non-compliance with the regimen. This paper examines a model-based approach in the spirit of Efron and Feldman utilizing drug and placebo compliance information, One of the assumptions of this analysis is 'comparability' of drug and placebo compliance. Robustness in estimation of subgroup and population treatment effects when this assumption is violated is investigated in a simulation study, We find that even moderate non-comparability (for example, normalized compliance correlations of 0.4) may produce severely biased estimates. The bias is modulated by the strength of the relationship between compliance and the response on placebo. C1 UNIV WISCONSIN,DEPT BIOSTAT,MADISON,WI 53706. UNIV WISCONSIN,DEPT STAT,MADISON,WI 53706. RP ALBERT, JM (reprint author), NIAID,BIOSTAT RES BRANCH,6003 EXEC BLVD,BETHESDA,MD 20892, USA. NR 8 TC 18 Z9 18 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 30 PY 1994 VL 13 IS 22 BP 2323 EP 2335 DI 10.1002/sim.4780132204 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PU264 UT WOS:A1994PU26400003 PM 7855466 ER PT J AU FELDER, CC SINGERLAHAT, D MATHES, C AF FELDER, CC SINGERLAHAT, D MATHES, C TI VOLTAGE-INDEPENDENT CALCIUM CHANNELS - REGULATION BY RECEPTORS AND INTRACELLULAR CALCIUM STORES SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE VOLTAGE-INDEPENDENT CALCIUM CHANNELS; CALCIUM INFLUX; RECEPTORS; DEPLETION-OPERATED CALCIUM CHANNELS; 2ND-MESSENGERS; CALCIUM; INOSITOL-1,4,5-TRISPHOSPHATE ID RAT MAST-CELLS; 1,4,5-TRISPHOSPHATE-SENSITIVE CA-2+ STORE; FURA-2-LOADED HUMAN-PLATELETS; FREE CYTOSOLIC CALCIUM; PAROTID ACINAR-CELLS; PLASMA-MEMBRANE; INOSITOL TRISPHOSPHATE; CA2+ INFLUX; EXTRACELLULAR ATP; TUMOR PROMOTER C1 UNIV CALIF LOS ANGELES,BRAIN RES INST,INTERDEPTMENTAL PROGRAM NEUROSCI,LOS ANGELES,CA 90024. RP FELDER, CC (reprint author), NIMH,CELL BIOL LAB,BLDG 36,RM 3A-15,BETHESDA,MD 20892, USA. NR 76 TC 58 Z9 58 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 29 PY 1994 VL 48 IS 11 BP 1997 EP 2004 DI 10.1016/0006-2952(94)90498-7 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PX444 UT WOS:A1994PX44400001 PM 7802688 ER PT J AU GREM, JL DAYCHILD, P DRAKE, J GEOFFROY, F TREPEL, JB PIRNIA, F ALLEGRA, CJ AF GREM, JL DAYCHILD, P DRAKE, J GEOFFROY, F TREPEL, JB PIRNIA, F ALLEGRA, CJ TI CYTOTOXICITY AND METABOLISM OF 4-METHOXY-8-(BETA-D-RIBOFURANOSYLAMINO)PYRIMIDO[5,4-D]PYRIMIDINE IN HCT-116 COLON-CANCER CELLS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE ANTIMETABOLITES; PURINES; PYRIMIDINES; EXPERIMENTAL THERAPEUTICS ID STEP ALKALINE ELUTION; CYCLOPENTENYL CYTOSINE; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; SYNTHETASE; ANTITUMOR; ARABINOSYL-5-AZACYTOSINE; 5-FLUOROURACIL; DIPYRIDAMOLE; INHIBITION; QUANTITIES AB We examined the cytotoxicity, biochemical effects and metabolism of 4-methoxy-8-(beta-D-ribofuranosylamino)pyrimido[5, 4-d]pyrimidine (MRPP), a synthetic nucleoside inhibitor of phosphoribosylpyrophosphate synthetase, in HCT 116 human colorectal cancer cells. A 4-hr exposure to 1 and 10 mu M MRPP inhibited cell growth over a 72-hr period by 76 and 89%, and inhibited clonogenic capacity by 36 and 65%, respectively. MRPP was avidly metabolized to the 5'-monophosphate derivative (MRPP-MP), and MRPP-MP formation increased with increasing MRPP exposure (mu M.hr). MRPP-MP was stable, and the intracellular half-life was in excess of 48 hr. A 4-hr exposure to 10 mu M MRPP resulted in significant decreases in ATP, UTP, GTP, CTP, dATP, dTTP, and PRPP pools. Near maximal ribonucleotide triphosphate depletion was achieved with greater than or equal to 24 mu M.hr MRPP, and growth inhibition as a function of MRPP mu M hr closely reflected the biochemical effects. Ribonucleotide triphosphate pools remained depleted for up to 48 hr after drug removal, apparently as a consequence of the prolonged retention of MRPP-MP. MRPP (10 mu M) inhibited the salvage of [H-3]guanine, [H-3]adenine and [H-3]guanosine, and concurrent exposure to MRPP and either 100 mu M adenine, hypoxanthine, or guanine did not reverse ATP or GTP depletion. Concurrent exposure to 10 mu M MRPP and either 10 mu M adenosine, uridine or thymidine was accompanied by repletion of ATP, UTP, and dTTP pools, respectively, but depletion of other nucleotide pools was not corrected. In contrast, 10 mu M guanosine did not correct GTP depletion in the presence of MRPP. The combination of 10 mu M each of thymidine, uridine, adenosine and guanosine during and following a 24-hr exposure to MRPP provided partial protection against 0.1 or 1 mu M MRPP, but did not affect the cytotoxicity associated with 10 mu M MRPP. MRPP is a novel antimetabolite that inhibits both de novo and salvage pathways for purine synthesis and de novo pyrimidine synthesis. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RP GREM, JL (reprint author), NCI,NATL NAVAL MED CTR,NAVY MED ONCOL BRANCH,BLDG 8,RM 5101,BETHESDA,MD 20889, USA. NR 21 TC 1 Z9 1 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 29 PY 1994 VL 48 IS 11 BP 2117 EP 2126 DI 10.1016/0006-2952(94)90513-4 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PX444 UT WOS:A1994PX44400016 PM 7528507 ER PT J AU OCHIENG, J FRIDMAN, R NANGIAMAKKER, P KLEINER, DE LIOTTA, LA STETLERSTEVENSON, WG RAZ, A AF OCHIENG, J FRIDMAN, R NANGIAMAKKER, P KLEINER, DE LIOTTA, LA STETLERSTEVENSON, WG RAZ, A TI GALECTIN-3 IS A NOVEL SUBSTRATE FOR HUMAN MATRIX METALLOPROTEINASE-2 AND METALLOPROTEINASE-9 SO BIOCHEMISTRY LA English DT Article ID CARBOHYDRATE-BINDING PROTEIN-35; IV COLLAGENASE; TISSUE INHIBITOR; PLASMA-MEMBRANE; MOLECULAR-CLONING; 72-KDA GELATINASE; TIMP-2; LECTIN; IDENTIFICATION; ACTIVATION AB The primary structure of galectin-3, a similar to 30 kDa galactoside-binding protein (aka CBP-35, mL-34, hL-31, L-29, Mac-2, and epsilon BP), reveals two structural domains: an amino-terminal domain consists of a Pro-Gly-rich motif, and a globular carboxyl-terminal domain containing a carbohydrate-binding site. In this study, we report that the amino-terminal domain of galectin-3 contains a cleavage site for two members of the matrix metalloproteinase family of enzymes: the 72 kDa (gelatinase A, MMP-2) and the 92 kDa (gelatinase B, MMP-9) proteinases. The major cleavage site for the gelatinases in galectin-3 is at the Ala(62)-Tyr(63) bond, and its hydrolysis by these enzymes was inhibited by TIMP-2. Cell-surface expression of galectin-3 was reduced following treatment of viable T47D human breast carcinoma cells with gelatinase A. These results suggest that galectin-3 may be a substrate for gelatinases and that its degradation may play a role in modulating the biological activities of galectin-3. C1 MICHIGAN CANC FDN,METASTASIS RES PROGRAM,DETROIT,MI 48201. WAYNE STATE UNIV,DEPT PATHOL,DETROIT,MI 48201. WAYNE STATE UNIV,DEPT RADIAT ONCOL,DETROIT,MI 48201. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [R01-CA46120, R01-CA51714-0AS1] NR 43 TC 158 Z9 164 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 29 PY 1994 VL 33 IS 47 BP 14109 EP 14114 DI 10.1021/bi00251a020 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU760 UT WOS:A1994PU76000020 PM 7947821 ER PT J AU CHRISTNER, DF LAKSHMAN, MK SAYER, JM JERINA, DM DIPPLE, A AF CHRISTNER, DF LAKSHMAN, MK SAYER, JM JERINA, DM DIPPLE, A TI PRIMER EXTENSION BY VARIOUS POLYMERASES USING OLIGONUCLEOTIDE TEMPLATES CONTAINING STEREOISOMERIC BENZO[A]PYRENE DEOXYADENOSINE ADDUCTS SO BIOCHEMISTRY LA English DT Article ID BENZOPHENANTHRENE DIHYDRODIOL EPOXIDES; SITE-SPECIFIC INCORPORATION; DOSE-DEPENDENT DIFFERENCES; INVITRO DNA-SYNTHESIS; DEOXYADENOSINE ADDUCTS; ESCHERICHIA-COLI; DIOL-EPOXIDE; SOLUTION CONFORMATION; BENZOPYRENE 7,8-DIOL-9,10-EPOXIDES; HYDROCARBON DEOXYADENOSINE AB Four isomeric benzo[a]pyrene-deoxyadenosine adducts, corresponding to the products of trans opening of the epoxide ring in the four configurationally isomeric benzo[a]pyrene dihydrodiol epoxides by the amino group of deoxyadenosine, were separately introduced into each of two 16-mer sequence contexts. The sequences were from the supF gene, and the site of the adducted adenine was known, for some hydrocarbon dihydrodiol epoxides, to be a hotspot for mutation in Context I and a coldspot for mutation in Context II. Using primers complementary to the 3' ends of these oligonucleotides, the abilities of several polymerases to replicate these templates in vitro were investigated. Each adduct proved to be an effective block to primer extension such that only with high concentrations of exo(-) Klenow fragment was any bypass of adducts seen. DNA polymerase alpha and HIV-1 reverse transcriptase were blocked 3' to the adduct when the configuration af C-10 of the hydrocarbon was S, and some introduction of thymine opposite the adenine adduct was seen with the R configuration. Incorporation of a nucleotide opposite the adduct occurred more readily with Sequenase and the Klenow fragment, and the mutagenic introduction of adenine was apparent in most cases. This corresponded to the A --> T transversions frequently seen in mutation studies with hydrocarbon dihydrodiol epoxides that react extensively with adenine in DNA. Overall, it was clear that sequence context, adduct stereochemistry, and the choice of polymerase all influenced the polymerization reaction. With these in vitro systems, no major differences correlating with the differing tumorigenicities of the isomeric dihydrodiol epoxides or with the hotspot or coldspot nature of the sequences were detected. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CO-74101] NR 49 TC 48 Z9 48 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 29 PY 1994 VL 33 IS 47 BP 14297 EP 14305 DI 10.1021/bi00251a043 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU760 UT WOS:A1994PU76000043 PM 7524675 ER PT J AU KLAUSNER, RD DANCIS, A AF KLAUSNER, RD DANCIS, A TI A GENETIC APPROACH TO ELUCIDATING EUKARYOTIC IRON-METABOLISM SO FEBS LETTERS LA English DT Review DE IRON; COPPER; TRANSPORT; FERRIC REDUCTASE; SACCHAROMYCES CEREVISIAE ID YEAST SACCHAROMYCES-CEREVISIAE; FERRIC REDUCTASE; FERRISIDEROPHORE REDUCTASES; ENDOCYTIC VESICLES; ESCHERICHIA-COLI; NADPH OXIDASE; MOBILIZATION; PHAGOCYTES AB Studies of mutants of the yeast Saccharomyces cerevisiae have led to the identification of genes required for high affinity iron uptake. Reduction of iron (III) outside the cell is accomplished by means of reductases encoded by FRE1 and FRE2, homologues of the gp91-phox component of the oxygen reductase of human granulocytes. High affinity iron (II) transport from the exterior to the interior of the cell occurs by means of a transport system that has not been molecularly characterized. However, the transport process requires the activity of a copper-containing oxidase encoded by FET3. The amino acid sequence of this protein resembles other multi-copper oxidases, including mammalian ceruloplasmin. High affinity copper uptake mediated by the copper transport protein encoded by CTR1 is required to provide the FET3 protein with copper, and thus copper uptake is indirectly required for ferrous iron uptake. These genetic elements of yeast and their relationships may be conserved in complex eukaryotic organisms. RP KLAUSNER, RD (reprint author), NICHHD, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. NR 32 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 EI 1873-3468 J9 FEBS LETT JI FEBS Lett. PD NOV 28 PY 1994 VL 355 IS 2 BP 109 EP 113 DI 10.1016/0014-5793(94)01111-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PV197 UT WOS:A1994PV19700001 PM 7982480 ER PT J AU DEHGHANI, A BAI, X MASCARELLA, SW BOWEN, WD CARROLL, FI AF DEHGHANI, A BAI, X MASCARELLA, SW BOWEN, WD CARROLL, FI TI A NOVEL STEREOSELECTIVE AND ENANTIOSELECTIVE SYNTHESIS OF TRANS-9-ALKYL-2-BENZYL-5-METHYL-6,7-BENZOMORPHANS SO TETRAHEDRON LETTERS LA English DT Article ID SIGMA AB The first stereo- and enantioselective syntheses of trans-9-alkyl-2-benzyl-5-methyl-6,7-benzo- morphans (12) are described. The addition of alkyl magnesium halides to (R)-2-naphthyl-4-phenyl-1,3-oxazolidine (7) followed by treatment with iodomethane and quenching with acid gave (1S,2S)-2-alkyl-1-methyl-1,2-dihydronaphthalenecarboxaldehyde (10). Homologation of 10 followed by reductive amination using benzylamine gave (1S,2S)-trans-2-alkyl-1-benzylaminoethyl-1-methyl-1,2-dihydronaphthalene (11). Mercuric acetate-assisted cyclization of 11 followed by LAK reduction afforded (1S,5S,9R)-12. C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NR 11 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 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD NOV 28 PY 1994 VL 35 IS 48 BP 8969 EP 8972 DI 10.1016/0040-4039(94)88402-1 PG 4 WC Chemistry, Organic SC Chemistry GA PV503 UT WOS:A1994PV50300015 ER PT J AU LEFFELL, MS STEINBERG, AG BIAS, WB MACHAN, CH ZACHARY, AA AF LEFFELL, MS STEINBERG, AG BIAS, WB MACHAN, CH ZACHARY, AA TI THE DISTRIBUTION OF HLA ANTIGENS AND PHENOTYPES AMONG DONORS AND PATIENTS IN THE UNOS REGISTRY SO TRANSPLANTATION LA English DT Article ID RENAL-TRANSPLANTATION; IMMUNE-RESPONSE; ALLOCATION; VACCINE AB We have analyzed HLA data from the UNOS* registry on 20,230 patients on the renal waiting list in 1991 and 18,708 donors from 1988-1992. Significant differences were found in the distribution of HLA antigens for comparisons of the total donor pool and the various racial groups of patients as well as for inter- and intraracial comparisons of donors and patients. Within a racial group, the frequencies of blanks and of broad antigens were usually higher in patients while those of splits were usually higher in donors. Comparisons between the total donor pool and the various racial groups of patients showed that the likelihood of mismatch was greater for African-Americans and Hispanics than for Caucasians but that the chance of mismatch is high for all groups and the average number of antigens mismatched will not vary greatly among the different races. Heterogeneity, as measured by the percentage of the population with different phenotypes, was higher in African-Americans (97.2-99.1%) and Hispanics (97.7-99.4%) than in Caucasians (83.3-86.5%) because of multiple occurrences of a few phenotypes, most containing A1, B8 and DR3, in Caucasians. However, the most common phenotypes of Caucasian donors differed from those of Caucasian patients. Ah phenotypes were rare (0.007-0.61%) and, with the exception of a small group of Caucasian patients, the likelihood of achieving a good match is low, regardless of race. These data explain the observations that, with the exception of the phenotypically identical match, HLA matching does not influence organ distribution significantly. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. CASE WESTERN RESERVE UNIV,DEPT BIOL,CLEVELAND,OH 44106. NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,BETHESDA,MD 20892. NR 28 TC 60 Z9 60 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 1994 VL 58 IS 10 BP 1119 EP 1130 DI 10.1097/00007890-199411270-00011 PG 12 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PV078 UT WOS:A1994PV07800011 PM 7974720 ER PT J AU RANDAZZO, PA TERUI, T STURCH, S KAHN, RA AF RANDAZZO, PA TERUI, T STURCH, S KAHN, RA TI THE AMINO-TERMINUS OF ADP-RIBOSYLATION FACTOR (ARF)-1 IS ESSENTIAL FOR INTERACTION WITH G(S) AND ARF GTPASE-ACTIVATING PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHOLERA-TOXIN; REGULATORY COMPONENT; ADENYLATE-CYCLASE; BINDING PROTEINS; PHOSPHOLIPASE-D; BOVINE BRAIN; COFACTOR; PURIFICATION; NUCLEOTIDES; EXPRESSION AB The role of the amino terminus in the actions of ADP-ribosylation factor 1 (ARF1) was examined by comparing wild type ARF1, a 13-residue NB-terminal deletion mutant ([Delta 13]ARF1), and a 17-residue NE(2)-terminal deletion mutant ([Delta 17]ARF1). The amino-terminal 13 residues of ARF1 are required for cofactor activity in the ADP-ribosylation by cholera toxin when G(s) is the substrate. This is in marked contrast to the finding that cofactor activity is the same for wild type and [Delta 13]ARF1 when agmatine is substrate (Pong J.-X., Haun, R. S., Tsai, S.-C., Moss, J., and Vaughan, M. (1994) J. Biol. Chem. 269, 9743-9745). These data support the conclusion that ARF1 interacts with both cholera toxin and G(s) and that the amino terminus of ARF1 is required specifically for binding G(s). Surprisingly, this result also clearly revealed that the two principal assays for ARF activity, cofactor activity for cholera toxin using either G(s) or agmatine as substrates, used for over 10 years in different laboratories, can yield quite different results. While both NH2-terminal deletion mutants failed to support the ADP-ribosylation of G(s) by cholera toxin, [Delta 13]ARF1, but not [Delta 17]ARF1, inhibited the activity of the wild type protein. The GTPase activity of [Delta 13]ARF1 was activated to a small extent by ARF GTPase-activating protein (GAP), whereas that of [Delta 17]ARF1 was unaffected. me conclude that residues 14-17 are involved in the interaction of ARF with both cholera toxin and ARF GAP. The co-purifying nucleotides, nucleotide exchange kinetics, and dependence of exchange on phospholipids for the mutant proteins were all different from the wild type ARF1 proteins. The importance of monitoring the nucleotide binding to ARF proteins under the conditions used in the ARF assay and expressing ARF activities as specific activities, normalized to GTP binding sites, particularly when comparisons between different proteins or preparations are made, is discussed. C1 NCI, BIOL CHEM LAB, BETHESDA, MD 20892 USA. NR 22 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1994 VL 269 IS 47 BP 29490 EP 29494 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU284 UT WOS:A1994PU28400030 PM 7961931 ER PT J AU WATTS, JD AFFOLTER, M KREBS, DL WANGE, RL SAMELSON, LE AEBERSOLD, R AF WATTS, JD AFFOLTER, M KREBS, DL WANGE, RL SAMELSON, LE AEBERSOLD, R TI IDENTIFICATION BY ELECTROSPRAY-IONIZATION MASS-SPECTROMETRY OF THE SITES OF TYROSINE PHOSPHORYLATION-INDUCED IN ACTIVATED JURKAT T-CELLS ON THE PROTEIN-TYROSINE KINASE ZAP-70 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANTIGEN RECEPTOR-ZETA; AFFINITY-CHROMATOGRAPHY; THYMOCYTE DEVELOPMENT; SIGNAL TRANSDUCTION; IL-2 RECEPTOR; TCR ZETA; P56LCK; P56(LCK); CHAIN; ASSOCIATION AB We have developed a rapid and sensitive two capillary-column chromatography and mass spectrometry-based method for the determination of protein phosphorylation sites following recovery of individual phosphopeptides from two-dimensional phosphopeptide maps. With a standard phosphopeptide, we demonstrate detection sensitivity of at least 250 fmol for this system. me applied this technique to the analysis of in vitro sites of tyrosine phosphorylation induced on the T cell-specific protein tyrosine kinase ZAP-70 in the absence and presence of p56(lck). me show that ZAP-70 has a primary autophosphorylation site at Tyr-292, with a secondary site at Tyr-126. We also show additional phosphorylation at Tyr-69, Tyr-178, Tyr-492, and Tyr-493 upon the addition of the protein tyrosine kinase, p56(lck). By comparative two-dimensional phosphopeptide mapping, we show that ZAP-70 isolated from Jurkat T cells also autophosphorylates at Tyr-292 and Tyr-126. Similar analysis of P-32-labeled Jurkat cells stimulated with anti-T cell receptor antibodies reveals Tyr-492 and Tyr-493 as the principal sites of T cell antigen receptor-induced tyrosine phosphorylation, with additional phosphorylation at the Tyr-292, but not the Tyr-126 autophosphorylation site. The high degree of sensitivity achieved with this technology should greatly facilitate the direct biochemical determination of inducible protein phosphorylation events, an experimental strategy that until now has been both time consuming and difficult. C1 UNIV BRITISH COLUMBIA, BIOMED RES CTR, VANCOUVER V6T 1Z3, BC, CANADA. NICHHD, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. NR 53 TC 203 Z9 205 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1994 VL 269 IS 47 BP 29520 EP 29529 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU284 UT WOS:A1994PU28400035 PM 7961936 ER PT J AU SINGH, SK MAURIZI, MR AF SINGH, SK MAURIZI, MR TI MUTATIONAL ANALYSIS DEMONSTRATES DIFFERENT FUNCTIONAL ROLES FOR THE 2 ATP-BINDING SITES IN CLPAP PROTEASE FROM ESCHERICHIA-COLI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTICATALYTIC PROTEINASE COMPLEX; DEPENDENT PROTEASE; DIRECTED MUTAGENESIS; UBIQUITIN; DEGRADATION; CELLS; PROTEOLYSIS; HYDROLYSIS; COMPONENT; BREAKDOWN AB ClpA, the regulatory subunit of Clp protease from Escherichia coli, has two ATP-binding sites in nonhomologous regions of the protein, referred to as domain I and domain II. We have mutated the invariant lysine in the ATP-binding sites of domain I and domain II and studied the enzymatic properties of the purified mutant ClpA proteins. The domain I mutant, ClpA-K220Q, was unable to form a hexamer in the presence of nucleotide, but the comparable domain II mutant, ClpA-K501Q, associated into a hexamer in the presence of ATP, indicating that nucleotide binding to domain I favors a conformation required to stabilize the quaternary structure of ClpA ClpA-K220Q was defective in ATPase activity and in the ability to activate protein and peptide degradation by ClpP, but the defects could be partially overcome by formation of hybrid hexamers with wildtype ClpA Another domain I mutant, ClpA-K220R, readily formed hexamers in the presence of ATP and retained greater than or equal to 60% of the wild-type ATPase activity and ability to activate ClpP. These results indicate that hexamer formation is a prerequisite for expression of enzymatic activity. Domain II mutants ClpA-K501Q and ClpA-K501R had very low ATPase activity (<10% of wild-type) and a severe defect in activation of protein degradation, which requires ATP hydrolysis. Domain II mutants were able to activate ClpP to degrade a peptide whose degradation required nucleotide binding but not hydrolysis. Nucleotide binding to domain II of ClpA is important to form a productive complex with ClpP, and domain II appears to be primarily responsible for an energy-requiring step in the catalytic cycle unique to the degradation of large proteins. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 47 TC 70 Z9 71 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1994 VL 269 IS 47 BP 29537 EP 29545 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU284 UT WOS:A1994PU28400037 PM 7961938 ER PT J AU JUNG, JE KAROOR, V SANDBAKEN, MG LEE, BJ OHAMA, T GESTELAND, RF ATKINS, JF MULLENBACH, GT HILL, KE WAHBA, AJ HATFIELD, DL AF JUNG, JE KAROOR, V SANDBAKEN, MG LEE, BJ OHAMA, T GESTELAND, RF ATKINS, JF MULLENBACH, GT HILL, KE WAHBA, AJ HATFIELD, DL TI UTILIZATION OF SELENOCYSTEYL-TRNA([SER]SEC) AND SERYL-TRNA([SER]SEC) IN PROTEIN-SYNTHESIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SELENOCYSTEINE TRANSFER RNASEC; GLUTATHIONE-PEROXIDASE GENE; I IODOTHYRONINE DEIODINASE; SERINE TRANSFER-RNA; MAMMALIAN-CELLS; UGA; CODON; SELENOPROTEIN; EXPRESSION; IDENTIFICATION AB The UGA selenocysteine (Sec) codon in glutathione peroxidase mRNA and in selenoprotein P and the UGA stop codon in rabbit beta-globin mRNA were employed to study the utilization of Sec-tRNA([Ser]Sec) and Ser-tRNA([Ser]Sec) in protein synthesis. In vitro Ser-tRNA([Sec]Sec) served as a suppressor of the UGA Sec codon as well as the UGA stop codon, while Sec-tRNA([Ser]Sec) did not. However, in vivo Sec-tRNA([Ser]Sec) did donate Sec to glutathione peroxidase in Xenopus oocytes microinjected with glutathione peroxidase mRNA and Sec-tRNA A ribosome binding assay was devised to investigate the interaction of aminoacyl-tRNA, rabbit reticulocyte ribosomes, and eukaryotic elongation factor 1 (eEF-1) in response to the appropriate trinucleoside diphosphate template. Ser tRNA([Sec]Sec) bound weakly to ribosomes in the presence of eEF-1 and UGA as compared to Phe-tRNA, Ser-tRNA(IGA) and Met-tRNA(m) which bound more efficiently in the presence of eEF-1 and the appropriate template. No increase in the binding of Sec-tRNA([Ser]Sec) was observed under the same conditions as Ser-tRNA([Ser]Sec.) The ribosome binding studies substantiated the finding that Ser-tRNA([Ser]Sec) serves as a suppressor of UGA codons in protein synthesis, but SectRNA([Ser]Sec) does not. In addition, these studies provide strong evidence that a specific elongation factor is required in mammalian cells for insertion of Sec into protein from Sec-tRNA([Ser]Sec). C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV MISSISSIPPI,MED CTR,DEPT BIOCHEM,JACKSON,MS 39216. UNIV UTAH,HOWARD HUGHES MED INST,SALT LAKE CITY,UT 84112. UNIV UTAH,ECCLES INST HUMAN GENET,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112. LYNX THERAPEUT INC,HAYWARD,CA 94545. VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. FU NIEHS NIH HHS [ES02497]; NIGMS NIH HHS [GM25451] NR 38 TC 32 Z9 33 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1994 VL 269 IS 47 BP 29739 EP 29745 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU284 UT WOS:A1994PU28400067 PM 7961966 ER PT J AU ISHIBASHI, T BOTTARO, DP MICHIELI, P KELLEY, CA AARONSON, SA AF ISHIBASHI, T BOTTARO, DP MICHIELI, P KELLEY, CA AARONSON, SA TI A NOVEL DUAL-SPECIFICITY PHOSPHATASE INDUCED BY SERUM STIMULATION AND HEAT-SHOCK SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; IMMEDIATE-EARLY GENE; VACCINIA VIRUS VH1; MAP KINASE; ACTIVATES P34CDC2; CLONING SYSTEM; HUMAN-PLACENTA; EXPRESSION; FAMILY; YEAST AB To identify new members of a family of protein-tyrosine phosphatases (PTPs), of which VH1 is prototype, we screened a B5/589 human mammary epithelial cell cDNA library by low stringency hybridization with probes for the catalytic domains of the human VHR and mouse 3CH134 phosphatases. Two overlapping clones of 1.8 and 2.5 kilobase pairs were detected by 3CH134 but not VHR probes. Sequence analysis of the largest clone, B23, revealed a 2470-nucleotide open reading frame encoding a novel protein. Within the 397 amino acid sequence, the HCXAGXXR signature sequence for PTPs was located at positions 261-268. The closest similarities were to 3CH134, its human homolog CL100, and PAC-1, PTPs induced as early response genes to mitogen stimulation. Less relatedness was observed with VHR and VH1 dual specificity phosphatases of human and vaccinia virus, respectively. A bacterially expressed recombinant protein containing the catalytic domain of B23 showed significant but consistently lower activity than VHR in vitro. Among the substrates tested, B23 displayed the highest relative activity toward phosphorylated extracellular signal regulated kinase-1, suggesting that it may be a target for B23 activity in vivo. The B23 transcript was detected in a wide variety of normal human tissues, with relatively high expression in pancreas and brain. B23 was induced by serum stimulation of human fibroblasts as well as by heat shock with similar kinetics to those observed with CL100. Thus, B23 is a new human protein phosphatase which appears to be regulated in response to mitogenic signaling and at least some forms of stress. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. MT SINAI MED CTR,RUTTENBERG CANC CTR,NEW YORK,NY 10029. RI Bottaro, Donald/F-8550-2010; Michieli, Paolo/A-2588-2011 OI Bottaro, Donald/0000-0002-5057-5334; NR 40 TC 128 Z9 131 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1994 VL 269 IS 47 BP 29897 EP 29902 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU284 UT WOS:A1994PU28400089 PM 7961985 ER PT J AU SERGEEV, Y LEE, B AF SERGEEV, Y LEE, B TI ALIGNMENT OF BETA-BARRELS IN (BETA/ALPHA)(8) PROTEINS USING HYDROGEN-BONDING PATTERN SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE TIM-BARREL; PARALLEL BETA-BARREL; STRUCTURAL ALIGNMENT; PATTERN RECOGNITION ID TRIOSEPHOSPHATE ISOMERASE; STRUCTURAL PRINCIPLES; REFINED STRUCTURE; PYRUVATE-KINASE; ALPHA-HELICES; RESOLUTION; EVOLUTION; PACKING; SHEET; YEAST AB A multiple alignment procedure for aligning the beta-sheet residues of the (beta/alpha)(8)-barrel structures is described. It uses a two-dimensional numbering scheme which is based on the covalent and hydrogen-bonding pattern of the beta-sheet. Two different scoring functions were used: one measured the sequence and topological similarity and the other the root-mean-square deviation of the coordinates of the matched residues. The procedure was applied to obtain multiple alignments of the beta-barrels often (beta/alpha)(8)-barrel proteins of known structure. Two kinds of alignments were derived: one in which the beta-strand numbering was preserved and another in which the beta-strands were allowed to be cyclically permuted. It is shown that preservation of the beta-strand numbering corresponds to aligning only the layer structure of the beta-barrels. In order to obtain the optimal rotational alignment of the barrels as well, the beta-strands must be allowed to be renumbered. Although the 2-fold or 4-fold rotational symmetry of the beta-barrels makes it difficult to obtain unique rotational alignment of the barrels, the results of the alignment indicate that the beta-strands in the beta-barrel of enolase, xylose isomerase, taka-amylase, and possibly fructose biphosphate aldolase, must be cyclically permuted in order to be optimally aligned to those of the other proteins, which include triose phosphate isomerase, the alpha-subunit of tryptophan synthetase, flavocytochrome b(2), ribulose-1,5-biphosphate carboxylase/oxygenase, and glycolate oxidase. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 38 TC 27 Z9 27 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 25 PY 1994 VL 244 IS 2 BP 168 EP 182 DI 10.1006/jmbi.1994.1717 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU761 UT WOS:A1994PU76100005 PM 7966329 ER PT J AU KIM, SJ LEWIS, MS KNUTSON, JR PORTER, DK KUMAR, A WILSON, SH AF KIM, SJ LEWIS, MS KNUTSON, JR PORTER, DK KUMAR, A WILSON, SH TI CHARACTERIZATION OF THE TRYPTOPHAN FLUORESCENCE AND HYDRODYNAMIC PROPERTIES OF RAT DNA-POLYMERASE-BETA SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DNA POLYMERASE BETA; ANALYTICAL ULTRACENTRIFUGATION; FLUORESCENCE ID LIVER ALCOHOL-DEHYDROGENASE; TIME-RESOLVED FLUORESCENCE; DECAY; PROTEINS; SPECTRA; IDENTIFICATION; RESOLUTION; EMISSION; DOMAIN AB We have examined the biophysical properties of DNA polymerase beta (beta-pol) in solution. Time-resolved and steady-state fluorescence were used to investigate the microenvironment of the lone tryptophanyl residue (Trp324), and a combination of sedimentation equilibrium, sedimentation velocity and fluorescence anisotropy decay measurements were used to study the hgdrodynamic properties of the enzyme. Trp324 appears to be exposed to water as judged by the tryptophan emission and steady-state and lifetime quenching experiments. The fluorescence is easily quenched by a neutral quencher acrylamide (k(q) = 1.59x10(9)M(-1)s(-1)), and by a negatively charged ionic quencher, I- (k(q) = 1.60x10(9) M(-1)s(-1)), but not by a positively charged ionic quencher, Cs+ (X(q) = 0.2x10(9) M(-1)s(-1)). The fluorescence lifetime of beta-pol is best described by the sum of two exponentials with a longer lifetime component of 8.4 ns and a shorter lifetime component of 1.3 ns. Decay associated spectra (DAS) show emission maxima at 340 nm and at 345 nm for the shorter lifetime and longer lifetime components, respectively, with corresponding centers of gravity at 347 nm and 348 nm. Sedimentation equilibrium experiments show that the enzyme exists as a monomer at the KCl concentrations (>0.05 M) studied in the absence of divalent metals. Zn2+ causes higher order aggregation, but no such aggregates are seen with Mg2+ and Mn2+. In the presence of 1 mM manganese, the average lifetime decreased approximately 10%, from 8.14 ns to 7.38 ns, with a concomitant increase of average rotational correlational time (phi) from 24 ns to 28 ns. The accessibility of the positively charged quencher (Cs+) to tryptophan also decreases approximately 50%, indicating alteration of the tryptophan microenvironment. By contrast, Mg2+ + causes minor changes in fluorescence properties. The hy drodynamic shape of the intact enzyme and its single-stranded (8 kDa) and double-stranded (31 kDa) DNA binding domains were further investigated by sedimentation velocity measurements. The value of SX(20.W)(0) for the intact enzyme is 2.97 S, and the calculated axial ratio is 5.0. In contrast to the 8 kDa domain. which has a less asymmetric shape with an axial ratio of 2.3, the 3 1 kDa domain shows an elongated structure with an axial ratio of 5.5. These data suggest that the axial ratio of the intact enzyme may be the result of marked bending of the molecule at the flexible hinge region between the two domains. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NHLBI,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NR 31 TC 23 Z9 23 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 25 PY 1994 VL 244 IS 2 BP 224 EP 235 DI 10.1006/jmbi.1994.1720 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU761 UT WOS:A1994PU76100008 PM 7966332 ER PT J AU PANYUTIN, IG NEUMANN, RD AF PANYUTIN, IG NEUMANN, RD TI SEQUENCE-SPECIFIC DNA DOUBLE-STRAND BREAKS INDUCED BY TRIPLEX FORMING I-125 LABELED OLIGONUCLEOTIDES SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MAMMALIAN-CELLS; HELIX FORMATION; DECAY; RADIOTOXICITY; DAMAGE; I125; LETHALITY; ANTISENSE; NUCLEAR; H-3 AB A triplex-forming oligonucleotide (TFO) complementary to the polypurine-polypyrimidine region of the nef gene of the Human Immunodeficiency Virus (HIV) was labeled with I-125 at the C5 position of a single deoxycytosine residue. Labeled TFO was incubated with a plasmid containing a fragment of the nef gene. Decay of I-125 was found to cause double-strand breaks (DSB) within the nef gene upon tripler formation in a sequence specific manner. No DSB were detected after incubation at ionic conditions preventing tripler formation or when TFO was labeled with P-32 instead of I-125. Mapping DSB sites with single base resolution showed that they are distributed within 10 bp of a maximum located exactly opposite the position of the [I-125] IdC in the TFO. We estimate that on average the amount of DSB produced per decay is close to one. RP PANYUTIN, IG (reprint author), NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892, USA. NR 23 TC 72 Z9 77 U1 1 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 25 PY 1994 VL 22 IS 23 BP 4979 EP 4982 DI 10.1093/nar/22.23.4979 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PW642 UT WOS:A1994PW64200018 PM 7800489 ER PT J AU WU, T IKEZONO, T ANGUS, CW SHELHAMER, JH AF WU, T IKEZONO, T ANGUS, CW SHELHAMER, JH TI CHARACTERIZATION OF THE PROMOTER FOR THE HUMAN 85 KDA CYTOSOLIC PHOSPHOLIPASE A(2) GENE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTIONAL INDUCTION; ARACHIDONIC-ACID; GAMMA-INTERFERON; ACTIVATION; EXPRESSION; PROTEIN; PHOSPHORYLATION; SEQUENCES; REGION; DNA AB The 85 kDa cytosolic phospholipase A(2) (cPLA(2)) plays a key role in the production of arachidonic acid and lysophospholipids, the precursors of eicosanoids and platelet-activating factor. Here we report the cloning of the promoter of the human cPLA(2) gene. A 5.7 kb EcoRI fragment containing the most 5' region of the cPLA(2) cDNA was sequenced. The transcription initiation site was identified by rapid amplification of 5'-cDNA ends (5'-RACE) and primer extension analysis. DNA sequence analysis of the 595 base pairs 5' of the transcription start site reveals a 48 base purine - pyrimidine dinucleotide repeat (CA repeat), five interferon-gamma response elements (gamma-IRE), one interferon-gamma activated sequence (GAS) and two glucocorticoid response elements (GRE). The promoter lacks a TATA box. It contains a possible CAAT box at - 111 and two octamer binding motifs. The 595 base fragment located immediately upstream of the transcriptional start site exhibited functional promoter activity in transient transfection assays in a bronchial epithelial cell line (BEAS 2B cells). Deletion analysis revealed that the CA repeat may confer an inhibitory effect on the cPLA(2) promoter activity. The characterization of the human cPLA(2) promoter sequence will allow further studies defining the molecular events regulating the expression of the cPLA(2) enzyme, especially the cytokine mediated cPLA(2) gene expression. C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 43 TC 73 Z9 74 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 25 PY 1994 VL 22 IS 23 BP 5093 EP 5098 DI 10.1093/nar/22.23.5093 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PW642 UT WOS:A1994PW64200035 PM 7800505 ER PT J AU SMITH, ML CHEN, IT ZHAN, QM BAE, IS CHEN, CY GILMER, TM KASTAN, MB OCONNOR, PM FORNACE, AJ AF SMITH, ML CHEN, IT ZHAN, QM BAE, IS CHEN, CY GILMER, TM KASTAN, MB OCONNOR, PM FORNACE, AJ TI INTERACTION OF THE P53-REGULATED PROTEIN GADD45 WITH PROLIFERATING CELL NUCLEAR ANTIGEN SO SCIENCE LA English DT Article ID CYCLIN-DEPENDENT KINASES; DNA-REPLICATION; EXCISION REPAIR; P53; PCNA AB GADD45 is a ubiquitously expressed mammalian gene that is induced by DNA damage and certain other stresses. Like another p53-regulated gene, p21(WAF1/CIP1), whose product binds to cyclin-dependent kinases (Cdk's) and proliferating cell nuclear antigen (PCNA), GADD45 has been associated with growth suppression. Gadd45 was found to bind to PCNA, a normal component of Cdk complexes and a protein involved in DNA replication and repair. Gadd45 stimulated DNA excision repair in vitro and inhibited entry of cells into S phase. These results establish GADD45 as a link between the p53-dependent cell cycle checkpoint and DNA repair. C1 NCI,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,CTR ONCOL,BALTIMORE,MD 21287. GLAXO INC,RES INST,RES TRIANGLE PK,NC 27709. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NIEHS NIH HHS [ES05777] NR 26 TC 850 Z9 875 U1 1 U2 14 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 25 PY 1994 VL 266 IS 5189 BP 1376 EP 1380 DI 10.1126/science.7973727 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PT632 UT WOS:A1994PT63200042 PM 7973727 ER PT J AU KELNER, GS KENNEDY, J BACON, KB KLEYENSTEUBER, S LARGAESPADA, DA JENKINS, NA COPELAND, NG BAZAN, JF MOORE, KW SCHALL, TJ ZLOTNIK, A AF KELNER, GS KENNEDY, J BACON, KB KLEYENSTEUBER, S LARGAESPADA, DA JENKINS, NA COPELAND, NG BAZAN, JF MOORE, KW SCHALL, TJ ZLOTNIK, A TI LYMPHOTACTIN - A CYTOKINE THAT REPRESENTS A NEW CLASS OF CHEMOKINE SO SCIENCE LA English DT Article ID EXPRESSION; FAMILY; RECEPTOR; CLONING; CELLS AB In this study, the cytokine-producing profile of progenitor T cells (pro-T cells) was determined. During screening of a complementary DNA library generated from activated mouse pro-T cells, a cytokine designated lymphotactin was discovered. Lymphotactin is similar to members of both the Cys-Cys and Cys-X-Cys chemokine families but lacks two of the four cysteine residues that are characteristic of the chemokines. Lymphotactin is also expressed in activated CD8(+) T cells and CD4(-)CD8(-) T cell receptor alpha beta(+) thymocytes. It has chemotactic activity for lymphocytes but not for monocytes or neutrophils. The gene encoding lymphotactin maps to chromosome one. Taken together, these observations suggest that lymphotactin represents a novel addition to the chemokine superfamily. C1 DNAX RES INST MOLEC & CELLULAR BIOL INC,DEPT IMMUNOL,PALO ALTO,CA 94304. NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Bazan, J. Fernando/B-4562-2010; Zlotnik, Albert/C-3791-2011; Largaespada, David/C-9832-2014 NR 18 TC 556 Z9 566 U1 1 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 25 PY 1994 VL 266 IS 5189 BP 1395 EP 1399 DI 10.1126/science.7973732 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PT632 UT WOS:A1994PT63200047 PM 7973732 ER PT J AU CHEN, HT JI, ZH WONG, LK SIUDA, JF NARAYANAN, VL AF CHEN, HT JI, ZH WONG, LK SIUDA, JF NARAYANAN, VL TI 2-(1-CYCLOPENTEN-1-YL)-2-[2-DIMETHYLAMINO)ETHYL]-5-(E)BENZYLIDENE CYCLOPENTANONE HYDROCHLORIDES - A NEW SERIES OF MODERATE CYTOTOXIC AGENTS SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID STYRYL KETONES AB A series of 2-(1-cyclopenten-1-yl)-2-[2-(dimethylamino)ethyl]-5-(E)-benzylidene cyclopentanone hydrochlorides 5, were synthesized and demonstrated cytotoxic activity toward human cancer cell lines. A possible mechanism of 5 at the molecular level is suggested. C1 SHENYANG COLL PHARM,SHENYANG,PEOPLES R CHINA. BIOVAIL,IWF RES,SCARBOROUGH M1L 4S4,ON,CANADA. NCI,DRUG SYNTH & CHEM BRANCH,BETHESDA,MD 20205. RP CHEN, HT (reprint author), UNIV PITTSBURGH,SCH PHARM,718 SALK HALL,PITTSBURGH,PA 15261, USA. NR 9 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 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 24 PY 1994 VL 4 IS 22 BP 2701 EP 2704 DI 10.1016/S0960-894X(01)80700-9 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA PV594 UT WOS:A1994PV59400013 ER PT J AU RAVETCH, JV MARGULIES, DH AF RAVETCH, JV MARGULIES, DH TI IMMUNOLOGY - NEW TRICKS FOR OLD MOLECULES SO NATURE LA English DT Editorial Material ID FC RECEPTOR C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP RAVETCH, JV (reprint author), MEM SLOAN KETTERING CANC CTR,PROGRAM MOLEC BIOL,1275 YORK AVE,NEW YORK,NY 10021, USA. RI Margulies, David/H-7089-2013 NR 10 TC 11 Z9 12 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 24 PY 1994 VL 372 IS 6504 BP 323 EP 324 DI 10.1038/372323a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PU287 UT WOS:A1994PU28700034 PM 7969486 ER PT J AU WILCOX, AJ AF WILCOX, AJ TI SMOKING MAKES KNAVES LITTLE - KILLS THEM, TOO SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP WILCOX, AJ (reprint author), NIEHS,RES TRIANGLE PK,NC, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 23 PY 1994 VL 272 IS 20 BP 1577 EP 1577 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PR405 UT WOS:A1994PR40500017 PM 7966864 ER PT J AU AMBUDKAR, I CUPPOLETTI, J AF AMBUDKAR, I CUPPOLETTI, J TI REGULATION OF MEMBRANE-PROTEINS - PREFACE SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Editorial Material C1 UNIV CINCINNATI,MED CTR,DEPT MOLEC & CELLULAR PHYSIOL,CINCINNATI,OH 45267. RP AMBUDKAR, I (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,SECRETORY PHYSIOL SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV 23 PY 1994 VL 140 IS 2 BP 91 EP 91 DI 10.1007/BF00926747 PG 1 WC Cell Biology SC Cell Biology GA PX917 UT WOS:A1994PX91700001 ER PT J AU ARISPE, N POLLARD, HB ROJAS, E AF ARISPE, N POLLARD, HB ROJAS, E TI BETA-AMYLOID CA2+-CHANNEL HYPOTHESIS FOR NEURONAL DEATH IN ALZHEIMER-DISEASE SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 4th Fall Symposium of the Membrane-Biophysics-Subgroup of the Biophysical-Society CY OCT, 1993 CL BEAUFORT, NC SP BIOPHYS SOC, MEMBRANE BIOPHYS SUBGRP DE AMYLOID PRECURSOR PROTEINS; TROMETHAMINE; A-BETA-P-AMYLOID; NEURODEGENERATION ID PRECURSOR PROTEIN; RAT-BRAIN; BILAYER-MEMBRANES; CA2+ HOMEOSTASIS; NEUROTOXICITY; PEPTIDES; AGGREGATION; FRAGMENT; CHANNELS; INVITRO AB The Alzheimer's Disease (AD) amyloid protein (A beta P[1-40]) forms cation selective channels when incorporated into planar lipid bilayers by fusion with liposomes containing the peptide. Since the peptide has been proposed to occur in vivo in both membrane-bound and soluble forms, we also tested the possibility of direct incorporation of the soluble A beta P[1-40] into the membrane. We found the peptide can also form similar channels in acidic phospholipid bilayers formed at the tip of a patch pipet, as well as in the planar lipid bilayer system. As in the case of liposome mediated incorporation, the A beta P[1-40]-channel in the solvent-free membrane patch exhibits multiple cation selectivity (Cs+>Li+>Ca(2+)greater than or equal to K+), and sensitivity to tromethamine. The fact that equivalentA beta P[1-40] amyloid channels can be detected by two different methods thus provides additional validation of our original observation. Further studies with a beta P-channels incorporated into planar lipid bilayers from the liposome complex have also revealed that the channel activity can express spontaneous transitions to a much higher range of conductances between 400 and 4000 pS. Under these conditions, the amyloid channel continues to be cation selective but loses its tromethamine sensitivity. By contrast, amyloid channels were insensitive to nitrendipine at either conductance range. We calculate that if such channels were expressed in cells, the ensuing ion fluxes down their electrochemical potential gradients would disrupt cellular homeostasis. We therefore interpret these data as providing further support for our beta-amyloid Ca2(+)-channel hypothesis for neuronal death in Alzheimer's Disease. RP ARISPE, N (reprint author), NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 46 TC 133 Z9 137 U1 0 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV 23 PY 1994 VL 140 IS 2 BP 119 EP 125 DI 10.1007/BF00926750 PG 7 WC Cell Biology SC Cell Biology GA PX917 UT WOS:A1994PX91700004 PM 7898484 ER PT J AU CARROLL, PB MOURA, AS ROJAS, E ATWATER, I AF CARROLL, PB MOURA, AS ROJAS, E ATWATER, I TI THE DIABETOGENIC AGENT ALLOXAN INCREASES K+ PERMEABILITY BY A MECHANISM INVOLVING ACTIVATION OF ATP-SENSITIVE K+-CHANNELS IN MOUSE PANCREATIC BETA-CELLS SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 4th Fall Symposium of the Membrane-Biophysics-Subgroup of the Biophysical-Society CY OCT, 1993 CL BEAUFORT, NC SP BIOPHYS SOC, MEMBRANE BIOPHYS SUBGRP DE ISLETS OF LANGERHANS; ALLOXAN; K+-CHANNEL; GLYBURIDE ID INSULIN-SECRETING CELLS; POTASSIUM CHANNEL; B-CELLS; HIGH-CONDUCTANCE; ISLET CELLS; GLUCOSE; RELEASE; LANGERHANS; CALCIUM; BLOCKS AB The effects of the diabetogenic agent, alloxan, on membrane potential, input resistance and electrical activity of normal mouse pancreatic beta-cells were studied. Tetraethylammonium (TEA), quinine and Glyburide were used to block K+-channels and to elucidate the mechanisms underlying alloxan's effects on beta-cell membrane potential. Exposure of the islet to alloxan (75-100 mu M) in the presence of glucose (11 mM), produced a rapid (15 sec), transient inhibition of electrical activity, often accompanied by hyperpolarization of the membrane, and this was followed by recovery of the burst pattern. This early effect of alloxan was followed after approximately 15 min by a complete inhibition of electrical activity and hyperpolarization. The inhibition accompanied by hyperpolarization was associated with a decrease in input resistance, indicating increased K+-conductance. Both the transient and delayed effects of alloxan were blocked by glucose (33 mM), quinine and glyburide but not by other conditions which induce continuous electrical activity such as elevated external [K+] (10 mM), ouabain, K+ removal, or TEA (20 mM). The transient inhibition induced by alloxan may be due to a direct competition with glucose transport/metabolism since it did not occur when alpha-keto isocaproic acid (KIC) was used to induce electrical activity. The delayed inhibition may reflect indirect effects of accumulation of this agent or its metabolites within the cell. Since both effects of alloxan are blocked by glyburide they appear to involve activation of the ATP-sensitive K+-channel (K-ATP). C1 NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [1F35DK07967-01] NR 35 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 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV 23 PY 1994 VL 140 IS 2 BP 127 EP 136 DI 10.1007/BF00926751 PG 10 WC Cell Biology SC Cell Biology GA PX917 UT WOS:A1994PX91700005 PM 7898485 ER PT J AU TEKLE, E ASTUMIAN, RD CHOCK, PB AF TEKLE, E ASTUMIAN, RD CHOCK, PB TI SELECTIVE AND ASYMMETRIC MOLECULAR-TRANSPORT ACROSS ELECTROPORATED CELL-MEMBRANES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ELECTROPORATION; ELECTROPERMEABILIZATION ID MESOPHYLL PROTOPLASTS; ELECTRIC-FIELD; ELECTROPERMEABILIZATION; BREAKDOWN; PULSE AB Transport of a divalent cation (Ca2+) and three DNA indicators [ethidium bromide (EB), propidium iodide (Pr), and ethidium homodimer (EthD-1)] across electroporated membranes of several mammalian cell lines was found to be selective and asymmetrical. In low salt medium, Ca2+ and EB were preferentially transported across the anodefacing cell membrane while PI and EthD-1 predominately entered at the site facing the cathode. In high salt medium, the entry site for Ca2+ and EB was reversed to the cathode-facing hemisphere while it remained unchanged for PI and EthD-1. In all these experiments, the observed transport patterns remained unaffected whether the dyes (or ion) were present during or added after the electroporating pulse. The data suggest that asymmetric pores are created on both sides of the membrane facing the electrodes, with smaller pore size (but greater in number) on the anode side and larger pores (with a lower population) on the cathode side. Furthermore, the rate of resealing of the membrane pores is significantly enhanced in high ionic strength medium, thus affecting the entry site. The asymmetric transport pattern is neither caused by electrophoresis induced by the externally applied electric field nor due to one-sided membrane breakdown as previously believed. C1 UNIV CHICAGO,DEPT SURG,PLAST & RECONSTRUCT SURG SECT,SURG BRAIN RES INST,CHICAGO,IL 60637. RP TEKLE, E (reprint author), NHLBI,BIOCHEM LAB,METAB REGULAT SECT,BLDG 3,ROOM 203,BETHESDA,MD 20892, USA. NR 24 TC 79 Z9 81 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 22 PY 1994 VL 91 IS 24 BP 11512 EP 11516 DI 10.1073/pnas.91.24.11512 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PU285 UT WOS:A1994PU28500047 PM 7972093 ER PT J AU OKAMOTO, A JIANG, W KIM, SJ SPILLARE, EA STONER, GD WEINSTEIN, IB HARRIS, CC AF OKAMOTO, A JIANG, W KIM, SJ SPILLARE, EA STONER, GD WEINSTEIN, IB HARRIS, CC TI OVEREXPRESSION OF HUMAN CYCLIN D1 REDUCES THE TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) TYPE-II RECEPTOR AND GROWTH-INHIBITION BY TGF-BETA-1 IN AN IMMORTALIZED HUMAN ESOPHAGEAL EPITHELIAL-CELL LINE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CARCINOGENESIS; G(1) CYCLIN; CELL CYCLE; CYCLIN DEPENDENT KINASE ID DEPENDENT KINASES; EXPRESSION; G1; GENES; G(1); PROLIFERATION; PROGRESSION; SUPPRESSION; FIBROBLASTS; CARCINOMA AB Cyclin D1 has been implicated in G(1) cell cycle progression and is frequently amplified, overtranscribed, and oversynthesized in human tumors, including esophageal carcinomas. To further address the role of cyclin D1 in cell cycle control and tumorigenesis, we have stably transfected the human cyclin D1 in the nontumorigenic esophageal epithelial cell line HET-1A. These transfected cells, which express increased amounts of cyclin D1, have enhanced colony-forming efficiency and saturation density and are resistant to growth inhibition by TGF-beta 1 compared with the parental cell line or a control vector cell clone. The clones which express increased amounts of cyclin D1 exhibited a decrease in the amount of TGF-beta type II receptor, indicating a plausible mechanism for their diminished response to TGF-beta 1. Therefore, deregulated expression of the cyclin D1 gene can modulate the negative growth factor pathway of TGF-beta 1 and may disturb the control of epithelial cell proliferation in esophageal carcinogenesis. C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. OHIO STATE UNIV,COLUMBUS,OH 43210. COLUMBIA UNIV,COLUMBIA PRESBYTERIAN CANC CTR,NEW YORK,NY 10032. FU NCI NIH HHS [CA02111] NR 40 TC 84 Z9 88 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 22 PY 1994 VL 91 IS 24 BP 11576 EP 11580 DI 10.1073/pnas.91.24.11576 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PU285 UT WOS:A1994PU28500060 PM 7972105 ER PT J AU KONG, SK CHOCK, PB AF KONG, SK CHOCK, PB TI PURIFICATION AND CHARACTERIZATION OF A UBIQUITIN CARRIER PROTEIN-KINASE FROM HELA-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIVATING ENZYME; MECHANISM; HISTONES; DISAPPEARANCE; CONJUGATION; RESOLUTION; ISOZYMES; INVITRO; MITOSIS AB Protein ubiquitination plays an important role in ATP-dependent protein turnover, and it also may regulate other cellular events. Covalent attachment of ubiquitin to other proteins is catalyzed by three different enzymes, E1, E2, and E3. We have previously shown that protein ubiquitination can be regulated by phosphorylation. In the present study, we show that 20-kDa E2, an E2 molecular mass isoform, is phosphorylated by a protein kinase from the cytosolic fraction of HeLa cells. This protein kinase was purified by a procedure involving ammonium sulfate precipitation and three column chromatographies (phenyl-Sepharose, Superose gel filtration, and DEAE-Sephacel). Gel-filtration chromatography indicated that the molecular mass of this protein kinase was about 300 kDa. However, SDS/PAGE showed that the purified protein kinase consists of three subunits with molecular masses of 120, 105, and 70 kDa, respectively. The stoichiometry of the phosphorylated 20-kDa E2 isozyme was found to be 0.45 mol of phosphate per mol of protein. The phosphorylation of 20-kDa E2 occurred only at the serine residue. The activity of this protein kinase required the presence of Mg2+; however, the enzyme was inhibited by a high concentration of Mg2+. RP KONG, SK (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,BETHESDA,MD 20892, USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 22 PY 1994 VL 91 IS 24 BP 11601 EP 11605 DI 10.1073/pnas.91.24.11601 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PU285 UT WOS:A1994PU28500065 PM 7972110 ER PT J AU BRODER, CC EARL, PL LONG, D ABEDON, ST MOSS, B DOMS, RW AF BRODER, CC EARL, PL LONG, D ABEDON, ST MOSS, B DOMS, RW TI ANTIGENIC IMPLICATIONS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE QUATERNARY STRUCTURE - OLIGOMER-SPECIFIC AND OLIGOMER-SENSITIVE MONOCLONAL-ANTIBODIES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NEUTRALIZING ANTIBODIES; HTLV-III; INTRACELLULAR-TRANSPORT; TRANSMEMBRANE PROTEIN; INFECTED INDIVIDUALS; INFLUENZA-VIRUS; GP120 IMPORTANT; CD4 BINDING; GLYCOPROTEIN; AIDS AB A majority of monoclonal antibodies (mAbs) raised against soluble oligomeric human immunodeficiency virus type 1 isolate IIIB (HIV-1(IIIB)) envelope (env) glycoprotein reacted with conformational epitopes within the gp120 or gp41 subunits. Of 35 mAbs directed against gp41, 21 preferentially reacted with oligomeric env. A subset of these mAbs reacted only with env oligomers (oligomer-specific mAbs). In contrast, only 1 of 27 mAbs directed against the gp120 subunit reacted more strongly with env oligomers than with monomers, and none were oligomer-specific. However, 50% of anti-gp120 mAbs preferentially recognized monomeric env, suggesting that some epitopes in gp120 are partially masked or altered by intersubunit contacts in the native env oligomer. Two mAbs to oligomer-dependent epitopes in gp41 neutralized HIV-1(IIIB) and HIV-1(SF2), and binding of these mAbs to env was blocked by preincubation with HIV-1-positive human serum. Thus, immunization with soluble, oligomeric env elicits antibodies to conserved, conformational epitopes including a newly defined class of neutralizing antibodies that bind to oligomer-specific epitopes in gp41, and may also minimize the production of antibodies that preferentially react with monomeric env protein. C1 UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. RP BRODER, CC (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [R01-AI-35383] NR 41 TC 116 Z9 119 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 22 PY 1994 VL 91 IS 24 BP 11699 EP 11703 DI 10.1073/pnas.91.24.11699 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PU285 UT WOS:A1994PU28500085 PM 7972127 ER PT J AU VLASSARA, H STRIKER, LJ TEICHBERG, S FUH, H LI, YM STEFFES, M AF VLASSARA, H STRIKER, LJ TEICHBERG, S FUH, H LI, YM STEFFES, M TI ADVANCED GLYCATION END-PRODUCTS INDUCE GLOMERULAR SCLEROSIS AND ALBUMINURIA IN NORMAL RATS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RENAL INSUFFICIENCY; DIABETES; AGING; ANIMAL MODEL; AMINOGUANIDINE ID DIABETIC NEPHROPATHY; VASCULAR DYSFUNCTION; PROTEINS; INVIVO; CELL AB High levels of tissue advanced glycation end products (AGEs) that result from the spontaneous modification of proteins by glucose occur in diabetes and aging. To address the potential pathogenic role of AGEs in the glomerulosclerosis of diabetes or nephrosclerosis of aging, doses of AGE-modified rat albumin (25 mg per kg per day, i.v.) sufficient to elevate circulating AGE levels to the range of diabetic serum were administered daily to healthy rats alone or in combination with the AGE inhibitor aminoguanidine. After 5 months, the AGE content of renal tissues in AGE-treated rats rose to 50% above controls (P < 0.025), whereas serum contained 2.8-fold greater AGE levels (P < 0.025), Light and electron microscopy of kidneys from AGE-treated rats revealed a more than 50% increase in glomerular volume compared to controls (P < 0.001), significant periodic acid/Schiff reagent-positive deposits, basement membrane widening, and mesangial extracellular matrix increase and indicated significant glomerulosclerosis compared to untreated (P < 0.002) or albumin-treated controls (P < 0.002). These changes were associated with significant loss of protein (P < 0.005) and albumin (P < 0.002) in the urine of AGE treated rats compared to controls. Cotreatment with aminoguanidine markedly limited both the structural and functional defects. These in vivo data demonstrate that AGEs influence glomerular structure and function in a manner leading to glomerulosclerosis. The effects are AGE-specific, as they are ameliorated by a pharmacological AGE inhibitor, aminoguanidine. C1 NIDDKD, RENAL CELL BIOL SECT, BETHESDA, MD 20892 USA. N SHORE UNIV HOSP, DEPT PATHOL & PEDIAT, MANHASSET, NY 11030 USA. UNIV MINNESOTA, DEPT LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA. RP VLASSARA, H (reprint author), PICOWER INST MED RES, 350 COMMUNITY DR, MANHASSET, NY 11030 USA. FU NIA NIH HHS [AGO-6943, AGO-8245, AGO-9453] NR 23 TC 350 Z9 356 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 22 PY 1994 VL 91 IS 24 BP 11704 EP 11708 DI 10.1073/pnas.91.24.11704 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PU285 UT WOS:A1994PU28500086 PM 7972128 ER PT J AU MASSENBURG, D HAN, JS LIYANAGE, M PATTON, WA RHEE, SG MOSS, J VAUGHAN, M AF MASSENBURG, D HAN, JS LIYANAGE, M PATTON, WA RHEE, SG MOSS, J VAUGHAN, M TI ACTIVATION OF RAT-BRAIN PHOSPHOLIPASE-D BY ADP-RIBOSYLATION FACTOR-1, FACTOR-5, AND FACTOR-6 - SEPARATION OF ADP-RIBOSYLATION FACTOR-DEPENDENT AND OLEATE-DEPENDENT ENZYMES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DIPALMITOYLPHOSPHATIDYLCHOLINE; GUANINE NUCLEOTIDE-BINDING PROTEIN; CHOLERA TOXIN; TRANSPHOSPHATIDYLATION ID CHOLERA-TOXIN; HL-60 GRANULOCYTES; PROTEIN; PHOSPHATIDYLCHOLINE; IDENTIFICATION; PHOSPHATIDATE; BINDING; CELLS; GTP; PHOSPHATIDYLETHANOL AB Two major forms of phospholipase D (PLD) activity, solubilized from rat brain membranes with Triton X-100, were separated by HPLC on a heparin-5PW column with buffer containing octyl glucoside. One form was completely dependent on sodium oleate for activity. The other, which was dramatically activated by the addition of ADP-ribosylation Factor (ARF) 1 and guanine 5' [gamma-thio]triphosphate, required the presence of phosphatidylinositol 4,5-bisphosphate in the phosphatidylcholine substrate for demonstration of activity, as described by others. Oleate dependent activity was unaffected by guanine 5' [gamma-thio]triphosphate, or phosphatidylinositol 4,5-bisphosphate. Both sodium oleate-and ARF-dependent activities catalyzed transphosphatidylation, thus identifying them as PLDs. ARF-dependent PLD was activated by recombinant ARF5 (class II) and ARF6 (class III), as well as ARF1 (class I). Myristoylated recombinant ARFs were more effective than their nonmyristoylated counterparts. ARFs were originally identified as activators of cholera toxin ADP-ribosyltransferase activity. The effects of recombinant ARF proteins from the three classes on cholera toxin activity (assayed under conditions identical to those used to assay PLD activity) did not, however, correlate with those on PLD, consistent with the notion that different aspects of ARF structure are involved in the two functions. C1 NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 37 TC 238 Z9 240 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 22 PY 1994 VL 91 IS 24 BP 11718 EP 11722 DI 10.1073/pnas.91.24.11718 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PU285 UT WOS:A1994PU28500089 PM 7972129 ER PT J AU CUTLER, R JOSEPH, JA YAMAGAMI, K VILLALOBOSMOLINA, R ROTH, GS AF CUTLER, R JOSEPH, JA YAMAGAMI, K VILLALOBOSMOLINA, R ROTH, GS TI AREA-SPECIFIC ALTERATIONS IN MUSCARINIC STIMULATED LOW K-M GTPASE ACTIVITY IN AGING AND ALZHEIMERS-DISEASE - IMPLICATIONS FOR ALTERED SIGNAL-TRANSDUCTION SO BRAIN RESEARCH LA English DT Article DE AGING; ALZHEIMERS DISEASE; MUSCARINIC SIGNAL TRANSDUCTION; GTPASE ID POSTMORTEM HUMAN-BRAIN; RAT-BRAIN; MESSENGER-RNA; AGED RAT; RECEPTORS; BINDING; HIPPOCAMPUS; MEMBRANES; PROTEINS; REGIONS AB Carbachol-stimulated low K-m GTPase activity (an index of muscarinic receptor-G protein coupling) was examined in hippocampus, basal ganglia, orbital frontal gyrus and superior frontal gyrus obtained from mature, aged and Alzheimer's Disease (AD) groups. Results indicated that carbachol-stimulated low K-m GTPase activities in basal ganglia were as follows: mature controls > aged > AD, and there was a trend toward a similar pattern of decline in the hippocampus. No differences were seen in the two cortical areas examined; however, carbachol-stimulated low K-m GTPase activity was small in the mature controls. Importantly, there were significant negative correlations between disease duration and carbachol-stimulated low K-m GTPase activity in all areas examined except the orbital frontal gyrus. The longer the duration of the disease the lower the carbachol-stimulated low K-m GTPase activity. Results suggest that age and disease-related changes in mAChR-G protein interactions in the basal ganglia may contribute to reduced signal transduction (ST). In addition, since decreased carbachol-stimulated low K-m GTPase activity has also been observed in the aged rat; thus, investigations of the factors involved in decrements in signal transduction in the aged rat may be useful for understanding these alterations in aged humans or victims of AD. C1 TUFTS UNIV, USDA ARS, HUMAN NUTR RES CTR AGING, BOSTON, MA 02111 USA. NIA, GERONTOL RES CTR, MOLEC PHYSIOL & GENET SECT, BALTIMORE, MD 21224 USA. YOSHITOMI PHARMACEUT IND LTD, IRUMA, SAITAMA 358, JAPAN. CINVESTAV IPN, DEPT PHARMACOL & TOXICOL, MEXICO CITY 16020, DF, MEXICO. RI Yamagami, Keiji/E-9500-2012 NR 30 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 21 PY 1994 VL 664 IS 1-2 BP 54 EP 60 DI 10.1016/0006-8993(94)91953-4 PG 7 WC Neurosciences SC Neurosciences & Neurology GA PR431 UT WOS:A1994PR43100008 PM 7895046 ER PT J AU SHI, YB LIANG, VCT PARKISON, C CHENG, SY AF SHI, YB LIANG, VCT PARKISON, C CHENG, SY TI TISSUE-DEPENDENT DEVELOPMENTAL EXPRESSION OF A CYTOSOLIC THYROID-HORMONE PROTEIN GENE IN XENOPUS - ITS ROLE IN THE REGULATION OF AMPHIBIAN METAMORPHOSIS SO FEBS LETTERS LA English DT Article DE THYROID HORMONE; AMPHIBIAN METAMORPHOSIS; BINDING OF THYROID HORMONE; GENE REGULATION; EXPRESSION OF A CYTOSOLIC PROTEIN ID PYRUVATE-KINASE AB We have cloned the cDNA encoding the Xenopus laevis homolog of mammalian cytosolic thyroid hormone binding protein (CTHBP). We found that while its mRNA level varies little in whole animals during development, the expression of CTHBP is inversely correlated with tissue-specific transformations during metamorphosis. A high level of its mRNA was observed in the tail of premetamorphic tadpoles. However, the expression is dramatically repressed with the onset of rapid tail resorption. In the hindlimb, the expression of CTHBP is very low during morphogenesis. Subsequently, its expression continuously increases during the period of limb growth. In contrast, a low level of CTHBP expression was detected in the intestine throughout metamorphosis. These results suggest that CTHBP could function to modulate the metamorphic process by regulating the level of intracellular thyroid hormones. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RP SHI, YB (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. NR 13 TC 35 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 21 PY 1994 VL 355 IS 1 BP 61 EP 64 DI 10.1016/0014-5793(94)01173-7 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PU124 UT WOS:A1994PU12400015 PM 7957964 ER PT J AU BANWELL, MG FAM, MA GABLE, RW HAMEL, E AF BANWELL, MG FAM, MA GABLE, RW HAMEL, E TI TOTAL SYNTHESES OF THE STRUCTURES ASSIGNED TO SALIMINE AND JERUSALEMINE, ALKALOIDS FROM COLCHICUM-DECAISNEI BOISS (LILIACEAE) SO JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS LA English DT Article ID ANALOGS; RING AB Total syntheses of the dibenzo[a,c]cycloheptylamines (+/-)-1 and (+/-)-2 have been developed; the spectroscopic properties of synthetic 2 match those reported for the alkaloid jerusalemine but compound 1 is different from the alkaloid salimine. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP BANWELL, MG (reprint author), UNIV MELBOURNE,SCH CHEM,PARKVILLE,VIC 3052,AUSTRALIA. RI Banwell, Martin/H-8354-2014 NR 18 TC 21 Z9 21 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0022-4936 J9 J CHEM SOC CHEM COMM JI J. Chem. Soc.-Chem. Commun. PD NOV 21 PY 1994 IS 22 BP 2647 EP 2649 DI 10.1039/c39940002647 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA PU259 UT WOS:A1994PU25900054 ER PT J AU NAVERI, L STROMBERG, C SAAVEDRA, JM AF NAVERI, L STROMBERG, C SAAVEDRA, JM TI ANGIOTENSIN-II AT(1) RECEPTOR-MEDIATED CONTRACTION OF THE PERFUSED RAT CEREBRAL-ARTERY SO NEUROREPORT LA English DT Article DE ANGIOTENSIN II; AT(1) RECEPTORS; AT(2) RECEPTORS; CONTRACTION; CEREBRAL ARTERIES; RAT ID BLOOD-FLOW; ARTERIOLES; VESSELS; DOG AB THE effect of angiotensin II on rat cerebral arteries was studied using isolated, perfused segments of anterior cerebral arteries. The infusion rate was set to maintain baseline intraluminal pressure at 75 mmHg. Angiotensin II (100nM) increased the intraluminal pressure by 22.5 +/- 2.2 mmHg. Losartan, an AT(1) antagonist, at 1 mu M, completely blocked the effect of angiotensin II, whereas the AT(2) ligands PD 123319 (1 mu M) and CGP 42112 (1 mu M) were ineffective. None of these AT(1) or AT(2) selective ligands alone displayed any agonist effects. The results show that angiotensin II induces contraction of the rat anterior cerebral artery by acting on AT(1) receptors. C1 NIMH,PHARMACOL SECT,CLIN SCI LAB,BETHESDA,MD 20892. NATL AGCY MED,DEPT PHARMACOL,SF-00300 HELSINKI,FINLAND. RP NAVERI, L (reprint author), UNIV HELSINKI,INST BIOMED,DEPT PHARMACOL & TOXICOL,POB 8,SILTAVUORENPENGER 10,SF-00014 HELSINKI,FINLAND. NR 15 TC 20 Z9 20 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 21 PY 1994 VL 5 IS 17 BP 2278 EP 2280 PG 3 WC Neurosciences SC Neurosciences & Neurology GA PW547 UT WOS:A1994PW54700018 PM 7881045 ER PT J AU ANDERSSONELLSTROM, A DILLNER, J HAGMAR, B SCHILLER, J FORSSMAN, L AF ANDERSSONELLSTROM, A DILLNER, J HAGMAR, B SCHILLER, J FORSSMAN, L TI NO SEROLOGICAL EVIDENCE FOR NONSEXUAL SPREAD OF HPV16 SO LANCET LA English DT Letter ID PAPILLOMAVIRUS C1 DIST HLTH CTR GRIPEN,KARLSTAD,SWEDEN. KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. OSLO UNIV HOSP,DEPT CLIN CYTOL,OSLO,NORWAY. NIH,OBSTET & GYNECOL LAB,BETHESDA,MD. OSTRA HOSP,DEPT OBSTET & GYNECOL,S-41685 GOTHENBURG,SWEDEN. RP ANDERSSONELLSTROM, A (reprint author), CTR PUBL HLTH RES,KARLSTAD,SWEDEN. NR 5 TC 29 Z9 31 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 19 PY 1994 VL 344 IS 8934 BP 1435 EP 1435 DI 10.1016/S0140-6736(94)90601-7 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PR786 UT WOS:A1994PR78600045 PM 7968093 ER PT J AU RASHIN, AA YOUNG, L TOPOL, IA BURT, SK AF RASHIN, AA YOUNG, L TOPOL, IA BURT, SK TI MOLECULAR DIPOLE-MOMENTS CALCULATED WITH DENSITY-FUNCTIONAL THEORY SO CHEMICAL PHYSICS LETTERS LA English DT Article ID ENERGIES; ENERGETICS; DYNAMICS; CHARGES AB Molecular dipole moments (MDM) of 32 molecules calculated with density functional (DFT) and Hartree-Fock (HF) methods are compared and analyzed. We found that calculations with DFT using a DZVPD (double-zeta plus polarization in valence orbitals and diffuse d functions on heavy atoms) basis set currently provide the best theoretical values of the vacuum MDM closest to the experimental values and to available results from large CI calculations. MDM from DFT using DZVPD basis set (DFT/DZVPD), DFT/DZVP2 and HF/6-31G* calculations lead to mean unsigned errors of 0.06, 0.18 and 0.30 D, respectively, relative to the experimental values. A use of triple zeta basis sets did not lead to further improvements in the computed MDM. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYN CORP,FREDERICK SUPERCOMP CTR,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. RP RASHIN, AA (reprint author), BIOCHEMCOMP INC,543 SAGAMORE AVE,TEANECK,NJ 07666, USA. NR 19 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD NOV 18 PY 1994 VL 230 IS 1-2 BP 182 EP 188 DI 10.1016/0009-2614(94)01150-8 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA PR847 UT WOS:A1994PR84700030 ER PT J AU PATEL, AP CERRUTI, C VAUGHAN, RA KUHAR, MJ AF PATEL, AP CERRUTI, C VAUGHAN, RA KUHAR, MJ TI DEVELOPMENTAL REGULATED GLYCOSYLATION OF DOPAMINE TRANSPORTER SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE DOPAMINE; TRANSPORTER; COCAINE; PHOTOAFFINITY; DEVELOPMENT; GLYCOSYLATION; STRIATUM ID RAT STRIATUM; LINKED OLIGOSACCHARIDES; CLONING; EXPRESSION; BRAIN; GLYCOBIOLOGY; ONTOGENESIS; AFFINITY; SITES; AGE AB The dopamine transporter (DAT) in rat striatum was examined during postnatal development and aging after photolabeling with [I-125]DEEP. The DAT-[I-125]DEEP protein complex from adult rats (2 months) appeared as a broad diffuse band in SDS-PAGE gels with average apparent molecular mass of about 80,000 Da as previously found. However, the molecular mass was lower at birth (day 0) and at postnatal ages 4 and 14 days. In aged rats (104 weeks), the molecular mass was slightly higher than that found in young adults (60 days). In binding experiments with [H-3]BTCP, there were age-related differences in K-d and B-max with decreases in both K-d and B-max found in aged rats. Treatment of photolabeled membranes with neuraminidase caused a reduction in DAT molecular mass, but age-related differences were maintained. Treatment with N-glycanase greatly reduced or eliminated the age-related differences. Several DAT peptide-specific polyclonal antibodies immunoprecipitated DAT[I-125]DEEP protein complex at different developmental ages. Taken together, these results suggest differential glycosylation of rat DAT occurs during postnatal development and aging; the increase is due to increases in the N-linked sugars rather than changes in either sialic acid content or the polypeptide. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. NR 31 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD NOV 18 PY 1994 VL 83 IS 1 BP 53 EP 58 DI 10.1016/0165-3806(94)90178-3 PG 6 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA PT353 UT WOS:A1994PT35300005 ER PT J AU BRADY, JP PIATIGORSKY, J AF BRADY, JP PIATIGORSKY, J TI A MOUSE CDNA-ENCODING A PROTEIN WITH ZINC-FINGERS AND A KRAB DOMAIN SHOWS SIMILARITY TO HUMAN PROFILAGGRIN SO GENE LA English DT Note DE NUCLEIC-ACID-BINDING DOMAIN; PCR; EVOLUTION; KERATIN-BINDING PROTEIN ID CARBOXYPEPTIDASE-A; MOLECULAR-CLONING; MESSENGER-RNA; GENE FAMILY; LENS; CRYSTALLIN; FILAGGRIN; SEQUENCE; SEARCH; DNA AB As part of our efforts to understand transcriptional regulation in the vertebrate eye lens: we have isolated a clone that encodes a zinc finger (Zf) protein from a newborn mouse lens cDNA library. Corresponding message for this protein is detectable in the lens, liver, heart, kidney, spleen and brain of newborn mice. A longer cDNA containing the complete ORF for the same protein was isolated from an adult mouse testis library. A conceptual translation of the testis cDNA sequence produces a 555-amino-acid (aa) protein that contains nine C-terminal Zf and an N-terminal domain found in a subset of C2H2 Zf, the Kruppel-associated box (KRAB). The aa sequence located between the KRAB domain and the Zf shows an unexpected similarity to human profilaggrin, a protein expressed in differentiating epidermal cells. Sequences that hybridize to this cDNA are detectable in ten other mammalian species. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 25 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 18 PY 1994 VL 149 IS 2 BP 299 EP 304 DI 10.1016/0378-1119(94)90165-1 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA PT811 UT WOS:A1994PT81100016 PM 7959006 ER PT J AU GAO, JL MURPHY, PM AF GAO, JL MURPHY, PM TI HUMAN CYTOMEGALOVIRUS OPEN READING FRAME US28 ENCODES A FUNCTIONAL BETA-CHEMOKINE RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID HUMAN INTERLEUKIN-8 RECEPTOR; HERPESVIRUS SAIMIRI; VIRUS; EXPRESSION; INFECTION; HOMOLOGS; CLONING AB Human cytomegalovirus infects epithelial, smooth muscle, and white blood cells in vivo causing acute, latent, and chronic infections. A data base search that the amino acid sequence of the putative protein encoded by open reading frame US28 of human cytomegalovirus is similar to 30% identical to those of the mammalian leukocyte receptors for alpha and beta chemokines. This suggested that US28 was originally copied from a human chemokine receptor gene, perhaps to provide the virus with a selective advantage through molecular mimicry. Chemokines regulate the trafficking and activation of mammalian leukocytes and activate calcium-mobilizing, heptahelical, G protein-coupled receptors. We now show that US28 encodes a promiscuous calcium-mobilizing receptor for the beta chemokines RANTES (regulated upon activation, normal T expressed and secreted), macrophage inflammatory protein-1 alpha, and monocyte chemoattractant protein-1, but not for the alpha chemokines interleukin-8 or gamma IP10. The chemokine selectivity of the US28 product is distinct from that of known mammalian beta chemokine receptors. This finding suggests a role for beta chemokines in the pathogenesis of human cytomegalovirus infection by transmembrane signaling via the product of US28. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 26 TC 265 Z9 270 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 28539 EP 28542 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800005 PM 7961796 ER PT J AU BAROUCH, W PRASAD, K GREENE, LE EISENBERG, E AF BAROUCH, W PRASAD, K GREENE, LE EISENBERG, E TI ATPASE ACTIVITY ASSOCIATED WITH THE UNCOATING OF CLATHRIN BASKETS BY HSP70 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK RESPONSE; COATED VESICLES; BOVINE BRAIN; ASSEMBLY PROTEIN; STRESS PROTEINS; DISSOCIATION; BINDING; TRANSLOCATION; POLYPEPTIDES; HYDROLYSIS AB In the presence of ATP, bovine brain hsp70 has been shown to remove clathrin from bovine brain clathrin-coated vesicles in a rapid stoichiometric initial burst followed by slow steady-state uncoating. In addition, it has been found recently that a 100-kDa cofactor is required for hsp70 to uncoat clathrin baskets prepared with the assembly protein AP-2. In this study the ATPase activity associated with uncoating was investigated, with baskets formed from clathrin and assembly proteins. Mixed assembly proteins or assembly protein AP-2 could not be used in ATPase studies because they activated the hsp70 ATPase activity even in the absence of clathrin. However, this was not the case with assembly protein AP(180). A stoichiometric initial burst of ATP hydrolysis was found to accompany the initial burst of uncoating of AP(180)-clathrin baskets by hsp70, with 1 mol of hydrolyzed ATP/mol of released clathrin heavy chain. Furthermore, the presence of a 100-kDa cofactor was needed for both processes. These results suggest that an initial burst of uncoating occurs with all clathrin baskets, that an initial burst of ATP hydrolysis accompanies this initial burst of uncoating, and that a 100-kDa cofactor is required for both. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 36 TC 34 Z9 34 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 28563 EP 28568 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800011 PM 7961802 ER PT J AU LETEURTRE, F FUJIMORI, A TANIZAWA, A CHHABRA, A MAZUMDER, A KOHLHAGEN, G NAKANO, H POMMIER, Y AF LETEURTRE, F FUJIMORI, A TANIZAWA, A CHHABRA, A MAZUMDER, A KOHLHAGEN, G NAKANO, H POMMIER, Y TI SAINTOPIN, A DUAL INHIBITOR OF DNA TOPOISOMERASE-I AND TOPOISOMERASE-II, AS A PROBE FOR DRUG-ENZYME INTERACTIONS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX-ASSOCIATED REGION; C-MYC; EUKARYOTIC TOPOISOMERASE; SEQUENCE REQUIREMENTS; INTOPLICINE RP-60475; INTERACTION DOMAINS; CLEAVAGE ACTIVITY; ANTITUMOR AGENT; CAMPTOTHECIN; PROTEIN AB Stabilization of the topoisomerase-cleavable complexes is the common initial event leading to the cytotoxicity of topoisomerase I and II (top1 and top2) inhibitors. Using saintopin (STP), a poison of both topoisomerases, we studied top1- and top2-cleavable complexes (Yamashita, Y., Kawada, S.-Z., Fujii, N., and Nakano, H. (1991) Biochemistry 30, 5838-5845). top1 and top2 sites induced in the presence of STP showed the same preferences for the base located 3' to the topoisomerase-induced DNA break (position +1): preference for G and not C. A camptothecin-resistant top1 with a mutation (Asn(722) --> Ser) next to the catalytic tyrosine (Tyr(723)) was cross-resistant to STP, suggesting that both STP and camptothecin interact with the protein near the catalytic tyrosine. These results are consistent with a dual interaction of the drug with the enzyme and the DNA and provide further evidence for the ''drug-stacking'' model. This model proposes that topoisomerase inhibitors bind, possibly through hydrogen bonding and/or stacking, with one of the bases flanking the DNA termini (guanine at position +1 in the case of STP) and within the enzyme catalytic pocket, most likely by stacking with the catalytic tyrosine. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. KYOWA HAKKO KOGYO CO LTD,TOKYO RES LABS,MACHIDA,TOKYO 194,JAPAN. NR 49 TC 65 Z9 66 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 28702 EP 28707 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800031 PM 7961822 ER PT J AU MYERS, MG GRAMMER, TC WANG, LM SUN, XJ PIERCE, JH BLENIS, J WHITE, MF AF MYERS, MG GRAMMER, TC WANG, LM SUN, XJ PIERCE, JH BLENIS, J WHITE, MF TI INSULIN-RECEPTOR SUBSTRATE-1 MEDIATES PHOSPHATIDYLINOSITOL 3'-KINASE AND P70(S6K) SIGNALING DURING INSULIN, INSULIN-LIKE GROWTH-FACTOR-I, AND INTERLEUKIN-4 STIMULATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASES; HEMATOPOIETIC-CELLS; IRS-1; PHOSPHORYLATION; TRANSDUCTION; ASSOCIATION; EXPRESSION; ACTIVATION; 3-KINASE; PDGF AB Insulin Receptor Substrate-1 (IRS-1) is an endogenous cellular protein that is tyrosine phosphorylated during stimulation of cells with insulin, IGF-1, and interleukin 4 (IL-4). Phosphorylated IRS-1 regulates multiple regulatory pathways by recruiting signaling molecules containing Src homology 2 domains (SH2 proteins). The 32D myeloid progenitor cell line contains few insulin receptors and no detectable IRS-1. Expression of the insulin receptor alone partially mediates insulin-stimulated microtubule-associated protein (MAP) kinase activation, and the addition of IRS-1 enhances this effect (Myers, M. G., Jr., Wang, L.-M., Sun, X. J., Zhang, Y., Yenush, L. P., Schlessinger, J., Pierce, J. H., and White, M. F. (1994) Mol. Cell. Biol. 14, 3577-3587). Alone, insulin receptors mediate phosphatidylinositol (PI) 3'-kinase and p70(S6k) activation poorly if at all during insulin stimulation. Expression of IRS-1 alone in 32D cells mediates the stimulation of p70(S6k) by insulin, IGF-1, or IL 4; addition of insulin receptor to these cells increases the sensitivity of the insulin response. In contrast, full insulin stimulation of PI 3'-kinase requires both the insulin receptor and IRS-1, suggesting that a high level of IRS-1 phosphorylation is required for insulin-stimulated PI 3'-kinase activation, whereas a low level of IRS-1 tyrosine phosphorylation transmits an essential signal to p70(S6k). Both insulin receptors and IRS-1 are required for mitogenic signaling in 32D cells suggesting that MAP kinase or p70(S6k) alone are not sufficient, and that both or additional unknown IRS-1-mediated signals are necessary. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,PROGRAM CELL & DEV BIOL,BOSTON,MA 02215. NIH,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 46595]; NIDDK NIH HHS [DK 38712, DK 43808] NR 40 TC 223 Z9 223 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 28783 EP 28789 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800043 PM 7961833 ER PT J AU LAWRENCE, R CHANG, LJ SIEBENLIST, U BRESSLER, P SONENSHEIN, GE AF LAWRENCE, R CHANG, LJ SIEBENLIST, U BRESSLER, P SONENSHEIN, GE TI VASCULAR SMOOTH-MUSCLE CELLS EXPRESS A CONSTITUTIVE NF-KAPPA-B-LIKE ACTIVITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING SUBUNIT; C-MYC PROMOTER; TRANSCRIPTION FACTOR; P65 SUBUNIT; GENE; REL; ACTIVATION; ALPHA; SITE; TRANSACTIVATION AB The NF-kappa B/Rel family of transcription factors is commonly expressed in non-hematopoietic cells in an inactive form within the cytoplasm, complexed with an inhibitor I kappa B protein. Thus, it was surprising that NF-kappa B element-driven heterologous promoter-reporter gene constructs were active upon transient transfection into vascular smooth muscle cells (VSMCs). Here, we report that VSMCs express a constitutive nuclear NF-kappa B-like activity. In electrophoretic mobility shift assays, nuclear extracts demonstrated binding to a wild type NF-kappa B element but not to those mutated at nucleotides critical for Rel-protein DNA interaction. Binding was abrogated by the presence of I kappa B-alpha. Furthermore, addition of an antibody to the p50 subunit of classical NF-kappa B (but not p65, c-Rel, or RelB) resulted in supershifted complexes. Transactivation of element-driven constructs was negatively affected by co-transfection of a vector expressing a dominant negative p50 subunit, which can dimerize with other Rel subunits but not bind DNA. The long terminal repeat of the human immunodeficiency virus-1, which is driven in part by two NF-kappa B elements, displayed strong activity within VSMCs. This activity was abrogated upon co-transfection of the vector expressing the dominant negative p50 mutant. Taken together, these experiments indicate that VSMCs constitutively express a functional NF-kappa B-like trans-acting factor, which may play a significant role in the regulation of proliferation and viral infection of these cells. C1 BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118. UNIV ALBERTA,GLAXO HERITAGE RES INST,DEPT MED MICROBIOL & INFECT DIS,EDMONTON T6G 2H7,AB,CANADA. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA36355]; NHLBI NIH HHS [HL13262]; NIA NIH HHS [AG00115] NR 37 TC 71 Z9 78 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 28913 EP 28918 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800063 PM 7961853 ER PT J AU SINGH, Y KLIMPEL, KR ARORA, N SHARMA, M LEPPLA, SH AF SINGH, Y KLIMPEL, KR ARORA, N SHARMA, M LEPPLA, SH TI THE CHYMOTRYPSIN-SENSITIVE SITE, FFD315, IN ANTHRAX TOXIN PROTECTIVE ANTIGEN IS REQUIRED FOR TRANSLOCATION OF LETHAL FACTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIPHTHERIA-TOXIN; BACILLUS-ANTHRACIS; PSEUDOMONAS EXOTOXIN; ADENYLATE-CYCLASE; LOW-PH; CELLS; SEQUENCE; CYTOSOL; ENTRY; MACROPHAGES AB The protective antigen (PA) component of anthrax toxin contains two sites that are uniquely sensitive to proteolytic cleavage. Cleavage at the sequence RKKR(167) by the cellular protease furin is absolutely required for toxicity, whereas cleavage by chymotrypsin or thermolysin at the sequence FFD315 inactivates the protein, apparently by blocking the ability of PA to translocate the catalytic moieties of the toxins, lethal factor (LF) and edema factor (EF), to the cytosol of eukaryotic cells. To specify the role of the chymotrypsin-sensitive site of PA in the translocation of LF, we altered residues 313-315. None of the mutations in this region interfered with the ability of PA to bind to its cellular receptor, be cleaved by cell surface furin, and bind LF. Substitution of Ala for Asp(315) Or for both Phe(313) and Phe(314) reduced the ability of PA to intoxicate cells in the presence of LF by 3- and 7-fold, respectively. Substitution of Phe(313) by Cys greatly reduced the rate of LF translocation and delayed toxicity. The rate at which the Cys-substituted PA killed cells was increased significantly by blocking the sulfhydryl group with iodoacetamide, suggesting that this added Cys interacts with cellular proteins and slows translocation of LF. Deletion of the 2 Phe rendered PA completely non-toxic. This deleted PA protein lacked the ability shown by native PA to form oligomers on cells and in solution and to induce release of Rb-86 from Chinese hamster ovary cells. These results suggest that the chymotrypsin-sensitive site in PA is required for membrane channel formation and translocation of LF into the cytosol. PA double mutants were constructed that cannot be cleaved at either the furin or chymotrypsin sites. These PA proteins were more stable in Bacillus anthracis culture supernatants and may therefore be useful as a replacement for PA in anthrax vaccines. C1 NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. CTR BIOCHEM TECHNOL,DELHI 110007,INDIA. NR 35 TC 72 Z9 74 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 29039 EP 29046 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800079 PM 7961869 ER PT J AU NOGUCHI, M MIYAMOTO, S SILVERMAN, TA SAFER, B AF NOGUCHI, M MIYAMOTO, S SILVERMAN, TA SAFER, B TI CHARACTERIZATION OF AN ANTISENSE INR ELEMENT IN THE EIF-2-ALPHA GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAJOR LATE PROMOTER; RNA POLYMERASE-II; EUKARYOTIC INITIATION FACTOR-2-ALPHA; HUMAN SQUAMOUS CARCINOMA; TRANSCRIPTION FACTOR; MAMMALIAN-CELLS; PROTEIN-SYNTHESIS; S-POMBE; EXPRESSION; BINDING AB We recently discovered an opposing initiator prometer (Inr) downstream of the sense promoter region of the eIF-2 alpha gene (Silverman, T., Noguchi, M., and Safer, B. (1992) J. Biol. Chem. 267, 9738-9742). By reverse transcriptase/polymerase chain reaction analysis of G(0) and activated (G(1)) T-lymphocyte RNAs, overlapping sense and antisense transcripts are now identified. Sense transcription of the eIF-2 alpha gene proceeds from left to right to generate alpha-mRNA; antisense transcription proceeds from right to left to generate RNA, having a sequence complementary to eIF-2 alpha mRNA. Upstream indicates a position 5' relative to the transcription start site. Using DNase I footprint analysis and EMSA, we have found a potential cis-regulatory sequence immediately upstream of the Inr which binds a 43-kDa protein. In addition to conferring protection against DNase I (+457 to +474), the factor also generates hypersensitive sites directly over the Inr (+447 to +457). Insertion of the Inr footprint region into a luciferase reporter gene construct increases expression 150-fold. While mutation of the Inr conserved sequence decreases luciferase activity by 50%, mutation of the 43-kDa factor binding site inhibits luciferase activity by 20%. Sense orientation of the Inr footprint region decreases activity by 80%. The 43-kDa Inr-associated binding protein may be involved in allowing access of RNA polymerase II transcription complexes to the initiation site of this TATA-less gene A model for the regulation of eIF-2 alpha expression involving the rapid degradation of dsRNA generated by the relative activities of the two overlapping and opposing promoters is proposed. C1 NHLBI,MOLEC HEMATOL BRANCH,PROT & RNA BIOSYNTH SECT,BETHESDA,MD 20892. NR 52 TC 31 Z9 31 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 29161 EP 29167 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800094 PM 7525581 ER PT J AU KOBAYASHI, T URABE, K ORLOW, SJ HIGASHI, K IMOKAWA, G KWON, BS POTTERF, B HEARING, VJ AF KOBAYASHI, T URABE, K ORLOW, SJ HIGASHI, K IMOKAWA, G KWON, BS POTTERF, B HEARING, VJ TI THE PMEL-17 SILVER LOCUS PROTEIN - CHARACTERIZATION AND INVESTIGATION OF ITS MELANOGENIC FUNCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAMMALIAN TYROSINASE; MELANIN BIOSYNTHESIS; DOPACHROME; IDENTIFICATION; PIGMENTATION; MELANOCYTES; GENE; TAUTOMERASE; EXPRESSION; CULTURE AB The silver mutation in mice causes progressive graying of hair due to the loss of functional follicular melanocytes. Recently the silver locus gene (called Pmel 17) has been cloned; its encoded product shares homology with a chick melanosomal matrix protein and a bovine retinal pigment epithelial protein. Although the sequence of the silver gene and the correlation of its expression with pigment production have been reported, its function in melanogenesis is still unknown. In an effort to characterize that function, we have synthesized the predicted carboxyl-terminal peptide of the mouse Pmel 17 protein and generated a rabbit polyclonal antibody (alpha PEP13) to it; that antibody recognized the silver protein specifically. The immunoaffinity-purified silver protein lacked all of the known melanogenic catalytic activities which other tyrosinase-related proteins (TRP) have, nor did it appear to modulate any of those TRP activities. Metabolic labeling experiments demonstrated that the silver protein disappears in vivo within a few hours, indicating that it is rapidly degraded, or quickly processed to lose its carboxyl terminus. Crossreactivity experiments showed that a recently reported anti-melanosomal matrix protein antibody (alpha MX) also recognizes the silver protein, although at a different epitope from that of alpha PEP13. Using Western immunoblotting, we analyzed subcellular fractions isolated from B16 F10 melanoma cells and found that the silver protein was rich in the melanosome fraction but was absent from coated vesicles which deliver TRPs to melanosomes. These results suggest that the silver locus product is a melanosomal matrix protein which may contribute to melanogenesis as a structural protein, although the possibility remains that it also has a novel catalytic function in melanogenesis. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. KAO INST FUNDAMENTAL RES,HAGA,TOCHIGI 32134,JAPAN. NYU,SCH MED,RONALD O PERELMAN DEPT DERMATOL,NEW YORK,NY 10016. NYU,SCH MED,DEPT CELL BIOL,NEW YORK,NY 10016. INDIANA UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. FU NIAMS NIH HHS [AR41880] NR 43 TC 123 Z9 123 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 29198 EP 29205 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800099 PM 7961886 ER PT J AU DOEGE, KJ GARRISON, K COULTER, SN YAMADA, Y AF DOEGE, KJ GARRISON, K COULTER, SN YAMADA, Y TI THE STRUCTURE OF THE RAT AGGRECAN GENE AND PRELIMINARY CHARACTERIZATION OF ITS PROMOTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEOGLYCAN CORE PROTEIN; CHONDROITIN SULFATE PROTEOGLYCAN; BOVINE CARTILAGE PROTEOGLYCAN; LINK PROTEIN; SEQUENCE-ANALYSIS; ADHESION RECEPTORS; MESSENGER-RNA; CHICK-EMBRYO; PARTIAL CDNA; CLONING AB Aggrecan is a major structural component of cartilage extracellular matrix and a specific gene product of differentiated chondrocytes, cDNA clones have been used to isolate rat aggrecan genomic clones from phage and cosmid libraries, producing over 80 kilobases (kb) of overlapping DNA containing the complete rat aggrecan gene, including 12 kb of 5'- and 8 kb of 3'-flanking DNA. DNA sequencing shows 18 exons, most of which encode structural or functional modules; exceptions are do mains G1-B and G2-B, which are split into two exons and the G3 lectin domain, which is encoded by three exons. There is one expressed epidermal growth factor-like exon and in addition a non-expressed ''pseudo-exon'' encoding a heavily mutated epidermal growth factor-like domain. Intron sizes have been determined by restriction mapping and inter exon polymerase chain reaction; a 30-kb intron separates exons 1 and 2. Exon 1 has been mapped by primer extension and S1 nuclease protection; it encodes 381 base pairs (bp) of 5'-untranslated sequence. There is a minor promoter which initiates transcription an additional 68 bp 5' of the major promoter start site. DNA sequence is reported for a 529-bp fragment encompassing exon 1, including 120 bp of 5'-flanking DNA comprising the promoter. This promoter is lacking the TATAA or CCAAT elements but has several putative binding sites for transcription factors. A 922-bp DNA fragment with 640-bp 5'-flanking DNA and 282-bp exon 1 sequence showed higher promoter activity in transfected chondrocytes than in fibroblasts, is completely inactive in the reverse orientation, and is strongly enhanceable in the forward direction by the SV40 enhancer. C1 OREGON HLTH SCI UNIV,DEPT BIOCHEM & MOLEC BIOL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT CELL BIOL & ANAT,PORTLAND,OR 97201. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP DOEGE, KJ (reprint author), OREGON HLTH SCI UNIV,SHRINERS HOSP CRIPPLED CHILDREN,RES UNIT,3101 SW SAM JACKSON PK RD,PORTLAND,OR 97201, USA. NR 56 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 29232 EP 29240 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800104 PM 7961891 ER PT J AU HICKMAN, AB PALMER, I ENGELMAN, A CRAIGIE, R WINGFIELD, P AF HICKMAN, AB PALMER, I ENGELMAN, A CRAIGIE, R WINGFIELD, P TI BIOPHYSICAL AND ENZYMATIC-PROPERTIES OF THE CATALYTIC DOMAIN OF HIV-1 INTEGRASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CIRCULAR DICHROIC ANALYSIS; DNA-BINDING; VIRAL-DNA; POLYNUCLEOTIDYL TRANSFER; SEQUENCE REQUIREMENTS; RETROVIRUS INTEGRASE; PROTEIN CONFORMATION; ANGSTROM RESOLUTION; MUTATIONAL ANALYSIS AB A deletion derivative of the integrase protein from human immunodeficiency virus type-1 (HIV-1) consisting of the central core domain (amino acids 50-212) has been characterized biophysically and biochemically. This deletion mutant is of particular interest for structural studies as it can carry out the disintegration reaction suggesting the presence of an active site and, under certain conditions, is more soluble than full-length integrase. The circular dichroism and fluorescence of the deletion mutant and the 288-residue full-length integrase were similar, indicating that the core residues maintain similar overall conformations in both proteins. The deletion mutant is approximately 10% more alpha-helical than the full-length protein. Analytical centrifugation demonstrated that both proteins undergo monomer-dimer association although the truncated protein showed slightly less tendency to dimerize; the dissociation constants were 2.5 x 10(-5) M for the full-length protein and 8.0 x 10(-5) M for the truncated protein. The disintegration activity of both proteins was also compared. Although a higher concentration of the truncation mutant was required for optimal activity, the mutant did not have altered pH or Mn2+ requirements relative to the full-length protein. The combined biophysical and enzymatic studies suggest that this truncated form of HIV-1 integrase is likely to be useful for structural studies. C1 NIDDK, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NIH, PROT EXPRESS LAB, OFF DIRECTOR, BETHESDA, MD 20892 USA. NR 66 TC 67 Z9 68 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 29279 EP 29287 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800111 PM 7961898 ER PT J AU WANG, N MAURIZI, MR EMMERTBUCK, L GOTTESMAN, MM AF WANG, N MAURIZI, MR EMMERTBUCK, L GOTTESMAN, MM TI SYNTHESIS, PROCESSING, AND LOCALIZATION OF HUMAN LON PROTEASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ATP-DEPENDENT PROTEASE; MITOCHONDRIAL MATRIX; LIVER-MITOCHONDRIA; TARGETING PEPTIDES; ESCHERICHIA-COLI; IMPORT MACHINERY; RAT-LIVER; PRECURSOR; PROTEINS; AMINOTRANSFERASE AB The synthesis, maturation, and localization of the human homolog of the bacterial ATP-dependent Lon protease have been studied in cultured cells and in a cell-free system. Immunofluorescence microscopy of cells transfected with a recombinant human Lon protease FLAG epitope chimeric protein confirmed the mitochondrial location of human Lon protease. The primary product of transcription and translation directed by a human LON cDNA in vitro had an apparent mass of similar to 107 kDa, and incubation of the translation product with isolated rat liver mitochondria converted the precursor into the similar to 100-kDa mature form. The latter pelleted with mitochondria and was resistant to trypsin digestion. Maturation of human Lon protease in vitro was dependent on mitochondrial inner membrane potential, as the uncoupling agent 2,4-dinitrophenol (DNP) completely blocked this process. In intact cultured cells treated with DNP, newly synthesized Lon protease also accumulated as the precursor form, and subsequent removal of DNP allowed the precursor to be translocated into mitochondria and cleaved to its mature form. A pulse-chase experiment in the absence of DNP showed that the Lon protease precursor is converted to the mature form with a half-time of <2 min and that the mature human Lon protease is indefinitely stable in intact cells. Submitochondrial fractionation and immunoblot analysis of rat liver mitochondrial proteins using the polyclonal antihuman Lon protease antiserum indicated that the protease is located exclusively in the matrix. These data demonstrate that the maturation of human Lon protease is characterized by steps similar to those reported for other mitochondrial matrix proteins. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. NR 41 TC 41 Z9 43 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 18 PY 1994 VL 269 IS 46 BP 29308 EP 29313 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU168 UT WOS:A1994PU16800114 PM 7961901 ER PT J AU DENEKAMP, C MANDELBAUM, A WEISZ, A ITO, Y AF DENEKAMP, C MANDELBAUM, A WEISZ, A ITO, Y TI PREPARATIVE SEPARATION OF STEREOISOMERIC 1-METHYL-4-METHOXYMETHYLCYCLOHEXANECARBOXYLIC ACIDS BY PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article ID ALKYLATION; BEHAVIOR AB The application of pH-zone-refining counter-current chromatography (CCC) to the preparative separation of stereoisomeric acids is described. The separation was accomplished on the basis of the difference in acidity of the two stereoisomers. pH-Zone-refining CCC of 400 mg of a crude synthetic mixture of stereoisomeric 1-methyl-4-methoxymethylcyclohexanecarboxylic acids yielded 49.5 and 40 mg of the pure Z- and E-stereoisomers, respectively. The two-phase solvent system consisted of hexane-ethyl acetate-methanol-water (1:1:1:1). Trifluoroacetic and octanoic acids were used as retainer acids. The eluent base was aqueous ammonia. The eluted fractions were monitored by gas chromatography-mass spectrometry. C1 TECHNION ISRAEL INST TECHNOL,DEPT CHEM,IL-32000 HAIFA,ISRAEL. US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 14 TC 25 Z9 25 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD NOV 18 PY 1994 VL 685 IS 2 BP 253 EP 257 DI 10.1016/0021-9673(94)00669-5 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PX989 UT WOS:A1994PX98900007 PM 7842145 ER PT J AU MA, Y ITO, Y SOKOLOSKY, E FALES, HM AF MA, Y ITO, Y SOKOLOSKY, E FALES, HM TI SEPARATION OF ALKALOIDS BY PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article AB pH-Zone-refining counter-current chromatography was applied to the separation of alkaloids from a crude extract of Crinum moorei using a multilayer coil planet centrifuge. After methyl tert.-butyl ether and water were equilibrated, triethylamine (5-10 mM) was added to the organic phase and hydrochloric acid (5-10 mM) to the aqueous phase. The separation was performed by eluting the column with either the organic phase (displacement mode) or the aqueous phase (reverse-displacement mode) while the other phase was used as the stationary phase. From 3 g of the extract, crinine, powelline and crinamidine were separated in 2.5-7 h with minimum overlapping. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 14 TC 38 Z9 40 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD NOV 18 PY 1994 VL 685 IS 2 BP 259 EP 262 DI 10.1016/0021-9673(94)00667-9 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PX989 UT WOS:A1994PX98900008 PM 7842146 ER PT J AU KIM, WJ BURKE, LP MORTIN, MA AF KIM, WJ BURKE, LP MORTIN, MA TI MOLECULAR MODELING OF RNA-POLYMERASE-II MUTATIONS ONTO DNA-POLYMERASE-I SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DNA POLYMERASE I; DROSOPHILA MELANOGASTER; MOLECULAR MODELING; RNA POLYMERASE II; SUPPRESSOR MUTATIONS ID ESCHERICHIA-COLI; DROSOPHILA-MELANOGASTER; CRYSTAL-STRUCTURE; KLENOW FRAGMENT; 3-DIMENSIONAL STRUCTURE; 2ND-LARGEST SUBUNIT; IDENTIFICATION; RESOLUTION; REGION; LOCUS AB Genetic and molecular analysis in Drosophila melanogaster identifies eight suppressor mutations in the second largest subunit of RNA polymerase II. The suppressor mutations fall into two classes: five are strong, result from the same serine to cysteine amino acid residue substitution and rescue one conditional lethal allele in the largest subunit of RNA polymerase II; three are mild, result from a change in the same methionine residue to either isoleucine or valine, are located seven amino acid residues away from the strong suppressors and rescue two conditional lethal alleles in the largest subunit. Sequence analysis of the three regions around these mutations demonstrates that they are located within highly conserved domains but fails to explain the observed genetic interactions. One of the conditional lethal alleles maps within a region previously reported to share sequence similarity to Escherichia coli DNA polymerase I. As the gross structure of RNA polymerase II and DNA polymerase I is similar, even though their primary sequence is not, we predict that more similarities exist but may be too highly divergent to be detected bg normal homology searches. We identify the most similar regions between each of the three conserved domains of RNA polymerase II, identified as functionally important because of the mutations we isolated, and DNA polymerase I. Molecular modeling these regions of RNA polymerase II onto the tertiary structure of DNA polymerase I predicts that all lie adjacent to the DNA binding cleft in positions such that they could interact with the phosphate backbone of DNA. This juxtaposition of mutations in the two largest subunits of RNA polymerase II suggest a mechanism for their genetic interactions. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. RI Burke, Lillian/A-7334-2008; Mortin, Mark/B-4251-2008 NR 42 TC 9 Z9 9 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 18 PY 1994 VL 244 IS 1 BP 13 EP 22 DI 10.1006/jmbi.1994.1700 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PT480 UT WOS:A1994PT48000003 PM 7966318 ER PT J AU KOONIN, EV TATUSOV, RL AF KOONIN, EV TATUSOV, RL TI COMPUTER-ANALYSIS OF BACTERIAL HALOACID DEHALOGENASES DEFINES A LARGE SUPERFAMILY OF HYDROLASES WITH DIVERSE SPECIFICITY - APPLICATION OF AN ITERATIVE APPROACH TO DATABASE SEARCH SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE CONSERVED SEQUENCE MOTIFS; PROTEIN SUPERFAMILIES; DEHALOGENASES; EPOXIDE HYDROLASES; PHOSPHATASES; ENZYME EVOLUTION ID 2-HALOALKANOIC ACID DEHALOGENASE; XANTHOBACTER-AUTOTROPHICUS GJ10; SP STRAIN CBS3; HALOALKANE DEHALOGENASE; ESCHERICHIA-COLI; PHOSPHOGLYCOLATE PHOSPHATASE; GENE; PURIFICATION; EXPRESSION; SEQUENCES AB Using an iterative approach to sequence database search that combines scanning with individual amino acid sequences and with alignment blocks, we show that bacterial haloacid dehalogenases (HADs) belong to a large superfamily of hydrolases with diverse substrate specificity. The superfamily also includes epoxide hydrolases, different types of phosphatases, and numerous uncharacterized proteins from eubacteria, eukaryotes, and Archaea. Nine putative proteins of the HAD superfamily with functions unknown, in addition to two known enzymes, were found in Escherichia coli alone, making it one of the largest groups of enzymes and indicating that a variety of hydrolytic enzyme activities remain to be described. Many of the proteins with known enzymatic activities in the HAD superfamily are involved in detoxification of xenobiotics or metabolic by-products. All the proteins in the superfamily contain three conserved sequence motifs. Along with the conservation of the predicted secondary structure, motifs I, II, and III include a conserved aspartic acid residue, a lysine, and a nucleophile, namely aspartic acid or serine, respectively. A specific role in the catalysis of the hydrolysis of carbon-halogen and other bonds is assigned to each of these residues. RP KOONIN, EV (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 36 TC 202 Z9 205 U1 1 U2 7 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 18 PY 1994 VL 244 IS 1 BP 125 EP 132 DI 10.1006/jmbi.1994.1711 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PT480 UT WOS:A1994PT48000014 PM 7966317 ER PT J AU PORTIER, CJ LUCIER, GW EDLER, L AF PORTIER, CJ LUCIER, GW EDLER, L TI RISK FROM LOW-DOSE EXPOSURES SO SCIENCE LA English DT Letter C1 GERMAN CANC RES CTR,W-6900 HEIDELBERG,GERMANY. RP PORTIER, CJ (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 0 TC 3 Z9 3 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 18 PY 1994 VL 266 IS 5188 BP 1141 EP 1142 DI 10.1126/science.7973685 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PT132 UT WOS:A1994PT13200003 PM 7973685 ER PT J AU REX, JH BENNETT, JE SUGAR, AM PAPPAS, PG VANDERHORST, CM EDWARDS, JE WASHBURN, RG SCHELD, WM KARCHMER, AW DINE, AP LEVENSTEIN, MJ WEBB, CD AF REX, JH BENNETT, JE SUGAR, AM PAPPAS, PG VANDERHORST, CM EDWARDS, JE WASHBURN, RG SCHELD, WM KARCHMER, AW DINE, AP LEVENSTEIN, MJ WEBB, CD TI A RANDOMIZED TRIAL COMPARING FLUCONAZOLE WITH AMPHOTERICIN-B FOR THE TREATMENT OF CANDIDEMIA IN PATIENTS WITHOUT NEUTROPENIA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FUNGEMIA; MORTALITY; FREQUENCY AB Background. Amphotericin B has long been the standard treatment for candidemia, but its use is complicated by its toxicity. More recently, fluconazole, a water-soluble triazole with activity against candida species and little toxicity, has become available. We conducted a multicenter randomized trial that compared amphotericin B with fluconazole as treatment for candidemia. Methods. To be eligible, patients had to have a positive blood culture for candida species, a neutrophil count greater than or equal to 500 per cubic millimeter, and no major immunodeficiency. Patients were randomly assigned to receive either amphotericin B (0.5 to 0.6 mg per kilogram of body weight per day) or fluconazole (400 mg per day), each continued for at least 14 days after the last positive blood culture. Outcomes were assessed by a group of investigators blinded to treatment assignment. Results. Of the 237 patients enrolled, 206 met all entry criteria. The most common diagnoses were renal failure, nonhematologic cancer, and gastrointestinal disease. There was no statistically significant difference in outcome: of the 103 patients treated with amphotericin B, 81 (79 percent) were judged to have been treated successfully, as were 72 of the 103 patients treated with fluconazole (70 percent; P = 0.22; 95 percent confidence interval for the difference, -5 to 23 percent). The bloodstream infection failed to clear in 12 patients in the amphotericin group and 15 in the fluconazole group; the species most commonly associated with failure was Candida albicans. There were 41 deaths in the amphotericin group and 34 deaths in the fluconazole group (P = 0.20). Intravascular catheters appeared to be the most frequent source of candidemia. There was less toxicity with fluconazole than with amphotericin B. Conclusions. In patients without neutropenia and without major immunodeficiency, fluconazole and amphotericin B are not significantly different in their effectiveness in treating candidemia.- C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. BOSTON UNIV HOSP,MED CTR,BOSTON,MA 02118. UNIV ALABAMA,BIRMINGHAM,AL. UNIV N CAROLINA,CHAPEL HILL,NC. UCLA,HARBOR MED CTR,TORRANCE,CA. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV VIRGINIA,CHARLOTTESVILLE,VA. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. ROERIG PFIZER,NEW YORK,NY. RP REX, JH (reprint author), UNIV TEXAS,SCH MED,6431 FANNIN 1728 JFB,HOUSTON,TX 77030, USA. FU NIAID NIH HHS [N01-AI-15082] NR 13 TC 712 Z9 731 U1 3 U2 11 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 17 PY 1994 VL 331 IS 20 BP 1325 EP 1330 DI 10.1056/NEJM199411173312001 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PR216 UT WOS:A1994PR21600001 PM 7935701 ER PT J AU ANTHONISEN, NR CONNETT, JE KILEY, JP ALTOSE, MD BAILEY, WC BUIST, AS CONWAY, WA ENRIGHT, PL KANNER, RE OHARA, P OWENS, GR SCANLON, PD TASHKIN, DP WISE, RA AF ANTHONISEN, NR CONNETT, JE KILEY, JP ALTOSE, MD BAILEY, WC BUIST, AS CONWAY, WA ENRIGHT, PL KANNER, RE OHARA, P OWENS, GR SCANLON, PD TASHKIN, DP WISE, RA TI EFFECTS OF SMOKING INTERVENTION AND THE USE OF AN INHALED ANTICHOLINERGIC BRONCHODILATOR ON THE RATE OF DECLINE OF FEV(1) - THE LUNG HEALTH STUDY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; FORCED EXPIRATORY VOLUME; CHRONIC-BRONCHITIS; CLINICAL-TRIAL; ONE 2ND; CANCER; RISK; PARTICIPANTS; DESIGN; MODELS AB Objective.-To determine whether a program incorporating smoking intervention and use of an inhaled bronchodilator can slow the rate of decline in forced expiratory volume in 1 second (FEV(1)) in smokers aged 35 to 60 years who have mild obstructive pulmonary disease. Design.-Randomized clinical trial. Participants randomized with equal probability to one of the following groups: (1) smoking intervention plus bronchodilator, (2) smoking intervention plus placebo, or (3) no intervention. Setting.-Ten clinical centers in the United States and Canada. Participants.-A total of 5887 male and female smokers, aged 35 to 60 years, with spirometric signs of early chronic obstructive pulmonary disease. Interventions.-Smoking intervention: intensive 12-session smoking cessation program combining behavior modification and use of nicotine gum, with continuing 5-year maintenance program to minimize relapse. Bronchodilator: ipratropium bromide prescribed three times daily (two puffs per time) from a metered-dose inhaler. Main Outcome Measures.-Rate of change and cumulative change in FEV(1) over a 5-year period. Results.-Participants in the two smoking intervention groups showed significantly smaller declines in FEV(1) than did those in the control group. Most of this difference occurred during the first year following entry into the study and was attributable to smoking cessation, with those who achieved sustained smoking cessation experiencing the largest benefit. The small noncumulative benefit associated with use of the active bronchodilator vanished after the bronchodilator was discontinued at the end of the study. Conclusions.-An aggressive smoking intervention program significantly reduces the age-related decline in FEV(1) in middle-aged smokers with mild airways obstruction. Use of an inhaled anticholinergic bronchodilator results in a relatively small improvement in FEV(1) that appears to be reversed after the drug is discontinued. Use of the bronchodilator did not influence the long-term decline of FEV(1). C1 UNIV MANITOBA,WINNIPEG,MB,CANADA. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NHLBI,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. UNIV ALABAMA,BIRMINGHAM,AL. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. HENRY FORD HOSP,DETROIT,MI 48202. UNIV ARIZONA,TUCSON,AZ. UNIV UTAH,SALT LAKE CITY,UT. UNIV MIAMI,MIAMI,FL 33152. UNIV PITTSBURGH,PITTSBURGH,PA. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. JOHNS HOPKINS UNIV,BALTIMORE,MD. FU NCRR NIH HHS [MO1-RR00064]; NHLBI NIH HHS [N01-HR-46002] NR 40 TC 1062 Z9 1090 U1 1 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 16 PY 1994 VL 272 IS 19 BP 1497 EP 1505 DI 10.1001/jama.272.19.1497 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA PQ900 UT WOS:A1994PQ90000028 PM 7966841 ER PT J AU ZHOU, HX AF ZHOU, HX TI EFFECTS OF MUTATIONS AND COMPLEX-FORMATION ON THE REDUCTION POTENTIALS OF CYTOCHROME-C AND CYTOCHROME-C PEROXIDASE SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; INTRAMOLECULAR ELECTRON-TRANSFER; YEAST ISO-1-CYTOCHROME-C; REDOX POTENTIALS; RHODOPSEUDOMONAS-VIRIDIS; CONFORMATIONAL-CHANGES; MOLECULAR-DYNAMICS; FERROCYTOCHROME-C; HYDROGEN-PEROXIDE; OXIDATION STATE AB A continuum model is used to calculate the effects of point mutations and complex formation on the reduction potentials of yeast iso-1-cytochrome c (cc) and yeast cytochrome c peroxidase (CCP). In this model a protein is represented by a low dielectric region embedded in the high dielectric solvent. Qualitative analysis shows that the model can account for a wide range of factors that determine the reduction potential. These include the charge and polarity of a surface residue, the polarity of an interior residue, and the size of a residue which controls the exposure of the heme to the solvent. The continuum model allows for a reasonably good reproduction of a demanding set of data on cc, consisting of the measured differences in reduction potential between the wild type and seven mutants (Arg38 --> Lys, His, Asn, and Ala, Tyr48 --> Phe, Asn52 --> Ile, and Phe82 --> Ser). In the case of CCP, continuum-model calculations on the effects of mutating Asp235 lead to the following conclusions: (1) The imidazolate character of wild-type His175, shown by resonance Raman spectroscopy and NMR, is critical in lowering the reduction potential of the wild type 70 mV from that of the Glu235 mutant, which has the same charge as the wild type. (2) A sixth ligand, such as a water molecule, is necessary for maintaining the reduction potential of the Ala235 mutant at a level that is only 35 mV above the reduction potential of the Glu235 mutant, which has an extra buried carboxylate. (3) That the Asn235 and Ala235 mutants have almost equal reduction potentials is due to the fact that the amide dipole of the Asn235 residue is oriented such that it does not stabilize or destabilize the charge on the heme. In contrast to previous expectations, complex formation is found to have only a small effect on the reduction potential of cc and no effect at all on that of CCP. The protein matrices are found to play an important role of reducing the outer reorganization energy from what would have been if the redox centers were embedded directly in the solvent and thus speeding up the electron transfer. By relating electron transfer to redox reactions, a method for obtaining the inner reorganization energy is proposed. RP ZHOU, HX (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Zhou, Huan-Xiang/M-5170-2016 OI Zhou, Huan-Xiang/0000-0001-9020-0302 NR 54 TC 58 Z9 58 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 16 PY 1994 VL 116 IS 23 BP 10362 EP 10375 DI 10.1021/ja00102a002 PG 14 WC Chemistry, Multidisciplinary SC Chemistry GA PT130 UT WOS:A1994PT13000002 ER PT J AU YAMAZAKI, T NICHOLSON, LK TORCHIA, DA WINGFIELD, P STAHL, SJ KAUFMAN, JD EYERMANN, CJ HODGE, CN LAM, PYS RU, Y JADHAV, PK CHANG, CH WEBER, PC AF YAMAZAKI, T NICHOLSON, LK TORCHIA, DA WINGFIELD, P STAHL, SJ KAUFMAN, JD EYERMANN, CJ HODGE, CN LAM, PYS RU, Y JADHAV, PK CHANG, CH WEBER, PC TI NMR AND X-RAY EVIDENCE THAT THE HIV PROTEASE CATALYTIC ASPARTYL GROUPS ARE PROTONATED IN THE COMPLEX FORMED BY THE PROTEASE AND A NONPEPTIDE CYCLIC UREA-BASED INHIBITOR SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID PROTEINS; C-13; ASSIGNMENT; RESIDUES; SPECTRA C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NIH,PROT EXPRESS LAB,BETHESDA,MD 20892. DUPONT MERCK PHARMACEUT CO,DEPT CHEM & PHYS SCI,WILMINGTON,DE 19880. NR 19 TC 117 Z9 117 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 16 PY 1994 VL 116 IS 23 BP 10791 EP 10792 DI 10.1021/ja00102a057 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA PT130 UT WOS:A1994PT13000057 ER PT J AU OLDEN, K AF OLDEN, K TI MUTAGEN HYPERSENSITIVITY AS A BIOMARKER OF GENETIC PREDISPOSITION TO CARCINOGENESIS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 NIH,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP OLDEN, K (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 3 TC 12 Z9 12 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 16 PY 1994 VL 86 IS 22 BP 1660 EP 1661 DI 10.1093/jnci/86.22.1660 PG 2 WC Oncology SC Oncology GA PQ347 UT WOS:A1994PQ34700001 PM 7966386 ER PT J AU CHRISTIAN, MC KORN, EL AF CHRISTIAN, MC KORN, EL TI THE LIMITED PRECISION OF PHASE-I TRIALS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CLINICAL-TRIALS; DESIGN C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BIOMETR RES BRANCH,BETHESDA,MD 20892. RP CHRISTIAN, MC (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVESTIGAT DRUG BRANCH,EPN 715,BETHESDA,MD 20892, USA. NR 9 TC 14 Z9 14 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 16 PY 1994 VL 86 IS 22 BP 1662 EP 1663 DI 10.1093/jnci/86.22.1662 PG 2 WC Oncology SC Oncology GA PQ347 UT WOS:A1994PQ34700002 PM 7966387 ER PT J AU ABRAMS, J CHEN, T GIUSTI, R AF ABRAMS, J CHEN, T GIUSTI, R TI SPECIAL COMMUNICATION FROM THE NATIONAL-CANCER-INSTITUTE - SURVIVAL AFTER BREAST-SPARING SURGERY VERSUS MASTECTOMY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material RP ABRAMS, J (reprint author), NCI,DIV CANC TREATMENT,BETHESDA,MD 20892, USA. NR 5 TC 12 Z9 12 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 16 PY 1994 VL 86 IS 22 BP 1672 EP 1673 DI 10.1093/jnci/86.22.1672 PG 2 WC Oncology SC Oncology GA PQ347 UT WOS:A1994PQ34700008 PM 7966392 ER PT J AU NOVAKOVIC, B GOLDSTEIN, AM WEXLER, LH TUCKER, MA AF NOVAKOVIC, B GOLDSTEIN, AM WEXLER, LH TUCKER, MA TI INCREASED RISK OF NEUROECTODERMAL TUMORS AND STOMACH-CANCER IN RELATIVES OF PATIENTS WITH EWINGS-SARCOMA FAMILY OF TUMORS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID 2ND MALIGNANT NEOPLASMS; SOFT-TISSUE SARCOMA; LINE P53 MUTATIONS; GERMLINE MUTATIONS; BONE SARCOMAS; CHILDREN; GENE AB Background: Previous studies of the genetic epidemiology of Ewing's sarcoma have shown neither an increased incidence nor a distinct pattern of cancers in family members of Ewing's sarcoma patients. Purpose: Because of a new biologic and cytogenetic classification of Ewing's sarcoma family of tumors, we wanted to reinvestigate the incidence and distribution of cancers in relatives of probands with Ewing's sarcoma family of tumors. Methods: Patients treated at the Pediatric Branch and the Radiation Oncology Branch of the National Cancer Institute between 1965 and December 1992, or their next of kin, were asked to complete a questionnaire on the history of canter in all first- and second-degree relatives. The incidence of canter in family members was compared with Connecticut Tumor Registry rates specific for sex, age, and 5-year calendar-year intervals. Observed/expected (O/E) ratios, 95% confidence intervals (CIs), and tests of homogeneity were calculated. Results: Four thousand six hundred seventy-eight family members with 196 640 person-years at risk entered the analysis. Overall, there was no increased risk of cancer (observed 472; O/E = 0.9; 95% CI = 0.8-1.0). However, several tumor types were found in significant excess. These tumors included stomach cancer (observed 34; O/E = 2.0; 95% CI = 1.4-2.8), melanoma (observed 23; O/E = 1.9; 95% CI = 1.2-2.8), brain tumor (observed 18; O/E = 1.9; 95% CI = 1.1-3.0), and bone cancer (observed 7; O/E = 4.2; 95% CI = 1.7-8.6). Risks of these cancers were higher among maternal than paternal relatives, but these differences were not statistically significant. There was a significant deficit of bladder cancer (observed 5; O/E = 0.2; 95% CI = 0.1-0.5) and rectal cancer (observed 0; O/E = 0.0; 95% CI = 0.0-0.1). Second-degree relatives had a significant cancer deficit (observed 389; O/E = 0.9; 95% CI = 0.8-0.95). This deficit was accounted for by the observed deficit of bladder and rectal cancer and is probably related to under-reporting or misclassification of cancer in second-degree relatives. Family members of 10 probands with second malignancies did not have an increased risk of all cancers (observed 20; O/E = 1.2; 95% CI = 0.7-1.8) but had an increased risk of both melanoma (observed 3; O/E = 7.3; 95% CI = 1.5-21.0) and breast cancer (observed 8; O/E = 3.2; 95% CI = 1.4-6.3). Conclusion: Finding an increased risk of neuroectodermal tumors and stomach cancer in families of patients with Ewing's sarcoma family of tumors suggests that these tumors might share a common etiology. Further studies should try to confirm this hypothesis and to examine if genetic factors may have a role in these families by assessing the mode of inheritance and examining families with multiple affected members. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RP NOVAKOVIC, B (reprint author), NCI,EPN,GENET EPIDEMIOL BRANCH,RM 400,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 22 TC 16 Z9 16 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 16 PY 1994 VL 86 IS 22 BP 1702 EP 1706 DI 10.1093/jnci/86.22.1702 PG 5 WC Oncology SC Oncology GA PQ347 UT WOS:A1994PQ34700014 PM 7966398 ER PT J AU RABKIN, CS YELLIN, F AF RABKIN, CS YELLIN, F TI CANCER INCIDENCE IN A POPULATION WITH A HIGH PREVALENCE OF INFECTION WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NON-HODGKINS-LYMPHOMA; EPSTEIN-BARR-VIRUS; HUMAN PAPILLOMAVIRUS INFECTION; KAPOSIS-SARCOMA; SYNDROME AIDS; HIV-INFECTION; SAN-FRANCISCO; HOMOSEXUAL MEN; HIGH-RISK; DISEASE AB Background: Human immunodeficiency virus type 1 (HIV-1) infection is known to increase the incidence of Kaposi's sarcoma and non-Hodgkin's lymphoma. Parallels with other causes of immunodeficiency suggest a possible effect of HIV-1 on additional cancers. Purpose: This study was designed to determine the types and rates of cancers occurring in excess in the presence of HIV-1 infection. Methods: We examined cancer incidence in a population-based open cohort with a high prevalence of HIV-1 infection. The study population was never-married men aged 25-54 years who resided in San Francisco, Calif., of whom an estimated 20 000 (24%) were HIV-1 seropositive as of late 1984. Cancer registration data covering 1 390 000 person-years of observation of these men from 1973 through 1990 were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. Standardized incidence rates and ratios of observed to expected cases (based on rates in the pre-acquired immunodeficiency syndrome [pre-AIDS] period [i.e., 1973-1979]) were calculated for cancers classified by site and by cell type. Results: The incidence of Kaposi's sarcoma in never-married men plateaued in 1988-1990 at 0.5% per year. The incidence of non-Hodgkin's lymphoma increased 20-fold between 1973-1979 and 1988-1990; increases were most pronounced in tumors of higher grade histology and extranodal (especially central nervous system) primary sites. The incidence of Burkitt's and Burkitt-like tumors peaked in 1985-1987, whereas that of large cell diffuse and immunoblastic lymphomas increased throughout the study period. The incidence of Hodgkin's disease was 2.0 (95% confidence interval [CI] = 1.3-3.0) times expected in 1988-1990. The incidence of anal cancer was 9.9 (95% CI = 4.5-18.7) times expected in 1973-1979 and 10.1 (95% CI = 5.0-18.0) times expected in 1988-1990. Ratios of observed to expected cancers of most other sites were 2.0 or less; the ratio of leiomyosarcomas (at any site) was 2.5 (95% CI = 0.5-7.4). Conclusions: As the HIV-1 epidemic has progressed, the increases in AIDS-related Kaposi's sarcoma, Burkitt's tumor, and other non-Hodgkin's lymphoma have followed different patterns. The effect of HIV-1 on other cancers has been nondetectable. In particular, HIV-1 is not related to the increased risk of anal cancer in homosexual men, which antedated the AIDS epidemic. Implications: These data suggest that the etiologic mechanisms of HIV-1-related malignancy differ for specific cancers and do not globally increase cancer risk. Control of HIV-1-related cancer remains an unsolved challenge in the management of HIV-1 infection. C1 ATLANTIC RES CORP,ROCKVILLE,MD. RP RABKIN, CS (reprint author), NCI,DIV CANC ETIOL,VIRAL EPIDEMIOL BRANCH,EPN-434,BETHESDA,MD 20892, USA. NR 48 TC 116 Z9 117 U1 1 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 16 PY 1994 VL 86 IS 22 BP 1711 EP 1716 DI 10.1093/jnci/86.22.1711 PG 6 WC Oncology SC Oncology GA PQ347 UT WOS:A1994PQ34700016 PM 7966400 ER PT J AU DOSEMECI, M HOOVER, RN BLAIR, A FIGGS, LW DEVESA, S GRAUMAN, D FRAUMENI, JF AF DOSEMECI, M HOOVER, RN BLAIR, A FIGGS, LW DEVESA, S GRAUMAN, D FRAUMENI, JF TI FARMING AND PROSTATE-CANCER AMONG AFRICAN-AMERICANS IN THE SOUTHEASTERN UNITED-STATES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID NEW-ZEALAND; FARMERS; OCCUPATION; MORTALITY; DEATH; RISKS; PATTERNS; INDUSTRY RP DOSEMECI, M (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EPN,RM 418,BETHESDA,MD 20892, USA. NR 29 TC 27 Z9 27 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 16 PY 1994 VL 86 IS 22 BP 1718 EP 1719 DI 10.1093/jnci/86.22.1718 PG 2 WC Oncology SC Oncology GA PQ347 UT WOS:A1994PQ34700017 PM 7966401 ER PT J AU KAISERKUPFER, MI CHAN, CC MARKELLO, TC CRAWFORD, MA CARUSO, RC CSAKY, KG GUO, JR GAHL, WA AF KAISERKUPFER, MI CHAN, CC MARKELLO, TC CRAWFORD, MA CARUSO, RC CSAKY, KG GUO, JR GAHL, WA TI CLINICAL BIOCHEMICAL AND PATHOLOGICAL CORRELATIONS IN BIETTIS CRYSTALLINE DYSTROPHY SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MARGINAL CORNEAL-DYSTROPHY; TAPETORETINAL DEGENERATION; RETINOPATHY; DISEASE AB We examined three affected members of a Chinese-American family with Bietti's crystalline retinopathy. The clinical characteristics of a 24-year-old proband are contrasted to the clinical findings of her grandmother, for whom we have 26 years of follow-up data. Lymphocytes and fibroblasts from a skin biopsy of the grandmother contained crystalline lysosomal material, which supports the diagnosis, Biochemical studies of the crystalline lysosomal material failed to identify the stored compounds but did not show them to be cholesterol or cholesterol ester. Finally, histopathologic studies performed for this condition demonstrated advanced panchorioretinal atrophy, with crystals and complex lipid inclusions seen in choroidal fibroblasts. C1 NICHHD,BETHESDA,MD 20892. RP KAISERKUPFER, MI (reprint author), NEI,10 CTR DR,BLDG 10,RM 10N226,BETHESDA,MD 20892, USA. NR 37 TC 64 Z9 69 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV 15 PY 1994 VL 118 IS 5 BP 569 EP 582 PG 14 WC Ophthalmology SC Ophthalmology GA PQ077 UT WOS:A1994PQ07700002 PM 7977570 ER PT J AU RADKO, SP GARNER, MM CAIAFA, G CHRAMBACH, A AF RADKO, SP GARNER, MM CAIAFA, G CHRAMBACH, A TI MOLECULAR-SIEVING OF POLYSTYRENE CARBOXYLATE OF A DIAMETER UP TO 10-MU-M IN SOLUTIONS OF UNCROSSLINKED POLYACRYLAMIDE OF M(R)-5X10(6) USING CAPILLARY ZONE ELECTROPHORESIS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID DNA; PARTICLES; AGAROSE AB Capillary zone electrophoresis of polystyrene carboxylate (PSC) up to 10 mu m in diameter in 0.1 to 0.9% solutions of uncrosslinked polyacrylamide (PA) of M(r) 5 X 10(6) demonstrates effective molecular sieving in that medium. The reduced mobility, however, is not constant in Tris-borate-EDTA (1 X TBE) buffer containing the polymer but increases in proportion to the load of PSC and inversely to the concentration of PA unless the TBE concentration is increased 10-fold or 50 mM 3-[(3-cholamidopropyl) dimethylammonio]propanesulfonic acid is added to the solution or in the absence of PA. Both the Ferguson plots [log(mobility) vs PA concentration] of PSC obtained at various PSC loads and the effects of the dissociating conditions, high ionic strength and detergent, signify that the variable mobilities are those of different PSC aggregation states. Thus, only the fully associated or dissociated states of PSC provide mobilities that are constant independently of PSC load. The study shows that the information inherent in Ferguson plots regarding particle and fiber properties can be exploited for particles up to 10 mu m in diameter by capillary zone electrophoresis in polymer solutions even if these particles form various aggregation states. Thus, such an analysis appears feasible in application to biologically relevant and functional complexes such as subcellular-sized particles or DNA-protein complexes, providing that these particles maintain their integrity and functionality under the selected electrophoretic conditions. (C) 1994 Academic Press, Inc. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892. NR 9 TC 26 Z9 27 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 NOV 15 PY 1994 VL 223 IS 1 BP 82 EP 87 DI 10.1006/abio.1994.1550 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PR654 UT WOS:A1994PR65400014 PM 7695106 ER PT J AU KIM, HY WANG, TCL MA, YC AF KIM, HY WANG, TCL MA, YC TI LIQUID-CHROMATOGRAPHY MASS-SPECTROMETRY OF PHOSPHOLIPIDS USING ELECTROSPRAY-IONIZATION SO ANALYTICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; BIOMOLECULES; SEPARATION; LIPIDS AB An improved technique for phospholipid molecular species analysis was developed using high-performance liquid chromatography/mass spectrometry with the electrospray interface. Using the 0.5% ammonium hydroxide in a water-methanol-hexane mixture and a C-18 column, complex mixtures of phospholipid molecular species were separated and detected mainly as protonated or natriated molecular species. The response was linear over 2 orders of magnitude, allowing quantification of each molecular species. In comparison to the existing LC/MS techniques, marked improvement in sensitivity was observed. The present quantification limit is approximately 0.5 pmol before split (5 fmol after 1/100 split). The relative responses were more dependent on the head group identity rather than fatty acyl composition within a phospholipid class. In general, phosphatidylcholine (PC) species are most sensitively detected followed by phosphatidylethanolamine (PE) species. The sensitivity of phosphatidylserine (PS) in the positive ion mode is approximately 20 times less in comparison to PC under our condition. C1 NIMH,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. RP KIM, HY (reprint author), NIAAA,MASS SPECTROMETRY SECT,MEMBRANE BIOCHEM & BIOPHYS LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 194 Z9 197 U1 1 U2 32 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 15 PY 1994 VL 66 IS 22 BP 3977 EP 3982 DI 10.1021/ac00094a020 PG 6 WC Chemistry, Analytical SC Chemistry GA PQ977 UT WOS:A1994PQ97700020 PM 7810900 ER PT J AU SACK, MN HOEG, JM AF SACK, MN HOEG, JM TI RESTRICTION ISOTYPING OF APOPROTEIN-E SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NHLBI,BETHESDA,MD 20892. RP SACK, MN (reprint author), GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007, USA. NR 2 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 NOV 15 PY 1994 VL 121 IS 10 BP 816 EP 816 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PQ928 UT WOS:A1994PQ92800017 PM 7944063 ER PT J AU WELSH, CJ ROBINSON, M WARNE, TR PIERCE, JH YEH, GC PHANG, JM AF WELSH, CJ ROBINSON, M WARNE, TR PIERCE, JH YEH, GC PHANG, JM TI ACCUMULATION OF FATTY ALCOHOL IN MCF-7 BREAST-CANCER CELLS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID MAMMARY EPITHELIAL-CELLS; SIGNAL TRANSDUCTION; PHOSPHOLIPASE-C; DIETARY-FAT; ACID; DIACYLGLYCEROL; CHROMATOGRAPHY; TUMORIGENESIS; HYDROLYSIS; ASSAYS AB The MCF-7 cell line (human breast epithelial cells) accumulates fatty alcohols. The fatty alcohols were identified as C16:0, C18:0, and C18:1 alcohols by thin-layer chromatography and gas chromatography/mass spectrometry. This accumulation of alcohols in MCF-7 was found in cultures of MCF-7 cells obtained from other laboratories but not in a variety of unrelated cell lines. The presence of the alcohols suggested an aberrant ether lipid metabolism in the MCF-7 cells. Therefore, the capacity for ether lipid biosynthesis was evaluated using cells incubated with either [C-14]stearyl alcohol or [C-14]stearic acid. MCF-7 cells incorporated less than 0.4% of the [C-14]alcohol into ether-linked phospholipids, whereas the AB589 breast epithelial cells, used as a ''normal control'' for comparisons, did not accumulate fatty alcohol and incorporated approximately 20% of the radiolabeled alcohol into phospholipids containing ether linkages. Although the MCF-7 cells were unable to effectively incorporate the fatty alcohol into ether linkages, the cells were able to oxidize the alcohol to fatty acid. When incubated with [C-14]stearic acid, the conversion to radiolabeled fatty alcohol in MCF-7 cells was approximately four times higher than the alcohol levels found in AB589 cells. While deficient in the ability to synthesize ether linkages, the MCF-7 cells did incorporate radiolabeled hexadecylglycerol, a precursor containing an ether linkage, into phospholipids. Collectively, the data indicate that the MCF-7 cells possess a deficiency in the alkyl DHAP synthase activity. A near absence of ether-linked lipids in the MCF-7 cells was indicated by the radiolabeling studies, and this finding was corroborated by results from HPLC analysis. Analyses of the partial glycerides, obtained from the enzymatic hydrolysis of cellular phospholipids, found only trace levels of ether lipids in the MCF-7 cells. The aberration in ether lipid biosynthesis did not correlate with the expression of the multidrug resistance phenotype in a series multidrug resistant MCF-7 variants. The results are discussed relative to the use of the MCF-7 cells as a model for investigations of ether lipid biosynthesis and the cellular physiology of ether lipids. (C) 1994 Academic Press, Inc. C1 NCI,NUTR & MOLEC REGULAT LAB,FREDERICK,MD 21701. E TENNESSEE STATE UNIV,JAMES H QUILLEN COLL MED,DEPT BIOCHEM,JOHNSON CITY,TN 37614. NCI,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK38660] NR 47 TC 14 Z9 14 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 15 PY 1994 VL 315 IS 1 BP 41 EP 47 DI 10.1006/abbi.1994.1468 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PQ997 UT WOS:A1994PQ99700006 PM 7979403 ER PT J AU MORALES, TI AF MORALES, TI TI TRANSFORMING GROWTH-FACTOR-BETA AND INSULIN-LIKE GROWTH-FACTOR-I RESTORE PROTEOGLYCAN METABOLISM OF BOVINE ARTICULAR-CARTILAGE AFTER DEPLETION BY RETINOIC ACID SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID ORGAN-CULTURES; EXPLANT CULTURES; STEADY-STATE; BIOSYNTHESIS; CHONDROCYTES; PROTEIN; ASSAY AB Previous studies showed that retinoic acid is a powerful resorbing agent for articular cartilage at physiological doses (10(-8) to 10(-10) M); the possible role of individual cytokines in the reversal of this effect is now explored in bovine articular cartilage organ cultures. Seven days of treatment with the retinoid under serum-free conditions, at 1 X 10(-8) M, led to a suppression of proteoglycan synthesis of 90 +/- 5% (n = 6; n = cultures from different animals; mean +/- SD) and to a net loss of 64 +/- 14% (n = 6). Removal of the retinoid from the feeding medium did not significantly increase proteoglycan synthesis nor diminish the further loss of proteoglycans. Thus, transforming growth factor-beta (TGF-beta) and insulin-like growth factor-1 (IGF-1), cytokines which independently maintain proteoglycan homeostasis (Morales and Roberts, 1988, J. Biol. Chem. 263, 828; and Luyten et al., 1988, Arch. Biochem. Biophys. 267, 416), were tested. TGF-beta (10 ng/ml) or IGE-1 (10 ng/ml) added for 7 days to serum-free medium following retinoic acid treatment led to recoveries of proteoglycan synthesis of 74 +/- 24% (n = 12) and 69 +/- 18% (n = 12), respectively, as compared to controls switched from serum-free conditions to corresponding cytokine treatments. TGF-beta + IGF-1 restored activity to 95 +/- 17% (n = 12) of controls. TGF-beta s 1-3 exhibited identical responses in control and experimental cultures. IGF-2 replaced IGF-1, but a fourfold higher concentration was required; insulin also had IGF-1-like effects, but even at 500 ng/ml it was 25% less effective than IGF-1. In contrast to the cultures switched from retinoic acid treatment to serum-free conditions, the cultures switched to IGF-1, TGF-beta, or IGF-1 + TGF-beta were stabilized from further proteoglycan loss by the treatment; after 1 week, tissue levels were 97 +/- 19, 96 +/- 22, and 114 +/- 15% (n = 6), respectively, compared to the content before switching. Measurements of catabolism were in agreement with these observations. It is proposed that retinoic acid, TGF-beta, and IGF-1 are parts of an endogenous system involved in the reversible modulation of proteoglycan homeostasis in articular cartilage. While the cytokines are able to reestablish the balance of the metabolic pathways to prevent further loss of proteoglycans, the finding that they did not replenish lost material during the 1-week recovery suggests that other factors, such as mechanical forces and/or other cytokines may be contribute to a more effective repair. (C) 1994 Academic Press, Inc. RP MORALES, TI (reprint author), NIDR,BONE RES BRANCH,BETHESDA,MD 20892, USA. NR 22 TC 49 Z9 49 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 15 PY 1994 VL 315 IS 1 BP 190 EP 198 DI 10.1006/abbi.1994.1489 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PQ997 UT WOS:A1994PQ99700027 PM 7979398 ER PT J AU KOMATSU, K DRISCOLL, WJ KOH, YC STROTT, CA AF KOMATSU, K DRISCOLL, WJ KOH, YC STROTT, CA TI A P-LOOP RELATED MOTIF (GXXGXXK) HIGHLY CONSERVED IN SULFOTRANSFERASES IS REQUIRED FOR BINDING THE ACTIVATED SULFATE DONOR SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID LIVER DEHYDROEPIANDROSTERONE SULFOTRANSFERASE; MOLECULAR-CLONING; RAT-LIVER; ESTROGEN SULFOTRANSFERASE; SEQUENCE-ANALYSIS; HYDROXYSTEROID SULFOTRANSFERASE; ARYL SULFOTRANSFERASE; MOUSE-LIVER; CDNA; EXPRESSION AB A nucleotide binding motif termed the P-loop has been described for ATP- and GTP-binding proteins. The primary structure typically consists of a glycine-rich region followed by a conserved lysine. A related structure (GxxGxxK) noted in sulfotransferases has been suggested to be important for the binding of the cofactor 3'-phosphoadenosine-5'-phosphosulfate (PAPS), the universal sulfate donor for this class of enzymes. Using molecular techniques, point mutations that substituted alanines for the putative critical residues were introduced into the cDNA for estrogen sulfotransferase. The altered construct, although fully expressed by Chinese hamster ovary-K1 cells, demonstrated negligible enzymatic activity and failed to photoaffinity label with [S-35]PAPS. In contrast, a construct in which three other amino acids in the region of the P-loop motif were similarly mutated retained activity and was photoaffinity labeled with [S-35]PAPS. These data strongly support the notion that the P-loop motif found in all cloned sulfotransferases constitutes, at least in part, the PAPS binding site for these enzymes. (C) 1994 Academic Press, Inc. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,STEROID REGULAT SECT,BETHESDA,MD 20892. NR 27 TC 55 Z9 56 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 15 PY 1994 VL 204 IS 3 BP 1178 EP 1185 DI 10.1006/bbrc.1994.2587 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PR980 UT WOS:A1994PR98000026 PM 7980593 ER PT J AU DYER, KD LAVIGNE, MC ROSENBERG, HF AF DYER, KD LAVIGNE, MC ROSENBERG, HF TI HSP70RY - FURTHER CHARACTERIZATION OF A NOVEL MEMBER OF THE HSP70 PROTEIN FAMILY (VOL 203, PG 577, 1994) SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Correction, Addition C1 GEORGETOWN UNIV,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20057. RP DYER, KD (reprint author), NIAID,HOST DEF LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 15 PY 1994 VL 204 IS 3 BP 1383 EP 1383 DI 10.1006/bbrc.1994.2617 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PR980 UT WOS:A1994PR98000056 ER PT J AU MARTIN, BM RAMIREZ, AN GURROLA, GB NOBILE, M PRESTIPINO, G POSSANI, LD AF MARTIN, BM RAMIREZ, AN GURROLA, GB NOBILE, M PRESTIPINO, G POSSANI, LD TI NOVEL K+-CHANNEL-BLOCKING TOXINS FROM THE VENOM OF THE SCORPION CENTRUROIDES LIMPIDUS LIMPIDUS KARSCH SO BIOCHEMICAL JOURNAL LA English DT Article ID ANDROCTONUS-MAURETANICUS-MAURETANICUS; DEPENDENT POTASSIUM CHANNELS; NUCLEAR-MAGNETIC-RESONANCE; LEIUROTOXIN-I SCYLLATOXIN; SYNTHETIC PEPTIDES; NOXIUS HOFFMANN; LYMPHOCYTES-T; BINDING-SITES; CHARYBDOTOXIN; PURIFICATION AB Two novel toxins were purified from the venom of the Mexican scorpion Centruroides limpidus limpidus, using an immunoassay based on antibodies raised against noxiustoxin (NTX), a known K+-channel-blocker-peptide. The primary structure of C. l. limpidus toxin 1 was obtained by Edman degradation and was shown to be composed of 38 amino acid residues, containing six half-cystines. The first 36 residues of C. l. limpidus toxin 2 were also determined. Both toxins are capable of displacing the binding of radio-labelled NTX to rat brain synaptosomes with high affinity (about 100 pM). These toxins are capable of inhibiting transient K+-currents (resembling I-A-type currents), in cultured rat cerebellar granule cells. About 50% of the peak currents are reduced by application of a 1.5 mu M solution of toxins 1 and 2. The Kf current reduction is partially reversible, under washing, but not voltage-dependent. Comparison of the primary structure of C. l. limpidus toxin 1 with other known toxins shows 74% identity with margatoxin, 64% with NTX, 51% with kaliotoxin, 39% with iberiotoxin, 37% with charybdotoxin and Lq2, and 29% with leirutoxin 1. The only invariant amino acids in all these toxins are the six cysteines, a glycine in position 26 and two lysines at positions 28 and 33, respectively. The relevance of these differences in terms of possible structure-function relationships is discussed. C1 UNIV NACL AUTONOMA MEXICO,INST BIOTECNOL,DEPT BIOQUIM,CUERNAVACA 62271,MORELOS,MEXICO. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET UNIT,BETHESDA,MD 20892. CNR,IST CIBERNET & BIOFIS,I-16146 GENOA,ITALY. RI Possani, Lourival/J-2397-2013 NR 48 TC 38 Z9 40 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 15 PY 1994 VL 304 BP 51 EP 56 PN 1 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU039 UT WOS:A1994PU03900009 PM 7998956 ER PT J AU FOWLER, DH KURASAWA, K SMITH, R ECKHAUS, MA GRESS, RE AF FOWLER, DH KURASAWA, K SMITH, R ECKHAUS, MA GRESS, RE TI DONOR CD4-ENRICHED CELLS OF TH2 CYTOKINE PHENOTYPE REGULATE GRAFT-VERSUS-HOST DISEASE WITHOUT IMPAIRING ALLOGENEIC ENGRAFTMENT IN SUBLETHALLY IRRADIATED MICE SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; T-CELLS; LYMPHOCYTES-T; HYBRID RESISTANCE; EFFECTOR; REJECTION; LEUKEMIA; INVITRO; HELPER; MECHANISMS AB We have recently shown that donor CD4-enriched cells of Th2 cytokine phenotype, generated by treating mice in vivo with a combination of interleukin-2 (IL-2) and IL-4, prevent lipopolysaccharide-induced, tumor necrosis factor-cu-mediated lethality during graft-versus-host reaction. To assess the potential regulatory role of such Th2-type cells in lethal graft-versus-host disease (GVHD) and graft rejection, we used a fully allogeneic murine transplant model using sublethally irradiated hosts (B6 --> C3H 500 cGy). Such recipients generated a strong host-versus-graft response, as reflected by their ability to reject T-cell-depleted inocula. The administration of T-cell-containing donor whole spleen inocula resulted in alloengraftment, but such recipients developed lethal GVHD. However, mice receiving sequential donor whole spleen (day 0) and CD4-enriched, Th2-type (day 1) populations engrafted, and had prolonged survival with protection from histologically defined tissue injury associated with GVHD. The findings in this fully allogeneic model thus extend our previous observations and indicate that the transfer of donor Th2-type cells may be an important strategy for regulating GVHD. Furthermore, the sequential ''Th1 --> Th2-type'' donor cell transfer described in this report represents a novel approach for abrogating graft rejection with concomitant control of GVHD and illustrates the importance of kinetics in the interaction of functionally distinct donor T-cell populations. (C) 1994 by The American Society of Hematology. C1 NIH,NATL CTR RES RESOURCES,BETHESDA,MD 20892. RP FOWLER, DH (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B51,BETHESDA,MD 20892, USA. NR 39 TC 121 Z9 121 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 BP 3540 EP 3549 PG 10 WC Hematology SC Hematology GA PR221 UT WOS:A1994PR22100035 PM 7949109 ER PT J AU ANDERSON, S KAWASE, M MOMOEDA, M MIYAMURA, K KAJIGAYA, S YOUNG, NS AF ANDERSON, S KAWASE, M MOMOEDA, M MIYAMURA, K KAJIGAYA, S YOUNG, NS TI IMMUNOGENICITY OF THE UNIQUE REGION OF THE MINOR CAPSID PROTEIN OF B19-PARVOVIRUS SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A120 EP A120 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400463 ER PT J AU BARLOGIE, B JAGANNATH, S VESOLE, D MILLER, L CHESON, B BRACY, D TRICOT, G AF BARLOGIE, B JAGANNATH, S VESOLE, D MILLER, L CHESON, B BRACY, D TRICOT, G TI TOTAL THERAPY (TT) FOR 202 NEWLY-DIAGNOSED PATIENTS (PTS) WITH MULTIPLE-MYELOMA (MM) SO BLOOD LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. NCI,BETHESDA,MD 20892. NR 0 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A386 EP A386 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401527 ER PT J AU BELCH, AR BERGSAGEL, PL SZCZEPEK, A LANSDORP, P PILARSKI, LM AF BELCH, AR BERGSAGEL, PL SZCZEPEK, A LANSDORP, P PILARSKI, LM TI CD34+ B-CELLS IN THE BLOOD OF PATIENTS WITH MULTIPLE-MYELOMA EXPRESS CLONOTYPIC IGH SEQUENCES SO BLOOD LA English DT Meeting Abstract C1 UNIV ALBERTA,EDMONTON T6G 2E1,ALBERTA,CANADA. NCI,BETHESDA,MD 20892. UNIV BRITISH COLUMBIA,VANCOUVER V6T 1W5,BC,CANADA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A385 EP A385 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401522 ER PT J AU BERGSAGEL, PL BELCH, AR PILARSKI, LM AF BERGSAGEL, PL BELCH, AR PILARSKI, LM TI THE BLOOD B-CELLS AND BONE-MARROW PLASMA-CELLS IN A PATIENT WITH MULTIPLE-MYELOMA INCLUDE CELLS WITH THE SAME N-RAS MUTATION SO BLOOD LA English DT Meeting Abstract C1 UNIV ALBERTA,EDMONTON T6G 2E1,ALBERTA,CANADA. NCI,NCI NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 NR 0 TC 16 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A524 EP A524 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402078 ER PT J AU BRIDGES, K BARABINO, G BRUGNARA, C CHRISTOPH, G CHO, M DOVER, G EATON, W EWENSTEIN, B GOLAN, D GUTTMANN, C HOFRICHTER, J MULKERN, R ZHANG, B AF BRIDGES, K BARABINO, G BRUGNARA, C CHRISTOPH, G CHO, M DOVER, G EATON, W EWENSTEIN, B GOLAN, D GUTTMANN, C HOFRICHTER, J MULKERN, R ZHANG, B TI HYDROXYUREA CHANGES SS RBC BIOCHEMICAL BIOPHYSICAL PROFILE TO THAT OF SC RBCS SO BLOOD LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,CHILDRENS HOSP,BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. NIH,BETHESDA,MD 20892. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 0 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A413 EP A413 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401634 ER PT J AU BRODSKY, RA HASEGAWA, S FIBACH, E DUNBAR, CE YOUNG, NS RODGERS, GP AF BRODSKY, RA HASEGAWA, S FIBACH, E DUNBAR, CE YOUNG, NS RODGERS, GP TI THE ROLE OF PROGESTERONE IN ACQUIRED SIDEROBLASTIC ANEMIA SO BLOOD LA English DT Meeting Abstract C1 NIH,HEMATOL BRANCH,BETHESDA,MD 20892. NIH,CHEM BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A12 EP A12 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400037 ER PT J AU BROWN, RL SZABO, J BASS, B DUSING, SK SCHWARTZ, GN AF BROWN, RL SZABO, J BASS, B DUSING, SK SCHWARTZ, GN TI A UNIQUE GEL SYSTEM FOR HEMATOPOIETIC COLONY FORMATION SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A564 EP A564 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402236 ER PT J AU COLONOTERO, G SOLBERG, LA MILLER, LL WILSON, D MARSCHKE, R FITCH, T MAPLES, WJ CAMORIANO, J CHA, SS WIEAND, HS AF COLONOTERO, G SOLBERG, LA MILLER, LL WILSON, D MARSCHKE, R FITCH, T MAPLES, WJ CAMORIANO, J CHA, SS WIEAND, HS TI A PHASE-I TRIAL OF CONTINUOUS INTRAVENOUS-INFUSION OF INTERLEUKIN-1BETA (IL-1-BETA) FOLLOWED BY CARBOPLATIN (CBDCA) AND CYCLOPHOSPHAMIDE (CTX) IN PATIENTS WITH ADVANCED MALIGNANCIES SO BLOOD LA English DT Meeting Abstract C1 MAYO CLIN,JACKSONVILLE,FL. MAYO CLIN,SCOTTSDALE,AZ. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A581 EP A581 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402304 ER PT J AU CONTASSOT, E DESCHASEAUX, M CERTOUX, JM REYNOLDS, CW KELLER, JR RUSCETTI, FW MERLE, C CHIANG, Y LONGO, DL CAHN, JY HERVE, P TIBERGHIEN, P AF CONTASSOT, E DESCHASEAUX, M CERTOUX, JM REYNOLDS, CW KELLER, JR RUSCETTI, FW MERLE, C CHIANG, Y LONGO, DL CAHN, JY HERVE, P TIBERGHIEN, P TI RETROVIRAL-MEDIATED TRANSFER OF HERPES-SIMPLEX THYMIDINE KINASE (HS-TK) GENE IN ALLOREACTIVE T-LYMPHOCYTES SO BLOOD LA English DT Meeting Abstract C1 CHU BESANCON,CRTS,F-25030 BESANCON,FRANCE. DYNCORP INC,NCI,FCRDC,PRI,BCDP,FREDERICK,MD. GTI,GAITHERSBURG,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A354 EP A354 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401399 ER PT J AU COURIEL, D COTTLERFOX, M BURT, RK DUNBAR, C HENSEL, N YOUNG, NS BARRETT, AJ AF COURIEL, D COTTLERFOX, M BURT, RK DUNBAR, C HENSEL, N YOUNG, NS BARRETT, AJ TI T-CELL DEPLETED MARROW TRANSPLANTS WITH DELAYED LYMPHOCYTE ADD-BACK TO PREVENT RELAPSE IN PATIENTS WITH LEUKEMIA AND MDS SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A334 EP A334 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401317 ER PT J AU DELACADENA, RA MILLER, M STADNICKI, A TROPEA, M AGOSTI, J COLMAN, RW SUFFREDINI, AF AF DELACADENA, RA MILLER, M STADNICKI, A TROPEA, M AGOSTI, J COLMAN, RW SUFFREDINI, AF TI RECOMBINANT TUMOR-NECROSIS-FACTOR RECEPTOR (TNFR-FC) ALTERS ENDOTOXIN-INDUCED ACTIVATION OF THE CONTACT (CS) AND FIBRINOLYTIC (FS) SYSTEMS IN HUMAN VOLUNTEERS SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. TEMPLE UNIV,HLTH SCI CTR,SCH MED,SOL SHERRY THROMBOSIS RES CTR,PHILADELPHIA,PA 19140. TEMPLE UNIV,HLTH SCI CTR,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19140. IMMUNEX CORP,SEATTLE,WA. TEMPLE UNIV,HLTH SCI CTR,SCH MED,DEPT MED,PHILADELPHIA,PA 19140. NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A189 EP A189 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400740 ER PT J AU DEMONTALEMBERT, M BELLOY, M BERNAUDIN, F DUCROCQ, R MAIERREDELSPERGER, M PHILIPPE, N SCHECHTER, A GIROT, R AF DEMONTALEMBERT, M BELLOY, M BERNAUDIN, F DUCROCQ, R MAIERREDELSPERGER, M PHILIPPE, N SCHECHTER, A GIROT, R TI CLINICAL AND HEMATOLOGICAL RESPONSE OF SICKLE-CELL CHILDREN TO TREATMENT WITH HYDROXYUREA SO BLOOD LA English DT Meeting Abstract C1 HOP ROBERT DEBRE,SERV HEMATOL,PARIS,FRANCE. NIDDKD,BETHESDA,MD. HOP NECKER ENFANTS MALAD,CTR TRANSFUS SANGUINE,F-75730 PARIS 15,FRANCE. CTR HOSP INTERCOMMUNAL CRETEIL,F-94010 CRETEIL,FRANCE. HOP TENON,HEMATOL LAB,F-75970 PARIS 20,FRANCE. HOP DEBROUSSE,SERV HEMATOL,F-69005 LYON,FRANCE. NR 0 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A219 EP A219 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400860 ER PT J AU DONAHUE, RE BYRNE, E THOMAS, TE KIRBY, MR AGRICOLA, BA SELLERS, SE GAUDERNACK, G KARLSSON, S LANSDORP, PM AF DONAHUE, RE BYRNE, E THOMAS, TE KIRBY, MR AGRICOLA, BA SELLERS, SE GAUDERNACK, G KARLSSON, S LANSDORP, PM TI SUCCESSFUL GENE-TRANSFER OF THE HUMAN GLUCOCEREBROSIDASE GENE INTO IMMUNOSELECTED PRIMATE CD34+THY-1+ CELLS SO BLOOD LA English DT Meeting Abstract C1 TERRY FOX LAB,VANCOUVER,BC,CANADA. NHLBI,HEMATOL BRANCH,ROCKVILLE,MD. NATL HOSP NORWAY,OSLO 1,NORWAY. NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A402 EP A402 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401590 ER PT J AU DONAHUE, RE KIRBY, MR METZGER, ME SELLERS, SE CULLIS, HM AF DONAHUE, RE KIRBY, MR METZGER, ME SELLERS, SE CULLIS, HM TI CIRCULATING AND BONE-MARROW-DERIVED CD34+ HEMATOPOIETIC STEM-CELLS DIFFER IN THY-1 EXPRESSION AND CELL-CYCLE STATUS SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. BAXTER HLTH CARE,DIV FENWAL,SILVER SPRING,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A273 EP A273 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401077 ER PT J AU DUNK, AM CLARK, CA LOMBARDI, D KIRSCH, I WEINBERG, K KURTZBERG, J AF DUNK, AM CLARK, CA LOMBARDI, D KIRSCH, I WEINBERG, K KURTZBERG, J TI THE PATHOGENESIS OF INTERLEUKIN-2 CYTOTOXICITY TO HUMAN STEM-CELL LEUKEMIA IN SCID MICE SO BLOOD LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM,NC 27710. NCI,BETHESDA,MD 20892. LA CHILDRENS HOSP,LOS ANGELES,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A47 EP A47 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400178 ER PT J AU EVSTER, ME SANDERS, JC BATTEGAY, M DIBISCEGLIE, AM AF EVSTER, ME SANDERS, JC BATTEGAY, M DIBISCEGLIE, AM TI SUPPRESSION OF HCV REPLICATION BY HDV IN HIV-INFECTED HEMOPHILIACS WITH CHRONIC HEPATITIS-B AND HEPATITIS-C SO BLOOD LA English DT Meeting Abstract C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,HERSHEY,PA 17033. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A466 EP A466 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401844 ER PT J AU FARINA, SF GIRARD, LJ VANIN, EF NIENHUIS, AW BODINE, DM AF FARINA, SF GIRARD, LJ VANIN, EF NIENHUIS, AW BODINE, DM TI DYSREGULATED EXPRESSION OF GATA-1 FOLLOWING RETROVIRAL TRANSFER INTO MURINE HEMATOPOIETIC STEM-CELLS INCREASES ERYTHROPOIESIS SO BLOOD LA English DT Meeting Abstract C1 NIH, NCHGR, HEMATOPOIESIS SEC, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A401 EP A401 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401585 ER PT J AU FAUST, L ELBENNA, J CHRISTENSEN, B BABIOR, BM CHANOCK, SJ AF FAUST, L ELBENNA, J CHRISTENSEN, B BABIOR, BM CHANOCK, SJ TI INACTIVATION OF THE RESPIRATORY BURST OXIDASE BY THE ELIMINATION OF PHOSPHORYLATION TARGETS IN P47PHOX SO BLOOD LA English DT Meeting Abstract C1 SCRIPPS RES INST, LA JOLLA, CA USA. NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A372 EP A372 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401470 ER PT J AU FIBACH, E HASEGAWA, S SCHECHTER, AN NOGUCHI, CT RODGERS, GP AF FIBACH, E HASEGAWA, S SCHECHTER, AN NOGUCHI, CT RODGERS, GP TI THE 2-PHASE LIQUID CULTURE OF HUMAN ERYTHROID PROGENITORS - APPLICATION TO STUDYING SICKLING OF ERYTHROBLASTS FROM PATIENTS WITH SICKLE-CELL-ANEMIA (SCA) SO BLOOD LA English DT Meeting Abstract C1 NIDDK,CHEM BIOL LAB,BETHESDA,MD. HADASSAH UNIV HOSP,DEPT HEMATOL,IL-91120 JERUSALEM,ISRAEL. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A405 EP A405 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401601 ER PT J AU FRANCHINI, G GIRI, A DIGILIO, L GALLO, RC AF FRANCHINI, G GIRI, A DIGILIO, L GALLO, RC TI CHARACTERIZATION OF A NOVEL STLV-I ISOLATE DISTANTLY RELATED TO HTLV-I AND HTLV-II SO BLOOD LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A247 EP A247 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400972 ER PT J AU FRANKLIN, JL NARESH, KN CACERES, E BHATIA, K OCONOR, G MAGRATH, I AF FRANKLIN, JL NARESH, KN CACERES, E BHATIA, K OCONOR, G MAGRATH, I TI P53 EXPRESSION, BCL-2 EXPRESSION AND EBV ASSOCIATION IN PERUVIAN NASAL LYMPHOMAS SO BLOOD LA English DT Meeting Abstract C1 INST NACL ENFERMEDADES NEOPLASICAS,LIMA,PERU. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A522 EP A522 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402067 ER PT J AU FRIEDMAN, AD LIU, P BRITOSBRAY, M KELLY, C ADELSTEIN, R SPECK, NA COLLINS, FS AF FRIEDMAN, AD LIU, P BRITOSBRAY, M KELLY, C ADELSTEIN, R SPECK, NA COLLINS, FS TI THE FAB M4EO ACUTE MYELOID-LEUKEMIA ONCOPROTEIN CBF-BETA-MYH11 REDUCES THE DNA-BINDING AND TRANSACTIVATION ACTIVITIES OF PEBP2-ALPHA AND INDUCES APOPTOSIS IN 32D C-13 MYELOID CELLS SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BALTIMORE,MD 21205. NCHGR,BETHESDA,MD. NHLBI,BETHESDA,MD 20892. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,HANOVER,NH 03756. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A374 EP A374 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401478 ER PT J AU GARG, A TOMASZEWSKI, JE BARBERAGUILLEM, E MURPHY, MJ AF GARG, A TOMASZEWSKI, JE BARBERAGUILLEM, E MURPHY, MJ TI IN-VITRO TOXICITY OF FLAVOPIRIDOL (NSC-649890) TO HUMAN, CANINE, AND MURINE HEMATOPOIETIC PROGENITOR CELLS SO BLOOD LA English DT Meeting Abstract C1 HIPPLE CANC RES CTR,DAYTON,OH. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A566 EP A566 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402244 ER PT J AU GAUWERKY, C RAFFELD, M CROCE, C AF GAUWERKY, C RAFFELD, M CROCE, C TI BCL-3 AT CHR-17Q22 IN B-CELL LYMPHOMA EVOLUTION - EXPRESSION IN HEMATOPOIETIC-CELLS AND NUCLEOTIDE ANALYSIS OF TRANSLOCATION BREAKPOINTS SO BLOOD LA English DT Meeting Abstract C1 THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A441 EP A441 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401745 ER PT J AU GRALNICK, HR WILLIAMS, S MCKEOWN, LP HANSMANN, K VAIL, M FENTON, J KRUTZSCH, H AF GRALNICK, HR WILLIAMS, S MCKEOWN, LP HANSMANN, K VAIL, M FENTON, J KRUTZSCH, H TI A GPIB-ALPHA MONOCLONAL-ANTIBODY INHIBITS THROMBIN BINDING TO GPIB AND THE 7-TRANSMEMBRANE DOMAIN RECEPTOR SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A533 EP A533 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402113 ER PT J AU GRALNICK, HR MCKEOWN, LP WILLIAMS, S HANSMANN, K KRUTZSCH, H AF GRALNICK, HR MCKEOWN, LP WILLIAMS, S HANSMANN, K KRUTZSCH, H TI GLYCOPROTEIN IBA PEPTIDES THAT ENHANCE THROMBIN BINDING TO PLATELETS AND INHIBIT THROMBIN-INDUCED PLATELET-AGGREGATION SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A476 EP A476 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401883 ER PT J AU GRANT, S FREEMERMAN, AJ JARVIS, WD TURNER, AJ BIRRER, MJ AF GRANT, S FREEMERMAN, AJ JARVIS, WD TURNER, AJ BIRRER, MJ TI INDUCTION OF APOPTOSIS IN HUMAN MYELOID-LEUKEMIA CELLS BY SPECIFIC PKC INHIBITORS AND THE NUCLEOSIDE ANALOG ARA-C IS ASSOCIATED WITH INCREASED EXPRESSION OF C-JUN - EVIDENCE FOR A PKC-INDEPENDENT MECHANISM OF GENE-REGULATION SO BLOOD LA English DT Meeting Abstract C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DIV HEMATOL ONCOL,RICHMOND,VA 23298. NCI,BIOMARKERS & PREVENT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A141 EP A141 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400549 ER PT J AU GREVER, MR BHATIA, K GIAVAZZI, R HOLLINGSHEAD, M MAGRATH, I MALSPEIS, L MAYO, J SHORES, R AF GREVER, MR BHATIA, K GIAVAZZI, R HOLLINGSHEAD, M MAGRATH, I MALSPEIS, L MAYO, J SHORES, R TI EXPERIMENTAL THERAPEUTIC AGENTS IN AN AIDS-RELATED SCID MOUSE MODEL SO BLOOD LA English DT Meeting Abstract C1 NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. NCI,FCRDC,PRI DYNCORP,FREDERICK,MD 21701. MARIO NEGRI INST PHARMACOL RES,BERGAMO,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A447 EP A447 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401771 ER PT J AU HE, RY REID, DM SHULMAN, NR AF HE, RY REID, DM SHULMAN, NR TI PEPTIDE AA326-346 OF GPI-BETA-ALPHA CONTAINS AN EXOSOLIC EPITOPE REACTIVE WITH SERUM ANTIBODIES FROM PATIENTS WITH CHRONIC IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP) SO BLOOD LA English DT Meeting Abstract C1 NIDDK,CLIN HEMATOL BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A527 EP A527 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402089 ER PT J AU HIEMENZ, JW ANAISSIE, E WALSH, TJ AF HIEMENZ, JW ANAISSIE, E WALSH, TJ TI AMPHOTERICIN-B LIPID COMPLEX (ABLC) FOR THE TREATMENT OF SEVERE SYSTEMIC MYCOSIS IN PATIENTS (PTS) WITH HEMATOLOGIC MALIGNANCIES SO BLOOD LA English DT Meeting Abstract C1 H LEE MOFFITT CANC CTR,TAMPA,FL. MD ANDERSON TUMOR INST,HOUSTON,TX. NCI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A305 EP A305 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401204 ER PT J AU HOANG, AT LEWIS, BC LUTTERBACH, B YANO, T CHOU, TY BARRETT, JF RAFFELD, M HANN, SR DANG, CV AF HOANG, AT LEWIS, BC LUTTERBACH, B YANO, T CHOU, TY BARRETT, JF RAFFELD, M HANN, SR DANG, CV TI INCREASED TRANSFORMING ACTIVITY OF LYMPHOMA-DERIVED MYC MUTANT ALLELES RESULTS FROM DEFECTIVE REGULATION BY THE GROWTH SUPPRESSOR P107 AND ALTERED PHOSPHORYLATION OF THE MYC TRANSACTIVATION DOMAIN SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV HEMATOL,BALTIMORE,MD 21205. VANDERBILT UNIV,DEPT CELL BIOL,NASHVILLE,TN 37240. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A38 EP A38 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400142 ER PT J AU HOANG, T PARADIS, E BRADY, G BILLIA, F ISCOVE, NN NAKAHARA, K KIRSCH, IR AF HOANG, T PARADIS, E BRADY, G BILLIA, F ISCOVE, NN NAKAHARA, K KIRSCH, IR TI ROLE OF THE BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR SCL IN HEMATOPOIESIS SO BLOOD LA English DT Meeting Abstract C1 CLIN RES INST MONTREAL, MONTREAL H2W 1R7, QUEBEC, CANADA. ONTARIO CANC INST, TORONTO M4X 1K9, ONTARIO, CANADA. NCI, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A365 EP A365 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401443 ER PT J AU HUANG, SZ ZENG, YT FIBACH, E REN, ZR HASEGAWA, S SCHECHTER, AN RODGERS, GP AF HUANG, SZ ZENG, YT FIBACH, E REN, ZR HASEGAWA, S SCHECHTER, AN RODGERS, GP TI EXPRESSION OF GLOBIN GENES IN HUMAN ADULT ERYTHROID (HAE) CULTURED-CELLS AND ITS ALTERATION WITH HYDROXYUREA (HU) SO BLOOD LA English DT Meeting Abstract C1 NIDDK,CHEM BIOL LAB,BETHESDA,MD. SHANGHAI INST MED GENET,SHANGHAI,PEOPLES R CHINA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A264 EP A264 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401038 ER PT J AU JIANG, YZ COURIEL, D MALKOVSKA, V LEWALLE, PA MAVROUDIS, DA HENSEL, NF BARRETT, AJ AF JIANG, YZ COURIEL, D MALKOVSKA, V LEWALLE, PA MAVROUDIS, DA HENSEL, NF BARRETT, AJ TI HLA-DR1 TRANSFECTED K562 CELLS INHIBIT NK CELL CYTOTOXICITY SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A289 EP A289 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401138 ER PT J AU KINGMA, DW WEISS, WB JAFFE, ES KUMAR, S RAFFELD, M AF KINGMA, DW WEISS, WB JAFFE, ES KUMAR, S RAFFELD, M TI EBV LMP1 ONCOGENE DELETIONS - CORRELATIONS WITH MALIGNANCY IN EBV-ASSOCIATED LYMPHOPROLIFERATIVE DISORDERS SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A644 EP A644 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402555 ER PT J AU LIU, K SANROMAN, J KAMALI, V NAUGHTON, BA KELLER, J RUSCETTI, FW ROODMAN, D BONEWALD, L MEAGHER, RM PURCHIO, AF TWARDZIK, DR AF LIU, K SANROMAN, J KAMALI, V NAUGHTON, BA KELLER, J RUSCETTI, FW ROODMAN, D BONEWALD, L MEAGHER, RM PURCHIO, AF TWARDZIK, DR TI PURIFICATION OF STEM-CELL PROLIFERATION FACTOR (SCPF), A CYTOKINE THAT STIMULATES THE EXPANSION OF HUMAN CD34+ CELLS IN-VITRO SO BLOOD LA English DT Meeting Abstract C1 ADV TISSUE SCI INC,LA JOLLA,CA. NCI,LEUKOCYTE BIOL LAB,FREDERICK,MD 21701. UNIV CINCINNATI,MED CTR,HOXWORTH BLOOD CTR,CINCINNATI,OH 45267. VET ADM MED CTR,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A275 EP A275 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401082 ER PT J AU MACIEJEWSKI, J SELLERI, C SATO, T CHO, H KEEFER, LK NATHAN, CF YOUNG, NS AF MACIEJEWSKI, J SELLERI, C SATO, T CHO, H KEEFER, LK NATHAN, CF YOUNG, NS TI NITRIC-OXIDE SUPPRESSION OF HUMAN HEMATOPOIESIS IN-VITRO - NITRIC-OXIDE SYNTHASE IS PRESENT IN CD34+ CELLS AND INDUCED BY INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. CORNELL UNIV,NEW YORK,NY 10021. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A421 EP A421 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401665 ER PT J AU MACIEJEWSKI, J SELLERI, C ANDERSON, S YOUNG, NS AF MACIEJEWSKI, J SELLERI, C ANDERSON, S YOUNG, NS TI FAS ANTIGEN EXPRESSION ON CD34+ CELLS IS INDUCED BY INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA AND POTENTIATES CYTOKINE SUPPRESSION OF HEMATOPOIESIS IN-VITRO SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A215 EP A215 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400844 ER PT J AU MAVROUDIS, DA JIANG, YZ HENSEL, NF COURIEL, D LEWALLE, PA BARRETT, AJ AF MAVROUDIS, DA JIANG, YZ HENSEL, NF COURIEL, D LEWALLE, PA BARRETT, AJ TI SELECTIVE T-CELL DEPLETION TO PREVENT GRAFT-VERSUS-HOST DISEASE (GVHD) IN HLA HAPLOTYPE MISMATCHED BONE-MARROW TRANSPLANTATION (BMT) SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A737 EP A737 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402928 ER PT J AU MILLER, JL PETERS, T ANDERSON, S BRODSKY, R NIENHUIS, AW YOUNG, NS AF MILLER, JL PETERS, T ANDERSON, S BRODSKY, R NIENHUIS, AW YOUNG, NS TI TRANSIENT AND STABLE GENE-EXPRESSION OF A CELL-SURFACE RECEPTOR MOLECULE USING RECOMBINANT ADENOASSOCIATED VIRUS SO BLOOD LA English DT Meeting Abstract C1 NHLBI, HEMATOL BRANCH, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A256 EP A256 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401006 ER PT J AU MILLS, NE HAYES, RB FISHMAN, CL YIN, SN LINET, ML TRAVIS, LB JACOBSON, DR AF MILLS, NE HAYES, RB FISHMAN, CL YIN, SN LINET, ML TRAVIS, LB JACOBSON, DR TI RAS MUTATIONS IN CHINESE PATIENTS WITH BENZENE-ASSOCIATED AND DE-NOVO ACUTE-LEUKEMIA SO BLOOD LA English DT Meeting Abstract C1 NYU MED CTR,DEPT MED,NEW YORK,NY 10016. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. CHINESE ACAD PREVENT MED,INST OCCUPAT MED,BEIJING,PEOPLES R CHINA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A47 EP A47 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400177 ER PT J AU MONAHAN, BP LIU, P BAREKMAN, CL COTELINGAM, J FRAME, JN COLLINS, FS DAHUT, WL AF MONAHAN, BP LIU, P BAREKMAN, CL COTELINGAM, J FRAME, JN COLLINS, FS DAHUT, WL TI NOVEL ASSOCIATION OF INVERSION-16 CHROMOSOME AT PRESENTATION IN ACUTE MYELOCYTIC-LEUKEMIA (M1) WITH ABNORMAL BONE-MARROW EOSINOPHILIA (M1EO) SO BLOOD LA English DT Meeting Abstract C1 NCHGR, BETHESDA, MD USA. NATL NAVAL MED CTR, BETHESDA, MD USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A610 EP A610 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402421 ER PT J AU NAGARAJAN, S BRODSKY, RA KIMBALL, J YOUNG, NS MEDOF, ME AF NAGARAJAN, S BRODSKY, RA KIMBALL, J YOUNG, NS MEDOF, ME TI PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA EVOLVING FROM APLASTIC-ANEMIA SO BLOOD LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. NIH,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A215 EP A215 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400845 ER PT J AU NEY, PA FARINA, SF BODINE, DM ANDREWS, NC ORKIN, SH NIENHUIS, AW AF NEY, PA FARINA, SF BODINE, DM ANDREWS, NC ORKIN, SH NIENHUIS, AW TI GENE-TRANSFER OF WILD-TYPE P45 NF-E2 INTO THE HEMATOPOIETIC-CELLS OF MK/MK MICE SO BLOOD LA English DT Meeting Abstract C1 ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38101 USA. ST JUDE CHILDRENS RES HOSP, DEPT EXPTL HEMATOL, MEMPHIS, TN 38101 USA. NCHGR, GENE TRANSFER LAB, HEMATOPOIESIS SECT, BETHESDA, MD USA. CHILDRENS HOSP MED CTR, DEPT PEDIAT, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HOWARD HUGHES MED INST, COCONUT GROVE, FL 33133 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A354 EP A354 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401398 ER PT J AU OAZILBASH, M LIU, J VLACHOS, A FRUCHTMAN, S MESSNER, H ZIPURSKY, A ALTER, BP YOUNG, NS AF OAZILBASH, M LIU, J VLACHOS, A FRUCHTMAN, S MESSNER, H ZIPURSKY, A ALTER, BP YOUNG, NS TI FAMILIAL APLASTIC-ANEMIA ASSOCIATED WITH CHRONIC LIVER-DISEASE SO BLOOD LA English DT Meeting Abstract C1 CUNY MT SINAI SCH MED,NEW YORK,NY 10029. HOSP SICK CHILDREN,TORONTO M5G 1X8,ONTARIO,CANADA. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A8 EP A8 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400022 ER PT J AU OONISHI, T SAKASHITA, K SCHECHTER, AN UYESAKA, N AF OONISHI, T SAKASHITA, K SCHECHTER, AN UYESAKA, N TI QUANTITATIVE CHARACTERIZATION OF THE P-GLYCOPROTEIN-MEDIATED TRANSPORT IN MDR1 GENE-TRANSFECTED L5178Y VMDR C.06 CELLS - A POSSIBLE MECHANISM OF ACTION OF THE MULTIDRUG TRANSPORTER SO BLOOD LA English DT Meeting Abstract C1 KANTO TEISHIN HOSP,INST MED INFORMAT,TOKYO 141,JAPAN. NIDDK,CHEM BIOL LAB,BETHESDA,MD. NIPPON MED COLL,DEPT PHYSIOL,TOKYO 113,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A143 EP A143 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400557 ER PT J AU OTSUKI, T CLARK, HM WELLMANN, A JAFFE, ES RAFFELD, M AF OTSUKI, T CLARK, HM WELLMANN, A JAFFE, ES RAFFELD, M TI INVOLVEMENT OF THE CDKN2 (P16INK4/MTS1) GENE IN HUMAN LYMPHOID MALIGNANCIES - HIGH-INCIDENCE OF HOMOZYGOUS DELETIONS IN T-ALL/LBL SO BLOOD LA English DT Meeting Abstract C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A438 EP A438 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401734 ER PT J AU PILARSKI, LM BELCH, AR SMITH, AM SZCZEPEK, A MANT, MJ BERGSAGEL, PL AF PILARSKI, LM BELCH, AR SMITH, AM SZCZEPEK, A MANT, MJ BERGSAGEL, PL TI CLONOTYPIC IGH REARRANGEMENTS IN IG+ B-LYMPHOCYTES IN BLOOD OF PATIENTS WITH MULTIPLE-MYELOMA SO BLOOD LA English DT Meeting Abstract C1 UNIV ALBERTA,EDMONTON T6G 2E1,ALBERTA,CANADA. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A180 EP A180 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400704 ER PT J AU PRINCE, GM MAI, NY LAZARUS, HM BRODSKY, RA LEON, WMM TERSTAPPEN MEDOF, ME AF PRINCE, GM MAI, NY LAZARUS, HM BRODSKY, RA LEON, WMM TERSTAPPEN MEDOF, ME TI PERIPHERAL-BLOOD HARVEST OF UNAFFECTED CD34+CD38- HEMATOPOIETIC PRECURSORS IN PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,IRELAND CANC CTR,CLEVELAND,OH 44106. BECTON DICKINSON IMMUNOCYTOMETRY SYST,SAN JOSE,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A350 EP A350 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401382 ER PT J AU REDDINGLALLINGER, R GLADEN, B KALOKOLA, FM JONES, G MMARI, MPW AF REDDINGLALLINGER, R GLADEN, B KALOKOLA, FM JONES, G MMARI, MPW TI THE HEMATOLOGIC AND IRON STATUS OF NEWBORNS AND THEIR MOTHERS IN TANZANIA - EVIDENCE FOR IRON-DEFICIENCY AT BIRTH SO BLOOD LA English DT Meeting Abstract C1 UNIV N CAROLINA HOSP,GEN CLIN RES CTR,CHAPEL HILL,NC. DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. DUKE UNIV,MED CTR,DIV INFECT DIS & INT HLTH,DURHAM,NC 27710. NIEHS,RES TRIANGLE PK,NC 27709. MUHIMBILI UNIV,COLL HLTH SCI,DEPT PEDIAT & CHILD HLTH,DAR ES SALAAM,TANZANIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A116 EP A116 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400449 ER PT J AU RICK, ME KRIZEK, DM AF RICK, ME KRIZEK, DM TI IDENTIFICATION OF A MOLECULAR DEFECT IN A PATIENT WITH VON-WILLEBRAND DISEASE AND DEFECTIVE BINDING OF FACTOR-VIII SO BLOOD LA English DT Meeting Abstract C1 NIH,CTR CLIN,HEMATOL SERV,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A59 EP A59 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400226 ER PT J AU SANTUCCI, M PIERCE, J GREENBERGER, J AF SANTUCCI, M PIERCE, J GREENBERGER, J TI EXPRESSION OF ACUTE LYMPHOBLASTIC LEUKEMIA-ASSOCIATED P185 BCR ABL ONCOPROTEIN ABROGATES GROWTH FACTOR-DEPENDENCE AND INCREASES RESISTANCE TO RADIATION-INDUCED DNA-DAMAGE IN A MURINE MYELOID CELL-LINE SO BLOOD LA English DT Meeting Abstract C1 UNIV BOLOGNA,IST EMATOL LA SERAGNOLI,I-40126 BOLOGNA,ITALY. NCI,BETHESDA,MD 20892. UNIV PITTSBURGH,MED CTR,PITTSBURGH,PA 15260. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A140 EP A140 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400544 ER PT J AU SAVILLE, MW LIETZAU, J PLUDA, JM WILSON, W BAILEY, J COHEN, R FEIGAL, E HUMPHREY, R BRODER, S YARCHOAN, R AF SAVILLE, MW LIETZAU, J PLUDA, JM WILSON, W BAILEY, J COHEN, R FEIGAL, E HUMPHREY, R BRODER, S YARCHOAN, R TI PHASE-II STUDY OF PACLITAXEL (TAXOL(TM)) FOR THE TREATMENT OF HIV-ASSOCIATED KAPOSIS-SARCOMA (KS) SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A248 EP A248 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400975 ER PT J AU SCHIFFMANN, R MEDIN, JA WARD, J STAHL, S COTTLERFOX, M KARLSSON, S AF SCHIFFMANN, R MEDIN, JA WARD, J STAHL, S COTTLERFOX, M KARLSSON, S TI TRANSFER OF THE HUMAN GLUCOCEREBROSIDASE (HGC) GENE INTO HEMATOPOIETIC STEM-CELLS OF NONABLATED MICE SO BLOOD LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A401 EP A401 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401586 ER PT J AU SCHWARTZ, GN SZABO, JM ROSE, WL GRESS, RE WARREN, MK AF SCHWARTZ, GN SZABO, JM ROSE, WL GRESS, RE WARREN, MK TI EFFECT OF GROWTH-FACTORS AND MARROW STROMAL CELL-LAYERS ON EXPANSION OF MEGAKARYOCYTES AND NEUTROPHILS FROM CD34+ CELLS SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. OTSUKA AMER PHARM INC,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A576 EP A576 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402283 ER PT J AU SCHWARTZ, GN WARREN, MK SZABO, JM MACKALL, C HAKIM, F RILEY, J RISEBERG, D SETZER, A NOONE, M COWAN, K OSHAUGHNESSY, J AF SCHWARTZ, GN WARREN, MK SZABO, JM MACKALL, C HAKIM, F RILEY, J RISEBERG, D SETZER, A NOONE, M COWAN, K OSHAUGHNESSY, J TI EFFECT OF STROMAL CELL-LAYERS FROM BONE-MARROW OF PATIENTS PRE-CHEMOTHERAPY AND POSTCHEMOTHERAPY ON GROWTH OF NORMAL CD34+ CELLS SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. OTSUKA AMER PHARM INC,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A343 EP A343 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401355 ER PT J AU SEKHAR, M SOMA, T DUNBAR, CE AF SEKHAR, M SOMA, T DUNBAR, CE TI LONG-TERM REPOPULATING ABILITY IN THE MURINE MODEL IS COMPROMISED BY EX-VIVO CULTURE IN SERUM-FREE MEDIA DESPITE PRESERVATION OF COMMITTED PROGENITOR NUMBERS SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. ROYAL FREE HOSP,LONDON,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A359 EP A359 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401416 ER PT J AU SEKHAR, M KOTANI, T DOREN, S AGARWAL, R MCGARRITY, G DUNBAR, CE AF SEKHAR, M KOTANI, T DOREN, S AGARWAL, R MCGARRITY, G DUNBAR, CE TI RETROVIRAL TRANSDUCTION OF CD34-ENRICHED HEMATOPOIETIC PROGENITORS USING CONCENTRATED VECTOR UNDER SERUM-FREE CONDITIONS SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. ROYAL FREE HOSP,LONDON,ENGLAND. CINCINNATI CHILDRENS HOSP,CINCINNATI,OH. GENET THERAPY INC,GAITHERSBURG,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A358 EP A358 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401415 ER PT J AU SELLERI, C ANDERSON, S YOUNG, NS MACIEJEWSKI, JP AF SELLERI, C ANDERSON, S YOUNG, NS MACIEJEWSKI, JP TI INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA SUPPRESS EARLY AND LATE STAGES OF HEMATOPOIESIS IN-VITRO AND INDUCE PROGRAMMED CELL-DEATH SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A215 EP A215 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400843 ER PT J AU SLOAND, EM RYAN, D KUMAR, P AF SLOAND, EM RYAN, D KUMAR, P TI PHASE-I STUDY OF AEROSOLIZED ALPHA-INTERFERON IN HIV-INFECTED PERSONS SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC 20007. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A481 EP A481 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401906 ER PT J AU SLOAND, EM YU, M KLEIN, HG AF SLOAND, EM YU, M KLEIN, HG TI EFFECT OF ANTICOAGULANT ON PLATELET MEMBRANE GLYCOPROTEIN (PMG) EXPRESSION IN PLATELET CONCENTRATES SO BLOOD LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A465 EP A465 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401843 ER PT J AU SOMA, T ORLIC, D DUNBAR, CE AF SOMA, T ORLIC, D DUNBAR, CE TI SUPPRESSIVE EFFECT OF TGF-BETA-1 AND PROTECTIVE EFFECT OF ANTI-TGF-BETA ANTIBODY ON PLURIPOTENT HEMATOPOIETIC STEM-CELLS SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NIH,NCHGR,HEMATOPOIESIS SECT,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A221 EP A221 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400866 ER PT J AU TRICOT, G JAGANNATH, S VESOLE, D NELSON, J TINDLE, S MILLER, L CHESON, B CROWLEY, J BARLOGIE, B AF TRICOT, G JAGANNATH, S VESOLE, D NELSON, J TINDLE, S MILLER, L CHESON, B CROWLEY, J BARLOGIE, B TI PERIPHERAL-BLOOD STEM-CELL TRANSPLANTS (PBSC) FOR MULTIPLE-MYELOMA (MM) IDENTIFICATION OF FAVORABLE VARIABLES FOR RAPID ENGRAFTMENT IN 225 PATIENTS SO BLOOD LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. NCI,BETHESDA,MD 20892. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A180 EP A180 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400706 ER PT J AU TUMAS, DB BROOKS, DM CHESEBRO, B SPANGRUDE, GJ AF TUMAS, DB BROOKS, DM CHESEBRO, B SPANGRUDE, GJ TI HIGH-FREQUENCY LONG-TERM IN-VIVO SURFACE EXPRESSION OF A FOREIGN GENE-PRODUCT AFTER HEMATOPOIETIC STEM-CELL TRANSDUCTION WITH A PSFF RETROVIRAL VECTOR SO BLOOD LA English DT Meeting Abstract C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LABS,HAMILTON,MT 59840. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A359 EP A359 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401418 ER PT J AU UYESAKA, N SOGAMI, M ERA, S HASEGAWA, S KATO, K SCHECHTER, AN AF UYESAKA, N SOGAMI, M ERA, S HASEGAWA, S KATO, K SCHECHTER, AN TI MAGNETIZATION-TRANSFER CHARACTERIZATION OF HEINZ-BODY-FORMING RED-CELLS SO BLOOD LA English DT Meeting Abstract C1 GIFU UNIV,SCH MED,DEPT PHYSIOL,GIFU 500,JAPAN. NIH,CHEM BIOL LAB,BETHESDA,MD 20892. NIPPON MED COLL,DEPT PHYSIOL,TOKYO 113,JAPAN. FUJITA HLTH UNIV,INST COMPREHENS MED SCI,TOYOAKE,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A546 EP A546 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402164 ER PT J AU VESOLE, D JAGANNATH, S TRICOT, G MILLER, L CHESON, B BRACY, D BARLOGIE, B AF VESOLE, D JAGANNATH, S TRICOT, G MILLER, L CHESON, B BRACY, D BARLOGIE, B TI 400 AUTOTRANSPLANTS (AT) FOR MULTIPLE-MYELOMA (MM) SO BLOOD LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A535 EP A535 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402121 ER PT J AU WALSH, CE LIU, JM WANG, S XIAO, X HASHMI, NJ ZWERDLING, T AGARWAL, R AF WALSH, CE LIU, JM WANG, S XIAO, X HASHMI, NJ ZWERDLING, T AGARWAL, R TI IN-VIVO GENE-TRANSFER WITH A NOVEL ADENOASSOCIATED VIRUS VECTOR TO HUMAN HEMATOPOIETIC-CELLS ENGRAFTED IN SCID-HU MICE SO BLOOD LA English DT Meeting Abstract C1 NHLBI,HEMATOL SERV,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC 27514. NR 2 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A256 EP A256 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401008 ER PT J AU WANG, Y RUSSO, TR CHANOCK, SJ LEVINE, M AF WANG, Y RUSSO, TR CHANOCK, SJ LEVINE, M TI RECYCLING OF ASCORBATE IN HUMAN NEUTROPHILS INDUCED BY BACTERIA SO BLOOD LA English DT Meeting Abstract C1 NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A137 EP A137 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400532 ER PT J AU WARREN, MK ROSE, WL GRABER, NL SCHWARTZ, GN AF WARREN, MK ROSE, WL GRABER, NL SCHWARTZ, GN TI EFFECT OF NEGATIVE REGULATORS ON SPECIFIC LINEAGE COMMITMENT OF HUMAN CD34+ CELLS IN LIQUID CULTURE SO BLOOD LA English DT Meeting Abstract C1 OTSUKA AMER PHARM INC,ROCKVILLE,MD. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A578 EP A578 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402292 ER PT J AU WEICHOLD, FF MACIEJEWSKI, JP GALLO, RC REITZ, M YOUNG, NS AF WEICHOLD, FF MACIEJEWSKI, JP GALLO, RC REITZ, M YOUNG, NS TI INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS-TYPE-1 (HIV-1) INFECTION IN-VITRO AFTER INTRACELLULAR EXPRESSION OF AN ANTIBODY FRAGMENT DIRECTED AGAINST REVERSE-TRANSCRIPTASE SO BLOOD LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A248 EP A248 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400976 ER PT J AU WEINBERG, JB BONAVENTURA, J FERRUZZI, G SAULS, DL MASON, RP CHAMULITRAT, W AF WEINBERG, JB BONAVENTURA, J FERRUZZI, G SAULS, DL MASON, RP CHAMULITRAT, W TI NITRIC-OXIDE COBALAMIN INTERACTIONS - IMPLICATIONS REGARDING VITAMIN-B12 DEFICIENCY STATES SO BLOOD LA English DT Meeting Abstract C1 VET ADM MED CTR,DURHAM,NC 27705. DUKE MED CTR,DURHAM,NC. DUKE MARINE BIOMED CTR,BEAUFORT,NC. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A118 EP A118 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400455 ER PT J AU WEINTRAUB, M FAN, S SPANGLER, G OCONNOR, P JUDDE, JG MAGRATH, LT BHATIA, K AF WEINTRAUB, M FAN, S SPANGLER, G OCONNOR, P JUDDE, JG MAGRATH, LT BHATIA, K TI WAF-1, A DOWNSTREAM MEDIATOR OF P53 IS RARELY MUTATED IN BURKITTS LYMPHOMAS SO BLOOD LA English DT Meeting Abstract C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,DEPT PHARMACOL,MOLECUL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A615 EP A615 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402441 ER PT J AU WEINTRAUB, M ADDE, M SHAD, A HORAK, I SEIBEL, N NEELY, J MAGRATH, I AF WEINTRAUB, M ADDE, M SHAD, A HORAK, I SEIBEL, N NEELY, J MAGRATH, I TI PROFOUND PERIPHERAL NEUROPATHY ASSOCIATED WITH THE ADMINISTRATION OF COLONY-STIMULATING FACTORS SO BLOOD LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. CHILDRENS HOSP,NATL MED CTR,NATL MED CTR,WASHINGTON,DC 20010. MS HERSHEY MED CTR,HERSHEY,PA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A128 EP A128 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400495 ER PT J AU WENG, LJ SAMID, D BURKE, PJ GORE, SD AF WENG, LJ SAMID, D BURKE, PJ GORE, SD TI IRREVERSIBLE INHIBITION OF PROLIFERATION OF PRIMARY ACUTE MYELOID LEUKEMIC (AML) CELLS BY PHENYL BUTYRATE (PB) SO BLOOD LA English DT Meeting Abstract C1 JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A628 EP A628 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75402491 ER PT J AU YANG, QE TOBIN, GJ GONDA, MA AF YANG, QE TOBIN, GJ GONDA, MA TI EXPANSION OF MURINE BONE-MARROW PLURIPOTENT STEM-CELLS IN-VITRO BY MULTIPLE CYTOKINE MEDIUM SO BLOOD LA English DT Meeting Abstract C1 NCI,FCRDC,PRI DYNCORP,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A101 EP A101 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75400390 ER PT J AU YASWEN, L KULKARNI, AB WARD, J SCHIFFMANN, R MOZES, E KARLSSON, S AF YASWEN, L KULKARNI, AB WARD, J SCHIFFMANN, R MOZES, E KARLSSON, S TI POTENTIAL AUTOIMMUNE ETIOLOGY IN TGF-BETA-1 KNOCKOUT MOUSE IMMUNE DYSREGULATION SO BLOOD LA English DT Meeting Abstract C1 NINCDS,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1994 VL 84 IS 10 SU 1 BP A496 EP A496 PG 1 WC Hematology SC Hematology GA PR754 UT WOS:A1994PR75401966 ER PT J AU THEODOSSIOU, C KROOG, G ETTINGHAUSEN, S TOLCHER, A COWAN, K OSHAUGHNESSY, J AF THEODOSSIOU, C KROOG, G ETTINGHAUSEN, S TOLCHER, A COWAN, K OSHAUGHNESSY, J TI ACUTE ARTERIAL THROMBOSIS IN A PATIENT WITH BREAST-CANCER AFTER CHEMOTHERAPY WITH 5-FLUOROURACIL, DOXORUBICIN, LEUCOVORIN, CYCLOPHOSPHAMIDE, AND INTERLEUKIN-3 SO CANCER LA English DT Article DE BREAST CANCER; ARTERIAL THROMBOSIS; INTERLEUKIN 3; HYPERCOAGULABLE STATE ID RECOMBINANT HUMAN INTERLEUKIN-3; COAGULATION; ABNORMALITIES; PROCOAGULANT; CARCINOMA AB Background. Interleukin-3 (IL-3) is an experimental agent used to ameliorate neutropenia in patients receiving chemotherapy. Arterial thrombotic episodes after use of IL-3 have not been reported previously. Methods. The case of a patient with Stage III adenocarcinoma of the breast who developed hypotension and acute cerebellar artery and superior mesenteric artery thrombosis after receiving chemotherapy and treatment with IL-3 is reported. Results. To the authors' knowledge, this is the first patient with arterial thrombosis reported after treatment with IL-3. Conclusions. Interleukin-5 may be associated with increased propensity for thrombosis. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. RP THEODOSSIOU, C (reprint author), NCI,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,ROOM B3B69,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 14 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 1994 VL 74 IS 10 BP 2808 EP 2810 DI 10.1002/1097-0142(19941115)74:10<2808::AID-CNCR2820741011>3.0.CO;2-V PG 3 WC Oncology SC Oncology GA PQ360 UT WOS:A1994PQ36000010 PM 7954241 ER PT J AU FAN, SJ ELDEIRY, WS BAE, I FREEMAN, J JONDLE, D BHATIA, K FORNACE, AJ MAGRATH, I KOHN, KW OCONNOR, PM AF FAN, SJ ELDEIRY, WS BAE, I FREEMAN, J JONDLE, D BHATIA, K FORNACE, AJ MAGRATH, I KOHN, KW OCONNOR, PM TI P53 GENE-MUTATIONS ARE ASSOCIATED WITH DECREASED SENSITIVITY OF HUMAN LYMPHOMA-CELLS TO DNA-DAMAGING AGENTS SO CANCER RESEARCH LA English DT Note ID INTERSTRAND CROSS-LINKS; TUMOR-SUPPRESSOR GENE; WILD-TYPE P53; NITROGEN-MUSTARD; INDUCED APOPTOSIS; CYCLE ARREST; CHECKPOINT; REPAIR; LINES; RNA AB The present study assessed the role of the p53 tumor suppressor gene in cell cycle arrest and apoptosis following treatment of Burkitt's lymphoma and lymphoblastoid cell lines with gamma-rays, etoposide, nitrogen mustard, and cisplatin. Cell cycle arrest was measured by flow cytometry; p53 and p21(Waf1/Cip1) protein levels were measured by Western blotting; cell survival was measured in 72-96-h growth inhibition assays and by trypan blue staining, and apoptotic DNA fragmentation was assessed by either agarose gel electrophoresis or a modified filter elution method. We found that gamma-rays and etoposide induced a strong G(1) arrest in the wild-type p53 lines while nitrogen mustard and cisplatin induced relatively little G(1) arrest. All agents failed to induce G(1) arrest in cells containing mutant p53 genes. The degree of G(1) arrest observed with these agents correlated with the rate of p53 and p21(Waf1/Cip1) protein accumulation: gamma-rays and etoposide induced rapid accumulation of both p53 and p21(Waf1/Cip1); nitrogen mustard and cisplatin induced slow accumulation of p53 and no major accumulation of the p21(Waf1/Cip1) protein. Despite differences in G(1) arrest and kinetics of p53 or p21(Waf1/Cip1) protein accumulation, all agents tended to decrease survival to a greater extent in the wild-type p53 lines compared to the mutant p53 lines. Cell death in the wild-tgpe p53 lines was associated with intracellular DNA degradation into oligonucleosomal sized DNA fragments, indicative of apoptosis. We also observed an inverse sensitivity relationship between nitrogen mustard/cisplatin and etoposide in the mutant p53 lines and this was found to correlate with topoisomerase II mRNA levels in the cells. Our results suggest that p53 gene status is an important determinant of both radio- and chemosensitivity in lymphoid cell lines and that p53 mutations are often associated with decreased sensitivity to DNA damaging agents. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD 21231. JOHNS HOPKINS UNIV,SCH MED,PROGRAM HUMAN GENET & MOLEC BIOL,BALTIMORE,MD 21231. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 34 TC 427 Z9 438 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1994 VL 54 IS 22 BP 5824 EP 5830 PG 7 WC Oncology SC Oncology GA PR217 UT WOS:A1994PR21700020 PM 7954409 ER PT J AU SHARMA, S STUTZMAN, JD KELLOFF, GJ STEELE, VE AF SHARMA, S STUTZMAN, JD KELLOFF, GJ STEELE, VE TI SCREENING OF POTENTIAL CHEMOPREVENTIVE AGENTS USING BIOCHEMICAL MARKERS OF CARCINOGENESIS SO CANCER RESEARCH LA English DT Article ID ORNITHINE DECARBOXYLASE ACTIVITY; MOUSE SKIN; TRANSFORMATION INVITRO; EPITHELIAL-CELLS; TUMOR PROMOTION; INHIBITION; INDUCTION; RAT; BENZOPYRENE; GLUTATHIONE AB Ninety potential chemopreventive agents were screened using 6 chemoprevention-associated biochemical end points. These compounds were tested using rodent (tracheal epithelial or liver) cells and human cells [neonatal foreskin fibroblasts, bronchial epithelial cells, or human leukemic cells (HL-60)]. The effects measured were: (a) inhibition of 12-O-tetraderanoylpherbol-13-acetate (TPA)-induced tyrosine kinase activity in HL-60 cells; (b) inhibition of TPA-induced ornithine decarboxylase (ODC) activity in rat tracheal epithelial cells; (c) inhibition of poly(ADP-ribose)polymerase in propane sultone-treated primary human fibroblasts; (d) inhibition of benzo[a]pyrene(B[a]P)-DNA binding in human bronchial epithelial cells; (e) induction of reduced glutathione in Buffalo rat liver cells; and (f) inhibition of TPA-induced free radical formation in primary human fibroblasts or HL-60 cells. Fifty compounds were highly effective in inhibiting TPA-induced tyrosine kinase activity. This assay identified compounds from a wide variety of chemical classes as effective inhibitors, including all the vitamins, retinoic acid analogues, protein kinase C inhibitors, and chemicals belonging to the amino acid category. Fifty-two chemicals were classified as highly positive compounds when examined for their ability to inhibit TPA-induced ODC activity. These agents showed a dose-dependent inhibition or inhibition at all doses. Retinoids, in general, exhibited strong inhibition of ODC activity. A category of compounds showing dose-dependent inhibition were the sulfur compounds, especially the thiols and thiones. Among the natural products, terpenes were strong inhibitors of ODC. Forty-seven compounds were classified as strong inhibitors of poly(ADP-ribose)polymerase. In the carcinogen-DNA binding inhibition assay, 21 compounds were identified as strong inhibitors, which include phenolic compounds as well as sulfur compounds. Vitamins and their analogues were also good inhibitors. Testing for induced glutathione yielded 19 compounds that were good inducers. Sulfur-containing compounds and most of the phenolic compounds were also inducers of glutathione. Twenty compounds were highly positive for inhibition of TPA-induced free radical formation. A significant number of phenolic and sulfur compounds were again strong oxygen radical scavengers. Some antiinflammatory agents were also identified as free radical inhibitors. In general, retinoids were quite active in all the assays. Eight compounds were positive in all of the six assays; these were vitamin C (ascorbic acid), bismuththiol, esculetin, etoperidone, folic acid, hydrocortisone, indole-3-carbinol, and tocopherol succinate. Agents that were positive in these assays may inhibit the carcinogenesis process by similar mechanisms in humans and are identified as candidates for development as chemopreventive agents. Agents capable of inhibiting multiple mechanisms are regarded as highly promising agents for cancer chemoprevention. C1 NCI,CHEMOPREVENT INVESTIGAT STUDIES BRANCH,BETHESDA,MD 20892. RP SHARMA, S (reprint author), MANTECH ENVIRONM TECHNOL INC,POB 12313,RES TRIANGLE PK,NC 27709, USA. FU NCI NIH HHS [N01-CN-95172-03] NR 40 TC 218 Z9 222 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 NOV 15 PY 1994 VL 54 IS 22 BP 5848 EP 5855 PG 8 WC Oncology SC Oncology GA PR217 UT WOS:A1994PR21700024 PM 7954413 ER PT J AU WU, JC MERLINO, G CVEKLOVA, K MOSINGER, B FAUSTO, N AF WU, JC MERLINO, G CVEKLOVA, K MOSINGER, B FAUSTO, N TI AUTONOMOUS GROWTH IN SERUM-FREE MEDIUM AND PRODUCTION OF HEPATOCELLULAR CARCINOMAS BY DIFFERENTIATED HEPATOCYTE LINES THAT OVEREXPRESS TRANSFORMING GROWTH-FACTOR-ALPHA SO CANCER RESEARCH LA English DT Article ID FACTOR-II; TRANSGENIC MICE; OVAL CELLS; C-MYC; LIVER-REGENERATION; EPITHELIAL-CELLS; RAT HEPATOCYTES; MOUSE; EXPRESSION; GENES AB Transforming growth factor alpha (TGF-alpha) is a polypeptide closely associated with hepatocyte proliferation in vivo and in vitro. In order to investigate the mechanisms by which TGF-alpha contributes to hepatocyte replication and transformation, me isolated hepatocytes from mice hearing a human TGF-alpha transgene and examined their growth properties and gene expression in defined, serum-free culture. The transgenic hepatocytes continued to overexpress human TGF-alpha mRNA and peptide, and were able to proliferate without exogenous growth factors in primary culture, in contrast to nontransgenic mouse hepatocytes. In short-term culture the transgenic hepatocytes underwent 1 wave of DNA replication at 72-96 h in culture before senescing, similar to nontransgenic hepatocytes supplemented with epidermal growth factor. Constitutive expression of TGF-alpha rendered the transgenic hepatocytes unresponsive to further grow,vth stimulation by exogenous TGF-alpha, as well as other mitogens such as epidermal growth factor and hepatocyte growth factor. However, it did not alter their sensitivity to growth inhibition by TGF beta 1, 2 and 3. The addition of nicotinamide to the culture medium enabled both transgenic and epidermal growth factor-supplemented normal hepatocytes to replicate repeatedly and survive for greater than or equal to 2 months in primary culture while maintaining differentiated traits. From these long-term primary cultures of transgenic and nontransgenic hepatocytes, me established immortalized cell lines (designated TAMH and NMB lines, respectively). Both lines continued to express differentiated adult hepatocytic markers such as albumin, alpha-1-antitrypsin, transferrin, and connexin 26 and 32 mRNAs, but also expressed mRNAs for the oncofetal markers alpha-fetoprotein and insulin-like growth factor II. Unlike the near-diploid NMH hepatocyte line, the transgenic TAMH hepatocyte line was quasi-tetraploid, strongly expressed human TGF-alpha mRNA, and was highly tumorigenic in nude mice. Well differentiated hepatocellular carcinomas developed in nude mice given injections of the TAMH line, and these appeared similar to the primary liver tumors seen in TGF-alpha transgenic mice with regard to histology and strong expression of mouse and human TGF-alpha, insulin-like growth factor II, and alpha-fetoprotein mRNAs. Our data show that TGF-alpha overexpression causes autonomous hepatocyte proliferation and contributes to neoplasia but that additional cellular alterations must occur for carcinogenesis. Inappropriate expression of insulin-like growth factor II may constitute one of these steps. The TGF-alpha transgenic mouse hepatocyte line TAMH appears to undergo transformation in a similar manner to that of hepatocytes overexpressing TGF-alpha in vivo, and should serve as an ideal system in which to study hepatocarcinogenesis. C1 BROWN UNIV,DEPT PATHOL & LAB MED,PROVIDENCE,RI 02912. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA 23226] NR 47 TC 71 Z9 71 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1994 VL 54 IS 22 BP 5964 EP 5973 PG 10 WC Oncology SC Oncology GA PR217 UT WOS:A1994PR21700041 PM 7525051 ER PT J AU PERSSON, B ZIGLER, JS JORNVALL, H AF PERSSON, B ZIGLER, JS JORNVALL, H TI A SUPER-FAMILY OF MEDIUM-CHAIN DEHYDROGENASES/REDUCTASES (MDR) - SUB-LINES INCLUDING XI-CRYSTALLIN, ALCOHOL AND POLYOL DEHYDROGENASES, QUINONE OXIDOREDUCTASES, ENOYL REDUCTASES, VAT-1 AND OTHER PROTEINS SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID GUINEA-PIG LENS; ZETA-CRYSTALLIN; HUMAN-LIVER; SORBITOL DEHYDROGENASES; HEREDITARY CATARACT; MOLECULAR-CLONING; GENE; SITE; TORPEDO; ENZYME AB The protein super-family of medium-chain alcohol dehydrogenases (and glutathione-dependent formaldehyde dehydrogenase), polyol dehydrogenases, threonine dehydrogenase, archaeon glucose dehydrogenase, and eye lens reductase-active zeta-crystallins also includes Escherichia coli quinone oxidoreductase, Torpedo VAT-1 protein, and enoyl reductases of mammalian fatty acid and yeast erythronolide synthases. In addition, two proteins with hitherto unknown function are shown to belong to this super-family of medium-chain dehydrogenases and reductases (MDR). Alignment of zeta-crystallins/quinone oxidoreductases/VAT-1 reveals 38 strictly conserved residues, of which approximately half are glycine residues, including those at several space-restricted turn positions and critical coenzyme-binding positions in the alcohol dehydrogenases. This indicates a conserved three-dimensional structure at the corresponding parts of these distantly related proteins and a conserved binding of a coenzyme in the two proteins with hitherto unknown function, thus ascribing a likely oxidoreductase function to these proteins. When all forms are aligned, including enoyl reductases, a zeta-crystallin homologue from Leishmania and the two proteins with hitherto unknown function, only three residues are strictly conserved among the 106 proteins characterised within the superfamily, and significantly these residues are all glycines, corresponding to Gly66, Gly86 and Gly201 of mammalian class I alcohol dehydrogenase. Notably, these residues are located in different domains. Hence, a distant origin and divergent functions, but related forms and interactions, appear to apply to the entire chains of the many prokaryotic and eukaryotic members. Additionally, in the zeta-crystallins/quinone oxidoreductases, a highly conserved tyrosine residue is found. This residue, in the three-dimensional structure of the homologous alcohol dehydrogenase, is positioned at the subunit cleft that contains the active site and could therefore be involved in catalysis. If so, this residue and its role may resemble the pattern of a conserved tyrosine residue in the different family of short-chain dehydrogenases/reductases (SDR). C1 EUROPEAN MOLEC BIOL LAB,HEIDELBERG,GERMANY. NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD. RP PERSSON, B (reprint author), KAROLINSKA INST,DEPT MED BIOCHEM & BIOPHYS,S-17177 STOCKHOLM,SWEDEN. NR 50 TC 136 Z9 137 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD NOV 15 PY 1994 VL 226 IS 1 BP 15 EP 22 DI 10.1111/j.1432-1033.1994.tb20021.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PR669 UT WOS:A1994PR66900002 PM 7957243 ER PT J AU KIESS, W TERRY, C BURGESS, WH LINDER, B LOPACZYNSKI, W NISSLEY, P AF KIESS, W TERRY, C BURGESS, WH LINDER, B LOPACZYNSKI, W NISSLEY, P TI INSULIN-LIKE GROWTH FACTOR-II IS A SUBSTRATE FOR DIPEPTIDYLPEPTIDASE-I (CATHEPSIN-C) - BIOLOGICAL PROPERTIES OF THE PRODUCT SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID MULTIPLICATION-STIMULATING ACTIVITY; IGF-II; RECEPTOR; RAT; BINDING; PURIFICATION; PROTEINS; CELLS; AFFINITY; MUTANTS AB We observed that the lysosomal enzyme, dipeptidylaminopeptidase I (DAP-I) caused the release of trichloroacetic-acid-soluble radioactivity from rat I-125-insulin-like growth factor-II (IGF-II). This activity could be blocked by dipeptide inhibitors of DAP-I, and was enhanced by chloride. Treatment of unlabeled rat IGF-II with DAP-I converted approximately 50% of the IGF-II to a species with a slightly shorter elution time on reverse-phase HPLC, whereas treatment of human IGF-II caused complete conversion to the species with the shorter elution time. Rat IGF-II purified from the rat BRL 3A cell line is a mixture of two molecules beginning with Ala-Tyr-Arg-Pro-Ser- and Tyr-Arg-Pro-Ser- [Marquardt, H., Todaro, G. J., Henderson, L. E. & Oroszlan, S. (1981) J. Biol. Chem. 256, 6859-6865] while human IGF-II begins with Ala-Tyr-Arg-Pro-Ser-. Determination of the N-terminal amino acid sequence of human IGF-II before and after digestion with DAP-I showed that DAPI cleaved Ala-Tyr, terminating at Arg-Pro-; the rat IGF-II species beginning with Tyr-Arg-Pro-Ser- was resistant to digestion. In order to compare DAP-I-treated IGF-II with native ICF-II for binding to IGF receptors and IGF-binding proteins and in a bioassay, rat and human IGF-II were treated with DAP-I and the digested and undigested species were isolated by reverse-phase HPLC. The IGF-II/mannose 6-phosphate receptor was purified from rat placental membranes, the IGF-I receptor. was solubilized from human placental membranes and IGF-binding proteins were partially purified from adult and three-day-old rat sera by sequential gel filtration on Sephadex G-200 (pH 8.0) and Sephadex G-50 (acid pH). The dose/response curves of the two IGF-II species were indistinguishable in radioreceptor assays utilizing the IGF-II/mannose 6-phosphate receptor and the IGF-I receptor and in IGF competitive binding assays utilizing partially purified IGF-binding proteins. The DAP-I-digested and native IGF-II species were also equipotent in stimulating [H-3]thymidine incorporation into DNA in the human osteosarcoma cell line, MG-63. We conclude that DAP-I cleaves an N-terminal dipeptide from IGF-II and that this does not result in a change in the biological activity of the molecule. C1 NICHHD,NCI,METAB BRANCH,BETHESDA,MD. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. AMER RED CROSS,JEROME H HOLLAND LAB,ROCKVILLE,MD. NR 26 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD NOV 15 PY 1994 VL 226 IS 1 BP 179 EP 184 DI 10.1111/j.1432-1033.1994.tb20039.x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PR669 UT WOS:A1994PR66900020 PM 7957246 ER PT J AU HEMESATH, TJ STEINGRIMSSON, E MCGILL, G HANSEN, MJ VAUGHT, J HODGKINSON, CA ARNHEITER, H COPELAND, NG JENKINS, NA FISHER, DE AF HEMESATH, TJ STEINGRIMSSON, E MCGILL, G HANSEN, MJ VAUGHT, J HODGKINSON, CA ARNHEITER, H COPELAND, NG JENKINS, NA FISHER, DE TI MICROPHTHALMIA, A CRITICAL FACTOR IN MELANOCYTE DEVELOPMENT, DEFINES A DISCRETE TRANSCRIPTION FACTOR FAMILY SO GENES & DEVELOPMENT LA English DT Article DE MICROPHTHALMIA; DIMERIZATION; DNA BINDING; M BOX; B-HLH-ZIP ID HELIX-LOOP-HELIX; DNA-BINDING ACTIVITY; C-MYC PROTEIN; LEUCINE-ZIPPER; NEGATIVE REGULATOR; MAST-CELLS; MAX; GENE; DIMERIZATION; HETERODIMERS AB The microphthalmia (mi) gene appears essential for pigment cell development and/or survival, based on its mutation in mi mice, It has also been linked to the human disorder Waardenburg Syndrome. The mi gene was recently cloned and predicts a basic/helix-loop-helix/leucine zipper (b-HLH-ZIP) factor with tissue-restricted expression. Here, we show that Mi protein binds DNA as a homo- or heterodimer with TEEB, TEE3, or TFEC, together constituting a new MiT family. Mi can also activate transcription through recognition of the M box, a highly conserved pigmentation gene promoter element, and may thereby determine tissue specific expression of pigmentation enzymes. Six mi mutations shown recently to cluster in the b-HLH-ZIP region produce surprising and instructive effects on DNA recognition and oligomerization. An alternatively spliced exon located outside of the b-HLH-ZIP region is shown to significantly modulate DNA recognition by the basic domain. These findings suggest that Mi's critical roles in melanocyte survival and pigmentation are mediated by MiT family interactions and transcriptional activities. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CO-74101] NR 58 TC 402 Z9 410 U1 1 U2 11 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 NOV 15 PY 1994 VL 8 IS 22 BP 2770 EP 2780 DI 10.1101/gad.8.22.2770 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA PU762 UT WOS:A1994PU76200009 PM 7958932 ER PT J AU KIRSCHNER, MA COPELAND, NG GILBERT, DJ JENKINS, NA AMARA, SG AF KIRSCHNER, MA COPELAND, NG GILBERT, DJ JENKINS, NA AMARA, SG TI MOUSE EXCITATORY AMINO-ACID TRANSPORTER EAAT2 - ISOLATION, CHARACTERIZATION, AND PROXIMITY TO NEUROEXCITABILITY LOCI ON MOUSE CHROMOSOME-2 SO GENOMICS LA English DT Article ID L-GLUTAMATE TRANSPORTER; GENETIC-LINKAGE MAP; NON-NMDA RECEPTORS; RAT-BRAIN; EPILEPSY; EXPRESSION; DISEASES; BLOCKADE; CLONING; RELEASE AB Glutamate and aspartate are excitatory neurotransmitters that have been implicated in a number of pathological states of the nervous system. Accumulation of extracellular excitatory amino acids can be cytotoxic and may also lower the seizure threshold in epilepsy. An important function of the Na+-dependent high-affinity excitatory amino acid transporter (EAAT) is the reuptake of secreted amino acid neurotransmitter, possibly maintaining extracellular amino acid concentrations at nontoxic and nonepileptogenic levels. We have isolated the mouse cDNA for EAAT2, a neurotransmitter transporter that shares extensive amino acid sequence homology with one of several previously cloned high-affinity glutamate transporters. The mouse EAAT2 amino acid sequence shares 99 and 97% identity with its rat and human homologues, respectively. It is expressed predominantly in the brain, where it may function as a glia-specific transporter. In an interspecific backcross analysis Eaat2 maps to the central region of mouse chromosome 2, where it is located near quantitative trait loci that modulate neuroexcitability and seizure frequency in mouse models of alcohol withdrawal and epilepsy. (C) 1994 Academic Press, Inc. C1 OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP KIRSCHNER, MA (reprint author), OREGON HLTH SCI UNIV,VOLLUM INST ADV BIOMED RES,3181 SAM JACKSON PK RD,PORTLAND,OR 97201, USA. FU NINDS NIH HHS [NS01342]; PHS HHS [N01-C0-74101] NR 34 TC 36 Z9 38 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1994 VL 24 IS 2 BP 218 EP 224 DI 10.1006/geno.1994.1609 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PX512 UT WOS:A1994PX51200003 PM 7698742 ER PT J AU ROTMAN, G SAVITSKY, K ZIV, Y COLE, CG HIGGINS, MJ BARAM, I DUNHAM, I BARSHIRA, A VANAGAITE, L QIN, SZ ZANG, JL NOWAK, NJ CHANDRASEKHARAPPA, SC LEHRACH, H AVIVI, L SHOWS, TB COLLINS, FS BENTLEY, DR SHILOH, Y AF ROTMAN, G SAVITSKY, K ZIV, Y COLE, CG HIGGINS, MJ BARAM, I DUNHAM, I BARSHIRA, A VANAGAITE, L QIN, SZ ZANG, JL NOWAK, NJ CHANDRASEKHARAPPA, SC LEHRACH, H AVIVI, L SHOWS, TB COLLINS, FS BENTLEY, DR SHILOH, Y TI A YAC CONTIG SPANNING THE ATAXIA-TELANGIECTASIA LOCUS (GROUP-A AND GROUP-C) AT 11Q22-Q23 SO GENOMICS LA English DT Article ID ARTIFICIAL-CHROMOSOME CLONES; POLYMERASE CHAIN-REACTION; INSITU SUPPRESSION HYBRIDIZATION; SEQUENCE-TAGGED SITES; HUMAN GENOME; ALU-PCR; REPETITIVE SEQUENCES; RAPID ISOLATION; DISEASE LOCUS; CELL HYBRIDS AB Ataxia-telangiectasia (A-T) is an autosomal recessive disease involving cerebellar degeneration, immunodeficiency, cancer predisposition, chromosomal instability and radiosensitivity. A-T is heterogeneous, and the majority of A-T cases are associated with two complementation groups, A and C. The ATA and ATC loci are closely linked at chromosome 11q22-q23. Recombination mapping and linkage disequilibrium analysis have confined both loci between the markers D11S1817 and D11S927, spaced approximately 3.5 Mb apart. Isolation in yeast artificial chromosomes of the genomic segment defined by these loci is essential to identify the gene or genes containing the ATA and ATC mutations. A YAC contig spanning 4.5 Mb, which includes the D11S1817-D11S927 interval, was constructed using two whole genome libraries (ICRF and St. Louis), and a chromosome 11-specific library. Construction of this contig was expedited by prior generation of a region-specific ICRF sublibrary using ALu-PCR products derived from a radiation hybrid. The contig was expanded further by screening the libraries with ALu-PCR products derived from YAC clones and with STSs from YAC ends. YAC clones were aligned by fingerprinting with moderately repetitive probes. (C) 1994 Academic Press, Inc. C1 SANGER CTR,CAMBRIDGE CB10 1RQ,ENGLAND. NEW YORK STATE DEPT HLTH,ROSWELL PK CANC INST,DEPT HUMAN GENET,BUFFALO,NY 14263. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. IMPERIAL CANC RES FUND,GENOME ANAL LAB,LONDON WC2A 3PX,ENGLAND. RP ROTMAN, G (reprint author), TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN GENET,IL-69978 RAMAT AVIV,ISRAEL. FU NHGRI NIH HHS [HG00359] NR 56 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1994 VL 24 IS 2 BP 234 EP 242 DI 10.1006/geno.1994.1611 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PX512 UT WOS:A1994PX51200005 PM 7698744 ER PT J AU WHITE, JK SHAW, MA BARTON, CH CERRETTI, DP WILLIAMS, H MOCK, BA CARTER, NP PEACOCK, CS BLACKWELL, JM AF WHITE, JK SHAW, MA BARTON, CH CERRETTI, DP WILLIAMS, H MOCK, BA CARTER, NP PEACOCK, CS BLACKWELL, JM TI GENETIC AND PHYSICAL MAPPING OF 2Q35 IN THE REGION OF THE NRAMP AND IL8R GENES - IDENTIFICATION OF A POLYMORPHIC REPEAT IN EXON-2 OF NRAMP SO GENOMICS LA English DT Article ID DISEASE RESISTANCE LOCUS; LSH-ITY-BCG; HUMAN INTERLEUKIN-8; NUCLEOTIDE-SEQUENCE; MOUSE CHROMOSOME-1; LINKAGE ANALYSIS; PROTEIN GENES; HUMAN GENOME; MAP; RECEPTOR AB Recent interest has focused on the region of conserved synteny between mouse chromosome 1 and human 2q33-q37, particularly over the region encoding the murine macrophage resistance gene Ity/Lsh/Bcg (candidate Nramp) and members of the Il8r interleukin-8 (IL8) receptor gene cluster. In this paper, identification of a restriction fragment length polymorphism in the IL8RB gene in 35 pedigrees previously typed for markers in the 2q33-q37 interval provided evidence (lod scores > 3) for linkage between IL8RB and the 2q34-q35 markers FN1, TNP1, VIL1, and DES. Physical mapping, using yeast artificial chromosomes isolated with VIL1, confirmed that IL8RA, IL8RB, and the IL8RB pseudogene map within the NRAMP-VIL1 interval, with the physical distance (155 kb) from 5' LSH to 3' VIL1 representing approximate to 3-fold that observed in the mouse. Partial sequencing of NRAMP confirmed the presence of the N-terminal proline/serine-rich putative SH3 binding domain in exon 2 of the human gene, Further analysis of Brazilian leprosy and visceral leishmaniasis pedigrees identified a rare second allele varying in a 9-nucleotide repeat motif of the exon 2 sequence but segregating independently of the disease phenotype. (C) 1994 Academic Press, Inc. C1 UNIV CAMBRIDGE, ADDENBROOKES HOSP, SCH CLIN, DEPT MED, CAMBRIDGE CB2 2QQ, ENGLAND. IMMUNEX RES & DEV CORP, SEATTLE, WA 98101 USA. NCI, GENET LAB, BETHESDA, MD 20892 USA. UNIV CAMBRIDGE, DEPT PATHOL, CAMBRIDGE CB2 1QP, ENGLAND. RI Peacock, Christopher/A-4052-2012; Blackwell, Jenefer/H-3015-2015 FU Wellcome Trust NR 38 TC 63 Z9 63 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD NOV 15 PY 1994 VL 24 IS 2 BP 295 EP 302 DI 10.1006/geno.1994.1619 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PX512 UT WOS:A1994PX51200013 PM 7698752 ER PT J AU GAUTAM, M MUDD, J COPELAND, NG GILBERT, DJ JENKINS, NA MERLIE, JP AF GAUTAM, M MUDD, J COPELAND, NG GILBERT, DJ JENKINS, NA MERLIE, JP TI CHARACTERIZATION AND MAPPING OF THE RAPSN GENE ENCODING THE 43-KDA ACETYLCHOLINE RECEPTOR-ASSOCIATED PROTEIN SO GENOMICS LA English DT Note ID LINKAGE MAP; MOUSE AB We have cloned and characterized mouse genomic DNA containing the gene for the 43-kDa acetylcholine receptor-associated protein. The gene extends over 12 kb and consists of 8 exons, RNase protection and sequence analysis have been used to define the intron/exon boundaries including 174 and 214 bp of 5' and 3' untranslated sequence in exons 1 and 8, respectively, Interestingly, the exon/intron organization is consistent with structural domains predicted from amino acid sequence conservation among 3 species of 43K. Finally, the 43K locus, designated Rapsn, has been mapped to the central region of mouse chromosome 2. (C) 1994 Academic Press, Inc. C1 WASHINGTON UNIV,SCH MED,DEPT MOLEC BIOL & PHARMACOL,ST LOUIS,MO 63110. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. OI Gautam, Medha/0000-0002-5418-4322 FU NCI NIH HHS [N01-CO-74101] NR 11 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1994 VL 24 IS 2 BP 366 EP 369 DI 10.1006/geno.1994.1629 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PX512 UT WOS:A1994PX51200023 PM 7698761 ER PT J AU ROSSO, P TERRACINI, B FEARS, TR JANKOVIC, M BELLANI, FF ARRIGHINI, A CARLI, M DIMONTEZEMOLO, LC GARRE, ML GUAZZELLI, C IZZI, G LOIACONO, G MANCINI, A TAMARO, P TESTI, AM MASERA, G HAUPT, R AF ROSSO, P TERRACINI, B FEARS, TR JANKOVIC, M BELLANI, FF ARRIGHINI, A CARLI, M DIMONTEZEMOLO, LC GARRE, ML GUAZZELLI, C IZZI, G LOIACONO, G MANCINI, A TAMARO, P TESTI, AM MASERA, G HAUPT, R TI 2ND MALIGNANT-TUMORS AFTER ELECTIVE END OF THERAPY FOR A FIRST CANCER IN CHILDHOOD - A MULTICENTER STUDY IN ITALY SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID LONG-TERM SURVIVORS; HODGKINS-DISEASE; THYROID-CANCER; 2ND; RISK; NEOPLASMS; LEUKEMIA; CHILDREN AB To evaluate the incidence of second malignant tumors in a cohort of subjects previously treated for childhood cancer, we analyzed data from the Off-Therapy Registry (OTR) of the Italian Association of pediatric Hematology/Oncology, which collects information on children treated for Hodgkin's disease, non-Hodgkin's lymphoma, Wilms' tumor, acute lymphoblastic leukemia (ALL) and acute non-lymphatic leukemia and who had been removed from treatment in the absence of clinical signs of disease, i.e. the off-therapy stage. Second malignant tumors (SMT), diagnosed before December 31, 1988, were identified through a special enquiry to the 36 institutions cooperating in the registry. Observed cases were compared to expected numbers estimated from age- and sex-specific incidence rates derived from the Cancer Registry of the Province of Varese. In a total of 3,3 10 study subjects, 27 SMTs have been registered. The Cumulative Risk (CR) of SMT was 2.9% 15 years after the end of treatment and the Standard Incidence Ratio (SIR) was 10.8. The ALL sub-cohort had the highest risk of SMT (SIR 13.6) and 9 cases of CNS tumor occurred in this group (SIR 58.9). All 9 had received prophylactic cranial radiotherapy (CRT) and 5 had been treated on one protocol, characterized by low-dose intrathecal methotrexate (IT MTX) given monthly for 2 years after CRT. The Off-Therapy Registry has unique criteria for inclusion; direct comparisons with similar studies are therefore somewhat problematic. However, our data suggest that the risk of SMT in childhood ALL cancer survivors may be greater than previously reported, and that CNS tumors are the most common SMT in this group. The administration schedule of IT MTX may be an important risk factor. (C) 1994 Wiley-Liss, Inc. C1 UNIV TURIN,DIV PEDIAT ONCOL,TURIN,ITALY. UNIV TURIN,DEPT BIOMED SCI & HUMAN ONCOL,I-10124 TURIN,ITALY. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. UNIV MILAN,DEPT PEDIAT,MONZA,ITALY. IST NAZL TUMORI,DEPT PEDIAT,I-20133 MILAN,ITALY. UNIV BRESCIA,DEPT PEDIAT,BRESCIA,ITALY. UNIV PADUA,DEPT PEDIAT,PADUA,ITALY. G GASLINI INST CHILDREN,DEPT PEDIAT HEMATOL ONCOL,GENOA,ITALY. UNIV FLORENCE,DEPT PEDIAT,FLORENCE,ITALY. UNIV PARMA,DEPT PEDIAT,I-43100 PARMA,ITALY. UNIV BARI,DEPT PEDIAT,BARI,ITALY. UNIV BOLOGNA,DEPT PEDIAT,BOLOGNA,ITALY. UNIV TRIESTE,DEPT PEDIAT,TRIESTE,ITALY. UNIV ROME,DIV HEMATOL,ROME,ITALY. RI Haupt, Riccardo/C-2237-2012 NR 25 TC 46 Z9 47 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 1994 VL 59 IS 4 BP 451 EP 456 DI 10.1002/ijc.2910590402 PG 6 WC Oncology SC Oncology GA QF964 UT WOS:A1994QF96400001 PM 7960210 ER PT J AU CHOW, WH MCLAUGHLIN, JK LINET, MS NIWA, S MANDEL, JS AF CHOW, WH MCLAUGHLIN, JK LINET, MS NIWA, S MANDEL, JS TI USE OF ANALGESICS AND RISK OF RENAL-CELL CANCER SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID KIDNEY CANCER; COHORT AB Although heavy or long-term use of analgesics has been related to risk of renal cell cancer in several studies, evidence for such an association remains inconclusive. In a population-based case-control study including 440 renal cell cancer cases, spouses of an additional 151 cases, and 691 controls, we assessed renal cell cancer risk associated with lifetime consumption among those who reported during in-person interviews regular (at least 2 or more times per week for I month or longer) use of analgesics. Odds ratios (OR) were computed using logistic regression analyses. No excess risk was associated with regular use of aspirin, acetaminophen, phenacetin or combinations of these agents, nor did risks rise with increasing cumulative intake of these analgesics. A non-significant increased risk (OR = 2.1, 95% CI = 0.6-6.9) was observed among women who used only acetaminophen-containing analgesics, but little excess was seen in men. Earlier studies reported a link to phenacetin-containing analgesics, but no one reported exclusive use of phenacetin-containing drugs in our study. The findings suggest that use of analgesics is not likely to play a major role in renal cell cancer development and that for cases diagnosed in the late 1980s or later, after the earlier withdrawal of phenacetin containing drugs from the market, a hazard from this analgesic no longer exists. (C) 1994 Wiley-Liss, Inc. C1 WESTAT CORP,ROCKVILLE,MD. UNIV MINNESOTA,SCH PUBL HLTH,DIV ENVIRONM & OCCUPAT HLTH,MINNEAPOLIS,MN 55455. RP CHOW, WH (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BIOSTAT BRANCH,6130 EXECUT BLVD,EPN 415,ROCKVILLE,MD 20852, USA. NR 21 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 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 1994 VL 59 IS 4 BP 467 EP 470 DI 10.1002/ijc.2910590406 PG 4 WC Oncology SC Oncology GA QF964 UT WOS:A1994QF96400005 PM 7960214 ER PT J AU LEVINE, PH CLEGHORN, F MANNS, A JAFFE, ES NAVARROROMAN, L BLATTNER, WA HANCHARD, B DEOLIVEIRA, MS MATUTES, E CATOVSKY, D SHIMOYAMA, M TAJIMA, K SONODA, S YAMAGUCHI, K TAKATSUKI, K AF LEVINE, PH CLEGHORN, F MANNS, A JAFFE, ES NAVARROROMAN, L BLATTNER, WA HANCHARD, B DEOLIVEIRA, MS MATUTES, E CATOVSKY, D SHIMOYAMA, M TAJIMA, K SONODA, S YAMAGUCHI, K TAKATSUKI, K TI ADULT T-CELL LEUKEMIA-LYMPHOMA - A WORKING POINT-SCORE CLASSIFICATION FOR EPIDEMIOLOGIC STUDIES SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NON-HODGKIN LYMPHOMA; HTLV-I; C RETROVIRUS; MALIGNANCIES; ANTIBODIES; PATIENT; SPECTRUM; FEATURES; BLACKS; ATL AB Adult T-cell leukemia/lymphoma (ATL) is a malignancy that occurs most frequently in south-western japan and the Caribbean basin. The primary etiologic agent for this disease, human T-lymphotropic virus type I (HTLV-I), is endemic in these areas. Only a small percentage of individuals infected with HTLV-I develop ATL. The factors that determine the development of malignant disease as an outcome of HTLV-I infection in an individual are unknown. ATL is histopathologically heterogeneous and firm diagnosis is made on the contribution of clinical, laboratory and histopathologic features. The wide variety of laboratory assays available to geographically diverse populations has led to a need to standardize the criteria for determining the diagnosis of this disease for epidemiologic studies. This report summarizes current information regarding ATL and proposes a classification facilitating comparison of case series in geographically and ethnically different populations. (C) 1994 Wiley-Liss, Inc. C1 UNIV W INDIES,DEPT PATHOL,KINGSTON 7,JAMAICA. INST NACL CANC,VERMELHO,BRAZIL. ROYAL MARSDEN HOSP,LONDON SW3 6JJ,ENGLAND. ROYAL MARSDEN HOSP,SURREY,ENGLAND. NATL CANC CTR,TOKYO,JAPAN. AICHI CANC CTR,NAGOYA,AICHI 464,JAPAN. KAGOSHIMA UNIV,KAGOSHIMA 890,JAPAN. KUMAMOTO UNIV,SCH MED,KUMAMOTO 860,JAPAN. RP LEVINE, PH (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 434,BETHESDA,MD 20892, USA. RI Pombo-de-Oliveira, Maria S./I-8884-2014 OI Pombo-de-Oliveira, Maria S./0000-0003-3986-8993 NR 33 TC 27 Z9 28 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 1994 VL 59 IS 4 BP 491 EP 493 DI 10.1002/ijc.2910590410 PG 3 WC Oncology SC Oncology GA QF964 UT WOS:A1994QF96400009 PM 7960218 ER PT J AU MCGINN, CJ MILLER, EM LINDSTROM, MJ KUNUGI, KA JOHNSTON, PG KINSELLA, TJ AF MCGINN, CJ MILLER, EM LINDSTROM, MJ KUNUGI, KA JOHNSTON, PG KINSELLA, TJ TI THE ROLE OF CELL-CYCLE REDISTRIBUTION IN RADIOSENSITIZATION - IMPLICATIONS REGARDING THE MECHANISM OF FLUORODEOXYURIDINE RADIOSENSITIZATION SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 11-15, 1993 CL NEW ORLEANS, LA SP AMER SOC THERAPEUT RADIOL & ONCOL DE CELL SYNCHRONY; RADIOSENSITIZATION; FLUOROPYRIMIDINES; COLCEMID; MIMOSINE; THYMIDYLATE SYNTHASE ID COLON CANCER-CELLS; THYMIDYLATE SYNTHASE; RADIATION SENSITIVITY; 5-FLUOROURACIL; CHEMOTHERAPY; CARCINOMA; RADIOTHERAPY; INHIBITION; MODULATION; INVITRO AB Purpose: Radiosensitization has previously been demonstrated in a human colon cancer cell line (HT-29) following a 2 h exposure to low, clinically relevant concentrations (0.05-0.5 mu M) of fluorodeoxyuridine (FdUrd) (15). The sensitizer enhancement ratio value (measured at 10% survival) plateaued at approximate to 1.7 between 16 and 32 h following removal of drug. Parallel studies investigating the effect of FdUrd on the distribution of cells throughout the cell cycle found that the percentage of cells in early S-phase increased to approximate to 70% during the same period that maximal radiosensitization was noted. As a follow-up to these findings, experiments have been designed to investigate the contribution of this early S-phase delay to radiosensitization. Methods and Materials: Synchronized populations of HT-29 cells have been obtained with three separate techniques. Two involve the induction of a reversible metaphase arrest (with high pressure N2O or colcemid) followed by a shakeoff of mitotic cells. The third uses a plant amino acid, mimosine, to induce a reversible block at the G(1)/S boundary. Flow cytometry was used to analyze the degree of synchrony based on bromodeoxyuridine (BrdUrd) uptake and propidium iodide (PI) staining. Radiation survival curves were obtained on these synchronized populations to investigate changes in radiosensitivity through the cell cycle. Additionally, levels of thymidylate synthase (TS), the primary target of FdUrd cytotoxicity, were measured in each phase of the cell cycle using the TS 106 monoclonal antibody against human TS. Results: Synchronization with mitotic shakeoff produced relatively pure populations of cells in G(1); however, the degree of synchrony in early S-phase was limited both by cells remaining in GI and by cells progressing into late S-phase. These techniques failed to reveal increased radiosensitivity in early S-phase at 10% survival. An 18 h exposure to mimosine resulted in populations that more closely resembled the early S-phase enrichment following FdUrd exposure and revealed increased radiosensitivity during early S-phase. TS levels were noted to be only 1.3 times higher in S phase than in G(0)/G(1). Conclusion: Radiation survival data from cells synchronized with mitotic shakeoff techniques suggest that early S-phase delay is unlikely to be the primary mechansim of FdUrd radiosensitizatian. In contrast, the increased sensitivity seen in early S-phase with mimosine synchronized cells is similar to that seen with FdUrd. Although confounding biochemical pertubations cannot be ruled out, these data continue to suggest an association between early S-phase enrichment and radiosensitization. The significance of TS inhibition as a mechanism of FdUrd radiosensitization remains unclear. C1 UNIV WISCONSIN,SCH MED,DEPT HUMAN ONCOL,MADISON,WI 53792. UNIV WISCONSIN,SCH MED,DEPT BIOSTAT,MADISON,WI 53792. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. FU NCI NIH HHS [CA52686, 5T32CA09614] NR 36 TC 37 Z9 40 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. PD NOV 15 PY 1994 VL 30 IS 4 BP 851 EP 859 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PR109 UT WOS:A1994PR10900016 PM 7960987 ER PT J AU WILT, SR BURGESS, AC NORMOLLE, DP TRENT, JM LAWRENCE, TS AF WILT, SR BURGESS, AC NORMOLLE, DP TRENT, JM LAWRENCE, TS TI USE OF FLUORESCENCE IN-SITU HYBRIDIZATION (FISH) TO STUDY CHROMOSOMAL DAMAGE-INDUCED BY RADIATION AND BROMODEOXYURIDINE IN HUMAN COLON-CANCER CELLS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 11-15, 1993 CL NEW ORLEANS, LA SP AMER SOC THERAPEUT RADIOL & ONCOL DE RADIOSENSITIZERS; BROMODEOXYURIDINE; FLUORESCENCE IN SITU HYBRIDIZATION; CHROMOSOME ABERRATIONS ID BREAKAGE; IDENTIFICATION; ABERRATIONS; INTERPHASE AB Purpose: Although the thymidine analog radiation sensitizer bromodeoxyuridine (BrdUrd) increases radiation-induced chromosomal aberrations, it is not known whether these aberrations are uniformly distributed among chromosomes. Using fluorescence in situ hybridization, we carried out a study to test the hypothesis that BrdUrd-induced radiosensitization may be mediated by nonuniform chromosomal damage. Methods and Materials: Log phase HT29 human colon cancer cells were exposed to 10 mu M BrdUrd (or media alone) for one cell cycle, and the G1 cells were separated by centrifugal elutriation. Half of the control and BrdUrd samples were irradiated with 8 Gy. Cells were then incubated for 24-28 h, and metaphase spreads were prepared. Fluorescence in situ hybridization was performed using paint probes for chromosomes 1 and 4. Results: We found that radiation induced 0.20 aberrations per chromosome in chromosome 4. Based on the ratio of the relative lengths of chromosome 1-4 (1.34), it was predicted that chromosome 1 would have approximate to 0.26 aberrations per chromosome. However, me observed 0.39 aberrations per chromosome 1, which was significantly greater than the predicted (p < 0.001 by chi-square). Incubation with BrdUrd prior to irradiation significantly increased the aberrations found in chromosome 1 (by a factor of 1.4) and chromosome 4 (by a factor of 1.9) compared to radiation alone (p < 0.001 for both chromosome 1 and 4). Conclusion: This study demonstrates that individual chromosomes in human colon cancer cells show significantly different rates of aberration after irradiation. Furthermore, the BrdUrd-mediated increase in radiation-induced chromosomal aberrations may not be uniform among chromosomes. C1 UNIV MICHIGAN,MED CTR,SCH MED,DEPT RADIAT ONCOL,DIV CANC BIOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,MED CTR,SCH PUBL HLTH,DEPT BIOSTAT,ANN ARBOR,MI. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. OI Normolle, Daniel/0000-0001-8675-5014 FU NCI NIH HHS [CA 42761, CA 46592, CA 53440] NR 20 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 1994 VL 30 IS 4 BP 861 EP 866 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PR109 UT WOS:A1994PR10900017 PM 7960988 ER PT J AU HERSCHER, LL KRISHNA, MC COOK, JA COLEMAN, CN BIAGLOW, JE TUTTLE, SW GONZALEZ, FJ MITCHELL, JB AF HERSCHER, LL KRISHNA, MC COOK, JA COLEMAN, CN BIAGLOW, JE TUTTLE, SW GONZALEZ, FJ MITCHELL, JB TI PROTECTION AGAINST SR-4233 (TIRAPAZAMINE) AEROBIC CYTOTOXICITY BY THE METAL CHELATORS DESFERRIOXAMINE AND TIRON SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE SR 4233; DESFERRIOXAMINE; TIRON; AEROBIC CYTOTOXICITY ID HYPOXIC CELL CYTOTOXIN; SR-4233; AGENT; REDUCTION; RADIOSENSITIZATION; ADRIAMYCIN; ENZYMOLOGY; TOXICITY; ICRF-198 AB Purpose: Metal chelating agents and antioxidants were evaluated as potential protectors against aerobic SR 4233 cytotoxicity in Chinese hamster V79 cells. The differential protection of aerobic and hypoxic cells by two metal chelators, desferrrioxamine and Tiron, is discussed in the context of their potential use in the on-going clinical trials with SR 4233. Methods and Materials: Cytotoxicity was evaluated using clonogenic assay. SR 4233 exposure was done in glass flasks as a function of time either alone or in the presence of the following agents: superoxide dismutase, catalase, 5,5-dimethyl-1-pyrroline, Trolox, ICRF-187, desferrioxamine, Tiron (1,2-dihydroxybenzene-3,5-disulfonate), and ascorbic acid. Experiments done under hypoxic conditions were carried out in specially designed glass flasks that were gassed with humidified nitrogen/carbon dioxide mixture and with a side-arm reservoir from which SR 4233 was added to cell media after hypoxia was obtained. Electron paramagnetic resonance studies were also performed. Results: Electron paramagnetic resonance and spectrophotometry experiments suggest that under aerobic conditions SR 4233 undergoes futile redox cycling to produce superoxide. Treatment of cells during aerobic exposure to SR 4233 with the enzymes superoxide dismutase and catalase, the spin trapping agent DMPO, the water-soluble vitamin E analog Trolox, and the metal chelator ICRF-187 provided little or no protection against aerobic SR 4233 cytotoxicity. However, two other metal chelators, desferrioxamine and Tiron, afforded significant protection against aerobic SR 4233 cytotoxicity (protection factors at 50% survival were 3.8 and 3.1, respectively), while exhibiting minimal protection to hypoxic cells treated with SR 4233. Conclusions: One potential mechanism of aerobic cytotoxicity is redox cycling of SR 4233 with molecular oxygen resulting in several potentially toxic oxidative species that overburden the intrinsic intracellular detoxification systems such as superoxide dismutase, catalase, and glutathione peroxidase. This study identifies two metal chelating agents, desferrioxamine and Tiron, that were able to protect against aerobic but not hypoxic SR 4233 cytotoxicity. C1 NCI,RADIAT ONCOL BRANCH,RADIAT BIOL SECT,BETHESDA,MD 20892. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. UNIV PENN,DEPT RADIAT ONCOL,PHILADELPHIA,PA 19104. FU NCI NIH HHS [CA44982] NR 23 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 1994 VL 30 IS 4 BP 879 EP 885 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PR109 UT WOS:A1994PR10900020 PM 7960991 ER PT J AU NAHIN, RL BYERS, MR AF NAHIN, RL BYERS, MR TI ADJUVANT-INDUCED INFLAMMATION OF RAT PAW IS ASSOCIATED WITH ALTERED CALCITONIN-GENE-RELATED PEPTIDE IMMUNOREACTIVITY WITHIN CELL-BODIES AND PERIPHERAL ENDINGS OF PRIMARY AFFERENT NEURONS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE DORSAL ROOT GANGLIA; IMMUNOCYTOCHEMISTRY; SCIATIC NERVE; PAIN; MAST CELLS ID PRIMARY SENSORY NEURONS; DORSAL-ROOT GANGLIA; PREPROTACHYKININ MESSENGER-RNA; SCIATIC-NERVE SECTION; I PROJECTION NEURONS; SUBSTANCE-P; SPINAL-CORD; HUMAN-SKIN; TRANSGANGLIONIC TRANSPORT; NEUROGENIC INFLAMMATION AB Local inflammation is associated with profound changes in the biochemistry and physiology of primary afferent nerve fibers and the central neurons responding to their signals. In some tissues, the neural changes accompanying inflammation include sprouting and cytochemical changes that are delayed several days after the initial injury. In the present study, we have analyzed the effect of complete Freund's adjuvant (CFA)-induced inflammation in the rat paw on calcitonin gene-related peptide (CGRP) immunoreactivity (IR) in dorsal root ganglia and within tissue of the inflamed paw. We quantified the CGRP-IR within the L(1), L(4), and L(6) ganglia, and in ankle, midpaw, joint and toe tissues. Analysis of the processed tissue revealed a significant increase in the percentage of CGRP-positive cells within Lq dorsal root ganglia ipsilateral to an inflamed hindpaw six days after administration of CFA. There was a parallel increase in the number and staining density of detectable CGRP-immunoreactive fibers in periarticular and perivascular tissues of the inflamed digits and inflamed ankle. The other tissues of the paw, including epidermis and the regions surrounding the abcesses, did not have detectable changes in CGRP-immunoreactive fibers, despite tissue swelling and dystrophic changes in the foot that included loss of mast cell staining. These data demonstrate that local inflammation of the rat paw has delayed influences on the peripheral nervous system, in addition to a number of previously characterized acute effects. The alterations of CGRP-IR were focused around specific tissue types, such as joints and subdermal blood vessels, and absent from others, such as epidermis or in the areas surrounding abscesses. This suggests production of local factors within reactive tissues that selectively interact with nerve fibers to induce changes in CGRP-IR within the fibers. (C) 1994 Wiley-Liss, Inc. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT ANESTHESIOL,SEATTLE,WA 98195. FU NIDCR NIH HHS [DE05159] NR 67 TC 38 Z9 39 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 15 PY 1994 VL 349 IS 3 BP 475 EP 485 DI 10.1002/cne.903490311 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA QF843 UT WOS:A1994QF84300010 PM 7852637 ER PT J AU GU, JJ HARRISS, JV OZATO, K GOTTLIEB, PD AF GU, JJ HARRISS, JV OZATO, K GOTTLIEB, PD TI INDUCTION BY CONCANAVALIN-A OF SPECIFIC MESSENGER-RNAS AND CYTOLYTIC FUNCTION IN A CD8-POSITIVE T-CELL HYBRIDOMA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTE-T; DNA FRAGMENTATION; C-MYC; NUCLEOTIDE-SEQUENCE; GRANZYME-A; PROTEIN; EXPRESSION; GENE; GRANULES; BINDING AB A previous report from this laboratory described the production of CD8(+), class I-specific T cell hybridomas which developed specific cytolytic activity and the ability to secrete IL-2 upon Con A or specific Ag stimulation. Unlike normal lymphocytes or long-term CTL lines for which exposure to Ag triggers both differentiation and proliferation, T cell hybridoma lines can be activated functionally against a background of continuous proliferation. They therefore provide a unique system with which to study the molecular events involved in the induction of cytolytic function. The expression of mRNA from a series of genes was evaluated by Northern hybridization at various times after Con A stimulation of the H-2L(d)-specific CD8(+) 3D9 hybridoma. Induction of the c-fos proto-oncogene by 45 min poststimulation was followed shortly by c-myc induction. Perforin mRNA was expressed at a low level in the unstimulated hybridomas, but was down-regulated upon Con A stimulation to levels undetectable by PCR. Interestingly, production of granzyme A mRNA was strongly induced by 45 min after Con A stimulation. In the CD8(+) RT-1.3G3 hybridoma, which is nonlytic and specific for the HIV-1 envelope glycoprotein, c-fos but not granzyme A mRNA was induced by 45 min poststimulation, and no granzyme A mRNA was detectable at any time. Thus, a significant role for granzyme A in the induction of cytolytic activity is suggested. Cytolysis by the 3 D9 hybridoma involved both target cell membrane damage and DNA fragmentation, and both Ca2+-dependent and Ca2+-independent cytolysis were observed. Although TNF-alpha mRNA was induced by 4 h poststimulation, Ab to TNF-alpha failed to inhibit the Ca2+-independent lysis observed, leaving the basis for the observed Ca2+-independent lysis unexplained. C1 UNIV TEXAS,DEPT MICROBIOL,AUSTIN,TX 78712. NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA30147] NR 61 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1994 VL 153 IS 10 BP 4408 EP 4417 PG 10 WC Immunology SC Immunology GA PR222 UT WOS:A1994PR22200007 PM 7963518 ER PT J AU RODRIGUES, M LI, SQ MURATA, K RODRIGUEZ, D RODRIGUEZ, JR BACIK, I BENNINK, JR YEWDELL, JW GARCIASASTRE, A NUSSENZWEIG, RS ESTEBAN, M PALESE, P ZAVALA, F AF RODRIGUES, M LI, SQ MURATA, K RODRIGUEZ, D RODRIGUEZ, JR BACIK, I BENNINK, JR YEWDELL, JW GARCIASASTRE, A NUSSENZWEIG, RS ESTEBAN, M PALESE, P ZAVALA, F TI INFLUENZA AND VACCINIA VIRUSES EXPRESSING MALARIA CD8(+) T-CELL AND B-CELL EPITOPES - COMPARISON OF THEIR IMMUNOGENICITY AND CAPACITY TO INDUCE PROTECTIVE IMMUNITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IFN-GAMMA; TH2 CELLS; IMMUNIZATION; ANTIBODIES; INFECTION; MUTANTS; PROTEIN; IL-5; CD4+ AB We compared the effectiveness of several recombinant influenza and vaccinia viruses to induce a malaria-specific immune response. The CD8(+) T cell epitope of the circumsporozoite (CS) protein of Plasmodium yoelii, a rodent malaria parasite, was expressed in two distinct influenza virus proteins, the hemagglutinin and the neuraminidase. These recombinant viruses were found to be equally efficient at inducing CS-specific CD8(+) T cells in mice. A third recombinant virus, which expresses a B cell epitope of the CS protein, induced neutralizing anti-sporozoite Abs. Expression in the same recombinant virus of the CD8(+) T cell epitope and of the B cell epitope did not impair the capacity of this recombinant virus to induce malaria-specific CD8(+) T cells and neutralizing Abs. The immunogenicity of a vaccinia virus, expressing the entire CS protein, was compared with that of a highly attenuated vaccinia strain expressing the same protein and with that of another vaccinia virus expressing only the CD8(+) T cell epitope. All three vaccinia virus recombinants elicited CS-specific CD8(+) cells and a potent inhibitory response against pre-erythrocytic stages of malaria parasites. Optimal levels of anti-sporozoite Abs, inhibition of liver stage development, and protection against malaria infection resulted from repeatedly immunizing the animals with recombinant influenza viruses followed by boosters with a recombinant vaccinia virus. These findings support the concept that live viral vectors expressing the appropriate proteins and/or epitopes can be used as promising vaccine candidates. C1 NYU,SCH MED,DEPT MED & MOLEC PARASITOL,NEW YORK,NY 10010. UNIV SALAMANCA,DEPT BIOCHEM & MOLEC BIOL,E-37008 SALAMANCA,SPAIN. CUNY MT SINAI SCH MED,DEPT MICROBIOL,NEW YORK,NY 10029. SUNY HLTH SCI CTR,DEPT BIOCHEM MICROBIOL & IMMUNOL,BROOKLYN,NY 11203. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012; Rodrigues, Mauricio/B-8512-2012 FU NIAID NIH HHS [AI 11823, AI 32361, AI-24460] NR 31 TC 96 Z9 97 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1994 VL 153 IS 10 BP 4636 EP 4648 PG 13 WC Immunology SC Immunology GA PR222 UT WOS:A1994PR22200031 PM 7525709 ER PT J AU HAMAWY, MM SWAIM, WD MINOGUCHI, K DEFEIJTER, AW MERGENHAGEN, SE SIRAGANIAN, RP AF HAMAWY, MM SWAIM, WD MINOGUCHI, K DEFEIJTER, AW MERGENHAGEN, SE SIRAGANIAN, RP TI THE AGGREGATION OF THE HIGH-AFFINITY IGE RECEPTOR INDUCES TYROSINE PHOSPHORYLATION OF PAXILLIN, A FOCAL ADHESION PROTEIN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; MAST-CELLS; SIGNAL TRANSDUCTION; IMMUNOGLOBULIN-E; HISTAMINE-RELEASE; 2H3 CELLS; CALCIUM SIGNAL; RBL-2H3 CELLS; 3T3 CELLS; KINASE-C AB Tyrosine phosphorylation of proteins is an essential component of high affinity IgE receptor (Fc epsilon RI) signaling and secretion. This signaling and secretion is also dependent on the organization of the cytoskeleton. Here we report that the aggregation of Fc epsilon RI on rat basophilic leukemia cells results in tyrosine phosphorylation of the cytoskeletal protein, paxillin. Tyrosine phosphorylation of paxillin is a relatively late event after Fc epsilon RI aggregation. Both the direct increase in intracellular Ca2+ with calcium ionophore and the activation of protein kinase C (PKC) with PMA induced tyrosine phosphorylation of paxillin. The optimal tyrosine phosphorylation of paxillin by Fc epsilon RI aggregation required PKC and extracellular Ca2+. However, there was also Fc epsilon RI-mediated tyrosine phosphorylation of paxillin independent of Ca2+ influx or PKC activation. By fluorescent microscopy, cell stimulation induced a redistribution of paxillin toward the periphery of the cells. Although Fc epsilon RI aggregation induced tyrosine phosphorylation of paxillin in nonadherent cells, adherence markedly enhanced this phosphorylation. Together, the data suggest a role for paxillin in Fc epsilon RI signaling. C1 MERIDIAN INSTRUMENTS INC,OKEMOS,MI 48864. RP HAMAWY, MM (reprint author), NIDR,IMMUNOL LAB,BLDG 10,RM 1N106,BETHESDA,MD 20892, USA. NR 51 TC 32 Z9 32 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1994 VL 153 IS 10 BP 4655 EP 4662 PG 8 WC Immunology SC Immunology GA PR222 UT WOS:A1994PR22200033 PM 7963537 ER PT J AU SHI, XL AF SHI, XL TI GENERATION OF SO3- AND OH RADICALS IN SO3(2-) REACTIONS WITH INORGANIC ENVIRONMENTAL-POLLUTANTS AND ITS IMPLICATIONS TO SO3(2-) TOXICITY SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article ID SULFUR-DIOXIDE; PHOTOCHEMICAL FORMATION; DENITRIFICATION SYSTEM; SULFITE; OXIDATION; ANION; DESULFURIZATION; REDUCTION; KINETICS; CLOUD AB Electron spin resonance (ESR) spin trapping and high performance liquid chromatography (HPLC) with electron chemical detection were utilized to investigate the generation of free radicals in reactions of sulfite (SO32-) with inorganic environmental pollutants. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Incubation of SO32- with nitrite (NO2-) generated sulfur trioxide anion radical (SO3-), whose yield approached saturation levels in approximately four minutes. Fe2+ promoted SO3- formation. MOlecular oxygen was required for radical generation. This was demonstrated by experiments carried out in an argon environment as well as by oxygen consumption measurements. Transition metal ions, CrO42-, VO2+, Fe3+, Mn2+, Ni2+, and Fe2+ enhanced SO3- generation from SO32- either through direct SO32- oxidation by metal ions or by metal ions-catalyzed SO32- oxidation by molecular oxygen. Incubation of SO32- with H2O2 generated both SO3- and OH radicals as verified by spin trapping competition measurements using ethanol and formate as OH radical scavengers. HPLC measurements showed that OH radicals generated by reaction of SO32- with H2O2 caused 2'-deoxyguanine hydroxylation to generate 8-hydroxy-2'-deoxyguanine, a DNA damage marker. The implications of SO3- and OH radical formation in relation to SO32- toxicity are discussed. RP SHI, XL (reprint author), NCI,EXPTL PATHOL LAB,BLDG 41,ROOM C301,BETHESDA,MD 20892, USA. RI Shi, Xianglin/B-8588-2012 NR 41 TC 94 Z9 98 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD NOV 15 PY 1994 VL 56 IS 3 BP 155 EP 165 DI 10.1016/0162-0134(94)85002-X PG 11 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA PN851 UT WOS:A1994PN85100002 PM 7798899 ER PT J AU BAKER, SG LINDEMAN, KS AF BAKER, SG LINDEMAN, KS TI THE PAIRED AVAILABILITY DESIGN - A PROPOSAL FOR EVALUATING EPIDURAL ANALGESIA DURING LABOR SO STATISTICS IN MEDICINE LA English DT Article ID RANDOMIZED CLINICAL-TRIALS; CESAREAN-SECTION; DYSTOCIA AB The paired availability design (PAD) can reduce selection bias when it is not possible to randomize subjects. PAD consists of independent pairs of experimental and control groups. Within each pair, the intervention is the availability of treatment not its receipt. In the experimental group, the new treatment is made available to all subjects although some may not receive it. In the control group, the experimental treatment is generally not available to subjects although some may receive it in special circumstances. We present a statistic to test a null hypothesis that the receipt of intervention will increase response by a specified non-zero amount delta. We propose this design for use in a study of the effect of epidural analgesia on the rate of Caesarean section. C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL CRIT CARE MED,DIV OBSTET ANESTHESIA,BALTIMORE,MD 21287. RP BAKER, SG (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EPN 344,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 69 Z9 69 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 1994 VL 13 IS 21 BP 2269 EP 2278 DI 10.1002/sim.4780132108 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PT066 UT WOS:A1994PT06600007 PM 7846425 ER PT J AU HURLEY, JH DEAN, AM AF HURLEY, JH DEAN, AM TI STRUCTURE OF 3-ISOPROPYLMALATE DEHYDROGENASE IN COMPLEX WITH NAD(+) - LIGAND-INDUCED LOOP CLOSING AND MECHANISM FOR COFACTOR SPECIFICITY SO STRUCTURE LA English DT Article DE CONFORMATIONAL CHANGE; DINUCLEOTIDE-BINDING FOLD; ISOCITRATE DEHYDROGENASE; ISOPROPYLMALATE DEHYDROGENASE ID DEPENDENT ISOCITRATE DEHYDROGENASE; THERMUS-THERMOPHILUS; RESOLUTION; PROGRAM; ENZYME; PHOSPHORYLATION; DECARBOXYLATION; REFINEMENT; PROTEINS; GENE AB Background: The leucine biosynthetic enzyme 3-isopropylmalate dehydrogenase (IMDH) belongs to a unique class of bifunctional decarboxylating dehydrogenases. The two best-known members of this family, IMDH and isocitrate dehydrogenase (IDH), share a common structural framework and catalytic mechanism but have different substrate and cofactor specificities. IMDH is NAD(+)-dependent, while IDHs occur in both NAD(+)-dependent and NADP(+)-dependent forms. Results: We have co-crystallized Thermus themophilus IMDH with NAD(+) and have determined the structure at 2.5 Angstrom resolution. NAD(+) binds in an extended conformation. Comparisons with the structure in the absence of cofactor show that binding induces structural changes of up to 2.5 Angstrom in the five loops which form the dinucleotide-binding site. The adenine and diphosphate moieties of NAD(+) are bound via interactions which are also present in the NADP(+)-IDH complex. Amino acids which interact with the NADP(+) 2'-phosphate in IDH are substituted or absent in IMDH. The adenosine ribose forms two hydrogen bonds with Asp278, and the nicotinamide and nicotinamide ribose interact with Glu87 and Asp78, all unique to IMDH. Conclusions: NAD(+) binding induces a conformational transition in IMDH, resulting in a structure that is intermediate between the most 'open' and 'closed' decarboxylating dehydrogenase conformations. Physiological specificity of IMDH for NAD(+) versus NADP(+) can be explained by the unique interaction between Asp278 and the free 2'-hydroxyl of the NAD(+) adenosine, discrimination against the presence of the 2'-phosphate by the negative charge on Asp278, and the absence of potential favorable interactions with the 2'-phosphate of NADP(+). C1 CHICAGO MED SCH,DEPT BIOL CHEM,CHICAGO,IL 60064. RP HURLEY, JH (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [1RO1-GM-48735-01] NR 28 TC 94 Z9 96 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD NOV 15 PY 1994 VL 2 IS 11 BP 1007 EP 1016 DI 10.1016/S0969-2126(94)00104-9 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PU660 UT WOS:A1994PU66000003 PM 7881901 ER PT J AU CLUBB, RT OMICHINSKI, JG SAVILAHTI, H MIZUUCHI, K GRONENBORN, AM CLORE, GM AF CLUBB, RT OMICHINSKI, JG SAVILAHTI, H MIZUUCHI, K GRONENBORN, AM CLORE, GM TI A NOVEL CLASS OF WINGED HELIX-TURN-HELIX PROTEIN - THE DNA-BINDING DOMAIN OF MU TRANSPOSASE SO STRUCTURE LA English DT Article DE DNA-BINDING DOMAIN; MU TRANSPOSASE; NMR SPECTROSCOPY; WINGED HELIX-TURN-HELIX MOTIF ID NUCLEAR MAGNETIC-RESONANCE; 3-DIMENSIONAL SOLUTION STRUCTURE; HETERONUCLEAR NMR-SPECTROSCOPY; RESTRAINED MOLECULAR-DYNAMICS; DISTANCE GEOMETRY; CRYSTAL-STRUCTURE; PHOSPHOTRANSFERASE SYSTEM; LARGER PROTEINS; PHAGE-MU; SITE AB Background: Mu transposase (MuA) is a multidomain protein encoded by the bacteriophage Mu genome. It is responsible for translocation of the Mu genome, which is the largest and most efficient transposon known. While the various domains of MuA have been delineated by means of biochemical methods, no data have been obtained to date relating to its tertiary structure. Results: We have solved the three-dimensional solution structure of the DNA-binding domain (residues 1-76; MuA(76)) of MuA by multidimensional heteronuclear NMR spectroscopy. The structure consists of a three-membered alpha-helical bundle buttressed by a three-stranded antiparallel beta-sheet. Helices H1 and H2 and the seven-residue turn connecting them comprise a helix-turn-helix (HTH) motif. In addition, there is a long nine-residue flexible loop or wing connecting strands B2 and B3 of the sheet. NMR studies of MUA(76) complexed with a consensus DNA site from the internal activation region of the Mu genome indicate that the wing and the second helix of the HTH motif are significantly perturbed upon DNA binding. Conclusions: While the general appearance of the DNA-binding domain of MuA(76) is similar to that of other winged HTH proteins, the connectivity of the secondary structure elements is permuted. Hence, the fold of MuA(76) represents a novel of winged HTH DNA-binding domain. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 58 TC 61 Z9 64 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD NOV 15 PY 1994 VL 2 IS 11 BP 1041 EP 1048 DI 10.1016/S0969-2126(94)00107-3 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PU660 UT WOS:A1994PU66000006 PM 7881904 ER PT J AU MONTEFIORI, DC CORNELL, RJ ZHOU, JY ZHOU, JT HIRSCH, VM JOHNSON, PR AF MONTEFIORI, DC CORNELL, RJ ZHOU, JY ZHOU, JT HIRSCH, VM JOHNSON, PR TI COMPLEMENT CONTROL PROTEINS, CD46, CD55, AND CD59, AS COMMON SURFACE CONSTITUENTS OF HUMAN AND SIMIAN IMMUNODEFICIENCY VIRUSES AND POSSIBLE TARGETS FOR VACCINE PROTECTION SO VIROLOGY LA English DT Article ID HUMAN-ERYTHROCYTES; MEMBRANE-PROTEINS; AIDS VACCINE; HUMAN-SERUM; CELL-LINE; MACAQUES; INFECTION; TYPE-1; LYSIS; GLYCOPROTEIN AB Complement control proteins include a group of membrane-bound surface antigens that protect cells from complement lysis by preventing formation of the membrane attack complex (MAC) of complement. HIV-1 and SIV are known to possess cellular proteins, making it possible that some of them contribute to the ability of these viruses to evade complement lysis. Three complement control proteins, CD46 (membrane cofactor protein), CD55 (decay accelerating protein), and CD59 (HRF20), were found by flow cytometry to be expressed on the surface of CD4(+) cell lines commonly used for HIV-1 and SIV synthesis. Monoclonal antibodies to each of these proteins precipitated HIV-1 IIIB and SIVdelta/B670 synthesized in CEMX174 cells and two primary HIV-1 isolates synthesized in peripheral blood mononuclear cells, indicating that CD46, CD55, and CD59 are physically associated with the virus membrane after the virus has been released from the surface of infected cells. Additional experiments showed that the precipitated material contained infectious virus, confirming that whole virus was precipitated. Evidence that CD46 and CD59 are immunogenic in macaques was found when anti-cell antibodies in plasmas from macaques immunized with human cell-grown SIV blocked anti-CD46 and anti-CD59 from binding to the surface of CEMX174 cells. Anti-cell antibodies rendered HIV-1 susceptible to complement lysis as measured by the release of p24 core protein, and consistently produced a complement-dependent reduction in HIV-1 and SIV infectivity of 1-3 logs. These results demonstrate that CD46, CD55, and CD59 are common surface constituents of HIV-1 and SIV. The results also raise the possibility that the mechanism of SIV vaccine protection attributed to anti-cell antibodies could have involved complement-mediated virolysis. (C) 1994 Academic Press, Inc. C1 NIAID,INFECT DIS LAB,ROCKVILLE,MD 20852. OHIO STATE UNIV,CHILDRENS HOSP,DEPT PEDIAT,COLUMBUS,OH 43205. RP MONTEFIORI, DC (reprint author), DUKE UNIV,MED CTR,DEPT SURG,POB 2926,DURHAM,NC 27710, USA. RI Johnson, Philip/A-6892-2009 FU NCPDCID CDC HHS [NCI-6S-1649]; NIAID NIH HHS [N01-AI-35166] NR 46 TC 96 Z9 98 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 15 PY 1994 VL 205 IS 1 BP 82 EP 92 DI 10.1006/viro.1994.1622 PG 11 WC Virology SC Virology GA PQ623 UT WOS:A1994PQ62300010 PM 7526538 ER PT J AU MORIUCHI, H MORIUCHI, M COHEN, JI AF MORIUCHI, H MORIUCHI, M COHEN, JI TI THE RING FINGER DOMAIN OF THE VARICELLA-ZOSTER VIRUS OPEN READING FRAME-61 PROTEIN IS REQUIRED FOR ITS TRANSREGULATORY FUNCTIONS SO VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; IMMEDIATE-EARLY PROTEIN; COMPLETE DNA-SEQUENCE; ZINC-FINGER; BINDING PROTEIN; GENE PROMOTERS; UNIQUE REGION; TYPE-1; IDENTIFICATION; EXPRESSION AB Varicella-zoster virus (VZV) open reading frame 61 (ORF61) protein transactivates expression of VZV promoters. VZV ORF61 is functionally homologous to herpes simplex virus type 1 (HSV-1)-infected cell protein 0 (ICP0); however, amino acid sequence homology of these two proteins is limited to the RING finger domains, a recently identified sequence motif composed of cysteine and histidine residues, located in their amino-terminal regions. A carboxy-terminal truncation mutant of ICP0 (which retains the RING finger domain) was previously shown to act as a potent transrepressor and as a dominant-negative mutant in the presence of full-length ICP0. We have shown that the corresponding region of ORF61 has similar properties. Amino-terminal truncation mutants of VN ORF61 and HSV-1 ICP0, which lack the RING finger domain, cannot transactivate VZV promoters; however, fusion of the amino portion of one protein to the carboxy portion of the other restored the transactivating activity of the full-length proteins. To further study the role of the ORF61 RING finger domain, cysteine or histidine residues of this domain were individually replaced with serine or aspargine, respectively. Each of these amino acid substitution mutants in the RING finger abolished the transactivating activity of the full-length ORF61 protein. Each of the substitutions also reduced the transrepressing and dominant-negative properties of a carboxy-terminal truncation mutant of ORF61. These results indicate that the RING finger domain is required for the transregulatory functions of ORF61. (C) 1994 Academic Press, Inc. RP MORIUCHI, H (reprint author), NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892, USA. NR 38 TC 43 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 15 PY 1994 VL 205 IS 1 BP 238 EP 246 DI 10.1006/viro.1994.1639 PG 9 WC Virology SC Virology GA PQ623 UT WOS:A1994PQ62300027 PM 7975220 ER PT J AU SUGATA, F CHEN, HS KANEKO, S PURCELL, RH MILLER, RH AF SUGATA, F CHEN, HS KANEKO, S PURCELL, RH MILLER, RH TI ANALYSIS OF THE X-GENE PROMOTER OF WOODCHUCK HEPATITIS-VIRUS SO VIROLOGY LA English DT Article ID B VIRUS; MAMMALIAN-CELLS; TRANSCRIPTIONAL ACTIVATION; NUCLEOTIDE-SEQUENCE; VIRAL REPLICATION; TRANS-ACTIVATION; BINDING-PROTEIN; III-PROMOTERS; NATURAL HOST; EXPRESSION AB During the course of woodchuck hepatitis virus (WHV) replication three virus-specific mRNA transcripts that encode four essential proteins are produced. The transcripts are 3.6, 2.3, and 0.7 kb in size. The 3.6-kb transcript serves as the replicative intermediate as well as the template for translation of the nucleocapsid and polymerase proteins. The 2.3-kb mRNA serves as the template for translation of the virus envelope proteins. Both the 3.6- and 2.3-kb transcripts are polyadenylated and are readily found in the cytoplasm of infected hepatocytes. However, the 0.7-kb transcript, specific for the X gene, accumulates in the nucleus of infected cells and is polyadenylated poorly in hepatocytes. Thus, while it is likely that the 0.7-kb transcript is the template for translation of the X protein, it is possible that it also has a function at the RNA level to regulate virus replication or gene expression. In order to characterize the WHV X promoter we cloned the region of the WHV8 genome encompassing the viral enhancer through the amino terminus of the X gene into the vector pSV0CAT. We transfected Huh-7 and WLC-3 cells with the WHV X promoter construct, along with a plasmid encoding human growth hormone to control for transfection efficiency, and assayed for the presence of chloramphenicol acetyl transferase activity. We found that the WHV X promoter was about one-half as active as the well-studied simian virus 40 early or Rous sarcoma virus promoters. Next, we made a series of 5' and 3' deletion mutants and mapped the WHV X promoter to a 21-nucleotide domain (1482-GGGGAAGCTGACGTCCmCC-1502) which is approximately 100 bp downstream of the corresponding promoter in hepatitis B virus. Further analysis, using oligonucleotide-directed mutagenesis, demonstrated that the essential nucleotides comprising the WHV X promoter are located in a 10-nucleotide domain near the initiation codon of the X gene. Mutation of either nucleotide T at position 1490 or G at position 1491 within this domain was sufficient to reduce the level of promoter activity by 100-fold. Thus, we have defined the important nucleotides within the promoter of the WHV X transcript which is a first step in understanding the role of this transcript in WHV replication and gene expression. (C) 1994 Academic Press, Inc. C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. KANAZAWA UNIV,DEPT INTERNAL MED 1,KANAZAWA,ISHIKAWA 920,JAPAN. NR 42 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 15 PY 1994 VL 205 IS 1 BP 314 EP 320 DI 10.1006/viro.1994.1647 PG 7 WC Virology SC Virology GA PQ623 UT WOS:A1994PQ62300035 PM 7975227 ER PT J AU CHRISTENSEN, ND KIRNBAUER, R SCHILLER, JT GHIM, SJ SCHLEGEL, R JENSON, AB KREIDER, JW AF CHRISTENSEN, ND KIRNBAUER, R SCHILLER, JT GHIM, SJ SCHLEGEL, R JENSON, AB KREIDER, JW TI HUMAN PAPILLOMAVIRUS TYPE-6 AND TYPE-11 HAVE ANTIGENICALLY DISTINCT STRONGLY IMMUNOGENIC CONFORMATIONALLY DEPENDENT NEUTRALIZING EPITOPES SO VIROLOGY LA English DT Article ID ANTIBODY-MEDIATED NEUTRALIZATION; VIRUS-LIKE PARTICLES; COTTONTAIL RABBIT PAPILLOMAVIRUS; MONOCLONAL-ANTIBODIES; HPV-11 INFECTION; L1 PROTEIN; BOVINE; EXPRESSION; CELLS; L2 AB Antibodies reactive to HPV types 6 and 11 were tested in ELISA and HPV-11 neutralization assays to determine whether these closely related types shared cross-reactive neutralizing epitopes. A series of HPV-11 neutralizing monoclonal antibodies (N-MAbs) that targeted conformational epitopes on infectious HPV-11 and HPV-11 L1 virus-like particles (VLPs) were tested for type-specificity of reactivity using intact HPV-6 L1 VLPs. Polyclonal antisera generated against intact HPV-6 L1 VLPs were also tested for HPV-11 neutralizing capacity using the athymic mouse xenograft system. The results demonstrated that conformationally dependent neutralizing epitopes on HPV-11 were Very type-specific. Three of the four HPV-11 N-MAbs were negative for binding to HPV-6 L1 VLP, and the fourth demonstrated binding to HPV-6 L1 VLPs that was several orders of magnitude weaker than its binding to HPV-11 L1 VLP. The polyclonal anti-HPV-6 L1 VLP antiserum was only partially protective against HPV-11 infectivity even at a low dilution of 1:100. In contrast, polyclonal anti-HPV-11 L1 VLP antiserum was completely protective at dilutions greater than 1:10,000. (C) 1994 Academic Press, Inc. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT MICROBIOL & IMMUNOL,HERSHEY,PA 17033. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20071. RP CHRISTENSEN, ND (reprint author), PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT PATHOL,HERSHEY,PA 17033, USA. FU NCI NIH HHS [CA47622, CA56460] NR 25 TC 113 Z9 121 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 15 PY 1994 VL 205 IS 1 BP 329 EP 335 DI 10.1006/viro.1994.1649 PG 7 WC Virology SC Virology GA PQ623 UT WOS:A1994PQ62300037 PM 7526536 ER PT J AU QUEZADO, ZMN NATANSON, C HOFFMAN, WD AF QUEZADO, ZMN NATANSON, C HOFFMAN, WD TI LOOKING BACK ON HA-1A SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID GRAM-NEGATIVE BACTEREMIA; CONTROLLED TRIAL; SEPTIC SHOCK; ANTIBODIES RP QUEZADO, ZMN (reprint author), NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 10 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 14 PY 1994 VL 154 IS 21 BP 2393 EP 2393 DI 10.1001/archinte.154.21.2393 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PR043 UT WOS:A1994PR04300001 PM 7979833 ER PT J AU SORLIE, PD JOHNSON, NJ BACKLUND, E BRADHAM, DD AF SORLIE, PD JOHNSON, NJ BACKLUND, E BRADHAM, DD TI MORTALITY IN THE UNINSURED COMPARED WITH THAT IN PERSONS WITH PUBLIC AND PRIVATE HEALTH-INSURANCE SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID NATIONAL-DEATH-INDEX; SOCIOECONOMIC-STATUS; MEDICAL-CARE; ASCERTAINMENT; MASSACHUSETTS; NUMBER AB Objective: To compare mortality in persons with employer-provided health insurance, Medicare, Medicaid, military health benefits, other private health insurance, and no health insurance, before and after adjustment for income and employment status. Design: Cohort study using national survey data containing information on social, economic, and demographic factors and health insurance, with deaths identified through matching to the National Death Index resulting in a mortality follow-up period of 5 years. Setting: Noninstitutionalized population of the United States. Participants: Approximately 150 000 respondents to national surveys conducted by the US Bureau of the Census (Current Population Surveys), aged 25 to 64 years. Results: After adjustment for age and income, persons with Medicare and Medicaid had the highest mortality in comparison with those with employer-provided insurance, with relative risks generally greater than 2. With adjustment for age and income, persons without insurance had higher mortality than those with employer-provided insurance, with relative risks of 1.2 for white men and 1.5 for white women. These relationships held after adjustment for employment status, with the working uninsured showing mortality between 1.2 and 1.3 times higher than that of the working insured. Mortality was higher in those with lower incomes after adjustment for insurance status. Those with annual income of $10 000 or less per year had mortality about two times that of persons with incomes greater than $25 000 per year. Conclusion: Mortality was lowest in employed persons with employer-provided health insurance. The higher mortality in those with public insurance or with no insurance reflects an indeterminate mix of selection on existing health status and access to medical care. C1 US BUR CENSUS,SUITLAND,MD. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. RP SORLIE, PD (reprint author), NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,FED BLDG,ROOM 3A10,BETHESDA,MD 20892, USA. NR 31 TC 70 Z9 71 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 14 PY 1994 VL 154 IS 21 BP 2409 EP 2416 DI 10.1001/archinte.154.21.2409 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PR043 UT WOS:A1994PR04300004 PM 7979836 ER PT J AU MAKAROV, AA PROTASEVICH, II LOBACHOV, VM KIRPICHNIKOV, MP YAKOVLEV, GI GILLI, RM BRIAND, CM HARTLEY, RW AF MAKAROV, AA PROTASEVICH, II LOBACHOV, VM KIRPICHNIKOV, MP YAKOVLEV, GI GILLI, RM BRIAND, CM HARTLEY, RW TI THERMOSTABILITY OF THE BARNASE-BARSTAR COMPLEX SO FEBS LETTERS LA English DT Article DE BARNASE BARSTAR COMPLEX; HEAT DENATURATION; SCANNING MICROCALORIMETRY; ISOTHERMAL MICROCALORIMETRY ID PROTEIN AB Scanning microcalorimetry was used to study heat denaturation of barnase in complex with its intracellular inhibitor barstar. The heat denaturation of the barnase-barstar complex is well approximated by two two-state transitions with the lower temperature transition corresponding to barstar denaturation and the higher temperature one to barnase denaturation. The temperature of barnase melting in its complex with barstar is 20 degrees C higher than that of the free enzyme. The barstar melting temperature is almost the same in the complex or alone (71 degrees C at pH 6.2 and 68 degrees C at pH 8.0). It seems possible that when barstar unfolds it can remain bound to barnase, while the latter unfolds only on dissociation of the denatured barstar. C1 FAC PHARM MARSEILLE,RECH INTERACT PROT PHARMACOL GRP,F-13385 MARSEILLE,FRANCE. NIDDKD,BETHESDA,MD 20892. RP MAKAROV, AA (reprint author), RUSSIAN ACAD SCI,VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA. RI Makarov, Alexander/P-5279-2016 NR 14 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 14 PY 1994 VL 354 IS 3 BP 251 EP 254 DI 10.1016/0014-5793(94)01127-3 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PT429 UT WOS:A1994PT42900003 PM 7957933 ER PT J AU YAKOVLEV, GI MOISEYEV, GP STRUMINSKAYA, NK BORZYKH, OA KIPENSKAYA, LV ZNAMENSKAYA, LV LESCHINSKAYA, IB CHERNOKALSKAYA, EB HARTLEY, RW AF YAKOVLEV, GI MOISEYEV, GP STRUMINSKAYA, NK BORZYKH, OA KIPENSKAYA, LV ZNAMENSKAYA, LV LESCHINSKAYA, IB CHERNOKALSKAYA, EB HARTLEY, RW TI MUTATIONAL ANALYSIS OF THE ACTIVE-SITE OF RNASE OF BACILLUS-INTERMEDIUS (BINASE) SO FEBS LETTERS LA English DT Article DE RIBONUCLEASE; CATALYTIC PROPERTY; SITE-DIRECTED MUTAGENESIS ID DIRECTED MUTAGENESIS; MICROBIAL RIBONUCLEASES; CATALYTIC MECHANISM; BARNASE; SPECIFICITY; SUBSITES; BARSTAR; GPC; 7P AB To elucidate the functional role of some residues in the active site,of binase, the extracellular ribonuclease of Bacillus intermedius, we used site-directed mutagenesis. On cleavage of various substrates the catalytic activity of binase mutant His(101)Glu is 2.0-2.7% of that for native enzyme. The decrease in activity is determined mainly by the decrease in molecular rate constant k(cat), with almost unchanged affinity of the enzyme for the substrate, characterized by K-M. This is the expected result if His(101) acts as an general acid, donating a proton to the leaving group on cleavage of a phosphodiester bond. The replacement of Lys(26) by Ala causes a reduction in the enzyme activity to 13-33%, depending on the substrate. The activity decreases are due to changes in both k(cat) and K-M for poly(I) and poly(A) but in k(cat) alone for GpA. In the latter case the effect is far less than that seen in the homologous mutation in the closely related enzyme, barnase. C1 KAZAN VI LENIN STATE UNIV,DEPT BIOL,KAZAN 420008,RUSSIA. NIDDK,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. RP YAKOVLEV, GI (reprint author), RUSSIAN ACAD SCI,VA ENGELHARDT MOLEC BIOL INST,VAVILOV STR 32,MOSCOW 117984,RUSSIA. NR 20 TC 28 Z9 31 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 14 PY 1994 VL 354 IS 3 BP 305 EP 306 DI 10.1016/0014-5793(94)01150-8 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PT429 UT WOS:A1994PT42900016 PM 7957945 ER PT J AU HOKE, F GALLO, RC AF HOKE, F GALLO, RC TI GALLO,ROBERT,C. LOOKS BEYOND NIH AND DEFENDS THE PAST SO SCIENTIST LA English DT Editorial Material AB In an exclusive interview with The Scientist, NIH retrovirologist Robert Gallo discusses reports that he will leave the health agency in the near future and reflects on pivotal past events. From the earliest days of AIDS research, Gallo has played a central role in advancing scientific understanding of HIV. In the mid-1980s, however, he was involved in a bitter dispute over appropriate credit for its discovery. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP HOKE, F (reprint author), SCIENTIST,3600 MARKET ST,SUITE 450,PHILADELPHIA,PA 19104, USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD NOV 14 PY 1994 VL 8 IS 22 BP 12 EP 12 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA PQ923 UT WOS:A1994PQ92300006 ER PT J AU BOICE, J LINET, M AF BOICE, J LINET, M TI FALLOUT FROM CHERNOBYL - EDITORIAL AUTHORS RESPONSE SO BRITISH MEDICAL JOURNAL LA English DT Letter RP BOICE, J (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD NOV 12 PY 1994 VL 309 IS 6964 BP 1300 EP 1300 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PT033 UT WOS:A1994PT03300048 ER PT J AU PARK, MH WOLFF, EC LEE, YB FOLK, JE AF PARK, MH WOLFF, EC LEE, YB FOLK, JE TI ANTIPROLIFERATIVE EFFECTS OF INHIBITORS OF DEOXYHYPUSINE SYNTHASE - INHIBITION OF GROWTH OF CHINESE-HAMSTER OVARY CELLS BY GUANYL DIAMINES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INITIATION-FACTOR EIF-4D; MURINE LEUKEMIA-CELLS; POSTTRANSLATIONAL FORMATION; SACCHAROMYCES-CEREVISIAE; HYPUSINE MODIFICATION; AMINO-ACID; PROTEIN; POLYAMINES; SPERMIDINE; IDENTIFICATION AB Certain guanyl diamines are effective inhibitors of deoxyhypusine synthase (Jakus, J., Wolff, E. C., Park, M. H., and Folk, J. E. (1993) J. Biol. Chem. 268, 18151-13159), the first enzyme involved in the biosynthesis of the unusual amino acid hypusine (N-epsilon-(4-amino-2-hydroxybutyl)lysine). Evidence that hypusine is implicated in cell growth prompted this study of the cellular effects of these inhibitors. In Chinese hamster ovary (CHO) cells, inhibition of hypusine biosynthesis followed by progressive arrest in cellular proliferation was observed with both N-mono- and N,N'-bisguanyl derivatives of 1,6-diaminohexane, 1,7-diaminoheptane and 1,8-diaminooctane. Cells treated with these compounds showed no significant change in polyamine distribution, suggesting that the observed growth inhibition is not mediated through an interference with polyamine metabolism. N-1-guanyl-1,7-diaminoheptane, the most potent inhibitor of deoxyhypusine synthase both in vitro and in cells, exhibited the highest antiproliferative activity toward CHO cells. No early cytotoxic effects were observed with this inhibitor, and its antiproliferative activity appeared to be reversible. Transport studies showed that N-1-guanyl-1,7-diaminoheptane is actively taken up by the polyamine transport system. Mutant CHO cells defective in polyamine transport were found to be resistant to growth inhibition by this compound. The findings suggest that the antiproliferative effect of N-1-guanyl-1,7-diaminoheptane is exerted intracellularly through inhibition of hypusine synthesis. RP PARK, MH (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,ENZYME CHEM SECT,BLDG 30,RM 211,30 CONVENT DR,MSC 4330,BETHESDA,MD 20892, USA. NR 35 TC 119 Z9 125 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 11 PY 1994 VL 269 IS 45 BP 27827 EP 27832 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV772 UT WOS:A1994PV77200012 PM 7961711 ER PT J AU QUON, MJ BUTTE, AJ ZARNOWSKI, MJ SESTI, G CUSHMAN, SW TAYLOR, SI AF QUON, MJ BUTTE, AJ ZARNOWSKI, MJ SESTI, G CUSHMAN, SW TAYLOR, SI TI INSULIN-RECEPTOR SUBSTRATE-1 MEDIATES THE STIMULATORY EFFECT OF INSULIN ON GLUT4 TRANSLOCATION IN TRANSFECTED RAT ADIPOSE-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUCOSE-TRANSPORT ACTIVITY; SIGNAL TRANSDUCTION; PLASMA-MEMBRANE; SH2 DOMAINS; IRS-1; SYSTEMS; GENE; SITE AB Insulin signaling is initiated at least in part by activation of the insulin receptor tyrosine kinase and subsequent phosphorylation of cellular substrates such as insulin receptor substrate 1 (IRS-l). Previous studies have focused on the role of IRS-1 in the mitogenic actions of insulin. We have now investigated the possible role of IRS 1 in mediating the effect of insulin to stimulate glucose transport in a physiologically relevant insulin target tissue. In this study, we transfected rat adipose cells in primary culture with an antisense ribozyme directed against rat IRS-l. Expression of the ribozyme in these cells caused a 4.4-fold increase in the concentration of insulin required to achieve half-maximal stimulation of the translocation of cotransfected epitope-tagged GLUT4 without changing the maximal insulin response. Overexpression of human IRS-1 increased the basal cell surface GLUT4 to nearly the maximal level in the absence of insulin. When the ribozyme (specific to rat IRS-1) was cotransfected along with human IRS-1, the insulin dose-response curve was shifted to the left when compared with cells transfected with the ribozyme alone. These data provide strong support for the hypothesis that IRS-1 plays a role in insulin-stimulated glucose transport in insulin-responsive cells. C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892. RI Quon, Michael/B-1970-2008; Sesti, Giorgio/B-1509-2012; OI Quon, Michael/0000-0002-9601-9915; Sesti, Giorgio/0000-0002-1618-7688; Quon , Michael /0000-0002-5289-3707 NR 28 TC 114 Z9 114 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 11 PY 1994 VL 269 IS 45 BP 27920 EP 27924 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV772 UT WOS:A1994PV77200026 PM 7525563 ER PT J AU KIM, SY KIM, IG CHUNG, SI STEINERT, PM AF KIM, SY KIM, IG CHUNG, SI STEINERT, PM TI THE STRUCTURE OF THE TRANSGLUTAMINASE-1 ENZYME - DELETION CLONING REVEALS DOMAINS THAT REGULATE ITS SPECIFIC ACTIVITY AND SUBSTRATE-SPECIFICITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; HUMAN EPIDERMAL TRANSGLUTAMINASE; PIG LIVER TRANSGLUTAMINASE; HUMAN FACTOR-XIII; KERATINOCYTE TRANSGLUTAMINASE; CORNIFIED ENVELOPE; GUINEA-PIG; MOLECULAR-CLONING; SQUAMOUS DIFFERENTIATION; PROTRANSGLUTAMINASE-E AB Transglutaminase 1 (TGase1) is one of three known enzymes involved in terminal differentiation in stratified squamous epithelia, possibly in the formation of a cornified cell envelope. Because the intact enzyme is particularly difficult to isolate in quantity from keratinocytes for characterization, comparatively little is known about its properties. We have expressed the full-length as well as a series of deletion forms of this enzyme in a bacterial system and analyzed their enzymatic properties. The specific activity of the full-length enzyme isolated and purified from the bacterial lysate was comparable to that of the native enzyme of keratinocytes. Analysis of several deletion constructs demonstrated that removal of the first 60-109 residues, which include sequences involved in membrane association, results in upwards of a 10-fold increase in the specific activity. Deletions beyond residue 109, into sequences conserved within the TGase family of proteins, result in lass of activity. Similarly, as many as 240 residues can be removed from its carboxyl-terminal end before activity is lost. Thus, a molecule of 466 residues, containing virtually only the conserved core sequences of TGases, retains a specific activity comparable to the intact enzyme. In addition, the various deletion forms display wide variations in substrate specificity toward a series of synthetic peptide substrates, designed from possible target TGase1 substrate proteins of epithelia. The data show that sequences between residues 62 and 92 are important in defining the substrate specificity of the TGase1 enzyme system. Furthermore, it may now be possible to design an enzyme with a defined substrate specificity. Together, these data suggest TGase1 has recruited additional sequences on its amino terminus in relation to other members of the TGase family, which have the net effect of permitting sequestration onto membranes, changing its specific activity and modifying its likely substrate specificities. C1 NIAMS,SKIN BIOL BRANCH,BETHESDA,MD 20892. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. NR 68 TC 72 Z9 72 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 11 PY 1994 VL 269 IS 45 BP 27979 EP 27986 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV772 UT WOS:A1994PV77200034 PM 7961731 ER PT J AU BEARD, WA STAHL, SJ KIM, HR BEBENEK, K KUMAR, A STRUB, MP BECERRA, SP KUNKEL, TA WILSON, SH AF BEARD, WA STAHL, SJ KIM, HR BEBENEK, K KUMAR, A STRUB, MP BECERRA, SP KUNKEL, TA WILSON, SH TI STRUCTURE-FUNCTION STUDIES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE - ALANINE SCANNING MUTAGENESIS OF AN ALPHA-HELIX IN THE THUMB SUBDOMAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STEADY-STATE KINETICS; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; BINDING DOMAIN; DNA; MECHANISM; HIV-1; SITE; IDENTIFICATION AB Human immunodeficiency virus type 1 reverse transcriptase has subunits of 66 and 51 kDa (p66 and p51, respectively). Structural studies indicate that each subunit consists of common subdomains. The polymerase domain of p66 forms a nucleic acid binding cleft, and, by analogy with a right hand, the subdomains are referred to as fingers, palm, and thumb (Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice, P. A., and Steitz, T. A. (1992) Science 256, 1783-1790). Residues 257-266 correspond to a highly conserved region of primary structure among retroviral pol genes. Crystallographic evidence indicates that these residues are in the thumb subdomain and form part of an alpha-helix (alpha H), which interacts with DNA (Jacobo-Molina, A., Ding, J., Nanni, R. G., Clark, A. D., Jr., Lu, X., Tantillo, C., Williams, R. L., Kamer, G., Ferris, A. L., Clark, P., Hizi, A., Hughes, S. H., and Arnold, E. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 6320-6324). To define the role of this region during catalytic cycling, we performed systematic site directed mutagenesis from position 253 through position 271 by changing each residue, one by one, to alanine. Each mutant protein was expressed and purified, and their substrate specific activities were surveyed. The results are consistent with alpha H (residues 255-268) of p66 interacting with the template and/or primer strand. The core of alpha H appears to play an important role in template-primer binding (residues Gln-258, Gly-262, and Trp-266), and in protein-protein interactions (residues Val-261 and Leu-264). The periodicity of the effects observed suggest that a segment of one face of alpha H interacts with the template-primer. The lower fidelity observed with alanine mutants of Gly-262 and Trp-266 correlated with an over 200-fold increase in the dissociation rate constant for template-primer relative to wild type enzyme and suggests that enzyme-DNA interactions in the template-primer stem are important fidelity determinants. C1 NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. UNIV TEXAS, SEALY CTR MOLEC SCI, MED BRANCH, GALVESTON, TX 77555 USA. NIEHS, MOLEC GENET LAB, RES TRIANGLE PK, NC 27709 USA. NIH, PROTEIN EXPRESS LAB, BETHESDA, MD 20892 USA. NR 30 TC 99 Z9 99 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 11 PY 1994 VL 269 IS 45 BP 28091 EP 28097 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV772 UT WOS:A1994PV77200050 PM 7525566 ER PT J AU TERUI, T KAHN, RA RANDAZZO, PA AF TERUI, T KAHN, RA RANDAZZO, PA TI EFFECTS OF ACID PHOSPHOLIPIDS ON NUCLEOTIDE EXCHANGE PROPERTIES OF ADP-RIBOSYLATION FACTOR-1 - EVIDENCE FOR SPECIFIC INTERACTION WITH PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHOLERA-TOXIN; REGULATORY COMPONENT; ADENYLATE-CYCLASE; PROTEIN COFACTOR; GOLGI MEMBRANES; BINDING; GTP; ARF; IDENTIFICATION; EXPRESSION AB ADP-ribosylation factors (ARFs) have been implicated as ubiquitous regulators of multiple steps in both exocytic and endocytic membrane traffic in yeast and mammalian cells. More specific interactions have also been described for ARF proteins with an ARF-specific GTPase-activating protein and as activators of phospholipase D activity. These protein interactions have defined requirements for phosphatidylinositol 4,5-bisphosphate (PIP2). Direct interactions between ARF1 and PIP2 or other phospholipids were tested by examining effects on guanine nucleotide binding kinetics. PIP2 (400 mu M) increased the rate of GDP dissociation >100-fold. Several other acid phospholipids had more modest effects (4-7-fold) on GDP dissociation rates, while other phospholipids had no effect. PIP2 also had the greatest effect on the rate of binding of guanosine 5'-(gamma-thio)triphosphate (GTP gamma S), increasing it almost 100-fold at early time points. However, at later times (>5 min), PIP2 caused a paradoxical loss of nucleotide binding to ARF1. PIP2 was found to stabilize the nucleotide-free form of ARF1 as subsequent dilution of PIP2 allowed ARF1 to bind GTP gamma S to high stoichiometry. The demonstration of direct interaction between ARF1 and PIP2 provides the basis for a model in which PIP2 acts as a cofactor in some of the interactions between ARF1 and other proteins. C1 NCI, DIV CANC TREATMENT, BIOL CHEM LAB, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. NR 29 TC 93 Z9 94 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 11 PY 1994 VL 269 IS 45 BP 28130 EP 28135 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV772 UT WOS:A1994PV77200055 PM 7961749 ER PT J AU CHANG, SC HOANG, B THOMAS, JT VUKICEVIC, S LUYTEN, FP RYBA, NJP KOZAK, CA REDDI, AH MOOS, M AF CHANG, SC HOANG, B THOMAS, JT VUKICEVIC, S LUYTEN, FP RYBA, NJP KOZAK, CA REDDI, AH MOOS, M TI CARTILAGE-DERIVED MORPHOGENETIC PROTEINS - NEW MEMBERS OF THE TRANSFORMING GROWTH-FACTOR-BETA SUPERFAMILY PREDOMINANTLY EXPRESSED IN LONG BONES DURING HUMAN EMBRYONIC-DEVELOPMENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOVINE OSTEOGENIC PROTEIN; VENTRALIZING FACTOR; INDUCTIVE PROTEIN; RNA; MOUSE; FAMILY; BMP-2A; OP-1; GENE; DIFFERENTIATION AB Partially purified extracts from newborn calf articular cartilage were found to induce cartilage and bone when subcutaneously implanted in rats. This activity showed characteristics of bone morphogenetic proteins (BMPs). Degenerate oligonucleotide primer sets derived from the highly conserved carboxyl-terminal region of the BMP family were designed and used in reverse transcription-polymerase chain reactions with poly(A)(+) RNA from articular cartilage as template to determine which BMPs are produced by chondrocytes. Two novel members of the transforming growth factor-beta (TGF-beta) superfamily were identified and designated cartilage-derived morphogenetic protein-1 (CDMP-1) and -2 (CDMP-2). Their carboxyl-terminal TGF-beta domains are 82% identical, thus defining a novel subfamily most closely related to BMP-B, BMP-6, and osteogenic protein-1. Northern analyses showed that both genes are predominantly expressed in cartilaginous tissues. In situ hybridization and immunostaining of sections from human embryos showed that CDMP-1 was predominantly found at the stage of precartilaginous mesenchymal condensation and throughout the cartilaginous cores of the developing long bones, whereas CDMP-2 expression was restricted to the hypertrophic chondrocytes of ossifying long bone centers. Neither gene was detectable in the axial skeleton during human embryonic development. The cartilage-specific localization pattern of these novel TGF-beta superfamily members, which contrasts with the more ubiquitous presence of other BMP family members, suggests a potential role for these proteins in chondrocyte differentiation and growth of long bones. C1 NIDR,BONE RES BRANCH,DEV BIOL PROGRAM,BETHESDA,MD 20892. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DEV BIOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT ORTHOPED SURG,MUSCULOSKELETAL BIOL LAB,BALTIMORE,MD 21205. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 48 TC 305 Z9 325 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 11 PY 1994 VL 269 IS 45 BP 28227 EP 28234 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV772 UT WOS:A1994PV77200069 PM 7961761 ER PT J AU RIBAS, JC FUJIMURA, T WICKNER, RB AF RIBAS, JC FUJIMURA, T WICKNER, RB TI ESSENTIAL RNA-BINDING AND PACKAGING DOMAINS OF THE GAG-POL FUSION PROTEIN OF THE L-A DOUBLE-STRANDED-RNA VIRUS OF SACCHAROMYCES-CEREVISIAE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROTAVIRUS NONSTRUCTURAL PROTEIN; HEPATITIS-B VIRUS; CONSENSUS SEQUENCE; VIRAL-RNA; YEAST; EXPRESSION; INVITRO; ENCAPSIDATION; REPLICATION; POLYMERASE AB The crucial process in the assembly of the L-A double-stranded RNA virus is the recognition of its (+) single-stranded RNA by the Gag-Pol protein. The Pol region of this protein has RNA binding activity and is necessary for RNA packaging. Here we show that there are actually two in vitro RNA-binding domains of Pol (residues 172-190 and 770-819), and both are necessary for viral propagation, (but not for particle assembly). Furthermore, the N-terminal RNA-binding domain is necessary for in vivo packaging of viral (+) single-stranded RNA. We precisely define the extent of the Pol packaging domain (residues 67-213), which includes the N-terminal RNA-binding domain. This suggests that the N-terminal RNA-binding domain is responsible for binding the genomic RNA in the process of packaging and that additional surrounding residues are responsible for the specificity of binding. RP RIBAS, JC (reprint author), NIDDK,BIOCHEM PHARMACOL LAB,GENET SIMPLE EUKARYOTES SECT,BETHESDA,MD 20892, USA. RI Fujimura, Tsutomu/K-5807-2014; Ribas, Juan/C-9864-2015 OI Fujimura, Tsutomu/0000-0002-9457-6769; Ribas, Juan/0000-0001-6430-0895 NR 39 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 11 PY 1994 VL 269 IS 45 BP 28420 EP 28428 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV772 UT WOS:A1994PV77200095 PM 7961783 ER PT J AU KELKAR, SV IZENWASSER, S KATZ, JL KLEIN, CL ZHU, NJ TRUDELL, ML AF KELKAR, SV IZENWASSER, S KATZ, JL KLEIN, CL ZHU, NJ TRUDELL, ML TI SYNTHESIS, COCAINE RECEPTOR AFFINITY, AND DOPAMINE UPTAKE INHIBITION OF SEVERAL NEW 2-BETA-SUBSTITUTED 3-BETA-PHENYLTROPANES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Note ID CENTRAL NERVOUS-SYSTEM; LIGAND-BINDING; ANALOGS; TRANSPORTERS; STRIATUM; NOREPINEPHRINE; SEROTONIN; ESTERS; MOUSE; SITE C1 UNIV NEW ORLEANS,DEPT CHEM,NEW ORLEANS,LA 70148. NIDA,INTRAMURAL RES PROGRAM,PSYCHOBIOL LAB,BALTIMORE,MD 21224. XAVIER UNIV,DEPT CHEM,NEW ORLEANS,LA 70125. RI Izenwasser, Sari/G-9193-2012 NR 27 TC 42 Z9 42 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 11 PY 1994 VL 37 IS 23 BP 3875 EP 3877 DI 10.1021/jm00049a004 PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PR950 UT WOS:A1994PR95000004 PM 7966147 ER PT J AU KIM, HO JI, XD MELMAN, N OLAH, ME STILES, GL JACOBSON, KA AF KIM, HO JI, XD MELMAN, N OLAH, ME STILES, GL JACOBSON, KA TI SELECTIVE LIGANDS FOR RAT A(3) ADENOSINE RECEPTORS - STRUCTURE-ACTIVITY-RELATIONSHIPS OF 1,3-DIALKYLXANTHINE 7-RIBOSIDE DERIVATIVES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MOLECULAR-CLONING; ANTI-MODE; BINDING; XANTHINE-7-RIBOSIDES; ANTAGONISTS; EXPRESSION; AGONIST; CELLS; BRAIN AB 1,3-Dibutylxanthine 7-riboside has been found to be a partial agonist at A(3) adenosine receptors (van Galen et al. Mol. Pharmacol. 1994, 45, 1101-1111). 1,3-Dialkylxanthine 7-riboside analogues modified at the 1-, 3-, and 8-purine positions and at the ribose 5'-position were synthesized. The nucleoside analogues were examined for affinity in radioligand binding assays at rat brain A(3) adenosine receptors stably expressed in CHO cells, using the radioligand [[I-125]-4-amino- 3-iodobenzyl]adenosine-5'-N-methyluronamide (AB-MECA). Affinity was assayed at rat brain A(1) and A(2a) receptors using [H-3]PIA and [H-3]CGS 21680, respectively. The affinity of xanthine 7-ribosides at A(3) receptors depended on the 1,3-dialkyl substituents in the order: Pent greater than or equal to. Bu >> Hx > Pr approximate to Me. 1,3-Dipentylxanthine 7-riboside was slightly selective for A(3) receptors (2-fold vs A(1) and 10-fold vs A(2a)). 8-Methoxy substitution was tolerated at A(3) receptors. 2-Thio vs 2-oxo substitution increased potency at all three subtypes and slightly increased A(3) vs A(1) selectivity. The 5'-uronamide modification, which was previously found to enhance A(3) selectivity in N-6-benzyladenosine derivatives, was also incorporated into the xanthine 7-ribosides, with similar results. The affinity of 1,3-dialkylxanthine 7-riboside 5'-uronamides at A(3) receptors depended on the N-alkyluronamide substituent in the order: MeNH > EtNH >> NH2 >> Me(2)N. Affinity of the 5'-uronamides at A(3) receptors was dependent on the 1,3-dialkyl substitution in the order: Bu > Pent > Hex. 1,3-Dibutylxanthine 7-riboside 5'-N-methylcarboxamide, with a K-i value of 229 nM at A(3) receptors, was 160-fold selective for rat A(3) vs A(1) receptors and > 400-fold selective vs A(2a) receptors. This derivative acted as a full agonist in the A(3) receptor-mediated inhibition of adenylate cyclase. C1 NIDDK,MOLEC RECOGNIT SECT,BIOORGAN CHEM LAB,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 40 TC 29 Z9 29 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 11 PY 1994 VL 37 IS 23 BP 4020 EP 4030 DI 10.1021/jm00049a021 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PR950 UT WOS:A1994PR95000021 PM 7966162 ER PT J AU STEVNSNER, T DING, RC SMULSON, M BOHR, VA AF STEVNSNER, T DING, RC SMULSON, M BOHR, VA TI INHIBITION OF GENE-SPECIFIC REPAIR OF ALKYLATION DAMAGE IN CELLS DEPLETED OF POLY(ADP-RIBOSE) POLYMERASE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POLY(ADENOSINE DIPHOSPHATE RIBOSE); INTERSTRAND CROSS-LINKS; HAMSTER OVARY CELLS; DNA EXCISION REPAIR; MAMMALIAN-CELLS; UV IRRADIATION; STRAND BREAKS; AGENTS; CHROMATIN; CISPLATIN AB The role of the enzyme poly(adenosine diphosphate-ribose) polymerase (PADPRP) in DNA repair at the level of the gene was investigated with human HeLa cells in which PADPRP antisense transcripts are inducible with dexamethasone. After such induction, the cellular content of PADPRP is reduced by 90%. DNA damage and its repair was studied in the essential dihydrofolate reductase (DHFR) gene after exposure of the cells to either ultraviolet (UV) irradiation or the alkylating agent nitrogen mustard. The expression of the antisense construct had no effect on gene-specific repair of UV-induced pyrimidine dimers. In contrast, induced antisense cells were deficient in the gene-specific repair of nitrogen mustard-induced lesions. Dexamethasone itself did not inhibit gene-specific repair in control cells. Thus, PADPRP appears to participate in the gene-specific repair of alkylation damage, but not in the repair of UV-induced pyrimidine dimers. Clonal survival assays revealed that cells depleted of PADPRP showed an increased susceptibility to nitrogen mustard, supporting the notion that repair of essential genes is critical for cellular survival. C1 NIA,GENET MOLEC LAB,BALTIMORE,MD 21224. GEORGETOWN UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20007. FU NCI NIH HHS [CA25344] NR 30 TC 28 Z9 29 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 11 PY 1994 VL 22 IS 22 BP 4620 EP 4624 DI 10.1093/nar/22.22.4620 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU199 UT WOS:A1994PU19900010 PM 7984410 ER PT J AU ZOLOTUKHIN, AS HARFORD, JB FELBER, BK AF ZOLOTUKHIN, AS HARFORD, JB FELBER, BK TI REV OF HUMAN-IMMUNODEFICIENCY-VIRUS AND REX OF THE HUMAN T-CELL LEUKEMIA-VIRUS TYPE CAN COUNTERACT AN MESSENGER-RNA DOWNREGULATORY ELEMENT OF THE TRANSFERRIN RECEPTOR MESSENGER-RNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID VIRAL MESSENGER-RNA; IRON-RESPONSIVE ELEMENTS; 3' UNTRANSLATED REGION; GENE-EXPRESSION; PROTEIN; TRANSLATION; STABILITY; SEQUENCES; IDENTIFICATION; TRANSPORT AB Expression of the structural proteins of the human immunodeficiency virus type 1 (HIV-1), the human T-cell leukemia virus type I (HTLV-I), and of the transferrin receptor (TfR) mRNA depends on posttranscriptional regulatory mechanisms involving both positive and negative elements. In these systems the presence of elements decreasing mRNA expression have been demonstrated. The regulatory proteins (Rev, Rex or iron response element binding protein IRE-BP) antagonize the effects of the downregulatory elements by interacting directly with specific mRNA sites (Rev responsive element, RRE, Rex responsive element, RXRE, or iron responsive elements, IREs) resulting in stabilization and efficient expression of the corresponding mRNAs. To investigate whether this strategy involves common pathways of mRNA utilization, we have studied expression from hybrid mRNAs that contained these previously identified HIV-1 or TfR instability determinants and the binding sites of the regulatory proteins Rev, Rex and/or IRE-BP. Out results demonstrate that only low levels of these hybrid mRNAs accumulate in the absence of the positive regulatory factors Rev, Rex or IRE-BP. The presence of these factors counteracts the effect of heterologous downregulatory elements resulting in increased accumulation of the hybrid mRNAs. However, while Rev or Rex regulation also resulted in efficient protein expression, the IRE-BP only affected mRNA levels without significantly affecting protein expression, suggesting that the pathways of mRNA stabilization/expression are different in these systems. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, HUMAN RETROVIRUS PATHOGENESIS GRP, FREDERICK, MD 21702 USA. NICHHD, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. FU NCI NIH HHS [N0-CO-74101] NR 47 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 11 PY 1994 VL 22 IS 22 BP 4725 EP 4732 DI 10.1093/nar/22.22.4725 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU199 UT WOS:A1994PU19900025 PM 7984424 ER PT J AU BORODOVSKY, M RUDD, KE KOONIN, EV AF BORODOVSKY, M RUDD, KE KOONIN, EV TI INTRINSIC AND EXTRINSIC APPROACHES FOR DETECTING GENES IN A BACTERIAL GENOME SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN-CODING REGIONS; ESCHERICHIA-COLI GENOME; ACID SUBSTITUTION MATRICES; DNA-SEQUENCES; CODON PREFERENCE; IDENTIFICATION; STATISTICS; MINUTES; RECOGNITION; PREDICTION AB The unannotated regions of the Escherichia coli genome DNA sequence from the EcoSeq6 database, totaling 1,278 'intergenic' sequences of the combined length of 359,279 basepairs, were analyzed using computer-assisted methods with the aim of identifying putative unknown genes. The proposed strategy for finding new genes includes two key elements: i) prediction of expressed open reading frames (ORFs) using the GeneMark method based on Markov chain models for coding and non-coding regions of Escherichia coli DNA, and ii) search for protein sequence similarities using programs based on the BLAST algorithm and programs for motif identification. A total of 354 putative expressed ORFs were predicted by GeneMark. Using the BLASTX and TBLASTN programs, it was shown that 208 ORFs located in the unannotated regions of the E.coli chromosome are significantly similar to other protein sequences. Identification of 182 ORFs as probable genes was supported by both GeneMark and BLAST, comprising 51.4% of the GeneMark 'hits' and 87.5% of the BLAST 'hits'. 73 putative new genes, comprising 20.6% of the GeneMark predictions, belong to ancient conserved protein families that include both eubacterial and eukaryotic members. This value is close to the overall proportion of highly conserved sequences among eubacterial proteins, indicating that the majority of the putative expressed ORFs that are predicted by GeneMark, but have no significant BLAST hits, nevertheless are likely to be real genes. The majority of the putative genes identified by BLAST search have been described since the release of the EcoSeq6 database, but about 70 genes have not been detected so far. Among these new identifications are genes encoding proteins with a variety of predicted functions including dehydrogenases, kinases, several other metabolic enzymes, ATPases, rRNA methyltransferases, membrane proteins, and different types of regulatory proteins. C1 NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. RP GEORGIA INST TECHNOL, SCH BIOL, ATLANTA, GA 30332 USA. FU NHGRI NIH HHS [HG00783]; NIGMS NIH HHS [GM47853] NR 64 TC 74 Z9 146 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 11 PY 1994 VL 22 IS 22 BP 4756 EP 4767 DI 10.1093/nar/22.22.4756 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU199 UT WOS:A1994PU19900029 PM 7984428 ER PT J AU DOBI, AL MATSUMOTO, K SANTHA, E VONAGOSTON, D AF DOBI, AL MATSUMOTO, K SANTHA, E VONAGOSTON, D TI GUANINE SPECIFIC CHEMICAL SEQUENCING OF DNA BY OSMIUM-TETROXIDE SO NUCLEIC ACIDS RESEARCH LA English DT Note ID CELLS C1 NICHHD,LDN,MOLEC CONTROL NEURODIFFERENT UNIT,BETHESDA,MD 20892. RI Matsumoto, Ken/F-9083-2013 OI Matsumoto, Ken/0000-0002-7864-3394 NR 10 TC 12 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 11 PY 1994 VL 22 IS 22 BP 4846 EP 4847 DI 10.1093/nar/22.22.4846 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU199 UT WOS:A1994PU19900044 PM 7984442 ER PT J AU CAUDLE, RM AF CAUDLE, RM TI FOSTERING YOUNG INVESTIGATORS SO SCIENCE LA English DT Letter RP CAUDLE, RM (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 11 PY 1994 VL 266 IS 5187 BP 953 EP 953 DI 10.1126/science.7973668 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ924 UT WOS:A1994PQ92400003 PM 7973668 ER PT J AU MCGAREY, BM AF MCGAREY, BM TI NIH RESEARCH COLLABORATION SO SCIENCE LA English DT Letter RP MCGAREY, BM (reprint author), NIH,OFF TECHNOL TRANSFER,BOX OTT,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 11 PY 1994 VL 266 IS 5187 BP 955 EP 955 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ924 UT WOS:A1994PQ92400009 PM 7973673 ER PT J AU BURTON, DR PYATI, J KODURI, R SHARP, SJ THORNTON, GB PARREN, PWHI SAWYER, LSW HENDRY, RM DUNLOP, N NARA, PL LAMACCHIA, M GARRATTY, E STIEHM, ER BRYSON, YJ CAO, YZ MOORE, JP HO, DD BARBAS, CF AF BURTON, DR PYATI, J KODURI, R SHARP, SJ THORNTON, GB PARREN, PWHI SAWYER, LSW HENDRY, RM DUNLOP, N NARA, PL LAMACCHIA, M GARRATTY, E STIEHM, ER BRYSON, YJ CAO, YZ MOORE, JP HO, DD BARBAS, CF TI EFFICIENT NEUTRALIZATION OF PRIMARY ISOLATES OF HIV-1 BY A RECOMBINANT HUMAN MONOCLONAL-ANTIBODY SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SOLUBLE CD4; COMBINATORIAL LIBRARIES; TYPE-1; GP120; ASSAY; VACCINE; BINDING; GP160; GENES AB The ability of antibodies to neutralize diverse primary isolates of human immunodeficiency virus-type 1 in vitro has been questioned, with implications for the likely efficacy of vaccines. A recombinant human antibody to envelope glycoprotein gp120 was generated and used to show that primary isolates are not refractory to antibody neutralization. The recombinant antibody neutralized more than 75 percent of the primary isolates tested at concentrations that could be achieved by passive immunization, for example, to interrupt maternal-fetal transmission of virus. The broad specificity and efficacy of the antibody implies the conservation of a structural feature on gp120, which could be important in vaccine design. C1 SCRIPPS RES INST, DEPT BIOL MOLEC, LA JOLLA, CA 92037 USA. RW JOHNSON PHARMACEUT RES INST, SAN DIEGO, CA 92121 USA. CALIF DEPT HLTH SERV, VIRAL & RICKETTSIAL DIS LAB, BERKELEY, CA 94704 USA. NCI, FREDERICK CANC RES & DEV CTR, TUMOR CELL BIOL LAB, VIRUS BIOL SECT, FREDERICK, MD 21702 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PEDIAT, LOS ANGELES, CA 90024 USA. NYU, SCH MED, AARON DIAMOND AIDS RES CTR, NEW YORK, NY 10016 USA. RP BURTON, DR (reprint author), SCRIPPS RES INST, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. OI Thornton, George/0000-0002-8744-4987; Parren, Paul/0000-0002-4365-3859 FU NIAID NIH HHS [AI27742, AI33292, AI35168] NR 38 TC 859 Z9 872 U1 1 U2 32 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 11 PY 1994 VL 266 IS 5187 BP 1024 EP 1027 DI 10.1126/science.7973652 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ924 UT WOS:A1994PQ92400038 PM 7973652 ER PT J AU RUSSELL, SM JOHNSTON, JA NOGUCHI, M KAWAMURA, M BACON, CM FRIEDMANN, M BERG, M MCVICAR, DW WITTHUHN, BA SILVENNOINEN, O GOLDMAN, AS SCHMALSTIEG, FC IHLE, JN OSHEA, JJ LEONARD, WJ AF RUSSELL, SM JOHNSTON, JA NOGUCHI, M KAWAMURA, M BACON, CM FRIEDMANN, M BERG, M MCVICAR, DW WITTHUHN, BA SILVENNOINEN, O GOLDMAN, AS SCHMALSTIEG, FC IHLE, JN OSHEA, JJ LEONARD, WJ TI INTERACTION OF IL-2R-BETA AND GAMMA(C) CHAINS WITH JAK1 AND JAK3 - IMPLICATIONS FOR XSCID AND XCID SO SCIENCE LA English DT Article ID HUMAN INTERLEUKIN-2 RECEPTOR; COMBINED IMMUNODEFICIENCY DISEASE; IL-2 RECEPTOR; TYROSINE PHOSPHORYLATION; FUNCTIONAL COMPONENT; HEMATOPOIETIC-CELLS; MOLECULAR-CLONING; LYMPHOCYTES-T; BETA; EXPRESSION AB Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta (IL-2R beta) and common gamma (gamma(c)) chains. Mutations of gamma(c) can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma(c)) and IL-9 (whose receptor is shown here to contain gamma(c)) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma(c), respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma(c) associations. Truncations of gamma(c), and a gamma(c), point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma(c)-Jak3 association. Thus, gamma(c) mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype. C1 NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, EXPTL IMMUNOL LAB, FREDERICK, MD 21702 USA. ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38163 USA. UNIV TEXAS, MED BRANCH, DEPT PEDIAT, DIV IMMUNOL & ALLERGY, GALVESTON, TX 77555 USA. RP NHLBI, MOLEC IMMUNOL LAB, BLDG 10, BETHESDA, MD 20892 USA. RI Russell, Sarah/B-9341-2009; McVicar, Daniel/G-1970-2015 OI Russell, Sarah/0000-0001-5826-9641; FU NCI NIH HHS [P30 CA21765]; NIDDK NIH HHS [R01 DK42932] NR 41 TC 570 Z9 578 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD NOV 11 PY 1994 VL 266 IS 5187 BP 1042 EP 1045 DI 10.1126/science.7973658 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ924 UT WOS:A1994PQ92400044 PM 7973658 ER PT J AU SHORES, EW HUANG, K TRAN, T LEE, E GRINBERG, A LOVE, PE AF SHORES, EW HUANG, K TRAN, T LEE, E GRINBERG, A LOVE, PE TI ROLE OF TCR ZETA-CHAIN IN T-CELL DEVELOPMENT AND SELECTION SO SCIENCE LA English DT Article ID ANTIGEN RECEPTOR; TRANSGENIC MICE; ACTIVATION; EXPRESSION; COMPLEX; THYMOCYTES; LACKING; DOMAIN; RAG-1; TAIL AB Signals mediated by the T cell receptor (TCR) are required for thymocyte maturation and selection. To examine the role of TCR zeta chain signals in development, TCR expression was restored in zeta-deficient mice with transgenic zeta chains that partially or completely lacked sequences required for signal transduction. The zeta chain played a role in thymic development by promoting TCR surface expression, but zeta-mediated signals were not essential because TCRs that contained signaling-deficient zeta chains promoted T cell maturation and transduced signals associated with thymic selection. C1 NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. RP SHORES, EW (reprint author), US FDA,CTR BIOL,DIV HEMATOL PROD,BETHESDA,MD 20892, USA. NR 33 TC 122 Z9 122 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 11 PY 1994 VL 266 IS 5187 BP 1047 EP 1050 DI 10.1126/science.7526464 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ924 UT WOS:A1994PQ92400046 PM 7526464 ER PT J AU RAULLI, RE JACKSON, B TANDON, N MATTSON, M RICE, K JAMIESON, GA AF RAULLI, RE JACKSON, B TANDON, N MATTSON, M RICE, K JAMIESON, GA TI PHENCYCLIDINE INHIBITS EPINEPHRINE-STIMULATED PLATELET-AGGREGATION INDEPENDENTLY OF HIGH-AFFINITY N-METHYL-D-ASPARTATE (NMDA)-TYPE GLUTAMATE RECEPTORS SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE PHENCYCLIDINE; PLATELET; EPINEPHRINE; AGGREGATION; NMDA RECEPTOR ID BLOOD-PLATELETS; RECEPTORS; BRAIN AB The psychotomimetic analgesic phencyclidine (PCP), which binds to a high affinity site on the neuronal N-methyl-D-aspartate (NMDA)-sensitive glutamate receptor, has previously been found to bind to platelets with high affinity and to specifically delay the onset of epinephrine-stimulated platelet aggregation (Jamieson et al. (1992) Biochem. J. 285, 35-39). We have now shown that the rank order of binding affinities of 14 synthetic PCP analogs at the high affinity binding site on platelets does not parallel the rank order of their affinities in binding to rat brain membranes, indicating that the high affinity PCP binding site in platelets is distinct from the neuronal NMDA receptor. The order of potency of six of these analogs in delaying the onset of epinephrine-stimulated platelet aggregation also did not parallel the rank order of their binding affinities for platelet or brain binding sites. These data indicate that the ability of PCP analogs to inhibit epinephrine-stimulated aggregation is not related to their ability to bind to the high affinity platelet PCP binding site. Furthermore, (+)MK-801, which binds to the same high affinity binding site in neurons as does PCP, failed to inhibit epinephrine-stimulated platelet aggregation, further suggesting that the site at which PCP acts in platelets is not related to the NMDA-type glutamate receptor. Further studies showed that 5-HT2 receptors and effects on platelet secretion are not involved in PCP-mediated inhibition of epinephrine-induced platelet aggregation. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RP RAULLI, RE (reprint author), AMER RED CROSS,DEPT CELL BIOL,15601 CRABBS BRANCH WAY,ROCKVILLE,MD 20855, USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD NOV 10 PY 1994 VL 1224 IS 2 BP 175 EP 180 DI 10.1016/0167-4889(94)90188-0 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PR790 UT WOS:A1994PR79000003 PM 7981230 ER PT J AU XIAO, W LI, GY LESIAK, K DONG, BH SILVERMAN, RH TORRENCE, PF AF XIAO, W LI, GY LESIAK, K DONG, BH SILVERMAN, RH TORRENCE, PF TI SYNTHESIS OF A 5'-THIOPHOSPHATE ANALOG OF 2-5A, A PHOSPHATASE RESISTANT ACTIVATOR OF THE 2-5A-DEPENDENT RIBONUCLEASE SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PHOSPHOROTHIOATE ANALOGS; NUCLEOTIDES AB The 5'-thiophosphate analogue of the small oligonucleotide mediator of the anti-picornavirus action of interferon was synthesized and shown to be highly resistant to enzymic 5'-dephosphorylation and to activate the 2-5A-dependent ribonuclease as effectively as parent p5'A2'p5'A2'p5'A itself. C1 NIDDK,MED CHEM LAB,BIOMED CHEM SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV ALLERGEN PROD & PARASITOL,BIOPHYS LAB,BETHESDA,MD 20892. CLEVELAND CLIN FDN,RES INST,DEPT CANC BIOL,CLEVELAND,OH 44195. NR 14 TC 25 Z9 25 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 10 PY 1994 VL 4 IS 21 BP 2609 EP 2614 DI 10.1016/S0960-894X(01)80294-8 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA PT379 UT WOS:A1994PT37900023 ER PT J AU LODI, P AF LODI, P TI MASCULINE VIEW SO NATURE LA English DT Letter RP LODI, P (reprint author), NIDDK,LCP,BLDG 5,ROOM B2-33,5 CTR DR MSC-0505,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 10 PY 1994 VL 372 IS 6502 BP 124 EP 124 DI 10.1038/372124e0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ688 UT WOS:A1994PQ68800024 ER PT J AU BARRETT, AJ HOROWITZ, MM POLLOCK, BH ZHANG, MJ BORTIN, MM BUCHANAN, GR CAMITTA, BM OCHS, J GRAHAMPOLE, J ROWLINGS, PA RIMM, AA KLEIN, JP SHUSTER, JJ SOBOCINSKI, KA GALE, RP AF BARRETT, AJ HOROWITZ, MM POLLOCK, BH ZHANG, MJ BORTIN, MM BUCHANAN, GR CAMITTA, BM OCHS, J GRAHAMPOLE, J ROWLINGS, PA RIMM, AA KLEIN, JP SHUSTER, JJ SOBOCINSKI, KA GALE, RP TI BONE-MARROW TRANSPLANTS FROM HLA-IDENTICAL SIBLINGS AS COMPARED WITH CHEMOTHERAPY FOR CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA IN A 2ND REMISSION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE LYMPHOCYTIC-LEUKEMIA; PEDIATRIC-ONCOLOGY-GROUP; TOTAL-BODY IRRADIATION; 2ND REMISSION; COMBINATION CHEMOTHERAPY; CYTOSINE-ARABINOSIDE; RELAPSE; THERAPY; 1ST AB Background. It is unclear how best to treat children with acute lymphoblastic leukemia who are in a second remission after a bone marrow relapse. For those with HLA-identical siblings, the question of whether to perform a bone marrow transplantation or to continue chemotherapy has not been answered. Methods. We compared the results of treatment with marrow transplants from HLA-identical siblings in 376 children, as reported to the International Bone Marrow Transplant Registry, with the results of chemotherapy in 540 children treated by the Pediatric Oncology Group. A preliminary analysis identified variables associated with treatment failure in both groups. We selected cohorts by matching these variables. A possible bias associated with differences in the interval between remission and treatment was controlled for by choosing matched pairs in which the duration of the second remission in the chemotherapy recipient was at least as long as the time between the second remission and transplantation in the transplant recipient. A total of 255 matched pairs were studied. Results. The mean (+/- SE) probability of a relapse at five years was significantly lower among the transplant recipients than among the chemotherapy recipients (45 +/- 4 percent vs. 80 +/- 3 percent, P < 0.001). At five years the probability of leukemia-free survival was higher after transplantation than after chemotherapy (40 +/- 3 percent vs. 17 +/- 3 percent, P < 0.001). The relative benefit of transplantation as compared with chemotherapy was similar in children with prognostic factors indicating a high or low risk of relapse (the duration of the first remission, age, leukocyte count at the time of the diagnosis, and phenotype of the leukemic cells). Conclusions. For children with acute lymphoblastic leukemia in a second remission, bone marrow transplants from HLA-identical siblings result in fewer relapses and longer leukemia-free survival than does chemotherapy. C1 MED COLL WISCONSIN, INT BONE MARROW TRANSPLANT REGISTRY, INST HLTH POLICY, MILWAUKEE, WI 53226 USA. NHLBI, BETHESDA, MD USA. MED COLL WISCONSIN, DEPT PEDIAT, MILWAUKEE, WI 53226 USA. MED COLL WISCONSIN, DEPT BIOSTAT, MILWAUKEE, WI USA. UNIV FLORIDA, PEDIAT ONCOL GRP, STAT OFF, GAINESVILLE, FL USA. UNIV FLORIDA, COLL MED, GAINESVILLE, FL USA. UNIV TEXAS, SW MED CTR, DALLAS, TX USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN USA. CASE WESTERN RESERVE UNIV, SCH MED, CLEVELAND, OH USA. SALICK HLTH CARE, LOS ANGELES, CA USA. FU NCI NIH HHS [CA-33625, U10-CA-29139, P01-CA-40053] NR 35 TC 186 Z9 189 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 10 PY 1994 VL 331 IS 19 BP 1253 EP 1258 DI 10.1056/NEJM199411103311902 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PP752 UT WOS:A1994PP75200002 PM 7935682 ER PT J AU LIE, RT WILCOX, AJ SKJERVEN, R AF LIE, RT WILCOX, AJ SKJERVEN, R TI RISK OF RECURRENCE OF BIRTH-DEFECTS - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIEHS,RES TRIANGLE PK,NC 27709. RP LIE, RT (reprint author), MED BIRTH REGISTRY NORWAY,N-5021 BERGEN,NORWAY. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 10 PY 1994 VL 331 IS 19 BP 1310 EP 1310 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PP752 UT WOS:A1994PP75200017 ER PT J AU BILSKY, EJ BERNSTEIN, RN DAVIS, P CALDERON, SN RICE, KC ROTHMAN, RB PORRECA, F AF BILSKY, EJ BERNSTEIN, RN DAVIS, P CALDERON, SN RICE, KC ROTHMAN, RB PORRECA, F TI CHARACTERIZATION OF ENANTIOMERS OF (+/-)BW373U86 AND RELATED-COMPOUNDS - HIGHLY SELECTIVE NONPEPTIDIC DELTA-OPIOID AGONISTS SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS C1 NIH,MED CHEM LAB,BETHESDA,MD 20892. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RP BILSKY, EJ (reprint author), UNIV ARIZONA,DEPT PHARMACOL,TUCSON,AZ 85724, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 25 EP 26 DI 10.1016/0167-0115(94)90371-9 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800014 ER PT J AU CHA, XY XU, H CALDERON, SN SMITH, LE RICE, KC PORRECA, F ROTHMAN, RB AF CHA, XY XU, H CALDERON, SN SMITH, LE RICE, KC PORRECA, F ROTHMAN, RB TI BW373U86, ITS ENANTIOMERS, AND RELATED-COMPOUNDS - INTERACTIONS OF NONPEPTIDE DELTA-AGONISTS AT MULTIPLE DELTA(CX) BINDING-SITES IN RAT-BRAIN SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS ID OPIOID RECEPTOR COMPLEX AB Previous studies delineated two classes of delta binding sites: a delta binding site not associated with the opioid receptor complex, termed the delta(ncx) site, and a delta site associated with the opioid receptor complex, termed the delta(cx) site (for review see (1)). More recent studies resolved two delta(cx) binding sites in rat brain termed delta(cx-1) and delta(cx-2) (2). Pretreatment of membranes with the delta-selective acylating agent (+)-trans-SUPERFIT depletes membranes of the delta(ncx) binding site which permits selective labeling of the delta(cx) binding sites with [H-3]DADLE (3). Ligand-selectivity studies of the non-peptide delta agonist, BW373U86, its enantiomers and related compounds showed that these drugs have higher affinities for delta sites than mu sites (4,5). This study determined the selectivity of these compounds for the two delta(cx) binding sites. The data indicate that (+)-4-[(alpha R)-alpha((2S,5R)-4-allyl-2,5-dimethyl-1- piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80) and deltorphin-II are highly selective for delta(cx-2) binding site (2758-fold and 700-fold respectively). In contrast, morphine is selective for delta(cx-1) binding site (78-fold). C1 NIDDK,BETHESDA,MD 20892. UNIV ARIZONA,DEPT PHARMACOL,TUCSON,AZ 85724. RP CHA, XY (reprint author), NIDA,IRP,1CPS,BALTIMORE,MD 21224, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 45 EP 46 DI 10.1016/0167-0115(94)90381-6 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800024 ER PT J AU GOODMAN, CB EMILIEN, B CADET, JL ROTHMAN, RB AF GOODMAN, CB EMILIEN, B CADET, JL ROTHMAN, RB TI CHRONIC ICV INFUSION OF MORPHINE AND NPFF DOWN-REGULATE MU-OPIOID RECEPTORS IN RAT-BRAIN - A QUANTITATIVE AUTORADIOGRAPHIC STUDY SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS AB Regulation of the opioid mu receptor by pharmacological manipulation has been extensively investigated using various radioreceptor binding techniques. However, unlike most receptor systems, where chronic agonist administration induces a characteristic down-regulation in receptor density, prolonged morphine treatment has shown conflicting results. Both up- and down-regulation of mu receptors by morphine have been reported (for review; see (1)). Our lab recently demonstrated that morphine modulating peptide, NPFF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2), down-regulates opioid it receptors (2). The purpose of this study was to compare the effects of chronic ICV infusion of morphine and NPFF on mu opioid binding sites using the in vitro techniques of whole brain homogenate receptor binding and autoradiography. C1 NIDA,IRP,MNS,BALTIMORE,MD 21224. RP GOODMAN, CB (reprint author), NIDA,IRP,CPS,BALTIMORE,MD 21224, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 107 EP 108 DI 10.1016/0167-0115(94)90412-X PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800055 ER PT J AU IZENWASSER, S AF IZENWASSER, S TI INCREASED MU-OPIOID EFFICACY FOR INHIBITION OF ADENYLYL-CYCLASE INDUCED BY CHRONIC TREATMENT WITH NALTREXONE OR COCAINE SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS RP IZENWASSER, S (reprint author), NIDA,INTRAMURAL RES PROGRAM,PSYCHOBIOL SECT,POB 5180,BALTIMORE,MD, USA. RI Izenwasser, Sari/G-9193-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 131 EP 131 DI 10.1016/0167-0115(94)90424-3 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800067 ER PT J AU JOHNSON, PS WANG, JB UHL, GR AF JOHNSON, PS WANG, JB UHL, GR TI MU-OPIATE RECEPTOR STRUCTURE-FUNCTION STUDIES .2. EFFECTS ON 2ND MESSENGER SYSTEMS SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS C1 NIDA,INTRAMURAL RES PROGRAM,OFF DIRECTOR,BALTIMORE,MD 21224. NIGMS,PHARMACOL RES ASSOCIATE PROGRAM,BETHESDA,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL & NEUROSCI,BALTIMORE,MD 21218. RP JOHNSON, PS (reprint author), NIDA,INTRAMURAL RES PROGRAM,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224, USA. NR 6 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 139 EP 140 DI 10.1016/0167-0115(94)90429-4 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800072 ER PT J AU LAI, J BILSKY, EJ BERNSTEIN, RN ROTHMAN, RB PASTERNAK, GW PORRECA, F AF LAI, J BILSKY, EJ BERNSTEIN, RN ROTHMAN, RB PASTERNAK, GW PORRECA, F TI ANTISENSE OLIGODEOXYNUCLEOTIDE TO THE CLONED DELTA-OPIOID RECEPTOR SELECTIVELY INHIBITS SUPRASPINAL, BUT NOT SPINAL, ANTINOCICEPTIVE EFFECTS OF [D-ALA(2),GLU(4)]DELTORPHIN SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS ID BENZOFURAN ANALOG NTB; DIFFERENTIAL ANTAGONISM; SUBTYPES; NALTRINDOLE; EXPRESSION; AGONISTS; CLONING; MICE C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. RP LAI, J (reprint author), UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT PHARMACOL,TUCSON,AZ 85724, USA. NR 13 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 159 EP 160 DI 10.1016/0167-0115(94)90439-1 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800082 ER PT J AU LONDON, ED VAUPEL, DB KIMES, AS AF LONDON, ED VAUPEL, DB KIMES, AS TI INHIBITORS OF NITRIC-OXIDE SYNTHASE AS POTENTIAL TREATMENTS FOR OPIOID WITHDRAWAL SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS RP LONDON, ED (reprint author), NATL INST DRUG ABUSE,NEUROIMAGING & DRUG ACT SECT,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD, USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 165 EP 166 DI 10.1016/0167-0115(94)90442-1 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800085 ER PT J AU MOUSA, SA MITCHELL, WM HASSAN, AHS CARTER, L STEIN, C AF MOUSA, SA MITCHELL, WM HASSAN, AHS CARTER, L STEIN, C TI CORTICOTROPIN-RELEASING FACTOR RECEPTORS IN INFLAMED TISSUE - AUTORADIOGRAPHIC IDENTIFICATION SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS AB We have shown that injecting corticotropin releasing factor (CRF) into inflamed rat paws causes the local release of endogenous opioids to inhibit pain. The purpose of the current study was to visualize CRF receptors by means of in vitro receptor autoradiography. We used I-125-CRF as a ligand on sections of popliteal lymph nodes, subcutaneous tissue of hind paws and spleen of rats. The density of I-125-CRF labelled receptors was higher in inflamed lymph nodes than in noninflamed lymph nodes (P=0.0431, Wilcoxon test). Similarly, the density of CRF receptors was significantly higher in inflamed than in noninflamed paws (P=0.0431, Wilcoxon test). This increase in CRF receptors indicates an upregulation of CRF binding sites in inflamed tissue. These findings are consistent with our in vivo studies which have shown potent antinoceciptive effects of locally applied CRF in inflamed but not in noninflamed tissue. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RP MOUSA, SA (reprint author), JOHNS HOPKINS UNIV,DEPT ANESTHESIOL,BALTIMORE,MD, USA. OI Stein, Christoph/0000-0001-5240-6836 NR 2 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 203 EP 204 DI 10.1016/0167-0115(94)90461-8 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800104 ER PT J AU NI, Q XU, H PARTILLA, JS PORRECA, F CALDERON, SN RICE, KC SMITH, LE MCNUTT, RW ROTHMAN, RB AF NI, Q XU, H PARTILLA, JS PORRECA, F CALDERON, SN RICE, KC SMITH, LE MCNUTT, RW ROTHMAN, RB TI [H-3] SNC121 - A NOVEL HIGH-AFFINITY LIGAND FOR RAT-BRAIN DELTA-RECEPTORS - PRELIMINARY STUDIES SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS ID NCX BINDING-SITES; OPIOID-PEPTIDES; BW373U86; AGONIST; HETEROGENEITY; DRUGS AB Calderon et al. (1) recently prepared the enantiomers and their methoxy precursors of the non-peptide delta agonist (+/-)-BW373U86 and its benzlic epimer (2). In one of these enantiomers, SNC80, the allyl function was reduced with tritium gas to the corresponding propyl derivative to yield [H-3]SNC121 (SA=26.8 Ci/mmol). Experiments with non-radioactive SNC-121 indicated that it had high affinity and selectivity (>1000-fold) for rat brain delta receptors. Incubations proceeded for 4-6 hr at 25 degrees C (equilibrium) in 50 mM Tris-HCl, pH 7.4 with rat brain membranes. [H-3]SNC121 labeled two binding sites: an opioid binding site and a non-opioid drug binding site. For the expetiments reported here, DADL (10 mu M) was used to define non-specific binding. Under these conditions, we obtained 70%-75% specific binding. [H-3]SNC121 labeled an apparent single class of binding sites with a delta-like ligand selectivity profile. GppNHp and sodium decreased [H-3]SNC121 binding by altering the K-d (P < 0.05) without changing the Bmax. GppNHp (20 mu M) failed to strikingly alter the IC50 and slope factor of DPDPE, Deltotphin-II and naltrindofe when displacing [H-3]-SNC121. Viewed collectively, [H-3]SNC121 selectively labels a single class of delta opioid receptors in a manner consistent with an agonist-type interaction. Future experiments will determine the nature and/or function of the non-opioid [H-3]-SNC121 binding site. C1 UNIV ARIZONA,DEPT PHARMACOL,TUCSON,AZ 85724. NIDDK,BETHESDA,MD 20892. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. RP NI, Q (reprint author), NIDA,IRP,CPS,BALTIMORE,MD 21224, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 209 EP 210 DI 10.1016/0167-0115(94)90464-2 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800107 ER PT J AU ROTHMAN, RB XU, H WANG, JB PARTILLA, JS KAYAKIRI, H RICE, KC UHL, GR AF ROTHMAN, RB XU, H WANG, JB PARTILLA, JS KAYAKIRI, H RICE, KC UHL, GR TI THE LIGAND-SELECTIVITY OF CLONED HUMAN AND RAT OPIATE MU-RECEPTORS STUDIED WITH [I-125]IOXY-AGO SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS ID FUNCTIONAL EXPRESSION; OPIOID RECEPTOR; CLONING; BRAIN AB The recent molecular cloning of mu, delta and kappa opiate receptors (1-5) has created new opportunities for the study of opiate receptors. The recent cloning of the human mu receptor (6) has shown that there is a high homology between the predicted human and rat mu receptor sequences, but also some differences in sequence. We therefore sought significant changes in the ligand-selectivity profile of these two receptors expressed in the COS and CHO cell lines under identical assay conditions. We used the novel agonist ligand [I-125]IOXY-AGO (6 beta-[(125)Iodo]-3,14-dihydroxy-17-methyl-4,5 alpha-epoxymorphinan) since its high specific activity (2200 Ci/mmol) and high affinity for mu opioid receptors generated a high signal-to-noise ratio with use of relatively few expressing cells. (7). The results indicate substantial similarities in ligand-selectivity profile of the human and rat mu receptors, but also modest differences. C1 NIDA,MNB,BALTIMORE,MD 21224. NIDA,IRP,BALTIMORE,MD 21224. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. RP ROTHMAN, RB (reprint author), NIDA,CPS,BALTIMORE,MD 21224, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 249 EP 250 DI 10.1016/0167-0115(94)90483-9 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800126 ER PT J AU SCHAFER, M CARTER, L STEIN, C AF SCHAFER, M CARTER, L STEIN, C TI INTERLEUKIN-1 AND CORTICOTROPIN-RELEASING FACTOR-INDUCED RELEASE OF D-ENDORPHIN FROM IMMUNE CELLS AND INHIBITION OF INFLAMMATORY PAIN SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS ID OPIOID RECEPTORS; INFLAMED TISSUE; PEPTIDES AB Local analgesic effects of exogenous opioid agonists are particularly prominent in painful inflammatory conditions and are mediated by opioid receptors on peripheral sensory nerves (1-3). The endogenous ligands of these receptors, opioid peptides, have been demonstrated in resident immune cells within inflamed tissue of animals and humans (4-6). This study demonstrates in vitro that interleukin-1 (IL-1) and corticotropin releasing factor (CRF) produce acute release of immunoreactive beta-endorphin in cell suspensions freshly prepared from inflamed lymph nodes (7). This effect was reversible by IL-1 receptor antagonist or alpha-helical CRF, respectivly. In in vivo experiments local, but not systemic application of IL-1 and CRF resulted in potent analgesia in inflamed paws. This effect was reversed by IL-1 receptor antagonist (IL-1ra) or alpha-helical CRF, respectively, and by cyclosporine A, In vivo administration of antibodies against opioid peptides indicates that the effects of IL-1 and CRF are mediated by beta-endorphin and, in addition, by dynorphin A and [Met]enkephalin, respectively. Correspondingly, IL-1 effects are inhibited by mu-, alpha- and kappa- opioid antagonists, whereas CRF effects are attenuated by all except a kappa- antagonist (7). In conclusion, both IL-1 and CRF activate their receptors on immune cells to release opioids (predominantly beta-endorphin) that subsequently occupy their corresponding receptors on sensory nerves and result in antinociception. Methods: For in vitro experiments popliteal lymph nodes were removed from male Wistar rats with unilateral Freund's adjuvant - induced inflammation of the hindpaw. The tissue was ground using a cell dissociation sieve, immune cell suspensions (0.05 - 0.15 x 10(8) cells per ml) prepared and viable cells counted using the Trypan Blue exclusion method. The suspensions were incubated (10 min) with various concentrations of IL-1 or CRF with or without the antagonists IL-1ra or alpha-helical CRF, respectively. After centrifugation, supernatants were assayed for beta-endorphin by radioimmunoassay. In in vivo experiments Wistar rats with unilateral hindpaw inflammation were tested for basal nociceptive thresholds by use of a paw pressure test (5, 8). IL-1 or CRF were injected i.pl or i.v. and their effects on paw pressure thresholds (PPT) reevaluated. Reversibility of these effects by IL-1ra or alpha-helical CRF, respectively and by pretreatment with cyclosporine A was tested. The involvement of opioid peptides was examined using antibodies against opioids, such as anti-beta-endorphin, anti-[Met]enkephalin and anti-dynorphin A. Seperate experiments assessed reversibility by naloxone and receptor selective antagonists. Results: In vitro experiments showed that both IL-1 and CRF produce dose-dependent release of immunoreactive D-endorphin from immune cell suspensions. IL-1 induced release was dose-dependently inhibited by IL-1ra, but not by alpha-helical CRF. CRF induced release was attenuated by a-helical CRF, but not by IL-1ra. In vivo, IL-1 and CRF (i.pl., but not i.v.) produced significant and dose-dependent elevations of PPT in inflamed, but not in noninflamed paws. These effects were dose-dependently reversed by IL-1ra and alpha-helical CRF, respectively, and by pretreatment with cyclosporine A. IL-1 effects were attenuated by passive immunization with anti-beta-endorphin and anti-dynorphin A, whereas CRF effects were inhibited by anti-beta-endorphin and anti-[Met]enkephalin. Naloxone, the mu- (CTOP) and the alpha- (ICI 174,864) antagonist attenuated both IL-1 and CRF- effects, but the kappa- antagonist only reversed the IL-1 effect. Conclusions: Both IL-1 and CRF induce the release of opioid peptides (predominantly beta-endorphin), via activation of their respective receptors on immunocytes. In addition, dynorphin A and [Met]enkephalin appear to be liberated by IL-1 and CRF, respectively. Under inflammatory pain conditions this release can lead to subsequent activation of corresponding opioid receptors located on peripheral sensory nerves and results in potent antinociception (7). C1 NIDA,ARC,BALTIMORE,MD 21287. RP SCHAFER, M (reprint author), JOHNS HOPKINS UNIV,DEPT ANESTHESIA,600 N WOLFE ST,BALTIMORE,MD 21287, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 255 EP 256 DI 10.1016/0167-0115(94)90486-3 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800129 ER PT J AU SHIPPENBERG, TS HEIDBREDER, C AF SHIPPENBERG, TS HEIDBREDER, C TI ROLE OF KAPPA-OPIOID AND DELTA-OPIOID SYSTEMS IN MODULATING SENSITIZATION TO THE REWARDING EFFECTS OF COCAINE SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS ID INCREASES RP SHIPPENBERG, TS (reprint author), NIDA,INTRAMURAL RES PROGRAM,PRECLIN PHARMACOL LAB,BALTIMORE,MD, USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 273 EP 274 DI 10.1016/0167-0115(94)90495-2 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800138 ER PT J AU SURRATT, CK JOHNSON, PS MORIWAKI, A SEIDLECK, BK BLASCHAK, CJ WANG, JB YUHASZ, S UHL, GR AF SURRATT, CK JOHNSON, PS MORIWAKI, A SEIDLECK, BK BLASCHAK, CJ WANG, JB YUHASZ, S UHL, GR TI MU-OPIATE RECEPTOR STRUCTURE/FUNCTION RELATIONSHIPS .3. SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS C1 NIDA,INTRAMURAL RES PROGRAM,OFF DIRECTOR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL & NEUROSCI,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOPHYS,BALTIMORE,MD 21224. NIGMS,BETHESDA,MD. RP SURRATT, CK (reprint author), NIDA,INTRAMURAL RES PROGRAM,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 289 EP 290 DI 10.1016/0167-0115(94)90503-7 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800146 ER PT J AU UNTERWALD, EM RUBENFELD, JM SPANGLER, R IMAI, Y WANG, JB UHL, GR KREEK, MJ AF UNTERWALD, EM RUBENFELD, JM SPANGLER, R IMAI, Y WANG, JB UHL, GR KREEK, MJ TI MU-OPIOID RECEPTOR MESSENGER-RNA LEVELS FOLLOWING CHRONIC NALTREXONE ADMINISTRATION SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS ID PREPROENKEPHALIN MESSENGER-RNA; SOLUTION HYBRIDIZATION ASSAY; EXPRESSION; TISSUES C1 NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. RP UNTERWALD, EM (reprint author), ROCKEFELLER UNIV,1230 YORK AVE,NEW YORK,NY 10021, USA. NR 6 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 307 EP 308 DI 10.1016/0167-0115(94)90512-6 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800155 ER PT J AU WANG, JB IMAI, Y JOHNSON, PS WALTHER, D STEIN, C SCHAEFER, M WU, JM WANG, WF MORIWAKI, A UHL, GR AF WANG, JB IMAI, Y JOHNSON, PS WALTHER, D STEIN, C SCHAEFER, M WU, JM WANG, WF MORIWAKI, A UHL, GR TI HUMAN MU-RECEPTOR - GENE STRUCTURE, EXPRESSION, AND MU/KAPPA CHIMERAS THAT DEFINE NONTRANSMEMBRANE DOMAINS INFLUENCING PEPTIDE BINDING AFFINITIES SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS C1 NIDA,INTRAMURAL RES PROGRAM,PRECLIN BRANCH,BALTIMORE,MD. NIGMS,PHARMACOL RES ASSOCIATE PROGRAM,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL,BALTIMORE,MD. RP WANG, JB (reprint author), NIDA,OFF DIRECTOR,BALTIMORE,MD 21224, USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 317 EP 320 DI 10.1016/0167-0115(94)90517-7 PG 4 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800160 ER PT J AU XU, H PARTILLA, JS BECKETTS, KM KAYAKIRI, H RICE, KC ROTHMAN, RB AF XU, H PARTILLA, JS BECKETTS, KM KAYAKIRI, H RICE, KC ROTHMAN, RB TI [I-125] IOXY-AGO - A HIGH-AFFINITY, MU-SELECTIVE AGONIST OPIOID RECEPTOR-LIGAND SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 25th International Narcotics Research Conference (INRC) - Opioids and Their Receptors: Cloning and Beyond CY JUL 16-21, 1994 CL N FALMOUTH, MA SP NIDA, BERLEX BIOSCI, BIO-DEV CORP, GLAXO GRP RES LTD, HOFFMAN LAROCHE INC, JOHNSON & JOHNSON, NEUROBIOLOG TECH, PARKE DAVIS, SIGMA CHEM CO, SMITHKLINE BEECHAM PHARM, UPJOHN LABS ID BINDING-SITES; RAT-BRAIN; EXPRESSION; CLONING AB We previously reported that epimeric 6 beta-iodo-3,14-dihydroxy-17-cyclopropylmethyl-4,5 alpha-epoxymorphinan (IOXY) was a potent opioid receptor antagonist with high affinity mu, kappa(1) and kappa(2) binding sites (1,2). In order to compare the binding of agonist and antagonist ligands at cloned mu opioid receptors (3-5) (see Rothman et al., this meeting), we prepared the agonist analog of IOXY, IOXY-AGO for ''IOXY-agonist'' (6 beta-iodo-3,14-dihydroxy-17-methyl-4,5 alpha epoxymorphinan). This paper reports on [I-125]IOXY-AGO binding to rat brain membranes. [I-125]IOXY-AGO was radioiodinated (2200 Ci/mmol) as reported for [I-125]IOXY (1) and the product purified by HPLC. High affinity, specific (90 %) and reversible binding was demonstrated. NaCl and GppNHp inhibited [I-125]IOXY-AGO binding indicating that it possesses agonist properties. Its Ki values at opioid receptor subtypes were 0.28+/-0.04 (mu), 18.7+/-0.9 (delta) and 33.9+/-2.2 nM (kappa(1)), respectively. Competition studies showed that [I-125]IOXY-AGO selectively labeled mu receptors: mu-ligands, morphine, naloxone and DAMGO had nanomolar Ki values while delta- and kappa-ligands had moderate or weak Ki values. Viewed collectively, these data indicate that [I-125]IOXY-AGO is a very useful ligand for studies of opioid receptors. C1 NIDDK,LMC,BETHESDA,MD 20892. RP XU, H (reprint author), NIDA,IRP,BALTIMORE,MD 21224, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 10 PY 1994 VL 54 IS 1 BP 331 EP 332 DI 10.1016/0167-0115(94)90523-1 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PT358 UT WOS:A1994PT35800166 ER PT J AU SEDDON, JM AJANI, UA SPERDUTO, RD HILLER, R BLAIR, N BURTON, TC FARBER, MD GRAGOUDAS, ES HALLER, J MILLER, DT YANNUZZI, LA WILLETT, W AF SEDDON, JM AJANI, UA SPERDUTO, RD HILLER, R BLAIR, N BURTON, TC FARBER, MD GRAGOUDAS, ES HALLER, J MILLER, DT YANNUZZI, LA WILLETT, W TI DIETARY CAROTENOIDS, VITAMIN-A, VITAMIN-C, AND VITAMIN-E, AND ADVANCED AGE-RELATED MACULAR DEGENERATION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CIGARETTE SMOKERS; RETINA; PLASMA; ASCORBATE; LIGHT; RATS AB Objective.-To evaluate the relationships between dietary intake of carotenoids and vitamins A, C, and E and the risk of neovascular age-related macular degeneration (AMD), the leading cause of irreversible blindness among adults. Design.-The multicenter Eye Disease Case-Control Study. Setting.-Five ophthalmology centers in the United States. Patients.-A total of 356 case subjects who were diagnosed with the advanced stage of AMD within 1 year prior to their enrollment, aged 55 to 80 years, and residing near a participating clinical center. The 520 control subjects were from the same geographic areas as case subjects, had other ocular diseases, and were frequency-matched to cases according to age and sex. Main Outcome Measures.-The relative risk for AMD was estimated according to dietary indicators of antioxidant status, controlling for smoking and other risk factors, by using multiple logistic-regression analyses. Results.-A higher dietary intake of carotenoids was associated with a lower risk for AMD. Adjusting for other risk factors for AMD, we found that those in the highest quintile of carotenoid intake had a 43% lower risk for AMD compared with those in the lowest quintile (odds ratio, 0.57; 95% confidence interval, 0.35 to 0.92; P for trend=.02). Among the specific carotenoids, lutein and zeaxanthin, which are primarily obtained from dark green, leafy vegetables, were most strongly associated with a reduced risk for AMD (P for trend=.001). Several food items rich in carotenoids were inversely associated with AMD. In particular, a higher frequency of intake of spinach or collard greens was associated with a substantially lower risk for AMD (P for trend<.001). The intake of preformed vitamin A (retinol) was not appreciably related to AMD. Neither vitamin E nor total vitamin C consumption was associated with a statistically significant reduced risk for AMD, although a possibly lower risk for AMD was suggested among those with higher intake of vitamin C, particularly from foods. Conclusion.-Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing advanced or exudative AMD, the most visually disabling form of macular degeneration among older people. These findings support the need for further studies of this relationship. C1 MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. NEI,BETHESDA,MD 20892. UNIV ILLINOIS,DEPT OPHTHALMOL,CHICAGO,IL 60680. MED COLL WISCONSIN,DEPT OPHTHALMOL,MILWAUKEE,WI 53226. WILMER EYE INST,BALTIMORE,MD. CTR DIS CONTROL & PREVENT,DIV ENVIRONM HLTH LAB SCI,ATLANTA,GA 30341. MANHATTAN EYE EAR & THROAT HOSP,NEW YORK,NY 10021. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RP SEDDON, JM (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EPIDEMIOL UNIT,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY09972] NR 27 TC 842 Z9 870 U1 6 U2 78 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 9 PY 1994 VL 272 IS 18 BP 1413 EP 1420 DI 10.1001/jama.272.18.1413 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PP690 UT WOS:A1994PP69000028 PM 7933422 ER PT J AU HAUPT, R FEARS, TR ROBISON, LL MILLS, JL NICHOLSON, HS ZELTZER, LK MEADOWS, AT BYRNE, J AF HAUPT, R FEARS, TR ROBISON, LL MILLS, JL NICHOLSON, HS ZELTZER, LK MEADOWS, AT BYRNE, J TI EDUCATIONAL-ATTAINMENT IN LONG-TERM SURVIVORS OF CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE LYMPHOCYTIC-LEUKEMIA; CENTRAL NERVOUS-SYSTEM; CRANIAL IRRADIATION; IQ SCORES; CHILDREN; SEQUELAE; CANCER; PROPHYLAXIS; THERAPY; AGE AB Objective.-To determine the impact of treatment on scholastic performance in the first cohort of survivors of childhood acute lymphoblastic leukemia who are old enough to have completed their educational experience. Design.-Retrospective cohort study. Setting.-Twenty-three institutions in the Childrens Cancer Group. Subjects.-A total of 593 adult survivors of childhood acute lymphoblastic leukemia and 409 sibling controls. Outcome Measures.-Enrollment in special programs, grades during high school, graduation from high school, college admission, and college graduation. Results.-After diagnosis, survivors were more likely than their sibling controls to enter a special education (relative risk [RR] =3.4; P<.01) or a learning disabled (RR=3.6; P<.01) program, while just as likely to enter gifted and talented programs (RR=1.0). The risk associated with special education and learning disabled programs increased with increasing dose of cranial radiotherapy. Despite these problems, survivors generally had the same probability as their siblings of finishing high school, entering college, and earning a bachelor's degree. However, survivors treated with 24 Gy and those diagnosed before 6 years of age were less likely to enter college (RR=0.67 and 0.6, respectively; P<.01). Conclusions.-This large study demonstrates that childhood acute lymphoblastic leukemia survivors have a greater likelihood of being placed in special education or learning disabled programs than their siblings, but that most are able to overcome these problems. Dose of cranial radiotherapy and age at diagnosis are the most important education-related risk factors. C1 NCI,CLIN EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. NICHHD,EPIDEMIOL BRANCH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. UNIV MINNESOTA,DEPT PEDIAT,MINNEAPOLIS,MN 55455. UNIV CALIF LOS ANGELES,MED CTR,DEPT PEDIAT,LOS ANGELES,CA 90024. RI Haupt, Riccardo/C-2237-2012 FU NCI NIH HHS [N0I-CP-61012, CPI-5602, CPO-5625] NR 27 TC 108 Z9 108 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 9 PY 1994 VL 272 IS 18 BP 1427 EP 1432 DI 10.1001/jama.272.18.1427 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PP690 UT WOS:A1994PP69000030 PM 7933424 ER PT J AU ESCALANTE, C QASBA, PK YANG, DCH AF ESCALANTE, C QASBA, PK YANG, DCH TI EXPRESSION OF HUMAN ASPARTYL-TRANSFER-RNA SYNTHETASE IN COS CELLS SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE MULTIENZYME COMPLEX; AMPHIPHILIC HELIX; EPITOPE TAGGING; AMINOACYL-TRANSFER-RNA SYNTHETASES; SUBCELLULAR LOCALIZATION; IMMUNOFLUORESCENCE ID TRANSFER-RNA-SYNTHETASE; AMINOACYL-TRANSFER-RNA; ESCHERICHIA-COLI; AMPHIPHILIC HELIX; ELONGATION-FACTOR; SHEEP LIVER; COMPLEX; PURIFICATION; PROTEINS; ACID AB Mammalian aspartyl-tRNA synthetase (DRS) occurs in a multi-enzyme complex of aminoacyl-tRNA synthetases, while DRS exists as free soluble enzymes in bacteria and yeast. The properties of human DRS transient expressed in COS cells were examined. After transfection of COS cells with the recombinant plasmids pSVL-63 that contained hDRS cDNA coding and noncoding sequences, and pSV-hDRS where the non-coding sequences were deleted, DRS in the transfected COS cells significantly increased compared to mock transfected cells. COS cells transfected with pSV-hDRS Delta 32 that contained N-terminal 32 residue-coding sequence deleted hDRS cDNA showed no increase in DRS activity. Northern blot analysis showed that concentrations of corresponding mRNAs of hDRS and hDRS Delta 32 were greatly enhanced in transfected cells. The increases in the level of the transcripts were much higher than those of the corresponding proteins. Gel filtration analysis showed that hDRS in pSV-hDRS transfected cells expressed as a low molecular weight form of hDRS and pSV-hDRS Delta 32 transfected cells did not. Epitope tagging and indirect immunofluorescence microscopy was used to localize hDRS. Both hDRSmyc and hDRS Delta 32myc were localized in the cytoplasm and showed diffused patterns. These results showed that hDRS has little tendency to aggregate in vivo and suggested that the N-terminal extension in hDRS was not involved in the expression and sub-cellular localization of hDRS, but may play a role in the maintenance of enzymatic activity of hDRS in COS cells. C1 GEORGETOWN UNIV,DEPT CHEM,WASHINGTON,DC 20057. NCI,MATH BIOL LAB,BETHESDA,MD 20814. RI Yang, David/A-7294-2009 FU NIGMS NIH HHS [GM-25848] NR 37 TC 4 Z9 4 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV 9 PY 1994 VL 140 IS 1 BP 55 EP 63 DI 10.1007/BF00928366 PG 9 WC Cell Biology SC Cell Biology GA PV684 UT WOS:A1994PV68400006 PM 7877598 ER PT J AU KUSUI, T BENYA, RV BATTEY, JF JENSEN, RT AF KUSUI, T BENYA, RV BATTEY, JF JENSEN, RT TI GLYCOSYLATION OF BOMBESIN RECEPTORS - CHARACTERIZATION, EFFECT ON BINDING, AND G-PROTEIN COUPLING SO BIOCHEMISTRY LA English DT Article ID SWISS 3T3 CELLS; SITE-DIRECTED MUTAGENESIS; PANCREATIC ACINAR-CELLS; LINKED OLIGOSACCHARIDE CHAINS; CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR RECEPTOR; NEUROMEDIN-B-RECEPTOR; PEPTIDE RECEPTOR; HORMONE-BINDING; N-GLYCOSYLATION AB In the present study, we investigated the nature and the importance of glycosylation of two mammalian bombesin receptors, the neuromedin B receptor (NMB-R) and the gastrin-releasing peptide receptor (GRP-R), using chemical cross-linking and enzymatic deglycosylation. [I-125]-(D-Tyr(0))NMB cross-linked to native NMB-R on rat C-6 glioblastoma cells or rat NMB-R transfected into BALB 3T3 cells revealed a single broad band, M(r) = 63 000, on both cell types that was not altered by DTT. NMB inhibited cross-linking specifically and saturably with an IC50 of 4.8 and 6.1 nM for C-6 and NMB-R transfected cells, respectively, and there was a close correlation between its ability to inhibit binding and its ability to inhibit cross-linking. A single broad band of M(r) = 82 000 was cross-linked with [I-125]GRP on mouse GRP-R transfected BALB 3T3 cells. Peptide-N-4-(N-acetyl-beta-glucosaminyl)asparagine amidase F (PNGase F) digestion increased the mobility of the original band in C-6, NMB-R, and GRP-R transfected cell membranes. Endoglycosidase H (Endo-H) and endoglycosidase F-2 (Endo-F-2) digestion had no effect on both transfected cells. Neuraminidase digestion slightly increased the mobility of the original band in NMB-R transfected cell membranes; however, it had no effect on GRP-R transfected cell membranes. Endo-alpha-N-acetylglucosaminidase (O-glycanase) digestion subsequent to neuraminidase treatment showed no additional effect on either receptor. Serial partial deglycosylation of cross-linked NMB-Rs with PNGase F treatment for different incubation periods revealed one band of partially glycosylated receptor (53 kDa) besides the fully glycosylated and fully deglycosylated ones, showing that NMB-R has two oligosaccharide chains. Similarly, three partially deglycosylated species (72, 62, and 52 kDa) are seen with the GRP-R, indicating that the GRP-R has four oligosaccharide chains. Treatment of unlabeled membranes with PNGase F followed by affinity labeling resulted in fully deglycosylated NMB-R or 75% deglycosylated GRP-R. Deglycosylation of the NMB-R did not alter its affinity for NMB or alter G-protein coupling; however, 75% deglycosylation of the GRP-R both decreased its affinity for GRP and altered its ability to couple to G-proteins. The present results demonstrate that NMB-R on native and transfected cells is an N-linked sialoglycoprotein with two triantenary and/or tetraantenary complex oligosaccharide chains. The apparent M(r) of this sialoglycoprotein is 63 000, and this protein does not contain disulfide-linked subunits or O-linked carbohydrates. GRP-R is a similar N-linked glycoprotein of an apparent M(r) = 82 000, with four triantenary and/or tetraantenary complex oligosaccharide chains containing no sialic acid. In NMBR, glycosylation is not required for full affinity or G-protein coupling, whereas in GRP-R it plays a significant role in maintaining full high affinity and G-protein coupling. C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NCI,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 84 TC 30 Z9 30 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 8 PY 1994 VL 33 IS 44 BP 12968 EP 12980 DI 10.1021/bi00248a005 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ489 UT WOS:A1994PQ48900005 PM 7947701 ER PT J AU TSUCHIDA, T PARKER, KC TURNER, RV MCFARLAND, HF COLIGAN, JE BIDDISON, WE AF TSUCHIDA, T PARKER, KC TURNER, RV MCFARLAND, HF COLIGAN, JE BIDDISON, WE TI AUTOREACTIVE CD8(+) T-CELL RESPONSES TO HUMAN MYELIN PROTEIN-DERIVED PEPTIDES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AUTOIMMUNITY; MAJOR HISTOCOMPATIBILITY COMPLEX ANTIGEN-BINDING PEPTIDES ID MULTIPLE-SCLEROSIS PATIENTS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; BASIC-PROTEIN; PROTEOLIPID PROTEIN; LYMPHOCYTE-T; OLIGODENDROCYTE GLYCOPROTEIN; AUTOIMMUNE DEMYELINATION; HEALTHY-INDIVIDUALS; CEREBROSPINAL-FLUID; ANTIGEN EXPRESSION AB Identification of the targets of autoreactive T cells is important for understanding the pathogenesis of many autoimmune diseases. In multiple sclerosis, myelin proteins are thought to be the targets of autoreactive T-cell responses. To date only major histocompatibility complex class II-restricted CD4(+) T-cell responses to myelin proteins have been investigated. In the present study, the ability of self peptides derived from human myelin proteins to induce autoreactive CD8(+) T-cell responses has been assessed. Peptide sequences from human myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), and myelin oligodendrocyte glycoprotein have been identified that bind to and form stable complexes with HLA-AZ. MBP 110-118, PLP 80-88, MAG 287-295, MAG 509-517, and MAG 556-564 were all able to induce peptide-specific HLA-A2-restricted CD8(+) cytotoxic T-lymphocyte (CTL) responses in vitro in HLA-A2(+) individuals. CTLs specific for MBP 110-118 and MAG 556-564 could recognize endogenously processed antigens presented by HLA-A2. CTL clones reactive to MBP 110-118 and MAG 556-564 produced tumor necrosis factor alpha and a subset of these clones also produced interferon gamma. These results demonstrate that (i) self peptides derived from human myelin proteins can induce autoreactive CD8(+) CTLs and (ii) these CD8(+) T cells produce cytokines thought to be important in mediating demyelinating disease. These studies provide an experimental approach for the assessment of CD8(+) T-cell responses in such autoimmune diseases. C1 NIAID,MOLEC STRUCT LAB,BETHESDA,MD 20892. RP TSUCHIDA, T (reprint author), NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 38 TC 123 Z9 126 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 1994 VL 91 IS 23 BP 10859 EP 10863 DI 10.1073/pnas.91.23.10859 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800022 PM 7526383 ER PT J AU RAMPINO, NJ BOHR, VA AF RAMPINO, NJ BOHR, VA TI RAPID GENE-SPECIFIC REPAIR OF CISPLATIN LESIONS AT THE HUMAN DUG/DHFR LOCUS COMPRISING THE DIVERGENT UPSTREAM GENE AND DIHYDROFOLATE-REDUCTASE GENE DURING EARLY G(1) PHASE OF THE CELL-CYCLE ASSAYED BY USING THE EXONUCLEOLYTIC ACTIVITY OF T4 DNA-POLYMERASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTERSTRAND CROSS-LINKS; CIS-DIAMMINEDICHLOROPLATINUM(II); QUANTITATION; EXONUCLEASE; SEQUENCE; ADDUCTS AB A novel assay to detect strand-specific DNA repair after cellular exposure to cisplatin at IC50 levels, is used to measure rapid repair in the divergent upstream gene (DUG), a human MutS homolog, and in the bidirectional promoter for dihydrofolate reductase gene (DHFR) and the contiguous upstream DUG. Single-stranded DNA capable of hybridizing to gene-specific probes is generated enzymatically by the 3'-5' exonuclease activity of T4 DNA polymerase. The presence of cisplatin lesions inhibit the exonucleolytic activity of T4 DNA polymerase and block the formation of single-stranded DNA. This decreases the amount of complementary sequence produced when assayed by gene-specific probe hybridization. With the progression of repair, increasing quantities of single-stranded DNA become available for probe hybridization. This assay was applied to human A2780 ovarian carcinoma cells treated with cisplatin at the beginning of G(1) phase. A dose-response experiment showed that the assay was applicable down to cisplatin concentrations of 2.5 mu M. To assay for strand-specific gene repair, the synchronized cells were treated with cisplatin and then allowed time to repair in drug-free medium. Extensive removal of cisplatin lesions after 2 hr of cellular repair during early G(1) phase in the DUG and the DUG/DHFR promoter was measured, with no evidence of repair in the unexpressed delta-globin gene. The extent of preferential DNA repair was much more distinct than has been observed previously at high-drug dosage in asynchronous cells. C1 NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. RP RAMPINO, NJ (reprint author), NIA,MOLEC GENET LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 30 TC 18 Z9 18 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 1994 VL 91 IS 23 BP 10977 EP 10981 DI 10.1073/pnas.91.23.10977 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800046 PM 7971995 ER PT J AU OKAMOTO, A DEMETRICK, DJ SPILLARE, EA HAGIWARA, K HUSSAIN, SP BENNETT, WP FORRESTER, K GERWIN, B SERRANO, M BEACH, DH HARRIS, CC AF OKAMOTO, A DEMETRICK, DJ SPILLARE, EA HAGIWARA, K HUSSAIN, SP BENNETT, WP FORRESTER, K GERWIN, B SERRANO, M BEACH, DH HARRIS, CC TI MUTATIONS AND ALTERED EXPRESSION OF P16(INK4) IN HUMAN CANCER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE P53 PROTEIN; TUMOR-SUPPRESSOR GENE; CYCLIN D1; RETINOBLASTOMA PROTEIN ID D-TYPE CYCLINS; RETINOBLASTOMA PROTEIN; HOMOZYGOUS DELETIONS; INTERFERON GENES; BINDING PROTEIN; CELL-LINES; P53; GROWTH; FIBROBLASTS; OVEREXPRESSION AB Cell cycle arrest at the G(1) checkpoint allows completion of critical macromolecular events prior to S phase. Regulators of the G(1) checkpoint include an inhibitor of cyclin-dependent kinase, p16(INK4); two tumor-suppressor proteins, p53 and RB (the product of the retinoblastoma-susceptibility gene); and cyclin D1. Neither p16(INK4) nor the RB protein was detected in 28 of 29 tumor cell lines from human lung, esophagus, liver, colon, and pancreas. The presence of p16(INK4) protein is inversely correlated with detectable RB or cyclin D1 proteins and is not correlated with p53 mutations. Homozygous deletions of p16(INK4) were detected in several cell lines, but intragenic mutations of this gene were unusual in either cell lines or primary tumors. Transfection of the p16(INK4) cDNA expression vector into carcinoma cells inhibits their colony-forming efficiency and the p16(INK4) expressing cells are selected against with continued passage in vitro. These results are consistent with the hypothesis that p16(INK4) is a tumor-suppressor protein and that genetic and epigenetic abnormalities in genes controlling the G(1) checkpoint can lead to both escape from senescence and cancer formation. C1 COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. RP OKAMOTO, A (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,BETHESDA,MD 20892, USA. RI Serrano, Manuel/H-2634-2015 OI Serrano, Manuel/0000-0001-7177-9312 NR 50 TC 588 Z9 610 U1 1 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 1994 VL 91 IS 23 BP 11045 EP 11049 DI 10.1073/pnas.91.23.11045 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800060 PM 7972006 ER PT J AU MIAO, GG SMEYNE, RJ DARCANGELO, G COPELAND, NG JENKINS, NA MORGAN, JI CURRAN, T AF MIAO, GG SMEYNE, RJ DARCANGELO, G COPELAND, NG JENKINS, NA MORGAN, JI CURRAN, T TI ISOLATION OF AN ALLELE OF REELER BY INSERTIONAL MUTAGENESIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; BRAIN-DEVELOPMENT; MUTANT MOUSE; FOS GENE; MICE; CEREBELLUM; MIGRATION; NEURONS AB Reeler (rl) is an autosomal recessive mutation that affects migration of postmitotic neurons in the mouse central nervous system. The reeler (rl/rl) mouse displays a disruption of laminar structures in both the cerebellum and the forebrain and it exhibits tremors, dystonia, and ataxia. The molecular basis of the reeler phenotype is unknown because the gene involved has not yet been identified. We report here the isolation and characterization of an allele of rl, reeler(trangene) (r1(tg)). This allele was generated by the fortuitous insertion of a transgene, supfos (sf), into the mouse rl locus. Crosses between rl/+ and rl(tg)/+ mice yielded offspring that exhibited the reeler phenotype, indicating that rl and rl(tg) are allelic. We cloned the genomic sequences flanking the transgene insertion site from the rl(tg)/rl(tg) mouse genome. Chromosomal mapping studies revealed that the 5' flanking cellular sequence maps to a locus, D5Gmr1, that lies in a region of mouse chromosome 5 that also contains the rl locus. Southern blot analysis using a probe derived from the D5Gmr1 locus revealed no gross structural rearrangement in the rl locus. Thus, unlike the two rl alleles described previously, rl(tg) provides a molecular probe that can now be used to identify and isolate the rl gene. C1 ROCHE INST MOLEC BIOL,NUTLEY,NJ 07110. COLUMBIA UNIV,DEPT BIOL SCI,NEW YORK,NY 10027. HOFFMANN LA ROCHE INC,DEPT CENT NERVOUS SYST RES,NEUROGENET UNIT,NUTLEY,NJ 07110. NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Curran, Tom/C-1164-2008; Curran, Tom/D-7515-2011; OI Curran, Tom/0000-0003-1444-7551; Smeyne, Richard/0000-0002-8459-5472 FU NCI NIH HHS [N01-CO-74101]; NINDS NIH HHS [NS09698-01] NR 21 TC 47 Z9 47 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 1994 VL 91 IS 23 BP 11050 EP 11054 DI 10.1073/pnas.91.23.11050 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800061 PM 7972007 ER PT J AU MAROULAKOU, IG ANVER, M GARRETT, L GREEN, JE AF MAROULAKOU, IG ANVER, M GARRETT, L GREEN, JE TI PROSTATE AND MAMMARY ADENOCARCINOMA IN TRANSGENIC MICE CARRYING A RAT C3(1) SIMIAN-VIRUS-40 LARGE TUMOR-ANTIGEN FUSION GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PROSTATIC STEROID-BINDING PROTEIN PROMOTER; MULTISTEP TUMORIGENESIS; HORMONE RESPONSE ELEMENT; METASTASIS; GENE TARGETING ID STEROID-BINDING-PROTEIN; TGF-ALPHA; HORMONAL-REGULATION; NEU ONCOGENE; C-3 GENES; HA-RAS; INDUCTION; HYPERPLASIA; EXPRESSION; GLAND AB A transgenic mouse model for prostate and mammary cancer has been developed in mice containing a recombinant gene expressing the simian virus 40 early-region transforming sequences under the regulatory control of the rat prostatic steroid binding protein [C3(1)] gene. Male transgenic mice develop prostatic hyperplasia in early life that progresses to adenoma or adenocarcinoma in most animals surviving to longer than 7 months of age. Prostate cancer metastases to lung have been observed. female animals from the same founder lines generally develop mammary hyperplasia by 3 months of age with subsequent development of mammary adenocarcinoma by 6 months of age in 100% of the animals. The development of tumors correlates with the expression of the transgene as determined by Northern blot and immunohistochemical analyses. The results of these experiments demonstrate that the C3(1) regulatory region used in these experiments is useful for targeting expression to the prostate and mammary gland. To our knowledge, this experimental system is the first reported transgenic mouse model for prostate cancer. These transgenic animals offer the opportunity to study hormone response elements in vivo and the multistage progression from normal tissue to carcinoma in the prostate and mammary glands. C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NR 37 TC 234 Z9 236 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 1994 VL 91 IS 23 BP 11236 EP 11240 DI 10.1073/pnas.91.23.11236 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800099 PM 7972041 ER PT J AU FEDERSPIEL, MJ BATES, P YOUNG, JAT VARMUS, HE HUGHES, SH AF FEDERSPIEL, MJ BATES, P YOUNG, JAT VARMUS, HE HUGHES, SH TI A SYSTEM FOR TISSUE-SPECIFIC GENE TARGETING - TRANSGENIC MICE SUSCEPTIBLE TO SUBGROUP-A AVIAN-LEUKOSIS VIRUS-BASED RETROVIRAL VECTORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ROUS-SARCOMA VIRUS; DNA-SYNTHESIS; CELLS; CHICKEN; EXPRESSION; FIBROBLASTS; INTEGRATION; INFECTION; THERAPY; EMBRYO AB Avian Leukosis viruses (ALVs) have been used extensively as genetic vectors in avian systems, but their utility in mammals or mammalian cell lines is compromised by inefficient viral entry. We have overcome this limitation by generating transgenic mice that express the receptor for the subgroup A ALV under the control of the chicken alpha(sk)-actin promoter. The skeletal muscles of these transgenic animals are susceptible to efficient infection by subgroup A ALV. Because infection is restricted to cell lineages that express the transgene, the method has utility for studies of development and oncogenesis and will provide models for tissue-specific gene therapy. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV PENN,DEPT MICROBIOL,PHILADELPHIA,PA 19104. GLADSTONE INST VIROL & IMMUNOL,SAN FRANCISCO,CA 94141. UNIV SAN FRANCISCO,SCH MED,DEPT MICROBIOL & IMMUNOL,SAN FRANCISCO,CA 94141. FU NCI NIH HHS [N01-CO-74101] NR 25 TC 94 Z9 97 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 1994 VL 91 IS 23 BP 11241 EP 11245 DI 10.1073/pnas.91.23.11241 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800100 PM 7972042 ER PT J AU PRIBLUDA, VS PRIBLUDA, C METZGER, H AF PRIBLUDA, VS PRIBLUDA, C METZGER, H TI TRANSPHOSPHORYLATION AS THE MECHANISM BY WHICH THE HIGH-AFFINITY RECEPTOR FOR IGE IS PHOSPHORYLATED UPON AGGREGATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MAST CELL; SIGNALING; TYROSINE KINASE; FC RECEPTOR ID BASOPHILIC LEUKEMIA-CELLS; PROTEIN-TYROSINE KINASE; SIGNAL-TRANSDUCTION; IMMUNOGLOBULIN-E; HISTAMINE-RELEASE; DEPHOSPHORYLATION; ENGAGEMENT; COMPONENT; COMPLEX; P34CDC2 AB When aggregated, the high-affinity receptors for IgE on mast cells (Fc epsilon RI) launch a series of phosphorylations, particularly of protein tyrosines. We have analyzed how aggregation initiates this cascade. We examined Fc epsilon RI from unstimulated cells and from cells exposed to a polyvalent hapten conjugate that aggregates the Fc epsilon RI via the receptor-bound anti-hapten IgE. We also examined the latter receptors after they had been disaggregated in vitro with monovalent hapten. By an in vitro kinase assay: (i) Unaggregated and disaggregated receptors are associated with a kinase that phosphorylates an exogenous (peptide) substrate but minimally, or not at all, the subunits of Fc epsilon RI or associated proteins (endogenous substrates). After aggregation, phosphorylation of the exogenous substrate is linear with time, but the modification of the endogenous substrates reaches a plateau, presumably because only those endogenous substrates that are adjacent to the kinase are phosphorylated. (ii) Aggregated receptors and disaggregated receptors have enhanced kinase activity toward exogenous substrate. The state of phosphorylation of the receptor correlates strongly with the yield of enhanced kinase activity. We propose that upon aggregation of Fc epsilon RI, a constitutively associated kinase phosphorylates endogenous substrates by transphosphorylation. As a result, additional kinase activity becomes manifest and this promotes further transphosphorylation. In view of the homology between Fc epsilon RI and other receptors central to the immune response, the latter receptors likely utilize a similar transphosphorylation mechanism, RP PRIBLUDA, VS (reprint author), NIAMS,ARTHRIT & RHEUMATISM BRANCH,CHEM IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 30 TC 160 Z9 160 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 1994 VL 91 IS 23 BP 11246 EP 11250 DI 10.1073/pnas.91.23.11246 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800101 PM 7526393 ER PT J AU YAMASHITA, T MAO, SY METZGER, H AF YAMASHITA, T MAO, SY METZGER, H TI AGGREGATION OF THE HIGH-AFFINITY IGE RECEPTOR AND ENHANCED ACTIVITY OF P53/56(LYN) PROTEIN-TYROSINE KINASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TRANSMEMBRANE SIGNALING; MAST CELLS; CHEMICAL CROSS-LINKING; PERMEABILIZATION; RAT BASOPHILIC LEUKEMIA CELLS ID IMMUNOGLOBULIN-E; HISTAMINE-RELEASE; PHOSPHORYLATION; COMPONENT; CELLS; ENGAGEMENT; SIGNAL AB Aggregation of the receptor with high affinity for IgE (Fc epsilon RI) on the surface of mast cells and basophils stimulates phosphorylation of protein tyrosines, a process in which p53/56(lyn) kinase has been implicated. We measured the association between Fc epsilon RI and the kinase, using chemical crosslinking to stabilize their interaction. In the rat basophilic leukemia mast cell line, 3-4%, and at most 20%, of Fc epsilon RI appear to be associated with the kinase prior to aggregation, even though there is an excess of total cell lyn kinase. Aggregating the Fc epsilon RI causes three to four times more of the kinase to associate with receptors, a process requiring a prior phosphorylation step. In an in vitro assay, the lyn associated with the aggregated receptors becomes disproportionately more phosphorylated than would be predicted from the amount of lyn associated with the receptors. These and other data are consistent with a model in which aggregation of the receptor leads to its transphosphorylation by constitutively associated lyn kinase. We propose that additional molecules of this kinase are thereby recruited and that this markedly enhances transphosphorylation of tyrosine on the receptor and associated proteins, thereby initiating a cascade of further biochemical changes. This model is also consistent with data on receptors such as the clonotypic receptors on B and T lymphocytes, which share structural and functional features with Fc epsilon RI. RP YAMASHITA, T (reprint author), NIAMS,ARTHRIT & RHEUMATISM BRANCH,CHEM IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 17 TC 149 Z9 149 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 1994 VL 91 IS 23 BP 11251 EP 11255 DI 10.1073/pnas.91.23.11251 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ938 UT WOS:A1994PQ93800102 PM 7526394 ER PT J AU KISS, A JEZOVA, D AGUILERA, G AF KISS, A JEZOVA, D AGUILERA, G TI ACTIVITY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND SYMPATHOADRENAL SYSTEM DURING FOOD AND WATER-DEPRIVATION IN THE RAT SO BRAIN RESEARCH LA English DT Article DE FOOD DEPRIVATION; WATER DEPRIVATION; HYPOTHALAMIC-PITUITARY-ADRENAL AXIS; PARAVENTRICULAR NUCLEUS; CORTICOTROPIN RELEASING HORMONE; VASOPRESSIN; RECEPTOR ID CORTICOTROPIN-RELEASING FACTOR; VASOPRESSIN MESSENGER-RNA; PARAVENTRICULAR NUCLEI; IMMOBILIZATION STRESS; ARGININE-VASOPRESSIN; HORMONE RECEPTORS; RESPONSES; CORTICOSTERONE; OXYTOCIN; GLUCOCORTICOIDS AB It has been previously shown that chronic water deprivation or hypertonic saline intake, osmotic stress models with concomitant decrease in food intake, decrease hypothalamic CRH mRNA levels and ACTH responses to acute stimulation, To determine the contribution of food restriction to the effects of osmotic stimulation, the function of the hypothalamic pituitary adrenal axis was analyzed in rats subjected to food deprivation, water deprivation or their combination for 60 h. In all three groups, basal levels of plasma corticosterone were increased, while ACTH and catecholamines were unchanged. Basal plasma vasopressin levels were normal in food deprived rats, but significantly increased in water deprived and simultaneously food and water deprived rats. In contrast to the 25% reduction of plasma ACTH responses to 30 min immobilization by water deprivation, food deprivation had no inhibitory effect and prevented the decreased ACTH responsiveness caused by water deprivation. In control rats, plasma corticosterone levels increased 22.5-fold 30 min after immobilization, and this response was significantly potentiated in the water deprived, food deprived and combined food and water deprived groups. The elevation in plasma catecholamines in response to acute immobilization was also enhanced in both water deprived and food deprived rats. In situ hybridization studies showed a 35% increase in VP mRNA levels in the PVN after water deprivation, whereas food deprivation caused a slight decrease and prevented the stimulatory effect of water deprivation. CRH mRNA in the PVN was reduced by 27% after food deprivation and by 67% after water deprivation, but simultaneous food and water deprivation caused a significantly smaller reduction similar to that in food deprivation alone. Anterior pituitary POMC mRNA levels were unchanged after water deprivation alone, but significantly increased after food deprivation and simultaneous food and water deprivation. The increased pituitary POMC mRNA and pituitary responsiveness despite enhanced corticosterone responses indicate an altered glucocorticoid feedback in food deprived rats. The data show that the effects of food deprivation on the PIPA axis function differ from those of water deprivation and that reduced food intake is unlikely to contribute to the inhibitory effect of osmotic stress on the HPA axis. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. SLOVAK ACAD SCI,INST EXPTL ENDOCRINOL,BRATISLAVA,SLOVAKIA. NR 40 TC 100 Z9 100 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 7 PY 1994 VL 663 IS 1 BP 84 EP 92 DI 10.1016/0006-8993(94)90465-0 PG 9 WC Neurosciences SC Neurosciences & Neurology GA PP616 UT WOS:A1994PP61600010 PM 7850474 ER PT J AU ZHANG, L AF ZHANG, L TI THE ROLE OF PROTEIN-KINASE-C IN INDUCING ALZHEIMERS A68 PROTEIN EXPRESSION IN THE CULTURE OF HUMAN NEUROBLASTOMA-CELLS SO NEUROSCIENCE LETTERS LA English DT Article DE A68 PROTEIN; ALZHEIMERS DISEASE; PROTEIN KINASE C; HUMAN NEUROBLASTOMA CELL CULTURE; IMMUNOCYTOCHEMISTRY; IMMUNOBLOTTING ID DISEASE; PHOSPHORYLATION; BRAIN AB By using the monoclonal antibody Alz50, we studied the role of protein kinase C (PKC) in inducing A68 protein expression in a human neuronal cell line. Both phorbol 12-myristate 13-acetate and H7 strongly induced A68 protein, while HA1004 and calphoslin C had no effect. The results suggest that the inhibitor and activator of PKC induce A68 protein expression by different mechanisms. C1 NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,MOLEC & CELLULAR BIOL LAB,BALTIMORE,MD 21224. RP ZHANG, L (reprint author), NIMH,CLIN SCI LAB,RM 4E18,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 7 PY 1994 VL 181 IS 1-2 BP 95 EP 97 DI 10.1016/0304-3940(94)90568-1 PG 3 WC Neurosciences SC Neurosciences & Neurology GA PT186 UT WOS:A1994PT18600023 PM 7898780 ER PT J AU SHIMKETS, RA WARNOCK, DG BOSITIS, CM NELSONWILLIAMS, C HANSSON, JH SCHAMBELAN, M GILL, JR ULICK, S MILORA, RV FINDLING, JW CANESSA, CM ROSSIER, BC LIFTON, RP AF SHIMKETS, RA WARNOCK, DG BOSITIS, CM NELSONWILLIAMS, C HANSSON, JH SCHAMBELAN, M GILL, JR ULICK, S MILORA, RV FINDLING, JW CANESSA, CM ROSSIER, BC LIFTON, RP TI LIDDLES SYNDROME - HERITABLE HUMAN HYPERTENSION CAUSED BY MUTATIONS IN THE BETA-SUBUNIT OF THE EPITHELIAL SODIUM-CHANNEL SO CELL LA English DT Article ID ALDOSTERONE SYNTHASE; GENE; DNA; LINKAGE; CELLS AB Liddle's syndrome (pseudoaldosteronism) is an autosomal dominant form of human hypertension characterized by a constellation of findings suggesting constitutive activation of the amiloride-sensitive distal renal epithelial sodium channel. We demonstrate complete linkage of the gene encoding the beta subunit of the epithelial sodium channel to Liddle's syndrome in Liddle's original kindred. Analysis of this gene reveals a premature stop codon that truncates the cytoplasmic carboxyl terminus of the encoded protein in affected subjects. Analysis of subjects with Liddle's syndrome from four additional kindreds demonstrates either premature termination or frameshift mutations in this same carboxy-terminal domain in all four. These findings demonstrate that Liddle's syndrome is caused by mutations in the beta subunit of the epithelial sodium channel and have implications for the regulation of this epithelial ion channel as well as blood pressure homeostasis. C1 YALE UNIV,SCH MED,BOYER CTR MOLEC MED,HOWARD HUGHES MED INST,DEPT MED,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,BOYER CTR MOLEC MED,DEPT GENET,NEW HAVEN,CT 06510. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PHYSIOL & BIOPHYS,BIRMINGHAM,AL 35294. VET AFFAIRS MED CTR,BIRMINGHAM,AL 35294. SAN FRANCISCO GEN HOSP,DEPT MED,SAN FRANCISCO,CA 94110. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94110. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. VET AFFAIRS HOSP,BRONX,NY 10468. CAPITAL DIST RENAL PHYSICIANS,ALBANY,NY 12208. MED COLL WISCONSIN,ST LUKES MED CTR,MILWAUKEE,WI 53215. UNIV LAUSANNE,INST PHARMACOL & TOXICOL,CH-1005 LAUSANNE,SWITZERLAND. NR 29 TC 966 Z9 979 U1 4 U2 25 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 4 PY 1994 VL 79 IS 3 BP 407 EP 414 DI 10.1016/0092-8674(94)90250-X PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PQ488 UT WOS:A1994PQ48800004 PM 7954808 ER PT J AU SZALLASI, Z SMITH, CB BLUMBERG, PM AF SZALLASI, Z SMITH, CB BLUMBERG, PM TI DISSOCIATION OF PHORBOL ESTERS LEADS TO IMMEDIATE REDISTRIBUTION TO THE CYTOSOL OF PROTEIN-KINASES C-ALPHA AND C-DELTA IN MOUSE KERATINOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID ISOZYMES; BINDING; CELLS; ACTIVATION; MEMBRANE; GROWTH; BRAIN AB We have measured the dissociation rate of phorbol 12-myristate 13-acetate (PMA), a potent tumor promoter, phorbol 12,13-dibutyrate (PDBu), a weak tumor promoter, and 12-deoxyphorbol 13-phenylacetate (dPP), an antitumor promoter, from intact mouse keratinocytes. PDBu and dPP showed a very rapid release from the cells (t(1/2) = 1 min), whereas PMA showed a slower release (t(1/2) = 9 min). Western blot analysis of the amounts of protein kinase C alpha (PKC alpha) and PHC delta in the soluble fraction and the Triton X-100-soluble particulate fraction revealed that translocation of both isozymes from the soluble to the particulate fraction was reversible when the phorbol esters were washed off. Washes of 5-15 min resulted in complete redistribution of the PKC isozymes when the cells were previously treated with 1 mu M dPP or 1 mu M PDBu for 5 min. In the case of treatment with 100 or 10 nar PMA, the redistribution required a longer time; nevertheless, the PHC isozymes returned to the soluble fraction within 60 min. Longer initial treatments with PMA dPP, and PDBu (up to 60 min) translocated PHC in a very similar, completely reversible fashion. We conclude that in this cell line phorbol esters do not induce the conversion of PHC isozymes to an integral membrane state. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 22 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 4 PY 1994 VL 269 IS 44 BP 27159 EP 27162 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV771 UT WOS:A1994PV77100002 PM 7961621 ER PT J AU URA, K WOLFFE, AP HAYES, JJ AF URA, K WOLFFE, AP HAYES, JJ TI CORE HISTONE ACETYLATION DOES NOT BLOCK LINKER HISTONE BINDING TO A NUCLEOSOME INCLUDING A XENOPUS-BOREALIS 5-S RIBOSOMAL-RNA GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID CHROMATIN; HYPERACETYLATION; DNA; PARTICLE; TRANSITIONS; EXPRESSION; TAILS AB We demonstrate that acetylation of core histone tails does not significantly impair the ability of linker histones to bind preferentially and asymmetrically to a defined sequence mononucleosome core reconstituted in vitro. Thus a simple inhibition mechanism cannot explain models whereby acetylation is causal for the observed reduction in the linker histone content in chromatin. Other models to explain this correlation are discussed. C1 NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 37 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 4 PY 1994 VL 269 IS 44 BP 27171 EP 27174 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV771 UT WOS:A1994PV77100005 PM 7961624 ER PT J AU MILLER, KJ HOFFMAN, BJ AF MILLER, KJ HOFFMAN, BJ TI ADENOSINE A(3) RECEPTORS REGULATE SEROTONIN TRANSPORT VIA NITRIC-OXIDE AND CGMP SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONG-TERM POTENTIATION; HIGH-AFFINITY UPTAKE; PROTEIN-KINASE-C; NEUROTRANSMITTER TRANSPORTERS; MEMBRANE-VESICLES; MOLECULAR-CLONING; CELL-CULTURES; GLUTAMATE; ACTIVATION; PHOSPHORYLATION AB Many antidepressants inhibit 5-hydroxytryptamine (5HT) transport resulting in increased 5HT levels in the synapse. However, physiological regulation of neurotransmitter uptake has not been demonstrated. We have examined the effect of receptor-activated second messengers on the 5HT transporter in rat basophilic leukemia cells (RBL 2H3). Here, we show that activation of an A(3) adenosine receptor results in an increase of 5HT uptake in RBL cells, due to an increase in maximum velocity (V-max). The A(3) adenosine receptor-stimulated increase in transport is blocked by inhibitors of nitric oxide synthase and by a cGMP dependent kinase inhibitor. In fact, compounds that generate nitric oxide (NO) and the cGMP analog 8-bromo-cGMP mimicked the effect of A(3) receptor stimulation, suggesting that the elevation in transport occurs through the generation of the gaseous second messenger NO and a subsequent elevation in cGMP. Additionally, the 5HT transporter is differentially regulated by second messengers since direct activation of protein kinase C by phorbol esters decreases 5HT uptake by decreasing V-max. Our results suggest that the changes in transport are due to a direct modification of the 5HT transporter, possibly by phosphorylation, which appears to alter the rate at which transport occurs. As the 5HT transporter in RBL cells is identical to that in neurons, our results suggest that analogous mechanisms may operate in the brain. RP NIMH, CELL BIOL LAB, ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 47 TC 154 Z9 155 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 4 PY 1994 VL 269 IS 44 BP 27351 EP 27356 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV771 UT WOS:A1994PV77100034 PM 7525554 ER PT J AU KUMAR, KN BABCOCK, KK JOHNSON, PS CHEN, XY EGGEMAN, KT MICHAELIS, EK AF KUMAR, KN BABCOCK, KK JOHNSON, PS CHEN, XY EGGEMAN, KT MICHAELIS, EK TI PURIFICATION AND PHARMACOLOGICAL AND IMMUNOCHEMICAL CHARACTERIZATION OF SYNAPTIC MEMBRANE-PROTEINS WITH LIGAND-BINDING PROPERTIES OF N-METHYL-D-ASPARTATE RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID H-3 MK-801 BINDING; NMDA-RECEPTOR; GLUTAMATE-RECEPTOR; RAT-BRAIN; COMPETITIVE ANTAGONISTS; PHENCYCLIDINE RECEPTOR; FUNCTIONAL EXPRESSION; HIPPOCAMPAL-NEURONS; MOLECULAR-CLONING; CHANNEL COMPLEX AB A method was developed for the solubilization of approximately 50% of proteins in synaptic membranes that have ligand-binding characteristics of N-methyl-D-aspartate (NMDA) receptors. Affinity chromatographic separation of the solubilized proteins through L-glutamate-derivatized matrices and subsequent elution by NMDA-containing buffers led to the purification of four predominant proteins with estimated sizes of 67-70, 53-62, 41-43, and 28-36 kDa. The co purification of NMDA-sensitive L-glutamate binding, dizocilpine-sensitive thienylcyclohexyl piperidine (TCP)-binding, and strychnine-insensitive glycine-binding proteins was achieved by this affinity chromatographic procedure. Glutamate, glycine, and the polyamine spermidine increased both the ''on'' rate and the equilibrium level of [H-3]TCP binding to the isolated proteins. The group of proteins eluted by NMDA from the glutamate-derivatized matrices could be further purified through size exclusion chromatography without loss of ligand binding activity or separation of the NMDA-sensitive glutamate-binding from the dizocilpine-sensitive TCP-binding proteins. Polyclonal and monoclonal antibodies to the cloned NMDA receptor protein NMDAR1 did not react with any proteins in the solubilized membrane proteins or the purified fractions. However, immunoreaction of antibodies raised against a glutamate binding protein and a phosphonoaminocarboxylic acid-binding protein indicated that these are two of the major proteins in the purified fractions. These studies indicate that these two proteins might be components of a complex that has some of the characteristics of NMDA receptors and that neuronal membranes may contain varieties of NMDA-like receptors composed of protein subunits that differ from the NMDAR1 and NMDAR2 receptor proteins. C1 UNIV KANSAS,DEPT PHARMACOL & TOXICOL,LAWRENCE,KS 66045. UNIV KANSAS,CTR NEUROBIOL & IMMUNOL RES,LAWRENCE,KS 66045. NIDA,MOLEC NEUROBIOL LAB,BALTIMORE,MD 21224. UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262. FU NIAAA NIH HHS [AA04732]; NIDA NIH HHS [DA 05472] NR 41 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 4 PY 1994 VL 269 IS 44 BP 27384 EP 27393 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV771 UT WOS:A1994PV77100039 PM 7961649 ER PT J AU CHAE, HZ CHUNG, SJ RHEE, SG AF CHAE, HZ CHUNG, SJ RHEE, SG TI THIOREDOXIN-DEPENDENT PEROXIDE REDUCTASE FROM YEAST SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALKYL HYDROPEROXIDE REDUCTASE; FLAVOPROTEIN DISULFIDE OXIDOREDUCTASES; SACCHAROMYCES-CEREVISIAE; SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; OXIDATIVE STRESS; SEQUENCE; PROTEIN; CLONING; ACIDS AB A 25-kDa antioxidant enzyme that provides protection against oxidation systems capable of generating reactive oxygen and sulfur species has previously been identified. The nature of the oxidant eliminated by and the physiological source of reducing equivalents for, this enzyme, however, were not known. The 25-kDa enzyme is now shown to be a peroxidase that reduces H2O2 and alkyl hydroperoxides with the use of hydrogens provided by thioredoxin, thioredoxin reductase, and NADPH. This protein is the first peroxidase to be identified that uses thioredoxin as the immediate hydrogen donor and is thus named thioredoxin peroxidase (TPx). TPx exists as a dimer of identical 25-kDa subunits that contain 2 cysteine residues, Cys(47) and Cys(170). Cys(47)-SH appears to be the site of oxidation by peroxides, and the oxidized Cys(47) probably reacts with Cys(170)-SH of the other subunit to form an intermolecular disulfide. Mutant TPx proteins lacking either Cys(47) or Cys(170), therefore, do not exhibit thioredoxin-coupled peroxidase activity. The TPx disulfide is specifically reduced by thioredoxin, but can also be reduced (less effectively) by a small molecular size thiol. The Saccharomyces cerevisiae thioredoxin reductase gene was also cloned and sequenced, and the deduced amino sequence was shown to be 51% identical with that of the Escherichia coli enzyme. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 27 TC 733 Z9 750 U1 1 U2 15 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 4 PY 1994 VL 269 IS 44 BP 27670 EP 27678 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV771 UT WOS:A1994PV77100080 PM 7961686 ER PT J AU AMATAYAKULCHANTLER, S QIAN, SW GAKENHEIMER, K BOTTINGER, EP ROBERTS, AB SPORN, MB AF AMATAYAKULCHANTLER, S QIAN, SW GAKENHEIMER, K BOTTINGER, EP ROBERTS, AB SPORN, MB TI [SER(77)] TRANSFORMING GROWTH-FACTOR-BETA-1 - SELECTIVE BIOLOGICAL-ACTIVITY AND RECEPTOR-BINDING IN MINK LUNG EPITHELIAL-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TGF-BETA; II RECEPTOR; CRYSTAL-STRUCTURE; CLONING; KINASE; SUPERFAMILY; GROWTH-FACTOR-BETA-2; IDENTIFICATION; EXPRESSION; TGF-BETA-1 AB Transforming growth factor-beta 1 (TGF-beta 1) is a homodimeric protein stabilized by a single disulfide bridge between Cys(77) on the respective monomers and two paired complementary hydrophobic interfaces between the two subunits. A TGF-beta 1 mutant with Cys(77) replaced by serine has been expressed in stably transfected Chinese hamster ovary cells and purified to homogeneity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirms that the sole interchain disulfide bond in TGF-beta 1 has been eliminated. It is 20% as potent as native TGF-beta 1 in the induction of plasminogen activator inhibitor-1 promoter expression in mink lung epithelial cells (Mv1Lu), although it is less than 1% as potent as native TGF-beta 1 in inhibition of growth in the same cell line. The mutant acts as a full agonist in both bioassays. [Ser(77)]TGF-beta 1 binds to soluble type II receptors and competes with native TGF-beta 1 in sandwich-enzyme-linked immunosorbent assays; however, in Mv1Lu cells, the mutant shows preferential cross-linking to type I rather than type II receptors. [Ser(77)]TGF-beta 1 is a useful tool for understanding the different ligand-receptor complexes and numerous biological activities of this multifunctional cytokine. RP AMATAYAKULCHANTLER, S (reprint author), NCI,CHEMOPREVENT LAB,BLDG 41,RM C-629,BETHESDA,MD 20892, USA. NR 35 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 4 PY 1994 VL 269 IS 44 BP 27687 EP 27691 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV771 UT WOS:A1994PV77100082 PM 7961688 ER PT J AU TAOUIS, M LEVYTOLEDANO, R ROACH, P TAYLOR, SI GORDEN, P AF TAOUIS, M LEVYTOLEDANO, R ROACH, P TAYLOR, SI GORDEN, P TI RESCUE AND ACTIVATION OF A BINDING DEFICIENT INSULIN-RECEPTOR - EVIDENCE FOR INTERMOLECULAR TRANSPHOSPHORYLATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; TYROSINE KINASE-ACTIVITY; STRUCTURAL BASIS; SIGNAL TRANSDUCTION; MUTATION; PHOSPHORYLATION; AUTOPHOSPHORYLATION; RESISTANCE; SUBSTRATE; PROTEIN AB Binding of insulin to the a subunit of the insulin receptor (IR) leads to autophosphorylation of the beta subunit. The reaction proceeds as intramolecular transphosphorylation between alpha beta half-receptors of the heterotetrameric receptor dimer (alpha(2) beta(2)). Since IRs are mobile in the plane of the plasma membrane, it is also possible that transphosphorylation may occur between adjacent holoreceptors (alpha(2) beta(2)) by an intermolecular reaction. To address this question, we cotransfected NIH-3T3 cells with two IR cDNA constructs: a truncated but functionally normal IR lacking the C-terminal 43 amino acids (Delta 43) and a full-length Leu(323) mutant receptor that is expressed on the cell surface but that does not bind insulin. A clonal cell line was selected from cells cotransfected with a 1/5 ratio of Delta 43 cDNA/Leu(323) cDNA. The two homodimers (Leu(323) and Delta 43) were expressed without detectable formation of hybrid receptors. By using specific antibodies, we demonstrate that in cells coexpressing both homodimers, the Leu(323) mutant receptor was phosphorylated in vivo by the Delta 43 IR in an insulin-dependent manner. However, when the Leu(323) mutant receptor was expressed alone, no phosphorylation was detected. In addition, we demonstrate the association of the phosphorylated Leu(323) mutant receptor with insulin receptor substrate-1 and with phosphatidylinositol 3-kinase. These findings indicate that insulin binding is not required for phosphorylation of the Leu(323) mutant receptor, that the phosphorylation of the Leu(323) mutant receptor occurs by an intermolecular transphosphorylation mechanism, and, finally, that the Leu(323) mutant receptor, once phosphorylated, can associate with insulin receptor substrate-1 and phosphatidylinositol 3-kinase. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. INRA,RECH AVICOLES STN,F-37380 NOUZILLY,FRANCE. NR 31 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 4 PY 1994 VL 269 IS 44 BP 27762 EP 27766 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV771 UT WOS:A1994PV77100093 PM 7525562 ER PT J AU BRADEN, BC SOUCHON, H EISELE, JL BENTLEY, GA BHAT, TN NAVAZA, J POLJAK, RJ AF BRADEN, BC SOUCHON, H EISELE, JL BENTLEY, GA BHAT, TN NAVAZA, J POLJAK, RJ TI 3-DIMENSIONAL STRUCTURES OF THE FREE AND THE ANTIGEN-COMPLEXED FAB FROM MONOCLONAL ANTILYSOZYME ANTIBODY-D44.1 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE MONOCLONAL ANTIBODY; 3-DIMENSIONAL STRUCTURE; ANTIGEN-ANTIBODY COMPLEX; CONFORMATIONAL CHANGE; X-RAY DIFFRACTION ID IMMUNOGLOBULIN VARIABLE DOMAINS; X-RAY-DIFFRACTION; 3-DIMENSIONAL STRUCTURE; MACROMOLECULAR STRUCTURES; CRYSTAL-STRUCTURES; REFINEMENT; PROTEINS; CHAIN; CRYSTALLIZATION; NEURAMINIDASE AB The three-dimensional structures of the free and antigen-complexed Fabs from the mouse monoclonal anti-hen egg white lysozyme antibody D44.1 have been solved and refined by X-ray cr crystallographic techniques. The crystals of the free and lysozyme-bound Fabs were grown under identical conditions and their X-rag diffraction data were collected to 2.1 and 2.5 Angstrom, respectively. Two molecules of the Fab-lysozyme complex in the asymmetric unit of the crystals show nearly identical conformations and thus confirm the essential structural features of the antigen-antibody interface. Three buried water molecules enhance the surface complementarity at the interface and provide hydrogen bonds to stabilize the complex. Two hydrophobic buried holes are present at the interface which, although large enough to accommodate solvent molecules, are void. The combining site residues of the complexed FabD44.1 exhibit reduced temperature factors compared with those of the free Fab. Furthermore, small perturbations in atomic positions and rearrangements of side-chains at the combining site, and a relative rearrangement of the variable domains of the light (V-L) and the heavy (V-H) chains, detail a Fab accommodation of the bound lysozyme. The amino acid sequence of the V-H domain, as well as the epitope of lysozyme recognized by D44.1 are very close to those previously reported for the monoclonal antibody HyHEL-5. A feature central to the FabD44.1 and FabHyHEL-5 complexes with lysozyme are three salt bridges between V-H glutamate residues 35 and 50 and lysozyme arginine residues 45 and 68. The presence of the three salt bridges in the D44.1-lysozyme inter face indicates that these bonds are not responsible for the 1000-fold increase in affinity for !yrsozyme that HyHEL-5 exhibits relative to D44.1. C1 UNIV MARYLAND,MARYLAND BIOTECHNOL INST,CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850. INST PASTEUR,F-75724 PARIS 15,FRANCE. NCI,FCRFDC,CTR SUPERCOMP BIOMED,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21202. RI Bentley, Graham/B-3623-2011 NR 55 TC 110 Z9 110 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 4 PY 1994 VL 243 IS 4 BP 767 EP 781 DI 10.1016/0022-2836(94)90046-9 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ663 UT WOS:A1994PQ66300018 PM 7966295 ER PT J AU LORI, F MALYKH, A CARA, A SUN, D WEINSTEIN, JN LISZIEWICZ, J GALLO, RC AF LORI, F MALYKH, A CARA, A SUN, D WEINSTEIN, JN LISZIEWICZ, J GALLO, RC TI HYDROXYUREA AS AN INHIBITOR OF HUMAN IMMUNODEFICIENCY VIRUS-TYPE-1 REPLICATION SO SCIENCE LA English DT Article ID DRUG-COMBINATIONS; HTLV-III; INFECTION; PROTEASE; AIDS; ACTIVATION; MECHANISM; THERAPY; INVITRO; TISSUE AB Hydroxyurea, a drug widely used in therapy of several human diseases, inhibits deoxynucleotide synthesis-and, consequently, DNA synthesis-by blocking the cellular enzyme ribonucleotide reductase. Hydroxyurea inhibits human immunodeficiency virus-type 1 (HIV-1) DNA synthesis in activated peripheral blood lymphocytes by decreasing the amount of intracellular deoxynucleotides, thus suggesting that this drug has an antiviral effect. Hydroxyurea has now been shown to block HIV-1 replication in acutely infected primary human lymphocytes (quiescent and activated) and macrophages, as well as in brood cells infected in vivo obtained from individuals with acquired immunodeficiency syndrome (AIDS). The antiviral effect was achieved at nontoxic doses of hydroxyurea, lower than those currently used in human therapy. Combination of hydroxyurea with the nucleoside analog didanosine (2',3'-dideoxyinosine, or ddl) generated a synergistic inhibitory effect without increasing toxicity. In some instances, inhibition of HIV-1 by hydroxyurea was irreversible, even several weeks after suspension of drug treatment. The indirect inhibition of HIV-1 by hydroxyurea is not expected to generate high rates of escape mutants. Hydroxyurea therefore appears to be a possible candidate for AIDS therapy. C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP LORI, F (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,BETHESDA,MD 20892, USA. RI Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 29 TC 305 Z9 310 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 4 PY 1994 VL 266 IS 5186 BP 801 EP 805 DI 10.1126/science.7973634 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP753 UT WOS:A1994PP75300039 PM 7973634 ER PT J AU UMAR, A BOYER, JC KUNKEL, TA AF UMAR, A BOYER, JC KUNKEL, TA TI DNA LOOP REPAIR BY HUMAN CELL-EXTRACTS SO SCIENCE LA English DT Article ID COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; ADENOCARCINOMA CELLS; GENETIC INSTABILITY; ESCHERICHIA-COLI; CARCINOMA; LINES; ESTABLISHMENT; MUTATIONS; SEQUENCES AB An activity in human cell extracts is described tt lat repairs DNA with loops of five or more unpaired bases. Repair is strand-specific and is directed by a nick located 5' or 3' to the loop. This repair is observed in a colorectal cancer cell line that is devoid of a wild-type hMLH1 gene and is deficient in repair of mismatches. However, a cell line with deletions in both hMSH2 alleles is deficient in repair of both loops and mismatches. Defects in loop repair may be relevant to the repetitive-sequence instability observed in cancers and other hereditary diseases. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NR 44 TC 129 Z9 129 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 4 PY 1994 VL 266 IS 5186 BP 814 EP 816 DI 10.1126/science.7973637 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP753 UT WOS:A1994PP75300043 PM 7973637 ER PT J AU MCDOWELL, JC ROBERTS, JW JIN, DJ GROSS, C AF MCDOWELL, JC ROBERTS, JW JIN, DJ GROSS, C TI DETERMINATION OF INTRINSIC TRANSCRIPTION TERMINATION EFFICIENCY BY RNA-POLYMERASE ELONGATION RATE SO SCIENCE LA English DT Article ID ESCHERICHIA-COLI RNA; OPERON LEADER REGION; PHAGE-LAMBDA; BACTERIOPHAGE-LAMBDA; PAUSE SITE; INVITRO; RHO; GENE; REQUIREMENTS; SEQUENCES AB Transcription terminators recognized by several RNA polymerases include a DNA segment encoding uridine-rich RNA and, for bacterial RNA polymerase, a hairpin loop located immediately upstream. Here, mutationally altered Escherichia coli RNA polymerase enzymes that have different termination efficiencies were used to show that the extent of transcription through the uridine-rich encoding segment is controlled by the substrate concentration of nucleoside triphosphate. This result implies that the rate of elongation determines the probability of transcript release. Moreover, the position of release sites suggests an important spatial relation between the RNA hairpin and the boundary of the terminator. C1 CORNELL UNIV,BIOCHEM MOLEC & CELL BIOL SECT,ITHACA,NY 14853. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV WISCONSIN,DEPT BACTERIOL,MADISON,WI 53706. NR 31 TC 87 Z9 88 U1 1 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 4 PY 1994 VL 266 IS 5186 BP 822 EP 825 DI 10.1126/science.7526463 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP753 UT WOS:A1994PP75300046 PM 7526463 ER PT J AU HOFFMAN, A GROSSMAN, E ABASSI, ZA KEISER, HR AF HOFFMAN, A GROSSMAN, E ABASSI, ZA KEISER, HR TI RENAL ENDOTHELIN AND HYPERTENSION SO NATURE LA English DT Letter ID RATS C1 TECHNION ISRAEL INST TECHNOL,FAC MED,IL-31096 HAIFA,ISRAEL. TEL AVIV UNIV,CHAIM SHEBA MED CTR,DEPT MED,IL-52621 TEL AVIV,ISRAEL. TEL AVIV UNIV,FAC MED,IL-52621 TEL AVIV,ISRAEL. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. RP HOFFMAN, A (reprint author), RAMBAM MED CTR,TRANSPLANT UNIT,IL-31096 HAIFA,ISRAEL. NR 7 TC 8 Z9 8 U1 1 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 3 PY 1994 VL 372 IS 6501 BP 50 EP 50 DI 10.1038/372050a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ348 UT WOS:A1994PQ34800063 PM 7818710 ER PT J AU MA, JY YEE, A BREWER, HB DAS, S POTTER, H AF MA, JY YEE, A BREWER, HB DAS, S POTTER, H TI AMYLOID-ASSOCIATED PROTEINS ALPHA(1)-ANTICHYMOTRYPSIN AND APOLIPOPROTEIN-E PROMOTE ASSEMBLY OF ALZHEIMER BETA-PROTEIN INTO FILAMENTS SO NATURE LA English DT Article ID INHIBITOR ALPHA-1-ANTICHYMOTRYPSIN; TYPE-4 ALLELE; DISEASE; PEPTIDE; DEPOSITS; BINDING; INVITRO; METABOLISM; FIBRILS; PLAQUE AB THE protease inhibitor alpha(1)-antichymotrypsin and the lipid transport protein apolipoprotein E (apoE) are intimately associated with the 42-amino-acid beta-peptide (A beta) in the filamentous amyloid deposits of Alzheimer's disease(1-3). We report here that these two amyloid-associated proteins serve a strong stimulatory role in the polymerization of A beta into amyloid filaments. Addition of either alpha(1)-antichymotrypsin or apoE to the A beta peptide promoted a 10- to 20-fold increase in filament formation, with apoE-4, the isoform recently linked to the development of late-onset Alzheimer's disease, showing the highest catalytic activity. These and other experiments suggest that Alzheimer amyloid deposits arise when A beta is induced to form filaments by amyloid-promoting factors (pathological chaperones) expressed in certain brain regions. C1 NHLBI,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. NR 31 TC 751 Z9 761 U1 2 U2 19 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 3 PY 1994 VL 372 IS 6501 BP 92 EP 94 DI 10.1038/372092a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PQ348 UT WOS:A1994PQ34800079 PM 7969426 ER PT J AU CONNOR, EM SPERLING, RS GELBER, R KISELEV, P SCOTT, G OSULLIVAN, MJ VANDYKE, R BEY, M SHEARER, W JACOBSON, RL JIMENEZ, E ONEILL, E BAZIN, B DELFRAISSY, JF CULNANE, M COOMBS, R ELKINS, M MOYE, J STRATTON, P BALSLEY, J AF CONNOR, EM SPERLING, RS GELBER, R KISELEV, P SCOTT, G OSULLIVAN, MJ VANDYKE, R BEY, M SHEARER, W JACOBSON, RL JIMENEZ, E ONEILL, E BAZIN, B DELFRAISSY, JF CULNANE, M COOMBS, R ELKINS, M MOYE, J STRATTON, P BALSLEY, J TI REDUCTION OF MATERNAL-INFANT TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 WITH ZIDOVUDINE TREATMENT SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CLINICAL-TRIALS GROUP; RETROVIRAL DISEASE; HIV-1 INFECTION; PREGNANCY; VIREMIA; EMBRYOS; THERAPY; 3'-AZIDO-3'-DEOXYTHYMIDINE; PHARMACOKINETICS; PREIMPLANTATION AB Background and Methods. Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 (HIV). We conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant women (14 to 34 weeks' gestation) with CD4+ T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled. The zidovudine regimen included antepartum zidovudine (100 mg orally five times daily), intrapartum zidovudine (2 mg per kilogram of body weight given intravenously over a one-hour period, then 1 mg per kilogram per hour until delivery), and zidovudine for the newborn (2 mg per kilogram orally every six hours for six weeks). Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected. Results. From April 1991 through December 20, 1993, the cutoff date for the first interim analysis of efficacy, 477 pregnant women were enrolled; during the study period, 409 gave birth to 415 live-born infants. HIV-infection status was known for 363 births (180 in the zidovudine group and 183 in the placebo group). Thirteen infants in the zidovudine group and 40 in the placebo group were HIV-infected. The proportions infected at 18 months, as estimated by the Kaplan-Meier method, were 8.3 percent (95 percent confidence interval, 3.9 to 12.8 percent) in the zidovudine group and 25.5 percent (95 percent confidence interval, 18.4 to 32.5 percent) in the placebo group. This corresponds to a 67.5 percent (95 percent confidence interval, 40.7 to 82.1 percent) relative reduction in the risk of HIV transmission (Z = 4.03, P = 0.00006). Minimal short-term toxic effects were observed. The level of hemoglobin at birth in the infants in the zidovudine group was significantly lower than that in the infants in the placebo group. By 12 weeks of age, hemoglobin values in the two groups were similar. Conclusions. In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds. C1 UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT PEDIAT,NEWARK,NJ 07103. CUNY MT SINAI SCH MED,DEPT OBSTET GYNECOL & REPROD SCI,NEW YORK,NY 10029. HARVARD UNIV,SCH PUBL HLTH,AIDS CLIN TRIALS GRP,CTR STAT & DATA ANAL,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA. UNIV MIAMI,SCH MED,DEPT PEDIAT,MIAMI,FL. UNIV MIAMI,SCH MED,DEPT OBSTET & GYNECOL,MIAMI,FL 33101. TULANE UNIV,SCH MED,DEPT PEDIAT,NEW ORLEANS,LA 70112. LOUISIANA STATE UNIV,SCH MED,DEPT OBSTET & GYNECOL,NEW ORLEANS,LA. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. UNIV TEXAS,SCH MED,DEPT OBSTET & GYNECOL,HOUSTON,TX. SAN JUAN CITY HOSP,DEPT PEDIAT,SAN JUAN,PR. SAN JUAN CITY HOSP,DEPT OBSTET & GYNECOL,SAN JUAN,PR. AGENCE NATL RECH SIDA,PARIS,FRANCE. UNIV WASHINGTON,SCH MED,SEATTLE,WA. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. NICHHD,BETHESDA,MD. NIAID,DIV AIDS,PEDIAT MED BRANCH,BETHESDA,MD 20892. RI Sandall, Jane/D-4146-2009; OI Sandall, Jane/0000-0003-2000-743X; moye, john/0000-0001-9976-8586 NR 39 TC 2459 Z9 2571 U1 10 U2 80 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 3 PY 1994 VL 331 IS 18 BP 1173 EP 1180 DI 10.1056/NEJM199411033311801 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PN806 UT WOS:A1994PN80600001 PM 7935654 ER PT J AU BILSKI, P RESZKA, K CHIGNELL, CF AF BILSKI, P RESZKA, K CHIGNELL, CF TI OXIDATION OF ACI-NITROMETHANE BY SINGLET OXYGEN IN AQUEOUS-SOLUTION SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DYE-SENSITIZED PHOTOOXYGENATION; NITRIC-OXIDE; ROSE-BENGAL; MOLECULAR-OXYGEN; PHOTOOXIDATION; CONSUMPTION; SOLUBILITY; RESONANCE; KINETICS; NITRATE AB In alkaline solution nitromethane (NM) forms a stable aci tautomer (H2C double bond NO2-) which may be used as a spin trap for radicals, including NO. and NO2.. We have noticed previously that in aerated photochemical systems NM can undergo photosensitized degradation (Bilski et al., J. Am. Chem. Soc. 1992, 114, 549), possibly via singlet oxygen (O-1(2)). We have now confirmed that aci-NM does indeed quench O-1(2) phosphorescence (k(q) 2.4 X 10(7) M(-1) s(-1)), and that the addition of O-1(2) to aci-NM is solely responsible for this chemical quenching, as confirmed by the high quantum yield of O-2 photoconsumption (phi = 0.65 for [NM] = 35 mM). To obtain ''labeled'' fragments from the decomposition of the resultant aci-NM-O-2 peroxy species we have applied another spin trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), in a novel way: we used an EPR silent hydroxylamine adduct (DMPOH/CH double bond NO2-) formed by nucleophilic addition of aci-NM to DMPO. Reaction of DMPOH/CH double bond NO2- with O-1(2) resulted in the generation of the DMPO/CO2.- radical, suggesting that in the absence of DMPO the following mechanism may occur: O-1(2) + CH2 double bond NO2- --> NO2- + HCOOH. We have found that nitrite and formate production accounts for most of the oxygen consumed. This suggests that O-1(2) reacts mainly with the carbon atom of NM producing a biradical transient which decomposes yielding thermodynamically stable products nitrite and formate. A minor product is peroxynitrite (OONO-) which must be produced via an ozonide-type intermediate formed by intramolecular recombination of the biradical. Prolonged irradiation of Rose Bengal and aci-NM resulted in accumulation of nitrite which was then photooxidized to NO2., trapped by unreacted aci-NM and identified as the NM/NO2. spin adduct. RP BILSKI, P (reprint author), NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709, USA. NR 42 TC 9 Z9 9 U1 3 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 2 PY 1994 VL 116 IS 22 BP 9883 EP 9889 DI 10.1021/ja00101a008 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA PP754 UT WOS:A1994PP75400008 ER PT J AU GRZESIEK, S BAX, A AF GRZESIEK, S BAX, A TI INTERFERENCE BETWEEN DIPOLAR AND QUADRUPOLAR INTERACTIONS IN THE SLOW TUMBLING LIMIT - A SOURCE OF LINE SHIFT AND RELAXATION IN H-2-LABELED COMPOUNDS SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID C-13 NMR-SPECTRA; ESCHERICHIA-COLI THIOREDOXIN; NUCLEAR MAGNETIC-RELAXATION; STRUCTURAL INFORMATION; SOLID-STATE; MULTISPIN SYSTEMS; SPIN-1/2 NUCLEI; MAGIC-ANGLE; PROTEINS; RESOLUTION AB Using Redfield's theory of relaxation, it is demonstrated that interference of the dipolar and quadrupolar interactions between a spin-1/2 and a spin-1 nucleus causes a frequency shift of the spin-1/2 transition coupled to the m = 0 state of the spin-1 nucleus relative to the transitions coupled to the m=+/-1 states. This frequency shift depends on the rotational correlation time: it vanishes in the fast tumbling limit and reaches a constant in the slow motion limit which coincides with the results for static powder samples. For a C-13 nucleus which is J-coupled to a directly bonded H-2, this results in an asymmetric triplet pattern for molecular motions slower than at the T-1 minimum of the spin-1 nucleus. The center component of the triplet is shifted downfield by an amount which depends inversely on the static magnetic field strength. Although rapid longitudinal relaxation of the spin-1 nucleus collapses both the J multiplet and the interference-induced splitting, the interference contribution to the line width of the spin-1/2 nucleus can only be removed in part by high-power decoupling of the spin-1 nucleus. Experimental results are demonstrated for the C-13 spectrum of perdeuterated glycerol, where the rotational correlation time is varied with temperature. Application of the theory to other nuclei indicates that dipolar/quadrupolar interference also results in additional line broadening for proteins in solution that are enriched in H-2, and for amide protons attached to N-14. RP GRZESIEK, S (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 42 TC 36 Z9 36 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 2 PY 1994 VL 116 IS 22 BP 10196 EP 10201 DI 10.1021/ja00101a045 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA PP754 UT WOS:A1994PP75400045 ER PT J AU TAYLOR, PR LI, JY LI, B BLOT, WJ AF TAYLOR, PR LI, JY LI, B BLOT, WJ TI NUTRITION INTERVENTION TRIALS IN LINXIAN, CHINA - SUPPLEMENTATION WITH SPECIFIC VITAMIN/MINERAL COMBINATIONS, CANCER INCIDENCE, AND DISEASE-SPECIFIC MORTALITY IN THE GENERAL-POPULATION - REPLY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID VITAMIN-C C1 INT EPIDEMIOL INST,ROCKVILLE,MD 20850. NCI,BETHESDA,MD 20892. CHINESE ACAD MED SCI,BEIJING 100037,PEOPLES R CHINA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 2 PY 1994 VL 86 IS 21 BP 1647 EP 1648 DI 10.1093/jnci/86.21.1647 PG 2 WC Oncology SC Oncology GA PP191 UT WOS:A1994PP19100020 ER PT J AU SCHATZKIN, A FREEDMAN, LS DAWSEY, SM LANZA, E AF SCHATZKIN, A FREEDMAN, LS DAWSEY, SM LANZA, E TI INTERPRETING PRECURSOR STUDIES - WHAT POLYP TRIALS TELL US ABOUT LARGE-BOWEL CANCER - REPLY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP SCHATZKIN, A (reprint author), NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,EPN,RM 211,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 2 PY 1994 VL 86 IS 21 BP 1648 EP 1649 DI 10.1093/jnci/86.21.1648-a PG 2 WC Oncology SC Oncology GA PP191 UT WOS:A1994PP19100022 ER PT J AU BALDWIN, W AF BALDWIN, W TI REINVENTING THE NIH EXTRAMURAL PROGRAMS SO ACADEMIC MEDICINE LA English DT Editorial Material RP BALDWIN, W (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 1994 VL 69 IS 11 BP 892 EP 893 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA PR858 UT WOS:A1994PR85800008 ER PT J AU LUBKOWSKI, J WLODAWER, A HOUSSET, D WEBER, IT AMMON, HL MURPHY, KC SWAIN, AL AF LUBKOWSKI, J WLODAWER, A HOUSSET, D WEBER, IT AMMON, HL MURPHY, KC SWAIN, AL TI REFINED CRYSTAL-STRUCTURE OF ACINETOBACTER GLUTAMINASIFICANS GLUTAMINASE ASPARAGINASE SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID ESCHERICHIA-COLI ASPARAGINASE; SITE-SPECIFIC MUTAGENESIS; ERWINIA-CHRYSANTHEMI; RESIDUES; HISTIDINE; CATALYSIS; ENZYMES AB The crystal structure of glutaminase-asparaginase from Acinetobacter glutaminasificans has been reinterpreted and refined to an R factor of 0.171 at 2.9 Angstrom resolution, using the same X-ray diffraction data that were used to build a preliminary model of this enzyme [Ammon, Weber, Wlodawer, Harrison, Gilliland, Murphy, Sjolin and Roberts (1988). J. Biol. Chem. 263, 150-156]. The current model, which does not include solvent, is based in part on the related structure of Escherichia coli asparaginase and is significantly different from the structure of the enzyme from A. glutaminasificans described previously. The reason for the discrepancies has been traced to insufficient phasing power of the original heavy-atom derivative data, which could not be compensated for fully by electron-density modification techniques. The corrected structure of A. glutaminasificans glutaminase-asparaginase is presented and compared with the preliminary model and with the structure of E. coli asparaginase. C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,COLLEGE PK,MD 20742. RP LUBKOWSKI, J (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702, USA. NR 25 TC 34 Z9 36 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD NOV 1 PY 1994 VL 50 BP 826 EP 832 DI 10.1107/S0907444994003446 PN 6 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA PR048 UT WOS:A1994PR04800004 PM 15299349 ER PT J AU SHIBUTANI, M AF SHIBUTANI, M TI NEURONAL LINEAGE IN ETHYL-NITROSOUREA-INDUCED BRAIN-TUMORS SO ACTA NEUROPATHOLOGICA LA English DT Letter ID PRIMITIVE NEUROECTODERMAL TUMORS; EXPRESSION RP SHIBUTANI, M (reprint author), NICHHD,GROWTH FACTORS SECT,BETHESDA,MD 20892, USA. RI Shibutani, Makoto/C-2510-2013 NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD NOV PY 1994 VL 88 IS 5 BP 490 EP 490 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA PP456 UT WOS:A1994PP45600016 PM 7847081 ER PT J AU GRANT, BF AF GRANT, BF TI ALCOHOL-CONSUMPTION, ALCOHOL-ABUSE AND ALCOHOL DEPENDENCE - THE UNITED-STATES AS AN EXAMPLE SO ADDICTION LA English DT Article ID DSM-III-R AB This paper presents national estimates of alcohol consumption and DSM-IV alcohol abuse and dependence in the United States. Fifty-two percent of the adults surveyed were classified as current drinkers and nearly 9.0% met criteria for DSM-IV alcohol abuse or dependence. Greater percentages of males and whites were classified as current drinkers and as alcohol abusers or dependent, compared with females and non-whites, respectively. There is a need for future epidemiological research to collect better data on drinking patterns as an aid to interpreting socio-demographic differentials and to estimate more precisely the association between alcohol consumption and abuse and dependence in multivariate statistical environments. The critical need to examine the unprecedented reversal of the abuse-to-dependence ratio resulting from the application of the DSM-IV classification is emphasized. The role of future longitudinal alcohol epidemiological research in elucidating the initiation and maintenance of consumption patterns and alcohol use disorders is stressed. RP GRANT, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,6000 EXECUT BLVD,SUITE 514,ROCKVILLE,MD 20892, USA. NR 11 TC 47 Z9 48 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD NOV PY 1994 VL 89 IS 11 BP 1357 EP 1365 DI 10.1111/j.1360-0443.1994.tb03730.x PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA PR833 UT WOS:A1994PR83300002 PM 7841843 ER PT J AU WINDLE, C AF WINDLE, C TI SOCIAL VALUES AND SERVICES RESEARCH - THE CASE OF RURAL SERVICES SO ADMINISTRATION AND POLICY IN MENTAL HEALTH LA English DT Article RP WINDLE, C (reprint author), NIMH,OFF RURAL MENTAL HLTH RES,5600 FISHERS LANE,ROOM 10-104,ROCKVILLE,MD 20857, USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD NOV PY 1994 VL 22 IS 2 BP 181 EP 188 DI 10.1007/BF02106552 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA PU392 UT WOS:A1994PU39200011 ER PT J AU OSMANOV, S BELSEY, EM HEYWARD, W ESPARZA, J GALVAOCASTRO, B VANDEPERRE, P KARITA, E WASI, C SEMPALA, S TUGUME, B BIRYAHWAHO, B RUBSAMENWAIGMANN, H VONBRIESEN, H ESSER, R GREZ, M HOLMES, H NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM GOUDSMIT, J DEWOLF, F HAHN, BH GAO, F YUE, L SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P FENYO, EM ALBERT, J MYERS, G KORBER, B AF OSMANOV, S BELSEY, EM HEYWARD, W ESPARZA, J GALVAOCASTRO, B VANDEPERRE, P KARITA, E WASI, C SEMPALA, S TUGUME, B BIRYAHWAHO, B RUBSAMENWAIGMANN, H VONBRIESEN, H ESSER, R GREZ, M HOLMES, H NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM GOUDSMIT, J DEWOLF, F HAHN, BH GAO, F YUE, L SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P FENYO, EM ALBERT, J MYERS, G KORBER, B TI HIV TYPE-1 VARIATION IN WORLD-HEALTH-ORGANIZATION-SPONSORED VACCINE EVALUATION SITES - GENETIC SCREENING, SEQUENCE-ANALYSIS, AND PRELIMINARY BIOLOGICAL CHARACTERIZATION OF SELECTED VIRAL STRAINS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMINO-ACID SUBSTITUTION; ANTIGENIC VARIATION; PRIMARY INFECTION; ENV GENES; PHENOTYPE; MUTATIONS; VARIANTS; PROTEIN; DOMAIN AB A laboratory network has been established by the World Health Organization (WHO) to systematically isolate and characterize HIV strains from different parts of the world, and to obtain information and reagents that would facilitate HIV vaccine development. Sixty-three HIV-1 isolates obtained from 224 specimens collected during 1992-1993 in Brazil, Rwanda, Thailand, and Uganda were characterized in this initial study. Virus strains were first genetically subtyped using three different screening methodologies: PCR-gag fingerprinting, RNase A mismatch, and heteroduplex mobility assay (HMA). In addition, selected viruses were sequenced in V3 (52 strains), C2-V3 (42 strains), gp120 (15 strains), and/or gp160 (8 strains) regions of their envelope genes. These studies identified viruses belonging to different sequence subtypes in the four countries: 16 subtype B and 1 subtype C strains in Brazil, 13 subtype A strains in Rwanda, 15 subtype E and 2 subtype B strains in Thailand, and 3 subtype A and 13 subtype D strains in Uganda. Comparison of sequence data with results from the genetic screening efforts identified the HMA as a rapid and reliable method for sequence subtype determinations. The majority of strains were collected from persons documented to have recently seroconverted to HIV-1 positivity, and most strains were found to have slow replication and low cytopathic characteristics and to be non-syncytium-inducing (slow/low-NSI phenotypes) in vitro, which, in many cases, correlated with the corresponding genotype and charge of the V3 loop amino acid sequences. This collection of HIV strains is presently being characterized immunologically and serologically, including neutralization assays, to define whether there are immunological correlates of the sequence subtypes. Identification of potential immunotypes would be of considerable importance for the further development of HIV vaccines. C1 GEORG SPEYER HAUS CHEMOTHERAPEUT FORSCHUNGSINST,FRANKFURT,GERMANY. NATL INST BIOL STAND & CONTROLS,LONDON NW3 6RB,ENGLAND. NIAID,DIV AIDS,BETHESDA,MD. WALTER REED ARMY INST RES,HENRY M JACKSON FDN RES LAB,ROCKVILLE,MD. INST SALUD CARLOS 3,CTR NACL BIOL CELULAR & RETROVIRUS,MADRID,SPAIN. STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. UNIV AMSTERDAM,HUMAN RETROVIRUS LAB,AMSTERDAM,NETHERLANDS. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. INST COCHIN GENET MOLEC,F-75014 PARIS,FRANCE. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. ST MARYS HOSP,SCH MED,LONDON,ENGLAND. NCI,FREDERICK,MD 21701. KAROLINSKA INST,STOCKHOLM,SWEDEN. SWEDISH INST INFECT DIS CONTROL,STOCKHOLM,SWEDEN. LOS ALAMOS NATL LAB,LOS ALAMOS,NM. RP OSMANOV, S (reprint author), WHO,GLOBAL PROGRAMME AIDS,DIV RES & INTERVENT DEV,VACCINE DEV UNIT,CH-1211 GENEVA 27,SWITZERLAND. RI Dopazo, Joaquin/A-9270-2014; Lopez-Galindez, Cecilio/A-3603-2008; Van de Perre, Philippe/B-9692-2008 OI Dopazo, Joaquin/0000-0003-3318-120X; Lopez-Galindez, Cecilio/0000-0002-2324-9584; Van de Perre, Philippe/0000-0002-3912-0427 NR 54 TC 110 Z9 110 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1994 VL 10 IS 11 BP 1327 EP 1343 DI 10.1089/aid.1994.10.1327 PG 17 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PV996 UT WOS:A1994PV99600003 ER PT J AU BACHMANN, MH DELWART, EL SHPAER, EG LINGENFELTER, P SINGAL, R MULLINS, JI OSMANOV, S BELSEY, EM HEYWARD, W ESPARZA, J GALVAOCASTRO, B VANDEPERRE, P KARITA, E WASI, C SEMPALA, S TUGUME, B BIRYAHWAHO, B RUBSAMENWAIGMANN, H VONBRIESEN, H ESSER, R GREZ, M HOLMES, H NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J GOUDSMIT, J DEWOLF, F HAHN, BH GAO, F YUE, L SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P FENYO, EM ALBERT, J MYERS, G KORBER, B AF BACHMANN, MH DELWART, EL SHPAER, EG LINGENFELTER, P SINGAL, R MULLINS, JI OSMANOV, S BELSEY, EM HEYWARD, W ESPARZA, J GALVAOCASTRO, B VANDEPERRE, P KARITA, E WASI, C SEMPALA, S TUGUME, B BIRYAHWAHO, B RUBSAMENWAIGMANN, H VONBRIESEN, H ESSER, R GREZ, M HOLMES, H NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J GOUDSMIT, J DEWOLF, F HAHN, BH GAO, F YUE, L SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P FENYO, EM ALBERT, J MYERS, G KORBER, B TI RAPID GENETIC-CHARACTERIZATION OF HIV TYPE-1 STRAINS FROM 4 WORLD-HEALTH-ORGANIZATION-SPONSORED VACCINE EVALUATION SITES USING A HETERODUPLEX MOBILITY ASSAY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID THAILAND; POPULATIONS; GENOTYPES AB To assist in the preparation for the testing of vaccines against human immunodeficiency virus (HIV) we, as part of the World Health Organization Network for HIV Isolation and Characterization (WHO-NHIC), evaluated the genotypic variation of HIV-1 in cohorts from Brazil, Rwanda, Thailand, and Uganda. Here we report the results from a pilot study of 65 HIV-1-infected individuals. In all cases in which viral envelope gene fragments could be amplified by polymerase chain reaction, subtypes could be assigned using a heteroduplex mobility assay (HMA)(1) by comparison with HIV-1 strains representing six HIV-1 envelope subtypes. All subtype classifications matched those found by envelope gene sequencing. Phylogenetic relationships were further clarified by heteroduplex formation between samples within each subtype. A relatively homogeneous subtype E virus population predominated over subtype B viruses in the sample set from Thailand. Viruses from the other countries were also limited to one or two subtypes but were more divergent within each subtype. All samples from Rwanda (13/13) and some from Uganda (3/16) were of subtype A; all Brazilian samples were of subtype B, except for one belonging to subtype C; most samples from Uganda (13/16) clustered with the subtype D. Analysis by HMA is therefore applicable for screening of HIV-1 genotypes in countries under consideration for large-scale vaccine trials. It should be generally useful when samples containing at least one variable genetic locus need to be rapidly classified by genotype and/or analyzed for epidemiological clustering. C1 UNIV WASHINGTON,DEPT MICROBIOL,SEATTLE,WA 98195. STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. WHO,WHO NETWORK HIV ISOLAT & CHARACT,GLOBAL PROGRAMME AIDS,GENEVA,SWITZERLAND. GEORG SPEYER HAUS CHEMOTHERAPEUT FORSCHUNGSINST,FRANKFURT,GERMANY. NATL INST BIOL STAND & CONTROLS,LONDON NW3 6RB,ENGLAND. NIAID,DIV AIDS,BETHESDA,MD. WALTER REED ARMY INST RES,HENRY M JACKSON FDN RES LAB,ROCKVILLE,MD. INST SALUD CARLOS 3,CTR NACL BIOL CELULAR & RETROVIRUS,MADRID,SPAIN. UNIV AMSTERDAM,HUMAN RETROVIRUS LAB,AMSTERDAM,NETHERLANDS. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. INST COCHIN GENET MOLEC,F-75014 PARIS,FRANCE. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. ST MARYS HOSP,SCH MED,LONDON,ENGLAND. NCI,VIRUS BIOL UNIT,FREDERICK,MD. KAROLINSKA INST,STOCKHOLM,SWEDEN. SWEDISH INST INFECT DIS CONTROL,STOCKHOLM,SWEDEN. LOS ALAMOS NATL LAB,LOS ALAMOS,NM. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. RI Dopazo, Joaquin/A-9270-2014; Lopez-Galindez, Cecilio/A-3603-2008; Van de Perre, Philippe/B-9692-2008; Bachmann, Michael/N-9339-2016; OI Dopazo, Joaquin/0000-0003-3318-120X; Lopez-Galindez, Cecilio/0000-0002-2324-9584; Van de Perre, Philippe/0000-0002-3912-0427; Bachmann, Michael/0000-0002-0204-3720; Delwart, Eric/0000-0002-6296-4484 FU NIAID NIH HHS [AI32885] NR 24 TC 77 Z9 80 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1994 VL 10 IS 11 BP 1345 EP 1353 DI 10.1089/aid.1994.10.1345 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PV996 UT WOS:A1994PV99600004 PM 7888187 ER PT J AU KORBER, BTM OSMANOV, S ESPARZA, J MYERS, G BELSEY, EM HEYWARD, W GALVAOCASTRO, B VANDEPERRE, P KARITA, E WASI, C SEMPALA, S TUGUME, B BIRYAHWAHO, B RUBSAMENWAIGMANN, H VONBRIESEN, H ESSER, R GREZ, M HOLMES, H NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM GOUDSMIT, J DEWOLF, F HAHN, BH GAO, F YUE, L SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P FENYO, EM ALBERT, J KORBER, B AF KORBER, BTM OSMANOV, S ESPARZA, J MYERS, G BELSEY, EM HEYWARD, W GALVAOCASTRO, B VANDEPERRE, P KARITA, E WASI, C SEMPALA, S TUGUME, B BIRYAHWAHO, B RUBSAMENWAIGMANN, H VONBRIESEN, H ESSER, R GREZ, M HOLMES, H NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM GOUDSMIT, J DEWOLF, F HAHN, BH GAO, F YUE, L SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P FENYO, EM ALBERT, J KORBER, B TI THE WORLD-HEALTH-ORGANIZATION GLOBAL PROGRAM ON AIDS PROPOSAL FOR STANDARDIZATION OF HIV SEQUENCE NOMENCLATURE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article AB The World Health Organization Global Programme on AIDS (WHO/GPA) is conducting a large-scale collaborative study of human immunodeficiency virus type 1 (HIV-1) variation, based in four potential vaccine-trial site countries: Brazil, Rwanda, Thailand, and Uganda.(1) Through the course of this study, it was crucial to keep track of certain attributes of the samples from which the viral nucleotide sequences were derived (e.g., country of origin and viral culture characterization), so that meaningful sequence comparisons could be made. Here we describe a system developed in the context of the WHO/GPA study that summarizes such critical attributes by representing them as standardized characters directly incorporated into sequence names. This nomenclature allows linkage of clinical, phenotypic, and geographic information with molecular data. We propose that other investigators involved in human immunodeficiency virus (HIV) nucleotide sequencing efforts adopt a similar standardized sequence nomenclature to facilitate cross-study sequence comparison. HIV sequence data are being generated at an ever-increasing rate; directly coupled to this increase is our deepening understanding of biological parameters that influence or result from sequence variability. A standardized sequence nomenclature that includes relevant biological information would enable researchers to better utilize the growing body of sequence data, and enhance their ability to interpret the biological implications of their own data through facilitating comparisons with previously published work. C1 SANTA FE INST,SANTA FE,NM 87501. WHO,GLOBAL PROGRAMME AIDS,WHO NETWORK HIV ISOLAT & CHARACT,VACCINE DEV UNIT,CH-1211 GENEVA,SWITZERLAND. GEORG SPEYER HAUS CHEMOTHERAPEUT FORSCHUNGSINST,FRANKFURT,GERMANY. NATL INST BIOL STAND & CONTROLS,LONDON NW3 6RB,ENGLAND. NIAID,DIV AIDS,BETHESDA,MD. WALTER REED ARMY INST RES,HENRY M JACKSON FDN RES LAB,ROCKVILLE,MD. INST SALUD CARLOS 3,CTR NACL BIOL CELULAR & RETROVIRUS,MADRID,SPAIN. STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA. UNIV AMSTERDAM,HUMAN RETROVIRUS LAB,AMSTERDAM,NETHERLANDS. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. INST COCHIN GENET MOLEC,F-75014 PARIS,FRANCE. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. ST MARYS HOSP,SCH MED,LONDON,ENGLAND. NCI,VIRUS BIOL UNIT,FREDERICK,MD. KAROLINSKA INST,STOCKHOLM,SWEDEN. SWEDISH INST INFECT DIS CONTROL,STOCKHOLM,SWEDEN. RP KORBER, BTM (reprint author), LOS ALAMOS NATL LAB,DIV THEORY,POB 1663,LOS ALAMOS,NM 87545, USA. RI Dopazo, Joaquin/A-9270-2014; Lopez-Galindez, Cecilio/A-3603-2008; Van de Perre, Philippe/B-9692-2008; OI Dopazo, Joaquin/0000-0003-3318-120X; Lopez-Galindez, Cecilio/0000-0002-2324-9584; Van de Perre, Philippe/0000-0002-3912-0427; Korber, Bette/0000-0002-2026-5757 NR 8 TC 39 Z9 39 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1994 VL 10 IS 11 BP 1355 EP 1358 DI 10.1089/aid.1994.10.1355 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PV996 UT WOS:A1994PV99600005 PM 7888188 ER PT J AU GAO, F YUE, L CRAIG, S THORNTON, CL ROBERTSON, DL MCCUTCHAN, FE BRADAC, JA SHARP, PM HAHN, BH OSMANOV, S BELSEY, EM HEYWARD, W ESPARZA, J GALVAOCASTRO, B VANDEPERRE, P KARITA, E WASI, C SEMPALA, S TUGUME, B BIRYAHWAHO, B RUBSAMENWAIGMANN, H VONBRIESEN, H ESSER, R GREZ, M HOLMES, H NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM GOUDSMIT, J DEWOLF, F SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P FENYO, EM ALBERT, J MYERS, G KORBER, B AF GAO, F YUE, L CRAIG, S THORNTON, CL ROBERTSON, DL MCCUTCHAN, FE BRADAC, JA SHARP, PM HAHN, BH OSMANOV, S BELSEY, EM HEYWARD, W ESPARZA, J GALVAOCASTRO, B VANDEPERRE, P KARITA, E WASI, C SEMPALA, S TUGUME, B BIRYAHWAHO, B RUBSAMENWAIGMANN, H VONBRIESEN, H ESSER, R GREZ, M HOLMES, H NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM GOUDSMIT, J DEWOLF, F SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P FENYO, EM ALBERT, J MYERS, G KORBER, B TI GENETIC-VARIATION OF HIV TYPE-1 IN 4 WORLD-HEALTH-ORGANIZATION-SPONSORED VACCINE EVALUATION SITES - GENERATION OF FUNCTIONAL ENVELOPE (GLYCOPROTEIN-160) CLONES REPRESENTATIVE OF SEQUENCE SUBTYPE-A, SUBTYPE-B, SUBTYPE-C, AND SUBTYPE-E SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; PHYLOGENETIC ANALYSIS; CD4 BINDING; NEUTRALIZATION; DIVERSITY; EPITOPES; REGION; IDENTIFICATION; GENOTYPES AB As part of the WHO Network for HIV Isolation and Characterization, we PCR amplified, cloned, and sequenced gp120 and gp160 genes from 12 HIV-1 isolates collected in four WHO-sponsored vaccine evaluation sites (Brazil, Rwanda, Thailand, Uganda). Envelope clones were derived from PBMC-grown isolates obtained from asymptomatic individuals within 2 years of seroconversion. Analysis of their deduced amino acid sequences identified all but one to contain an uninterrupted open reading frame. Transient expression and biological characterization of selected gp160 constructs identified six clones to encode full length and functional envelope glycoproteins. Phylogenetic analysis of their nucleotide sequences revealed that they represent HIV-1 subtypes A, B, C, and E. Since current knowledge of HIV-1 envelope immunobiology is almost exclusively derived from subtype B viruses, these reagents should facilitate future envelope structure, function and antigenicity studies on a broader spectrum of viruses. This should assist in the design and evaluation of effective vaccines against HIV-1. C1 UNIV ALABAMA, DEPT MED, BIRMINGHAM, AL 35294 USA. UNIV ALABAMA, DEPT MICROBIOL, BIRMINGHAM, AL 35294 USA. UNIV NOTTINGHAM, QUEENS MED CTR, DEPT GENET, NOTTINGHAM NG7 2UH, ENGLAND. WALTER REED ARMY INST RES, HENRY M JACKSON FDN RES LAB, ROCKVILLE, MD 20850 USA. NIAID, VACCINE RES & DEV BRANCH, BETHESDA, MD 20892 USA. WHO, WHO NETWORK HIV ISOLAT & CHARACT, GLOBAL PROGRAMME AIDS, CH-1211 GENEVA, SWITZERLAND. GEORG SPEYER HAUS CHEMOTHERAPEUT FORSCHUNGSINST, FRANKFURT, GERMANY. NATL INST BIOL STAND & CONTROLS, LONDON NW3 6RB, ENGLAND. NIAID, DIV AIDS, BETHESDA, MD 20892 USA. WALTER REED ARMY INST RES, HENRY M JACKSON FDN RES LAB, ROCKVILLE, MD USA. INST SALUD CARLOS 3, CTR NACL BIOL CELULAR & RETROVIRUS, MADRID, SPAIN. STANFORD UNIV, SCH MED, DEPT MICROBIOL & IMMUNOL, STANFORD, CA 94305 USA. UNIV AMSTERDAM, HUMAN RETROVIRUS LAB, AMSTERDAM, NETHERLANDS. UNIV ALABAMA, DEPT MED, BIRMINGHAM, AL 35294 USA. INST COCHIN GENET MOLEC, F-75014 PARIS, FRANCE. CTR DIS CONTROL & PREVENT, ATLANTA, GA 30341 USA. ST MARYS HOSP, SCH MED, LONDON, ENGLAND. NCI, VIRUS BIOL UNIT, FREDERICK, MD 21701 USA. KAROLINSKA INST, STOCKHOLM, SWEDEN. SWEDISH INST INFECT DIS CONTROL, STOCKHOLM, SWEDEN. LOS ALAMOS NATL LAB, LOS ALAMOS, NM USA. RI Sharp, Paul/F-5783-2010; Dopazo, Joaquin/A-9270-2014; Lopez-Galindez, Cecilio/A-3603-2008; Van de Perre, Philippe/B-9692-2008 OI Sharp, Paul/0000-0001-9771-543X; Dopazo, Joaquin/0000-0003-3318-120X; Lopez-Galindez, Cecilio/0000-0002-2324-9584; Van de Perre, Philippe/0000-0002-3912-0427 FU NIAID NIH HHS [P30 AI27767, R01 AI25291] NR 50 TC 105 Z9 107 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1994 VL 10 IS 11 BP 1359 EP 1368 DI 10.1089/aid.1994.10.1359 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PV996 UT WOS:A1994PV99600006 PM 7888189 ER PT J AU PAU, CP KAI, M HOLLOMANCANDAL, DL LUO, CC KALISH, ML SCHOCHETMAN, G BYERS, B GEORGE, JR OSMANOV, S BELSEY, EM HEYWARD, W ESPARZA, J GALVAOCASTRO, B VANDEPERRE, P KARITA, E WASI, C SEMPALA, S TUGUME, B BIRYAHWAHO, B RUBSAMENWAIGMANN, H VONBRIESEN, H ESSER, R GREZ, M HOLMES, H NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM GOUDSMIT, J DEWOLF, F HAHN, BH GAO, F YUE, L SARAGOSTI, S KALISH, M GEORGE, R WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P FENYO, EM ALBERT, J MYERS, G KORBER, B AF PAU, CP KAI, M HOLLOMANCANDAL, DL LUO, CC KALISH, ML SCHOCHETMAN, G BYERS, B GEORGE, JR OSMANOV, S BELSEY, EM HEYWARD, W ESPARZA, J GALVAOCASTRO, B VANDEPERRE, P KARITA, E WASI, C SEMPALA, S TUGUME, B BIRYAHWAHO, B RUBSAMENWAIGMANN, H VONBRIESEN, H ESSER, R GREZ, M HOLMES, H NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM GOUDSMIT, J DEWOLF, F HAHN, BH GAO, F YUE, L SARAGOSTI, S KALISH, M GEORGE, R WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P FENYO, EM ALBERT, J MYERS, G KORBER, B TI ANTIGENIC VARIATION AND SEROTYPING OF HIV TYPE-1 FROM 4 WORLD-HEALTH-ORGANIZATION-SPONSORED HIV VACCINE SITES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID EPITOPES AB Serologic reactivities of serum or plasma from 55 HIV-1 subjects in four countries-Brazil, Rwanda, Thailand, and Uganda-were examined by V3 peptide immunoassay. Forty-seven (85.5%) of the 55 specimens tested positive to the homologous peptide. A strong correlation between serotype (i.e., pattern of serologic reactivity with a panel of peptides) and genotype was not found. However, the V3 peptide immunoassays may be useful for epidemiologic studies to trace the distinctive HIV-1 strains from different geographic regions of the world. The serology data obtained may be useful for the development of effective V3-based vaccines. C1 WHO,GLOBAL PROGRAMME AIDS,WHO NETWORK HIV ISOLAT & CHARACT,CH-1211 GENEVA,SWITZERLAND. GEORG SPEYER HAUS CHEMOTHERAPEUT FORSCHUNGSINST,FRANKFURT,GERMANY. NATL INST BIOL STAND & CONTROLS,LONDON NW3 6RB,ENGLAND. NIAID,DIV AIDS,BETHESDA,MD 20892. WALTER REED ARMY INST RES,HENRY M JACKSON FDN RES LAB,ROCKVILLE,MD. INST SALUD CARLOS 3,CTR NACL BIOL CELULAR & RETROVIRUS,MADRID,SPAIN. STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. UNIV AMSTERDAM,HUMAN RETROVIRUS LAB,AMSTERDAM,NETHERLANDS. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL. INST COCHIN GENET MOLEC,F-75014 PARIS,FRANCE. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. ST MARYS HOSP,SCH MED,LONDON,ENGLAND. NCI,FREDERICK,MD 21701. KAROLINSKA INST,STOCKHOLM,SWEDEN. SWEDISH INST INFECT DIS CONTROL,STOCKHOLM,SWEDEN. LOS ALAMOS NATL LAB,LOS ALAMOS,NM. RP PAU, CP (reprint author), CTR DIS CONTROL,NATL CTR INFECT DIS,DIV HIV AIDS,1600 CLIFTON RD,ATLANTA,GA 30333, USA. RI Dopazo, Joaquin/A-9270-2014; Lopez-Galindez, Cecilio/A-3603-2008; Van de Perre, Philippe/B-9692-2008 OI Dopazo, Joaquin/0000-0003-3318-120X; Lopez-Galindez, Cecilio/0000-0002-2324-9584; Van de Perre, Philippe/0000-0002-3912-0427 NR 12 TC 63 Z9 63 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1994 VL 10 IS 11 BP 1369 EP 1377 DI 10.1089/aid.1994.10.1369 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PV996 UT WOS:A1994PV99600007 PM 7888190 ER PT J AU CHEINGSONGPOPOV, R LISTER, S CALLOW, D KALEEBU, P BEDDOWS, S WEBER, J OSMANOV, S BELSEY, EM HEYWARD, W ESPARZA, J GALVAOCASTRO, B VANDEPERRE, P KARITA, E WASI, C SEMPALA, S TUGUME, B BIRYAHWAHO, B RUBSAMENWAIGMANN, H VONBRIESEN, H ESSER, R GREZ, M HOLMES, H NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM GOUDSMIT, J DEWOLF, F HAHN, BH GAO, F YUE, L SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP NARA, P FENYO, EM ALBERT, J MYERS, G KORBER, B AF CHEINGSONGPOPOV, R LISTER, S CALLOW, D KALEEBU, P BEDDOWS, S WEBER, J OSMANOV, S BELSEY, EM HEYWARD, W ESPARZA, J GALVAOCASTRO, B VANDEPERRE, P KARITA, E WASI, C SEMPALA, S TUGUME, B BIRYAHWAHO, B RUBSAMENWAIGMANN, H VONBRIESEN, H ESSER, R GREZ, M HOLMES, H NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM GOUDSMIT, J DEWOLF, F HAHN, BH GAO, F YUE, L SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP NARA, P FENYO, EM ALBERT, J MYERS, G KORBER, B TI SEROTYPING HIV TYPE-1 BY ANTIBODY-BINDING TO THE V3 LOOP - RELATIONSHIP TO VIRAL GENOTYPE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRINCIPAL NEUTRALIZING DETERMINANT; MONOCLONAL-ANTIBODY; DOMAIN; GP120; ENVELOPE; SEQUENCE; IDENTIFICATION; CHIMPANZEES; EPITOPES AB We have investigated whether peptides representing the HIV-1 principal neutralization domain (V3) can be used as antigens in antibody-binding assays to predict the genotypes of the subjects' virus. Serum samples collected from HIV-1-infected subjects from the four WHO-sponsored vaccine evaluation sites (Uganda, Rwanda, Thailand, and Brazil) were characterized by antibody binding to a panel of synthetic V3 peptides that were derived from the consensus sequences of the V3 region of the HIV-1 subgroups according to the env phylogenetic analysis (A-E). An indirect V3 peptide-binding assay was used for primary screening, and a V3 peptide antigen-limiting ELISA was then used as a secondary assay to discriminate cross-reactivity if the screening assay was equivocal. In general, V3 peptide serology could predict HIV-1 genotypes. In sera for which the genotype of the virus was known, peptide assays could predict the correct genotype in approximately 90% of cases for genotypes A, B, C, and E; Ugandan sera of genotype D were more broadly reactive. There was considerable serological cross-reactivity between some HIV-1 genotypes, in particular between A and C, and, to a lesser extent, B and D subtypes. Owing to polymorphism at the crown of the V3 loop, an additional B peptide (B') was required to type Brazilian B genotype sera. These simple assays may help facilitate the determination and distribution of HIV-1 genotypes circulating in populations. C1 WHO,GLOBAL PROGRAMME AIDS,WHO NETWORK HIV ISOLAT & CHARACT,CH-1211 GENEVA,SWITZERLAND. GEORG SPEYER HAUS CHEMOTHERAPEUT FORSCHUNGSINST,FRANKFURT,GERMANY. NATL INST BIOL STAND & CONTROLS,LONDON NW3 6RB,ENGLAND. NIAID,DIV AIDS,BETHESDA,MD 20892. WALTER REED ARMY INST RES,HENRY M JACKSON FDN RES LAB,ROCKVILLE,MD. INST SALUD CARLOS 3,CTR NACL BIOL CELULAR & RETROVIRUS,MADRID,SPAIN. STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. UNIV AMSTERDAM,HUMAN RETROVIRUS LAB,AMSTERDAM,NETHERLANDS. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. INST COCHIN GENET MOLEC,F-75014 PARIS,FRANCE. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. ST MARYS HOSP,SCH MED,LONDON,ENGLAND. NCI,VIRUS BIOL UNIT,FREDERICK,MD 21701. KAROLINSKA INST,STOCKHOLM,SWEDEN. SWEDISH INST INFECT DIS CONTROL,STOCKHOLM,SWEDEN. LOS ALAMOS NATL LAB,LOS ALAMOS,NM. RP CHEINGSONGPOPOV, R (reprint author), ST MARYS HOSP,SCH MED,DEPT GENITOURINARY MED & COMMUNICABLE DIS,PRAED ST,LONDON W2 1NY,ENGLAND. RI Dopazo, Joaquin/A-9270-2014; Lopez-Galindez, Cecilio/A-3603-2008; Van de Perre, Philippe/B-9692-2008 OI Dopazo, Joaquin/0000-0003-3318-120X; Lopez-Galindez, Cecilio/0000-0002-2324-9584; Van de Perre, Philippe/0000-0002-3912-0427 NR 29 TC 85 Z9 86 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1994 VL 10 IS 11 BP 1379 EP 1386 DI 10.1089/aid.1994.10.1379 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PV996 UT WOS:A1994PV99600008 PM 7888191 ER PT J AU DEWOLF, F HOGERVORST, E GOUDSMIT, J FENYO, EM RUBSAMENWAIGMANN, H HOLMES, H GALVAOCASTRO, B KARITA, E WASI, C SEMPALA, SDK BAAN, E ZORGDRAGER, F LUKASHOV, V OSMANOV, S KUIKEN, C CORNELISSEN, M BELSEY, EM HEYWARD, W ESPARZA, J VANDEPERRE, P SEMPALA, S TUGUME, B BIRYAHWAHO, B VONBRIESEN, H ESSER, R GREZ, M NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM HAHN, BH GAO, F YUE, L SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P ALBERT, J MYERS, G KORBER, B AF DEWOLF, F HOGERVORST, E GOUDSMIT, J FENYO, EM RUBSAMENWAIGMANN, H HOLMES, H GALVAOCASTRO, B KARITA, E WASI, C SEMPALA, SDK BAAN, E ZORGDRAGER, F LUKASHOV, V OSMANOV, S KUIKEN, C CORNELISSEN, M BELSEY, EM HEYWARD, W ESPARZA, J VANDEPERRE, P SEMPALA, S TUGUME, B BIRYAHWAHO, B VONBRIESEN, H ESSER, R GREZ, M NEWBERRY, A RANJBAR, S TOMLINSON, P BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM HAHN, BH GAO, F YUE, L SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P ALBERT, J MYERS, G KORBER, B TI SYNCYTIUM-INDUCING AND NON-SYNCYTIUM-INDUCING CAPACITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SUBTYPES OTHER THAN B - PHENOTYPIC AND GENOTYPIC CHARACTERISTICS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SURFACE ENVELOPE GLYCOPROTEIN; AMINO-ACID SUBSTITUTION; T-CELL-LINE; ANTIGENIC VARIATION; V3 LOOP; NEUTRALIZING ANTIBODIES; SYNTHETIC PEPTIDES; INFECTED INDIVIDUALS; BIOLOGICAL PHENOTYPE; MACROPHAGE TROPISM AB Positively charged amino acid substitutions at positions 11 and 25 within the loop of the third variable region (V3) of HIV-1 subtype B envelope have been shown to be associated with the syncytium-inducing (SI) phenotype of the virus. The present study was designed to examine SI and NSI-associated V3 mutations in HIV-1 subtypes other than B. HIV-1 RNA was isolated from 53 virus stocks and 26 homologous plasma samples from 53 recently infected individuals from Brazil, Rwanda, Thailand, and Uganda. The C2-V3 region of the viral envelope was converted to cDNA, amplified, and sequenced. Of 53 primary virus stock samples 49 were biologically phenotyped through measurement of the syncytium-inducing capacity in MT-2 cells (to differentiate between SI and NSI phenotypes). In addition, after passage of primary isolates through PHA stimulated donor PBMC, the replication capacity was determined in U937-2, CEM, MT-2, and Jurkat-tat cell lines (to differentiate rapid/high and slow/low phenotypes). According to the sequence analysis 9 (17.0%) of the viruses belonged to subtype A, 15 (28.3%) to subtype B, 1 (1.9%) to subtype C, 13 (24.5%) to subtype D, and 15 (28.3%) to subtype E. Sequence analysis of virus RNA, obtained from 26 homologous plasma samples, confirmed the homogeneity of sequence populations in plasma compared to primary virus isolates. Of the 49 viruses tested 12 had the SI phenotype, 5 were confirmed to be rapid/high, and 4 appeared to be slow/low pattern 3 replicating. Of 49, 29 had the NSI phenotype, 24 were confirmed to be slow/low pattern 1 or 2, and 3 appeared to be slow/low pattern 3 replicating. Analysis of mutations at V3 loop amino acid positions 11 and 25 revealed that 10/12 (83.3%) of the SI viruses had SI-associated V3 mutations and that 28/29 (96.6%) of the NSI viruses lacked these mutations. V3 loop heterogeneity, length polymorphism, and a high number of positively charged amino acid substitutions were most frequently found among subtype D variants. These results indicate that both the phenotypic distinction between SI and NSI viruses and the association of biological phenotype with V3 mutations is present among HIV-1 subtypes other than B. C1 KAROLINSKA INST,DEPT MICROBIOL & TUMORBIOL,STOCKHOLM,SWEDEN. BAYER AG,ZENTRUM PHARMAFORSCH,INST VIROL,W-5600 WUPPERTAL,GERMANY. CHEMOTHERAPEUT FORSCHUNGSINST GEORG SPEYER HAUS,FRANKFURT,GERMANY. NATL INST BIOL STAND & CONTROLS,POTTERS BAR EN6 3QG,HERTS,ENGLAND. BRAZILIAN NETWORK HIV ISOLAT & CHARACTERIZAT,REFERENCE LAB,SALVADOR,BA,BRAZIL. NATL AIDS CONTROL PROGRAMME,REFERENCE LAB,KIGALI,RWANDA. MAHIDOL UNIV,SIRIRAJ HOSP,FAC MED,DIV VIROL,BANGKOK 10700,THAILAND. UGANDA VIRUS RES INST,ENTEBBE,UGANDA. WHO,GLOBAL PROGRAMME AIDS,WHO NETWORK HIV ISOLAT & CHARACT,VACCINE DEV UNIT,CH-1211 GENEVA,SWITZERLAND. NATL INST BIOL STAND & CONTROLS,LONDON NW3 6RB,ENGLAND. NIAID,DIV AIDS,BETHESDA,MD 20892. WALTER REED ARMY INST RES,HENRY M JACKSON FDN RES LAB,ROCKVILLE,MD. INST SALUD CARLOS 3,CTR NACL BIOL CELULAR & RETROVIRUS,MADRID,SPAIN. STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. UNIV AMSTERDAM,HUMAN RETROVIRUS LAB,AMSTERDAM,NETHERLANDS. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. INST COCHIN GENET MOLEC,F-75014 PARIS,FRANCE. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. ST MARYS HOSP,SCH MED,LONDON,ENGLAND. NCI,VIROL BIOL UNIT,FREDERICK,MD 21701. KAROLINSKA INST,STOCKHOLM,SWEDEN. SWEDISH INST INFECT DIS CONTROL,STOCKHOLM,SWEDEN. LOS ALAMOS NATL LAB,LOS ALAMOS,NM. RP DEWOLF, F (reprint author), UNIV AMSTERDAM,ACAD MED CTR,DEPT VIROL,HUMAN RETROVIRUS LAB,K3-368,MEIBERGDREEF 15,1105 AZ AMSTERDAM,NETHERLANDS. RI Dopazo, Joaquin/A-9270-2014; Lopez-Galindez, Cecilio/A-3603-2008; Van de Perre, Philippe/B-9692-2008 OI Dopazo, Joaquin/0000-0003-3318-120X; Lopez-Galindez, Cecilio/0000-0002-2324-9584; Van de Perre, Philippe/0000-0002-3912-0427 NR 82 TC 145 Z9 145 U1 0 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1994 VL 10 IS 11 BP 1387 EP 1400 DI 10.1089/aid.1994.10.1387 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PV996 UT WOS:A1994PV99600009 PM 7888192 ER PT J AU RUBSAMENWAIGMANN, H VONBRIESEN, H HOLMES, H BJORNDAL, A KORBER, B ESSER, R RANJBAR, S TOMLINSON, P GALVAOCASTRO, B KARITA, E SEMPALA, S WASI, C OSMANOV, S FENYO, EM BELSEY, EM HEYWARD, W ESPARZA, J VANDEPERRE, P TUGUME, B BIRYAHWAHO, B GREZ, M NEWBERRY, A BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM GOUDSMIT, J DEWOLF, F HAHN, BH GAO, F YUE, L SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P ALBERT, J MYERS, G AF RUBSAMENWAIGMANN, H VONBRIESEN, H HOLMES, H BJORNDAL, A KORBER, B ESSER, R RANJBAR, S TOMLINSON, P GALVAOCASTRO, B KARITA, E SEMPALA, S WASI, C OSMANOV, S FENYO, EM BELSEY, EM HEYWARD, W ESPARZA, J VANDEPERRE, P TUGUME, B BIRYAHWAHO, B GREZ, M NEWBERRY, A BRADAC, J MCCUTCHAN, F LOUWAGIE, J HEGERICH, P LOPEZGALINDEZ, C OLIVARES, I DOPAZO, J MULLINS, JI DELWART, EL BACHMANN, HM GOUDSMIT, J DEWOLF, F HAHN, BH GAO, F YUE, L SARAGOSTI, S SCHOCHETMAN, G KALISH, M LUO, CC GEORGE, R PAU, CP WEBER, J CHEINGSONGPOPOV, R KALEEBU, P NARA, P ALBERT, J MYERS, G TI STANDARD CONDITIONS OF VIRUS ISOLATION REVEAL BIOLOGICAL VARIABILITY OF HIV TYPE-1 IN DIFFERENT REGIONS OF THE WORLD SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNCYTIUM-INDUCING PHENOTYPE; REPLICATIVE CAPACITY; PROGRESSION; INDIVIDUALS; INFECTION; SEVERITY; DISEASE; DOMAIN; ASSAY AB HIV-1 isolates were obtained from four countries within the framework of the WHO Network for HIV Isolation and Characterization. The use of standard HIV isolation procedures allowed us to compare the biological properties of 126 HIV-1 isolates spanning five genetic subtypes. In primary isolation cultures, viruses from Uganda and Brazil appeared early and replicated without delay, whereas the replication of Thai viruses was delayed by several weeks. Regardless of genetic subtype or country of origin, blood samples collected more than 2 years after seroconversion yielded virus that replicated efficiently in the primary isolation cultures. None of the isolates obtained from Thailand or Rwanda replicated in cell lines, whereas 5 of the 13 Brazilian isolates and 7 of the 11 Ugandan isolates replicated and induced syncytia in MT-2 cells. As expected for virus isolates obtained early in HIV-1 infection (within 2 years of seroconversion), all viruses from Brazil, Rwanda, and Thailand showed a slow/low replicative pattern. For the Ugandan samples, the time from seroconversion was known precisely for a few of the samples and only in one case was less than 2 years. This may explain why the five viruses that were able to replicate in all cell lines, and thus classified as rapid/high, were of Ugandan origin. Viruses able to induce syncytia in MT-2 cells, also induced syncytia in PBMC. However, 8 slow/low viruses (out of 27) gave discordant results, inducing syncytia in PBMC but not in MT-2 cells. Furthermore, using syncytium induction as a marker, changes in virus populations during early in vitro passage in PBMC could be observed. The results indicate that biological variation is a general property of HIV-1 in different regions of the world. Moreover, the time from HIV-1 infection, rather than genetic subtype, seems to be linked to viral phenotype. C1 KAROLINSKA INST,CTR MICROBIOL & TUMORBIOL,S-17177 STOCKHOLM,SWEDEN. GEORG SPEYER HAUS CHEMOTHERAPEUT FORSCHUNSINST,FRANKFURT,GERMANY. NATL INST BIOL STAND & CONTROLS,LONDON NW3 6RB,ENGLAND. LOS ALAMOS NATL LAB,HIV SEQUENCE DATABASE,LOS ALAMOS,NM. FIOCRUZ MS,SALVADOR,BA,BRAZIL. INST TROP MED,DEPT MICROBIOL,B-2000 ANTWERP,BELGIUM. UGANDA VIRUS RES INST,ENTEBBE,UGANDA. MAHIDOL UNIV,SIRIRAJ HOSP,FAC MED,DEPT MICROBIOL,DIV VIROL,BANGKOK 10700,THAILAND. WHO,GLOBAL PROGRAMME AIDS,WHO NETWORK HIV ISOLAT & CHARACT,CH-1211 GENEVA,SWITZERLAND. NIAID,DIV AIDS,BETHESDA,MD 20892. WALTER REED ARMY INST RES,HENRY M JACKSON FDN RES LAB,ROCKVILLE,MD. INST SALUD CARLOS 3,CTR NACL BIOL CELULAR & RETROVIRUS,MADRID,SPAIN. STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. UNIV AMSTERDAM,HUMAN RETROVIRUS LAB,AMSTERDAM,NETHERLANDS. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. INST COCHIN GENET MOLEC,F-75014 PARIS,FRANCE. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. ST MARYS HOSP,SCH MED,LONDON,ENGLAND. NCI,VIRUS BIOL UNIT,FREDERICK,MD 21701. KAROLINSKA INST,STOCKHOLM,SWEDEN. SWEDISH INST INFECT DIS CONTROL,STOCKHOLM,SWEDEN. LOS ALAMOS NATL LAB,LOS ALAMOS,NM. RI Dopazo, Joaquin/A-9270-2014; Lopez-Galindez, Cecilio/A-3603-2008; Van de Perre, Philippe/B-9692-2008; OI Dopazo, Joaquin/0000-0003-3318-120X; Lopez-Galindez, Cecilio/0000-0002-2324-9584; Van de Perre, Philippe/0000-0002-3912-0427; Korber, Bette/0000-0002-2026-5757 NR 24 TC 50 Z9 50 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1994 VL 10 IS 11 BP 1401 EP 1408 DI 10.1089/aid.1994.10.1401 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PV996 UT WOS:A1994PV99600010 PM 7888193 ER PT J AU MORGAN, RA BALERBITTERLICH, G RAGHEB, JA WONGSTAAL, F GALLO, RC ANDERSON, WF AF MORGAN, RA BALERBITTERLICH, G RAGHEB, JA WONGSTAAL, F GALLO, RC ANDERSON, WF TI FURTHER EVALUATION OF SOLUBLE CD4 AS AN ANTI-HIV TYPE-1 GENE-THERAPY - DEMONSTRATION OF PROTECTION OF PRIMARY HUMAN PERIPHERAL-BLOOD LYMPHOCYTES FROM INFECTION BY HIV TYPE-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-INFILTRATING LYMPHOCYTES; AIDS-RELATED COMPLEX; RETROVIRAL VECTORS; T-CELLS; INTRACELLULAR IMMUNIZATION; TRANSDOMINANT MUTANTS; HAIRPIN RIBOZYME; DIVERSE STRAINS; IMMUNE FUNCTION AB We previously reported on the construction of retroviral vectors that produce a secreted form of the HIV-1 receptor, T cell antigen CD4 (Morgan et al., AIDS Res Hum Retroviruses 1990;6:183-191). In this article we test the ability of these sCD4-expressing retroviral vectors to protect human T-cell lines or primary T cells from HIV-1 infection. To demonstrate that protection from HIV-1 infection is mediated by the soluble nature of this protein, two coculture protection experiments were conducted. In these experiments, sCD4-expressing retroviral vectors were used to engineer mouse NIH 3T3 cells. In one coculture experiment the human SupT1 cell line was added directly to the culture of sCD4-producing NIH 3T3 cells, and in another experiment the two cell types were separated physically by a semipermeable membrane. In both coculture configurations, the T cell line was protected from HIV-1 challenge as measured by syncytium formation and indirect immunofluorescent assays. In addition, the SupT1 line was directly engineered with sCD4-expressing retroviral vectors and shown to be protected from HIV-1 challenge. As a prelude to further preclinical studies, we tested the ability of retroviral vectors to transduce primary human peripheral blood lymphocytes (PBLs). Conditions used to stimulate T cell growth resulted in significant shifts in the CD4/CD8 cell in favor of CD8 cells. Retroviral-mediated gene transfer under these conditions resulted in low levels of gene transfer (<5%). By applying appropriate selection conditions, cell populations that are 30-50% gene containing can be obtained. Challenge of sCD4-engineered bulk PBLs with HIV-1 demonstrates a 50-75% inhibition in HIV-1 production. HIV-1 challenge of a coculture of sCD4-engineered CD8 PBLs with the SupT1 T cells showed diminished HIV-1 infection of the SupT1 cell line, again suggesting the ability of sCD4-engineered cells to protect unengineered HIV-1 target cells in solution. C1 NHLBI,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. NR 77 TC 24 Z9 26 U1 0 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1994 VL 10 IS 11 BP 1507 EP 1515 DI 10.1089/aid.1994.10.1507 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PV996 UT WOS:A1994PV99600023 PM 7888205 ER PT J AU NEUMANN, M HARRISON, J SALTARELLI, M HADZIYANNIS, E ERFLE, V FELBER, BK PAVLAKIS, GN AF NEUMANN, M HARRISON, J SALTARELLI, M HADZIYANNIS, E ERFLE, V FELBER, BK PAVLAKIS, GN TI SPLICING VARIABILITY IN HIV TYPE-1 REVEALED BY QUANTITATIVE POLYMERASE CHAIN-REACTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL MESSENGER-RNA; INFECTED INDIVIDUALS; REV PROTEIN; GENE-EXPRESSION; PLASMA; CELLS; ENV; REPLICATION; TAT AB A quantitative RNA-polymerase chain reaction (PCR) method able to detect the majority of mRNAs produced by human immunodeficiency virus type 1 (HIV-1) was developed and used to study expression of different HIV-1 clones in human cells. Amplified mRNAs were compared to known cDNA standards. This comparison permitted the optimization of PCR conditions and eliminated the generation of artifactual PCR bands. The use of RNA and cDNA standards demonstrated that the RNA amplification is linear within the tested range and suggested that it can be used to quantitate individual mRNAs. The results demonstrate the overall conservation of splicing in different HIV-1 clones. Although, in general, splicing was conserved, extensive qualitative and quantitative variability was observed in different HIV-1 clones. This variability is likely one determinant of the biological characteristics of the different HIV-1 clones, and demonstrates a great plasticity of the HIV-1 genome. The described RNA-PCR methodology was used for the study of HIV-1 expression in unstimulated peripheral blood mononuclear cells (PBMCs) of infected individuals. In general, the same mRNAs were identified in HIV-infected cultured cell lines and in unstimulated PBMCs. Analysis of a variant band found after amplification of PBMC RNA from an HIV-infected individual revealed a new splice site for the generation of Rev/Nef-encoding mRNAs. The availability of a sensitive, rapid, and essentially quantitative method to examine the major HIV-1 mRNAs will facilitate the detailed analysis of HIV-1 expression in human cells. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. GSF,INST MOLEC VIROL,D-85758 OBERSCHLEISSHEIM,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 39 TC 40 Z9 41 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1994 VL 10 IS 11 BP 1531 EP 1542 DI 10.1089/aid.1994.10.1531 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PV996 UT WOS:A1994PV99600026 PM 7888208 ER PT J AU ABIMIKU, AG STERN, TL ZWANDOR, A MARKHAM, PD CALEF, C KYARI, S SAXINGER, WC GALLO, RC ROBERTGUROFF, M REITZ, MS AF ABIMIKU, AG STERN, TL ZWANDOR, A MARKHAM, PD CALEF, C KYARI, S SAXINGER, WC GALLO, RC ROBERTGUROFF, M REITZ, MS TI SUBGROUP-G HIV TYPE-1 ISOLATES FROM NIGERIA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Note ID SEQUENCE C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. MINIST HLTH,JOS,NIGERIA. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. LOS ALAMOS NATL LAB,DIV THEORET,LOS ALAMOS,NM 87545. PLATEAU STATE HOSP,ICSC,WL AIDS CTR,JOS,NIGERIA. NR 8 TC 46 Z9 47 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 1994 VL 10 IS 11 BP 1581 EP 1583 DI 10.1089/aid.1994.10.1581 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PV996 UT WOS:A1994PV99600033 PM 7888214 ER PT J AU DELBOCA, FK MATTSON, ME AF DELBOCA, FK MATTSON, ME TI DEVELOPMENTS IN ALCOHOLISM-TREATMENT RESEARCH - PATIENT TREATMENT MATCHING SO ALCOHOL LA English DT Article; Proceedings Paper CT NOBEL Symposium on Treatment of Alcoholism as a Chronic Disorder CY OCT 28-29, 1993 CL GREENVILLE, NC DE ALCOHOLISM TREATMENT; TREATMENT OUTCOME RESEARCH; TREATMENT MATCHING ID EMPIRICALLY DERIVED TYPOLOGY AB This article describes patient-treatment matching, a recent advance in alcoholism treatment research. A general description of the concept is presented and the challenges patient-treatment matching poses for investigators and for treatment providers are described. Project MATCH, a multisite clinical trial designed to test the matching hypothesis is used to illustrate approaches to addressing the research challenge. Two additional avenues of promising patient-treatment matching research, one relating to patient characteristics and the other to pharmacological treatments, are also summarized. The article concludes with a brief prescription for individual providers to implement and test treatment matching strategies in their own clinical practice. C1 NIAAA,ROCKVILLE,MD 20857. RP DELBOCA, FK (reprint author), UNIV CONNECTICUT,SCH MED,ALCOHOL RES CTR,DEPT PSYCHIAT,MC1410,FARMINGTON,CT 06030, USA. FU NIAAA NIH HHS [AA08430] NR 14 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD NOV-DEC PY 1994 VL 11 IS 6 BP 471 EP 475 DI 10.1016/0741-8329(94)90069-8 PG 5 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA PU784 UT WOS:A1994PU78400009 PM 7865145 ER PT J AU MALHOTRA, V FERRANS, VJ VIRMANI, R AF MALHOTRA, V FERRANS, VJ VIRMANI, R TI INFANTILE HISTIOCYTOID CARDIOMYOPATHY - 3 CASES AND LITERATURE-REVIEW SO AMERICAN HEART JOURNAL LA English DT Review ID FOAMY MYOCARDIAL TRANSFORMATION; CARDIAC-MUSCLE-CELLS; MITOCHONDRIAL CARDIOMYOPATHY; RESPIRATORY-CHAIN; SUDDEN-DEATH; TUMOR; RHABDOMYOMA; INFANCY; HEART C1 NHLBI, PATHOL BRANCH, ULTRASTRUCT SECT, BETHESDA, MD 20892 USA. ARMED FORCES INST PATHOL, DEPT CARDIOVASC PATHOL, WASHINGTON, DC 20306 USA. NR 52 TC 33 Z9 34 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD NOV PY 1994 VL 128 IS 5 BP 1009 EP 1021 DI 10.1016/0002-8703(94)90601-7 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PN864 UT WOS:A1994PN86400023 PM 7942464 ER PT J AU SHIRANI, J ZAFARI, AM HILL, VE ROBERTS, WC AF SHIRANI, J ZAFARI, AM HILL, VE ROBERTS, WC TI LONG ASYMPTOMATIC SURVIVAL WITH A BULLET ADJACENT TO THE LEFT MAIN CORONARY-ARTERY, THE ONLY SITE OF ATHEROSCLEROTIC PLAQUE IN THE CORONARY TREE SO AMERICAN HEART JOURNAL LA English DT Note RP SHIRANI, J (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 1994 VL 128 IS 5 BP 1043 EP 1044 DI 10.1016/0002-8703(94)90606-8 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PN864 UT WOS:A1994PN86400028 PM 7942469 ER PT J AU KATZEL, LI SORKIN, JD COLMAN, E GOLDBERG, AP BUSBYWHITEHEAD, MJ LAKATTA, LE BECKER, LC LAKATTA, EG FLEG, JL AF KATZEL, LI SORKIN, JD COLMAN, E GOLDBERG, AP BUSBYWHITEHEAD, MJ LAKATTA, LE BECKER, LC LAKATTA, EG FLEG, JL TI RISK-FACTORS FOR EXERCISE-INDUCED SILENT-MYOCARDIAL-ISCHEMIA IN HEALTHY-VOLUNTEERS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-ARTERY DISEASE; OLDER MEN; ASYMPTOMATIC MEN; SCINTIGRAPHY; MORTALITY; OBESITY; PROGNOSIS; PATIENT; FOLLOW AB This study determined the risk factors for exercise-induced silent ischemia (SI) in 281 apparently healthy volunteers aged 40 to 87 years and compared their risk factor profiles with those of 132 patients with overt coronary artery disease (CAD). SI (concordant exercise-induced asymptomatic ST-segment depression on electrocardiography and perfusion defects on tomographic thallium-201 scintigraphy) was detected in 37 of 225 men (16%), versus 2 of 56 women (4%, p <0.05). The prevalence of SI increased with age from 6% in men aged <55 years to 18% in men aged 55 to 70 years, and to 25% in men aged >70 years (p <0.001). Compared with the 118 men with concordant normal exercise electrocardiogram and thallium scan (normals), men with SI were older (p <0.001), and had a higher waist-to-hip ratio (p <0.005), higher plasma triglyceride levels (p <0.001), and lower high-density lipoprotein (HDL) cholesterol levels (p <0.001). In stepwise logistic regression analysis, age, waist-to-hip ratio, and HDL levels were independent predictors of SI in men. Compared with 108 men with overt CAD, men with SI were younger (67 +/- 2 vs 73 +/- 1 years, p <0.001) but had similar plasma lipids and waist-to-hip ratio. Thus, older age, male gender, abdominal obesity, and reduced HDL levels-all well-established risk factors for overt CAD-were risk factors for exercise-induced SI in these asymptomatic volunteers. C1 UNIV MARYLAND,SCH MED,DEPT MED,DIV GERONTOL,BALTIMORE,MD 21201. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV GERIAT MED & GERONTOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD 21224. RP KATZEL, LI (reprint author), VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,GERIATR SERV 18,METAB SECT,CLIN PHYSIOL LAB,BALTIMORE,MD 21201, USA. FU NIA NIH HHS [5-KO8-AG00497, P01 AG04402-05, 5-K08-AG00383-02] NR 30 TC 30 Z9 31 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 1994 VL 74 IS 9 BP 869 EP 874 DI 10.1016/0002-9149(94)90578-9 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP130 UT WOS:A1994PP13000006 PM 7977116 ER PT J AU OBARZANEK, E LESEM, MD JIMERSON, DC AF OBARZANEK, E LESEM, MD JIMERSON, DC TI RESTING METABOLIC-RATE OF ANOREXIA-NERVOSA PATIENTS DURING WEIGHT-GAIN SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ANOREXIA NERVOSA; RESTING METABOLIC RATE; ENERGY METABOLISM; THERMOGENESIS ID ENERGY-EXPENDITURE; BODY-COMPOSITION; YOUNG MEN; THERMOGENESIS; RECOVERY; ADAPTATION; EXERCISE; OBESITY; WOMEN; NOREPINEPHRINE AB To determine whether changes in energy metabolism may contribute to the difficulty of weight gain observed in anorexic patients, resting metabolic rate (RMR) and neuroendocrine function were studied in 10 patients diagnosed with anorexia nervosa. RMR per kilogram lean body mass (+/-SEM) was not significantly different from that of healthy volunteers on admission (95.9 +/- 5.6 vs 103.6 +/- 3.3 kJ/kg, respectively), during early refeeding (108.6 +/- 6.9 kJ/kg), or at target weight (102.1 +/- 3.8 kJ/kg). At late refeeding RMR was significantly higher (132.1 +/- 4.9 kJ/kg, P < 0.0001). There were no significant correlations between plasma norepinephrine and thyroid hormones and RMR. The rise in RMR during refeeding is at least double that observed in other studies in which normal-weight subjects are experimentally overfed or experimentally underfed and then refed. These results suggest that the increase in RMR during refeeding is disproportionate to weight gain and this large magnitude of increase may be unique to anorexia nervosa. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. FU NIMH NIH HHS [F32-MH09183] NR 71 TC 54 Z9 54 U1 1 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 1994 VL 60 IS 5 BP 666 EP 675 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PN572 UT WOS:A1994PN57200004 PM 7942571 ER PT J AU ELIN, RJ AF ELIN, RJ TI MAGNESIUM - THE 5TH BUT FORGOTTEN ELECTROLYTE SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Review DE MAGNESIUM; METABOLISM; LABORATORY TESTS; HYPOMAGNESEMIA ID ACUTE MYOCARDIAL-INFARCTION; INTRACELLULAR FREE MAGNESIUM; NUCLEAR MAGNETIC-RESONANCE; INTRAVENOUS LOADING TEST; ISCHEMIC HEART-DISEASE; BLOOD-CELL MAGNESIUM; ESSENTIAL-HYPERTENSION; FLUORESCENT INDICATOR; PREMENSTRUAL-SYNDROME; DIETARY MAGNESIUM AB Magnesium (Mg) is the second most abundant intracellular cation and is a cofactor in more than 300 enzymatic reactions involving energy metabolism and protein and nucleic acid synthesis. Ionized Mg is the physiologically active form of the element. Protein-bound and chelated Mg buffer the ionized pool. Approximately half the total Mg in the body is present intracellularly in soft tissue, and the other half is present in bone. Less than 1% of the total body Mg is present in blood. However, the majority of our clinical laboratory information comes from the determination of total Mg in serum. Currently, the clinical laboratory evaluation of Mg status is limited primarily to the total serum Mg concentration and a 24-hour urinary excretion. Instrumentation to determine ionized Mg in serum (ion-selective electrode) and in soft tissue (nuclear magnetic resonance spectroscopy) should be available in the near future. Magnesium may be a factor in the treatment of acute myocardial infarction and the rate of atherosclerosis. Chronic changes of Mg status, that may be latent, are poorly understood and require a better knowledge of ionized Mg metabolism. RP ELIN, RJ (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,CLIN CHEM SERV,9000 ROCKVILLE PIKE,BLDG 10,BETHESDA,MD 20892, USA. NR 78 TC 126 Z9 128 U1 1 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 1994 VL 102 IS 5 BP 616 EP 622 PG 7 WC Pathology SC Pathology GA PQ162 UT WOS:A1994PQ16200012 PM 7942627 ER PT J AU MOSKALUK, CA POGREBNIAK, HW PASS, HI GALLIN, JI TRAVIS, WD AF MOSKALUK, CA POGREBNIAK, HW PASS, HI GALLIN, JI TRAVIS, WD TI SURGICAL PATHOLOGY OF THE LUNG IN CHRONIC GRANULOMATOUS-DISEASE SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE CHRONIC GRANULOMATOUS DISEASE; PNEUMONIA; INTERFERON ID INTERFERON-GAMMA; MANAGEMENT; INFECTIONS; PHAGOCYTE; PATIENT AB The pathologic features in pulmonary specimens are reported from 32 open thoracotomies of 20 patients with chronic granulomatous disease (CGD). The pattern of inflammation present in the resected material varied, but a granulomatous component was present in each case. In 78% of the specimens, a distinctive form of granuloma was found: a neutrophilic microabscess surrounded by palisading histiocytes. In four specimens eosinophils were also found within the microabscesses. This feature was found exclusively in cases of fungal infection. Fungal organisms were found by culture in 18 specimens (56%) and in 17 of these specimens (94%), they also were seen by histopathology. In 9 cases (28%) routine bacterial cultures were positive, and in one case an atypical Mycobacterium was cultured. These organisms were not prospectively identified on special stains of histologic sections in any of the cases. Abscess formation was found more commonly in pure fungal infections (41%) than in pure bacterial infections (14%). In contrast to earlier reports, well-formed granulomas with giant cells were not specific for fungal infections. In this series, they were present in 57% of cases with pure bacterial infections. A subset of the patients received gamma interferon therapy or granulocyte transfusions before the surgical procedures. No differences in the histopathology of the inflammation were associated with granulocyte transfusions, but gamma interferon therapy,vas associated with a reduction in necrotizing granulomatous inflammation. Additionally, one case of severe cytomegalovirus pneumonitis is described in a CGD patient receiving chronic steroid therapy. C1 NCI,PATHOL LAB,BETHESDA,MD. NCI,SURG BRANCH,THORAC ONCOL SECT,BETHESDA,MD. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NR 20 TC 27 Z9 30 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 1994 VL 102 IS 5 BP 684 EP 691 PG 8 WC Pathology SC Pathology GA PQ162 UT WOS:A1994PQ16200023 PM 7942637 ER PT J AU WACHOLDER, S SCHATZKIN, A FREEDMAN, LS KIPNIS, V HARTMAN, A BROWN, CC AF WACHOLDER, S SCHATZKIN, A FREEDMAN, LS KIPNIS, V HARTMAN, A BROWN, CC TI CAN ENERGY ADJUSTMENT SEPARATE THE EFFECTS OF ENERGY FROM THOSE OF SPECIFIC MACRONUTRIENTS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BIOMETRY; CALORIC INTAKE; DIET; DIETARY CARBOHYDRATES; DIETARY FATS; DIETARY PROTEINS; EPIDEMIOLOGIC METHODS; REGRESSION ANALYSIS ID EPIDEMIOLOGIC ANALYSES; MODELS; CANCER; PERIOD; RATES; AGE AB Energy adjustment is used in nutritional epidemiology in an attempt to separate specific effects of macronutrients (carbohydrate, fat, and protein) from one another and from the generic effect of the total quantity of energy consumed. However, models in which the risk of disease is allowed to depend simultaneously on daily total energy consumption and separate components of energy that sum to the total are not identifiable: the specific effects of individual macronutrients and the generic effect of energy cannot be disentangled by multivariate analysis. The standard, residual, and partition methods exclude one or more macronutrients from consideration, thereby allowing estimation, but the parameters that are estimated no longer represent specific macronutrient or generic energy effects. Therefore, an interpretation of a regression coefficient from these methods as a specific effect of a macronutrient or as the generic effect of energy requires additional, almost always questionable, assumptions. For example, a conclusion based on data alone that there is a specific fat effect upon the development of breast cancer but no specific effects of other macronutrients and no generic energy effect is not possible. Notwithstanding these serious problems, some useful etiologic inference still can be made. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP WACHOLDER, S (reprint author), NCI,DIV CANC ETIOL,BIOSTAT BRANCH,EPIDEMIOL METHODS SECT,6130 EXECUT BLVD,EPN 403,ROCKVILLE,MD 20852, USA. NR 13 TC 62 Z9 62 U1 1 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1994 VL 140 IS 9 BP 848 EP 855 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PQ069 UT WOS:A1994PQ06900010 PM 7977295 ER PT J AU SIDRANSKY, E GINNS, EI WESTMAN, JA EHMANN, WC AF SIDRANSKY, E GINNS, EI WESTMAN, JA EHMANN, WC TI PATHOLOGICAL FRACTURES MAY DEVELOP IN GAUCHER PATIENTS RECEIVING ENZYME REPLACEMENT THERAPY SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID DISEASE C1 CHILDRENS HOSP,COLUMBUS,OH 43205. PENN STATE UNIV,COLL MED,HERSHEY,PA. RP SIDRANSKY, E (reprint author), NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD, USA. RI Westman, Judith/E-4294-2011 NR 5 TC 16 Z9 16 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD NOV PY 1994 VL 47 IS 3 BP 247 EP 249 DI 10.1002/ajh.2830470325 PG 3 WC Hematology SC Hematology GA PM928 UT WOS:A1994PM92800024 PM 7942798 ER PT J AU BENYA, RV METZ, DC VENZON, DJ FISHBEYN, VA STRADER, DB ORBUCH, M JENSEN, RT AF BENYA, RV METZ, DC VENZON, DJ FISHBEYN, VA STRADER, DB ORBUCH, M JENSEN, RT TI ZOLLINGER-ELLISON SYNDROME CAN BE THE INITIAL ENDOCRINE MANIFESTATION IN PATIENTS WITH MULTIPLE ENDOCRINE NEOPLASIA-TYPE-I SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID GASTRIC-ACID SECRETION; ISLET CELL TUMORS; PARATHYROID-HORMONE; MANAGEMENT; RESECTION; GENE; HYPERPARATHYROIDISM; CHROMOSOME-11; LOCALIZATION; GLUCAGONOMA AB PURPOSE: To determine whether patients with multiple endocrine neoplasia type I (MEN-I) can initially present with Zollinger-Ellison syndrome (ZES), and to learn whether ZES exhibits any distinguishing features when it occurs as a first manifestation of MEN-I. PATIENTS AND METHODS: Sixty patients who had been referred to a clinical research center with ZES were examined by cohort analysis. Twenty-eight had MEN-I and 32 did not. In patients with MEN-I, we analyzed the temporal relationships between the clinical and biochemical manifestations of ZES and the other endocrinopathies associated with the neoplasia. To determine whether patients who had ZES as a first manifestation of MEN-I (n = 8) had any distinguishing clinical characteristics, we compared them to a cohort of patients with established sporadic ZES (n = 32) matched for age, sex, and time since the onset of symptoms consistent with ZES. RESULTS: Of the 28 patients with ZES and MEN-I, 11 initially presented with ZES and hyperparathyroidism (HP) and 1 with evidence only for pituitary disease. Eight patients (29%) presented with features of ZES and developed clinical and biochemical evidence for HP later, while the same number developed these 2 endocrinopathies in the opposite order. In whichever order ZES and HP occurred, the time from the diagnosis of the first to the diagnosis of the second was similar. It ranged from 9 to 177 months in patients who presented with ZES first, and from 12 to 264 months in patients who presented with HP first. At the time of initial diagnosis, the patients who presented with ZES as a manifestation of MEN-I had no distinguishing ZES-related symptoms, biochemical assays, or tumor imaging results compared to the cohort of patients who had the syndrome sporadically. CONCLUSION: Patients with MEN-I can initially present with a symptomatic pancreatic endocrine tumor syndrome without any other disease manifestations. In patients with ZES and MEN-I, up to one third may present with ZES without evidence of any other endocrinopathy. Consequently, patients with presumed sporadic ZES should undergo continual biochemical screening for other endocrinopathies characteristic of MEN-I and, in the future, genetic studies for the MEN-I gene. C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NCI,DEPT STAT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 53 TC 91 Z9 91 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 1994 VL 97 IS 5 BP 436 EP 444 DI 10.1016/0002-9343(94)90323-9 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA PR028 UT WOS:A1994PR02800006 PM 7977432 ER PT J AU MINKOFF, H MOFENSON, LM AF MINKOFF, H MOFENSON, LM TI THE ROLE OF OBSTETRIC INTERVENTIONS IN THE PREVENTION OF PEDIATRIC HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE PERINATAL HUMAN IMMUNODEFICIENCY VIRUS INFECTION; CESAREAN SECTION; VIRUCIDE ID POLYMERASE CHAIN-REACTION; PERINATAL HIV-INFECTION; GROUP-B STREPTOCOCCI; EARLY DIAGNOSIS; SEROPOSITIVE WOMEN; PREGNANCY OUTCOMES; CHILD TRANSMISSION; CESAREAN-SECTION; IGA ANTIBODIES; INFANTS BORN AB By the end of the decade 10 million children will be infected with human immunodeficiency virus. Several potential means of preventing vertical transmission of human immunodeficiency virus are under study. Although the perinatal use of antiretroviral agents can prevent some of these infections, those agents are neither uniformly effective nor universally available. A significant portion of vertical transmission may be an intrapartum phenomenon, potentially amenable to obstetric interventions, such as cesarean section or vaginal virucides. The utility of these obstetric interventions will be determined in large part by the timing of vertical transmission. This work reviews the evidence that human immunodeficiency virus can be transmitted during the intrapartum period and critically reviews the data supporting a role for obstetric interventions. Finally, we outline the necessary elements for the conduct of a conclusive efficacy trial and delineate a mechanism to arrive at a definitive standard of care in the absence or anticipation of a trial. C1 NICHHD,CTR RES MOTHERS & CHILDREN,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,ROCKVILLE,MD. RP MINKOFF, H (reprint author), SUNY HLTH SCI CTR,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED & OBSTET,450 CLARKSON AVE,BOX 24,BROOKLYN,NY 11203, USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 96 TC 30 Z9 31 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 1994 VL 171 IS 5 BP 1167 EP 1175 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PT265 UT WOS:A1994PT26500001 PM 7977514 ER PT J AU GUADAGNI, F MARTH, C ZEIMET, AG FERRONI, P SPILA, A ABBOLITO, R ROSELLI, M GREINER, JW SCHLOM, J AF GUADAGNI, F MARTH, C ZEIMET, AG FERRONI, P SPILA, A ABBOLITO, R ROSELLI, M GREINER, JW SCHLOM, J TI EVALUATION OF TUMOR-ASSOCIATED GLYCOPROTEIN-72 AND CA-125 SERUM MARKERS IN PATIENTS WITH GYNECOLOGIC DISEASES SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE TUMOR-ASSOCIATED GLYCOPROTEIN-72; CA 125; OVARIAN CANCER ID MONOCLONAL-ANTIBODY B72.3; OVARIAN-CANCER; ANTIGEN LEVELS; CARCINOEMBRYONIC ANTIGEN; CARCINOMA; TAG-72; RADIOIMMUNOASSAY; MANAGEMENT; ASSAY; CA125 AB OBJECTIVE: This study was performed to evaluate the clinical values of tumor-associated glycoprotein-72 serum levels alone or in combination with CA 125 in the diagnosis and monitoring of patients with ovarian cancer. STUDY DESIGN: Serum samples from 293 patients, 142 with primary carcinoma and 151 with benign diseases of the genital tract, were evaluated for the presence of CA 125, tumor-associated glycoprotein-72, and carcinoembryonic antigen. All patients underwent surgery for the primary tumor, and stage was defined according to the classification of International Federation of Gynecology and Obstetrics. RESULTS: When the measurement of serum tumor-associated glycoprotein-72 is combined with that of CA 125, the sensitivity for the detection of primary ovarian cancer increased from 60% to 73%, with no significant change in specificity, and resulted in a more accurate clinical assessment for detection of residual disease before the second-look procedure. in fact, when both markers were positive, 100% specificity was achieved; conversely, when both markers were negative, no residual disease was found. CONCLUSION: These findings suggest that tumor-associated glycoprotein-72 may be considered as a supplementary serum marker for CA 125, providing further clinical information for the diagnosis of primary and recurrent ovarian cancer. C1 UNIV INNSBRUCK, DEPT OBSTET & GYNECOL, A-6020 INNSBRUCK, AUSTRIA. UNIV ROMA LA SAPIENZA, DEPT EXPTL MED, I-00185 ROME, ITALY. UNIV ROMA TOR VERGATA, SCH MED, DEPT SURG, ROME, ITALY. NCI, TUMOR IMMUNOL & BIOL LAB, BETHESDA, MD 20892 USA. RP GUADAGNI, F (reprint author), REGINA ELENA INST CANC RES, CLIN PATHOL LAB, VIALE REGINA ELENA 291, I-00161 ROME, ITALY. RI Guadagni, Fiorella/J-4432-2013; Ferroni, Patrizia/C-2705-2017 OI Guadagni, Fiorella/0000-0003-3652-0457; Ferroni, Patrizia/0000-0002-9877-8712 NR 25 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 1994 VL 171 IS 5 BP 1183 EP 1191 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PT265 UT WOS:A1994PT26500003 PM 7977516 ER PT J AU WARING, PM ROMERO, R LAHAM, N GOMEZ, R RICE, GE AF WARING, PM ROMERO, R LAHAM, N GOMEZ, R RICE, GE TI LEUKEMIA INHIBITORY FACTOR - ASSOCIATION WITH INTRAAMNIOTIC INFECTION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE LEUKEMIA INHIBITORY FACTOR; AMNIOTIC; INFECTION ID TUMOR NECROSIS FACTOR; PREGNANCY-ASSOCIATED INCREASE; AMNIOTIC-FLUID INTERLEUKIN-6; HUMAN DECIDUA; PROSTAGLANDIN PRODUCTION; PRETERM PARTURITION; MOUSE SERUM; LABOR; CELLS; BIOSYNTHESIS AB OBJECTIVE: Our purpose was to investigate whether leukemia inhibitory factor is associated with intraamniotic infection. STUDY DESIGN: A comparative clinical study of amniotic fluid leukemia inhibitory factor concentrations was performed. RESULTS: Leukemia inhibitory factor was undetectable (<1 ng/ml) by radioreceptor assay during normal pregnancy at midtrimester and at term. Among women in labor those with intraamniotic infection had higher leukemia factor concentrations than those without infection before term (p < 0.001) and at term (p < 0.005). The leukemia inhibitory factor concentrations correlated with the amniotic fluid white blood cell counts (r = 0.47) (p < 0.001). In cultured human gestational tissue explants, leukemia inhibitory factor release was significantly enhanced by endotoxin, interleukin-1 alpha, and tumor necrosis factor-alpha however, leukemia inhibitory factor did not enhance the release of prostaglandin E(2) by these tissues. CONCLUSIONS: Amniotic fluid leukemia inhibitory factor concentrations were elevated during intraamniotic infection and gestational tissues released leukemia inhibitory factor in response to bacterial products and inflammatory mediators. C1 ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,CANC RES UNIT,MELBOURNE,VIC,AUSTRALIA. ROYAL WOMENS HOSP,DEPT PERINATAL MED,MELBOURNE,VIC,AUSTRALIA. WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT OBSTET & GYNECOL,DETROIT,MI 48201. NICHHD,PERINATAL BRANCH,BETHESDA,MD 20892. RI RICE, GREGORY/F-2412-2010 OI RICE, GREGORY/0000-0001-7177-0246 NR 28 TC 13 Z9 13 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 1994 VL 171 IS 5 BP 1335 EP 1341 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PT265 UT WOS:A1994PT26500031 PM 7977543 ER PT J AU HESSELING, SC VANBLITTERSWIJK, CA LIM, DJ DEMARIA, TF BAKALETZ, LO GROTE, JJ AF HESSELING, SC VANBLITTERSWIJK, CA LIM, DJ DEMARIA, TF BAKALETZ, LO GROTE, JJ TI EFFECT OF ENDOTOXIN ON CULTURED RAT MIDDLE-EAR EPITHELIUM, RAT MEATAL EPIDERMIS, AND HUMAN KERATINOCYTES SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; TERMINAL DIFFERENTIATION; OTITIS-MEDIA; INVITRO; EFFUSION AB Several factors seem to contribute to the series of events in the pathogenesis of otitis media and cholesteatoma. Endotoxin is likely to be one of these factors, since it has been found in human middle ear effusions and since injection of this substance into the middle ear, in animal experiments, gave rise to prominent reactions. Provoking of epithelial cells in vitro with endotoxin led to distinct cell responses that might be associated with cholesteatoma formation. In this study the effect of endotoxin on serially cultured rat middle ear epithelium, rat meatal epidermis, and human keratinocytes was investigated. Endotoxin strongly stimulated the proliferation of middle ear epithelium and human keratinocytes and inhibited that of meatal epidermis. Furthermore, endotoxin affected the morphology of the three types of tissue. Rat middle ear epithelium revealed epithelial cell tracks with interconnecting bridge-like structures protruding above the culture plane, whereas rat meatal epidermis showed increased terminal differentiation expressing large areas of blister-like structures detaching from the culture dish. Cross-linked envelope analysis of human keratinocytes showed an increased terminal differentiation that was morphologically confirmed but was not confirmed by cytokeratin analysis. The results of this study support the hypothesis that endotoxin may play an important role in the pathogenesis of otitis media and cholesteatoma. C1 OHIO STATE UNIV,DEPT OTOLARYNGOL,OTOL RES LABS,COLUMBUS,OH. NIDCD,BETHESDA,MD. RP HESSELING, SC (reprint author), LEIDEN UNIV HOSP,DEPT EAR NOSE & THROAT,OTOBIOL & BIOCOMPATIBIL LAB,RIJNSBURGERWEG 10,2333 AA LEIDEN,NETHERLANDS. OI van Blitterswijk, Clemens/0000-0003-2371-4615 NR 25 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD NOV PY 1994 VL 15 IS 6 BP 762 EP 768 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA PQ076 UT WOS:A1994PQ07600012 PM 8572089 ER PT J AU SCOPA, CD MASTORAKOS, G FRIEDMAN, TC MELACHRINOU, M MERINO, MJ CHROUSOS, GP AF SCOPA, CD MASTORAKOS, G FRIEDMAN, TC MELACHRINOU, M MERINO, MJ CHROUSOS, GP TI PRESENCE OF IMMUNOREACTIVE CORTICOTROPIN-RELEASING HORMONE IN THYROID LESIONS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SYMPATHETIC NERVOUS-SYSTEM; RAT LEYDIG-CELLS; FACTOR RECEPTORS; HUMAN-PLACENTA; IMMUNOCYTOCHEMICAL LOCALIZATION; BETA-ENDORPHIN; FACTOR CRF; SECRETION; ESTROGEN; TESTIS AB Corticotropin-releasing hormone (CRH) functions as a regulator of the hypothalamic-pituitary-adrenal axis and coordinator of the stress response. Immunoreactive CRH (IrCRH) is also produced in a variety of inflammatory sites, where this peptide acts as a proinflammatory cytokine. To detect CRH in autoimmune thyroid disease as well as in disorders that may be associated with an inflammatory reaction within this gland, we examined immunohistochemically 45 thyroid lesions, including 12 nodular goiters, 9 cases of Hashimoto thyroiditis, 6 follicular adenomas, 4 follicular and 8 papillary carcinomas, 4 Hurthle cell tumors, 1 medullary cancer, and 1 insular thyroid carcinoma. We also examined the presence of IrCRH in the adjacent normal thyroid parenchyma. The avidin-biotin complex method was employed on formalin-fixed, paraffin-embedded tissue, using a highly specific, affinity-purified polyclonal rabbit anti-CRH antibody. Granular cytoplasmic immunostaining of follicular cells tons observed in 100% of the cases of Hashimoto thyroiditis, 77% of the neoplasms and 42% of goiters. The intensity of the staining was more pronounced in Hashimoto thyroiditis and Hurthle cell tumors, whereas the remaining lesions exhibited a heterogeneous staining pattern. No IrCRH was observed in the normal thyroid parenchyma. Using a specific radioimmunoassay, the IrCRH in extracts of simple thyroid goiters, papillary carcinomas, and Hurthle cell tumors ranged between 0.031 and 0.224 pmol/g of wet tissue but was undetectable in normal thyroid parenchyma. The IrCRH molecule in the thyroid gland elated at the same fraction as synthetic rat/human CRH 1-41 in reverse phase high pressure liquid chromatography. We conclude that IrCRH is present in thyroid lesions, predominantly in those related to autoimmune phenomena, suggesting that this neuropeptide may be directly and/or indirectly involved with inflammatory processes taking place in this gland. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. UNIV PATRAS,SCH MED,DEPT PATHOL,GR-26110 PATRAI,GREECE. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 55 TC 49 Z9 50 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1994 VL 145 IS 5 BP 1159 EP 1167 PG 9 WC Pathology SC Pathology GA PQ086 UT WOS:A1994PQ08600020 PM 7977646 ER PT J AU SHERER, DM AF SHERER, DM TI BLUNTED FETAL RESPONSE TO VIBROACOUSTIC STIMULATION ASSOCIATED WITH MATERNAL INTRAVENOUS MAGNESIUM-SULFATE THERAPY SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE MAGNESIUM SULFATE; VIBROACOUSTIC STIMULATION; FETAL HEART RATE AB Maternal intravenous magnesium sulfate (MgSO4) therapy has been associated with decreased fetal heart rate (FHR) variability and reactivity, resulting in an increased incidence of nonreactive nonstress tests, frequently requiring further assessment of fetal well-being. This study was designed to assess fetal response to vibroacoustic stimulation in association with maternal intravenous MgSO4 therapy. Five gravidas with singleton gestations with normal fetal anatomy, intact membranes, and normal amniotic fluid volume at 31 weeks or more presenting with preterm labor were included. Vibroacoustic stimulation was performed prior to and during subsequent intravenous MgSO4 therapy so that each fetus served as its own control. Ultrasound was applied during vibroacoustic stimulation to assess fetal movement response. Response to vibroacoustic stimulation was considered normal if a FHR acceleration of at least 15 beats/min for at least 15 seconds occurred within 15 seconds after the stimulation with prolonged fetal movements. Maternal serum magnesium levels were obtained prior to each stimulation. All fetal responses prior to treatment were normal. All subsequent fetal responses in association with intravenous MgSO4 were abnormal, consisting of blunted FHR accelerations of 10 to 15 beats/min and ranging between 10 and 15 seconds in duration associated with brief limited fetal movements. Mean maternal serum magnesium levels(+/- standard error) during vibroacoustic stimulation, prior to and following intravenous MgSO4, were 1.4 +/- 0.1 and 5.2 +/- 0.4 mEq/L, respectively (P = 0.008). All 5-minute Apgar scores were 8 or higher. This occurrence may reflect an effect of magnesium on the fetus as either a central nervous system depressant or alternatively as a peripheral neuromuscular relaxant. These results indicate that caution should be exercised in interpreting fetal response to vibroacoustic stimulation in the presence of therapeutic maternal serum magnesium levels. RP SHERER, DM (reprint author), GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,NICHD,DIV INTRAMURAL,PERINATOL RES BRANCH,3PHC,WASHINGTON,DC 20007, USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD NOV PY 1994 VL 11 IS 6 BP 401 EP 403 DI 10.1055/s-2007-994605 PG 3 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA PV565 UT WOS:A1994PV56500005 PM 7857429 ER PT J AU NISHIKAWA, S MOORE, RC NONOMURA, N OKA, T AF NISHIKAWA, S MOORE, RC NONOMURA, N OKA, T TI PROGESTERONE AND EGF INHIBIT MOUSE MAMMARY-GLAND PROLACTIN RECEPTOR AND BETA-CASEIN GENE-EXPRESSION SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE LONG FORM OF PROLACTIN RECEPTOR; MESSENGER RIBONUCLEIC ACID ID EPIDERMAL GROWTH-FACTOR; STIMULATES CELL-PROLIFERATION; POLYMERASE CHAIN-REACTION; EPITHELIAL-CELLS; SUBMANDIBULAR-GLAND; HORMONAL INDUCTION; PROTEIN-SYNTHESIS; FEMALE MICE; DIFFERENTIATION; TRANSCRIPTION AB Regulation of mouse mammary gland long-form prolactin receptor (PRL-RL) mRNA levels by progesterone and epidermal growth factor (EGF) and the relationship between PRL-RL and beta-casein gene expression were examined in vivo and in vitro. PRL-RL and beta-casein mRNA levels increased approximately 6- and 15-fold from the pregnant to the lactating period, respectively, when normalized to the level of p-actin mRNA. Ovariectomy of pregnant mice rapidly reduced the serum concentration of progesterone and increased the level of PRL-RL and beta-casein mRNAs approximately three- and fourfold compared with sham-operated animals 24 h after the operation. Injection of progesterone, but not estrogen, inhibited the increase in both mRNA levels. PRL-RL and p-casein mRNA levels in cultured mammary epithelium increased in response to insulin, hydrocortisone, and prolactin, whereas progesterone or EGF caused inhibition. The combination of EGF and progesterone produced a greater inhibition than either hormone alone. These results indicate that both progesterone and EGF serve as negative regulators of lactogenesis. C1 NIDDK, LMCB, BETHESDA, MD 20892 USA. NR 35 TC 32 Z9 32 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 1994 VL 267 IS 5 BP C1467 EP C1472 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA PW518 UT WOS:A1994PW51800035 ER PT J AU FONTVIEILLE, AM RISING, R SPRAUL, M LARSON, DE RAVUSSIN, E AF FONTVIEILLE, AM RISING, R SPRAUL, M LARSON, DE RAVUSSIN, E TI RELATIONSHIP BETWEEN SLEEP STAGES AND METABOLIC-RATE IN HUMANS SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE INDIRECT CALORIMETRY; BODY COMPOSITION; ELECTROENCEPHALOGRAM; OBESITY ID ENERGY-EXPENDITURE; THERMOREGULATION; HEAT; COLD; MEN AB Differences in sleeping metabolic rate (SMR) among subjects may be related to-different levels of energy expenditure associated with sleep stages. The relationship between energy expenditure and sleep stages was investigated overnight in 29 subjects (14 Caucasians and 15 Pima Indians, 18 males and 11 females; mean +/- SD, 31 +/- 7 yr, 83 +/- 26 kg, 27 +/- 11% fat). Sleep stages were determined by electroencephalogram recording, whereas energy expenditure was measured in a 1,000-liter Plexiglas sleep box constructed around a bed as a fast-response open-circuit indirect calorimeter. Eighty-five percent of the interindividual variability in SMR was explained by differences in fat-free mass, fat mass, age, sex, and race (r(2) = 0.85). The intra-individual variance in SMR over time was related to sleep stages and to clock time. Within subjects, SMR in stage 3 was significantly lower than in stage 2 (-39 +/- 18 kcal/day; P < 0.05) and rapid eye movement sleep (-51 +/- 23 kcal/day; P < 0.05). Also, sleep stages were associated with different respiratory quotients. Because sleep stages are associated with only small differences in energy metabolism, our results suggest that sleep stages play a minor role in the variance of SMR among subjects. However, the duration of sleep may contribute to the variability of 24-h energy expenditure. C1 NIDDKD, CLIN DIABET & NUTR SECT, PHOENIX, AZ 85016 USA. NR 28 TC 41 Z9 41 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 1994 VL 267 IS 5 BP E732 EP E737 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PW563 UT WOS:A1994PW56300014 PM 7977724 ER PT J AU KHALIL, N OCONNOR, RN FLANDERS, KC SHING, W WHITMAN, CI AF KHALIL, N OCONNOR, RN FLANDERS, KC SHING, W WHITMAN, CI TI REGULATION OF TYPE-II ALVEOLAR EPITHELIAL-CELL PROLIFERATION BY TGF-BETA DURING BLEOMYCIN-INDUCED LUNG INJURY IN RATS SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE TRANSFORMING GROWTH FACTOR-BETA-1, 2, AND 3; DNA SYNTHESIS; LUNG INFLAMMATION; LUNG REPAIR ID GROWTH-FACTOR-BETA; INDUCED PULMONARY FIBROSIS; EXTRACELLULAR-MATRIX; PARTIAL PNEUMONECTOMY; FACTOR-BETA-1; INHIBITION; EXPRESSION; COLLAGEN; INVITRO; DIFFERENTIATION AB Three isoforms of transforming growth factor-beta (TGF-beta) are found in mammalian cells and are potent regulators of inflammation, connective tissue synthesis, cellular proliferation, and differentiation. To determine the distribution and regulation of TGF-beta isoforms during pulmonary injury, a rat model of bleomycin induced lung inflammation and repair was used. Using immunohistochemistry, we demonstrate that TGF-beta 2 and TGF-beta 3 were localized to alveolar macrophages as well as epithelial and smooth muscle cells of both normal rat lungs and rat lungs obtained at all time intervals after bleomycin administration. Early in bleomycin-induced lung injury, when there is active proliferation of type II alveolar epithelial cells, there was an increase in the number of type II alveolar epithelial cells isolated per lung and an increase in DNA synthesis by explanted type II alveolar epithelial cells. At this time, the secretion of biologically active TGF-beta 1-3, which are potent inhibitors of epithelial cell proliferation, was decreased. However, the secretion of TGF-beta 1-3 activity was markedly increased later in the injury response and coincided with a reduction in the number of type II alveolar epithelial cells isolated per lung and DNA synthesis in vitro. Furthermore, the addition of TGF-beta 1, 2, and 3 to cultures of actively proliferating type II alveolar epithelial cells resulted in inhibition of [H-3]thymidine incorporation, whereas, in the presence of anti-TGF-beta 1-3 antibody, there was an increase in [H-3]thymidine incorporation. Our findings suggest that altered secretion of TGF-beta 1-3 activity by type II alveolar epithelial cells during bleomycin-induced lung injury may regulate pulmonary alveolar epithelial cell proliferation during injury and repair phases. C1 UNIV MANITOBA, DEPT MED, WINNIPEG, MB R3E 0V9, CANADA. UNIV MANITOBA, DEPT PATHOL, WINNIPEG, MB R3E 0V9, CANADA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. RP KHALIL, N (reprint author), UNIV MANITOBA, MANITOBA INST CELL BIOL, 100 OLIVIA ST, WINNIPEG, MB R3E 0V9, CANADA. NR 38 TC 47 Z9 49 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD NOV PY 1994 VL 267 IS 5 BP L498 EP L507 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA PW556 UT WOS:A1994PW55600002 PM 7526703 ER PT J AU MORRISON, JA PAYNE, G BARTON, BA KHOURY, PR CRAWFORD, P AF MORRISON, JA PAYNE, G BARTON, BA KHOURY, PR CRAWFORD, P TI MOTHER-DAUGHTER CORRELATIONS OF OBESITY AND CARDIOVASCULAR-DISEASE RISK-FACTORS IN BLACK-AND-WHITE HOUSEHOLDS - THE NHLBI GROWTH AND HEALTH STUDY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID DENSITY LIPOPROTEIN CHOLESTEROL; SCHOOL-DISTRICT-FAMILY; BODY-MASS; ASSOCIATIONS; TRIGLYCERIDE; ENVIRONMENTS; CHILDHOOD; CHILDREN; MEMBERS; FATNESS AB Objectives. This study sought to evaluate obesity as a potential explanatory factor for the increased relative risk for cardiovascular disease ease in Black compared with White women. Methods. Familial associations for obesity and cardiovascular disease risk factors were assessed in 720 White and 580 Black mother-daughter pairs from the National, Heart, Lung, and Blood Institute's Growth and Health Study by using Pearson's chi square, Spearman's correlations, and partial correlations. Results. Black girls and mothers were significantly heavier and had higher body mass indices than their White counterparts. Tn each racial group, significant, positive mother-daughter correlations existed for weight, body mass index, and triceps skinfolds, and for all cardiovascular disease risk factors. Obesity measures correlated positively with systolic blood pressure and triglycerides, and inversely,with high-density lipoprotein cholesterol in girls and mothers of both races. Correlations between mothers and daughters for exercise and ideal body shape were weak and did not explain obesity associations. Conclusions. Intrafamilial associations of obesity, cardiovascular disease risk factors, and the obesity-cardiovascular disease risk factor relationship support the position that increased cardiovascular disease morbidity and mortality rates in Black women may be linked to excess obesity in Black women compared with White ones. C1 MARYLAND MED RES INST,BALTIMORE,MD 21210. CHILDRENS HOSP,MED CTR,DIV CARDIOL,CINCINNATI,OH 45229. UNIV CINCINNATI,COLL MED,DEPT PEDIAT,CINCINNATI,OH. NHLBI,BETHESDA,MD 20892. UNIV CALIF BERKELEY,DEPT PUBL HLTH,BERKELEY,CA 94720. OI Barton, Bruce/0000-0001-7878-8895 FU NHLBI NIH HHS [HC 55023-25] NR 41 TC 35 Z9 35 U1 1 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 1994 VL 84 IS 11 BP 1761 EP 1767 DI 10.2105/AJPH.84.11.1761 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PR448 UT WOS:A1994PR44800011 PM 7977914 ER PT J AU WAGNERECHEAGARAY, FA SCHUTZ, CG CHILCOAT, HD ANTHONY, JC AF WAGNERECHEAGARAY, FA SCHUTZ, CG CHILCOAT, HD ANTHONY, JC TI DEGREE OF ACCULTURATION AND THE RISK OF CRACK COCAINE SMOKING AMONG HISPANIC-AMERICANS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID DRUG-USE; PUERTO-RICAN AB Epidemiologic data from three national surveys conducted in 1988, 1990, and 1991 were used to investigate the association between acculturation and use of crack cocaine among Hispanic Americans living in the United States. Poststratification and conditional logistic regression were used to hold constant shared aspects of neighborhood environment age, sex, and education. The analyses showed a strong inverse relationship between degree of acculturation and crack smoking among Mexican Americans (relative odds = 0.12, 95% confidence interval = 0.04, 0.34) but not among other Hispanics in the study population. This observed variation within the US Hispanic American population deserves special attention in future research. C1 NIDA,ADDICT RES CTR,ETIOL BRANCH,BALTIMORE,MD 21224. CTR INTEGRAC JUVENIL,MEXICO CITY,DF,MEXICO. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MENTAL HYG,BALTIMORE,MD. NR 20 TC 31 Z9 32 U1 7 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 1994 VL 84 IS 11 BP 1825 EP 1827 DI 10.2105/AJPH.84.11.1825 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PR448 UT WOS:A1994PR44800023 PM 7977926 ER PT J AU GERWIN, BI AF GERWIN, BI TI ASBESTOS AND THE MESOTHELIAL CELL - A MOLECULAR TRAIL TO MITOGENIC STIMULI AND SUPPRESSOR GENE SUSPECTS SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Editorial Material ID HUMAN-MALIGNANT MESOTHELIOMA; WILMS-TUMOR; GROWTH-FACTOR; WT1; LINES; EXPRESSION; RECRUITMENT; INDUCTION; BINDING; FIBERS RP GERWIN, BI (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C15,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 33 TC 14 Z9 14 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD NOV PY 1994 VL 11 IS 5 BP 507 EP 508 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA PT264 UT WOS:A1994PT26400001 PM 7946379 ER PT J AU CORSINI, E LUSTER, MI MAHLER, J CRAIG, WA BLAZKA, ME ROSENTHAL, GJ AF CORSINI, E LUSTER, MI MAHLER, J CRAIG, WA BLAZKA, ME ROSENTHAL, GJ TI A PROTECTIVE ROLE FOR T-LYMPHOCYTES IN ASBESTOS-INDUCED PULMONARY INFLAMMATION AND COLLAGEN DEPOSITION SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID BRONCHOALVEOLAR LAVAGE; FIBRONECTIN; RELEASE; MACROPHAGES; EXPOSURE; FIBROSIS; CELLS; LUNG; METABOLITES; EXPRESSION AB Several lines of evidence have suggested that specific (i.e., lymphocyte) immunity plays a role in chemical-induced pulmonary diseases, including asbestosis. To evaluate the influence of cell-mediated immunity in pulmonary inflammation and fibrosis evoked by asbestos fibers, we compared the effects of asbestos in immunodeficient mice (Balb/c nu/nu and severe combined immunodeficient [C3H-SCID]), immunologically normal mice of the same genetic background, and immunodeficient mice reconstituted with syngeneic T lymphocytes. Increases in lavaged cell numbers occurred in asbestos-treated immunodeficient mice compared with asbestos-treated immunocompetent or immunodeficient mice that received T lymphocytes. Differential analysis of the collected cells in treated mice demonstrated a predominantly neutrophilic infiltrate that correlated with increased levels of leukotriene B-4 and prostaglandin E(2). There were no significant differences between immunocompetent and athymic asbestos-treated mice in bronchoalveolar lavaged total protein. However, asbestos-treated SCID mice revealed a significant increase in protein content and lactate dehydrogenase activity compared with asbestos-treated normal mice, which did not occur in T lymphocyte-reconstituted SCID mice. Fibronectin levels were elevated in asbestos-exposed athymic mice when compared with air-exposed athymic mice or asbestos-exposed immunocompetent mice. Both asbestos-treated athymic and SCID mice showed a significant increase in total lung hydroxyproline when compared with asbestos-treated immunocompetent mice. Lung hydroxyproline was also reduced in asbestos-exposed SCID mice after T lymphocyte reconstitution and, conversely, increased in T cell-depleted Balb/c mice. Microscopically, asbestos exposure was associated with both cellular and fibrogenic inflammatory responses with asbestos-exposed SCID mice, revealing a more severe cellular response than similarly exposed normal mice. Using polymerase chain reaction analysis to detect relatively rare mRNA species, the lungs from control and asbestos-treated animals appeared to have similar levels of mRNA transcripts for interferon-gamma, a T cell cytokine with putative antifibrotic activity. Taken together, these data indicate that T cells influence asbestos-induced lung damage by minimizing both the inflammatory and fibrotic responses and are consistent with a protective role for T lymphocytes in asbestosis. C1 NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,LBRA,RES TRIANGLE PK,NC 27709. INST PHARMACOL SCI,MILAN,ITALY. NIEHS,EXPTL PATHOL LAB,RES TRIANGLE PK,NC. RI Corsini, Emanuela/B-5602-2011 NR 43 TC 31 Z9 31 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD NOV PY 1994 VL 11 IS 5 BP 531 EP 539 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA PT264 UT WOS:A1994PT26400005 PM 7946383 ER PT J AU MASON, RJ LESLIE, CC MCCORMICKSHANNON, K DETERDING, RR NAKAMURA, T RUBIN, JS SHANNON, JM AF MASON, RJ LESLIE, CC MCCORMICKSHANNON, K DETERDING, RR NAKAMURA, T RUBIN, JS SHANNON, JM TI HEPATOCYTE GROWTH-FACTOR IS A GROWTH-FACTOR FOR RAT ALVEOLAR TYPE-II CELLS SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID STIMULATE DNA-SYNTHESIS; FACTOR HEPATOPOIETIN-A; FACTOR SCATTER FACTOR; FACTOR MESSENGER-RNA; EPITHELIAL-CELLS; FACTOR RECEPTOR; TISSUE DISTRIBUTION; PARTIAL-HEPATECTOMY; CONDITIONED MEDIUM; MOLECULAR-CLONING AB Proliferation of alveolar type II cells is thought to be critical for restoration of gas exchange units after diffuse alveolar damage. However, the factors that regulate type II cell proliferation are not well understood. Hepatocyte growth factor (HGF) is a potentially important mitogen because it causes epithelial cells but not fibroblasts to proliferate and is found in the lung. We used rat alveolar type II cells in primary culture to demonstrate that HGF stimulates DNA synthesis in a concentration-dependent manner. The half maximal effect on stimulation of thymidine incorporation was less than 1 ng/ml. By autoradiography, HGF increased nuclear labeling from 1.3% of type II cells with medium alone to 9.4% with 5 ng/ml HGF. During this time, HGF modestly increased cell number in comparison to control media. However, in an assay of colony formation in low-density cultures, HGF did not consistently increase colony formation by alveolar type II cells and was less effective than acidic fibroblast growth factor or bronchoalveolar lavage fluid in this assay. The receptor for HGF (c-met proto-oncogene) was expressed in rat type II cells and whole lung but not in macrophages. In contrast, the mRNA for HGF was detected in rat macrophages and lung but not in type II cells. However, HGF message was not detected in human alveolar macrophages under conditions in which the HGF message was detected in rat alveolar macrophages and in human fibroblasts. Hence, HGF is a potential paracrine growth factor for alveolar type II cells, but there may be important species differences in the relative level of expression. C1 NATL JEWISH CTR IMMUNOL & RESP MED,DEPT PEDIAT,DENVER,CO 80206. UNIV COLORADO,HLTH SCI CTR,DEPT PATHOL,DENVER,CO. UNIV COLORADO,HLTH SCI CTR,DEPT MED,DENVER,CO. OSAKA UNIV,SCH MED,BIOMED RES CTR,DEPT ONCOL,OSAKA,JAPAN. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP MASON, RJ (reprint author), NATL JEWISH CTR IMMUNOL & RESP MED,DEPT MED,1400 JACKSON ST,DENVER,CO 80206, USA. FU NHLBI NIH HHS [HL-27353, HL-29891] NR 51 TC 105 Z9 105 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD NOV PY 1994 VL 11 IS 5 BP 561 EP 567 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA PT264 UT WOS:A1994PT26400008 PM 7524567 ER PT J AU HOLLINGSWORTH, HC STETLERSTEVENSON, M GAGNETEN, D KINGMA, DW RAFFELD, M JAFFE, ES AF HOLLINGSWORTH, HC STETLERSTEVENSON, M GAGNETEN, D KINGMA, DW RAFFELD, M JAFFE, ES TI IMMUNODEFICIENCY-ASSOCIATED MALIGNANT-LYMPHOMA - 3 CASES SHOWING GENOTYPIC EVIDENCE OF BOTH T-CELL AND B-CELL LINEAGES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE MALIGNANT LYMPHOMA; IMMUNODEFICIENCY; IMMUNOPHENOTYPE; EPSTEIN-BARR VIRUS; GENOTYPE ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EPSTEIN-BARR-VIRUS; RECEPTOR GENE REARRANGEMENTS; CHRONIC LYMPHOCYTIC-LEUKEMIA; ANGIOIMMUNOBLASTIC LYMPHADENOPATHY; ANTIGEN RECEPTOR; BETA-CHAIN; LYMPHOPROLIFERATIVE DISORDERS; IMMUNOGLOBULIN GENES; MOLECULAR-GENETICS AB Dual rearrangement of both immunoglobulin and T-cell receptor (TCR) genes has been described in up to 30% of precursor lymphoid neoplasms, but this phenomenon occurs rarely in lymphomas with a mature phenotype. We describe three cases of immunodeficiency-associated lymphomas, two in patients with acquired immunodeficiency syndrome (AIDS) and one in a patient with a renal transplant, in which both immunoglobulin and TCR gene rearrangements were identified. Two cases exhibited clonal J(H), clonal J(K), and clonal TCR beta gene rearrangements; the other case had clonal J(K) and TCR beta gene rearrangements with deletion of J(H). Two of these bigenotypic lesions exhibited a B-cell phenotype, and the other exhibited evidence of both a B- and T-cell phenotype, containing cytoplasmic CD3 as well as monoclonal kappa light chain. In addition, two of the cases exhibited the presence of clonal Epstein-Barr viral DNA. These observations suggest that lymphomas arising in immunodeficiency states may be more prone to disordered differentiation than those arising in an intact immune system. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 40 TC 43 Z9 44 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 NOV PY 1994 VL 18 IS 11 BP 1092 EP 1101 DI 10.1097/00000478-199411000-00003 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA PN368 UT WOS:A1994PN36800002 PM 7943530 ER PT J AU JAFFE, ES KUMAR, S AF JAFFE, ES KUMAR, S TI EBV T-CELL LYMPHOMA - REPLY SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter RP JAFFE, ES (reprint author), NCI,PATHOL LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 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 NOV PY 1994 VL 18 IS 11 BP 1181 EP 1181 DI 10.1097/00000478-199411000-00018 PG 1 WC Pathology; Surgery SC Pathology; Surgery GA PN368 UT WOS:A1994PN36800017 ER PT J AU ALEXANDER, KA MACLACHLAN, NJ KAT, PW HOUSE, C OBRIEN, SJ LERCHE, NW SAWYER, M FRANK, LG HOLEKAMP, K SMALE, L MCNUTT, JW LAURENSON, MK MILLS, MGL OSBURN, BI AF ALEXANDER, KA MACLACHLAN, NJ KAT, PW HOUSE, C OBRIEN, SJ LERCHE, NW SAWYER, M FRANK, LG HOLEKAMP, K SMALE, L MCNUTT, JW LAURENSON, MK MILLS, MGL OSBURN, BI TI EVIDENCE OF NATURAL BLUETONGUE VIRUS-INFECTION AMONG AFRICAN CARNIVORES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ANTIBODIES; KENYA AB Bluetongue is an International Office of Epizootics List A disease described as the century's most economically devastating affliction of sheep. Bluetongue (BLU) viruses were thought to infect only ruminants, shrews, and some rodents, but recently, inadvertent administration of BLU virus-contaminated vaccine resulted in mortality and abortion among domestic dogs. We present evidence of natural BLU virus infection among African carnivores that dramatically widens the spectrum of susceptible hosts. We hypothesize that such infection occurred after ingestion of meat and organs from BLU virus-infected prey species. The effect of BLU virus on endangered carnivores such as the cheetah and African wild dog requires urgent investigation. Also, the role of carnivores in the epizootiology of this disease needs elucidation. C1 USDA,FOREIGN ANIM DIS DIAGNOST LAB,GREENPORT,NY 11944. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV CALIF DAVIS,CALIF REG PRIMATE RES CTR,DAVIS,CA 95616. UNIV CALIF BERKELEY,DEPT PSYCHOL,BERKELEY,CA 94720. MICHIGAN STATE UNIV,DEPT PSYCHOL,E LANSING,MI 48824. UNIV CALIF DAVIS,DIV ENVIRONM STUDIES,DAVIS,CA 95616. GAME CONSERVANCY,UPLAND RES GRP,NEWTONMORE PH20 1BE,INVERNESS,SCOTLAND. NATL PK BOARD,KRUGER NATL PK,TRANSVAAL 1350,SOUTH AFRICA. RP ALEXANDER, KA (reprint author), UNIV CALIF DAVIS,SCH VET MED,DEPT VET PATHOL MICROBIOL & IMMUNOL,DAVIS,CA 95616, USA. RI Alexander, Kathleen/A-9765-2010 OI Alexander, Kathleen/0000-0001-7338-5341 NR 42 TC 52 Z9 52 U1 0 U2 9 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 NOV PY 1994 VL 51 IS 5 BP 568 EP 576 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA PW466 UT WOS:A1994PW46600008 PM 7985748 ER PT J AU ASHWELL, G BERLIN, WK GABRIEL, O AF ASHWELL, G BERLIN, WK GABRIEL, O TI ALPHA-2-8 SIALIC-ACID POLYMERS - SIZE, STRUCTURE, AND COMPOSITIONAL ANALYSIS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID POLYSIALIC ACID; GLYCOPROTEINS; BIOSYNTHESIS AB A series of three variable assay procedures is described to provide overlapping information on the size, structure, and composition of the alpha 2-8 linked polysialic acid chains present on a wide variety of critical cell surface glycoproteins. Technical advances in instrumentation have permitted the development of new applications for a methodology involving the sequential use of periodate and borohydride to modify terminal sialic acid residues. The procedures described here provide a rapid and facile assay for (a) the determination of polysialic acid chain length, (b) the simultaneous identification of N-acetylneuraminic acid, N-glycolylneuraminic acid, and KDN (deaminated sialic acid) when present in a single preparation, (c) the ability to distinguish qualitatively between reducing and nonreducing polymers, and (d) the ability to determine the number of chains bound to a glycoprotein of known molecular weight. (C) 1994 Academic Press, Inc. RP ASHWELL, G (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 14 TC 12 Z9 12 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 NOV 1 PY 1994 VL 222 IS 2 BP 495 EP 502 DI 10.1006/abio.1994.1523 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PN665 UT WOS:A1994PN66500029 PM 7864379 ER PT J AU CROSBY, G MAROTA, JJA GOTO, T UHL, GR AF CROSBY, G MAROTA, JJA GOTO, T UHL, GR TI SUBARACHNOID MORPHINE REDUCES STIMULATION-INDUCED BUT NOT BASAL EXPRESSION OF PREPROENKEPHALIN IN RAT SPINAL-CORD SO ANESTHESIOLOGY LA English DT Article DE ANALGESIA; ANALGESICS, OPIOID, MORPHINE; ANESTHETICS, INTRATHECAL, MORPHINE; CELLS, METABOLISM; METABOLISM, DNA, RNA; PAIN, EXPERIMENTAL; POLYPEPTIDES, ENKEPHALINS; SPINAL CORD, MORPHINE ID NUCLEUS CAUDALIS NEURONS; DORSAL HORN NEURONS; GENE-EXPRESSION; C-FOS; MESSENGER-RNA; AFFERENT-FIBERS; NERVOUS-SYSTEM; SUBSTANCE-P; PROENKEPHALIN; INFLAMMATION AB Background: To evaluate directly the possibility that the potent exogenous opioid analgesic morphine may alter neuronal expression of opioid peptide genes, we assessed the effect of subarachnoid morphine on basal and noxious stimulation-induced expression of preproenkephalin in spinal cord neurons. Methods: Twenty male Sprague-Dawley rats were prepared 48 h in advance with lumbar subarachnoid catheters. In the first phase, basal expression was evaluated in rats that received morphine 10 mu g or saline intrathecally (n = 5 per group). Subsequently, the experiment was repeated (n = 5 per group), except that 10 min after morphine or saline administration rats received a hindpaw footpad injection of 50 mu l 5% formalin. Rats were killed during pentobarbital anesthesia 2 h later, and messenger RNA transcribed from preproenkephalin was measured in lumbar spinal cord with quantitative in situ hybridization with a complementary sulfur 35-labeled oligonucleotide probe and emulsion autoradiography. Results: In control (nonstimulated) rats, 20% of the neurons in laminae I-II and 10% of those in laminae III-IV expressed preproenkephalin. Injection of formalin increased the fraction of positive neurons by 34% (P < 0.05) and 20% (P < 0.05) in laminae I-II and V-VI, respectively, but had no effect on expression in laminae III-IV. Subarachnoid morphine did not alter basal expression of preproenkephalin but markedly attenuated the noxious stimulation-induced increase in laminae I-II (P < 0.01) and V-VI (P < 0.05) by preventing the stimulation-evoked recruitment of preproenkephalin-expressing neurons that otherwise would have occurred. Conclusions: Subarachnoid morphine does not acutely alter basal expression of preproenkephalin in spinal cord neurons but inhibits the increase in preproenkephalin expression that would otherwise occur after noxious stimulation. C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. NIDA,ADDICT RES CTR,MOLEC NEUROBIOL LAB,LEXINGTON,KY. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21218. RP CROSBY, G (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [R01-GM42466] NR 39 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 1994 VL 81 IS 5 BP 1270 EP 1276 DI 10.1097/00000542-199411000-00022 PG 7 WC Anesthesiology SC Anesthesiology GA PP715 UT WOS:A1994PP71500025 PM 7978486 ER PT J AU GOLDSTEIN, RA PAUL, WE METCALFE, DD BUSSE, WW REECE, ER AF GOLDSTEIN, RA PAUL, WE METCALFE, DD BUSSE, WW REECE, ER TI ASTHMA SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID COLONY-STIMULATING FACTOR; HUMAN MAST-CELLS; CD4+ T-CELLS; HUMAN EOSINOPHILS; MUCOSAL INFLAMMATION; MONOCLONAL-ANTIBODY; AIRWAY INFLAMMATION; CHANGING PATTERNS; INTERFERON-GAMMA; PROGENITOR CELLS AB Asthma is characterized by inflammation, reversible airway obstruction, and increased airway responsiveness to various stimuli. It has received wide public attention in recent years because of increasing morbidity and deaths,(-1) particularly among black persons. The important role of inflammation in the immunopathogenesis of asthma has led to a newer therapeutic approach directed at interrupting this inflammatory process. Among immune regulatory pathways involved in asthma pathogenesis, two lymphokines appear to be particularly important in controlling IgE production. Interleukin-4 is required for IgE production; without it, IgE production is inhibited. interferon-gamma can diminish cell priming for interleukin-4 production. Thus, the interplay of these two cytokines will determine whether cells that can make interleukin-4 will be produced and, therefore, whether IgE will be produced in response to allergic stimuli. Further, in response to appropriate stimuli, mast cells and eosinophils are attracted to airways and release cytokines, lipid mediators, and preformed substances that cause inflammation. Modern asthma treatment is directed at interrupting this inflammatory process and places a much greater emphasis on use of anti-inflammatory agents, such as aerosolized or parenteral corticosteroids, and on nonsteroidal anti-inflammatory agents, such as cromolyn sodium and nedocromil sodium. Research advances without therapeutic application, however, limit success. Projects such as the National Institute of Allergy and Infectious Diseases' National Cooperative Inner-City Asthma Study, which is directed toward underserved populations, are intended to identify more clearly the factors responsible for increasing morbidity and to develop appropriate therapeutic interventions. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. UNIV WISCONSIN,MADISON,WI. HOWARD UNIV,COLL MED,MED CTR,ALLERGY & IMMUNOL SECT,WASHINGTON,DC 20059. RP GOLDSTEIN, RA (reprint author), NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,SOLAR BLDG,ROOM 4A18,BETHESDA,MD 20892, USA. NR 76 TC 52 Z9 53 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 NOV 1 PY 1994 VL 121 IS 9 BP 698 EP 708 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA PN450 UT WOS:A1994PN45000011 PM 7944080 ER PT J AU DHIBJALBUT, S HOFFMAN, PM YAMABE, T SUN, D XIA, J EISENBERG, H BERGEY, G RUSCETTI, FW AF DHIBJALBUT, S HOFFMAN, PM YAMABE, T SUN, D XIA, J EISENBERG, H BERGEY, G RUSCETTI, FW TI EXTRACELLULAR HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I TAX PROTEIN INDUCES CYTOKINE PRODUCTION IN ADULT HUMAN MICROGLIAL CELLS SO ANNALS OF NEUROLOGY LA English DT Note ID TROPICAL SPASTIC PARAPARESIS; INFECTION; MYELOPATHY AB Tropical spastic paraparesis (HAM/TSP) is caused by human T-cell lymphotropic virus type I (HTLV-I) infection. Although the virus infects T cells in vivo and is capable of infecting microglia in vitro, the inflammatory demyelination has not been linked to virus in central nervous system tissue. Thus, indirect mechanisms (e.g., cytokines) could be involved in demyelination and inflammation. The ability of HTLV-I Tax protein to induce tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 in primary adult human microglia and peripheral blood macrophages (PBMs) was examined by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction (RT-PCR). Tax (20 ng/ml) induced TNF-alpha in microglia (from undetectable or low basal levels to 215-1,075 pg/ml, mean 576 +/- 375 pg/ml, n = 4) and in PBMs (70-1,900, mean 646 +/- 844 pg/ml, n = 4). This induction was dose dependent, Tax specific, and maximal at 8 hours after stimulation. IL-6 levels in microglia increased from a basal level of 368 +/- 194 to 664 +/- 270 pg/ml 24 hours after Tax stimulation. In contrast, IL-1 beta levels were modestly induced (less than or equal to 26 pg/ml). An increase in mRNA levels of the three cytokines was observed by semiquantitative RT-PCR (TNF-alpha = 28-fold; IL-6 = 5.6-fold; IL-1 beta = 3.6-fold). Thus, in HAM/TSP, extracellular Tax released from infiltrating T cells could induce cytokine release by microglia and contribute to demyelination and inflammation in the absence of detectable virus. C1 UNIV MARYLAND,DEPT NEUROL,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT NEUROSURG,BALTIMORE,MD 21201. VET ADM MED CTR,CTR RETROVIRUS RES,BALTIMORE,MD 21218. NCI,FREDERICK CANC RES & DEV CTR,LEUKOCYTE BIOL LAB,FREDERICK,MD. NR 15 TC 52 Z9 52 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1994 VL 36 IS 5 BP 787 EP 790 DI 10.1002/ana.410360516 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PR051 UT WOS:A1994PR05100015 PM 7979225 ER PT J AU SIMPSON, IA DAVIES, P AF SIMPSON, IA DAVIES, P TI REDUCED GLUCOSE-TRANSPORTER CONCENTRATIONS IN BRAINS OF PATIENTS WITH ALZHEIMERS-DISEASE SO ANNALS OF NEUROLOGY LA English DT Letter C1 ALBERT EINSTEIN COLL MED,DEPT PATHOL,BRONX,NY 10467. ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10467. RP SIMPSON, IA (reprint author), NIDDKD,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892, USA. NR 3 TC 13 Z9 13 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1994 VL 36 IS 5 BP 800 EP 801 DI 10.1002/ana.410360522 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PR051 UT WOS:A1994PR05100021 PM 7979229 ER PT J AU OSTEEN, RT WINCHESTER, DP HUSSEY, DH CLIVE, RE FRIEDMAN, MA CADY, B CHMIEL, JS KRAYBILL, WG URIST, MM DOGGETT, RLS AF OSTEEN, RT WINCHESTER, DP HUSSEY, DH CLIVE, RE FRIEDMAN, MA CADY, B CHMIEL, JS KRAYBILL, WG URIST, MM DOGGETT, RLS TI INSURANCE-COVERAGE OF PATIENTS WITH BREAST-CANCER IN THE 1991 COMMISSION ON CANCER-PATIENT CARE EVALUATION STUDY SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE BREAST CANCER; INSURANCE; STAGE; TREATMENT ID QUALITY; BLACK; WOMEN AB Background: Trends in the care of patients with cancer are monitored annually by the Commission on Cancer of the American College of Surgeons. In 1991 a patient care evaluation study of breast cancer was conducted, which among other questions examined the correlation of health insurance with type or quality of care delivered for breast cancer on a national basis. Methods: The tumor registry system of the American College of Surgeons was used to obtain data on patients with breast cancer diagnosed in 1983 and 1990. Trends in diagnosis and treatment were correlated with the type of insurance or lack of insurance. Results: Data were obtained from hospitals in 50 states on a total of 41,651 patients. The largest number of patients were covered by Medicare, Fewer than 5% were considered medically indigent. Medically indigent patients presented with higher stage disease and did not participate in a trend toward downstaging, which occurred between the two study years. The treatment of medically indigent patients appeared to be appropriate and comparable with better insured patients. Insurance type (health maintenance organization vs. private) did not affect stage, treatment, or outcome. Decisions to use controversial therapies, such as chemotherapy for stage I disease, did not appear to be financially driven. Conclusion: A nationwide pattern of care study for breast cancer indicates that medically indigent patients present with more advanced disease compared with better insured patients, but once the diagnosis is made, treatment and outcome have little to do with insurance type. C1 NORTHWESTERN UNIV,DEPT SURG,EVANSTON,IL. UNIV IOWA,DIV RADIAT ONCOL,IOWA CITY,IA. AMER COLL SURGEONS,CHICAGO,IL. NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02215. NORTHWESTERN UNIV,SCH MED,CANC BIOMETRY SECT,CHICAGO,IL. BARNES HOSP,DEPT SURG,ST LOUIS,MO 63110. UNIV ALABAMA,DEPT SURG,BIRMINGHAM,AL 35294. RADIAT ONCOL CTR,SACRAMENTO,CA. RP OSTEEN, RT (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT SURG,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 10 TC 30 Z9 30 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD NOV PY 1994 VL 1 IS 6 BP 462 EP 467 DI 10.1007/BF02303610 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA PN370 UT WOS:A1994PN37000006 PM 7850551 ER PT J AU TEMECK, BK PASS, HI AF TEMECK, BK PASS, HI TI A METHOD TO FACILITATE SUBXIPHOID PERICARDIOTOMY - REPLY SO ANNALS OF THORACIC SURGERY LA English DT Letter RP TEMECK, BK (reprint author), NCI,THORAC ONCOL SECT,BLDG 10,RM 2B07,BETHESDA,MD 20892, USA. NR 2 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 1994 VL 58 IS 5 BP 1567 EP 1567 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PQ159 UT WOS:A1994PQ15900079 ER PT J AU LUNN, G SANSONE, EB AF LUNN, G SANSONE, EB TI SAFE DISPOSAL OF DIISOPROPYL FLUOROPHOSPHATE (DFP) SO APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY LA English DT Article DE SAFETY; DEGRADATION; STABILITY; ENZYME INHIBITOR; DIISOPROPYL FLUOROPHOSPHATE; DYFLOS; ISOFLUROPHATE ID PURIFICATION; DEGRADATION AB Diisopropyl fluorophosphate (DFP), a volatile highly toxic enzyme inhibitor, in buffer (pH 3, pH 5, pH 7, pH 9, pH 11, Hank's, Dulbecco's, PBS, TBE, and HEPES) or water (10 mM), in DMF solution (200 mM), and bulk quantities can be degraded by adding 1M NaOH. The DFP was completely degraded, as determined by enzymatic assay, and the final reaction mixtures were not mutagenic. RP LUNN, G (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,ENVIRONM CONTROL & RES PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 24 TC 4 Z9 4 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0273-2289 J9 APPL BIOCHEM BIOTECH JI Appl. Biochem. Biotechnol. PD NOV PY 1994 VL 49 IS 2 BP 165 EP 172 DI 10.1007/BF02788550 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA PT258 UT WOS:A1994PT25800007 PM 7818266 ER PT J AU SHI, D NIKODIJEVIC, O JACOBSON, KA DALY, JW AF SHI, D NIKODIJEVIC, O JACOBSON, KA DALY, JW TI EFFECTS OF CHRONIC CAFFEINE ON ADENOSINE, DOPAMINE AND ACETYLCHOLINE SYSTEMS IN MICE SO ARCHIVES INTERNATIONALES DE PHARMACODYNAMIE ET DE THERAPIE LA English DT Article ID ADENYLATE CYCLASE SYSTEM; RAT CEREBRAL-CORTEX; LOCOMOTOR-ACTIVITY; OPIOID RECEPTORS; BINDING; METHYLXANTHINES; BRAIN; WITHDRAWAL; INGESTION; SITES AB Chronic ingestion of caffeine by male NIH Swiss strain mice leads in about 3 days to a significant increase in A(1)-adenosine, nicotinic and muscarinic receptors, and a significant decrease of beta(1)-adrenoceptors in cerebral cortical membranes. Plasma levels of caffeine in the chronically treated mice range from 0.70 to 5.7 mu g/ml. The changes in receptors reverse after withdrawal of caffeine within 7 days. An increase in nitrendipine binding sites, associated with L-type calcium channels, also occurs within 4 days and has reversed in 7 days after withdrawal. There is no change in the levels of striatal nicotinic receptors or D-2-dopamine receptors, nor of [H-3]cocaine binding to dopamine uptake sites. Levels of opioid receptors are either increased (delta) or unaltered (mu, kappa). sigma-Receptors are unaltered. Stimulations of striatal adenylate cyclase by forskolin, dopamine and NECA are not significantly affected after chronic caffeine ingestion. The adenosine agonist, NECA, reverses the amphetamine-elicited increases in locomotor activity and partly reverses the cocaine-elicited increases. The NECA dose-response curve is multiphasic (depression, stimulation and then depression) versus amphetamine in control mice, but only depressant versus amphetamine in chronic caffeine mice, while being multiphasic versus cocaine in both control and chronic caffeine mice. NECA reverses the stimulation of locomotor activity elicited by the muscarinic antagonist, scopolamine, and is more effective in the chronic caffeine mice. The behavioral depressant effects of the muscarinic agonist, oxotremorine, are not markedly altered after chronic caffeine ingestion. The behavioral depressant effects of nicotine are abolished after chronic caffeine ingestion, while the behavioral depressant effects of the nicotinic antagonist, mecamylamine, are not markedly altered after chronic caffeine ingestion. In combination with caffeine, nicotine has depressant effects in control mice, while having biphasic effects, consisting of initial stimulation followed by depression, in chronic caffeine mice. C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 30 TC 23 Z9 23 U1 0 U2 1 PU ARCH INT PHARMACODYNAMIE PI GHENT PA DE PINTELAAN 185, B-9000 GHENT, BELGIUM SN 0003-9780 J9 ARCH INT PHARMACOD T JI Arch. Int. Pharmacodyn. Ther. PD NOV-DEC PY 1994 VL 328 IS 3 BP 261 EP 287 PG 27 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QQ412 UT WOS:A1994QQ41200002 PM 7625882 ER PT J AU NIMS, RW FOX, SD ISSAQ, HJ LUBET, RA AF NIMS, RW FOX, SD ISSAQ, HJ LUBET, RA TI ACCUMULATION AND PERSISTENCE OF INDIVIDUAL POLYCHLORINATED BIPHENYL CONGENERS IN LIVER, BLOOD, AND ADIPOSE-TISSUE OF RATS FOLLOWING DIETARY EXPOSURE TO AROCLOR(R)-1254 SO ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID IRISH COASTAL WATERS; EATING SEA BIRDS; MOLECULAR-FEATURES; HEPATIC CYP1A; PCB ISOMERS; AROCLOR-1254; INDUCTION; DISPOSITION; MICROSOMES; EXCRETION AB Female F344/NCr rats were exposed continuously to Aroclor (R) 1254 (1, 3.3, 10, 33, or 100 ppm in the diet) for 7, 28, or 84 days in order to assess the accumulation of polychlorinated biphenyls (PCBs) in liver, blood, and adipose tissue. The persistence of the individual PCB congeners which are detected in liver was examined in the three tissues of additional groups of rats exposed for 7 days followed by 21 days on control diet, or for 28 days followed by 56 days on control diet. Limited accumulation of PCB congeners with low chlorine substitution (tri- and tetrachlorobiphenyls) in the liver and blood, and preferential retention of highly substituted PCB congeners (penta- and hexachlorobiphenyls) were observed in rats continuously exposed to Aroclor. In these rats, time- and dose-dependent increases in the relative levels of two congeners which cause profound phenobarbital-type induction [2,2',3,4,4',5'-hexachlorobiphenyl (BZ# 138) and 2,2',4,4',5,5'-hexachlorobiphenyl (BZ# 153)] were detected in the liver and adipose tissue. Rats receiving control diet following Aroclor treatment displayed a time- and dose-dependent decrease in the relative levels in blood, adipose and hepatic tissue of 2,3,3',4,4'-pentachlorobiphenyl (BZ# 105) and 2,3',4,4',5-pentachlorobiphenyl (BZ# 118), two of the major congeners showing both TCDD- and phenobarbital-type induction. These rats also displayed increases in the relative adipose levels of another relatively potent mixed-type inducer, 2,3,3',4,4',5-hexachlorobiphenyl (BZ# 156), and increases in adipose and hepatic levels of the pure phenobarbital-type inducer, 2,2',4,4',5-pentachlorobiphenyl (BZ# 99). C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. RP NIMS, RW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. NR 30 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0090-4341 J9 ARCH ENVIRON CON TOX JI Arch. Environ. Contam. Toxicol. PD NOV PY 1994 VL 27 IS 4 BP 513 EP 520 PG 8 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA PP458 UT WOS:A1994PP45800011 PM 7811109 ER PT J AU NURNBERGER, JI BLEHAR, MC KAUFMANN, CA YORKCOOLER, C SIMPSON, SG HARKAVYFRIEDMAN, J SEVERE, JB MALASPINA, D REICH, T MILLER, M BOWMAN, ES DEPAULO, JR CLONINGER, CR ROBINSON, G MODLIN, S GERSHON, ES MAXWELL, E GUROFF, JJ KIRCH, D WYNNE, D BERG, K TSUANG, MT FARAONE, SV PEPPLE, JR RITZ, AL AF NURNBERGER, JI BLEHAR, MC KAUFMANN, CA YORKCOOLER, C SIMPSON, SG HARKAVYFRIEDMAN, J SEVERE, JB MALASPINA, D REICH, T MILLER, M BOWMAN, ES DEPAULO, JR CLONINGER, CR ROBINSON, G MODLIN, S GERSHON, ES MAXWELL, E GUROFF, JJ KIRCH, D WYNNE, D BERG, K TSUANG, MT FARAONE, SV PEPPLE, JR RITZ, AL TI DIAGNOSTIC INTERVIEW FOR GENETIC-STUDIES - RATIONALE, UNIQUE FEATURES, AND TRAINING SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID LIFETIME PSYCHIATRIC-DIAGNOSIS; STRUCTURED CLINICAL INTERVIEW; AFFECTIVE-DISORDERS; FAMILIAL TRANSMISSION; 1ST-DEGREE RELATIVES; CAGE QUESTIONNAIRE; FOLLOW-UP; SCHIZOPHRENIA; DEPRESSION; RELIABILITY AB This article reports on the development and reliability of the Diagnostic Interview for Genetic Studies (DIGS), a clinical interview especially constructed for the assessment of major mood and psychotic disorders and their spectrum conditions. The DIGS, which was developed and piloted as a collaborative effort of investigators from sites in the National Institute of Mental Health (NIMH) Genetics Initiative, has the following additional features: (1) polydiagnostic capacity; (2) a detailed assessment of the course of the illness, chronology of psychotic and mood syndromes, and comorbidity; (3) additional phenomenologic assessments of symptoms; and (4) algorithmic scoring capability. The DIGS is designed to be employed by interviewers who exercise significant clinical judgment and who summarize information-in narrative form as well as in ratings. A two-phase test-retest (within-site, between-site) reliability study was carried out for DSM-III-R criteria-based major depression, bipolar disorder, schizophrenia, and schizoaffective disorder. Reliabilities using algorithms were excellent (0.73 to 0.95), except for schizoaffective disorder, for which disagreement on estimates of duration of mood syndromes relative to psychosis reduced reliability. A final best-estimate process using medical records and information from relatives as well as algorithmic diagnoses is expected to be more reliable in making these distinctions. The DIGS should be useful as part of archival data gathering for genetic studies of major affective disorders, schizophrenia, and related conditions. C1 INDIANA UNIV,MED CTR,DEPT PSYCHIAT,INDIANAPOLIS,IN. COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY 10032. JOHNS HOPKINS UNIV,DEPT PSYCHIAT,BALTIMORE,MD. WASHINGTON UNIV,DEPT PSYCHIAT,ST LOUIS,MO. NIMH,DIV CLIN & TREATMENT RES,ROCKVILLE,MD 20857. NIMH,INTRAMURAL RES PROGRAM,ROCKVILLE,MD 20857. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BROCKTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. SRA TECHNOL INC,FALLS CHURCH,VA. RI Cloninger, Claude/F-5357-2012; OI Cloninger, Claude/0000-0003-3096-4807; Harkavy-Friedman, Jill/0000-0002-1449-0667; Nurnberger, John/0000-0002-7674-1767 FU NIMH NIH HHS [U01 MH46276]; PHS HHS [46289, 46313] NR 60 TC 1215 Z9 1225 U1 3 U2 27 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 NOV PY 1994 VL 51 IS 11 BP 849 EP 859 PG 11 WC Psychiatry SC Psychiatry GA PQ612 UT WOS:A1994PQ61200001 PM 7944874 ER PT J AU RAO, PA PICKAR, D GEJMAN, PV RAM, A GERSHON, ES GELERNTER, J AF RAO, PA PICKAR, D GEJMAN, PV RAM, A GERSHON, ES GELERNTER, J TI ALLELIC VARIATION IN THE D(4) DOPAMINE-RECEPTOR (DRD4) GENE DOES NOT PREDICT RESPONSE TO CLOZAPINE SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ATYPICAL ANTIPSYCHOTIC-DRUGS; SEROTONIN RECEPTOR; MOLECULAR-CLONING; HIGH-AFFINITY; SCHIZOPHRENIA; NEUROLEPTICS; D4; POLYMORPHISM; ALCOHOLISM; EXPRESSION AB Objective: To test the hypothesis that interindividual differences in response to clozapine therapy might be attributable to the D-4 dopamine receptor (DRD4) alleles they carry. Different alleles of the D-4 dopamine receptor, coded by the DRD4 gene, differ in the affinity with which they bind the atypical antipsychotic drug clozapine in vitro. This may have physiologic implications. Clinical response to clozapine therapy varies among patients. The observation that, in vitro, clozapine binds the protein products of different DRD4 alleles with differing affinity characteristics suggested this hypothesis. Method: The region of the DRD4 gene that encodes the putative third cytoplasmic loop of the D-4 receptor contains a 48-base pair sequence repeated a variable number of times. With use of polymerase chain reaction amplification, we assessed this variable number of tandem rep eats polymorphism in a series of schizophrenic and schizoaffective subjects who had been treated with clozapine, and related genotype with treatment response, to test the hypothesis that DRD4 alleles lead to varying response to clozapine. Results: Allelic variation at the DRD4 locus does not predict clinical response to clozapine relative to either fluphenazine hydrochloride or placebo in subjects with treatment-refractory schizophrenia or schizoaffective disorder. Conclusions: DRD4 alleles do not predict therapeutic response to clozapine in schizophrenic and schizoaffective patients. There are implications from these data for the pathophysiology of schizophrenia and the mechanism of clozapine's therapeutic effect are discussed. C1 W HAVEN VET AFFAIRS MED CTR,DEPT PSYCHIAT,W HAVEN,CT 06516. YALE UNIV,SCH MED,DEPT PSYCHIAT,DIV MOLEC PSYCHIAT,NEW HAVEN,CT. NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD. NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. FU NIMH NIH HHS [MH00931, MH30929] NR 41 TC 92 Z9 92 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 NOV PY 1994 VL 51 IS 11 BP 912 EP 917 PG 6 WC Psychiatry SC Psychiatry GA PQ612 UT WOS:A1994PQ61200008 PM 7944879 ER PT J AU DECARLI, C MURPHY, DGM MCINTOSH, AR HORWITZ, B AF DECARLI, C MURPHY, DGM MCINTOSH, AR HORWITZ, B TI DISCRIMINANT-ANALYSIS OF ALZHEIMERS-DISEASE SO ARCHIVES OF NEUROLOGY LA English DT Letter ID QUANTIFICATION; BRAIN RP DECARLI, C (reprint author), NIA,NEUROSCI LAB,BETHESDA,MD 20892, USA. RI DeCarli, Charles/B-5541-2009; McIntosh, Anthony/G-4955-2011 NR 8 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 1994 VL 51 IS 11 BP 1088 EP 1088 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA PQ075 UT WOS:A1994PQ07500001 PM 7980101 ER PT J AU CUMMINGS, NB AF CUMMINGS, NB TI ETHICAL ISSUES AND THE BREAST-CANCER PATIENT SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article AB The association of cancer and death in laypeoples' thinking has resulted in discussions of cancer diagnoses often being held sub rosa. Open acceptance of a diagnosis of canter cannot only help to dispel associated fears but also can serve to educate other persons to recognize that cancers can be cured, Open discussion of diagnoses of breast cancer by well-known public figures increasingly has focused media attention on related issues. Numerous ethical issues applicable to breast cancer (and to other chronic and/or canter diagnoses) include: informed consent; education of relatives, friends, and public; patients' comfort in discussion of their diagnoses and treatment; access to care; and allocation of scarce resources. Genuine informed consent involves discussions of all relevant medical issues with the patient so that she understands the ramifications of the diagnoses, treatment, risks, and benefits of undergoing or of refusing treatment; acid enables the patient to make a reasoned autonomous decision. Sufficient time must be allowed for development of this understanding because all persons, but especially apprehensive patients, tend to be selective in their hearing of explanations: to hear what they are afraid to hear, what they want to hear, and what they ape prepared to hear. Limitations of funding for health care raise further questions about access to needed treatment. The concerns of the NIH Office of Research on Women's Health and of the Women's Health Initiative include breast dancer, as do those of the populace at large. RP CUMMINGS, NB (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 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 NOV PY 1994 VL 118 IS 11 BP 1077 EP 1080 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA PQ704 UT WOS:A1994PQ70400005 PM 7979890 ER PT J AU BROWN, AK SLEEPER, LA PEGELOW, CH MILLER, ST GILL, FM WACLAWIW, MA AF BROWN, AK SLEEPER, LA PEGELOW, CH MILLER, ST GILL, FM WACLAWIW, MA TI THE INFLUENCE OF INFANT AND MATERNAL SICKLE-CELL DISEASE ON BIRTH OUTCOME AND NEONATAL COURSE SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID ALPHA-GLOBIN GENE; BLACKS; WEIGHT AB Objective: To compare the influence of maternal hemoglobin phenotype as well as that of the infant on birth outcome and neonatal complications. Research Design: Prospective, natural history study with retrospective chart review for neonatal complications. Setting: Nineteen pediatric sickle cell centers across the United States. Patients: Four hundred eighty infants with sickle cell disease (SCD) who were enrolled in the Cooperative Study of Sickle Cell Disease at less than 6 months of age, as well as a comparison cohort of 118 infants with sickle cell trait born to women with sickle cell anemia in the Cooperative Study. Results: In the SCD cohort, overall rates of preterm (<37 weeks), low-birth-weight (<2500 g), and small-for-gestational age births were 9%, 10%, and 8%, respectively; no significant differences were found according to infant hemoglobin phenotype. Term births accounted for 59% of the infants with low birth weight, significantly higher than the 41% US rate for black low-birth-weight infants (P=.014). Expectant mothers with sickle cell anemia are 2.5 times more likely to bear newborns who are small for gestational age than are women with other types of sickle cell disease, sickle trait, or C-trait. The most common prepartum and neonatal complications in infants with SCD were jaundice (25%), fetal distress (13%), anemia (10%), and respiratory distress (6%). Complication rates did not differ significantly by hemoglobin phenotype in the infants with SCD, but infants born to women with sickle cell anemia had higher rates of jaundice (P<.0001). Conclusions: Rates of adverse birth outcomes and neonatal complications in infants with SCD are similar to the rates for normal infants, although preterm birth accounts for fewer of the low-birth-weight outcomes among newborns with SCD relative to US black newborns. The hemoglobin phenotype of infants with SCD does not influence birth outcome and neonatal course, but infants born to women with sickle cell anemia are at greater risk of preterm birth, low birth weight, being small for gestational age, and neonatal jaundice. C1 SUNY HLTH SCI CTR,DEPT PEDIAT,BROOKLYN,NY 11203. NEW ENGLAND RES INST,WATERTOWN,MA 02172. UNIV MIAMI,DIV PEDIAT HEMATOL,MIAMI,FL 33152. UNIV PENN,CHILDRENS HOSP,SCH MED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. NR 18 TC 12 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD NOV PY 1994 VL 148 IS 11 BP 1156 EP 1162 PG 7 WC Pediatrics SC Pediatrics GA PQ621 UT WOS:A1994PQ62100006 PM 7921116 ER PT J AU CROFFORD, LJ PILLEMER, SR KALOGERAS, KT CASH, JM MICHELSON, D KLING, MA STERNBERG, EM GOLD, PW CHROUSOS, GP WILDER, RL AF CROFFORD, LJ PILLEMER, SR KALOGERAS, KT CASH, JM MICHELSON, D KLING, MA STERNBERG, EM GOLD, PW CHROUSOS, GP WILDER, RL TI HYPOTHALAMIC-PITUITARY-ADRENAL AXIS PERTURBATIONS IN PATIENTS WITH FIBROMYALGIA SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; CHRONIC FATIGUE SYNDROME; CENTRAL NERVOUS-SYSTEM; NEUROPEPTIDE-Y; FIBROSITIS SYNDROME; BETA-ENDORPHIN; LEWIS RATS; INDUCED ARTHRITIS; STRESS RESPONSE; HORMONE AB Objective. To examine basal and stimulated hypothalamic-pituitary-adrenal (HPA) axis and related hormone levels, including adrenocorticotropin (ACTH), cortisol, arginine vasopressin (AVP), and neuropeptide Y (NPY), in patients with fibromyalgia (FM). Methods. Basal and ovine corticotropin-releasing hormone (oCRH)-stimulated HPA axis function were assessed in 12 patients with FM and in age- and sex-matched normal subjects. Basal plasma AVP levels and AVP release after postural change were assessed, and plasma NPY levels were measured in the same samples. Results. Patients with FM had low 24-hour urinary free cortisol, but normal peak and elevated trough plasma cortisol levels, compared with normal subjects. The net integrated ACTH response to oCRH in FM was not significantly different from that in normal subjects, but tended toward an exaggerated response. There was a significant decrease in net integrated cortisol response to oCRH in FM patients, indicating adrenal hyporesponsiveness. AVP levels were not significantly different between FM patients and control subjects, but variability was greater among the FM patients. Plasma NPY levels were significantly lower in FM patients than in normal subjects. Conclusion. These data support the view that HPA axis function is perturbed in patients with FM. Further study is required to ascertain the cause of HPA axis perturbations and their relationship to symptoms in patients with FM. C1 NIAMSD, BETHESDA, MD 20892 USA. NIMH, BETHESDA, MD 20892 USA. NICHHD, BETHESDA, MD 20892 USA. RI Kling, Mitchel/F-4152-2010; Crofford, Leslie/J-8010-2013 OI Kling, Mitchel/0000-0002-2232-1409; NR 51 TC 369 Z9 374 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD NOV PY 1994 VL 37 IS 11 BP 1583 EP 1592 DI 10.1002/art.1780371105 PG 10 WC Rheumatology SC Rheumatology GA PQ615 UT WOS:A1994PQ61500005 PM 7980669 ER PT J AU WALSH, TJ KARP, J HATHORN, JW PIZZO, PA AF WALSH, TJ KARP, J HATHORN, JW PIZZO, PA TI PREVENTION OF BACTERIAL-INFECTIONS IN NEUTROPENIC PATIENTS SO BAILLIERES CLINICAL INFECTIOUS DISEASES LA English DT Review ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ORAL TRIMETHOPRIM-SULFAMETHOXAZOLE; RESISTANT ENTEROCOCCUS-FAECALIS; BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; PLACEBO-CONTROLLED TRIAL; PROPHYLACTIC ANTIBIOTIC PROGRAM; NON-ABSORBABLE ANTIBIOTICS; ANTI-MICROBIAL MODULATION; ACUTE MYELOCYTIC-LEUKEMIA C1 DUKE UNIV, MED CTR, DIV MED ONCOL, DURHAM, NC 27710 USA. UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20814 USA. RP WALSH, TJ (reprint author), NCI, PEDIAT BRANCH, INFECT DIS SECT, BETHESDA, MD 20892 USA. NR 152 TC 8 Z9 8 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1071-6564 J9 BAILLIERE CLIN INF D JI Baillieres Clin. Infect. Dis. PD NOV PY 1994 VL 1 IS 3 BP 469 EP 498 PG 30 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QA997 UT WOS:A1994QA99700006 ER PT J AU WITT, ED AF WITT, ED TI MECHANISMS OF ALCOHOL-ABUSE AND ALCOHOLISM IN ADOLESCENTS - A CASE FOR DEVELOPING ANIMAL-MODELS SO BEHAVIORAL AND NEURAL BIOLOGY LA English DT Review ID NUCLEUS-ACCUMBENS; DEVELOPMENTAL-CHANGES; POSTNATAL-DEVELOPMENT; DOPAMINE RELEASE; CEREBRAL-CORTEX; FRONTAL-CORTEX; HUMAN-BRAIN; ETHANOL; RATS; ANTAGONIST AB This paper reviews the ontogeny of neurotransmitter systems and neuropharmacological challenge within transmitter systems and discusses the actions of alcohol on such systems during the juvenile through adolescent periods. To place the animal research within the context of human development, an attempt is made to first examine some fundamental principles of developmental research as they relate to the adolescent period. Evidence presented from animal studies indicates that unique neurochemical and behavioral changes are occurring during postnatal development, including adolescence, that could mediate the response to alcohol. The limited number of studies on the neurochemical and behavioral response to alcohol during adolescence has employed rats and has been restricted by the relatively brief adolescent period in that species. While one alternative is to use primates, it is suggested that innovative behavioral paradigms be developed for adolescent animals in other species to study behaviors such as alcohol self-administration or alcohol stimulus discrimination. It is also suggested that existing behavioral models that are more easily adapted to younger age ranges (e.g., conditioned place preference, conditioned taste aversion, thermal response to ethanol) be extended to make ontogenetic comparisons through adolescence and adulthood. This may further our understanding of alcohol's immediate consequences during each maturational stage and, more important, the contribution of early alcohol exposure to excessive drinking and abnormal cognitive and social functioning during subsequent stages of development. (C) 1994 Academic Press, Inc. RP WITT, ED (reprint author), NIAAA,NEUROSCI & BEHAV RES BRANCH,6000 EXECUT BLVD,SUITE 402,ROCKVILLE,MD 20892, USA. NR 88 TC 70 Z9 73 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0163-1047 J9 BEHAV NEURAL BIOL JI Behav. Neural Biol. PD NOV PY 1994 VL 62 IS 3 BP 168 EP 177 DI 10.1016/S0163-1047(05)80015-9 PG 10 WC Behavioral Sciences; Neurosciences; Psychology SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA PP755 UT WOS:A1994PP75500001 PM 7857239 ER PT J AU SRIVASTAVA, M GIBSON, KR POLLARD, HB FLEMING, PJ AF SRIVASTAVA, M GIBSON, KR POLLARD, HB FLEMING, PJ TI HUMAN CYTOCHROME B(561) - A REVISED HYPOTHESIS FOR CONFORMATION IN MEMBRANES WHICH RECONCILES SEQUENCE AND FUNCTIONAL INFORMATION SO BIOCHEMICAL JOURNAL LA English DT Article ID CHROMAFFIN GRANULE MEMBRANE; TRANSMEMBRANE ELECTRON-TRANSFER; ASCORBIC-ACID; PROTEINS; ORIENTATION AB Cytochrome b(561) is a major transmembrane protein of catecholamine and neuropeptide secretory vesicles. In this report, we describe the cloning and properties of a full-length cDNA encoding human neuroendocrine cytochrome b(561) from a human caudate cDNA library and a human peripheral blood genomic library. The human cDNA contains two major transcription start sites and only one translation start site that codes for an apocytochrome b(561), which is 22 amino acid residues smaller than the previously deduced amino acid sequence from bovine cDNA. This smaller version of cytochrome b(561) may contain only five transmembrane segments rather than the previously proposed six segments. The new model is in agreement with our previous results on transmembrane topology of the gene product. Northern-blot analysis shows an expanded tissue distribution of cytochrome mRNA expression where previous immunological assays were negative. These results support the hypothesis that cytochrome b(561) is a marker for peptidergic and adrenergic tissues. C1 GEORGETOWN UNIV, MED CTR, DEPT BIOCHEM & MOLEC BIOL, WASHINGTON, DC 20007 USA. RP SRIVASTAVA, M (reprint author), NIDDKD, CELL BIOL & GENET LAB, BETHESDA, MD 20892 USA. RI Fleming, Karen/E-7892-2011 NR 26 TC 22 Z9 23 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 1994 VL 303 BP 915 EP 921 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ056 UT WOS:A1994PQ05600034 PM 7980462 ER PT J AU CARRIER, F CHANG, CY DUH, JL NEBERT, DW PUGA, A AF CARRIER, F CHANG, CY DUH, JL NEBERT, DW PUGA, A TI INTERACTION OF THE REGULATORY DOMAINS OF THE MURINE CYP1A1 GENE WITH 2 DNA-BINDING PROTEINS IN ADDITION TO THE AH RECEPTOR AND THE AH RECEPTOR NUCLEAR TRANSLOCATOR (ARNT) SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE CYTOCHROME P450; TRANSCRIPTIONAL REGULATION; AH RECEPTOR; CYP1A1 GENE; GEL RETARDATION; IN VIVO FOOTPRINTING ID DIOXIN-RESPONSIVE ENHANCER; HALOGENATED AROMATIC-HYDROCARBONS; CYTOCHROME P-450C GENE; LIGATION MEDIATED PCR; RECOGNITION SITE; ELEMENT; MECHANISM; EXPRESSION; TRANSCRIPTION; TOXICITY AB The aromatic hydrocarbon (Ah) receptor complex is a ligand-activated transcriptional activator consisting of at least two protein components. The ligand-binding component is the AhR protein, a cytosolic receptor encoded by the Ahr gene, which, upon ligand binding, translocates to the nucleus in a heterodimeric complex with the ARNT (Ah receptor nuclear translocator) component. The complex binds to several discrete DNA domains containing aromatic hydrocarbon responsive elements (AhRE) present in the regulatory region of the murine cytochrome P(1)450 Cyp1a1 gene and of the other genes in the [Ah] gene battery. As a consequence of binding, a transcriptional complex is formed that activates the expression of these genes by as yet unidentified mechanisms. We have analyzed DNA-protein interactions in four of these domains, specifically, the AhREs located between -1085 and -482 (sites A, C, E, and D) of the upstream regulatory region of the murine Cyp1a1 gene. We found that two DNA-binding proteins, present in cytosolic and nuclear extracts of mouse Hepa-1 cells, showed overlapping DNA-binding specificities to those of the Ah receptor. One of these proteins had an apparent molecular mass of 35-40 kDa, bound only to AhRE3 (site D), and has been identified tentatively as a member of the C/EBP family of transcription factors. The second protein, purified by DNA-affinity chromatography, had an apparent molecular mass of 95 kDa and bound to a larger DNA motif that included the AhRE sequence, in AhRE3 and AhRE5 (sites D and A), but not in AhRE1 or AhRE2 (sites C and E). This protein was not AhR nor was it ARNT, since it was found in receptorless (Ahr(-)) and in nuclear translocation-defective (Arnt(-)) cells, as well as in cells that had not been exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin), a potent inducer of Cyp1a1 expression. Evidence from in vivo methylation protection indicated that two G residues flanking AhRE3, one of which is required for binding of the 95-kDa protein, may be protected from methylation in uninduced cells and become exposed upon dioxin treatment, suggesting that the 95-kDa protein may be constitutively bound to AhRE3, and be displaced by binding of the Ah receptor complex. These results lend support to the concept that the transcriptional regulation of the [Ah] battery genes could be modulated by combinatorial interactions of the Ah receptor complex with other transcription factors. C1 UNIV CINCINNATI,MED CTR,DEPT ENVIRONM HLTH,CINCINNATI,OH 45267. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RI Puga, Alvaro/B-7676-2008; Carrier, France/C-3063-2008 FU NIEHS NIH HHS [ES06096, ES06273, ES07278] NR 57 TC 30 Z9 34 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 1 PY 1994 VL 48 IS 9 BP 1767 EP 1778 DI 10.1016/0006-2952(94)90463-4 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PT239 UT WOS:A1994PT23900014 PM 7980646 ER PT J AU BURROWS, SD DOYLE, ML MURPHY, KP FRANKLIN, SG WHITE, JR BROOKS, I MCNULTY, DE SCOTT, MO KNUTSON, JR PORTER, D YOUNG, PR HENSLEY, P AF BURROWS, SD DOYLE, ML MURPHY, KP FRANKLIN, SG WHITE, JR BROOKS, I MCNULTY, DE SCOTT, MO KNUTSON, JR PORTER, D YOUNG, PR HENSLEY, P TI DETERMINATION OF THE MONOMER-DIMER EQUILIBRIUM OF INTERLEUKIN-8 REVEALS IT IS A MONOMER AT PHYSIOLOGICAL CONCENTRATIONS SO BIOCHEMISTRY LA English DT Article ID POLYMORPHONUCLEAR LEUKOCYTES; RECEPTOR-BINDING; CHEMOTAXIS; EXPRESSION; CYTOKINE; RESIDUES; PROTEINS AB Interleukin-8 has been shown by X-ray crystallography and NMR to be a homodimer, suggesting that this is the form which binds to its receptor. Here we measure, for the first time, the monomer-dimer equilibrium of interleukin-8 using analytical ultracentrifugation and titration microcalorimetry and find that it dissociates readily to monomers with an equilibrium dissociation constant of 18 +/- 6 mu M at 37 degrees C. The present findings suggest that the monomer is the form which binds to the receptor. Comparison of experimental and structure-based calculated thermodynamics of interleukin-8 dimerization argues for limited subunit conformational changes upon dissociation to monomer. C1 SMITHKLINE BEECHAM PHARMACEUT,DEPT MOLEC IMMUNOL,KING OF PRUSSIA,PA 19406. SMITHKLINE BEECHAM PHARMACEUT,DEPT MACROMOLEC SCI,KING OF PRUSSIA,PA 19406. SMITHKLINE BEECHAM PHARMACEUT,DEPT PROT BIOCHEM,KING OF PRUSSIA,PA 19406. SMITHKLINE BEECHAM PHARMACEUT,DEPT GENE EXPRESS SCI,KING OF PRUSSIA,PA 19406. UNIV IOWA,DEPT BIOCHEM,IOWA CITY,IA 52242. NHLBI,CELLULAR BIOL LAB,BETHESDA,MD 20892. RI Brooks, Ian/E-7052-2010 NR 35 TC 132 Z9 132 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 1 PY 1994 VL 33 IS 43 BP 12741 EP 12745 DI 10.1021/bi00209a002 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PP527 UT WOS:A1994PP52700002 PM 7947677 ER PT J AU MITCHELL, DC LITMAN, BJ AF MITCHELL, DC LITMAN, BJ TI EFFECT OF ETHANOL ON METARHODOPSIN II FORMATION IS POTENTIATED BY PHOSPHOLIPID POLYUNSATURATION SO BIOCHEMISTRY LA English DT Article ID CHAIN PHOSPHATIDYLCHOLINE VESICLES; LIPID PROTEIN INTERACTIONS; HIGHER-ORDER ANALYSIS; GENERAL-ANESTHETICS; RECOMBINANT MEMBRANES; BOVINE RHODOPSIN; ANISOTROPY DECAY; EQUILIBRIUM; CHOLESTEROL; INTERFACE AB The role of phospholipids in modulating the effect of ethanol on membrane receptor activation was investigated by studying the extent of metarhodopsin II (MII) formation in vesicles formed from POPC (1-parmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and PDPC(1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine) and in native rod outer segment disk membranes as a function of ethanol concentration. The equilibrium concentration of MII, the G protein-activating form of photoactivated rhodopsin, was found to increase as a function of ethanol concentration in all three bilayers. Phospholipid composition had a marked effect on ethanol potency, with the presence of polyunsaturated phospholipid acyl chains increasing ethanol potency by 40%. The effects of ethanol on lipid acyl chain packing in POPC and PDPC were investigated using frequency domain anisotropy decay measurements of the fluorescent membrane probe 1,6-diphenyl-1,3,5-hexatriene. Enhanced formation of MII due to the presence of ethanol was correlated with the effects of ethanol on acyl chain packing properties. These findings support a phospholipid-mediated mechanism for the action of ethanol in modulating integral membrane receptor conformation. C1 NIAAA,FLUORESCENCE STUDIES SECT,MEMBRANE BIOCHEM & BIOPHYS LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [1 PO1GM47525-01] NR 29 TC 21 Z9 21 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 1 PY 1994 VL 33 IS 43 BP 12752 EP 12756 DI 10.1021/bi00209a004 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PP527 UT WOS:A1994PP52700004 PM 7947679 ER PT J AU OKAZAKI, IJ ZOLKIEWSKA, A NIGHTINGALE, MS MOSS, J AF OKAZAKI, IJ ZOLKIEWSKA, A NIGHTINGALE, MS MOSS, J TI IMMUNOLOGICAL AND STRUCTURAL CONSERVATION OF MAMMALIAN SKELETAL-MUSCLE GLYCOSYLPHOSPHATIDYLINOSITOL-LINKED ADP-RIBOSYLTRANSFERASES SO BIOCHEMISTRY LA English DT Article ID GLYCOSYL-PHOSPHATIDYLINOSITOL; TURKEY ERYTHROCYTES; RIBOSYLATION; SURFACE; PROTEIN; IDENTIFICATION; PURIFICATION; ANCHORS; SUBSTRATE; HYDROLASE AB NAD:arginine ADP-ribosyltransferases catalyze the ADP-ribosylation of arginine residues in proteins. Coding region nucleic acid and deduced amino acid sequences of a human skeletal muscle ADP-ribosyltransferase cDNA were, respectively, 80.8% and 81.3% identical to those of the rabbit skeletal muscle transferase. A human transferase-specific cDNA probe detected major mRNA of 1.2 kb (mouse and rat), 3.0 kb (rabbit), 3.8 kb (monkey), and 5.7 kb (human) upon Northern analysis. Polyclonal anti-rabbit ADP-ribosyltransferase antibodies reacted with 36 000 M(r) proteins in partially purified transferase preparations from bovine, dog, and rabbit heart muscle and a 40 000 M(r) protein from human skeletal muscle. The human muscle ADP-ribosyltransferase cDNA, like the previously cloned rabbit muscle transferase, predicts predominantly hydrophobic amino- and carboxy-terminal amino acid sequences, which is characteristic of glycosylphosphatidylinositol (GPI)-anchored proteins. On immunoblots of partially purified rabbit and human skeletal muscle ADP-ribosyltransferases, anti-cross-reacting determinant antibodies detected at 36 000 and 40 000 M(r), respectively, phosphatidylinositol-specific, phospholipase C-sensitive, GPI-anchored proteins. These data are consistent with the conclusion that GPI-anchored skeletal and cardiac muscle ADP-ribosyltransferases are conserved across mammalian species. RP OKAZAKI, IJ (reprint author), NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892, USA. NR 34 TC 83 Z9 84 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 1 PY 1994 VL 33 IS 43 BP 12828 EP 12836 DI 10.1021/bi00209a014 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PP527 UT WOS:A1994PP52700014 PM 7947688 ER PT J AU SACKETT, DL BHATTACHARYYA, B WOLFF, J AF SACKETT, DL BHATTACHARYYA, B WOLFF, J TI LOCAL UNFOLDING AND THE STEPWISE LOSS OF THE FUNCTIONAL-PROPERTIES OF TUBULIN SO BIOCHEMISTRY LA English DT Article ID MICROTUBULE-ASSOCIATED PROTEINS; COLCHICINE-BINDING SITE; MOLTEN GLOBULE; ESCHERICHIA-COLI; GUANIDINE-HYDROCHLORIDE; BETA-TUBULIN; DISSOCIATION; DENATURATION; SUBUNIT; DIMER AB Tubulin exhibits a number of characteristic functions that can be used to identify it. They include the ability to polymerize to microtubules, GTPase activity, and the binding of numerous antimitotic drugs and fluorophores. These functions can be differentially modified by low (0.1-1.0 M) urea concentrations, and such urea-induced modifications are stable over time periods of minutes to hours. These intermediate states suggest the existence of restricted regions in the protein each of which is associated with a function and its own urea sensitivity. In order of decreasing sensitivity to urea these effects are decreased rate of polymerization of tubulin to microtubules > decreased extent of polymerization approximate to decreased GTPase activity > enhanced fluorescence of a rapidly binding analogue of colchicine-MTPT [2-methoxy-5-(2',3',4-trimethoxyphenyl)tropone] approximate to decreased proteolysis by trypsin (after alpha Arg339) and by chymotrypsin (after beta Tyr281) > enhanced fluorescence of 1-anilino-8-naphthalenesulfonic acid (ANS). Additional evidence for the independent behavior of the restricted regions stems from the markedly different time dependence of the response to urea. These low urea concentrations do not induce significant changes in tryptophan fluorescence, suggesting that the observed effects are due to local unfolding. At higher urea concentrations (2-4 M), the enhanced fluorescence of the ligands is abolished; MTPT fluorescence decreases at lower urea concentrations than ANS fluorescence. Moreover, tubulin becomes highly susceptible to proteolysis at multiple sites, and tryptophan emission shows a red-shift, as expected. Multistep unfolding in response to denaturants has been reported for some other proteins. Tubulin appears to be an extreme example of such local responses that proceed under milder conditions than the global transition to the unfolded state. RP SACKETT, DL (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BLDG 8,BETHESDA,MD 20892, USA. NR 61 TC 37 Z9 37 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 1 PY 1994 VL 33 IS 43 BP 12868 EP 12878 DI 10.1021/bi00209a019 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PP527 UT WOS:A1994PP52700019 PM 7947693 ER PT J AU CHEH, AM YAGI, H JERINA, DM AF CHEH, AM YAGI, H JERINA, DM TI EFFECT OF DNA-BASE SEQUENCE ON THE CONFIGURATION OF DEOXYADENOSINE ADDUCTS FORMED BY THE FJORD REGION DIOL EPOXIDE, (+)-(1R,2S,3R,4S)-3,4-DIHYDROXY-1,2-EPOXY-1,2,3,4-TETRAHYDROBENZO[C]PHEN ANTHRENE SO BIOCHEMISTRY LA English DT Article ID SOLUTION CONFORMATION; DIHYDRODIOL EPOXIDES; COVALENT BINDING; BENZOPYRENE; BENZOPHENANTHRENE; INTERCALATION; 3,4-DIOL-1,2-EPOXIDES; 1,2-EPOXIDES; SPECIFICITY; DEPENDENCE AB The carcinogen (+)-(1R,2S,3R,4S)-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (in which the 4-OH group and epoxide oxygen are cis) was reacted with duplexes formed from self-complementary oligodeoxyribonucleotides, producing 1S or 1R configured adducts through trans or cis epoxide ring opening, respectively, by the exocyclic amino group of a central target A. Sequences containing 5'-AT-3' generated much higher S vs R ratios than the average of 3.38 observed with calf thymus DNA samples, while sequences containing 5'-TA-3' generated much lower ratios. Sequences with G in the position immediately 5' to the central AT or TA, and C in the position immediately 3', generated moderately higher ratios than did sequences with adjacent 5' C and 3' G. When thymidine was replaced by deoxyuridine in several sequences, the ratios of S vs R configured dA adducts and dA adducts vs dG adducts were substantially and uniformly reduced, but otherwise varied with the choice of nearest neighbors in patterns similar to those observed with the T containing sequences. Two hypothetical mechanisms are proposed to explain the effect of nearest neighbors on the S vs R dA adduct ratio; in both, diol epoxide intercalation precedes covalent bonding. In one mechanism, intercalation to the 5' side of the target A yields an S adduct while intercalation to the 3' side yields an R adduct, and the extent of adduct formation follows the nearest neighbor series G > C > T. In the other, which is more consistent with the limited evidence available, intercalation to the 5' side of the target A yields an R adduct while intercalation to the 3' side yields an S adduct, and the extent of adduct formation follows the nearest neighbor series T > C > G. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP CHEH, AM (reprint author), AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016, USA. FU NCI NIH HHS [CA52043] NR 41 TC 6 Z9 6 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 1 PY 1994 VL 33 IS 43 BP 12911 EP 12919 DI 10.1021/bi00209a023 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PP527 UT WOS:A1994PP52700023 PM 7947697 ER PT J AU WONG, P AF WONG, P TI APOPTOSIS, RETINITIS-PIGMENTOSA, AND DEGENERATION SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article; Proceedings Paper CT 10th International Symposium on Cellular Endocrinology - Molecular and Cell Biology of Apoptosis in Development, Disease, and Cancer CY SEP 29-OCT 03, 1994 CL LAKE PLACID, NY SP ARGONEX, BURROUGHS WELLCOME, GLAXO RES INST, ONCOR, SCHERING PLOUGH RES INST, UPJOHN CO, WYETH AYERST RES DE RETINAL DEGENERATION; APOPTOSIS; RETINITIS PIGMENTOSA; CLUSTERIN; DNA FRAGMENTATION ID INHERITED RETINAL DYSTROPHY; RAT VENTRAL PROSTATE; GANGLION-CELL DEATH; RETE TESTIS FLUID; RD MOUSE RETINAS; SULFATED GLYCOPROTEIN-2; GENE-EXPRESSION; MESSENGER-RNA; BETA-SUBUNIT; DEVELOPMENTAL EXPRESSION AB The mechanism of photoreceptor cell death in different inherited retinal degenerations is not fully understood. Mutations in a number of different genes (such as rhodopsin, the beta subunit of cGMP phosphodiesterase, and peripherin) have been identified as the primary genetic lesion in different forms of human retinitis pigmentosa, one of the most common causes of inherited blindness. In all cases the manifestation of the disorder regardless of the specific primary genetic lesion is similar, resulting in photoreceptor cell degeneration and blindness. A recent hypothesis is that the active photoreceptor cell death, which is characteristic of these genetically distinct disorders, is mediated by a common induction of apoptosis. In the present review, the current evidence for active cell death during retinal cell death in several different rodent models of retinitis pigmentosa and retinal degeneration is examined. RP WONG, P (reprint author), NEI,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 82 TC 58 Z9 61 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD NOV-DEC PY 1994 VL 72 IS 11-12 BP 489 EP 498 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QY489 UT WOS:A1994QY48900008 PM 7654322 ER PT J AU WONG, P KUTTY, RK DARROW, RM SHIVARAM, S KUTTY, G FLETCHER, RT WIGGERT, B CHADER, G ORGANISCIAK, DT AF WONG, P KUTTY, RK DARROW, RM SHIVARAM, S KUTTY, G FLETCHER, RT WIGGERT, B CHADER, G ORGANISCIAK, DT TI CHANGES IN CLUSTERIN EXPRESSION ASSOCIATED WITH LIGHT-INDUCED RETINAL DAMAGE IN RATS SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article; Proceedings Paper CT 10th International Symposium on Cellular Endocrinology - Molecular and Cell Biology of Apoptosis in Development, Disease, and Cancer CY SEP 29-OCT 03, 1994 CL LAKE PLACID, NY SP ARGONEX, BURROUGHS WELLCOME, GLAXO RES INST, ONCOR, SCHERING PLOUGH RES INST, UPJOHN CO, WYETH AYERST RES DE RETINAL DEGENERATION; CLUSTERIN; APOPTOSIS; RETINITIS PIGMENTOSA ID GENE-EXPRESSION; INTERMITTENT LIGHT; VENTRAL PROSTATE; ALBINO-RATS; CELL-DEATH; DIMETHYLTHIOUREA; ILLUMINATION; APOPTOSIS; ASCORBATE; EXPOSURE AB Prolonged periods of high-intensity visible light exposure lead to photoreceptor cell degeneration, but the mechanism of damage is not understood. Increased clusterin mRNA levels have been found in several models of apoptosis, as well as in neurodegeneration. We report here that changes in clusterin mRNA levels are also associated with light-induced retinal damage in adult male albino rats. Animals previously maintained in darkness or a weak cyclic light environment were exposed to intense visible green light for up to 24 h. Some rats were pretreated with a synthetic antioxidant, dimethylthiourea (DMTU), which reduces photoreceptor cell degeneration. Clusterin mRNA steady state levels increased with the duration of light exposure in both cyclic light and dark reared animals, suggesting that an apoptotic mechanism may be involved. Animals pretreated with DMTU showed a delay in the initial increase in clusterin mRNA levels, suggesting that oxidative damage is involved in the damage mechanism. However, the incomplete suppression of increasing steady-state clusterin mRNA levels by DMTU suggests that either oxidative damage triggers a second pathway or multiple damage mechanisms are induced in the retina by light exposure. C1 WRIGHT STATE UNIV,DEPT BIOCHEM & MOLEC BIOL,DAYTON,OH 45435. NEI,BETHESDA,MD 20892. WRIGHT STATE UNIV,DEPT OPHTHALMOL,DAYTON,OH 45435. RP WONG, P (reprint author), NEI,ROOM 337,BLDG 6,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NEI NIH HHS [EY01959] NR 28 TC 24 Z9 24 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD NOV-DEC PY 1994 VL 72 IS 11-12 BP 499 EP 503 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QY489 UT WOS:A1994QY48900009 PM 7654323 ER PT J AU WONG, P SMITH, SB BORA, N GENTLEMAN, S AF WONG, P SMITH, SB BORA, N GENTLEMAN, S TI THE USE OF C(0)T-1 PROBE DNA FOR THE DETECTION OF LOW-LEVELS OF DNA FRAGMENTATION SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article; Proceedings Paper CT 10th International Symposium on Cellular Endocrinology - Molecular and Cell Biology of Apoptosis in Development, Disease, and Cancer CY SEP 29-OCT 03, 1994 CL LAKE PLACID, NY SP ARGONEX, BURROUGHS WELLCOME, GLAXO RES INST, ONCOR, SCHERING PLOUGH RES INST, UPJOHN CO, WYETH AYERST RES DE DNA FRAGMENTATION; APOPTOSIS; C(0)T-1 ID PROGRAMMED CELL-DEATH; ENDONUCLEASE ACTIVATION; APOPTOSIS; LINE AB In many apoptotic systems the final demise of the DNA results in the generation of multinucleosomal-sized DNA fragments, which appear as a DNA ladder after agarose electrophoresis. Extensive DNA fragmentation can be detected by ethidium bromide staining. Visualization of low levels of DNA fragmentation, however, requires both a more sensitive detection system, as well as a method of DNA extraction, that limits the extent of high molecular weight DNA shearing. We have found that the use of C(0)t-1 repetitive DNA as a probe for Southern analysis of DNA ladders is a sensitive method to detect low levels of DNA fragmentation. We have applied this methodology in the detection of DNA fragmentation in the normal developing C57BL/6 mouse retina at stages in which there is known DNA fragmentation, as well as in human Y-79 retinoblastoma cells grown in culture. We have found that in many instances in which there is no detectable DNA ladder with ethidium bromide staining a very definitive DNA ladder can be visualized via Southern blot analysis with a C(0)t-1 DNA probe. C1 MED COLL GEORGIA,DEPT CELL BIOL & ANAT,AUGUSTA,GA 30912. RP WONG, P (reprint author), NEI,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NEI NIH HHS [EY09682] NR 13 TC 16 Z9 16 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD NOV-DEC PY 1994 VL 72 IS 11-12 BP 649 EP 653 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QY489 UT WOS:A1994QY48900027 PM 7654339 ER PT J AU KIHARA, A PASTAN, I AF KIHARA, A PASTAN, I TI ANALYSIS OF SEQUENCES REQUIRED FOR THE CYTOTOXIC ACTION OF A CHIMERIC TOXIN COMPOSED OF PSEUDOMONAS EXOTOXIN AND TRANSFORMING GROWTH-FACTOR-ALPHA SO BIOCONJUGATE CHEMISTRY LA English DT Article ID SINGLE-CHAIN IMMUNOTOXINS; FUSION PROTEIN; FACTOR RECEPTOR; BLADDER-CANCER; ESCHERICHIA-COLI; RECOMBINANT FORM; CALMETTE-GUERIN; FRAGMENT; TUMORS; IMMUNOTHERAPY AB Chimeric toxins composed of transforming growth factor a fused to mutant forms of Pseudomonas exotoxin bind to the EGF receptor and kill cells bearing these receptors. In early experiments, the binding domain of Pseudomonas exotoxin was deleted and replaced with TGF alpha to make TGF alpha-PE40. This chimeric toxin required proteolytic processing within the target cell to be converted to its active form (Siegall et al. (1989) FASEB J. 3, 2647-2652). Subsequently, recombinant toxins that do not require proteolytic processing were constructed by inserting TGF alpha near the carboxyl terminus of domain III and deleting toxin residues up to the processing site at position 280. In addition, the carboxyl terminus of this toxin was converted from REDLK to KDEL to increase its activity. Recombinant toxins of this type, termed PE37/TGF alpha/KDEL, are about 100-fold more potent than TGF alpha-PE40. To determine if other sequences can be removed from such chimeric toxins to make a smaller molecule that can penetrate tissues better, we have carried out a deletion analysis of sequences present within domains II and Ib. We find that all of domain Ib and a portion of domain II can be deleted without significant loss of cytotoxic activity, but larger deletions extending further into domain II lose cytotoxic activity. We also find that inserting a small linking peptide (Gly)(4)Ser between residual sequences in domain II and domain III, in molecules with diminished cytotoxic activity, enhances cytotoxicity suggesting that one role of domain Ib is to prevent undesirable interactions between domains II and III. These new chimeric toxins are very active on A431 epidermoid carcinoma cells which contain many EGF receptors. One of these was also tested in animals and showed strong antitumor activity against A431 tumors growing in nude mice. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 33 TC 13 Z9 13 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 1994 VL 5 IS 6 BP 532 EP 538 DI 10.1021/bc00030a008 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA PV063 UT WOS:A1994PV06300008 PM 7873657 ER PT J AU ENGELMAN, A AF ENGELMAN, A TI MOST OF THE AVIAN GENOME APPEARS AVAILABLE FOR RETROVIRAL DNA INTEGRATION SO BIOESSAYS LA English DT Note ID III TRANSCRIPTION INITIATION; I-HYPERSENSITIVE SITES; PREFERRED TARGETS; INVITRO; CHROMATIN; PROTEIN; MAP; RECOMBINATION; METHYLATION; REGIONS AB Although retroviral integration requires specific viral DNA sequences, factors which govern the choice of a chromosomal target site within an infected cell are less clear. For example, certain chromosomal regions may be inaccessible to the viral integration machinery, while others may favor integration. A recent paper by Withers-Ward et al.((1)) addresses this issue using a polymerase chain reaction-based assay capable of identifying single integration events within a large population of infected cells. Their results show that integration can occur into many different chromosomal regions, and that local DNA structure can influence the site of integration within a given region. RP ENGELMAN, A (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 25 TC 8 Z9 8 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD NOV PY 1994 VL 16 IS 11 BP 797 EP 799 DI 10.1002/bies.950161105 PG 3 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA PU045 UT WOS:A1994PU04500004 PM 7840756 ER PT J AU EGAN, MF WING, L LI, R KIRCH, DG WYATT, RJ AF EGAN, MF WING, L LI, R KIRCH, DG WYATT, RJ TI EFFECTS OF CHRONIC COCAINE TREATMENT ON RAT-BRAIN - LONG-TERM REDUCTION IN FRONTAL CORTICAL SEROTONIN SO BIOLOGICAL PSYCHIATRY LA English DT Note DE COCAINE; SEROTONIN; FRONTAL CORTEX; STRIATUM; HYPOTHALAMUS ID DOPAMINE SYNTHESIS; CORTEX; CATECHOLAMINES; BINDING RP EGAN, MF (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,2700 MARTIN LUTHER KING JR BLVD SE,WASHINGTON,DC 20032, USA. NR 26 TC 16 Z9 18 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 1994 VL 36 IS 9 BP 637 EP 640 DI 10.1016/0006-3223(94)90079-5 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PQ961 UT WOS:A1994PQ96100013 PM 7530497 ER PT J AU SETOGUCHI, Y DANEL, C CRYSTAL, RG AF SETOGUCHI, Y DANEL, C CRYSTAL, RG TI STIMULATION OF ERYTHROPOIESIS BY IN-VIVO GENE-THERAPY - PHYSIOLOGICAL CONSEQUENCES OF TRANSFER OF THE HUMAN ERYTHROPOIETIN GENE TO EXPERIMENTAL-ANIMALS USING AN ADENOVIRUS VECTOR SO BLOOD LA English DT Article ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; HEMATOPOIETIC GROWTH-FACTORS; HAMSTER OVARY CELLS; STRUCTURAL CHARACTERIZATION; REGULATORY ELEMENTS; MEDIATED TRANSFER; EXPRESSION; INVIVO; BIOLOGY; DISEASE AB Erythropoietin (Epo), a 30.4-kD glycoprotein, is the principal regulator of erythropoiesis. To evaluate the concept that in vivo gene transfer might be used as an alternative to recombinant human Epo (rhEpo) in applications requiring a 1- to 3-week stimulation of erythropoiesis, the replication-deficient recombinant adenovirus AdMLP.Epo was constructed by deleting the majority of E1 from adenovirus type 5, and replacing E1 with an expression cassette containing the adenovirus type 5 major late promoter (MLP) and the human Epo gene, including the 3' cis-acting hypoxia response element. In vitro studies showed that infection of the human hepatocyte cell line Hep3B with AdMLP.Epo resulted in a 15-fold increase in Epo production in 24 hours that was enhanced to 116-fold in the presence of a hypoxic stimulus. One-time in vivo administration of AdMLP.Epo (7 x 10(9) plaque-forming units/kg) to the peritoneum of cotton rats caused a marked increase in red blood cell production, with a 2.6-fold increase in bone marrow erythroid precursors by day 4, and sevenfold increase in reticulocyte count by day 7. The hematocrit increased gradually, with a maximum of 64% +/- 4% at day 14 (compared with an untreated baseline of 46% +/- 2%), and a level of 55% +/- 1% at day 24. Furthermore, one-time subcutaneous administration of AdMLP.Epo caused an increase in hematocrit that peaked at 14 days (57% +/- 2%) and was still elevated at day 42. Hematocrit lever in animals receiving subcutaneous administration of AdMLP.Epo sustained a long-term increase compared with animals receiving intraperitoneal administration. In the context of these observations, gene therapy with a single administration of an adenovirus vector containing the human EPO gene may provide a means of significantly augmenting the circulating red blood cell mass over the 1- to 3-week period necessary for many clinical applications. (C) 1994 by The American Society of Hematology. C1 NEW YORK HOSP,CORNELL MED CTR,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. NHLBI,PULM BRANCH,BETHESDA,MD 20892. NR 50 TC 64 Z9 64 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1994 VL 84 IS 9 BP 2946 EP 2953 PG 8 WC Hematology SC Hematology GA PP021 UT WOS:A1994PP02100014 PM 7949166 ER PT J AU MAIERREDELSPERGER, M NOGUCHI, CT DEMONTALEMBERT, M RODGERS, GP SCHECHTER, AN GOURBIL, A BLANCHARD, D JAIS, JP DUCROCQ, R PELTIER, JY COTTAT, MC LACAILLE, F BELLOY, M ELION, J LABIE, D GIROT, R AF MAIERREDELSPERGER, M NOGUCHI, CT DEMONTALEMBERT, M RODGERS, GP SCHECHTER, AN GOURBIL, A BLANCHARD, D JAIS, JP DUCROCQ, R PELTIER, JY COTTAT, MC LACAILLE, F BELLOY, M ELION, J LABIE, D GIROT, R TI VARIATION IN FETAL HEMOGLOBIN PARAMETERS AND PREDICTED HEMOGLOBIN-S POLYMERIZATION IN SICKLE-CELL CHILDREN IN THE FIRST 2 YEARS OF LIFE - PARISIAN PROSPECTIVE-STUDY ON SICKLE-CELL DISEASE SO BLOOD LA English DT Article ID F-CELLS; INTRACELLULAR POLYMERIZATION; CLINICAL SEVERITY; ERYTHROCYTES; ANEMIA; HYDROXYUREA; GENE; ERYTHROPOIETIN; DEOXYGENATION; INDIVIDUALS AB Intracellular hemoglobin S (HbS) polymerization is most likely to be the primary determinant of the clinical and biologic manifestations of sickle cell disease (SCD). Fetal hemoglobin (HbF) does not enter the HbS polymer and its intracellular expression in sickle erythrocytes inhibits polymerization. HbF levels, high at birth but decreasing thereafter, protect the newborn from the clinical manifestations of this hemoglobinopathy. We have measured the sequential changes in HbF, F reticulocytes, and F cells in the first 2 years of life in 25 children with SCD and compared the results with those obtained in 30 normal children (AA). We have also calculated HbF per F cell (F/F cell), the preferential survival of F cells Versus non-F cells, as measured by the ratio F cells versus F reticulocytes (FC/FR) and polymer tendency at 40% and 70% oxygen saturation. HbF levels decreased from about 80.4% +/- 4.0% at birth to 9.2% +/- 2.9% at 24 months. During this time, we observed a regular decrease of the F reticulocytes and the F cells. The kinetics of the decline of F/F cell was comparable with the decline of HbF, rapid from birth (mean, 27.0 +/- 3.6 pg) to 12 months of age (mean, 8.5 +/- 1.5 pg) and then slower from 12 to 24 months of age (mean, 6.2 +/- 1.0 pg) in the SCD children. In the AA children, the decrease in HbF, due to changes in both numbers of F cells and F/F cell, was more precipitous, reaching steady-state revels by 10 months of age. Calculated values for mean polymer tendency in the F-cell population showed that polymerization should begin to occur at 40% oxygen saturation at about 3 months and increase progressively with age, whereas polymerization at 70% oxygen saturation would not occur until about 24 months. These values correspond to HbF levels of 50.8% +/- 10.8% and 9.2% +/- 2.9%, respectively, and F/F cell levels of 15.6 +/- 4.5 pg and 6.2 +/- 1.0 pg, respectively. In the non-F-cell population, polymerization was expected at birth at both oxygen saturation values. Three individuals had significantly greater predicted polymerization tendency than the remainder of the group because of early decreases in HbF, These individuals in particular, the remainder of the cohort, as well as other recruited newborns, will be studied prospectively to ascertain the relationship among hematologic parameters, which determine polymerization tendency and the various clinical manifestations of SCD. (C) 1994 by The American Society of Hematology. C1 NIDDKD, BIOL CHEM LAB, BETHESDA, MD USA. HOP NECKER ENFANTS MALAD, HEMATOL LAB, PARIS, FRANCE. CTR TRANSFUS SANGUINE, NANTES, FRANCE. HOP NECKER ENFANTS MALAD, BIOSTAT LAB, PARIS, FRANCE. HOP ROBERT DEBRE, INSERM, U120, PARIS, FRANCE. RP MAIERREDELSPERGER, M (reprint author), HOP TENON, HEMATOL LAB, 4 RUE CHINE, F-75970 PARIS 20, FRANCE. RI JAIS, Jean-Philippe/B-2993-2009; Elion, Jacques/A-1048-2014 OI JAIS, Jean-Philippe/0000-0002-0708-8776; NR 42 TC 29 Z9 29 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1994 VL 84 IS 9 BP 3182 EP 3188 PG 7 WC Hematology SC Hematology GA PP021 UT WOS:A1994PP02100044 PM 7524767 ER PT J AU TANAKA, H QUARTO, R WILLIAMS, S BARNES, J LIANG, CT AF TANAKA, H QUARTO, R WILLIAMS, S BARNES, J LIANG, CT TI IN-VIVO AND IN-VITRO EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) ON FEMORAL MESSENGER-RNA EXPRESSION IN OLD RATS SO BONE LA English DT Article DE IGF-I; GENE EXPRESSION; STROMAL CELLS; FEMUR; MARROW ABLATION; AGING ID BONE-FORMATION; COLLAGEN-SYNTHESIS; MESSENGER-RNA; PROTEIN; HORMONE; INVIVO; CELLS; DNA; SOMATOMEDIN; INVITRO AB The in vivo response of bone to IGF-I infusion in a marrow ablation model and the effect of IGF-I on bone marrow stromal cells in vitro was evaluated. IGF-I (25 ng/day), infused directly into femur, stimulated the expression of alkaline phosphatase, procollagen a, (I) and osteopontin mRNA, while osteocalcin mRNA was not affected. The dose dependency to IGF-I was bi-phasic, with stimulation at 25 and 50 ng but not at 150 ng/day. The effect of IGF-I was observed in the aged but not in the adult rat femur. However, the elevated mRNA levels in old bones with IGF-I treatment were still below those observed in adult bones. The effect of IGF-I was also examined in cultured stromal cells. IGF-I (50 ng/ml) stimulates the expression of alkaline phosphatase, procollagen a, (I), osteopontin and osteocalcin mRNA in stromal cells from both adult and old rats. These results suggest that the lack of response of adult bone to IGF-I in vivo was not due to the impaired response of the stromal cells to IGF-I. Differences in the responses of stromal cells from adult and old animals were noted. In the presence of serum (10%), stromal cells from adult rats were stimulated to synthesize DNA at lower levels of IGF-I than stromal cells from old animals. Our results show that IGF-I can stimulate mRNA expression of osteoblast markers in vivo in aged rats in a marrow ablation model and enhance DNA synthesis and gene expression in cultured marrow stromal cells from old rats. Thus, it is possible that exogenous IGF-I could be beneficial in treating age-associated osteopenia. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 32 TC 47 Z9 50 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD NOV-DEC PY 1994 VL 15 IS 6 BP 647 EP 653 DI 10.1016/8756-3282(94)90313-1 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PK882 UT WOS:A1994PK88200009 PM 7873293 ER PT J AU FRENKEL, N KATSAFANAS, GC WYATT, LS YOSHIKAWA, T ASANO, Y AF FRENKEL, N KATSAFANAS, GC WYATT, LS YOSHIKAWA, T ASANO, Y TI BONE-MARROW TRANSPLANT RECIPIENTS HARBOR THE B-VARIANT OF HUMAN HERPESVIRUS-6 SO BONE MARROW TRANSPLANTATION LA English DT Article ID EXANTHEM-SUBITUM; RENAL-TRANSPLANTATION; ANTIGENIC PROPERTIES; FULMINANT-HEPATITIS; T-CELLS; INFECTION; INFANTS; CHILDREN; IDENTIFICATION; PNEUMONITIS AB Lymphotropic herpesviruses have recently been isolated from patients undergoing kidney, liver and bone marrow transplantation (BMT). We have molecularly characterized isolates of HHV-6 from children undergoing allogenic BMT. We show that viruses recovered from the BMT recipients correspond to the B variant of human herpesvirus 6, the etiological agent of exanthem subitum. HHV-6 B strains are known to be associated with infections in the majority of children in infancy or early childhood. Infection in the BMT recipients most likely reflects the reactivation of these viruses during immunosuppressive treatment. Each of the reactivated viruses has its own characteristic heterogeneous (het) sequence. We show that the het sequence is stably unique for each HHV-6 strain. We also show that prolonged viremia can be documented with some of the patients, unlike the characteristic short duration febrile sickness in the exanthem subitum cases of infancy. The mechanism of HHV-6 B reactivation from latency is not known. Furthermore, the full clinical outcome of HHV-6 B viremia in the BMT patients requires further investigation. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. FUJITA HLTH UNIV,SCH MED,DEPT PEDIAT,TOYOAKE,AICHI 47011,JAPAN. RP FRENKEL, N (reprint author), TEL AVIV UNIV,DEPT CELL RES & IMMUNOL,RAMAT AVIV,ISRAEL. RI Asano, Yoshizo/F-6870-2012 NR 36 TC 38 Z9 38 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 1994 VL 14 IS 5 BP 839 EP 843 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA PY425 UT WOS:A1994PY42500023 PM 7889017 ER PT J AU HUANG, SZ ZENG, FY REN, ZR LU, ZH RODGERS, GP SCHECHTER, AN ZENG, YT AF HUANG, SZ ZENG, FY REN, ZR LU, ZH RODGERS, GP SCHECHTER, AN ZENG, YT TI RNA TRANSCRIPTS OF THE BETA-THALASSEMIA ALLELE IVS-2-654 C-]T - A SMALL AMOUNT OF NORMALLY PROCESSED BETA-GLOBIN MESSENGER-RNA IS STILL PRODUCED FROM THE MUTANT-GENE SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE BETA-THALASSEMIA; GENE MUTATION; MESSENGER-RNA; RT-PCR ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA; PRENATAL-DIAGNOSIS; THALASSEMIA MUTATIONS; MOLECULAR-BASIS; CHINESE; DEFECTS; DNA AB IVS-2-654 C --> T is a common Chinese beta-thalassaemia mutation. Previous studies report that this mutation resulted in the formation of an abnormally spliced mRNA and the absence of detectable normal beta-globin mRNA, hence the mutation was considered to cause beta degrees-thalassaemia. We recently used the method of PCR amplified cDNA copies of circulating erythroid cell mRNA to analyse the mutant gene transcripts and found that this IVS-2-654 mutation does not abolish normal RNA processing entirely, but that a significant amount (over 15%) of normally processed beta-globin mRNA is produced. Microglobin chain biosynthetic analysis using the HPLC method showed that beta-globin chain was also present in the blood of patients with IVS-2-654 C --> T mutation. Accordingly, this mutant allele leads to a beta(+)-thalassaemia. Further, the methodology described in this paper provides a new approach towards the detection of RNA transcripts of beta-thalassaemia alleles as well as the study of gene expression in beta-thalassaemia and other genetic diseases. C1 SHANGHAI CHILDRENS HOSP,SHANGHAI INST MED GENET,SHANGHAI 200040,PEOPLES R CHINA. NIDDK,CHEM BIOL LAB,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL-29623] NR 25 TC 18 Z9 28 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 1994 VL 88 IS 3 BP 541 EP 546 DI 10.1111/j.1365-2141.1994.tb05071.x PG 6 WC Hematology SC Hematology GA PQ058 UT WOS:A1994PQ05800013 PM 7819066 ER PT J AU WILLIAMS, SB MCKEOWN, LP KRUTZSCH, H HANSMANN, K GRALNICK, HR AF WILLIAMS, SB MCKEOWN, LP KRUTZSCH, H HANSMANN, K GRALNICK, HR TI PURIFICATION AND CHARACTERIZATION OF HUMAN PLATELET VON-WILLEBRAND-FACTOR SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE PLATELET ADHESION; THROMBOSIS; HEMOSTASIS; PLATELET; VON WILLEBRAND FACTOR ID THROMBIN-STIMULATED PLATELETS; PLASMA VONWILLEBRAND-FACTOR; MURINE MONOCLONAL-ANTIBODY; RISTOCETIN-INDUCED BINDING; GLYCOPROTEIN-IIB-IIIA; VIII-RELATED ANTIGEN; MULTIMERIC STRUCTURE; FACTOR PROTEIN; ADENOSINE-DIPHOSPHATE; DISEASE AB Platelet von Willebrand factor (vWf) was purified from human platelet concentrates. The multimeric structure of the purified platelet vWf was similar to that observed in the initial platelet lysate, and, like the platelet lysate, the purified platelet vWf contained higher molecular weight multimers than plasma vWf. The apparent molecular weight of the reduced platelet vWf subunit was similar to the plasma vWf subunit. The N-terminal amino acid of the purified platelet and plasma vWf was blocked. In concentration dependent binding to botrocetin- or ristocetin-stimulated platelets, I-125-plasma vWf bound with a higher affinity than platelet. The ristocetin cofactor activity per mg of purified plasma vWf was 5-fold greater than the platelet vWf activity. Platelet and plasma vWf bound to collagen with similar affinities: however, platelet vWf bound to thrombin-stimulated platelets and to heparin with a higher affinity than plasma vWf. The differences in the binding affinity(s) of plasma and platelet vWf to platelet GPIb and GPIIb/IIIa and extracellular matrix proteins may reflect different roles for plasma and platelet vWf in the initial stages of haemostasis and thrombosis. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,CTR CLIN,SERV HEMATOL,BETHESDA,MD 20892. NR 41 TC 23 Z9 23 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 1994 VL 88 IS 3 BP 582 EP 591 DI 10.1111/j.1365-2141.1994.tb05077.x PG 10 WC Hematology SC Hematology GA PQ058 UT WOS:A1994PQ05800019 PM 7819071 ER PT J AU EBELING, PR YERGEY, AL VIEIRA, NE BURRITT, MF OFALLON, WM KUMAR, R RIGGS, BL AF EBELING, PR YERGEY, AL VIEIRA, NE BURRITT, MF OFALLON, WM KUMAR, R RIGGS, BL TI INFLUENCE OF AGE ON EFFECTS OF ENDOGENOUS 1,25-DIHYDROXYVITAMIN-D ON CALCIUM-ABSORPTION IN NORMAL WOMEN SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE AGE; VITAMIN-D; CALCIUM ABSORPTION ID IMMUNOREACTIVE PARATHYROID-HORMONE; VITAMIN-D METABOLISM; PHOSPHORUS-METABOLISM; LIQUID-CHROMATOGRAPHY; OSTEOPOROTIC PATIENTS; RENAL-FUNCTION; BONE; ASSAY; RESISTANCE; RECEPTOR AB Recent reports of increases in serum 1,25-dihydroxyvitamin D [1,25(OH2)D] concentration with aging despite no changes or decreases in calcium absorption suggest that elderly women have intestinal resistance to vitamin D action. Thus, in 15 young adult (30 +/- 1 year) and 15 elderly (74 +/- 1 year) women (mean +/- SE), we assessed the responsiveness of intestinal calcium absorption to increases in circulating 1,25(OH)(2)D induced by 4 days of an experimental diet (150 mg calcium and 1600 mg phosphorus daily). True fractional calcium absorption (FCA) (Ca-44 mixed with food and Ca-42 given intravenously, then their ratio in urine measured by mass spectrometry) was determined. Baseline serum intact parathyroid hormone (PTH) concentration was higher in the older women (P = 0.01) whereas serum 1,25(OH)(2)D concentration and true FCA were similar. In both groups, serum 1,25(OH)(2)D concentrations increased (P < 0.002) on the experimental diet. After 4 days on the diet, serum 1,25(OH)(2)D increased over baseline by 30.5 and 35.6% and, despite these increases, true FCA was 40 +/- 3 versus 40 +/- 4%/24 hours (NS between groups) in the young and elderly women, respectively. These data suggest that either elderly women have normal intestinal responsiveness to vitamin D or that the resistance to it is too mild to be detected by these methods. C1 MAYO CLIN & MAYO FDN,ENDOCRINE RES UNIT,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DEPT LAB MED & PATHOL,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DEPT HLTH SCI RES,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DIV NEPHROL,ROCHESTER,MN 55905. NICHHD,METAB ANAL & MASS SPECTROMETRY SECT,BETHESDA,MD 20892. RI Ebeling, Peter/A-9129-2012 FU NCRR NIH HHS [RR-00585]; NIA NIH HHS [AG-04875]; NIDDK NIH HHS [R01 DK025409, R01 DK058546] NR 39 TC 22 Z9 22 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD NOV PY 1994 VL 55 IS 5 BP 330 EP 334 DI 10.1007/BF00299309 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN666 UT WOS:A1994PN66600003 PM 7866911 ER PT J AU PETTIT, GR XU, JP ICHIHARA, Y WILLIAMS, MD BOYD, MR AF PETTIT, GR XU, JP ICHIHARA, Y WILLIAMS, MD BOYD, MR TI ANTINEOPLASTIC AGENTS .285. ISOLATION AND STRUCTURES OF CEPHALOSTATIN-14 AND CEPHALOSTATIN-15 SO CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE LA English DT Article ID MARINE BRYOZOAN; TUNICATE; ALKALOIDS; CARTERI AB The tube-inhabiting marine worm, Cephalodiscus gilchristi has been found to produce a series of cytotoxic and antineoplastic disteroidal alkaloids. A substantial study concerned with discovery of new cell growth inhibitory constituents of this marine animal has led to isolation of cephalostatins 14 (5a) and 15 (5b). The structures were determined by interpretation of spectral data, principally high-field (400 and 500 MHz) NMR and HRFABMS combined with NMR spectral relationships to cephalostatin 1 (4) where the structure was previously assigned by X-ray crystal structure analysis. The stereochemical assignments were established employing the ROESY NMR technique. Both new cephalostatins significantly inhibited growth of the P388 lymphocytic leukemia and a selection of human cancer cell lines. The two new cephalostatins further enhance knowledge of structure-activity parameters for these potentially important steroidal alkaloids. C1 ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. RP PETTIT, GR (reprint author), ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287, USA. NR 29 TC 32 Z9 35 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4042 J9 CAN J CHEM JI Can. J. Chem.-Rev. Can. Chim. PD NOV PY 1994 VL 72 IS 11 BP 2260 EP 2267 DI 10.1139/v94-288 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA PU872 UT WOS:A1994PU87200010 ER PT J AU KELLEY, CA ADELSTEIN, RS AF KELLEY, CA ADELSTEIN, RS TI CHARACTERIZATION OF ISOFORM DIVERSITY IN SMOOTH-MUSCLE MYOSIN HEAVY-CHAINS SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT Symposium on Smooth Muscle Contraction - Recent Advances CY AUG 23-27, 1993 CL MINAKI, CANADA DE MYOSIN; HEAVY CHAIN ISOFORMS ID PROTEIN-KINASE-C; VERTEBRATE NONMUSCLE MYOSIN; AMINO-ACID-SEQUENCE; LIGHT CHAIN; ACANTHAMOEBA MYOSIN; MULTIGENE FAMILY; MESSENGER-RNAS; CDNA CLONING; BRAIN MYOSIN; DNA-SEQUENCE AB In this paper we review some of our recent work on the structural and biochemical characterization of isoforms of the heavy chain of vertebrate smooth muscle myosin II. There exist both amino-terminal and carboxyl-terminal alternatively spliced isoforms of the smooth muscle myosin heavy chain (MHC). mRNA splicing at the 3' end generates two MHCs, which differ in length and amino acid sequence in the carboxyl terminus. We will refer to the longer, 204-kDa isoform as MHC(204) and the shorter, 200-kDa isoform as MHC(200). We found that MHC(204), but not MHC(200), can be phosphorylated by casein kinase II on a serine near the carboxyl terminus, suggesting that these isoforms may be differentially regulated. The physiological significance of this phosphorylation is not known. However, as demonstrated in this paper, phosphorylation does not appear to affect filament formation, velocity of movement of actin filaments by myosin in an in vitro motility assay, actin-activated Mg2+ ATPase activity, or myosin conformation. Our results also show that MHC(204) and MHC(200) form homodimers, but not heterodimers. Purified MHC(204) and MHC(200) homodimers are not enzymatically different, at least as measured using an in vitro motility assay. The amino-terminal spliced MHC(204) and MHC(200) isoforms are the result of the specific insertion or deletion of seven amino acids near the ATP-binding region in the myosin head. We refer to these isoforms as inserted (MHC(204)-I; MHC(200)-I) or noninserted (MHC(204); MHC(200)), respectively. In contrast to the carboxyl-terminal spliced isoforms, the amino-terminal spliced inserted and noninserted myosin heavy chain isoforms are enzymatically different. The inserted isoform, which is expressed in intestinal, phasic-type smooth muscle, has a higher actin-activated Mg ATPase activity and moves actin filaments at a greater velocity in an in vitro motility assay than the noninserted MHC isoform, which is expressed in tonic-type vascular smooth muscle. The results presented in this review suggest that the alternative splicing of smooth muscle mRNA results in at least four different isoforms of the myosin heavy chain molecule. The potential relevance of these molecular isoforms to smooth muscle function is discussed. RP KELLEY, CA (reprint author), NHLBI,MOLEC CARDIOL LAB,BLDG 10,ROOM 8N-202,BETHESDA,MD 20892, USA. OI Adelstein, Robert/0000-0002-8683-2144 NR 55 TC 16 Z9 16 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD NOV PY 1994 VL 72 IS 11 BP 1351 EP 1360 PG 10 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA QE878 UT WOS:A1994QE87800016 PM 7767878 ER PT J AU ASMAR, L GEHAN, EA NEWTON, WA WEBBER, BL MARSDEN, HB VANUNNIK, AJM HAMOUDI, AB SHIMADA, H TSOKOS, M HARMS, D NINFO, V SCHMIDT, D CAVAZZANA, A GONZALESCRUSSI, F PARHAM, DM REIMAN, HM BELTANGADY, MS SACHS, N TRICHE, TJ MAURER, HM AF ASMAR, L GEHAN, EA NEWTON, WA WEBBER, BL MARSDEN, HB VANUNNIK, AJM HAMOUDI, AB SHIMADA, H TSOKOS, M HARMS, D NINFO, V SCHMIDT, D CAVAZZANA, A GONZALESCRUSSI, F PARHAM, DM REIMAN, HM BELTANGADY, MS SACHS, N TRICHE, TJ MAURER, HM TI AGREEMENT AMONG AND WITHIN GROUPS OF PATHOLOGISTS IN THE CLASSIFICATION OF RHABDOMYOSARCOMA AND RELATED CHILDHOOD SARCOMAS - REPORT OF AN INTERNATIONAL STUDY OF 4 PATHOLOGY CLASSIFICATIONS SO CANCER LA English DT Article DE CLASSIFICATION; RHABDOMYOSARCOMA; MEASURE OF AGREEMENT; PATHOLOGY; AND CHILDHOOD SARCOMA ID INTERGROUP RHABDOMYOSARCOMA; STUDY-II AB Background. An International Pathology study was conducted to measure the agreement demonstrated among and within groups of pathologists involved in the categorization of childhood rhabdomyosarcoma according to four pathology classifications. Data concerning agreement and survival experience according to patho- new subtypes were used as a basis for selection of a proposed new pathologic classification. Methods. A random sample of 800 eligible patients was chosen from the Intergroup Rhabdomyosarcoma Study II (IRS-II) and was reviewed by pathologists representing eight institutions, A 20% sample of the 800 patients was then rereviewed by the pathologists to determine the level of agreement with their original classification. In each instance the patients were classified according to four pathology systems: the conventional system, the International Society for Pediatric Oncology system (SIOP), the National Cancer Institute (NCI) system,and the cytohistologic system. Results. Among the groups of pathologists, the highest measure of agreement was a Kappa value of K = 0.451 for the conventional system, followed by K = 0.406 for the SIOP system, K = 0.384 for the NCI system, and K = 0.328 for the cytohistologic system. For reproducibility within the groups of pathologists, the highest measure of agreement was K = 0.605 for the conventional system, followed by K = 0.579 for the NCI system, K = 0.573 for the SIOP system, and K = 0.508 for the cytohistologic system. Conclusions. There was a general similarity between the agreement reached within the modified conventional, SIOP, and NCI systems, with the modified conventional system having the highest Kappa values, and thus the highest measure of agreement, both among and within the groups of pathologists. Also, the subtypes of the conventional system demonstrated a highly significant relationship to survival time. Hence, based on criteria of reproducibility and prognostic significance, the proposed classification will essentially be a modification of the conventional system with elements of the SIOP and NCI systems. C1 PEDIAT ONCOL GRP,HOUSTON,TX. PEDIAT INTERGRP STAT CTR,HOUSTON,TX. CHILDRENS CANC GRP,HOUSTON,TX. NCI,HOUSTON,TX. INT SOC PEDIAT ONCOL,HOUSTON,TX. GERMAN ITALIAN COOPERAT SOFT TISSUE SARCOMAS STUD,HOUSTON,TX. FU NCI NIH HHS [CA-24507, CA-30138] NR 13 TC 51 Z9 52 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1994 VL 74 IS 9 BP 2579 EP 2588 DI 10.1002/1097-0142(19941101)74:9<2579::AID-CNCR2820740928>3.0.CO;2-A PG 10 WC Oncology SC Oncology GA PP485 UT WOS:A1994PP48500027 PM 7923014 ER PT J AU SIMON, R AF SIMON, R TI RANDOMIZED CLINICAL-TRIALS IN ONCOLOGY - PRINCIPLES AND OBSTACLES SO CANCER LA English DT Article; Proceedings Paper CT American-Cancer-Society National Conference on Clinical Trials CY NOV 03-05, 1993 CL ATLANTA, GA SP AMER CANC SOC, AMER COLL SURGEONS COMMISS CANC, AMER ACAD FAMILY PHYSICIANS, ONCOL NURSING SOC DE RANDOMIZED; CLINICAL TRIALS; INTERIM ANALYSIS; LARGE SIMPLE TRIAL; METAANALYSIS; STATISTICS AB Cancer clinical trials have two broad objectives: To identify promising treatments and to determine whether such treatments really do reduce morbidity and mortality. These two objectives generally require different types of clinical trials. The guiding principle of clinical trials is to ask an important question and get a reliable answer. Asking an important question generally means asking a question that has the potential for influencing medical practice, using a control treatment that is widely accepted, using an experimental treatment that is widely applicable, using an endpoint that is a direct measure of patient benefit, and studying a group of patients who are broadly representative. Getting a reliable answer also has many components, including randomized treatment assignment, adequate sample size, intent-to-treat analysis, and testing of prestated hypotheses on mature data. These components are discussed. Several recent developments in clinical trials methodology: interim monitoring boundaries, large simple trials, and metaanalysis, are highlighted here. Major obstacles to conducting randomized clinical trials are also described. RP SIMON, R (reprint author), NCI,BIOMETR RES BRANCH,6130 EXECUT BLVD,ROOM 739,ROCKVILLE,MD 20852, USA. NR 12 TC 22 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 NOV 1 PY 1994 VL 74 IS 9 SU S BP 2614 EP 2619 DI 10.1002/1097-0142(19941101)74:9+<2620::AID-CNCR2820741805>3.0.CO;2-8 PG 6 WC Oncology SC Oncology GA PQ269 UT WOS:A1994PQ26900004 PM 7954274 ER PT J AU FORD, LG BRAWLEY, OW PERLMAN, JA NAYFIELD, SG JOHNSON, KA KRAMER, BS AF FORD, LG BRAWLEY, OW PERLMAN, JA NAYFIELD, SG JOHNSON, KA KRAMER, BS TI THE POTENTIAL FOR HORMONAL PREVENTION TRIALS SO CANCER LA English DT Article; Proceedings Paper CT American-Cancer-Society National Conference on Clinical Trials CY NOV 03-05, 1993 CL ATLANTA, GA SP AMER CANC SOC, AMER COLL SURGEONS COMMISS CANC, AMER ACAD FAMILY PHYSICIANS, ONCOL NURSING SOC DE PROSTATE CANCER; BREAST CANCER; PREVENTION; HORMONAL CANCERS ID BENIGN PROSTATIC HYPERPLASIA; STEROID 5ALPHA-REDUCTASE DEFICIENCY; RANDOMIZED CLINICAL-TRIAL; TERM TAMOXIFEN THERAPY; ADVANCED BREAST-CANCER; 5-ALPHA-REDUCTASE INHIBITOR; MALE PSEUDOHERMAPHRODITISM; ADJUVANT TAMOXIFEN; ANDROGEN RECEPTOR; ENVIRONMENTAL-FACTORS AB Breast and prostate cancer are significant causes of morbidity and mortality and are very similar in etiology, epidemiology, and modalities of treatment. Investigational strategies in the prevention of these malignancies also have strong parallels. The National Cancer Institute is sponsoring several large scale clinical trials involving hormonal manipulation and cancer prevention. In the Breast Cancer Prevention Trial, 16,000 women at high risk for breast cancer are being randomized to receive the antiestrogen agent tamoxifen or placebo for 5 years in an effort to determine if breast cancer development can be inhibited. In a similar trial, the Prostate Cancer Prevention Trial, 18,000 men older than 55 years of age will be randomized to receive finasteride, a 5-alpha-reductase inhibitor, or placebo to determine if inhibition of dihydrotestosterone synthesis in the prostate over a prolonged period will lead to a decreased incidence of prostate cancer. Both clinical trials offer the possibility of demonstrating that a hormonal intervention can decrease an individual's risk of developing breast or prostate cancer. They also have the potential of providing critical information about cancer risk, etiology, screening, and genetics, as well as quantifying the risks and benefits of specific preventive interventions. RP FORD, LG (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 80 TC 17 Z9 17 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1994 VL 74 IS 9 SU S BP 2726 EP 2733 DI 10.1002/1097-0142(19941101)74:9+<2726::AID-CNCR2820741823>3.0.CO;2-S PG 8 WC Oncology SC Oncology GA PQ269 UT WOS:A1994PQ26900024 PM 7954293 ER PT J AU SCHAIRER, C BYRNE, C KEYL, PM BRINTON, LA STURGEON, SR HOOVER, RN AF SCHAIRER, C BYRNE, C KEYL, PM BRINTON, LA STURGEON, SR HOOVER, RN TI MENOPAUSAL ESTROGEN AND ESTROGEN-PROGESTIN REPLACEMENT THERAPY AND RISK OF BREAST-CANCER (UNITED-STATES) SO CANCER CAUSES & CONTROL LA English DT Article DE BREAST CANCER; ESTROGENS; HORMONE REPLACEMENT THERAPY; PROGESTINS; UNITED-STATES AB This study examines the relationship between menopausal estrogen and estrogen-progestin replacement therapy and risk of breast cancer, focusing on whether associations differ according to whether the tumors are in situ or invasive. Data are from a prospective study conducted 1980-89 on 49,017 selected participants in the Breast Cancer Detection Demonstration Project, a five-year screening program conducted between 1973 and 1980 in the United States. Overall, the rate ratio for estrogen-only use compared with no-hormone use was 1.0, and that for the estrogen-progestin combination was 1.2 (95 percent confidence interval [CI] = 1.0-1.6). However, the associations differed according to whether the tumors were in situ or invasive. The rate ratios of in situ breast cancer associated with use of estrogens alone and the combination regimen were 1.4 (CI = 1.0-2.0) and 2.3 (CI = 1.3-3.9), respectively. Duration of estrogen-only use also was associated with risk of in situ tumors, with users for 10 or more years at twice the risk of nonusers (P-value for trend test = 0.02). Duration of use was not associated with risk of invasive cancer. Our results are consistent with the hypothesis that hormone replacement therapy is related to earlier-stage breast cancer; however, the possibility that the results reflect increased breast cancer surveillance among those taking hormones cannot be ruled out. RP SCHAIRER, C (reprint author), NCI,6130 EXECUT BLVD,EPN 443,ROCKVILLE,MD 20852, USA. RI Brinton, Louise/G-7486-2015; Byrne, Celia/K-2964-2015 OI Brinton, Louise/0000-0003-3853-8562; Byrne, Celia/0000-0001-8289-4252 NR 0 TC 126 Z9 126 U1 0 U2 4 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 1994 VL 5 IS 6 BP 491 EP 500 DI 10.1007/BF01831376 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PU328 UT WOS:A1994PU32800001 PM 7827235 ER PT J AU KALEBIC, T TSOKOS, M HELMAN, LJ AF KALEBIC, T TSOKOS, M HELMAN, LJ TI IN-VIVO TREATMENT WITH ANTIBODY AGAINST IGF-1 RECEPTOR SUPPRESSES GROWTH OF HUMAN RHABDOMYOSARCOMA AND DOWN-REGULATES P34(CDC2) SO CANCER RESEARCH LA English DT Note ID FACTOR-I; AUTOCRINE GROWTH; RAT GLIOBLASTOMA; ATHYMIC MICE; CELL-CYCLE; M-PHASE; EXPRESSION; INHIBITION; CULTURE; TUMORS AB In a previous study, we have shown that insulin-like growth factor type 2 (IGF-2) functions as an autocrine growth factor in human rhabdomyosarcoma (RMS) cell lines. In addition, we demonstrated that the inhibition of binding of IGF-2 to the IGF-1 receptor, mediated by suramin, blocked the growth of RMS cells in vitro. We now report that, iii vivo, a specific IGF-1 receptor blocking antibody (alpha IR-3), but not suramin, suppresses RMS tumor growth. Both progression of tumor growth in tumor-bearing animals and formation of newly established tumors were suppressed by treatment with alpha IR3. Histological analysis of tumors from treated animals did not reveal necrotic lesions, implying that the treatments had no cytotoxic effect. The decrease in tumor growth was associated with a decrease of p34(cdc2), a cellular protein involved in cell cycle regulation, suggesting that treatment resulted in the arrest of cellular proliferation. We speculate, therefore, that agents which block the IGF signaling pathway may find application in treatment of RMS. C1 NCI,DEPT PATHOL,BETHESDA,MD 20892. RP KALEBIC, T (reprint author), NCI,PEDIAT BRANCH,MOLEC ONCOL SECT,BLDG 10-13N240,BETHESDA,MD 20892, USA. NR 23 TC 148 Z9 153 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1994 VL 54 IS 21 BP 5531 EP 5534 PG 4 WC Oncology SC Oncology GA PP190 UT WOS:A1994PP19000008 PM 7923191 ER PT J AU RAHMAN, A KORZEKWA, KR GROGAN, J GONZALEZ, FJ HARRIS, JW AF RAHMAN, A KORZEKWA, KR GROGAN, J GONZALEZ, FJ HARRIS, JW TI SELECTIVE BIOTRANSFORMATION OF TAXOL TO 6-ALPHA-HYDROXYTAXOL BY HUMAN CYTOCHROME-P450 2C8 SO CANCER RESEARCH LA English DT Note ID HUMAN-LIVER; CYP2C SUBFAMILY; METABOLISM; NARINGENIN AB The principal taxol biotransformation reaction of humans and of human hepatic in vivo preparations is 6 alpha-hydroxylation of the taxane ring, but a separate, minor hydroxylation pathway (metabolite B formation) also exists. Taxol metabolism was studied using membrane fractions from Hep G(2) cells infected with recombinant vaccinia viruses that contain complementary DNAs encoding several human cytochrome P450 enzymes. Only P450 2C8 formed detectable 6 alpha-hydroxytaxol. Metabolite B formation was catalyzed by complementary DNA-expressed 3A3 and 3A4, but not by 3A5. Each P450 3A preparation catalyzed felodipine oxidation. The apparent K-m and V-max values for taxol 6 alpha-hydroxylation were 5.4 +/- 1.0 mu M and 30 +/- 1.5 nmol/min/nmol P450, respectively, for complementary DNA-expressed P450 2C8; the values were 4.0 +/- 1.0 mu M and 0.87 +/- 0.06 nmol/min/mg protein, respectively, for human hepatic microsomes. The inhibition of 6 alpha-hydroxytaxol formation by quercetin was competitive with an apparent K-i of 1.3 or 1.1 mu M with 2C8 or hepatic microsomes, respectively; retinoic acid was inhibitory, showing an apparent K-i of 27 mu M with hepatic microsomes; inhibition by tolbutamide was complex, weak, and unlikely to be clinically relevant. The correlation between hepatic 2C8 protein content and 6 alpha-hydroxytaxol formation was high (r(2) = 0.82), while the correlation with 2C9 content was low (r(2) = 0.38). These data show that human biotransformation routes of taxol result from catalysis by specific enzymes of two P450 families and that taxol 6 alpha-hydroxylation is a useful indicator of P450 2C8 activity in human hepatic microsomes. C1 US FDA,CTR DRUG EVALUAT & RES,DIV BIOPHARMACEUT,ROCKVILLE,MD 20857. US FDA,CTR DRUG EVALUAT & RES,DIV CLIN PHARMACOL,ROCKVILLE,MD 20857. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 21 TC 323 Z9 332 U1 4 U2 8 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 NOV 1 PY 1994 VL 54 IS 21 BP 5543 EP 5546 PG 4 WC Oncology SC Oncology GA PP190 UT WOS:A1994PP19000011 PM 7923194 ER PT J AU HODGE, JW ABRAMS, S SCHLOM, J KANTOR, JA AF HODGE, JW ABRAMS, S SCHLOM, J KANTOR, JA TI INDUCTION OF ANTITUMOR IMMUNITY BY RECOMBINANT VACCINIA VIRUSES EXPRESSING B7-1 OR B7-2 COSTIMULATORY MOLECULES SO CANCER RESEARCH LA English DT Note ID CTLA-4; LYMPHOCYTES; CD28 AB Activation of T cells requires at least two signals: an antigen-specific signal delivered through the T-cell receptor and a costimulatory signal mediated through molecules designated B7-1 and B7-2. Previous studies have shown that introduction of B7-1 and B7-2 into tumors using retroviral vectors has led to enhanced antitumor effects. A limiting factor for potential clinical applications using this approach is the low efficiency of infection of retroviral vectors and consequent manipulations of infected cells. Vaccinia virus thus represents an alternative vector for B7 gene expression in tumor cells. In this report we describe the construction and characterization of recombinant vaccinia viruses containing the murine B7-1 and B7-2 genes (designated rV-B7-1 and rV-B7-2). Infection of BSC-1 cells with these constructs results in rapid and efficient cell surface expression of both B7-1 and B7-2 (>97% of cells at 4 h). Infection of murine carcinoma cells with low multiplicity of infection of wild-type vaccinia virus leads to the death of the host following tumor transplantation. In contrast, inoculation of rV-B7-1- or rV-B7-2-infected tumor cells into immunocompetent animals resulted in no tumor growth. These studies demonstrate the utility of recombinant vaccinia viruses to deliver B7 molecules to tumor cells for potential gene therapy and recombinant approaches to cancer immunotherapy. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 16 TC 163 Z9 166 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1994 VL 54 IS 21 BP 5552 EP 5555 PG 4 WC Oncology SC Oncology GA PP190 UT WOS:A1994PP19000013 PM 7522961 ER PT J AU CLAUDIO, PP HOWARD, CM BALDI, A DELUCA, A FU, Y CONDORELLI, G SUN, Y COLBURN, N CALABRETTA, B GIORDANO, A AF CLAUDIO, PP HOWARD, CM BALDI, A DELUCA, A FU, Y CONDORELLI, G SUN, Y COLBURN, N CALABRETTA, B GIORDANO, A TI P130/PRB2 HAS GROWTH SUPPRESSIVE PROPERTIES SIMILAR TO YET DISTINCTIVE FROM THOSE OF RETINOBLASTOMA FAMILY MEMBERS PRB AND P107 SO CANCER RESEARCH LA English DT Note ID TRANSCRIPTION FACTOR E2F; CELL-CYCLE; NASOPHARYNGEAL CARCINOMA; POINT MUTATION; GENE-PRODUCT; HUMAN CANCER; RB GENE; PROTEIN; BINDING; ASSOCIATION AB The retinoblastoma tumor suppressor gene product, as well as its related protein p107, has been shown clearly to exert its growth suppressive effects in a cell cycle dependent manner. In this study we demonstrate that the introduction of our recently cloned Rb family member p130/pRb2 causes growth arrest in three tumor cell lines. In addition, in the nasopharyngeal carcinoma derived cell line HONE-1, we identified a low level of expression of p130/pRb2, possibly due to gene rearrangement, and a drastic reduction in proliferation upon introduction of a constitutive active p130/pRb2 complementary DNA clone. Furthermore, we were able to dissect distinct properties of the ph family by demonstrating that p130/pRb2 inhibits proliferation of the glioblastoma cell line T98G, which is resistant to the growth suppressive effects of both pRb and p107. Our studies demonstrate that the Rb family proteins identified to date may complement each other but they are not fully functionally redundant. C1 TEMPLE UNIV,SCH MED,FELS INST CANC RES & MOLEC BIOL,DEPT PATHOL,PHILADELPHIA,PA 19140. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD 21702. RI Giordano, Antonio/F-1927-2010; OI Giordano, Antonio/0000-0002-5959-016X; Baldi, Alfonso/0000-0002-8693-3842; Claudio, Pier Paolo/0000-0001-7790-1622; Condorelli, Gianluigi/0000-0003-0481-6843 FU NCI NIH HHS [R01 CA60999] NR 39 TC 222 Z9 223 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1994 VL 54 IS 21 BP 5556 EP 5560 PG 5 WC Oncology SC Oncology GA PP190 UT WOS:A1994PP19000014 PM 7923196 ER PT J AU WEINBERG, WC AZZOLI, CG KADIWAR, N YUSPA, SH AF WEINBERG, WC AZZOLI, CG KADIWAR, N YUSPA, SH TI P53 GENE DOSAGE MODIFIES GROWTH AND MALIGNANT PROGRESSION OF KERATINOCYTES EXPRESSING THE V-RAS(HA) ONCOGENE SO CANCER RESEARCH LA English DT Article ID WILD-TYPE P53; TUMOR-SUPPRESSOR GENE; MOUSE SKIN CARCINOGENESIS; SQUAMOUS-CELL CARCINOMAS; TATA-BINDING PROTEIN; V-HA-RAS; FACTOR-BETA; TGF-ALPHA; C-MYC; REPRESSES TRANSCRIPTION AB Epidermal keratinocyte cultures were established from newborn mice expressing a null mutation in the p53 gene to explore the contribution of p53 to epidermal growth regulation and neoplasia. Keratinocytes were initiated by transduction with a replication-defective retrovirus encoding the v-ras(Ha) oncogene and grafted onto nude mouse hosts. Tumors arising from keratinocytes heterozygous or null for functional p53 in the presence of v-ras(Ha) have growth rates approximately 5-fold higher than those derived from p53(+/+) controls and rapidly form carcinomas, in contrast to the benign phenotype observed in p53(+/+)/v-ras(Ha) grafts. In vitro, p53-deficient keratinocytes with and without v-ras(Ha) expression display decreased responsiveness to the negative growth regulators transforming growth factors beta(1) and beta(2). In combination with v-ras(Ha), p53-deficient keratinocytes also exhibit decreased responsiveness to elevated Ca2+. These differences between genotypes cannot be attributed to changes in transforming growth factor beta receptor types present or altered levels of epidermal growth factor receptor and are independent of c-myc transcript levels. mRNA expression for the p-53 inducible protein WAF1 correlates with p53 gene dosage, but low levels are still detectable in p53(-/-) keratinocytes. The altered responsiveness of p53 deficient keratinocytes to negative growth regulators may provide a growth advantage to such cells in vivo and render them more susceptible to genetic alterations and malignant conversion. RP WEINBERG, WC (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,ROOM 3B25,BETHESDA,MD 20892, USA. RI Weinberg, Wendy/A-8920-2009 NR 68 TC 47 Z9 47 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1994 VL 54 IS 21 BP 5584 EP 5592 PG 9 WC Oncology SC Oncology GA PP190 UT WOS:A1994PP19000019 PM 7923201 ER PT J AU JACKMAN, J ALAMO, I FORNACE, AJ AF JACKMAN, J ALAMO, I FORNACE, AJ TI GENOTOXIC STRESS CONFERS PREFERENTIAL AND COORDINATE MESSENGER-RNA STABILITY ON THE 5 GADD GENES SO CANCER RESEARCH LA English DT Article ID DNA-DAMAGING AGENTS; C-FOS; DESTABILIZING ELEMENTS; UNTRANSLATED REGIONS; BINDING PROTEIN; MAMMALIAN-CELLS; GROWTH; DIFFERENTIATION; DEGRADATION; ACTIVATION AB The growth arrest and DNA damage-inducible (gadd) genes represent a group of five stress-inducible genes that are coordinately regulated at the transcriptional level. Posttranscriptional regulation of gadd153, gadd45, gadd34, gadd33, and gadd7 was studied after exposure to DNA damaging agents or other growth arrest treatments in hamster cells. Relative transcript levels were measured following treatment with the transcriptional inhibitor actinomycin D. After exposure to methylmethane sulfonate or UV radiation, all five gadd messages demonstrated a coordinate increase in mRNA stability compared to untreated exponentially growing cells. This enhanced stability was not an universal response to genotoxic stress since other DNA damage-inducible genes, such as c-jun and c-fos, did not show an appreciable increase in mRNA half-life. In contrast, induction of growth arrest by media depletion (starvation) or by treatment with the growth inhibitor prostaglandin A, did not induce such an increase in mRNA stability in all gadd genes. Comparison of overall RNA turnover by H-3 labeling of total cellular RNA also indicated that the preferential stabilization of the gadd transcripts by DNA-damaging agents was not an artifactual response due to variations in overall RNA metabolism within each treatment group. However, DNA-damaging agents were ineffective in inducing stabilization of gadd153 mRNA in growth-arrested cells. This suggests that the signal(s) that give rise to gadd mRNA stability may also be affected by the state of cellular proliferation. Together, these results suggest that the global posttranscriptional response of the gadd genes to DNA-damaging agents is specific and unique to actively growing cells, and further implicates the role of the gadd genes in the DNA damage response of cycling cells. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 40 TC 109 Z9 112 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1994 VL 54 IS 21 BP 5656 EP 5662 PG 7 WC Oncology SC Oncology GA PP190 UT WOS:A1994PP19000031 PM 7923213 ER PT J AU MONSKY, WL LIN, CY AOYAMA, A KELLY, T AKIYAMA, SK MUELLER, SC CHEN, WT AF MONSKY, WL LIN, CY AOYAMA, A KELLY, T AKIYAMA, SK MUELLER, SC CHEN, WT TI A POTENTIAL MARKER PROTEASE OF INVASIVENESS, SEPRASE, IS LOCALIZED ON INVADOPODIA OF HUMAN-MALIGNANT MELANOMA-CELLS SO CANCER RESEARCH LA English DT Article ID HUMAN CANCER-CELLS; TUMOR-CELL; PLASMINOGEN ACTIVATION; TRANSFORMED-CELLS; PLASMA-MEMBRANE; IV COLLAGENASE; EXTRACELLULAR-MATRIX; METASTASIS MODEL; CONTACT SITES; CATHEPSIN-B AB Seprase, a large, gelatin-degrading membrane-protease complex, is expressed at the invasive front of malignant melanoma cells on invadopodia, and its surface expression contributes to the invasive phenotype. An ia vitro assay was used to determine the matrix-degrading activity of four malignant human melanoma cell lines. The lines differ in matrix-degrading activity with LOX > RPMI7951 > A375 > SKMEL28. The seprase and Gelatinase A activities of these cell lines were also investigated. Seprase and active gelatinase A are found in cell membranes of LOX and RPMI7951 cells but not those of SKMEL28 cells. Experiments using anti-seprase monoclonal antibodies in conjunction with a cell fractionation technique indicate that seprase consists of M(r) 97,000 polypeptides and is enriched on the ventral membrane of LOX in contact with planar extracellular matrix substratum. Confocal microscopy further substantiates our biochemical findings that seprase, as well as Gelatinase A, is localized on invadopodia membranes with a 6-fold increase of seprase and 4-fold increase of Gelatinase A intensity over the level expressed on dorsal membranes. In addition, LOX cells expressing higher levels of seprase at the cell surface, as selected by fluorescence-activated cell sorting, are significantly more degradative than LOX Fells with lower seprase expression. Taken together, our data show a concordance between seprase and Gelatinase A expression on the cell surface at invadopodia and the matrix-degrading activity of human malignant melanoma cells. Seprase and major secreted proteases may act in concert to degrade components of the extracellular matrix during invasion. C1 GEORGETOWN UNIV,MED CTR,SCH MED,DEPT CELL BIOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,SCH MED,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RI Aoyama, Atsuko/M-4826-2014 FU NCI NIH HHS [R01CA39077, IP30-CA-51008] NR 49 TC 173 Z9 181 U1 1 U2 6 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 NOV 1 PY 1994 VL 54 IS 21 BP 5702 EP 5710 PG 9 WC Oncology SC Oncology GA PP190 UT WOS:A1994PP19000038 PM 7923219 ER PT J AU GHOSHAL, A PREISEGGER, KH TAKAYAMA, S THORGEIRSSON, SS SNYDERWINE, EG AF GHOSHAL, A PREISEGGER, KH TAKAYAMA, S THORGEIRSSON, SS SNYDERWINE, EG TI INDUCTION OF MAMMARY-TUMORS IN FEMALE SPRAGUE-DAWLEY RATS BY THE FOOD-DERIVED CARCINOGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE AND EFFECT OF DIETARY-FAT SO CARCINOGENESIS LA English DT Article ID BREAST-CANCER; TUMORIGENESIS; BIOLOGY; DISEASE; PROTEIN AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen found in cooked meat, was determined to be a mammary carcinogen in female Sprague-Dawley rats on a high fat diet. Forty-three-day-old female Sprague-Dawley rats received 10 doses of PhIP (75 mg/kg, p.o., days 1-5 and 8-12). Two days after the last dose of PhIP, animals were placed on a high polyunsaturated fat diet (23.5% corn oil) or a standard low fat diet (5% corn oil). After 25 weeks on the defined diet, mammary tumor incidence (average tumor mass +/- SE) was 53% (5.7 +/- 1.3 g) and 16% (2.4 +/- 0.9 g) in rats on a high fat and standard low fat diet, respectively. The histological differences in mammary gland tumors found in animals on the standard low fat diet and the high fat diet were striking. Mammary gland tumors found in PhIP-treated rats on the low fat diet were all histologically benign. The histopathological changes in these tumors included hypertrophic changes resembling the normal mammary gland, fibrocystic changes, and sclerosing adenosis. However, 80% of the mammary gland tumors found in PhIP-treated rats on a high fat diet were histologically malignant. These tumors had several malignant phenotypes including intraductal carcinoma (papillary, cribriform, and comedo-type), tubular adenocarcinoma, and infiltrating duct carcinoma. The data indicate that a high fat diet in combination with a heterocyclic amine carcinogen derived from cooked meat may enhance the incidence and severity of mammary gland cancer. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,OFF DIRECTOR,BETHESDA,MD 20892. NR 19 TC 111 Z9 112 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1994 VL 15 IS 11 BP 2429 EP 2433 DI 10.1093/carcin/15.11.2429 PG 5 WC Oncology SC Oncology GA PT041 UT WOS:A1994PT04100003 PM 7955086 ER PT J AU GRINBERGFUNES, RA SINGH, VN PERERA, FP BELL, DA YOUNG, TL DICKEY, C WANG, LW SANTELLA, RM AF GRINBERGFUNES, RA SINGH, VN PERERA, FP BELL, DA YOUNG, TL DICKEY, C WANG, LW SANTELLA, RM TI POLYCYCLIC AROMATIC HYDROCARBON-DNA ADDUCTS IN SMOKERS AND THEIR RELATIONSHIP TO MICRONUTRIENT LEVELS AND THE GLUTATHIONE-S-TRANSFERASE M1 GENOTYPE SO CARCINOGENESIS LA English DT Article ID WHITE BLOOD-CELLS; LUNG-CANCER RISK; SISTER CHROMATID EXCHANGE; VITAMIN-A; ALPHA-TOCOPHEROL; HYDROXYLASE-ACTIVITY; CARCINOGEN-METABOLISM; CIGARETTE-SMOKING; BETA-CAROTENE; SERUM AB Sixty-three male cigarette smokers were entered into a cross-sectional study to determine whether inverse associations existed between polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels and intake/serum levels of vitamin A, vitamin C and vitamin E. Associations between PAH-DNA adducts and intakes of carotene, as well as serum levels of beta-carotene, were also determined. Fasting blood samples were collected for assays of PAH-DNA adducts in circulating mononuclear cells, plasma cotinine and serum levels of vitamin A, beta-carotene, vitamin C and vitamin E. Since genetic deficiency in the detoxifying enzyme glutathione S-transferase M1 (GSTM1) has been associated with increased risk of lung cancer, GSTM1 genotype was also determined. Analysis of PAH-DNA adducts by competitive enzyme-linked immunosorbent assay (ELISA) indicated that 70% of the subjects had detectable adducts, with a mean of 4.38 adducts/10(8) nucleotides (range 1.00-24.1/10(8)). Pearson's method was utilized to determine whether any associations existed between the various host variables and PAH-DNA adducts. Previously, no significant associations were found between PAH-DNA adducts and cigarettes smoked/day, pack-years, daily/lifetime tar exposures or plasma cotinine levels (Santella et al., Carcinogenesis, 13, 2041-2045, 1992). PAH-DNA adducts were inversely associated with serum cholesterol-adjusted vitamin E levels (r = -0.25, P less than or equal to 0.05) and with smoking-adjusted vitamin C serum levels (r = -0.22, P less than or equal to 0.09). Stratification by GSTM1 genotype indicated that these associations were limited to subjects with the null genotype. The relationship between adducts and serum cholesterol-adjusted vitamin E was significant in those of the null genotype (r = -0.38, P less than or equal to 0.04), but not in those with the gene present (r = -0.12, P = 0.5). Similarly, for smoking-adjusted vitamin C, the relationship with adducts was stronger in subjects with the null genotype (r = -0.35, P less than or equal to 0.06) than in those with GSTM1 present (r = -0.05, P = 0.77). These results are consistent with findings of prior epidemiological studies identifying significant inverse associations between anti-oxidant micronutrient status or GSTM1 genotype and the incidence of lung cancer. Additional studies should be conducted to confirm a possible role for vitamin E in PAH-DNA adduct formation and to explore further the possible roles of vitamin A, beta-carotene and vitamin C in modulating adduct formation and lung cancer risk. C1 COLUMBIA PRESBYTERIAN MED CTR,CTR CANC,DIV ENVIRONM SCI,NEW YORK,NY 10032. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. COLUMBIA UNIV,SCH PUBL HLTH,NEW YORK,NY 10032. NIEHS,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA 21111] NR 65 TC 90 Z9 90 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1994 VL 15 IS 11 BP 2449 EP 2454 DI 10.1093/carcin/15.11.2449 PG 6 WC Oncology SC Oncology GA PT041 UT WOS:A1994PT04100007 PM 7955090 ER PT J AU SHI, XL MAO, Y KNAPTON, AD DING, M ROJANASAKUL, Y GANNETT, PM DALAL, N LIU, KJ AF SHI, XL MAO, Y KNAPTON, AD DING, M ROJANASAKUL, Y GANNETT, PM DALAL, N LIU, KJ TI REACTION OF CR(VI) WITH ASCORBATE AND HYDROGEN-PEROXIDE GENERATES HYDROXYL RADICALS AND CAUSES DNA-DAMAGE - ROLE OF A CR(IV)-MEDIATED FENTON-LIKE REACTION SO CARCINOGENESIS LA English DT Article ID CARCINOGEN CHROMATE; GLUTATHIONE-REDUCTASE; METAL CARCINOGENESIS; CHROMIUM(V); COMPLEXES; MECHANISM AB Incubation of Cr(VI) with ascorbate generated Cr(V), Cr(IV) and ascorbate-derived carbon-centered alkyl radicals, as well as formyl radicals. H2O2 caused generation of hydroxyl radicals ((OH)-O-.) and much higher levels of Cr(V), showing that (OH)-O-. can be generated via a Cr(IV)-mediated Fenton-like reaction (Cr(IV) + H2O2-->Cr(V) + (OH)-O-. + OH-). 1,10-Phenanthroline and deferoxamine inhibited the formation of both (OH)-O-. and Cr(V) from the reaction of Cr(VI) with ascorbate in the presence of H2O2. Electrophoretic assays showed that ascorbate-derived free radicals caused DNA double-strand breaks. (OH)-O-. radicals generated by Cr(V)- and Cr(IV)-mediated Fenton-like reactions also caused DNA double-strand breaks. HPLC measurements showed that .H-O radicals generated by Cr(IV) and Cr(V) from H2O2 caused 2'-deoxyguanine hydroxylation to form 8-hydroxy-2'-deoxyguanine. C1 DARTMOUTH COLL,DEPT RADIOL,HANOVER,NH 03755. NCI,EXPTL PATHOL LAB,BETHESDA,MD 20892. NCI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. W VIRGINIA UNIV,DEPT BASIC PHARMACEUT SCI,MORGANTOWN,WV 26506. W VIRGINIA UNIV,DEPT CHEM,MORGANTOWN,WV 26506. RI Shi, Xianglin/B-8588-2012; Gannett, Peter/J-3347-2015; OI Gannett, Peter/0000-0002-7859-5468; Rojanasakul, Yon/0000-0002-8839-6462 NR 25 TC 149 Z9 152 U1 1 U2 6 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1994 VL 15 IS 11 BP 2475 EP 2478 DI 10.1093/carcin/15.11.2475 PG 4 WC Oncology SC Oncology GA PT041 UT WOS:A1994PT04100011 PM 7955094 ER PT J AU RUSSO, P CIMOLI, G VALENTI, M DESESSA, F PARODI, S POMMIER, Y AF RUSSO, P CIMOLI, G VALENTI, M DESESSA, F PARODI, S POMMIER, Y TI INDUCTION OF DNA DOUBLE-STRAND BREAKS BY 8-METHOXYCAFFEINE - CELL-CYCLE DEPENDENCE AND COMPARISON WITH TOPOISOMERASE-II INHIBITORS SO CARCINOGENESIS LA English DT Article ID ALKALINE ELUTION; HUMAN-LYMPHOCYTES; ANTITUMOR DRUGS; CYTO-TOXICITY; L1210 CELLS; LEUKEMIA; EXPRESSION; RESISTANCE; CAFFEINE; NUCLEI AB We have studied the ability of 8-methoxycaffeine (8-MOC)-one of the most effective caffeine derivatives in inducing chromosomal aberrations-to induce DNA double strand breaks (DSB) in purified human T lymphocytes during the cell cycle. Etoposide- or ellipticine-mediated DNA break frequency was used as a parameter of topoisomerase II activity. DNA-DSB induced by either 8-MOC or VP16 or ellipticine rose co-ordinately with the level of DNA topoisomerase II and with the onset of DNA replication. At concentrations between 10 and 50 mu M 8-MOC was similar to 75% as active in terms of DSB as VP16 and ellipticine. By contrast with VP16 and ellipticine, 8-MOC was not cytotoxic. In conclusion, our data suggest that 8-MOC is an agent that efficiently induces DNA-DSB at non-toxic concentrations, and without direct inhibition of topoisomerase II. C1 NCI,DEPT MOLEC PHARMACOL,DNA TOPOL SECT,BETHESDA,MD 20892. UNITA SANIT LOCALE GENOVA 3,DEPT BONE SURG,I-16036 GENOA,ITALY. RP RUSSO, P (reprint author), IST NAZL RIC CANC,DEPT CHEM CARCINOGENESIS,I-16132 GENOA,ITALY. NR 27 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1994 VL 15 IS 11 BP 2491 EP 2496 DI 10.1093/carcin/15.11.2491 PG 6 WC Oncology SC Oncology GA PT041 UT WOS:A1994PT04100014 PM 7955097 ER PT J AU SCHRENK, D GANT, TW MICHALKE, A ORZECHOWSKI, A SILVERMAN, JA BATTULA, N THORGEIRSSON, SS AF SCHRENK, D GANT, TW MICHALKE, A ORZECHOWSKI, A SILVERMAN, JA BATTULA, N THORGEIRSSON, SS TI METABOLIC-ACTIVATION OF 2-ACETYLAMINOFLUORENE IS REQUIRED FOR INDUCTION OF MULTIDRUG-RESISTANCE GENE-EXPRESSION IN RAT-LIVER CELLS SO CARCINOGENESIS LA English DT Article ID P-GLYCOPROTEIN; HEPATOCYTE CULTURES; HUMAN-TISSUES; FAMILY; 3-METHYLCHOLANTHRENE; CYTOCHROME-P-450; TRANSFERASES; CARCINOGENS; CHEMICALS; MEMBERS AB P-Glycoprotein the multidrug resistance (mdr) efflux transporter is encoded by class 1 mdr genes (mdr1) in humans and rodent species. In rat liver and in rat hepatocytes in primary culture, expression of mdr1 genes can be induced with the carcinogenic aromatic amine 2-acetylaminofluorene (2-AAF). As a consequence, increased P-glycoprotein levels led to an accelerated efflux of vinblastine from the hepatocytes and to resistance towards vinblastine-mediated cytotoxicity. N-Hydroxylation, an obligatory initial step in the activation of 2-AAF into electrophilic DNA-binding metabolites is catalyzed predominantly by cytochrome P450 (CYP)1A2, an isozyme present in normal rat liver. In rat hepatocytes in primary culture, mdr1 induction with 2-AAF could be inhibited by addition of the CYP1A-inhibitor alpha-naphthoflavone, indicating the requirement for metabolic conversion of 2-AAF to act as an inducer of mdr1 gene expression. Both N-hydroxy-2-AAF and the mutagenic 2-AAF derivative N-acetoxy-2-AAF (AAAF) were more potent than 2-AAF as mdr1 inducers. mdr1 induction also decreased when deacetylation of AAAF, which strongly accelerates its conversion into a mutagen, was inhibited with paraoxon. Furthermore, rat liver epithelial cells stably transfected with mouse CYP1A2 showed inducibility of mdr1 gene expression with 2-AAF, whereas the parental cell line, which is devoid of CYP1A2 activity, did not. These findings indicate that electrophilic metabolites formed during 2-AAF or AAAF metabolism are responsible for mdr1 induction in rat hepatocytes. The increased mdr1 gene expression mag reflect an adaptive cellular response to electrophiles which includes enhanced synthesis of P-glycoprotein aimed to protect the cell from further damage. C1 MRC,TOXICOL UNIT,LEICESTER,ENGLAND. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. US FDA,ROCKVILLE,MD 20857. RP SCHRENK, D (reprint author), UNIV TUBINGEN,INST TOXICOL,D-72074 TUBINGEN,GERMANY. NR 46 TC 44 Z9 44 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1994 VL 15 IS 11 BP 2541 EP 2546 DI 10.1093/carcin/15.11.2541 PG 6 WC Oncology SC Oncology GA PT041 UT WOS:A1994PT04100021 PM 7955103 ER PT J AU HUITFELDT, HS BELAND, FA FULLERTON, NF POIRIER, MC AF HUITFELDT, HS BELAND, FA FULLERTON, NF POIRIER, MC TI IMMUNOHISTOCHEMICAL AND MICROFLUOROMETRIC DETERMINATION OF HEPATIC DNA ADDUCT REMOVAL IN RATS FED 2-ACETYLAMINOFLUORENE SO CARCINOGENESIS LA English DT Article ID LIVER-CELL POPULATIONS; CHEMICAL CARCINOGENESIS; B6C3F1 MICE; REPAIR; N-HYDROXY-2-ACETYLAMINOFLUORENE; PROLIFERATION; INITIATION; BINDING AB Biphasic removal of DNA adducts has previously been demonstrated by radioimmunoassay in whole liver DNA from rats chronically fed 2-acetylaminofluorene for 28 days. In the present study, removal of N-(deoxyguanosin-8-yl)-2-aminofluorene was observed in situ by microfluorometry. Frozen liver sections from animals fed 0.02% 2-acetylaminofluorene for 28 days, followed by a control diet for 3, 7, 14, 21 and 28 days, were examined immunohistochemically for localization of N-(deoxyguanosin-8-yl)-2-aminofluorene with fluorescein-conjugated secondary antiserum. In addition, bile ducts and oval cells were stained with antibodies to keratins using Texas red-labelled indirect immunofluorescence. Hoechst dye was used to identify DNA in nuclei. During the 28 days on the control diet, after 28 days of feeding 2-acetylaminofluorene, the DNA adduct concentrations of parenchymal liver cells were reduced by 85%, as compared to animals fed only the carcinogen for 28 days. Periportal hepatocytes exhibited biphasic (fast and slow) adduct removal. Only fast adduct removal was demonstrated in midzonal and centrilobular hepatocytes, since the adduct levels were below the detectable range in these regions after 7 days on the control diet. After 28 days on the control diet, N-(deoxyguanosin-8-yl)-2-aminofluorene was detected in similar to 50% of periportal hepatocytes. These results are compatible with the previously observed biphasic removal profile determined by radioimmunoassay of whole liver DNA adducts and indicate that periportal hepatocytes remove adducts from two distinct genomic compartments. C1 NATL INST PUBL HLTH,DEPT ENVIRONM MED,N-0462 OSLO 4,NORWAY. NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP HUITFELDT, HS (reprint author), UNIV OSLO,NATL HOSP,RIKSHOSP,IMMUNOHISTOCHEM & IMMUNOPATHOL LAB,N-0027 OSLO 1,NORWAY. NR 24 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1994 VL 15 IS 11 BP 2599 EP 2603 DI 10.1093/carcin/15.11.2599 PG 5 WC Oncology SC Oncology GA PT041 UT WOS:A1994PT04100030 PM 7955112 ER PT J AU SIPE, HJ JORDAN, SJ HANNA, PM MASON, RP AF SIPE, HJ JORDAN, SJ HANNA, PM MASON, RP TI THE METABOLISM OF 17-BETA-ESTRADIOL BY LACTOPEROXIDASE - A POSSIBLE SOURCE OF OXIDATIVE STRESS IN BREAST-CANCER SO CARCINOGENESIS LA English DT Article ID ELECTRON-SPIN-RESONANCE; PEROXIDASE-MEDIATED OXIDATION; HORSERADISH-PEROXIDASE; REDUCED GLUTATHIONE; SYRIAN-HAMSTERS; ESTROGEN ACTION; RADICALS; DNA; SUPEROXIDE; OXYGEN AB Electron spin resonance (ESR) spectroscopy and oxygen consumption measurements using a Clark-type oxygen electrode have been used to study the metabolism of the estrogen 17 beta-estradiol by lactoperoxidase. Evidence for a one-electron oxidation of estradiol to its reactive phenoxyl radical intermediate is presented. The phenoxyl radical metabolite abstracts hydrogen from reduced glutathione generating the glutathione thiyl radical, which is spin trapped by 5,5-dimethy1-1-pyrroline N-oxide (DMPO) and subsequently detected by ESR spectroscopy. In the absence of DMPO, molecular oxygen is consumed by a sequence of reactions initiated by the glutathione thiyl radical. Similarly, the estradiol phenoxyl radical abstracts hydrogen from reduced beta-nicotinamide-adenine dinucleotide (NADH) to generate the NAD radical. The NAD radical is not spin trapped by DMPO, but instead reduces molecular oxygen to the superoxide radical, which is then spin-trapped by DMPO. The superoxide generated may either spontaneously dismutate to form hydrogen peroxide or react with another NADH to form NAD, thus propagating a chain reaction leading to oxygen consumption and hydrogen peroxide accumulation. Ascorbate inhibits oxygen consumption when estradiol is metabolized in the presence of either glutathione or NADH by reducing radical intermediates back to their parent molecules and forming the relatively stable ascorbate radical. These results demonstrate that the futile metabolism of micromolar quantities of estradiol catalyzes the oxidation of much greater concentrations of biochemical reducing cofactors, such as glutathione and NADH, with hydrogen peroxide produced as a consequence. The accumulation of intracellular hydrogen peroxide could explain the hydroxyl radical-induced DNA base lesions recently reported for female breast cancer tissue. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. HAMPDEN SYDNEY COLL,DEPT CHEM,HAMPDEN SYDNEY,VA 23943. NR 43 TC 80 Z9 81 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1994 VL 15 IS 11 BP 2637 EP 2643 DI 10.1093/carcin/15.11.2637 PG 7 WC Oncology SC Oncology GA PT041 UT WOS:A1994PT04100036 PM 7955118 ER PT J AU GOODROW, TL NICHOLS, WW STORER, RD ANDERSON, MW MARONPOT, RR AF GOODROW, TL NICHOLS, WW STORER, RD ANDERSON, MW MARONPOT, RR TI ACTIVATION OF H-RAS IS PREVALENT IN 1,3-BUTADIENE-INDUCED AND SPONTANEOUSLY OCCURRING MURINE HARDERIAN-GLAND TUMORS SO CARCINOGENESIS LA English DT Note ID TRANSGENIC MICE; INHALATION TOXICITY; CARCINOGENICITY; GENE; MUTATIONS; ONCOGENES; EXPOSURE; F1-MICE; TISSUES; RATS AB Treatment of B6C3F(1) mice with concentrations of 62.5-625 p.p.m. 1,3-butadiene by inhalation for up to 2 years causes a significantly increased incidence of Harderian gland (HG) neoplasms over untreated controls (Melnick,R., Huff, J., Chou, B.J. and Miller, R.A. Cancer Res., 50, 6592-6599, 1990). Since a specific K-r as mutation (codon 13 GGC-->CGC) had previously been described in lung and liver tumors from 1,3-butadiene-treated B6C3F(1) mice, we analyzed 23 adenomas and six adenocarcinomas of the HG from mice exposed to 1,3-butadiene for this mutation and mutations in the H-ms gene. We also examined ras activation in 16 spontaneously occurring HG adenomas and one adenocarcinoma. DNA samples were prepared from paraffin-embedded tissues and analyzed by PCR followed by direct sequencing methods. Only one 1,3-butadiene-induced HG tumor contained the K-ras codon 13 mutation previously detected in lung and liver tumors. However, 16/29 HG tumors from the treated B6C3F(1) mice contained H-ms codon 61 mutations. The mutations detected were: 12 CAA-->CGA transitions, two CAA-->CTA and two CAA-->AAA transversions. Eleven of 17 spontaneous HG tumors contained mutations in H-ras codon 61: five CAA-->CGA transitions, two CAA-->CTA transversions and four CAA-->AAA transversions. While the spectrum of ras mutations did not differ between the spontaneously occurring and chemically induced tumors, these data indicate that activation of H-ras contributes to the process of HG tumorigenesis in both groups of these neoplasms. C1 MERCK SHARP & DOHME LTD,RES LABS,W POINT,PA 19486. NIEHS,RES TRIANGLE PK,NC 27709. ST MARYS HOSP,CANC RES INST,GRAND JCT,CO 81501. RP GOODROW, TL (reprint author), FOX CHASE CANC CTR,PHILADELPHIA,PA 19090, USA. NR 22 TC 21 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1994 VL 15 IS 11 BP 2665 EP 2667 DI 10.1093/carcin/15.11.2665 PG 3 WC Oncology SC Oncology GA PT041 UT WOS:A1994PT04100042 PM 7955123 ER PT J AU WIGGERT, B VANVEEN, T KUTTY, G LEE, L NICKERSON, J SI, JS NILSSON, SEG CHADER, GJ NARFSTROM, K AF WIGGERT, B VANVEEN, T KUTTY, G LEE, L NICKERSON, J SI, JS NILSSON, SEG CHADER, GJ NARFSTROM, K TI AN EARLY DECREASE IN INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN GENE EXPRESSION IN ABYSSINIAN CATS HOMOZYGOUS FOR HEREDITARY ROD-CONE DEGENERATION SO CELL AND TISSUE RESEARCH LA English DT Article DE GENE EXPRESSION; HEREDITARY RETINAL DEGENERATION; INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN (IRBP); ROD-CONE DEGENERATION; OPSIN; CAT, ABYSSINIAN ID MESSENGER-RNA; FATTY-ACIDS; IRBP; ATROPHY; RHODOPSIN; SINGLE; RD AB Levels of interphotoreceptor retinoid-binding protein (IRBP) protein and message in retinas of Abyssinian cats homozygous for progressive rod-cone degeneration were determined at early ages, well before the onset of clinical retinal degeneration. IRBP gene expression was assessed by immunochemical quantitation of IRBP protein, and by Northern blotting and slot-blotting of total RNA using a human IRBP cDNA probe. Morphology was assessed by electron microscopy and immunocytochemistry. Levels of both IRBP protein and message in affected Abyssinian cat retinas were significantly reduced below normal as early as 4 weeks of age at the earliest stage of retinal disorientation. Opsin mRNA was more abundant in affected Abyssininian cat retinas than in control retinas. This was at least 1 year before the onset of clinical symptoms. The reduction in IRBP gene expression to levels significantly below normal well before the onset of retinal degeneration in affected Abyssinian cat retinas indicates that this represents a primary defect or at least an early problem that could itself cause adverse effects. C1 SWEDISH UNIV AGR SCI,DEPT MED & SURG,UPPSALA,SWEDEN. GOTHENBURG UNIV,DEPT ZOOL,S-40031 GOTHENBURG,SWEDEN. EMORY UNIV,DEPT OPHTHALMOL,ATLANTA,GA 30322. LINKOPING UNIV,DEPT OPHTHALMOL,LINKOPING,SWEDEN. RP WIGGERT, B (reprint author), NEI,BLDG 6,ROOM 338,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD NOV PY 1994 VL 278 IS 2 BP 291 EP 298 DI 10.1007/BF00414173 PG 8 WC Cell Biology SC Cell Biology GA PM034 UT WOS:A1994PM03400013 PM 8001085 ER PT J AU KAWAMURA, M WHEELER, CJ NOTKINS, AL BICHTHUY, LT AF KAWAMURA, M WHEELER, CJ NOTKINS, AL BICHTHUY, LT TI MODULATION OF THE EXPRESSION OF CD5 ANTIGEN ON THE SURFACE OF HUMAN PERIPHERAL B-LYMPHOCYTES SO CELLULAR IMMUNOLOGY LA English DT Article ID GENE-EXPRESSION; CELL LINEAGES; IMMUNOGLOBULIN; LEUKEMIA; MATURATION; AUTOIMMUNE; ACTIVATION; INDUCTION; ORIGIN; LEU-1 AB In this study, we investigated the expression of CD5 molecules on the surface of mature human peripheral B lymphocytes. Human CD5(+) B cells were isolated from tonsils and peripheral blood. Their terminal differentiation into plasma cells was induced with IL-2. In the presence of this lymphokine, a subset of CD5(+) B cells ceased to express CD5 proteins on their surface. When CD5(+) B cells and non-B cells were removed from the suspension, CD5 antigens were spontaneously reexpressed on the surface of CD5(-) B cells. This suggests that the CD5(-) phenotype of a subset of B cells in these suspensions resulted from pressure(s) exerted on them by the other cellular components of the suspensions. B cells which have reexpressed membrane CD5 in the absence of CD5(+) B cells and non-B cells retained their ability to reprogress to CD5(-) phenotype and to undergo terminal differentiation into plasma cells when stimulated with IL-2. A short exposure (4 hr) of CD5(-) B cells to 5 nM IL-2 resulted in the loss of their capability to spontaneously reexpress surface CD5 in the absence of other lymphoid cells. Taken together, these data suggest that the expression of CD5 antigens on B cell membrane is governed by a network-type balance between all cellular compartments within the suspension. Fluctuations of this equilibrium results in the shuttling of B cells between CD5(+) and CD5(-) phenotypes until they become irreversibly engaged in the terminal differentiation pathway. The interconversion CD5(+) <-> CD5(-) on B cell membrane does not argue for CD5 molecule as the marker of a distinct B cell lineage. (C) 1994 Academic Press, Inc. C1 NIDR, ORAL MED LAB, BETHESDA, MD 20892 USA. NR 31 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV PY 1994 VL 159 IS 1 BP 61 EP 76 DI 10.1006/cimm.1994.1295 PG 16 WC Cell Biology; Immunology SC Cell Biology; Immunology GA PP995 UT WOS:A1994PP99500006 PM 7525082 ER PT J AU KOKKINAKIS, DM MOSCHEL, RC PEGG, AE DOLAN, ME SCHOLD, SC AF KOKKINAKIS, DM MOSCHEL, RC PEGG, AE DOLAN, ME SCHOLD, SC TI METABOLISM AND DISPOSITION OF O-6-BENZYL-2'-DEOXYGUANOSINE IN SPRAGUE-DAWLEY RATS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID AGENT 6-METHOXYPURINE ARABINOSIDE; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; HUMAN ERYTHROCYTES; CYTO-TOXICITY; DNA; CELLS; O-6-METHYLGUANINE; METHYLTRANSFERASE; O6-METHYLGUANINE; TRANSPORT AB O-6-Benzyl-2'-deoxyguanosine is a potential antitumor drug modulator that is intended to reduce or eliminate O-6-alkylguanine-DNA alkyltransferase activity in tumors prior to treatment with genotoxic chemotherapeutic alkylating agents. The rationale for using this compound instead of the more active O-6-benzylguanine and its substituted benzyl derivatives at the benzyl ring is its greater solubility in aqueous media and potential pharmacologic advantage. Metabolism and disposition of O-6-benzyl-2'-deoxyguanosine was determined in adult male Sprague-Dawley rats following an ip injection of 100 mg/kg. Under these conditions, the compound was partially metabolized to yield a glucuronic acid conjugate, which was secreted exclusively in the bile. Removal of the 2'-deoxyribose or the benzyl group to yield O-6-benzylguanine and 2'-deoxyguanosine, respectively, occurred to a lesser extent. Metabolism accounted for the clearance of at least 58% of the total dose and took place primarily in the liver. Direct excretion of unchanged drug, mainly in urine, accounted for the remainder of the dose. Analysis of venous blood showed the presence of O-6-benzyl-2'-deoxyguanosine and O-6-benzylguanine at concentrations which are considered to be effective in depleting alkyltransferase activity. Levels of the nucleoside reached a maximum of 45 mu M at 2 h, while those of O-6-benzylguanine peaked to 20 mu M at 4 h and remained at that level for at least 4 more hours. Transport of O-6-benzyl-2'-deoxyguanosine in C6 glioma cells increased linearly with the extracellular concentration of the drug up to 600 mu M. Intracellular levels of the drug reached 1.2 pmol per mu M of extracellular compound per 10(6) cells as soon as 30 s after exposure and remained as high for at least 1 h. Such levels indicate that entrapment of the nucleoside inside cells by either phosphorylation or other means is probably not an important feature for this drug. The extensive glucuronidation of O-6-benzyl-2'-deoxyguanosine may result in the inactivation of the drug as an alkyltransferase inhibitor, thus protecting the intestinal epithelium from being sensitized to alkylating agents. However, hydrolysis of the conjugate by bacterial beta-glucuronidases could restore the inhibitory effect of the drug in the colon, which could have pharmacologic implications in the treatment of colon cancers. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT CELL & MOLEC PHYSIOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PHARMACOL,HERSHEY,PA 17033. UNIV CHICAGO,MED CTR,DIV HEMATOL ONCOL,CHICAGO,IL 60637. RP KOKKINAKIS, DM (reprint author), UNIV TEXAS,SW MED CTR,DEPT NEUROL,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. FU NCI NIH HHS [N01-CA74101, CA57725, CA47228] NR 40 TC 8 Z9 8 U1 2 U2 2 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 NOV-DEC PY 1994 VL 7 IS 6 BP 762 EP 769 DI 10.1021/tx00042a008 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA PT194 UT WOS:A1994PT19400008 PM 7696530 ER PT J AU KADIISKA, MB XIANG, QH MASON, RP AF KADIISKA, MB XIANG, QH MASON, RP TI IN-VIVO FREE-RADICAL GENERATION BY CHROMIUM(VI) - AN ELECTRON-SPIN-RESONANCE SPIN-TRAPPING INVESTIGATION SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SINGLE-STRAND BREAKS; HEXAVALENT CHROMIUM; HYDROGEN-PEROXIDE; LIPID-PEROXIDATION; DNA LESIONS; GLUTATHIONE-REDUCTASE; SODIUM CHROMATE(VI); CARCINOGEN CHROMATE; RAT-KIDNEY; CELL-LINES AB Although studies in chemical and biological systems have demonstrated that free radical formation is mediated by Cr(VI), no ESR evidence for the generation of free radicals in vivo has been reported. We have employed an ESR spin-trapping technique to detect an adduct of the spin trap alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN) in the bile of animals given an intragastric dose of potassium dichromate. In this study, we provide evidence for in vivo radical generation resulting from Cr(VI)-poisoned rats. Upon the administration of Cr(VI) and 4-POBN, the ESR spectrum of the radical adducts present in the bile exhibited hyperfine coupling constants a(N) = 15.71 G and a(beta)(H) = 2.90 G. We suggest that the radical responsible for this 4-POBN adduct is carbon-centered and derived from endogenous lipids. The radical adducts detected in the bile from Cr(VI)-treated rats are proposed to be formed and trapped in the liver and excreted into bile. This is the first report of electron spin resonance evidence for the in vivo generation of free radicals by Cr(VI). C1 NIEHS,LAB MOLEC BIOPHYS,RES TRIANGLE PK,NC 27709. BULGARIAN ACAD SCI,INST PHYSIOL,BU-1113 SOFIA,BULGARIA. HUMAN MED UNIV CHANGSHA,FAC PREVENT MED,CHANGSHA 410078,PEOPLES R CHINA. NR 59 TC 33 Z9 34 U1 0 U2 0 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 NOV-DEC PY 1994 VL 7 IS 6 BP 800 EP 805 DI 10.1021/tx00042a013 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA PT194 UT WOS:A1994PT19400013 PM 7696535 ER PT J AU SUGIYAMA, K WOODS, A COTTER, RJ HIGHET, RJ DARBYSHIRE, JF OSAWA, Y GILLETTE, JR AF SUGIYAMA, K WOODS, A COTTER, RJ HIGHET, RJ DARBYSHIRE, JF OSAWA, Y GILLETTE, JR TI INACTIVATION OF HORSERADISH-PEROXIDASE BY 3,5-DICARBETHOXY-2,6-DIMETHYL-4-ETHYL-1,4-DIHYDROPYRIDINE SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CATALYTIC MECHANISM; SUBSTRATE OXIDATION; HEME EDGE; CYTOCHROME-P-450; ALKYLHYDRAZINES AB In the presence of H2O2, horseradish peroxidase (HRP) catalyzes the one-electron oxidation of a porphyrinogenic agent, 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine (DDEP), leading to formation of an ethyl radical, inactivation of the enzyme, and formation of an altered heme product. The loss of heme during the inactivation of HRP was dependent on the duration of exposure to DDEP as well as the concentration of H2O2 and DDEP, The pseudo first order rate constant for the oxidation of DDEP by compound I of HRP at pH 7.4 was 0.07 min(-1), and the maximal extent of heme loss was 35%. The altered heme product, which was isolated by reverse phase HPLC, was characterized by the use of mass and H-1 NMR spectrometry as a substitution product of a C2H4OH moiety for a meso proton of the prosthetic heme [meso-(hydroxyethyl)heme]. The source of the oxygen in the C2H4OH moiety appeared not to be H2O2 or H2O as O-18 was not incorporated in the heme adduct when (H2O2)-O-18 or (H2O)-O-18 was used. The DDEP-mediated reaction did not form the expected delta-meso-ethylheme adduct analogous to the ethyl radical-mediated inactivation of HRP by ethylhydrazine (EH) [Ator et al. (1987) J. Biol. Chem. 262, 14954-14960]. However, we have found that meso-(hydroxyethyl)heme was formed in the EH-mediated reaction, albeit in apparently lower amounts than delta-meso-ethylheme. Perhaps the proximity of the heme to the ethyl radical may play a role in determining the nature of the heme products formed. C1 NHLBI, CHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. NHLBI, BIOPHYS CHEM LAB, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, SCH MED, MIDDLE ATLANTIC MASS SPECT LAB, BALTIMORE, MD 21205 USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV-DEC PY 1994 VL 7 IS 6 BP 843 EP 849 DI 10.1021/tx00042a019 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA PT194 UT WOS:A1994PT19400019 PM 7696541 ER PT J AU MOTTEN, AG SIK, RH CHIGNELL, CF HAYDEN, PJ AF MOTTEN, AG SIK, RH CHIGNELL, CF HAYDEN, PJ TI AN EPR STUDY OF FREE-RADICALS FORMED BY ANTIPSORIATIC AND TUMOR-PROMOTING 9-ANTHRONES IN NONPOLAR-SOLVENTS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SPIN-RESONANCE SPECTRUM; DITHRANOL ANTHRALIN; 10-ACYL ANALOGS; SENCAR MICE; SKIN; 1,8-DIHYDROXY-9-ANTHRONE; IRRITATION; GENERATION AB Certain 9-anthrone derivatives are useful in treating psoriasis and are also known to be tumor promoters in mouse skin. Their therapeutic use is accompanied by side effects of severe skin inflammation, irritation, and staining. The precise biochemical mechanisms of therapeutic action, tumor promotion, and side effects are presently uncertain, although the corresponding 9-anthron-10-yl radicals have been proposed as important intermediates. In order to gain insight into the possilbe role of anthrone-derived radicals in mediating the biological effects of these compounds, in the present study free radicals from a number of anthrone derivatives were generated by thermolysis in nonpolar solvents. Hyperfine splitting constants (hfsc) of the radicals were determined by electron paramagnetic resonance (EPR) spectroscopy. The experimentally determined hfsc's were also compared with spin densities obtained by molecular calculations (MOPAC 6.0). The experimental and theoretical data were found to be consistent in all cases. The formation of 9-anthron-10-yl radicals appears to be a general phenomenon among 9-anthrones regardless of therapeutic or tumor-promoting effectiveness, although there is a trend toward easier radical formation for the more active componds. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 36 TC 4 Z9 4 U1 0 U2 2 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 NOV-DEC PY 1994 VL 7 IS 6 BP 877 EP 881 DI 10.1021/tx00042a024 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA PT194 UT WOS:A1994PT19400024 PM 7696546 ER PT J AU NAKAJIMA, T ELOVAARA, E GONZALEZ, FJ GELBOIN, HV RAUNIO, H PELKONEN, O VAINIO, H AOYAMA, T AF NAKAJIMA, T ELOVAARA, E GONZALEZ, FJ GELBOIN, HV RAUNIO, H PELKONEN, O VAINIO, H AOYAMA, T TI STYRENE METABOLISM BY CDNA-EXPRESSED HUMAN HEPATIC AND PULMONARY CYTOCHROMES P450 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HUMAN-LIVER; CATALYTIC ACTIVITY; VACCINIA VIRUS; HUMAN-LUNG; RAT-LIVER; MUTAGEN ACTIVATION; MORTALITY; OXIDATION; SEQUENCE; WORKERS AB The rate of formation of styrene glycol from styrene was compared in human, rat, and mouse liver microsomes. At a low styrene concentration (0.085 mM), the rates decreased in the order, mouse (2.43 +/- 0.29 nmol(mg of protein.min)) > rat (1.07 +/- 0.20) > human (0.73 +/- 0.45); at a high concentration (1.85 mM), the order was rat (4.21 +/- 0.72) > mouse (2.72 +/- 0.11) > human (1.91 +/- 0.84). Kinetic analysis indicated the presence of at least two forms of styrene metabolizing cytochrome P450s with different K-m values in human liver microsomes. Styrene was also metabolized in human lung microsomes: the rate of styrene glycol formation was higher in the lung microsomes from smokers than in those from current nonsmokers. The P450 forms responsible for transforming styrene to styrene glycol were determined by analyzing cDNA-expressed individual P450 forms produced in cultured hepatoma G2 cells by recombinant vaccinia viruses. Of the 12 human P450 forms studied, CYP2B6 and CYP2E1 existing in human liver and/or lungs and CYPBF1 in human lungs were the most active in the forming of styrene glycol, followed by CYP1A2 and CYP2C8. Human CYP3A3, CYP3A4, CYP3A5, and CYP4B1 also catalyzed the metabolism but were much less active. CYP2A6, CYP2C9, and CYP2D6 had only a little detectable activity. CYP1A2, CYP2B6, CYP2C8, CYP2E1, and CYP3A4/3A3 were expressed in human liver microsomes, and CYP2C8 was expressed in human lung microsomes, although the expression of CYP2F1 and CYP4B1 could not be investigated. These data indicate that several human hepatic C1 SHINSHU UNIV,SCH MED,DEPT BIOCHEM,MATSUMOTO,NAGANO 390,JAPAN. INST OCCUPAT HLTH,DEPT IND HYG & TOXICOL,SF-00250 HELSINKI,FINLAND. NCI,BETHESDA,MD 20892. UNIV OULU,DEPT PHARMACOL & TOXICOL,SF-90220 OULU,FINLAND. INT AGCY RES CANC,F-69372 LYON,FRANCE. RP NAKAJIMA, T (reprint author), SHINSHU UNIV,SCH MED,DEPT HYG,MATSUMOTO,NAGANO 390,JAPAN. NR 42 TC 100 Z9 102 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 NOV-DEC PY 1994 VL 7 IS 6 BP 891 EP 896 DI 10.1021/tx00042a026 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA PT194 UT WOS:A1994PT19400026 PM 7696548 ER PT J AU OBATA, T SHIBUSAWA, Y ITO, Y AF OBATA, T SHIBUSAWA, Y ITO, Y TI PURIFICATION OF SOLUBLE MONOAMINE-OXIDASE IN RAT-LIVER CYTOSOL BY COUNTERCURRENT CHROMATOGRAPHY SO CHROMATOGRAPHIA LA English DT Note DE COUNTERCURRENT CHROMATOGRAPHY; MONOAMINE OXIDASE (MAO); RAT LIVER CYTOSOL; ENDOGENOUS MAO MODULATOR ID MONO-AMINE OXIDASE; THYROID-HORMONE; INHIBITOR; MODULATORS; URINARY; PLASMA; BRAIN; MAO AB An endogenous monoamine oxidase (MAO) inhibitory modulator and cytosolic MAO coexisting in the rat liver cytosol were fractionated by gel filtration following ultracentrifugation. High molecular weight fractions exhibiting MAO activity were further purified by countercurrent chromatography (CCC). MAO activity, detected using beta-phenylethylamine (beta-PEA) and 5-hydroxytryptamine (5-HT) as substrates, was eluted in two separate peaks (fractions M-1, M-2) from the CCC column. Both the M-1 and M-2 fractions displayed high enzymatic activities on beta-PEA whereas the M-2 fraction showed a very low MAO activity on 5-HT. This result might indicate a lack of type A MAO in the M-2 fraction due to the selective separation of endogenous MAO inhibitor. We may conclude that ''endogenous MAO modulator'' is present in rat liver cytosol. C1 TOKYO COLL PHARM,DEPT ANALYT CHEM,HACHIOJI,TOKYO 19203,JAPAN. OITA MED UNIV,DEPT PHARMACOL,OITA 87955,JAPAN. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 17 TC 1 Z9 1 U1 0 U2 0 PU FRIEDR VIEWEG SOHN VERLAG GMBH PI WIESBADEN 1 PA PO BOX 5829, W-6200 WIESBADEN 1, GERMANY SN 0009-5893 J9 CHROMATOGRAPHIA JI Chromatographia PD NOV PY 1994 VL 39 IS 9-10 BP 624 EP 626 DI 10.1007/BF02268291 PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PW372 UT WOS:A1994PW37200019 ER PT J AU LENFANT, C AF LENFANT, C TI RESEARCH NEEDS AND OPPORTUNITIES - MAINTAINING THE MOMENTUM SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV PY 1994 VL 90 IS 5 BP 2192 EP 2193 PN 1 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PR286 UT WOS:A1994PR28600002 PM 7955172 ER PT J AU KANNAM, JP LEVY, D LARSON, M WILSON, PWF AF KANNAM, JP LEVY, D LARSON, M WILSON, PWF TI SHORT STATURE AND RISK FOR MORTALITY AND CARDIOVASCULAR-DISEASE EVENTS - THE FRAMINGHAM HEART-STUDY SO CIRCULATION LA English DT Article DE HEIGHT; MORTALITY; CARDIOVASCULAR DISEASE; INFARCTION ID HEIGHT; POPULATION AB Background Several studies have observed an inverse association between height and risk for coronary disease, but it is unclear whether other traditional coronary disease risk factors may have confounded this association. We examined the original Framingham Heart Study cohort to determine whether short stature is associated with all-cause mortality, cardiovascular disease mortality, and myocardial infarction after adjusting for age and other traditional coronary heart disease risk factors. Methods and Results A total of 2019 men and 2585 women were followed up to 35.6 years. Subjects were stratified by sex and divided into quartiles according to height. Risk ratios were calculated from proportional hazards analyses comparing the first, second, and third quartiles of height to the tallest quartile before and after adjusting for age, hypertension, smoking, serum cholesterol, diabetes, relative weight, and alcohol intake. In both sexes, there were significant differences in the unadjusted event rates between the shortest and the tallest quartile for all-cause mortality, cardiovascular mortality, and myocardial infarction. Once the analyses were age adjusted, differences among height quartiles persisted only for risk of myocardial infarction in women. Further adjustment for other clinical variables had little additional impact on the results. Conclusions After considering age and other coronary disease risk factors, short stature was not associated with increased risk for all-cause or cardiovascular mortality in either sex. It was associated with increased risk for myocardial infarction in women but not in men. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. NHLBI,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,DIV EPIDEMIOL & PREVENT MED,BOSTON,MA. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. FU NHLBI NIH HHS [N01-HC-38038] NR 23 TC 68 Z9 70 U1 1 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV PY 1994 VL 90 IS 5 BP 2241 EP 2247 PN 1 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PR286 UT WOS:A1994PR28600012 PM 7955180 ER PT J AU LEAF, A JORGENSEN, MB JACOBS, AK COTE, G SCHOENFELD, DA SCHEER, J WEINER, BH SLACK, JD KELLETT, MA RAIZNER, AE WEBER, PC MAHRER, PR ROSSOUW, JE AF LEAF, A JORGENSEN, MB JACOBS, AK COTE, G SCHOENFELD, DA SCHEER, J WEINER, BH SLACK, JD KELLETT, MA RAIZNER, AE WEBER, PC MAHRER, PR ROSSOUW, JE TI DO FISH OILS PREVENT RESTENOSIS AFTER CORONARY ANGIOPLASTY SO CIRCULATION LA English DT Article DE RESTENOSIS; ANGIOPLASTY; FISH OIL; FATTY ACIDS ID EICOSAPENTAENOIC ACID; GREENLAND ESKIMOS; FATTY-ACIDS; SUPPLEMENTS; DISEASE; TRIAL; DIET; ATHEROSCLEROSIS; THROMBOLYSIS; THROMBOXANE AB Background The omega-3 polyunsaturated fatty acids derived from fish oils have been shown to modulate many factors believed to affect the pathogenesis of atherosclerosis. Because certain features of restenosis following angioplasty mimic some of the early changes of atherogenesis, some researchers have suggested that fish oil might prevent restenosis following angioplasty. We report the effects of omega-3 fatty acids on the rate of restenosis following percutaneous intraluminal coronary angioplasty (PTCA). Methods and Results From August 1989 through September 1992, 551 patients were randomized to start receiving a daily dietary supplement of ten 1.0-g capsules containing 80.6% ethyl esters of omega-3 fatty acids providing 4.1 g eicosapentaenoic acid (EPA) and 2.8 g docosahexaenoic acid (DHA) for 6 months or an equal amount of an ethyl ester of corn oil. Four hundred seventy subjects who were well matched for risk factors completed successful angioplasty of one or multiple lesions in native coronary vessels and constituted the study cohort, of whom 447 were evaluable at 6 months after PTCA. The criteria for restenosis were that the quantitative coronary angiography at 6 months show a >30% increase in narrowing at the stenosis site or loss of at least half of the gain achieved at the time of PTCA and final restenosis with <50% luminal diameter remaining, In 93% of the patients, the end point was determined by angiography and in all except 1% of these by quantitative coronary angiography. Compliance with the fish oil supplement was good as judged by incorporation of EPA and DHA in plasma and red blood cell phospholipids. The restenosis rate among analyzable patients was 46% for corn oil and 52% for fish oil (P=.37). The addition of 200 mg alpha-tocopherol for all subjects during the study had no effect on restenosis rates. Conclusions This was the largest of such trials to date, and a supplement of 8 g/d of omega-3 fatty acids failed to prevent the usual high rate of restenosis after PTCA. No adverse effects were attributable to this large daily supplement of omega-3 fatty acids. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. KAISER PERMANENTE, LOS ANGELES, CA USA. UNIV BOSTON HOSP, MED CTR, BOSTON, MA 02118 USA. MONTREAL HEART INST, MONTREAL H1T 1C8, PQ, CANADA. UNIV MASSACHUSETTS, MED CTR, WORCESTER, MA USA. SMITH & PINKERTON CARDIOL INC, INDIANAPOLIS, IN USA. MAINE MED CTR, PORTLAND, ME 04102 USA. METHODIST HOSP, HOUSTON, TX 77030 USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. UNIV MUNICH, INST PROPHYLAXE & EPIDEMIOL KREISLAUFKRANKHEITEN, MUNICH, GERMANY. NHLBI, LIPID METAB ATHEROGENESIS BRANCH, BETHESDA, MD 20892 USA. FU NHLBI NIH HHS [UO1-HL-40548] NR 34 TC 171 Z9 173 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV PY 1994 VL 90 IS 5 BP 2248 EP 2257 PN 1 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PR286 UT WOS:A1994PR28600013 PM 7955181 ER PT J AU FLEG, JL SCHULMAN, S OCONNOR, F BECKER, LC GERSTENBLITH, G CLULOW, JF RENLUND, DG LAKATTA, EG AF FLEG, JL SCHULMAN, S OCONNOR, F BECKER, LC GERSTENBLITH, G CLULOW, JF RENLUND, DG LAKATTA, EG TI EFFECTS OF ACUTE BETA-ADRENERGIC-RECEPTOR BLOCKADE ON AGE-ASSOCIATED CHANGES IN CARDIOVASCULAR PERFORMANCE DURING DYNAMIC EXERCISE SO CIRCULATION LA English DT Article DE AGING; EXERCISE; HEMODYNAMICS ID PLASMA-CATECHOLAMINES; ADRENOCEPTOR BLOCKADE; UPRIGHT EXERCISE; ADVANCING AGE; HEART-RATE; NORMAL MEN; PROPRANOLOL; DECREASE; ISOPROTERENOL; CONTRACTILE AB The cardiovascular response to beta-adrenergic stimulation is markedly blunted with advancing age, and this blunting may underlie some of the prominent age-associated changes in the hemodynamic profile during dynamic exercise. To examine this hypothesis, we administered the nonselective beta-adrenergic receptor blocker propranolol (0.15 mg/kg IV) to 25 healthy normotensive men ages 28 to 72 years from the Baltimore Longitudinal Study of Aging (BLSA) immediately before maximal upright cycle ergometry with Tc-99m gated cardiac blood pool scintigraphy. Their hemodynamic responses to exercise were compared with those of 70 age-matched healthy unmedicated male BLSA control subjects. The maximal cycle work rate achieved was similar in propranolol-treated men (158+/-32 W) and control subjects (148+/-32 W) and declined similarly with age in both groups. Hemodynamics at seated rest were not age-related in either group; however, propranolol-treated men had lower heart rates (HR), systolic blood pressure (SBP), ejection fraction, and cardiac index than control subjects but higher end-diastolic volume index (EDVI) and end-systolic volume index (ESVI) by covariance analysis. At maximal effort, several striking age-drug interactions were evident: Propranolol caused a greater reduction in HR and greater increases in EDVI and stroke volume index (SVI) in younger than in older men. Hence, at maximal work rate, HR declined less with age in the propranolol group (0.46 versus 1.09 beats per minute per year, P<.05 by covariance analysis); EDVI and SVI decreased with age (0.27 and 0.48 mL/m(2) per year, respectively) after propranolol compared with increases of 0.47 and 0.16 mL/m(2) per year in control subjects, respectively, each P less than or equal to.05 by covariance analysis. The left ventricular contractility index, SBP/ESVI, at exhaustion was reduced by propranolol to a greater extent in younger than older men. Thus, acute beta-adrenergic blockade reverses the age-associated ventricular dilation at end diastole and end systole observed during upright cycle exercise and blunts the decline in maximal HR and myocardial contractility. These data suggest that the age-associated declines in maximal HR and left ventricular contractility during vigorous; exercise are manifestations of reduced beta-adrenergic responsivity with advancing age which is partially offset by exercise-induced ventricular dilation. C1 JOHNS HOPKINS UNIV,SCH MED,DIV CARDIOL,BALTIMORE,MD. RP FLEG, JL (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. FU NIA NIH HHS [N01-AG-4-2109] NR 38 TC 64 Z9 69 U1 5 U2 7 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV PY 1994 VL 90 IS 5 BP 2333 EP 2341 PN 1 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PR286 UT WOS:A1994PR28600023 PM 7955191 ER PT J AU CROWE, JE CHEUNG, PYK WALLACE, EF CHANOCK, RM LARRICK, JW MURPHY, BR FRY, K AF CROWE, JE CHEUNG, PYK WALLACE, EF CHANOCK, RM LARRICK, JW MURPHY, BR FRY, K TI ISOLATION AND CHARACTERIZATION OF A CHIMPANZEE MONOCLONAL-ANTIBODY TO THE G-GLYCOPROTEIN OF HUMAN RESPIRATORY SYNCYTIAL VIRUS SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID F-GLYCOPROTEIN; COTTON RATS; YOUNG-CHILDREN; SUBGROUP-A; INFECTION; NEUTRALIZATION; PURIFICATION; SEQUENCE; PROTEINS; INFANTS AB Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory tract disease in infants and young children. In this study a hybridoma line secreting a chimpanzee monoclonal antibody that neutralizes RSV was isolated. Two chimpanzees were immunized with recombinant vaccinia viruses that express the RSV F or G surface glycoprotein and 1 month later were infected intranasally with the wild-type RSV strain A2. Peripheral blood lymphocytes obtained from the animals were transformed with Epstein-Barr virus, and lymphoblastoid cell lines that secreted anti-RSV antibodies were identified by an RSV antigen-binding enzyme-linked immunosorbent assay. Supernatants from RSV antibody-secreting lymphoblastoid cell lines were tested for in vitro virus neutralization before being fused to the heteromyeloma cell GLI-H7. A chimpanzee antibody [immunoglobulin G3(lambda) subclass] produced from a hybridoma line designated E1.4/2 was shown to bind to the RSV G glycoprotein and neutralize a panel of subgroup A viruses, but not subgroup B viruses, at low (nanomolar) concentrations. Mice passively immunized with this antibody were partially resistant to RSV strain A2 challenge. The usefulness of such antibodies in immunoprophylaxis and immunotherapy of RSV infection is discussed. C1 GENELABS TECHNOL INC,REDWOOD CITY,CA 94063. RP CROWE, JE (reprint author), NIAID,INFECT DIS LAB,RESP VIRUSES SECT,BLDG 7,ROOM 106,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 NR 31 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 1994 VL 1 IS 6 BP 701 EP 706 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PV209 UT WOS:A1994PV20900015 PM 8556524 ER PT J AU GORSE, GJ SCHWARTZ, DH GRAHAM, BS MATTHEWS, TJ STABLEIN, DM FREY, SE BELSHE, RB CLEMENTS, ML WRIGHT, PF EIBL, M FAST, PE AF GORSE, GJ SCHWARTZ, DH GRAHAM, BS MATTHEWS, TJ STABLEIN, DM FREY, SE BELSHE, RB CLEMENTS, ML WRIGHT, PF EIBL, M FAST, PE TI HIV-1 RECOMBINANT GP160 VACCINE GIVEN IN ACCELERATED DOSE SCHEDULES SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE VACCINE; HIV-1 ENVELOPE GLYCOPROTEIN; IMMUNOGENICITY; HUMORAL; IMMUNITY; LYMPHOCYTE PROLIFERATION ID IMMUNODEFICIENCY-VIRUS TYPE-1; LYMPHOCYTE PROLIFERATIVE RESPONSES; MONOCLONAL-ANTIBODY; SCID MICE; INFECTION; IMMUNIZATION; CHIMPANZEES; GP120; IMMUNOGENICITY; PROTECTION AB The purpose of this randomized, double-blind study was to test the safety and immunogenicity of an HIV-1(LAI) recombinant gp160 (rgp160) vaccine in healthy, uninfected volunteers using accelerated dosing schedules. Thirty volunteers were randomly assigned to receive 50-mu g doses of rgp160 in one of two immunization schedules. Group 1 received rgp160 at times 0, 1, 2 and 5 months; and group 2 received rgp160 at times 0, 1, 2, 3 and 4 months. The vaccine was safe and stimulated high levels of HIV-1 envelope-specific binding antibody and T cell memory. There was a trend (P < 0.10) suggesting neutralizing antibodies were better induced by the regimen incorporating a rest period before the final immunization in group 1 volunteers. Both accelerated immunization schedules induced immune responses at levels similar to or better than those achieved by four rgp160 vaccine injections given over 12-18 months in other studies. C1 DEPT VET AFFAIRS MED CTR,ST LOUIS,MO. JOHNS HOPKINS UNIV,CTR IMMUNIZAT RES,BALTIMORE,MD. VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT PAEDIAT,NASHVILLE,TN 37212. DUKE UNIV,SCH MED,DEPT SURG,DURHAM,NC. EMMES CORP,POTOMAC,MD. IMMUNO AG WIEN,VIENNA,AUSTRIA. NIAID,DIV AIDS,VACCINE RES & DEV BRANCH,ROCKVILLE,MD. RP GORSE, GJ (reprint author), ST LOUIS UNIV,SCH MED,DEPT INTERNAL MED,DIV INFECT DIS,3635 VISTA AVE,FDT 8N,POB 15250,ST LOUIS,MO 63110, USA. FU NIAID NIH HHS [N01-AI-05064, N01-AI-45211, N01-AI-05061] NR 26 TC 25 Z9 25 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 1994 VL 98 IS 2 BP 178 EP 184 PG 7 WC Immunology SC Immunology GA PQ006 UT WOS:A1994PQ00600002 PM 7955519 ER PT J AU KROLL, MH ELIN, RJ AF KROLL, MH ELIN, RJ TI INTERFERENCE WITH CLINICAL LABORATORY ANALYSES SO CLINICAL CHEMISTRY LA English DT Review DE VARIATION, SOURCE OF; DRUG METABOLITES; HEMOGLOBIN; BILIRUBIN; LIPEMIA; PARAPROTEINEMIA ID CREATININE CONCENTRATION; JAFFE REACTION; HEMOLYSIS; ASSAYS; SERUM; IMMUNOASSAYS; CHOLESTEROL; MECHANISM; TESTS; DRUGS AB Interference by endogenous and exogenous substances with assays for clinical analytes is a common problem in laboratory medicine. For this review, we defined interference as ''the effect of a substance present in the sample that alters the correct value of the result, usually expressed as concentration or activity, for an analyte.'' There are four major endogenous compounds that consistently interfere with laboratory results: hemoglobin, bilirubin, lipids, and paraproteins. The major exogenous sources of interference are drugs prescribed for the patient; and there are several excellent compendia of the effect of drugs on clinical laboratory tests. We recommend determining whether the interference is dependent or independent of the analyte for the assay. Further, we propose an approach to the identification and resolution of an interference problem for the clinical laboratory and make recommendations to manufacturers. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,CLIN CHEM SERV,BETHESDA,MD 20892. NR 103 TC 125 Z9 132 U1 0 U2 15 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 1994 VL 40 IS 11 BP 1996 EP 2005 PN 1 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PP749 UT WOS:A1994PP74900003 PM 7955368 ER PT J AU SHEARER, GM CLERICI, M AF SHEARER, GM CLERICI, M TI IN-VITRO ANALYSIS OF CELL-MEDIATED-IMMUNITY - CLINICAL RELEVANCE SO CLINICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 17th Annual Arnold O Beckman Conference in Clinical Chemistry on Immune Disorders - The Role of the Laboratory in Clinical Management CY FEB 06-07, 1994 CL HUNTINGTON BEACH, CA DE IMMUNE SYSTEM; T HELPER CELLS; LYMPHOKINES; CYTOKINES; HIV; SYSTEMIC LUPUS ERYTHEMATOSUS; HODGKIN DISEASE ID INFECTED INDIVIDUALS; ZIDOVUDINE THERAPY; HOMOSEXUAL MEN; IN-VITRO; HIV; RESPONSES; CHILDREN; VACCINATION; PATTERNS; PARTNERS AB Cellular immunity, a major component of the immune system, contributes to protection against infections and plays a role in the rejection of foreign allografts. T helper cells and the antigen-presenting cells with which they interact provide important functions for cellular immune responses by generating helper signals via soluble molecules known as lymphokines or cytokines. As described here, in vitro analysis of markers of cellular immune function can be used for clinical diagnosis and assessment of therapeutic efficacy and to elucidate the mechanisms of immune dysregulation. Not all helper signals necessarily have the same augmenting effect, because immunoregulatory cytokines that up-regulate the cellular arm of the immune system can conversely down-regulate the humoral arm, and vice versa. The interplay between cross-regulatory cytokines determines which component of the immune system is dominant and can influence the clinical outcome of immunologically controlled diseases. Given the apparent dramatic effects of these cytokines, assays performed in future clinical laboratories should include profiles of immunoregulatory cytokines. C1 UNIV MILAN,CATTEDRA IMMUNOL,I-20133 MILAN,ITALY. RP SHEARER, GM (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 31 TC 12 Z9 16 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 1994 VL 40 IS 11B BP 2162 EP 2165 PN 2 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PP750 UT WOS:A1994PP75000006 PM 7955403 ER PT J AU KELLNERCOUSIN, K BOULO, V LACROIX, I MIALHE, E MATHIEU, M AF KELLNERCOUSIN, K BOULO, V LACROIX, I MIALHE, E MATHIEU, M TI USE OF MONOCLONAL-ANTIBODIES FOR IDENTIFICATION OF GROWTH-CONTROLLING NEUROPEPTIDES IN THE MUSSEL MYTILUS-EDULIS (MOLLUSCA, BIVALVIA) SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-PHYSIOLOGY LA English DT Article DE MONOCLONAL ANTIBODIES; GROWTH-CONTROLLING NEUROPEPTIDES; MYTILUS EDULIS ID INSULIN-RELATED PEPTIDE; LYMNAEA-STAGNALIS; NERVOUS-SYSTEM; CELLS; IMMUNIZATION; BRAIN AB Monoclonal antibodies were developed against cerebral ganglia (CG) of the mussel Mytilus edulis by the immunization of mice with unpurified homogenates of these organs. Tbe screening protocol of hybridoma was based upon immunohistological observations of cytocentrifugated ganglia cells. A panel of 29 monoclonal antibodies (MABs) specific of CG epitopes was harvested and subsequently used for the immunocytochemical study of CG cells. Several subpopulations of ganglia cells were specifically revealed by MABs. Identification of epitopes involved in growth control was approached via the application of a bioassay allowing the assessment of protein synthesis stimulation. MAB 42 and 46 affected amino acid incorporation induced by CG extract. These results lead to the conclusion that the epitopes recognised by these antibodies are involved in growth control. An immunoenzymatic assay was performed with CG extracts for quantitative analyses of epitopes. C1 UNIV MONTPELLIER 2,IFREMER,DRIM,URM 9947,F-34095 MONTPELLIER 5,FRANCE. NIAID,MALARIA RES LAB,BETHESDA,MD 20892. RP KELLNERCOUSIN, K (reprint author), IBBA,IFREMER,BIOL & BIOTECHNOL MARINES LAB,EQUIPE RECH MARINE,URM 14,ESPLANADE PAIX,F-14032 CAEN,FRANCE. NR 33 TC 2 Z9 2 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0300-9629 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Physiol. PD NOV PY 1994 VL 109 IS 3 BP 689 EP 698 DI 10.1016/0300-9629(94)90211-9 PG 10 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA PR865 UT WOS:A1994PR86500020 PM 8529010 ER PT J AU KAFADAR, K AF KAFADAR, K TI CHOOSING AMONG 2-DIMENSIONAL SMOOTHERS IN PRACTICE SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE MOVING WEIGHTED AVERAGE; LOESS; NONLINEAR SMOOTHERS; MEDIAN POLISH; GEOGRAPHIC ANALYSIS ID LOCALLY WEIGHTED REGRESSION AB Seven smoothers representing two general classes of smoothers are evaluated in terms of their ability to capture patterns and ignore random fluctuations in two-dimensional structures. Two patterns are generated as responses at locations representing the coordinates of 86 counties within 500 miles of San Francisco: a null pattern, having a constant level surface, and a structured pattern, having a ridge, peak, and a depression in the surface. Three levels of Gaussian noise are assessed as typical of the sizes of variation that arise in connection with measurement error models or with disease mortality rates. Two criteria used to evaluate the smoothers suggest that weighted averages (weights inversely proportional to the square of the distance) and a nonlinear smoother proposed by Tukey (headbanging) are likely to be the most successful in practice. C1 NCI,DCPC,BIOMETRY BRANCH,BETHESDA,MD 20892. NR 26 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD NOV PY 1994 VL 18 IS 4 BP 419 EP 439 DI 10.1016/0167-9473(94)90160-0 PG 21 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA PN345 UT WOS:A1994PN34500003 ER PT J AU MAGNO, BV LASA, MSM FREIDLIN, V DATILES, MB AF MAGNO, BV LASA, MSM FREIDLIN, V DATILES, MB TI COMPARISON OF LINEAR, MULTILINEAR AND MASK MICRODENSITOMETRIC ANALYSES OF SCHEIMPFLUG IMAGES OF THE LENS NUCLEUS SO CURRENT EYE RESEARCH LA English DT Article DE LINEAR DENSITOMETRY; MASK DENSITOMETRY; MULTILINEAR DENSITOMETRY; NUCLEAR CATARACTS; SCHEIMPFLUG IMAGES ID CATARACT; CLASSIFICATION; CAMERA AB We wanted to determine the agreement among three methods currently used to measure the average density of the nucleus from a Scheimpflug video image of the lens, namely, the multilinear, linear and mask techniques. Using the NEI Scheimpflug Cataract Imaging System, video images of the lens were obtained from 49 eyes of 31 consecutive patients with predominantly nuclear opacities of varying severities. For each image, 3 separate determinations of the average nuclear density [in optical density units (odu)] were obtained by one analyst sequentially applying each of the three methods. Repeat measurements were obtained by the same analyst one week apart to evaluate reproducibility (using 95% error range) of each of the methods. Pairwise comparisons of the 3 methods were also done. Only the error due to outlining of the nucleus was assessed. Reproducibility of each method was excellent. The 95 % error ranges were +/- 0.015 odu for the linear, +/- 0.013 odu for the multilinear, and +/- 0.017 odu for the mask methods. Very strong linear relationships were observed between the linear and multilinear methods (R(2) = 0.99), between the linear and mask methods (R(2) = 0.97), and between the multilinear and mask methods (R(2) = 0.98). Simple linear regressions calibrating these three methods against each other would facilitate comparison of density measurements using any of these methods for analysis of Scheimpflug images of the lens nucleus. C1 NEI,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD 20892. RP MAGNO, BV (reprint author), NEI,OPHTHALM GENET & CLIN SERV BRANCH,BLDG 10,ROOM 10N226,10 CTR DR MSC 1860,BETHESDA,MD 20892, USA. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 16 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD NOV PY 1994 VL 13 IS 11 BP 825 EP 831 DI 10.3109/02713689409025138 PG 7 WC Ophthalmology SC Ophthalmology GA PQ859 UT WOS:A1994PQ85900007 PM 7851118 ER PT J AU SASAMOTO, Y KOTAKE, S YOSHIKAWA, K WIGGERT, B GERY, I MATSUDA, H AF SASAMOTO, Y KOTAKE, S YOSHIKAWA, K WIGGERT, B GERY, I MATSUDA, H TI INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN-DERIVED PEPTIDE CAN INDUCE EXPERIMENTAL AUTOIMMUNE UVEORETINITIS IN VARIOUS RAT STRAINS SO CURRENT EYE RESEARCH LA English DT Note DE EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU); GENETIC CONTROL; INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN (IRBP); MAJOR HISTOCOMPATIBILITY COMPLEX (MHC); RT1; RAT ID MYELIN BASIC-PROTEIN; S-ANTIGEN; IMMUNODOMINANT; UVEITIS; SUSCEPTIBILITY; IDENTIFICATION; DETERMINANT; IRBP; MHC; ASSOCIATION AB Experimental autoimmune uveoretinitis (EAU) is an intraocular inflammatory disease model induced by retinal specific antigens such as S-antigen and interphotoreceptor retinoid-binding protein (IRBP). The present study was aimed at testing the uveitogenicity of IRBP and an IRBP-derived peptide in various strains of rats with different RT1 (major histocompatibility complex in rats) haplotypes. Immunization with IRBP induced distinct EAU in LEW (RT1(l)), WKAH (RT1(k)), W/M (RT1(k)), LEJ (RT1(j)), and BUF (RT1(b)) rats. IRBP also induced a low grade of EAU in SDJ (RT1(u)), but no disease was detected in TO rats, another strain of the RT1(u) haplotype. IRBP-derived peptide R16 (aa 1177-1191) induced severe EAU in LEW rats and moderate disease in the WKAH and W/M strains. Immunization with R16 also induced low levels of inflammation in eyes of 75% and 20% of LEJ and BUF rats, respectively, but this peptide did not cause any disease in SDJ and TO rats. Injection of Bordetella pertussis had minimum or no effect on the induction of EAU by peptide R16 in this study. These data thus indicate that peptide R16 can bind to various RT1 molecules in addition to RT1(l). Further, our observations support the notion that certain epitopes of IRBP could be uveitogenic in humans with different HLA haplotypes. C1 NEI,BETHESDA,MD 20892. RP SASAMOTO, Y (reprint author), HOKKAIDO UNIV,SCH MED,DEPT OPHTHALMOL,KITA KU,KITA 15,NISHI 7,SAPPORO,HOKKAIDO 060,JAPAN. NR 30 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD NOV PY 1994 VL 13 IS 11 BP 845 EP 849 DI 10.3109/02713689409025141 PG 5 WC Ophthalmology SC Ophthalmology GA PQ859 UT WOS:A1994PQ85900010 PM 7851121 ER PT J AU ALEXANDER, HR BILLINGSLEY, KG BLOCK, MI FRAKER, DL AF ALEXANDER, HR BILLINGSLEY, KG BLOCK, MI FRAKER, DL TI D-FACTOR LEUKEMIA INHIBITORY FACTOR - EVIDENCE FOR ITS ROLE AS A MEDIATOR IN ACUTE AND CHRONIC INFLAMMATORY DISEASE SO CYTOKINE LA English DT Review ID TUMOR-NECROSIS-FACTOR; DIFFERENTIATION-STIMULATING FACTOR; EXPERIMENTAL CANCER CACHEXIA; FACTOR-INDUCED INCREASE; IL-6 SIGNAL TRANSDUCER; MELANOMA CELL-LINE; LIPOPROTEIN-LIPASE; HUMAN INTERLEUKIN; SUPEROXIDE-DISMUTASE; FACTOR-RECEPTOR RP ALEXANDER, HR (reprint author), NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. NR 62 TC 22 Z9 22 U1 1 U2 1 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 NOV PY 1994 VL 6 IS 6 BP 589 EP 596 DI 10.1016/1043-4666(94)90045-0 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA PT901 UT WOS:A1994PT90100001 PM 7893967 ER PT J AU BOBER, E BRANDSABERI, B EBENSPERGER, C WILTING, J BALLING, R PATERSON, BM ARNOLD, HH CHRIST, B AF BOBER, E BRANDSABERI, B EBENSPERGER, C WILTING, J BALLING, R PATERSON, BM ARNOLD, HH CHRIST, B TI INITIAL STEPS OF MYOGENESIS IN SOMITES ARE INDEPENDENT OF INFLUENCE FROM AXIAL STRUCTURES SO DEVELOPMENT LA English DT Article DE SOMITES; MYOGENIC BHLH FACTOR GENES; NEURAL TUBE; NOTOCHORD; MYOTOME; MUSCLE DIFFERENTIATION ID CHICK-EMBRYO; REGULATORY GENE; SKELETAL-MUSCLE; AVIAN EMBRYOS; MOUSE EMBRYO; FLOOR PLATE; NEURAL-TUBE; TAIL BUD; DIFFERENTIATION; NOTOCHORD AB Formation of paraxial muscles in vertebrate embryos depends upon interactions between early somites and the neural tube and notochord, Removal of both axial structures results in a complete loss of epaxial myotomal muscle, whereas hypaxial and limb muscles develop normally. We report that chicken embryos, after surgical removal of the neural tube at the level of the unsegmented paraxial mesoderm, start to develop myotomal cells that express transcripts for the muscle-specific regulators MyoD and myogenin. These cells also make desmin, indicating that the initial steps of axial skeletal muscle formation tan occur in the absence of the neural tube, However, a few days following the extirpation, the expression of MyoD and myogenin transcripts gradually disappears, and becomes almost undetectable after 4 days, From these observations we conclude that the neural tube is not required for the generation of the skeletal muscle cell lineage, but may support the survival or maitenance of further differentiation of the myotomal cell compartment. Notochord transplanted medially or laterally to the unsegmented paraxial mesoderm leads to a ventralization of axial structures but does not entirely prevent the early appearance of myoblasts expressing MyoD transcripts, However, the additional notochord inhibits subsequent development and maturation of myotomes. Taken together, our data suggest that neural tube promotes, and notochord inhibits, the process of myogenesis in axial muscles at a developmental step following the initial expression of myogenic bHLH regulators. C1 UNIV FREIBURG,INST ANAT,D-79001 FREIBURG,GERMANY. MAX PLANCK INST IMMUNOBIOL,DEPT DEV BIOL,D-79108 FREIBURG,GERMANY. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP BOBER, E (reprint author), TECH UNIV CAROLO WILHELMINA BRAUNSCHWEIG,DEPT CELL & MOLEC BIOL,SPIELMANNSTR 7,D-38106 BRAUNSCHWEIG,GERMANY. NR 43 TC 81 Z9 81 U1 0 U2 0 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 NOV PY 1994 VL 120 IS 11 BP 3073 EP 3082 PG 10 WC Developmental Biology SC Developmental Biology GA PV971 UT WOS:A1994PV97100003 PM 7720553 ER PT J AU CHENG, LZ GEARING, DP WHITE, LS COMPTON, DL SCHOOLEY, K DONOVAN, PJ AF CHENG, LZ GEARING, DP WHITE, LS COMPTON, DL SCHOOLEY, K DONOVAN, PJ TI ROLE OF LEUKEMIA INHIBITORY FACTOR AND ITS RECEPTOR IN MOUSE PRIMORDIAL GERM-CELL GROWTH SO DEVELOPMENT LA English DT Article DE PRIMORDIAL GERM CELLS (PGCS); LEUKEMIA INHIBITORY FACTOR (LIF); ONCOSTATIN M (OSM); CILIARY NEUROTROPHIC FACTOR (CNTF); INTERLEUKIN-6 (IL-6); BASIC FIBROBLAST GROWTH FACTOR (BFGF); STEEL FACTOR (SLF); C-KIT RECEPTOR TYROSINE KINASE; LIF RECEPTOR (LIFR); EMBRYONIC STEM (ES) CELLS; EMBRYONIC GERM (EG) CELLS ID CILIARY NEUROTROPHIC FACTOR; EMBRYONIC STEM-CELLS; IL-6 SIGNAL TRANSDUCER; MOLECULAR-CLONING; ONCOSTATIN-M; HUMAN INTERLEUKIN; FACTOR MAINTAINS; FACTOR LIF; DA CELLS; C-KIT AB The pleiotropic cytokine leukemia inhibitory factor (LIF) is able to promote the growth of mouse primordial germ cells (PGCs) in culture. It is unclear whether LIF acts directly on PGCs or indirectly via feeder cells or embryonic somatic cells. To understand the role of LIF in PGC growth, we have carried out molecular and cell culture analyses to investigate the role of both the LIF ligand and its receptor in PGC development. LIF is able to stimulate PGC growth independently of the presence of feeder cells supporting the hypothesis that LIF acts directly on PGCs to promote their growth. We show here that transcripts for the low-affinity LIF receptor (LIFR), an integral component of the functional LIF receptor complex, are expressed in the developing gonad. Fluorescence-activated cell sorter (FACS) analysis, using an anti-LIFR antiserum, demonstrates that LIFR is present on the surface of PGCs, suggesting that PGCs are likely to be a direct target of LIF action in culture. Signalling via LIFR is essential for PGC growth in culture since the anti-LIFR antiserum, which blocks LIF binding to its receptor, abolishes PGC survival in culture. Two LIF-related cytokines, namely oncostatin M and ciliary neurotrophic factor, can also promote PGC growth in culture in addition to LIF. Thus one or more of these LIFR-dependent cytokines may play an important role in PGC development in mice. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CELL BIOL DEV & DIFFERENTIAT GRP,FREDERICK,MD 21702. IMMUNEX RES & DEV CORP,SEATTLE,WA 98101. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 52 TC 80 Z9 92 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 1994 VL 120 IS 11 BP 3145 EP 3153 PG 9 WC Developmental Biology SC Developmental Biology GA PV971 UT WOS:A1994PV97100009 PM 7720558 ER PT J AU ROS, MA LYONS, GE MACKEM, S FALLON, JF AF ROS, MA LYONS, GE MACKEM, S FALLON, JF TI RECOMBINANT LIMBS AS A MODEL TO STUDY HOMEOBOX GENE-REGULATION DURING LIMB DEVELOPMENT SO DEVELOPMENTAL BIOLOGY LA English DT Article ID APICAL ECTODERMAL RIDGE; DEVELOPING VERTEBRATE LIMBS; PROGRAMMED CELL-DEATH; CHICK WING BUD; PATTERN-FORMATION; HOX-4 GENES; ANTEROPOSTERIOR POLARITY; MOUSE EMBRYO; EXPRESSION; GHOX-8 AB Recombinant limb buds constructed of an ectodermal jacket containing dissociated anterior wing bud mesoderm cells form limb-like structures lacking anteroposterior polarity. Polarity can be restored by implanting a small piece of polarizing region into the recombinant limb. We used recombinant limbs to study expression of Msx1 and Msx2 and 5' Hoxd genes in limb development. Detectable mesodermal expression of Msx1 and Msx2 was lost during preparation of the recombinants. When expression was restored both genes were expressed in a symmetrical fashion in the apical mesoderm whether or not the recombinant was polarized. The normal anterior pattern of Msx1 and Msx2 was never reestablished. The roles Msx1 and Msx2 play in limb patterning are at present not clear. In nonpolarized recombinant limbs the 5' Hoxd genes were sequentially and uniformly expressed in the subridge mesoderm across the anteroposterior axis. They exhibited nested domains of expression showing exclusively distal restriction. In polarized recombinants the 5' Hoxd genes were expressed progressively in an asymmetric, nested fashion adjacent to the implanted polarizing region; there was also a distal mesodermal region further from the implant that did not express the most 5' Hoxd genes. Both of these observations are similar to the normal limb. Our results demonstrate that the polarizing region is not necessary for the activation or maintenance of 5' Hoxd gene expression but that its presence is required in order for the normal pattern to be established. We propose that the expression of the Hoxd genes is an intrinsic property of rapidly growing limb cells and that their expression is related to the limb bud proximodistal outgrowth. Our data also support the influence of the polarizing region upon Hoxd gene expression in two ways. First there is a short-range action responsible for the normal asymmetric expression and second a long-range effect suppressing the expression of 5'-Hoxd genes by the anterior cells. (C) 1994 Academic Press, Inc. C1 UNIV WISCONSIN,DEPT ANAT,MADISON,WI 53706. UNIV CANTABRIA,DEPT ANAT & BIOL CELULAR,E-39011 SANTANDER,SPAIN. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Ros, Maria /K-8160-2014 OI Ros, Maria /0000-0002-1224-7671 FU NICHD NIH HHS [HD29471, HD20743] NR 70 TC 57 Z9 58 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV PY 1994 VL 166 IS 1 BP 59 EP 72 DI 10.1006/dbio.1994.1296 PG 14 WC Developmental Biology SC Developmental Biology GA PT492 UT WOS:A1994PT49200005 PM 7958460 ER PT J AU KRAUSE, M HARRISON, SW XU, SQ CHEN, LS FIRE, A AF KRAUSE, M HARRISON, SW XU, SQ CHEN, LS FIRE, A TI ELEMENTS REGULATING CELL-SPECIFIC AND STAGE-SPECIFIC EXPRESSION OF THE C-ELEGANS MYOD FAMILY HOMOLOG HLH-1 SO DEVELOPMENTAL BIOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; MYOGENIN GENE; MUSCLE DIFFERENTIATION; TRANSGENIC NEMATODES; SEQUENCE COMPARISONS; DROSOPHILA; TRANSCRIPTION; MEMBER; EMBRYOGENESIS AB We investigated the cis-acting sequences regulating expression of the Caenorhabditis elegans gene hlh-1, a homolog of the MyoD family of myogenic regulatory factors. The hlh-1 gene is expressed in mature body wall muscle, in clonal muscle precursors, in a set of early embryonic blastomeres (the MS-granddaughters), and in six glial-like cells called GLRs. The entire natural hlh-1 expression pattern is recapitulated in transgenic animals containing an hlh-1:: lacZ fusion with 5.1 kb of hlh-1 sequences beginning upstream of the coding region and extending into the second exon. Deletions and rearrangements in this 5.1-kb sequence were assayed for their effects on reporter gene expression in transgenic animals. Deletions removing a segment 434-550 bp upstream of the coding region resulted in a loss of all aspects of the expression pattern, suggesting that at least one common regulatory factor is required for all expression. Deletions of other regulatory elements affected distinct aspects of the expression pattern; hence, each expression subpattern exhibits a different set of sequence requirements. Interspecies sequence comparison and lacZ expression constructs with the related nematode Caenorhabditis briggsae indicated that the C. briggsae and C. elegans genes contain equivalent sets of control signals. The results from this work implicate the hlh-1 promoter as an integration point for diverse temporal and spatial control signals. (C) 1994 Academic Press, Inc. C1 CARNEGIE INST WASHINGTON,DEPT EMBRYOL,BALTIMORE,MD 21210. RP KRAUSE, M (reprint author), NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. OI Krause, Michael/0000-0001-6127-3940 FU NIGMS NIH HHS [R01 GM037706, GM37706] NR 50 TC 80 Z9 83 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV PY 1994 VL 166 IS 1 BP 133 EP 148 DI 10.1006/dbio.1994.1302 PG 16 WC Developmental Biology SC Developmental Biology GA PT492 UT WOS:A1994PT49200011 PM 7958441 ER PT J AU LIU, ZY CHIN, K NOGUCHI, CT AF LIU, ZY CHIN, K NOGUCHI, CT TI TISSUE-SPECIFIC EXPRESSION OF HUMAN ERYTHROPOIETIN RECEPTOR IN TRANSGENIC MICE SO DEVELOPMENTAL BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR; ENDOTHELIAL-CELLS; ERYTHROID-CELLS; LIGAND-BINDING; GENE; CLONING; ACTIVATION; MUTATIONS; REGION; FAMILY AB We have made transgenic mice using the human erythropoietin receptor (hEpoR) encoding gene contained within a 15-kb DNA fragment. The transgenic mice that incorporated the hEpoR transgene into the genome were analyzed for tissue specific expression of hEpoR mRNA using reverse transcriptase and DNA amplification. In the control animals, endogenous EpoR transcripts were identified in bone marrow and spleen; no transcripts were detected in heart, kidney, liver, or brain. In the transgenic mice, hEpoR transcripts were detected in bone marrow and spleen but not in heart, kidney, or liver, suggesting that the transgene contains sufficient genetic information to direct appropriate expression in hematopoietically active tissues. The hematological parameters of the transgenic mice were within normal limits, consistent with the relatively low level of hEpoR transcripts detected. Surprisingly, hEpoR transcripts but not mouse EpoR transcripts were detected in the brains of the transgenic mice. Brain hEpoR transcripts were observed in all transgenic mice assayed, indicating that transgene expression in the brain did not result from the effects of aberrant integration sites. Comparable expression of the transgene was also observed in the embryonic brain. Interestingly, we observed significant expression of the endogenous EpoR gene in the early embryonic brain (Day 10) of normal mice at levels comparable to that observed in the adult spleen and bone marrow. The level of endogenous EpoR expression in the brain decreased during embryonic development to nondetectable levels prior to birth preceding the decrease of endogenous EpoR expression in the fetal liver, while hEpoR expression in the brains of transgenic mice persisted throughout embryonic development into adulthood. These data suggest that the hEpoR transgene contains appropriate regulatory sequences to direct tissue specific expression in tissues associated with hematopoietic activity and in the embryonic brain, but lacks the control elements to provide levels of expression comparable to that of the endogenous gene or to selectively silence brain expression in the adult mouse. (C) 1994 Academic Press, Inc. RP LIU, ZY (reprint author), NIDDK,BIOL CHEM LAB,BETHESDA,MD 20892, USA. NR 41 TC 74 Z9 77 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV PY 1994 VL 166 IS 1 BP 159 EP 169 DI 10.1006/dbio.1994.1304 PG 11 WC Developmental Biology SC Developmental Biology GA PT492 UT WOS:A1994PT49200013 PM 7958443 ER PT J AU LIN, TP LABOSKY, PA GRABEL, LB KOZAK, CA PITMAN, JL KLEEMAN, J MACLEOD, CL AF LIN, TP LABOSKY, PA GRABEL, LB KOZAK, CA PITMAN, JL KLEEMAN, J MACLEOD, CL TI THE PEM HOMEOBOX GENE IS X-LINKED AND EXCLUSIVELY EXPRESSED IN EXTRAEMBRYONIC TISSUES DURING EARLY MURINE DEVELOPMENT SO DEVELOPMENTAL BIOLOGY LA English DT Article ID ONCOFETAL GENE; MESSENGER-RNA; VISCERAL ENDODERM; CELL-INTERACTIONS; EMBRYOID BODIES; MOUSE; HOMEODOMAIN; PROTEIN; LOCALIZATION; DIFFERENTIATION AB We previously reported the isolation of a cDNA clone for a homeobox-containing gene designated Pem, shown by Northern analysis of Day 7 through Day 16 mouse embryos to be expressed in extraembryonic tissues. In this study, Pem gene expression was further examined using in situ hybridization and immunocytochemistry to determine the spatial distribution of Pem transcripts and protein in peri-implantation embryos and in embryoid bodies (EBs). Low amounts of Pem mRNA were detected in undifferentiated EBs. When EBs were induced to differentiate, the outer cell layer of visceral or parietal endoderm expressed both Pem mRNA and protein. In developing embryos, no Pem protein was detectable in the uncompacted morula; 12% of the nuclei in compacted morulae were Pem positive, while 25% of the blastocyst trophectoderm and 15% of inner cell mass cells expressed Pem protein. Shortly after implantation, in 5.5 and 6.5 d.p.c. embryos, Pem expression was limited to extraembryonic tissues and was present in distal and proximal visceral endoderm, parietal endoderm, and ectoplacental cone. By 7.5-8.5 d.p.c. neither Pem RNA nor protein was found in the distal squamous visceral endoderm, which surrounds the embryonic region of the egg cylinder, nor in the parietal endoderm. Expression was retained in the proximal columnar epithelium of the visceral endoderm. Prominent Pem expression was observed in the chorion, in trophoblast-derived cells of the ectoplacental cone, and in secondary giant cells, localized in the nuclear compartment. Pem was localized to the X chromosome and found to be expressed in cell lineages where only the maternal X chromosome is active. The data indicate a possible role for Pem in regulating genes involved in the differentiation of extraembryonic tissues. (C) 1994 Academic Press, Inc. C1 UNIV CALIF SAN DIEGO,CTR CANC,CANC GENET PROGRAM,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,GRAD PROGRAM BIOMED SCI,LA JOLLA,CA 92093. WESLEYAN UNIV,DEPT BIOL,MIDDLETOWN,CT 06459. NIAID,BETHESDA,MD 20892. RP LIN, TP (reprint author), UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093, USA. FU NCI NIH HHS [CA57588, R01-CA57588]; NIGMS NIH HHS [GM07752] NR 45 TC 90 Z9 93 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV PY 1994 VL 166 IS 1 BP 170 EP 179 DI 10.1006/dbio.1994.1305 PG 10 WC Developmental Biology SC Developmental Biology GA PT492 UT WOS:A1994PT49200014 PM 7958444 ER PT J AU RAPOPORT, SI SCHINZEL, AAGL AF RAPOPORT, SI SCHINZEL, AAGL TI 3RD INT SYMP ON BRAIN-DYSFUNCTION - INTRODUCTION SO DEVELOPMENTAL BRAIN DYSFUNCTION LA English DT Editorial Material ID DOWN-SYNDROME; DEMENTIA; DISEASE C1 UNIV ZURICH,DEPT MED GENET,CH-8001 ZURICH,SWITZERLAND. RP RAPOPORT, SI (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C103,BETHESDA,MD 20829, USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1019-5815 J9 DEV BRAIN DYSFUNCT JI Dev. Brain Dysfunction PD NOV-DEC PY 1994 VL 7 IS 6 BP 263 EP 264 PG 2 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA RG662 UT WOS:A1994RG66200001 ER PT J AU RAPOPORT, SI GALDZICKI, Z AF RAPOPORT, SI GALDZICKI, Z TI ELECTRICAL STUDIES OF CULTURED FETAL HUMAN TRISOMY-21 AND MOUSE TRISOMY-16 NEURONS IDENTIFY FUNCTIONAL DEFICITS THAT MAY LEAD TO MENTAL-RETARDATION IN DOWN-SYNDROME SO DEVELOPMENTAL BRAIN DYSFUNCTION LA English DT Article; Proceedings Paper CT OASI Symposium on Down Syndrome, Alzheimer Disease and Chromosome 21 CY SEP 28-30, 1994 CL TROINA, ITALY SP OASI DE DORSAL ROOT GANGLION; BRAIN; HIPPOCAMPUS; PATCH CLAMP; ACTION POTENTIAL; DOWN SYNDROME; TRISOMY 21; TRISOMY 16; NERVE GROWTH FACTOR; RETARDATION; ELECTRICAL PROPERTIES; CONDUCTION; NEURODEVELOPMENT ID DORSAL-ROOT GANGLION; NERVE GROWTH-FACTOR; HIPPOCAMPAL CA1 NEURONS; ADULT DOWNS-SYNDROME; PROTEIN-KINASE-C; ALZHEIMERS-DISEASE; CALCIUM CHANNELS; SENSORY NEURONS; SODIUM-CHANNELS; MEMBRANE-PROPERTIES AB There are no consistent and disease-specific anatomic changes in brains of fetuses and young healthy adults with Down syndrome (trisomy 21; Ts21). Thus, it is likely that mental retardation in Down syndrome is due to functional abnormalities in brain neurons and their networks. This interpretation is consistent with electrophysiological studies of cultured neurons from human Ts21 and mouse trisomy 16 (Ts16) fetuses. Fetal Ts21 dorsal root ganglia (DRG) neurons demonstrate a shortened action potential with accelerated depolarization and repolarization due to accelerated kinetics of inward Na and outward K currents as compared with normal diploid human DRG neurons. Cultured DRG neurons from the Ts16 but not from the trisomy 19 fetal mouse show similar abnormalities. Thus, the Ts16 mouse is an appropriate model of neuronal dysfunction in Down syndrome. In contrast, mouse Ts16 hippocampal neurons exhibit slowed depolarization of the action potential and a reduced inward Na current due to fewer Na channels, as well as an increased voltage-dependent inward Ca current mediated by an L-type Ca channel. Abnormal active membrane properties exist also in mouse Ts16 septal neurons, different from those in Ts16 DRG and hippocampal neurons. These results suggest that Ts21/Ts16 leads to dysregulation of neuron-specific active ionic currents, possibly by influencing subunits that compose ion channels which determine these currents. During brain development and maturation, abnormal neuronal electrical properties can lead to abnormal development of synapses and neural networks. Suboptimal integrated brain activity resulting from these changes is postulated to contribute to mental retardation in Down syndrome. RP NIA, NEUROSCI LAB, BLDG 10, ROOM 6C103, BETHESDA, MD 20829 USA. NR 103 TC 12 Z9 12 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1019-5815 J9 DEV BRAIN DYSFUNCT JI Dev. Brain Dysfunct. PD NOV-DEC PY 1994 VL 7 IS 6 BP 265 EP 288 PG 24 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA RG662 UT WOS:A1994RG66200002 ER PT J AU COLE, PM ZAHNWAXLER, C SMITH, KD AF COLE, PM ZAHNWAXLER, C SMITH, KD TI EXPRESSIVE CONTROL DURING A DISAPPOINTMENT - VARIATIONS RELATED TO PRESCHOOLERS BEHAVIOR PROBLEMS SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 1993 Biennial Meeting of the Society-for-Research-in-Child-Development CY APR, 1993 CL NEW ORLEANS, LA SP Soc Res Child Dev ID DEVELOPMENTAL PERSPECTIVE; DISPLAY RULES; DELINQUENCY; STABILITY; CHILD AB Individual differences in expressive control during a disappointment were examined in relation to preschool boys' and girls' concurrent behavior and to their risk for developing disruptive behavior disorders. A disappointment paradigm was used to examine expressive control in 79 4- and 5-year-old children with low, moderate, or high risk. Boys at risk showed more negative emotion in the experimenter's (E's) presence than low-risk boys. In E's absence, low-risk boys' negative emotion was equivalent to at-risk boys'. Boys' negative emotion, particularly anger, predicted their disruptiveness during the disappointment and general symptoms of oppositionality. At-risk girls differed from low-risk girls after E left, displaying less negative emotion than low-risk girls. Girls' minimization of negative emotion predicted attention deficit and conduct disorder symptoms. Gender-specific expressive control is discussed in terms of gender differences in emotion regulation and psychopathology. C1 NIMH,BETHESDA,MD 20892. NR 44 TC 150 Z9 152 U1 1 U2 11 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 NOV PY 1994 VL 30 IS 6 BP 835 EP 846 DI 10.1037/0012-1649.30.6.835 PG 12 WC Psychology, Developmental SC Psychology GA PT354 UT WOS:A1994PT35400004 ER PT J AU PETTITT, DJ BENNETT, PH HANSON, RL NARAYAN, KMV KNOWLER, WC AF PETTITT, DJ BENNETT, PH HANSON, RL NARAYAN, KMV KNOWLER, WC TI COMPARISON OF WORLD-HEALTH-ORGANIZATION AND NATIONAL-DIABETES-DATA-GROUP PROCEDURES TO DETECT ABNORMALITIES AT GLUCOSE-TOLERANCE DURING PREGNANCY SO DIABETES CARE LA English DT Article ID PIMA INDIAN WOMEN; TESTS; COMPLICATIONS; CARBOHYDRATE; METABOLISM; MELLITUS; CRITERIA; OBESITY; LOADS AB OBJECTIVE - To compare the one-step procedure proposed by the World Health Organization (WHO) with the two-step procedure proposed by the National Diabetes Data Group (NDDG) for the identification of abnormalities of glucose tolerance during pregnancy. RESEARCH DESIGN AND METHODS - One hundred twenty-seven nondiabetic Pima Indian women had a 75-g 2-h glucose tolerance lest (WHO criteria). Those with an elevated 1-h glucose concentration (greater than or equal to 7.8 mmol/l) were referred for a 100-g 3-h glucose tolerance test (National Diabetes Data Group criteria). The effectiveness of the two test procedures was determined by comparing the frequency of macrosomia and cesarean section as outcomes of pregnancy. RESULTS - Of 42 women with 1-h plasma glucose concentrations greater than or equal to 7.8 mmol/l, 13 had no 100-g test, 27 had a normal test, and 2 had an abnormal test. Both women (100%) with abnormal two-step 100-g tests also had abnormal one-step 75-g tests, but only 2 of the 11 women (18%) with an abnormal one-step test had an abnormal two-step test. Sixteen of the 127 women delivered babies weighing greater than or equal to 4,000 g. Six of these women (38%) were correctly identified as abnormal using the one-step test and one (6%) using the two-step test. Of seven women delivering by cesarean section, four (57%) had abnormal one-step tests, but none had an abnormal two-step test. CONCLUSIONS - The one-step WHO test for glucose tolerance during pregnancy was abnormal in a greater percentage of women with adverse outcomes than the more cumbersome two-step NDDG test. The one-step test has the added advantage of being directly comparable to the standard glucose tolerance test used in nonpregnant women. RP PETTITT, DJ (reprint author), NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DIABET & ARTHRIT EPIDEMIOL SECT,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. RI Narayan, K.M. Venkat /J-9819-2012; Hanson, Robert/O-3238-2015 OI Narayan, K.M. Venkat /0000-0001-8621-5405; Hanson, Robert/0000-0002-4252-7068 NR 27 TC 44 Z9 44 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1994 VL 17 IS 11 BP 1264 EP 1268 DI 10.2337/diacare.17.11.1264 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN843 UT WOS:A1994PN84300004 PM 7821165 ER PT J AU HARRIS, MI ROBBINS, DC AF HARRIS, MI ROBBINS, DC TI PREVALENCE OF ADULT-ONSET IDDM IN THE US POPULATION SO DIABETES CARE LA English DT Note ID ISLET-CELL ANTIBODIES; C-PEPTIDE RESPONSE; DIABETES-MELLITUS; UNITED-STATES; CLINICAL TYPE; INSULIN; DIAGNOSIS AB OBJECTIVE - To investigate the prevalence of adult-onset insulin-dependent diabetes mellitus (IDDM) in a nationally representative sample of adults 30-74 years of age. Although it is a widely held belief that onset of IDDM in adults is rare, there are few objective data to support this. Adult-onset IDDM may represent a disease that is biologically distinct from youth-onset IDDM, and it would be important to distinguish these two entities. RESEARCH DESIGN AND METHODS - The Second National Health and Nutrition Examination Survey (NHANES II) contained a national probability sample of 12,102 subjects 30-74 years of age in the U.S. population. All subjects with diabetes diagnosed by a physician before the survey were identified. Cases of IDDM defined by age at diagnosis greater than or equal to 30 years, continuous or nearly continuous insulin treatment since diagnosis of diabetes, and relative body weight less than or equal to 125 were classified as adult-onset IDDM. RESULTS- Subjects with adult-onset IDDM represented 0.30% of the U.S. population 30-74 years of age and 7.4% of all diabetic patients diagnosed at 30-74 years of age. CONCLUSIONS - These data indicate that onset of IDDM in adults is uncommon. Given the limitations of the survey instrument, subclinical or slowly progressive IDDM (as distinguished from non-insulin-dependent diabetes mellitus with progressive loss of beta-cell function) would not have been detected, and these would constitute additional cases of adult-onset IDDM. However, the data suggest that a very large population base would be required to identify sufficient numbers of adult-onset IDDM cases for study of the etiology and pathogenesis of this disease. C1 NIDDKD, NATL DIABET DATA GRP, BETHESDA, MD USA. MEDLANTIC RES INST, WASHINGTON, DC USA. NR 26 TC 39 Z9 41 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1994 VL 17 IS 11 BP 1337 EP 1340 DI 10.2337/diacare.17.11.1337 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN843 UT WOS:A1994PN84300015 PM 7821176 ER PT J AU TAHA, TE JUSTESEN, A PATERSON, K MTIMAVALYE, LAR MUNTHALI, P CANNER, JK BROADHEAD, RL CHIPHANGWI, JD MIOTTI, PG BIGGAR, RJ AF TAHA, TE JUSTESEN, A PATERSON, K MTIMAVALYE, LAR MUNTHALI, P CANNER, JK BROADHEAD, RL CHIPHANGWI, JD MIOTTI, PG BIGGAR, RJ TI AN INTERVENTION TO REDUCE THE RISK OF MOTHER-TO-INFANT HIV TRANSMISSION - RESULTS OF A PILOT TOXICITY STUDY SO EAST AFRICAN MEDICAL JOURNAL LA English DT Article AB Although unproven, vaginal cleansing with antiseptics during labour could be a practical approach to reducing the rate of transmission of HIV infection from mother to infant. Before initiating a large scale clinical trial of the antiseptic chlorhexidine, we conducted a study to assess possible toxic effects as well as beneficial outcomes in 160 women volunteers: 40 non-pregnant chlorhexidine washed, 40 pregnant not washed, 40 pregnant saline washed, and 40 pregnant chlorhexidine washed. The wash was easily administered by the nurse-midwives. The participants generally felt better after the procedure, and had no complaints or adverse reactions in the subsequent 24 hours. Bacteriologically, the procedures lowered the carriage of Group B streptococcus and Staphylococcus aureus, but did not affect the frequency of T. vaginalis detection. No clinical problems were seen, and therefore the larger clinical trial of efficacy will proceed. Results of this trial are expected in late 1995. C1 UNIV MALAWI,COLL MED,ZOMBA,MALAWI. NCI,BETHESDA,MD 20892. RP TAHA, TE (reprint author), JOHNS HOPKINS UNIV,MINIST HLTH RES PROJECT,POB 1131,BLANTYRE,MALAWI. NR 4 TC 7 Z9 7 U1 0 U2 0 PU EAST AFRICAN MEDICAL JOURNAL PI NAIROBI PA CHYULU ROAD PO BOX 41632, NAIROBI, KENYA SN 0012-835X J9 E AFR MED J JI East Afr. Med. J. PD NOV PY 1994 VL 71 IS 11 BP 712 EP 715 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA QR839 UT WOS:A1994QR83900004 PM 7859654 ER PT J AU STRATAKIS, CA RENNERT, OM AF STRATAKIS, CA RENNERT, OM TI TURNER SYNDROME - MOLECULAR AND CYTOGENETICS, DYSMORPHOLOGY, ENDOCRINE, AND OTHER CLINICAL MANIFESTATIONS AND THEIR MANAGEMENT SO ENDOCRINOLOGIST LA English DT Article ID PREPUBERTAL GIRLS; GROWTH-HORMONE; SECRETION AB In 1938, Dr. Henry H. Turner wrote: ''the triad, infantilism, webbing of the neck, and deformity of the elbow (cubitus valgus), occurring in the same individual is unusual...'' and continued, saying that ''...it is sufficiently interesting to warrant this report...''. These are the first words describing the genetic syndrome that today bears his name. Turner syndrome is now recognized in 1 of 2,000 live-born phenotypic girls and may be present in 1 of 15 spontaneous abortions. It is a form of mild skeletal dysplasia with short stature its primary manifestation and several other associated defects, a number of them secondary to in utero deformations, and an endocrine disorder, consisting mainly of sexual infantilism caused by premature ovarian failure. All girls with Turner syndrome have an abnormal sex-chromosomal constitution that ranges from simple monosomy of the X chromosome (45,X karyotype) to complex cytogenetic aberrations involving the XX chromosomal pair (46,XX karyotype with deletions, translocations, inversions, and/or ring formations of the X chromosomic material). To date, the molecular genetics of the syndrome have not been elucidated, despite recent advances such as the cloning of the sex-determining gene SRY and its counterparts on chromosome X, SOX genes. The phenotype of Turner syndrome is the result of a complex interaction of the in utero and post natal expression of a number of genes located on the X chromosome responsible for sex determination and function, final height, skeletal maturation, and development of other structures of mesenchymal origin. In this review, we discuss Turner syndrome from the aspect of the clinician geneticist, endocrinologist, and general practitioner. C1 GEORGETOWN UNIV,CHILDRENS MED CTR,DEPT PEDIAT,DIV GENET & METAB DIS,WASHINGTON,DC 20007. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 26 TC 20 Z9 20 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD NOV PY 1994 VL 4 IS 6 BP 442 EP 453 DI 10.1097/00019616-199411000-00007 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PU889 UT WOS:A1994PU88900007 ER PT J AU REINHARDT, RR BONDY, CA AF REINHARDT, RR BONDY, CA TI INSULIN-LIKE GROWTH-FACTORS CROSS THE BLOOD-BRAIN-BARRIER SO ENDOCRINOLOGY LA English DT Article ID FACTOR-I RECEPTORS; RAT-BRAIN; QUANTITATIVE AUTORADIOGRAPHY; COMPUTERIZED DENSITOMETRY; INVITRO AUTORADIOGRAPHY; GENE-EXPRESSION; BINDING-SITES; IGF-I; LOCALIZATION; HETEROGENEITY AB Although evidence exists that insulin may cross the blood-brain barrier, little is known about the ability of insulin-like growth factors (IGF-I and -II) to cross this barrier. In the present studies, equimolar concentrations of equal specific activity I-125-labeled IGF-I, IGF-II, or insulin were infused into the carotid artery of anesthetized adult rats. The perfusions were carried out for 3 min in the presence or absence of excess unlabeled ligand or insulin, with three or more animals in each group. Immediately after the perfusion, brains were frozen and sectioned for autoradiography. All ligands were detected in choroid plexus, median eminence, and blood vessels, but [I-125]IGF-I and -II were also prominently localized in brain parenchyma. Densitometric analysis of film autoradiographs (28-day exposure for all ligands) revealed that radiolabeled IGFs, especially IGF-I, were significantly more abundant throughout the forebrain than [I-125]insulin, especially in the paraventricular nucleus, where [I-125]IGF-I was 10-fold and [I-125] IGF-II was 5-fold more abundant than [I-125]insulin. The difference in [I-125]IGF-I vs. [I-125]insulin accumulation was confirmed by parallel measurements of radioactivity in anatomically matched brain sections using a gamma-spectrometer. The uptake of radiolabeled IGF-I, IGF-II, and insulin by brain parenchyma and vasculature was completely inhibited by excess (1,000-fold) unlabeled ligand; however, insulin (10,000-fold excess) did not completely abolish [I-125]IGF-I and -II accumulation. Microscopic evaluation of nuclear emulsion-coated brain sections revealed that radioactivity associated with [I-125]IGF-I and -II perfusions was selectively concentrated in capillaries and medium-sized parenchymal cells in the paraventricular nucleus and, to a lesser extent, the supraoptic nucleus and anterior nucleus of the thalamus, whereas in other brain regions the radioligands were mostly bound to capillaries. These results suggest that radiolabeled IGF-I and -II bind to brain capillaries and cross the blood-brain barrier into brain parenchyma more readily than radiolabeled insulin. RP REINHARDT, RR (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 26 TC 246 Z9 254 U1 2 U2 5 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1994 VL 135 IS 5 BP 1753 EP 1761 DI 10.1210/en.135.5.1753 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PR667 UT WOS:A1994PR66700006 PM 7525251 ER PT J AU TOMIC, M CESNJAJ, M CATT, KJ STOJILKOVIC, SS AF TOMIC, M CESNJAJ, M CATT, KJ STOJILKOVIC, SS TI DEVELOPMENTAL AND PHYSIOLOGICAL-ASPECTS OF CA2+ SIGNALING IN AGONIST-STIMULATED PITUITARY GONADOTROPHS SO ENDOCRINOLOGY LA English DT Article ID LUTEINIZING-HORMONE SECRETION; MESSENGER-RNA LEVELS; INDUCED CALCIUM OSCILLATIONS; RAT ESTROUS-CYCLE; INDIVIDUAL GONADOTROPES; CYTOPLASMIC CALCIUM; RIBONUCLEIC-ACIDS; FEMALE RATS; CELLS; PROGESTERONE AB GnRH-induced Ca2+ signaling was analyzed in gonadotrophs from pituitary glands of neonatal, prepubertal, peripubertal, cycling, and ovariectomized female and adult male rats. In all cases, single cell studies showed three types of Ca2+ responses to increasing GnRH concentrations: subthreshold, baseline oscillatory, and biphasic (an early transient followed by sustained oscillations or a plateau). An increase in the frequency, but not the amplitude, of spiking, and the presence of both baseline oscillatory and biphasic Ca2+ responses were observed in single cells from all groups exposed to low and subsequently to higher GnRH concentrations. Thus, modulation of the frequency of Ca2+ spiking at low to medium GnRH concentrations and suppression of the oscillatory response at high agonist concentrations are characteristics of the gonadotroph that are not affected by age, sex, stage of the estrous cycle, or gonadectomy. Ca2+ influx through plasma membrane channels contributed to both baseline oscillatory and biphasic responses, and both types of Ca2+ signaling were associated with LH release. The sensitivity of gonadotrophs to GnRH stimulation was group of donors, but varied according to age and physiological status. Thus, sensitivity was low in neonatal gonadotrophs and progressively increased in postnatal cells. In cycling females, gonadotrophs from proestrous animals were more sensitive than those from estrous and diestrous animals. Ca2+ signaling was more uniform in gonadotrophs from ovariectomized than in those from normal females. During prolonged culture there was an increase in the frequency of Ca2+ spiking in response to 1 nM GnRH over the first 3 days, followed by a gradual decrease over 7-10 days and loss of the response in older cultures. These changes in Ca2+ signaling were accompanied by similar changes in the GnRH-induced secretory responses. These data indicate that frequency-controlled spiking, with suppression of the oscillatory mechanism at high agonist concentrations, is a characteristic of Ca2+ signaling in rat gonadotrophs. In addition, developmental, physiological, and in vitro changes in pituitary sensitivity to GnRH are expressed through modulation of the Ca2+ signal and the consequent secretory response. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, BETHESDA, MD 20892 USA. RI Tomic, Melanija/C-3371-2016 NR 52 TC 40 Z9 40 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1994 VL 135 IS 5 BP 1762 EP 1771 DI 10.1210/en.135.5.1762 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PR667 UT WOS:A1994PR66700007 PM 7956899 ER PT J AU JAHNKE, GD CHAO, J WALKER, MP DIAUGUSTINE, RP AF JAHNKE, GD CHAO, J WALKER, MP DIAUGUSTINE, RP TI DETECTION OF A KALLIKREIN IN THE MOUSE LACTATING MAMMARY-GLAND - A POSSIBLE PROCESSING ENZYME FOR THE EPIDERMAL GROWTH-FACTOR PRECURSOR SO ENDOCRINOLOGY LA English DT Article ID SUBMANDIBULAR-GLAND; PROSTATE KALLIKREIN; TISSUE KALLIKREIN; KIDNEY MEMBRANES; T-KININOGENASE; FACTOR-ALPHA; RAT; GENES; IDENTIFICATION; EXPRESSION AB Kallikreins are a multigene subfamily of serine proteases that may have a role in processing precursors of polypeptide hormones and growth factors. The epidermal growth factor (EGF) immunoreactivity in mouse milk is derived from the membrane-bound EGF precursor located on the lumenal border of the alveolar cells in the mammary gland. Release of EGF into the milk requires the hydrolysis of the EGF precursor at Arg-X cleavage sites. We report the presence of a candidate EGF precursor-processing enzyme in the lactating mouse mammary gland. Kallikrein transcripts in the mouse lactating mammary gland were detected by primer-directed enzyme amplification of complementary DNA (cDNA). Primers to selected consented regions of the kallikrein cDNA resulted in an amplified product of the predicted size (573 basepairs). Sequence analysis of the product over three nonconserved regions identified mGK-6 (mouse renal kallikrein) as the primary kallikrein in BALB/c mouse lactating mammary gland. Transcription products for the EGF-binding protein (mGK-9), mGK-1, mGK-3, and mGK-4 were not detected by enzyme amplification with specific primers corresponding to these kallikrein cDNAs, Positive immunohistochemical staining of the apical membrane of mammary alveolar cells was detected with a polyclonal antiserum to mouse kallikrein. Incubation of cell membranes isolated from lactating mammary glands released soluble EGF-immunoreactive material. Aprotinin partially inhibited the release of this material, whereas other protease inhibitors, such as leupeptin, benzamidine, and limabean trypsin inhibitor, had no detectable effect. These results support the hypothesis that the release of EGF-immunoreactive material into the milk is in part dependent upon a kallikrein enzyme (mGK-6) in the BALB/c mouse lactating mammary gland. C1 MED UNIV S CAROLINA,DEPT BIOCHEM & MOLEC BIOL,CHARLESTON,SC 29425. RP JAHNKE, GD (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,HORMONES & CANC WORK GRP,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NHLBI NIH HHS [HL-29397] NR 37 TC 23 Z9 24 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1994 VL 135 IS 5 BP 2022 EP 2029 DI 10.1210/en.135.5.2022 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PR667 UT WOS:A1994PR66700041 PM 7525260 ER PT J AU PERFETTI, R SCOTT, LA SHULDINER, AR AF PERFETTI, R SCOTT, LA SHULDINER, AR TI THE 2 NONALLELIC INSULIN-LIKE GROWTH-FACTOR-I GENES IN XENOPUS-LAEVIS ARE DIFFERENTIALLY REGULATED DURING DEVELOPMENT SO ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACIDS; IGF-I; EMBRYONIC-DEVELOPMENT; NEURITE FORMATION; SENSORY NEURONS; HUMAN-FETUS; RAT; EXPRESSION; RNA; SOMATOMEDIN AB To study the potential role of insulin-like growth factor-I (IGF-I) during early embryogenesis, we have used the amphibian Xenopus laevis, a versatile model of vertebrate development. Using polymerase chain reaction (PCR)-based cloning strategies, we have previously identified two different nonallelic Xenopus IGF-I genes (IGF-I' and IGF-I''). Both are expressed in similar quantities in adult liver. We now report the use of a modification of the reverse transcription-PCR method, designated RNA template-specific PCR (RS-PCR), to detect IGF-I messenger RNA (mRNA) from single oocytes and embryos. The same primer pair was used to amplify both IGF-I' and IGF-I'' mRNAs. Slot blot analysis of the RS-PCR products with internal oligonucleotide probes that specifically recognize IGF-I' or IGF-I'' sequences revealed that only IGF-I' mRNA was present in follicles surrounding mature (stage VI) oocytes; neither IGF-I mRNA was present in follicles sur rounding less mature oocytes (stages I and IV) or within oocytes or unfertilized eggs. After fertilization, IGF-I' mRNA was first detected during early organogenesis (stages 21-23), and increased during subsequent stages of development. To localize early IGF-I' expression, a stage 27 embryo was sliced into 24-mu m cross-sections; RS-PCR and slot blot analysis were performed on RNA extracts from consecutive sections. IGF-I' mRNA was expressed in all sections, but was most abundant in the body region from which the visceral organs were developing. In contrast, to the early expression of IGF-I', IGF-I'' mRNA was not detected until stage 41, a period corresponding to premetamorphic growth. Reverse PCR for Xenopus GH mRNA demonstrated that the onset of GH gene expression was coincident with the onset of IGF-I'' gene expression (stage 41). These data suggest that the early expression of IGF-I' may be GH independent, whereas later expression of IGF-I'' is GH dependent. We conclude that the two nonallelic IGF-I genes are expressed differentially in a stage-specific manner and suggest that IGF-I' may play an important cole during early organogenesis, whereas IGF-I'' may be important for premetamorphic growth. C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DIV GERIATR MED & GERONTOL,BALTIMORE,MD 21224. RP PERFETTI, R (reprint author), NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,DIABET UNIT,4940 EASTERN AVE,ROOM 2B02,BALTIMORE,MD 21224, USA. NR 56 TC 12 Z9 12 U1 0 U2 4 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1994 VL 135 IS 5 BP 2037 EP 2044 DI 10.1210/en.135.5.2037 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PR667 UT WOS:A1994PR66700043 PM 7956926 ER PT J AU EGAN, JM MONTROSERAFIZADEH, C WANG, YH BERNIER, M ROTH, J AF EGAN, JM MONTROSERAFIZADEH, C WANG, YH BERNIER, M ROTH, J TI GLUCAGON-LIKE PEPTIDE-1(7-36) AMIDE (GLP-1) ENHANCES INSULIN-STIMULATED GLUCOSE-METABOLISM IN 3T3-L1 ADIPOCYTES - ONE OF SEVERAL POTENTIAL EXTRAPANCREATIC SITES OF GLP-1 ACTION SO ENDOCRINOLOGY LA English DT Article ID RAT ADIPOSE-TISSUE; DIABETES-MELLITUS; RIBONUCLEIC-ACID; TRUNCATED GLP-1; SKELETAL-MUSCLE; 7-36 AMIDE; RECEPTOR; RELEASE; PROGLUCAGON; EXPRESSION AB We investigated the effects of glucagon-like peptide-1(7-36) amide, GLP-1, on glucose metabolism in 3T3-L1 adipocytes and we used polymerase chain reaction to search for the presence of GLP-1 receptors in various rat tissues. GLP-1 at 1 nM significantly increased insulin-mediated 2-deoxyglucose uptake by 40% while having no effect on basal uptake. In conjunction with the elevated uptake, the insulin-dependent incorporation of C-14-glucose into fatty acids was also increased. Moreover, neither glycogen synthesis nor insulin binding to its receptor were affected by GLP-1. In addition to the presence of GLP-1 receptor in pancreas we found messenger RNA for this receptor in brain, kidney, heart, fat, skeletal muscle, liver, and intestine. This study indicates that GLP-1, in addition to its well known effect of stimulating insulin secretion, may improve insulin responsiveness by promoting fatty acid synthesis in adipose cells and possibly modulating insulin signaling in other insulin sensitive tissues. C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21224. RP EGAN, JM (reprint author), NIA,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Bernier, Michel/0000-0002-5948-368X NR 34 TC 103 Z9 105 U1 0 U2 5 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1994 VL 135 IS 5 BP 2070 EP 2075 DI 10.1210/en.135.5.2070 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PR667 UT WOS:A1994PR66700047 PM 7956929 ER PT J AU BACH, LA HSIEH, S BROWN, AL RECHLER, MM AF BACH, LA HSIEH, S BROWN, AL RECHLER, MM TI RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR (IGF)-BINDING PROTEIN-6 INHIBITS IGF-II-INDUCED DIFFERENTIATION OF L6A1 MYOBLASTS SO ENDOCRINOLOGY LA English DT Article ID FACTOR-BINDING PROTEIN-6; MOLECULAR-CLONING; HUMAN FIBROBLASTS; GENE-EXPRESSION; CELLS; IDENTIFICATION; PURIFICATION; POTENTIATION; SEQUENCE; AFFINITY AB Insulin-like growth factor-binding protein-6 (IGFBP-6) is an O-linked glycoprotein that binds insulin-like growth factor-II (IGF-II) with marked preferential affinity over IGF-I. Recombinant human IGFBP-6 (rhIGFBP-6) was synthesized by COS-7 monkey kidney cells that were transiently transfected with a eukaryotic expression vector into which a complementary DNA for IGFBP-6 modified for optimal translation had been inserted. rhIGFBP-6 was similar to IGFBP-6 purified from human cerebrospinal fluid with respect to IGF binding and O-glycosylation. The effect of rhIGFBP-6 on IGF-induced L6A1 myoblast differentiation was studied using creatine kinase activity as an index of differentiation. rhIGFBP-6 inhibited differentiation initiated by IGF-II in a dose-dependent manner; inhibition was complete when rhIGFBP-6 was present in a slight molar excess. In contrast, rhIGFBP-6 had no effect on IGF-I-induced differentiation, even when coincubated in a 5-fold molar excess. These results are consistent with the preferential affinity of IGFBP-6 for IGF-II. As cell association and proteolysis have been associated with the potentiation, rather than the inhibition, of IGF action by IGFBPs, we investigated whether they occurred in the L6A1 myoblast system. After incubation of L6A1 myoblasts with rhIGFBP-6, IGFBP-6 was recovered from the medium, but not from cell lysates or extracellular matrix. In addition, [I-125]-IGFBP-6 did not bind to myoblast monolayers, and there was no evidence that proteolysis had occurred. Together, these results indicate that rhIGFBP-6 remains intact and soluble and, hence, inhibits IGF-II-induced differentiation. The fidelity of the IGFBP-6 expression system used for these studies will enable us to use this system to determine how structural modifications of the protein affect the modulation of IGF action by IGFBP-6. C1 NIDDKD,GROWTH & DEV SECT,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD 20892. OI Bach, Leon/0000-0002-9062-1518 NR 44 TC 67 Z9 68 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1994 VL 135 IS 5 BP 2168 EP 2176 DI 10.1210/en.135.5.2168 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PR667 UT WOS:A1994PR66700059 PM 7525263 ER PT J AU WONG, ML LICINIO, J PASTERNAK, KI GOLD, PW AF WONG, ML LICINIO, J PASTERNAK, KI GOLD, PW TI LOCALIZATION OF CORTICOTROPIN-RELEASING HORMONE (CRH) RECEPTOR MESSENGER-RNA IN ADULT-RAT BRAIN BY IN-SITU HYBRIDIZATION HISTOCHEMISTRY SO ENDOCRINOLOGY LA English DT Note ID PITUITARY-ADRENAL AXIS; CENTRAL NERVOUS-SYSTEM; LEWIS RATS; EXPRESSION; SECRETION; CLONING; IMMUNOREACTIVITY; ACTIVATION; ARTHRITIS; DISEASE AB Even though functional CRH receptors have been identified in several brain regions by ligand binding, the identity of brain areas expressing the CRH receptor gene has not been described. The recent cloning of the rat CRH receptor gene has permitted us to conduct an in situ hybridization histochemistry study to localize CRH receptor mRNA in brain, using an antisense S-35-labeled riboprobe and autoradiography. In virus- and pathogen-free, unstressed, adult male Sprague-Dawley rats we observed CRH receptor gene expression in several brain regions, most of which had been previously shown to bind radiolabeled CRH. Those regions include the pituitary, olfactory bulb, hippocampal formation, cerebral and cerebellar cortexes, hypothalamus, median eminence, amygdala, olfactory tubercle, choroid plexus, thalamus, and inferior colliculus. Further studies are needed to determine the cell types expressing both CRH receptor mRNA and the CRH receptor peptide in nervous system as well as in peripheral tissues. RP WONG, ML (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,INTRAMURAL RES PROGRAM,BLDG 10,RM 3S231,BETHESDA,MD 20892, USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 31 TC 81 Z9 81 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1994 VL 135 IS 5 BP 2275 EP 2278 DI 10.1210/en.135.5.2275 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PR667 UT WOS:A1994PR66700071 PM 7956950 ER PT J AU CHAPIN, RE KU, WW AF CHAPIN, RE KU, WW TI THE REPRODUCTIVE TOXICITY OF BORIC-ACID SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Symposium on Health Effects of Boron and Its Compounds CY SEP 16-17, 1992 CL UNIV CALIF IRVINE, IRVINE, CA HO UNIV CALIF IRVINE DE BORIC ACID; SPERMATOGENESIS; RATS; INHIBITED SPERMIATION; ATROPHY; RECOVERY FROM; THRESHOLD ID F344 RATS; BORON; EXPOSURE AB Previous studies on the reproductive toxicity of boric acid have indicated that male rodents suffer testicular atrophy after treatment. There were, however, no studies of the potential effects on female fertility or on the neonate. In addition, no study described the development of the testicular lesion, thought to be related to the mechanism of toxicity. A Reproductive Assessment by Continuous Breeding (RACB) study using mice exposed to boric acid al 1000, 4500, and 9000 ppm in the diet indicated that there are probably multiple sites of action, although male fertility appears Very sensitive. Possible effects on female fertility cannot be separated from potential developmental toxicity and need additional investigation. Decrements in sperm motility were observed at all exposure levels, and testicular atrophy was confirmed in high- and middle-dose-group males. This was investigated further by timed serial-sacrifice studies using 9000 ppm in the diet of rats, which found that the first lesion seen in the testis was an inhibition of spermiation (release of mature spermatids). With continued dosing, this was followed by a disorganization of the normal ordered layering of the seminiferous epithelium, germ cell sloughing and death, and finally. atrophy. Subsequent studies using additional doses (2000, 3000, 4500, 6000, and 9000 ppm) found that it was possible to observe inhibited spermiation that did not progress to atrophy (4500 ppm and below) within the 9-week exposure period. Also, once atrophic (from 9000- and 6000-ppm exposures), there was no return of spermatogenesis after refeeding of normal diet for 8, 16, 24, or 32 weeks, despite the presence of a normal-sized population of spermatogonia that was seen to divide. No effects were observed in rats treated with 2000 ppm. Testicular boron concentrations remained steady during exposure at the same level as found in blood. and declined to background levels within 72 hr after cessation of exposure. Bone boron levels were greater than those found in blood, and maintained slightly elevated levels even 32 weeks after the cessation of exposure. These studies document the effects of boric acid on functional and structural aspects of the male reproductive system; demonstrate that the tissue concentration of boron, and not total dose, is important for the testicular toxicity, and show that there is a threshold for these effects. These studies also suggest that the potential for recovery from boric acid-induced testicular atrophy should be examined in other species to evaluate the significance of the persistent atrophy seen in the rats. RP CHAPIN, RE (reprint author), NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Chapin, Robert/0000-0002-5997-1261 NR 16 TC 42 Z9 51 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1994 VL 102 SU 7 BP 87 EP 91 DI 10.2307/3431969 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PY063 UT WOS:A1994PY06300015 PM 7889888 ER PT J AU DIETER, MP AF DIETER, MP TI TOXICITY AND CARCINOGENICITY STUDIES OF BORIC-ACID IN MALE AND FEMALE B6C3F(1) MICE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Symposium on Health Effects of Boron and Its Compounds CY SEP 16-17, 1992 CL UNIV CALIF IRVINE, IRVINE, CA HO UNIV CALIF IRVINE DE FEEDING STUDY; 14-DAY REPEATED DOSE; 13-WEEK SUBCHRONIC; 2-YEAR CHRONIC; B6C3F(1) MICE; TESTICULAR TOXICITY; CARCINOGEN BIOASSAY AB Toxicity and potential carcinogenicity studies of boric acid were investigated in mice to verify in a second rodent species that this was a noncarcinogenic chemical. Earlier chronic studies in rats indicated boric acid was not a carcinogen. The chemical is nominated for testing because over 200 tons are produced annually, there are multiple uses for the product, and there is potential for widespread human exposure, both orally and dermally. Both sexes of B6C3F(1) mice were offered diets mixed with boric acid for 14 days, 13 weeks, or 2 years. Dietary doses used in the acute, 14-day study were 0, 0.62, 1.25, 2.5, 5, and 10%; those in the subchronic, 13-week study were 0, 0.12, 0.25, 0.50, 1, and 2%; and doses in the 2-year, chronic study were 0, 0.25, and 0.50% in the diet. Mortality, clinical signs of toxicity, estimates of food consumption, body weight gain, and histopathologic examination of selected tissues constituted the variables measured. In the 14-day study mortality was proportional to dose and time of exposure in both sexes, occurring in dose groups as low as 2.5% and as early as 7 days of exposure. Body weights were depressed more than 10% below controls in the higher dose groups of both sexes. Mortality in the 13-week study was confined to the two highest dose groups in male mice and to the 2%-dose group in females. Body weight depression from 8 to 23% below those of controls occurred in the 0.50% and higher dose groups of both sexes. Minimal to mild extramedullary hematopoiesis in spleens of both sexes was a common occurrence in all dose groups, but the most severe lesion was testicular degeneration or atrophy of the seminiferous tubules in male mice fed 0.50 to 2.0% boric acid. Dietary doses of 0.25 and 0.50% were selected for both sexes of mice in 2-year studies based on body weights and mortality Survival of male mice was reduced in the high-dose group after week 63, and after week 84 in the low-dose group; survival in female mice was not affected at either dose of boric acid. Reductions in body weight gain occurred in the high-dose group of both sexes. Based on estimates of food consumption, the average amount of boric acid ingested per mouse per day was calculated to be 400 to 500 mg/kg in the low-dose and 1100 to 1200 mg/kg in the high-dose groups of both sexes. Again the most prominent lesion was an increased incidence of testicular atrophy (3/49, 6/50, 27/47) and interstitial cell hyperplasia (0/49, 0/50, 7/47) in high-dose male mice. There was a slight increase in spleen lymphoid depletion in dosed male mice, which was considered secondary to stress and debilitation. Although there were marginal increases in subcutaneous tissue tumors and hepatic tumors in dosed male mice, these fell within the historical control range and were not believed to be related to chemical treatment. These particular tumors are highly variable in historical controls, only occurred in the low-dose group, and were not significant by an incidental tumor test, which is appropriate for tumors that are not a cause of death. There were also no indications that boric acid is genotoxic, since tests with prokaryotic and eukaryotic cells were uniformly negative, and there were no effects on sister-chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells. RP DIETER, MP (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 14 Z9 14 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1994 VL 102 SU 7 BP 93 EP 97 DI 10.2307/3431970 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PY063 UT WOS:A1994PY06300016 PM 7889889 ER PT J AU KU, WW CHAPIN, RE AF KU, WW CHAPIN, RE TI MECHANISM OF THE TESTICULAR TOXICITY OF BORIC-ACID IN RATS - IN-VIVO AND IN-VITRO STUDIES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Symposium on Health Effects of Boron and Its Compounds CY SEP 16-17, 1992 CL UNIV CALIF IRVINE, IRVINE, CA HO UNIV CALIF IRVINE DE BORIC ACID; TOXICITY; RATS; TESTIS; CULTURED CELLS ID STIMULATED CAMP ACCUMULATION; SERTOLI CELLS; PLASMINOGEN-ACTIVATOR; HORMONAL-STIMULATION; CULTURES; TESTIS; BORON; SPERMATOGENESIS; STEROIDOGENESIS; INHIBITION AB High-dose boric acid (BA) exposure produces testicular lesions in adult rats characterized by inhibited spermiation (IS) that may progress to atrophy. In vivo and in vitro studies addressed possible mechanisms. in vivo, boron tissue disposition was examined, since no detailed data existed, and relevant boron concentrations for in vitro studies needed to be set. Since BA induces riboflavinuria and also affects calcium/phosphorus homeostasis, and testis zinc appears essential for normal testis function, we examined BA effects on flavin status and testis levels of phosphorus (P), calcium (Ca) and zinc (Zn). Data showed that the testicular toxicity and central nervous system (CNS) hormonal effect were not due to selective boron accumulation in testis or brain/hypothalamus, with testis boron concentrations at approximately 1 to 2 mM; that riboflavin deficiency is not involved, due to both the absence of overt signs of deficiency and effects on tissue flavin content during BA exposure; and that changes in testis P, Ca and Zn levels did not precede atrophy, and are therefore unlikely to be mechanistically relevant. In vitro studies addressed the hallmarks of the BA testicular toxicity: the mild hormone effect, the initial IS, and atrophy. No effect of BA on the steroidogenic function of isolated Leydig cells was observed, supporting the contention of a CNS-mediated rather than a direct hormone effect. Since increased testicular cyclic adenosine monophosphate (cAMP) produces IS, and a role for the serine proteases plasminogen activators (PAs) in spermiation has been proposed, we examined in vitro BA effects on both Sertoli cell cAMP accumulation and PA activity, respectively. Results showed that the iS is not due to BA effects on either process. To address the atrophy, we evaluated BA effects in Sertoli-germ cell cocultures on: Sertoli cell energy metabolism, since lactate, secreted by Sertoli cells, is a preferred energy source for germ cells; and also on DNA/RNA synthesis, since germ cells synthesize DNA/RNA and BA impairs nucleic acid synthesis in liver. and may do so in testis. The most sensitive in vitro endpoint was DNA synthesis of mitotic/meiotic germ cells, with energy metabolism in Sertoli or germ cells affected to a lesser extent. The in vitro effect on DNA synthesis was manifest in vivo as a decrease in the early germ cell/Sertoli cell ratio prior to atrophy in testes from BA-exposed rats. Overall, these combined studies revealed some changes offering a plausible explanation for the atrophy aspect of the BA testicular lesion. However, the mechanism for the IS is still undefined, and should be the subject of future work. C1 NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. OI Chapin, Robert/0000-0002-5997-1261 NR 46 TC 23 Z9 29 U1 0 U2 4 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1994 VL 102 SU 7 BP 99 EP 105 DI 10.2307/3431971 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PY063 UT WOS:A1994PY06300017 PM 7889890 ER PT J AU HEINDEL, JJ PRICE, CJ SCHWETZ, BA AF HEINDEL, JJ PRICE, CJ SCHWETZ, BA TI THE DEVELOPMENTAL TOXICITY OF BORIC-ACID IN MICE, RATS, AND RABBITS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Symposium on Health Effects of Boron and Its Compounds CY SEP 16-17, 1992 CL UNIV CALIF IRVINE, IRVINE, CA HO UNIV CALIF IRVINE DE BORIC ACID; DEVELOPMENTAL TOXICITY; MALFORMATIONS; MATERNAL TOXICITY; NOAEL ID TERATOGENICITY AB Boric acid (BA) is a naturally occurring agent used in manufacturing processes and numerous consumer products. Because of the potential for both industrial and consumer exposure to boron-containing compounds, and the lack of developmental toxicity data, the National Toxicology Program evaluated the potential for boric acid to cause developmental toxicity in pregnant Swiss (CD-1) mice, Sprague-Dawley rats (n = 26-28/group), and New Zealand rabbits (n = 18-23/group). BA was provided in the feed to mice and rats at 0, 0.1, 0.2, or 0.4% throughout gestation to attain steady-state exposure as early as possible during development. Average doses (mg/kg/day) were 248, 452, or 1003 for mice, and 78, 163, or 330 in rats. A separate group of rats received 0.8% BA in the feed, or 539 mg/kg/day only on gestation days (gd) 6 to 15. Rabbits were given BA (0, 62.5, 125, or 250 mg/kg) by gavage administration on gd 6 to 19. Maternal body weight, food and/or water consumption and signs of toxicity were monitored at regular intervals. At termination, gd 17 (mice), 20 (rats), or 30 (rabbits), the uterus was examined to determine the number of resorptions, dead, or live fetuses. Fetuses were weighed and live fetuses were examined for external, visceral, and skeletal defects. Mouse darns exhibited mild renal lesions (greater than or equal to 248 mg/kg/day BA). increased water intake and relative kidney weight (1003 mg/kg/day BA), and decreased weight gain during treatment. Maternal rats exhibited increased liver and kidney weights at greater than or equal to 163 mg/kg/day BA, altered water and/or food intake at >163 mg/kg/day BA, and decreased weight gain at >330 mg/kg/day BA. In rabbits, signs of toxicity included decreased food consumption during treatment. and vaginal bleeding associated with pregnancy loss at 250 mg/kg/day. Maternal body weight (gd 9 to 30), weight gain during treatment, and gravid uterine weight decreased at 250 mg/kg/day. Relative maternal kidney weight (but not absolute weight) was increased at 250 mg/kg/day, but microscopic evaluation did not indicate any renal pathology associated with BA exposure. BA is a developmental toxicant in all three species. The lowest-observed-adverse-effect level (LOAEL) for developmental toxicity was 78 mg/kg/day for rats (fetal weight reduction), 250 mg/kg/day for rabbits (prenatal mortality and malformations), and 452 mg/kg/day for mice (fetal weight reduction). The no-observed-adverse-effect levels (NOAELs) for developmental toxicity in these species were <78 mg/kg/day (rats), 125 mg/kg/day (rabbits), and 248 mg/kg/day (mice). With regard to maternal toxicity. the rat was the most sensitive (163 mg/kg/day), while both the mouse and rabbit showed maternal toxicity at 250 mg/kg/day. Thus, developmental toxicity occurred below maternally toxic levels in the rat, and only in the presence of maternal toxicity in mice or rabbits. C1 CTR LIFE SCI & TOXICOL, RES TRIANGLE PK, NC USA. RP HEINDEL, JJ (reprint author), NIEHS, NATL TOXICOL PROGRAM, DEV & REPROD TOXICOL GRP, POB 12233, MD 3-03, RES TRIANGLE PK, NC 27709 USA. NR 22 TC 38 Z9 38 U1 0 U2 4 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1994 VL 102 SU 7 BP 107 EP 112 DI 10.2307/3431972 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PY063 UT WOS:A1994PY06300018 PM 7889869 ER PT J AU FISHER, B AF FISHER, B TI BRIDGING THE GREEN RESEARCH GAPS - THE PROPOSED NIE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material RP FISHER, B (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1994 VL 102 IS 11 BP 930 EP 931 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PV437 UT WOS:A1994PV43700005 ER PT J AU LEE, L MCHUGH, L RIBAUDO, RK KOZLOWSKI, S MARGULIES, DH MAGE, MG AF LEE, L MCHUGH, L RIBAUDO, RK KOZLOWSKI, S MARGULIES, DH MAGE, MG TI FUNCTIONAL CELL-SURFACE EXPRESSION BY A RECOMBINANT SINGLE-CHAIN CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULE WITH A CIS-ACTIVE BETA(2)-MICROGLOBULIN DOMAIN SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I; SINGLE CHAIN; BETA(2)-MICROGLOBULIN ID TOXIC LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; PEPTIDE; BETA-2-MICROGLOBULIN; BINDING; ANTIGENS; GENES; REASSOCIATION; EPITOPES; INVITRO AB As a preliminary step towards the use of cell surface single-chain class I major histocompatibility complex (MHC) molecules as T cell immunogens, we have engineered a recombinant gene encoding a full-length cell surface single-chain version of the H-2D(d) class I MHC molecule (SC beta D(d)m) which has beta(2)-microglobulin (beta(2)m) covalently linked to the amino terminus of a full-length H-2D(d) heavy chain via a peptide spacer. The single-chain protein is correctly folded and stably expressed on the surface of transfected L cells. It can present an antigenic peptide to an H-2D(d)-restricted antigen-specific T cell hybridoma. When expressed in peptide-transport-deficient cells, SC beta D(d)m can be stabilized and pulsed for antigen presentation by incubation with extracellular peptide at 27 degrees or 37 degrees C, allowing the preparation of cells with single-chain molecules that are loaded with a single chosen antigenic peptide. SC beta D(d)m can be stably expressed in beta(2)m-negative cells, showing that the single-chain molecule uses its own beta(2)m domain to achieve correct folding and surface expression. Furthermore, the beta(2)m domain of SC beta D(d)m, unlike transfected free beta(2)m, does not rescue surface expression of endogenous class I MHC in the beta(2)m-negative cells. This strict cis activity of the beta(2)m domain of SC beta D(d)m makes possible the investigation of class I MHC function in cells, and potentially in animals, that express but a single type of class I MHC molecule. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 44 TC 20 Z9 20 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 1994 VL 24 IS 11 BP 2633 EP 2639 DI 10.1002/eji.1830241110 PG 7 WC Immunology SC Immunology GA PT424 UT WOS:A1994PT42400010 PM 7957555 ER PT J AU BORKOWSKI, TA VANDYKE, BJ SCHWARZENBERGER, K MCFARLAND, VW FARR, AG UDEY, MC AF BORKOWSKI, TA VANDYKE, BJ SCHWARZENBERGER, K MCFARLAND, VW FARR, AG UDEY, MC TI EXPRESSION OF E-CADHERIN BY MURINE DENDRITIC CELLS - E-CADHERIN AS A DENDRITIC CELL-DIFFERENTIATION ANTIGEN CHARACTERISTIC OF EPIDERMAL LANGERHANS CELLS AND RELATED CELLS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE ADHESION; LOCALIZATION; LEUKOCYTE; EPITHELIA ID COLONY-STIMULATING FACTOR; LYMPH-NODES; MONOCLONAL-ANTIBODY; ADHESION MOLECULE; T-CELLS; FLUORESCEIN ISOTHIOCYANATE; IMMUNE-RESPONSES; RECEPTORS; SKIN; MACROPHAGE AB Murine epidermal Langerhans cells (LC) synthesize and express E-cadherin, a homophilic adhesion molecule that mediates adhesion of LC to keratinocytes in vitro. To determine if E-cadherin expression is characteristic of LC or is a feature of all dendritic cells (DC), we studied DC from various lymphoid tissues and peripheral blood for reactivity with anti-E-cadherin monoclonal antibody. By flow cytometry, DC prepared from skin-associated lymph nodes (LN) expressed E-cadherin, whereas DC prepared from gut-associated LN and spleen did not. However, direct comparison revealed that levels of E-cadherin expressed by DC from skin-associated LN were similar to fivefold lower than those expressed by freshly-prepared LC. Immunohistochemical studies confirmed that E-cadherin was expressed by DC in skin-associated LN in situ, and demonstrated that the number of E-cadherin(+) DC in LN draining skin previously treated with the contact allergen 2,4,6-trinitrochlorobenzene was increased relative to the number of E-cadherin(+) DC present in LN draining normal skin. DC propagated from the blood of cyclophosphamide-treated mice in granulocyte/macrophage-colony stimulating factor-supplemented media also expressed E-cadherin. E-cadherin immunoprecipitated from DC co-migrated in SDS polyacrylamide gels with that from fibroblasts transfected with murine E-cadherin cDNA, and mRNA encoding extracellular and intracellular regions of E-cadherin was present in DC propagated from blood. These results indicate that E-cadherin expressed by murine dendritic cells is identical to E-cadherin expressed by epithelial cells, and suggest that E-cadherin represents a DC differentiation antigen characteristic of LC and lineage-related cells (skin-associated LN DC). C1 NCI, DERMATOL BRANCH, BETHESDA, MD 20892 USA. UNIV WASHINGTON, DEPT BIOL STRUCT, SEATTLE, WA 98195 USA. FU NIA NIH HHS [AG 04360]; NIAID NIH HHS [AI 24137] NR 48 TC 68 Z9 68 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 1994 VL 24 IS 11 BP 2767 EP 2774 DI 10.1002/eji.1830241129 PG 8 WC Immunology SC Immunology GA PT424 UT WOS:A1994PT42400029 PM 7957569 ER PT J AU HERRMANN, K ANTONINI, A SHATZ, CJ AF HERRMANN, K ANTONINI, A SHATZ, CJ TI ULTRASTRUCTURAL EVIDENCE FOR SYNAPTIC-INTERACTIONS BETWEEN THALAMOCORTICAL AXONS AND SUBPLATE NEURONS SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE PHASEOLUS LECTIN LEUKOAGGLUTININ; ELECTRON MICROSCOPE; FERRET; SYNAPTOGENESIS; SUBPLATE NEURONS; THALAMOCORTICAL DEVELOPMENT ID LATERAL GENICULATE-NUCLEUS; RAT CEREBRAL-CORTEX; CAT VISUAL-CORTEX; ELECTRON-MICROSCOPIC ANALYSIS; EARLIEST GENERATED CELLS; LEUKOAGGLUTININ PHA-L; POSTNATAL-DEVELOPMENT; PRENATAL DEVELOPMENT; CORTICAL-NEURONS; TEMPORAL CORTEX AB Thalamic axons are known to accumulate in the subplate for a protracted period prior to invading the cortical plate and contacting their ultimate targets, the neurons of layer 4. We have examined the synaptic contacts made by visual and somatosensory thalamic axons during the transition period in which axons begin to leave the subplate and invade the cortical plate in the ferret. We first determined when geniculocortical axons leave the subplate and begin to grow into layer 4 of the visual cortex by injecting 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine (Dil) into the lateral geniculate nucleus (LGN). By birth most LGN axons are still confined to the subplate. Over the next 10 days LGN axons grow into layer 4, but many axons retain axonal branches within the subplate. To establish whether thalamic axons make synaptic contacts within the subplate, the anterograde tracer PHA-L was injected into thalamic nuclei of neonatal ferrets between postnatal day 3 and 12 to label thalamic axons at the electron microscope level. The analysis of the PHA-L injections confirmed the Dil data regarding the timing of ingrowth of thalamic axons into the cortical plate. At the electron microscope level, PHA-L-labelled axons were found to form synaptic contacts in the subplate. The thalamic axon terminals were presynaptic primarily to dendritic shafts and dendritic spines. Between postnatal days 12 and 20 labelled synapses were also observed within layer 4 of the cortex. The ultrastructural appearance of the synapses did not differ significantly in the subplate and cortical plate, with regard to type of postsynaptic profiles, length of postsynaptic density or presynaptic terminal size. These observations provide direct evidence that thalamocortical axons make synaptic contacts with subplate neurons, the only cell type within the subplate possessing mature dendrites and dendritic spines; they also suggest that functional interactions between thalamic axons and subplate neurons could play a role in the establishment of appropriate thalamocortical connections. C1 UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,DIV NEUROBIOL,BERKELEY,CA 94720. RP HERRMANN, K (reprint author), NIMH,NEUROPHYSIOL LAB,POB 608,POOLESVILLE,MD 20837, USA. FU NEI NIH HHS [EY02858] NR 78 TC 83 Z9 84 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV 1 PY 1994 VL 6 IS 11 BP 1729 EP 1742 DI 10.1111/j.1460-9568.1994.tb00565.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA PR423 UT WOS:A1994PR42300010 PM 7874312 ER PT J AU MCCRAE, RR AF MCCRAE, RR TI OPENNESS TO EXPERIENCE - EXPANDING THE BOUNDARIES OF FACTOR-V SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article ID 5-FACTOR MODEL; IMPORTED CONSTRUCTS; PERSONALITY-TRAITS; DIMENSIONS; PERCEPTION; ABSORPTION; PSYCHOSIS; DISORDER; JAPANESE AB The fifth factor in lexical studies of trait adjectives is commonly interpreted as Intellect, whereas the corresponding factor derived from questionnaire studies is typically identified as Openness to Experience. Intellect as a construct is problematic because it erroneously suggests an equivalence of Factor V with intelligence, describes aspects of Factor III (Conscientiousness) as well as of Factor V, and fails to suggest the diverse psychological correlates that Factor V is known to have. By contrast, Openness to Experience is a broader construct that implies both receptivity to many varieties of experience and a fluid and permeable structure of consciousness. Data from analyses of adjectives, established personality questionnaires, and Hartman's (1991) new Boundary Questionnaire support these interpretations. The construct of Openness can be transported across geographical and cultural boundaries to function as a universal dimension of personality structure. RP MCCRAE, RR (reprint author), NIA,GERONTOL RES CTR,PERSONAL STRESS & COPING SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 102 TC 145 Z9 145 U1 4 U2 34 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD NOV PY 1994 VL 8 IS 4 BP 251 EP 272 DI 10.1002/per.2410080404 PG 22 WC Psychology, Social SC Psychology GA PV479 UT WOS:A1994PV47900003 ER PT J AU PELKONEN, P LANG, MA WILD, CP NEGISHI, M JUVONEN, RO AF PELKONEN, P LANG, MA WILD, CP NEGISHI, M JUVONEN, RO TI ACTIVATION OF ANATOXIN B-1 BY MOUSE CYP2A ENZYMES AND CYTOTOXICITY IN RECOMBINANT YEAST-CELLS SO EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION LA English DT Article DE AFLATOXIN B-1; SACCHAROMYCES CEREVISIAE; CYP2A; METABOLIC ACTIVATION ID SITE-DIRECTED MUTAGENESIS; HUMAN LIVER-MICROSOMES; COUMARIN 7-HYDROXYLASE; STABLE EXPRESSION; STEROID 15-ALPHA-HYDROXYLASE; METABOLIC-ACTIVATION; II P-45015-ALPHA; AFLATOXIN-B1; CYTOCHROME-P-450; CDNA AB The ability of three highly homologous mouse liver CYP2A enzymes to activate aflatoxin B-1 was studied by expressing them in recombinant AH22 Saccharomyces cerevisiae yeast cells. The reconstituted monooxygenase complex with CYP2A5 purified from yeast cell microsomes produced epoxide at a rate of 17.2 nmol/min per nmol P450 in the presence of 50 mu M aflatoxin B-1 while CYP2A4 had about 10% and P4507 alpha only 1.5% of this activity. However, K-m values were 530 and 10 mu M and V-max values 12.5 and 14.3 nmol/min per nmol P450 for CYP2A4 and CYP2A5, respectively. When recombinant yeast cells were exposed to aflatoxin B-1 LC(50) concentrations were 7.5 +/- 5.5 mu M for CYP2A4, 0.45 +/- 0.10 mu M for CYP2A5 and > 320 mu M for P4507 alpha expressing yeast cells. Aflatoxin B-1-DNA adduct levels in the same yeast cells were 50, 890 pmol/mg DNA and below detection limit when 3.0 mu M aflatoxin B-1 was used in the incubation mixture. Coumarin an inhibitor for CYP2A4 and a substrate for CYP2A5 diminished the toxicity of aflatoxin B-1 in a dose-dependent manner for these recombinant yeast cells. These data demonstrate that (1) highly homologous mouse CYP2A enzymes activate aflatordn B-1 in a different manner and (2) that recombinant yeast cells expressing mammalian CYP enzymes are a useful and inexpensive system to test the role of different enzymes in aflatoxin B-1 toxicity. The data also indicate that mouse CYP2A5 and its counterpart in other species could have a significant role in aflatoxin B-1 toxicity in organs where it is expressed at high levels. C1 UNIV KUOPIO,DEPT PHARMACOL & TOXICOL,SF-70211 KUOPIO,FINLAND. INT AGCY RES CANC,F-69372 LYON 08,FRANCE. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RI Lang, Matti/C-9948-2009 FU NIEHS NIH HHS [1POIES06052-01] NR 37 TC 28 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6917 J9 EUR J PHARM-ENVIRON JI Eur. J. Pharmacol.-Environ. Toxicol. Pharmacol. Sect. PD NOV 1 PY 1994 VL 292 IS 1 BP 67 EP 73 DI 10.1016/0926-6917(94)90027-2 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PQ374 UT WOS:A1994PQ37400006 PM 7867691 ER PT J AU RAY, JM STETLERSTEVENSON, WG AF RAY, JM STETLERSTEVENSON, WG TI THE ROLE OF MATRIX METALLOPROTEASES AND THEIR INHIBITORS IN TUMOR INVASION, METASTASIS AND ANGIOGENESIS SO EUROPEAN RESPIRATORY JOURNAL LA English DT Review DE ANGIOGENESIS; CANCER; INVASION; MATRIX METALLOPROTEASES; METASTASIS; TISSUE INHIBITORS OF METALLOPROTEASES ID ERYTHROID-POTENTIATING ACTIVITY; HUMAN-TISSUE INHIBITOR; FIBROBLAST COLLAGENASE INHIBITOR; BASEMENT-MEMBRANE COLLAGEN; CHICKEN-EMBRYO FIBROBLASTS; SQUAMOUS-CELL CARCINOMAS; MESSENGER-RNA EXPRESSION; IV COLLAGENASE; INTERSTITIAL COLLAGENASE; PLASMINOGEN-ACTIVATOR AB One critical event of tumour invasion that signals the initiation of the metastatic cascade is thought to be interaction of the tumour cell with the basement membrane. Basement membranes may also pose as barriers to tumour cell invasion at multiple points later in the metastatic cascade, including during the processes of vascular infiltration and extravasation. Thus, an important proteolytic event in the metastatic cascade, and also angiogenesis, appears to be degradation of basement membrane components. A specific class of extracellular matrix degrading metalloenzymes, the matrix metalloproteases, and their endogenous inhibitors, the tissue inhibitors of metalloproteases, are thought to have a role in the creation of the proteolytic defect in basement membrane type IV collagen. We will review the evidence which indicates that matrix metalloproteases and tissue inhibitors of metalloproteases are essential for tumour cell invasion and angiogenesis. The regulation of matrix metalloproteases will be discussed, including gene activation and transcription, messenger ribonucleic acid (mRNA) stability, binding of proenzymes to cell. membranes and/or matrix components, proenzyme activation, and inactivation by endogenous inhibitors. We will also discuss the mechanism for tissue inhibitor of metalloproteases-mediated inhibition of tumour invasion and angiogenesis. This appears, at least in part, to be through inhibition of protease activity required for cellular invasion, although recent observations suggest that tissue inhibitors of metalloproteases affect other distinct groups of biological activities through mechanisms other than matrix metalloprotease inhibition. RP RAY, JM (reprint author), NEI, PATHOL LAB, EXTRACELLULAR MATRIX PATHOL SECT, 9000 ROCKVILLE PIKE, BLDG 10 RM 2A33, BETHESDA, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 124 TC 338 Z9 355 U1 0 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD NOV PY 1994 VL 7 IS 11 BP 2062 EP 2072 PG 11 WC Respiratory System SC Respiratory System GA PW671 UT WOS:A1994PW67100026 PM 7533104 ER PT J AU IVANOVA, VS BONNER, WM AF IVANOVA, VS BONNER, WM TI EXPRESSION OF A MARKED H2A HISTONE PROTEIN IN MAMMALIAN-CELLS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID SEQUENCE; VARIANT; GENE; ISOPROTEIN; RNA AB Histone protein sequences are highly conserved. In order to determine whether histones with sequences not found in nature would be tolerated in the chromatin of tissue culture cells, a gene for histone H2A.1a was altered by extending the protein coding region with eight amino acids, including three residues for methionine which are lacking in H2A.1a. Isolated clones of HeLa cells transfected with the gene construct were found to produce a novel protein which was resolved from other histone proteins on AUT-AUC two-dimensional gels. One clone, HeLa-B4, in which the novel protein named H2A.E accounted for about 10% of total H2A protein, was studied further. The linkage of H2A.E mRNA concentrations to the rates of DNA and protein synthesis was found to be the same as that of other replication-linked histone mRNA species. The stability of H2A.E in chromatin as well as the partitioning of nascent H2A.E protein between soluble and nuclear fractions was found to be indistinguishable from that of other histone species. This study shows that histone proteins with sequences other than the conserved sequences found in nature may be utilized in tissue culture cells. (c) 1994 Academic Press, Inc. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 21 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV PY 1994 VL 215 IS 1 BP 63 EP 67 DI 10.1006/excr.1994.1315 PG 5 WC Oncology; Cell Biology SC Oncology; Cell Biology GA PP613 UT WOS:A1994PP61300010 PM 7957682 ER PT J AU ROTTEM, M HULL, G METCALFE, DD AF ROTTEM, M HULL, G METCALFE, DD TI DEMONSTRATION OF DIFFERENTIAL-EFFECTS OF CYTOKINES ON MAST-CELLS DERIVED FROM MURINE BONE-MARROW AND PERIPHERAL-BLOOD MONONUCLEAR-CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE MAST CELLS; CYTOKINES; SCF; IL-3 ID GROWTH-FACTOR ACTIVITY; C-KIT LIGAND; HEMATOPOIETIC PROGENITOR CELLS; COLONY-STIMULATING FACTOR; FC-EPSILON-RI; FACTOR-I; P-CELL; IMMUNOGLOBULIN-E; KINASE RECEPTOR; CDNA CLONE AB Mouse bone marrow (BM) was cultured in the presence of recombinant mouse (rm) interleukin-3 (IL-3), rmIL-4, rmIL-5, rmIL-7, purified mouse (m) IL-9, rmIL-lO, recombinant human (rh) macrophage-colony-stimulating factors (M-CSF), rm granulocyte-macrophage colony-stimulating factors (GMCSF), rm stem cell factor (SCF), rh interferon-alpha (IFN-alpha), rmIFN-gamma, and mNGF to determine which cytokine would give rise to mast cells in murine BM cultures. From a starting population of 1x10(7) cells, 1.55x10(7) mast cells developed within 14 days in cultures supplemented by rmIL-3. No mast cells were seen at day 14 when any of the other cytokines were present alone, except for rmSCF, which supported the growth of <0.01% of mast cells observed in IL-3-dependent BM cultures. When rmIL-4, -5, -7, -10, mIL-9, rhM-CSF, rmGM-CSE, rmSCF, rhIFN-alpha, gamma, or mNGF were added to BM cultures in the presence of rmIL-3, mast cell growth increased 200% with the addition of rmSCF, and 10% when rmIL-4 or IL-9 was added. However, the addition of rhM-CSF, rmGM-CSF, rmIFN-gamma, and mNGF decreased the number of mast cells. Mast cell number, as determined by metachromatic stains, generally approximated the number of Fc epsilon RI(+) cells as assessed by PACS analysis. Among the cytokines, only rmIL-4 and rmSCF were able to support the survival of mast cell progenitors in the absence of obvious mast cell proliferation, similarly to rmIL-3. Only rmSCF alone, or in combination with rmIL-3 or -4, supported the growth of mast cells from mouse peripheral blood mononuclear cells (PBMC) where the number of mast cell precursors was about 90 per 10(6) PBMC. With time, mouse BM cells cultured in rmIL-3 became more responsive to rmSCF. Taken together, these data demonstrate that IL-3 is a major early mast cell growth factor, that mast cells become more dependent on SCF with time, and that the effects of IL-3 and SCF are upregulated (IL-4) or downregulated (M-CSF, GM-CSF, IFN-gamma) by both growth factors and proinflammatory cytokines. RP ROTTEM, M (reprint author), NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BLDG 10,ROOM 11C205,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 52 TC 34 Z9 35 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD NOV PY 1994 VL 22 IS 12 BP 1147 EP 1155 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PM860 UT WOS:A1994PM86000004 PM 7523167 ER PT J AU PIMENTA, PFP DASILVA, PP RANGARAJAN, D SMITH, DF SACKS, DL AF PIMENTA, PFP DASILVA, PP RANGARAJAN, D SMITH, DF SACKS, DL TI LEISHMANIA-MAJOR - ASSOCIATION OF THE DIFFERENTIALLY EXPRESSED GENE B-PROTEIN AND THE SURFACE LIPOPHOSPHOGLYCAN AS REVEALED BY MEMBRANE CAPPING SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE LEISHMANIA; CAPPING; LIPOPHOSPHOGLYCAN; GENE B PROTEIN; CYTOCHEMISTRY; ULTRASTRUCTURE; PHOSPHATE-BUFFERED SALINE; FLUORESCEIN ISOTHIOCYANATE; TETRAMETHYLRHODAMINE ISOTHIOCYANATE ID FINE-STRUCTURE; FRACTURE-FLIP; CELL-SURFACES; STAGE; PROMASTIGOTES; DONOVANI; RELEASE; REDISTRIBUTION; AMASTIGOTES; SERUM AB The lipophosphoglycan (LPG) of Leishmania promastigotes forms a dense glycocalyx which effectively covers the entire surface of the cell, and which undergoes structural modifications during the differentiation of promastigotes to the infective or metacyclic stage. Recently, the first protein marker for metacyclic promastigotes of Leishmania major has been characterized. This protein, termed gene B protein, is located on the cell surface, yet it lacks any hydrophobic sequence for membrane attachment. It does contain an unusual amino acid repeat that is related to the peptidoglycan binding domain of protein A from Staphylococcus aureus, suggesting that the protein might interact with metacyclic LPG via this domain for attachment to the cell. We have studied the distribution of LPG, gene B protein, and the major surface protease, gp63, by labeling them with immunogold or immunofluorescence prior to and during capping events. Thin sections of double-labeled parasites revealed that the gene B protein-gold particles were colocalized with the LPG-gold particles in the LPG capping structures at the extremities of the cell. Cocapping of LPG and gene B protein was also observed with two-color fluorescence. No similar redistribution was seen in gp63 or with integral membrane proteins. In contrast to the gene B protein, gp63 could only be immunogold labeled on the metacyclic surface after capping and shedding of the LPG, providing further evidence that it and other membrane-associated proteins are normally buried under the LPG coat. The unusual surface exposure of the gene B protein is consistent with its hydrophilic and LPG binding properties, which allow it to become incorporated into the cell coat and to localize to the most external aspects Of the cell. (C) 1994 Academic Press, Inc. C1 NCI,MEMBRANE BIOL SECT,FREDERICK,MD 21701. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT BIOCHEM,LONDON,ENGLAND. RP PIMENTA, PFP (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. FU Wellcome Trust NR 30 TC 23 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD NOV PY 1994 VL 79 IS 3 BP 468 EP 479 DI 10.1006/expr.1994.1108 PG 12 WC Parasitology SC Parasitology GA PR139 UT WOS:A1994PR13900024 PM 7957764 ER PT J AU WARD, GE FUJIOKA, H AIKAWA, M MILLER, LH AF WARD, GE FUJIOKA, H AIKAWA, M MILLER, LH TI STAUROSPORINE INHIBITS INVASION OF ERYTHROCYTES BY MALARIAL MEROZOITES SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE MALARIA; PLASMODIUM KNOWLESI; ERYTHROCYTE; INVASION; STAUROSPORINE; OKADAIC ACID; PROTEIN KINASES; PROTEIN PHOSPHATASES; ACTIN; PARASITOPHOROUS VACUOLE MEMBRANE ID PLASMODIUM-FALCIPARUM; PROTEIN-KINASE; INFECTED ERYTHROCYTES; CELL INVASION; OKADAIC ACID; ACTIN; PHOSPHORYLATION; CALMODULIN; CYTOSKELETON; CYTOCHALASIN AB Staurosporine, a protein kinase inhibitor, inhibits the invasion of rhesus monkey erythrocytes by Plasmodium knowlesi merozoites with an IC50 of 250 nM. The drug exerts its effects primarily on the merozoite, with little or no effect on the erythrocyte. Okadaic acid, an inhibitor of protein phosphatases, can partially abrogate the inhibitory effects of staurosporine. Staurosporine arrests invasion at a step which is ultrastructurally similar to the arrest caused by cytochalasins B and D: the merozoite attaches, apically reorients, and forms a junction with the erythrocyte, but it does not internalize. These results suggest that protein phosphorylation within the merozoite plays an important role in the internalization Step of invasion. (C) 1994 Academic Press, Inc. C1 CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. RP WARD, GE (reprint author), NIAID,MALARIA RES LAB,BETHESDA,MD 20892, USA. OI Ward, Gary/0000-0003-4138-3055 FU NIAID NIH HHS [AI-10645] NR 29 TC 64 Z9 66 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD NOV PY 1994 VL 79 IS 3 BP 480 EP 487 DI 10.1006/expr.1994.1109 PG 8 WC Parasitology SC Parasitology GA PR139 UT WOS:A1994PR13900025 PM 7957765 ER PT J AU SCHWARTZ, SM JAMES, BF AF SCHWARTZ, SM JAMES, BF TI IMPROVING ETHNIC DIVERSITY IN RESEARCH TRAINING-PROGRAMS SO FASEB JOURNAL LA English DT Editorial Material C1 NHLBI,BETHESDA,MD 20892. RP SCHWARTZ, SM (reprint author), UNIV WASHINGTON,SCH MED,DEPT PATHOL SJ-60,1959 PACIFIC ST,HSB 1420,SEATTLE,WA 98195, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 1994 VL 8 IS 14 BP 1105 EP 1109 PG 5 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA PT128 UT WOS:A1994PT12800002 PM 7958613 ER PT J AU ALEXANDER, NJ ANDREWS, LB CONEY, P DECHERNEY, AH GARCIA, CR GROBSTEIN, C HODGEN, GD JONES, HW MCCARTHY, CR MCCORMICK, RA MARRS, R NAMATH, CH PAULSEN, CA ROBERTSON, J WALLACH, EE WALTERS, L SCHRADER, C LANZENDORF, SE ZEITZ, JC AF ALEXANDER, NJ ANDREWS, LB CONEY, P DECHERNEY, AH GARCIA, CR GROBSTEIN, C HODGEN, GD JONES, HW MCCARTHY, CR MCCORMICK, RA MARRS, R NAMATH, CH PAULSEN, CA ROBERTSON, J WALLACH, EE WALTERS, L SCHRADER, C LANZENDORF, SE ZEITZ, JC TI ETHICAL CONSIDERATIONS OF ASSISTED REPRODUCTIVE TECHNOLOGIES SO FERTILITY AND STERILITY LA English DT Review ID HUMAN INVITRO FERTILIZATION; OVARIAN-CANCER RISK; STATES CASE-CONTROL; INTRACYTOPLASMIC SPERM INJECTION; GAMETE INTRAFALLOPIAN TRANSFER; HUMAN PREIMPLANTATION EMBRYOS; HUMAN PREEMBRYO BIOPSY; HUMAN OOCYTES; UNITED-STATES; COLLABORATIVE ANALYSIS C1 AMER BAR FDN,MED LAW,CHICAGO,IL. UNIV ARIZONA,HLTH SCI CTR,TUCSON,AZ 85724. TUFTS UNIV,SCH MED,NEW ENGLAND MED CTR,DEPT OBSTET & GYNECOL,BOSTON,MA. UNIV PENN HOSP & SCH MED,PHILADELPHIA,PA. UNIV CALIF SAN DIEGO,SAN DIEGO,CA. EASTERN VIRGINIA MED SCH,JONES INST REPROD MED,NORFOLK,VA 23501. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21218. GEORGETOWN UNIV,KENNEDY INST ETH,WASHINGTON,DC 20057. UNIV NOTRE DAME,NOTRE DAME,IN. SANTA MONICA HOSP MED CTR,MED CTR,CTR ASSISTED REPROD MED,SANTA MONICA,CA. NAMATH HANGER INVESTMENT CORP,BETHESDA,MD. UNIV WASHINGTON,SEATTLE,WA. UNIV TEXAS,SCH LAW,AUSTIN,TX 78712. JOHNS HOPKINS UNIV,SCH MED,DEPT GYNECOL & OBSTET,BALTIMORE,MD. RP ALEXANDER, NJ (reprint author), NICHHD,CONTRACEPT DEV BRANCH,BETHESDA,MD 20892, USA. NR 160 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 1994 VL 62 IS 5 SU 1 BP R3 EP & PG 0 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA PN384 UT WOS:A1994PN38400001 ER PT J AU KRISHNA, MC HALEVY, RF ZHANG, RL GUTIERREZ, PL SAMUNI, A AF KRISHNA, MC HALEVY, RF ZHANG, RL GUTIERREZ, PL SAMUNI, A TI MODULATION OF STREPTONIGRIN CYTOTOXICITY BY NITROXIDE SOD MIMICS SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE EPR; FREE RADICALS; H2O2; ESCHERICHIA-COLI B; SEMIQUINONE; SUPEROXIDE; SPIN-LABELS; OXIDATIVE STRESS; SPIN-TRAPPING; DMPO ID SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; ESCHERICHIA-COLI; FREE-RADICALS; OXIDATIVE DAMAGE; IRON-CHELATORS; CYTO-TOXICITY; SPIN LABELS; INHIBITION; OXYGEN AB Nitroxides are cell-permeable, stable radicals that react readily with paramagnetic species such as transition metals or short-lived free radicals, though not generally with diamagnetic molecules. Nitroxides can undergo one-electron selective redox reactions and thereby potentially modify the activity of cytotoxic drugs. Streptonigrin (SN) toxicity requires bioreduction to yield the semiquinone radical, and the toxicity is reportedly mediated by transition metals and oxygen-derived reactive species via redox-cycling of the semiquinone intermediate. The present study shows that (1) nitroxides protected isolated DNA and also aerated or hypoxic bacterial cells from SN toxicity; (2) H2O2 potentiated the hypoxic cytotoxicity of the drug but inhibited the damage to aerated cells; (3) pretreatment of cells with H2O2 conferred some protection, but not when the drug alone was preexposed to H2O2; and (4) desferrioxamine and 2,2-dipyridyl, though neither diethylenetriamino pentaacetate, exogenous catalase, or superoxide dismutase, decreased SN-induced cell killing. The mechanisms by which nitroxides protect from SN toxicity involve both a selective radical-radical reaction with SN semiquinone and the reoxidation of reduced cellular transition metal ions. On the other hand, H2O2 appears to exert two opposing effects: (1) facilitation of cell killing by the Fenton reaction and (2) lowering the cellular level of reducing equivalents, thus inhibiting the bioreductive activation of SN. C1 UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,IL-91010 JERUSALEM,ISRAEL. RP KRISHNA, MC (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,RADIAT BIOL BRANCH,BLDG 10,RM B3 B69,BETHESDA,MD 20892, USA. NR 40 TC 24 Z9 24 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. PD NOV PY 1994 VL 17 IS 5 BP 379 EP 388 DI 10.1016/0891-5849(94)90164-3 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA PK699 UT WOS:A1994PK69900001 PM 7835744 ER PT J AU SHACTER, E WILLIAMS, JA LIM, M LEVINE, RL AF SHACTER, E WILLIAMS, JA LIM, M LEVINE, RL TI DIFFERENTIAL SUSCEPTIBILITY OF PLASMA-PROTEINS TO OXIDATIVE MODIFICATION - EXAMINATION BY WESTERN-BLOT IMMUNOASSAY SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE OXIDATIVE MODIFICATION; PROTEIN CARBONYLS; TISSUES; PLASMA; FIBRINOGEN; WESTERN BLOT; IMMUNOASSAY; FREE RADICALS ID METAL-CATALYZED OXIDATION; GLUTAMINE-SYNTHETASE; FREE-RADICALS; OXYGEN RADICALS; REPERFUSION INJURY; CARBONYL CONTENT; HUMAN-DISEASE; DAMAGE; INACTIVATION; DEGRADATION AB Plasma proteins are exposed to oxidants in a variety of circumstances in vivo, such as during tissue injury and inflammation. In this report, the relative susceptibility of each of the major plasma proteins to oxidative modification was assessed by exposing whole plasma to a metal-catalyzed radical generating system and detecting oxidation (protein carbonyl groups) using a novel Western blot immunoassay. Proteins were derivitized with dinitrophenylhydrazine, separated by SDS-gel electrophoresis, and screened with antibodies against dinitrophenyl groups. As little as I pmol of protein-associated carbonyls could be detected (100 ng of a 50 kD protein containing 0.5 mol carbonyl/mol protein). Individual plasma proteins were identified by their comigration with standards, crossreactivity with specific antibodies, and by comparison of plasma to serum. Using this approach, we found that plasma fibrinogen was much more susceptible to oxidative modification compared to the other major plasma proteins, albumin, immunoglobulins, and transferrin. The results emphasize the utility of this method for studying oxidation of proteins in cell extracts and tissues and indicate that experiments on the effects of oxidation on fibrinogen function are merited. C1 NCI,GENET LAB,BETHESDA,MD 20892. NHLBI,BIOCHEM LAB,BETHESDA,MD. RI Levine, Rodney/D-9885-2011 NR 61 TC 295 Z9 307 U1 4 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV PY 1994 VL 17 IS 5 BP 429 EP 437 DI 10.1016/0891-5849(94)90169-4 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA PK699 UT WOS:A1994PK69900006 PM 7835749 ER PT J AU ROST, K KASHNER, TM SMITH, GR AF ROST, K KASHNER, TM SMITH, GR TI EFFECTIVENESS OF PSYCHIATRIC INTERVENTION WITH SOMATIZATION DISORDER PATIENTS - IMPROVED OUTCOMES AT REDUCED COSTS SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID CONSULTATION; CARE AB In order to determine the health effects of an intervention that reduces the cost of care for somatization disorder (SD) patients, 59 primary care physicians were randomized to receive a psychiatric consultation letter providing treatment recommendations for 73 patients either at baseline or the end of the year-long study. Seventy of these patients (96%) were followed every 4 months for 1 year by a research assistant blind to randomization. A year following the intervention, patients of experimental physicians reported greater physical capacity than patients of control physicians (xBAR difference = 17.9, 95% CI 1.0-34.9) with a $466 reduction (95% CI $132-$699) in health care charges. In addition to a net 21% reduction in health care charges for the typical SD patient, the consultation letter improved physical functioning in a group of highly impaired subjects. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PSYCHIAT & BEHAV SCI,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,NIMH,CTR RURAL MENTAL HLTH CARE RES,LITTLE ROCK,AR 72205. FU NIMH NIH HHS [K02 MH00843, P50 MH48197, R01 MH46090] NR 16 TC 70 Z9 70 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV PY 1994 VL 16 IS 6 BP 381 EP 387 DI 10.1016/0163-8343(94)90113-9 PG 7 WC Psychiatry SC Psychiatry GA PR841 UT WOS:A1994PR84100002 PM 7843574 ER PT J AU SANTOS, ME DRAKE, JW AF SANTOS, ME DRAKE, JW TI RATES OF SPONTANEOUS MUTATION IN BACTERIOPHAGE-T4 ARE INDEPENDENT OF HOST FIDELITY DETERMINANTS SO GENETICS LA English DT Review ID ESCHERICHIA-COLI K-12; FORMAMIDOPYRIMIDINE-DNA GLYCOSYLASE; MISMATCH-REPAIR; SPONTANEOUS MUTAGENESIS; FRAMESHIFT MUTATION; BASE SUBSTITUTIONS; STRAINS LACKING; GENE-PRODUCTS; LAC REPRESSOR; POLYMERASE AB Bacteriophage T4 encodes most of the genes whose products are required for its DNA metabolism, and host (Escherichia coli) genes can only infrequently complement mutationally inactivated T4 genes. We screened the following host mutator mutations for effects on spontaneous mutation rates in T4: mutT (destruction of aberrant dGTPs), polA, polB and polC (DNA polymerases), dnaQ (exonucleolytic proofreading), mutH, mutS, mutL and uvrD (methyl-directed DNA mismatch repair), mutM and mutY (excision repair of oxygen-damaged DNA), mutA (function unknown), and topB and osmZ (affecting DNA topology). None increased T4 spontaneous mutation rates within a resolving power of about twofold (nor did optA, which is not a mutator but overexpresses a host dGTPase). Previous screens in T4 have revealed strong mutator mutations only in the gene encoding the viral DNA polymerase and proofreading S'-exonuclease, plus weak mutators in several polymerase accessory proteins or determinants of dNTP pool sizes. T4 maintains a spontaneous mutation rate per base pair about 30-fold greater than that of its host. Thus, the joint high fidelity of insertion by T4 DNA polymerase and proofreading by its associated 3'-exonuclease appear to determine the T4 spontaneous mutation rate, whereas the host requires numerous additional systems to achieve high replication fidelity. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NR 112 TC 24 Z9 24 U1 1 U2 4 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 1994 VL 138 IS 3 BP 553 EP 564 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA PP050 UT WOS:A1994PP05000002 PM 7851754 ER PT J AU ADAMSON, MC DENNIS, C DELANEY, S CHRISTIANSEN, J MONKLEY, S KOZAK, CA WAINWRIGHT, B AF ADAMSON, MC DENNIS, C DELANEY, S CHRISTIANSEN, J MONKLEY, S KOZAK, CA WAINWRIGHT, B TI ISOLATION AND GENETIC-MAPPING OF 2 NOVEL MEMBERS OF THE MURINE WNT GENE FAMILY, WNT11 AND WNT12, AND THE MAPPING OF WNT5A AND WNT7A SO GENOMICS LA English DT Article ID INT-1 PROTOONCOGENE; MOUSE CHROMOSOME-6; EXPRESSION; SUBUNIT; LOCALIZATION; SEQUENCES; RECEPTOR; WINGLESS; HOMOLOG; CLONING AB The murine Wnt genes are implicated in the control of a variety of developmental processes. Using a PCR-based approach, we have isolated two novel members of the murine Wnt gene family, Wnt11 and Wnt12. These cDNAs display an amino acid sequence identity of between 38 and 49% with all other murine Wnts over the regions that we have isolated. In addition, two previously described Wnt genes, Wnt5a and Wnt7a, were detected in RT-PCR products. Interspecific crosses were used to demonstrate close linkage between Wnt12 and Wnt1 on Chromosome (Chr) 15. Wnt7a was mapped to mouse Chr 6, Wnt5a to the centromeric region of Chr 14, and Wnt11 to Chr7. (C) 1994 Academic Press,Inc. C1 UNIV QUEENSLAND,CTR MOLEC BIOL & BIOTECHNOL,ST LUCIA,QLD 4072,AUSTRALIA. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 30 TC 33 Z9 33 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 1 PY 1994 VL 24 IS 1 BP 9 EP 13 DI 10.1006/geno.1994.1575 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PT473 UT WOS:A1994PT47300002 PM 7896292 ER PT J AU FLETCHER, FA RENSHAW, B HOLLINGSWORTH, J BAUM, P LYMAN, SD JENKINS, NA GILBERT, DJ COPELAND, NG DAVISON, BL AF FLETCHER, FA RENSHAW, B HOLLINGSWORTH, J BAUM, P LYMAN, SD JENKINS, NA GILBERT, DJ COPELAND, NG DAVISON, BL TI GENOMIC ORGANIZATION AND CHROMOSOMAL LOCALIZATION OF MOUSE EPLG2, A GENE ENCODING A BINDING-PROTEIN FOR THE RECEPTOR TYROSINE KINASE ELK SO GENOMICS LA English DT Article ID FAMILY; PHOSPHORYLATION; IDENTIFICATION; SEQUENCES; MEMBERS; CLONING; CHICKEN; SITES; MAP AB The human gene EPLG2 (Eph ligand-2) encodes a potential ligand for the receptor tyrosine kinase elk. High sequence conservation between the human and the rat cDNAs and developmentally regulated expression of the rat gene suggest that the protein encoded by EPLGS plays an important role in mammalian development. To facilitate analysis of the physiological role of the protein, we have cloned and characterized a 24-kb region of mouse genomic DNA containing the mouse homologue of EPLG2 (Eplg2), including 5'- and 3'-flanking sequences. Restriction mapping, coupled with Southern blot hybridization and sequencing, was used to determine the structural organization of the gene. The Eplg2 genomic locus spans a region of approximately 12 kb, encoding five exons and four introns. The first intron comprises approximately 8.5 kb of the entire 12-kb genomic sequence. Eplg2 was mapped to the mouse X chromosome by interspecific backcross analysis and is tightly linked to the androgen receptor (Ar) locus. (C) 1994 Academic Press, Inc. C1 IMMUNEX RES & DEV CORP,DEPT MOLEC IMMUNOL,SEATTLE,WA 98101. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; PHS HHS [U07598] NR 29 TC 18 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 1 PY 1994 VL 24 IS 1 BP 127 EP 132 DI 10.1006/geno.1994.1589 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PT473 UT WOS:A1994PT47300016 PM 7896266 ER PT J AU TAPPERO, G NATOLI, G ANFOSSI, G ROSINA, F NEGRO, F SMEDILE, A BONINO, F ANGELI, A PURCELL, RH RIZZETTO, M LEVRERO, M AF TAPPERO, G NATOLI, G ANFOSSI, G ROSINA, F NEGRO, F SMEDILE, A BONINO, F ANGELI, A PURCELL, RH RIZZETTO, M LEVRERO, M TI EXPRESSION OF THE C-MYC PROTOONCOGENE PRODUCT IN CELLS INFECTED WITH THE HEPATITIS-DELTA VIRUS SO HEPATOLOGY LA English DT Article ID B SURFACE-ANTIGEN; HEPATOCELLULAR-CARCINOMA; LEUCINE ZIPPER; DISEASE; REPLICATION; PROTEINS; RNA; CARRIERS; BIOLOGY; LINE AB The intrahepatic accumulation of the c-myc protooncogene product was observed on immunofluorescence in each of six patients with chronic hepatitis delta virus infection who exhibited the hepatitis D antigen in their livers. The c-myc product was stained in the same nuclei that contained the hepatitis D antigen. C-myc was not observed in acute hepatitis D or in cases of chronic hepatitis delta virus infection without expression of the hepatitis D antigen. The protooncogene product was detected in only 1 of 32 viral and nonviral liver disorders unrelated to hepatitis delta virus. To confirm these observations, we transfected HBsAg-positive (PCL/PRF/5) and HBsAg-negative (HepG2) transformed liver cell lines with a plasmid containing a hepatitis delta virus cDNA trimer under the control of the SV40 early enhancer/promoter sequences. Whereas baseline c-myc expression was barely detectable in mock-transfected PLC/PRF/5 or HepG2 cells, strong c-myc nuclear fluorescence was observed when these same cells were transfected with the hepatitis D antigen expression vector. Similar results were obtained after infection of HeLa cells with a recombinant vaccinia virus expressing the hepatitis D antigen. Detection of c-myc mRNA sequences by means of in situ hybridization suggested that the c-myc product accumulation was not due to increased amounts of its mRNA. The c-myc protein accumulates selectively in the livers of patients with chronic hepatitis delta virus infection and in the same nuclei that contain the hepatitis D antigen. The expression of c-myc in hepatitis D antigen-containing cells does not require the presence of hepatitis B virus infection. C1 OSPED MOLINETTE,DEPT GASTROENTEROL,I-10126 TURIN,ITALY. UNIV TURIN,SCH MED,MED GEN CLIN,I-10043 ORBASSANO,ITALY. UNIV TURIN,SCH MED,DEPT CLIN & BIOL SCI,I-10043 ORBASSANO,ITALY. UNIV ROMA LA SAPIENZA,MED CLIN 1,I-00100 ROME,ITALY. NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. RI Negro, Francesco/E-2183-2012; OI Bonino, Ferruccio/0000-0001-9942-0328 NR 36 TC 4 Z9 4 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 1994 VL 20 IS 5 BP 1109 EP 1114 DI 10.1016/0270-9139(94)90744-7 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PN755 UT WOS:A1994PN75500001 PM 7523269 ER PT J AU JANINI, GM MUSCHIK, GM ISSAQ, HJ AF JANINI, GM MUSCHIK, GM ISSAQ, HJ TI CAPILLARY ELECTROPHORESIS SEPARATION OF HETEROCYCLIC NITROSOAMINO ACID-CONFORMERS AT SUB-AMBIENT TEMPERATURES SO HRC-JOURNAL OF HIGH RESOLUTION CHROMATOGRAPHY LA English DT Article DE CAPILLARY ELECTROPHORESIS; NITROSAMINES; SUBAMBIENT TEMPERATURE; SYN AND ANTI ISOMERS AB The separation of a selected group of naturally occurring, heterocyclic nitrosoamino acids was achieved by capillary zone electrophoresis and the resolution of the syn and anti conformers improved as the temperature was lowered to 5 degrees C. The double peaks observed for each nitrosoamino acid are probably caused by the slow kinetics of conformational isomerism. The experimental setup consisted of a P/ACE 5510 electrophoresis system, a 57 cm polyacrylamide-coated capillary, and a 10 mM phosphate buffer, pH 7.2, containing 2 mM of 3-(N-N-dimethylmyristylammonio)propanesulfonate (DMMAPS) and 0.1% Tween 20. Our study shows that (a) the lower the temperature, the greater the resolution and the longer the migration times; and (b) different nitrosoamino acid conformers were resolved at different temperatures because of differences in the rate of isomerization. For example, the conformers of N-nitrosothiazolidine-4-carboxylic acid were partially resolved at 30 degrees C while those of N-nitrosoproline were well resolved at the same temperature. RP JANINI, GM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,POB B,FREDERICK,MD 21702, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU DR ALFRED HUTHIG VERLAG GMBH PI HEIDELBERG 1 PA POSTFACH 102869, W-69018 HEIDELBERG 1, GERMANY SN 0935-6304 J9 HRC-J HIGH RES CHROM JI HRC-J. High Resolut. Chromatogr. PD NOV PY 1994 VL 17 IS 11 BP 753 EP 755 PG 3 WC Chemistry, Analytical SC Chemistry GA PX377 UT WOS:A1994PX37700003 ER PT J AU LAMB, ME AF LAMB, ME TI HOW FATHERS CARE FOR THE NEXT-GENERATION - A 4-DECADE STUDY - SNAREY,J SO HUMAN DEVELOPMENT LA English DT Book Review RP LAMB, ME (reprint author), NICHHD,SOCIAL & EMOT DEV SECT,BSA BLDG,ROOM 331,9190 ROCKVILLE PIKE,BETHESDA,MD 20814, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0018-716X J9 HUM DEV JI Hum. Dev. PD NOV-DEC PY 1994 VL 37 IS 6 BP 385 EP 387 PG 3 WC Psychology, Developmental SC Psychology GA PR568 UT WOS:A1994PR56800006 ER PT J AU GREGOR, P GASTON, SM YANG, XD OREGAN, JP ROSEN, DR TANZI, RE PATTERSON, D HAINES, JL HORVITZ, HR UHL, GR BROWN, RH AF GREGOR, P GASTON, SM YANG, XD OREGAN, JP ROSEN, DR TANZI, RE PATTERSON, D HAINES, JL HORVITZ, HR UHL, GR BROWN, RH TI GENETIC AND PHYSICAL MAPPING OF THE GLUR5 GLUTAMATE-RECEPTOR GENE ON HUMAN-CHROMOSOME-21 SO HUMAN GENETICS LA English DT Note ID AMYOTROPHIC-LATERAL-SCLEROSIS; EXPRESSION; SUBUNIT; LOCALIZATION; CHANNELS; LIBRARY; CLONES; CLONING; KAINATE; PROTEIN AB Glutamate receptors (GluRs) mediate excitatory neurotransmission and may have important roles in central nervous system disorders. To characterize the human GLUR5 gene, which is located on human chromosome 21q22.1, we isolated cDNAs, genomic phage lambda clones, and yeast artificial chromosomes (YACs) and developed sequence tagged sites (STSs) and simple sequence length polymorphisms (SSLPs) for GLUR5. Genetic mapping with a tetranucleotide AGAT repeat named GLUR5/AGAT (six alleles observed, 70% heterozygosity) placed GLUR5 5 cM telomeric to APP (D21S210) and 3cM centromeric to SOD1 (D21S223). The human GLUR5 gene is located near the familial amyotrophic lateral sclerosis (FALS) locus; linkage analysis of GLUR5 SSLPs in FALS pedigrees yielded negative lod scores, consistent with the recent association of the FALS locus with the SOD1 gene. Physical mapping of GLUR5 using a YAC contig suggested that the GLUR5 gene spans approximately 400-500kb, and is within 280kb of D21S213. The large size of the GLUR5 gene raises questions regarding its functional significance. Our GLUR5 YAC contig includes clones found in the Genethon chromosome 21 YAC contig, and reference to the larger contig indicates the orientation centromere - D21S213 - GLUR5 5' end-GLUR5/AGAT - GLUR5 3'- end - SOD1. The development of GLUR5/AGAT should permit rapid determination of the status of the GLUR5 gene in individuals with partial trisomy or monosomy of chromosome 21. Such studies may provide insights concerning the possible role of GLUR5 in Down syndrome. C1 MASSACHUSETTS GEN HOSP,GENET & AGING LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DAY NEUROMUSC RES CTR,BOSTON,MA 02129. ELEANOR ROOSEVELT INST CANC RES,DENVER,CO 80206. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. MIT,HOWARD HUGHES MED INST,DEPT BIOL,CAMBRIDGE,MA 02139. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. RP GREGOR, P (reprint author), NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224, USA. RI Haines, Jonathan/C-3374-2012 FU NHGRI NIH HHS [HG00324]; NIA NIH HHS [AG00029]; NICHD NIH HHS [HD17449] NR 23 TC 13 Z9 13 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 1994 VL 94 IS 5 BP 565 EP 570 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA PP896 UT WOS:A1994PP89600022 PM 7959697 ER PT J AU PRAS, E AKSENTIJEVICH, I LEVY, E GRUBERG, L PROSEN, L DEAN, M PRAS, M KASTNER, DL AF PRAS, E AKSENTIJEVICH, I LEVY, E GRUBERG, L PROSEN, L DEAN, M PRAS, M KASTNER, DL TI THE GENE CAUSING FAMILIAL MEDITERRANEAN FEVER MAPS TO THE SHORT ARM OF CHROMOSOME-16 IN DRUZE AND MOSLEM ARAB FAMILIES SO HUMAN GENETICS LA English DT Note AB The gene causing familial Mediterranean fever maps to the short arm of chromosome 16 in Druze and Moslem Arab families. C1 NIAMS,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. CHAIM SHEBA MED CTR,DEPT MED F,IL-52621 TEL HASHOMER,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 6 TC 24 Z9 24 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 NOV PY 1994 VL 94 IS 5 BP 576 EP 577 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA PP896 UT WOS:A1994PP89600025 PM 7959700 ER PT J AU CARRINGTON, M STEPHENS, JC KLITZ, W BEGOVICH, AB ERLICH, HA MANN, D AF CARRINGTON, M STEPHENS, JC KLITZ, W BEGOVICH, AB ERLICH, HA MANN, D TI MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II HAPLOTYPES AND LINKAGE DISEQUILIBRIUM VALUES OBSERVED IN THE CEPH FAMILIES SO HUMAN IMMUNOLOGY LA English DT Note ID HLA; POLYMORPHISM; REGION; GENES; RECOMBINATION; ALLELES; TAP1; SB C1 NCI,FREDERICK CANC RES FACIL,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. UNIV CALIF BERKELEY,DEPT INTEGRAT BIOL,BERKELEY,CA 94720. ROCHE MOLEC SYST,DEPT HUMAN GENET,ALAMEDA,CA. RP CARRINGTON, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA. NR 18 TC 40 Z9 42 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. PD NOV PY 1994 VL 41 IS 3 BP 234 EP 240 DI 10.1016/0198-8859(94)90041-8 PG 7 WC Immunology SC Immunology GA PT917 UT WOS:A1994PT91700009 PM 7868379 ER PT J AU NEUHAUSEN, SL SWENSEN, J MIKI, Y LIU, Q TAVTIGIAN, S SHATTUCKEIDENS, D KAMB, A HOBBS, MR GINGRICH, J SHIZUYA, H KIM, UJ COCHRAN, C FUTREAL, PA WISEMAN, RW LYNCH, HT TONIN, P NAROD, S CANNONALBRIGHT, L SKOLNICK, MH GOLDGAR, DE AF NEUHAUSEN, SL SWENSEN, J MIKI, Y LIU, Q TAVTIGIAN, S SHATTUCKEIDENS, D KAMB, A HOBBS, MR GINGRICH, J SHIZUYA, H KIM, UJ COCHRAN, C FUTREAL, PA WISEMAN, RW LYNCH, HT TONIN, P NAROD, S CANNONALBRIGHT, L SKOLNICK, MH GOLDGAR, DE TI A P1-BASED PHYSICAL MAP OF THE REGION FROM D17S776 TO D17S78 CONTAINING THE BREAST-CANCER SUSCEPTIBILITY GENE BRCA1 SO HUMAN MOLECULAR GENETICS LA English DT Article ID YEAST ARTIFICIAL CHROMOSOMES; HUNTINGTON DISEASE REGION; FAMILIAL BREAST; OVARIAN-CANCER; DNA; CLONING; LIBRARY; CONSTRUCTION; LINKAGE; CONTIG AB BRCA1, a breast and ovarian cancer susceptibility locus, has been isolated and maps to 17q21. A physical map of the BRCA1 region which extended from the proximal boundary at D17S776 to the distal boundary at D17S78 was constructed and consists of 51 sequence tagged sites (STSs) from P1 and YAC ends, nine new short-tandem repeat (STR) polymorphic markers, and eight identified genes. The contig, which spans the estimated 2.3 Mb region, contains 29 P1s, 11 YACs, two BACs, and one cosmid. Based on key recombinants in two linked families, BRCA1 was further localized to a region bounded by D17S1321 on the proximal side and D17S1325 on the distal side. Within this estimated 600 kb region, the contig was composed completely of P1s and BACs ordered by STS-content mapping and confirmed by DNA restriction fragment fingerprinting. C1 UNIV UTAH,MED CTR,DEPT HUMAN GENET,SALT LAKE CITY,UT 84132. UNIV UTAH,MED CTR,DEPT INTERNAL MED,SALT LAKE CITY,UT 84132. MYRIAD GENET INC,SALT LAKE CITY,UT 84108. UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,CTR HUMAN GENOME,BERKELEY,CA 94720. CALTECH,DIV BIOL,147-75,PASADENA,CA 91125. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. CREIGHTON UNIV,DEPT PREVENT MED,OMAHA,NE. MCGILL UNIV,DEPT MED GENET,MONTREAL,PQ,CANADA. RP NEUHAUSEN, SL (reprint author), UNIV UTAH,MED CTR,DEPT MED INFORMAT,SALT LAKE CITY,UT 84132, USA. OI albright, lisa/0000-0003-2602-3668 FU NCI NIH HHS [CA-48711, CA-55914] NR 34 TC 64 Z9 64 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1994 VL 3 IS 11 BP 1919 EP 1926 DI 10.1093/hmg/3.11.1919 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PT231 UT WOS:A1994PT23100001 PM 7874107 ER PT J AU LAWRENCE, BJ SCHWABE, W KIOSCHIS, P COY, JF POUSTKA, A BRENNAN, MB HOCHGESCHWENDER, U AF LAWRENCE, BJ SCHWABE, W KIOSCHIS, P COY, JF POUSTKA, A BRENNAN, MB HOCHGESCHWENDER, U TI RAPID IDENTIFICATION OF GENE-SEQUENCES FOR TRANSCRIPTIONAL MAP ASSEMBLY BY DIRECT CDNA SCREENING OF GENOMIC REFERENCE LIBRARIES SO HUMAN MOLECULAR GENETICS LA English DT Article ID GTP-BINDING PROTEIN; PYRUVATE-DEHYDROGENASE COMPLEX; GDP DISSOCIATION INHIBITOR; SMG P25A; REGULATORY PROTEIN; E1-ALPHA SUBUNIT; MESSENGER-RNA; X-CHROMOSOME; XQ28 REGION; CLONING AB We have used the direct cDNA screening protocol to identify sequences transcribed in cerebral cortex from a reference library of human Xq28. To derive coding sequences from these genomic clones, we first identified fragments containing transcribed sequences and subjected these to exon trapping or to partial sequencing and analysis by Grail. In a preliminary analysis of three clones, coding sequences from two novel genes expressed in brain were identified. This method allows the rapid identification of coding sequences of genes expressed in specific tissues without recourse to cDNA libraries. The approach is amenable to large scale applications and should be useful for isolating candidate disease genes and in particular for assembling integrated transcriptional maps from large genomic regions. C1 NIMH,GENOM UNIT,BETHESDA,MD 20892. DEUTSCH KREBSFORSCHUNGSZENTRUM,W-6900 HEIDELBERG,GERMANY. NR 35 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1994 VL 3 IS 11 BP 2019 EP 2023 DI 10.1093/hmg/3.11.2019 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PT231 UT WOS:A1994PT23100016 PM 7874120 ER PT J AU NASR, SZ STRONG, TV COLLINS, FS AF NASR, SZ STRONG, TV COLLINS, FS TI IDENTIFICATION OF A CFTR FRAMESHIFT MUTATION (1013-DELAA) IN TRANS TO DELTA-F508 IN A PANCREATIC SUFFICIENT CYSTIC-FIBROSIS PATIENT SO HUMAN MOLECULAR GENETICS LA English DT Note ID GENETIC-ANALYSIS; DNA-SEQUENCE C1 UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP NASR, SZ (reprint author), UNIV MICHIGAN,DEPT PEDIAT,ANN ARBOR,MI 48109, USA. NR 20 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1994 VL 3 IS 11 BP 2063 EP 2064 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PT231 UT WOS:A1994PT23100024 PM 7533026 ER PT J AU ROTMAN, G VANAGAITE, L COLLINS, FS SHILOH, Y AF ROTMAN, G VANAGAITE, L COLLINS, FS SHILOH, Y TI 3 DINUCLEOTIDE REPEAT POLYMORPHISMS AT THE ATAXIA-TELANGIECTASIA LOCUS SO HUMAN MOLECULAR GENETICS LA English DT Note C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN GENET,IL-69978 TEL AVIV,ISRAEL. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 2 TC 14 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1994 VL 3 IS 11 BP 2079 EP 2079 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PT231 UT WOS:A1994PT23100031 PM 7874134 ER PT J AU JONES, JE HUCKABY, CS STAFFORD, MD LINNOILA, RI AF JONES, JE HUCKABY, CS STAFFORD, MD LINNOILA, RI TI AN MSPI RFLP OF THE HUMAN AHR GENE SO HUMAN MOLECULAR GENETICS LA English DT Note C1 BIOS LABS,NEW HAVEN,CT 06511. RP JONES, JE (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,9610 MED CTR DR,SUITE 300,ROCKVILLE,MD 20850, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1994 VL 3 IS 11 BP 2083 EP 2083 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PT231 UT WOS:A1994PT23100038 PM 7533027 ER PT J AU SHARARA, FI BEATSE, SN BAILEY, SA NEAL, GS CODDINGTON, CC SCOTT, RT AF SHARARA, FI BEATSE, SN BAILEY, SA NEAL, GS CODDINGTON, CC SCOTT, RT TI CHARACTERIZATION OF TRU-TRAX IN-VITRO PENETRATION TESTING OF CERVICAL-MUCUS SO HUMAN REPRODUCTION LA English DT Article DE CERVICAL MUCUS; POST-COITAL TEST; SPERMATOZOA ID SPERM PENETRATION; HUMAN-SPERMATOZOA; CLINICAL-SIGNIFICANCE; INVITRO; INFERTILITY AB To determine the distribution of results of an in-vitro cervical mucus penetration system employing both human and bovine mucus (Tru-Trax) in a general infertility population, 133 couples prospectively underwent in-vitro and post-coital testing of cervical mucus. The distribution of Tru-Trax results in couples with normal semen analyses and Insler scores showed significantly greater penetration in bovine (22.3 +/- 6.0 mm) than in human mucus (20.3 +/- 5.4 mm) (P < 0.001). However, the lower limit of the 95% confidence interval of the normal population with either type of mucus was similar to 10 mm. This limit was significantly lower than that described by the kit manufacturer. The predictive value for post-coital tests using human mucus in the Tru-Trax system was good (>90%) in all groups. The overall penetration into either human or bovine mucus was significantly correlated with the percentage of motile spermatozoa in the semen sample (P < 0.001). In conclusion, in-vitro cervical mucus penetration tests with the Tru-Trax system are related to in-vivo post-coital tests, although the lower limit of the range of anticipated results in the normal population was significantly lower than that described by the manufacturer. The ultimate value of this type of testing will await clinical trials which evaluate clinical end-points such as pregnancy rates. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. WILFORD HALL USAF MED CTR,LACKLAND AFB,TX. EASTERN VIRGINIA MED SCH,JONES INST REPROD MED,NORFOLK,VA. NR 29 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 1994 VL 9 IS 11 BP 2027 EP 2031 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA PU209 UT WOS:A1994PU20900016 PM 7868668 ER PT J AU POST, WS LARSON, MG LEVY, D AF POST, WS LARSON, MG LEVY, D TI HEMODYNAMIC PREDICTORS OF INCIDENT HYPERTENSION - THE FRAMINGHAM HEART-STUDY SO HYPERTENSION LA English DT Article DE HYPERTENSION, ESSENTIAL; HEMODYNAMICS; ECHOCARDIOGRAPHY; CARDIAC OUTPUT; EPIDEMIOLOGY ID LEFT-VENTRICULAR HYPERTROPHY; END-SYSTOLIC STRESS; BLOOD-PRESSURE; CONTRACTILITY; PERFORMANCE; STATE; MASS AB Previous reports indicate that cardiac output is increased early in the course of hypertension. The purpose of this study was to identify with echocardiography hemodynamic features in normotensive adults that predicted the development of hypertension. Framingham Heart Study subjects were eligible for this investigation if they were normotensive at the baseline examination (systolic blood pressure <140 mm Hg, diastolic blood pressure <90 mm Hg, and no antihypertensive medications) and if they were free of coronary heart disease, congestive heart failure, valvular heart disease, atrial fibrillation, hypertrophic cardiomyopathy, diabetes mellitus, and renal insufficiency. The study included 1118 men (mean age, 44 years) and 1559 women (mean age, 46 years). After 4 years of follow-up, of this normotensive cohort, 201 men (18.0%) and 257 women (16.5%) had developed hypertension. In separate, age-adjusted multivariable logistic regression analyses, increased cardiac index (men: odds ratio=1.19 for one standard deviation increment, P=.03; women: odds ratio=1.17, P=.02) and end-systolic wall stress (men: odds ratio=1.24, P=.006; women: odds ratio=1.43, P<.001) were related to the development of hypertension in both sexes. In addition, increased heart rate in men (odds ratio=1.25, P=.006) was a significant predictor of hypertension. After adjustment for age and baseline blood pressure, none of the hemodynamic variables was a significant predictor of hypertension. In addition, load-independent indexes of contractility revealed only a minimally greater proportion of subjects with increased contractility at baseline in the group that developed hypertension compared with those who remained normotensive. The present study revealed a hemodynamic profile in the preclinical stage of hypertension in age-adjusted analyses that was similar to the hyperkinetic circulatory phase found in the early stage of hypertension in some previous studies; however, after controlling for age and baseline blood pressure, none of the hemodynamic parameters were significant predictors of the development of hypertension. Knowledge of an individual's hemodynamic profile does not improve the prediction of hypertension risk that can be obtained from baseline blood pressure and age alone. Further studies are warranted to investigate hemodynamic features in various stages of hypertension after adjustment for age and blood pressure. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. NHLBI,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,DIV EPIDEMIOL,BOSTON,MA. BOSTON UNIV,SCH MED,DIV PREVENT MED,BOSTON,MA. NR 28 TC 20 Z9 20 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 1994 VL 24 IS 5 BP 585 EP 590 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PQ804 UT WOS:A1994PQ80400009 PM 7960017 ER PT J AU UNSER, M ALDROUBI, A AF UNSER, M ALDROUBI, A TI A GENERAL SAMPLING THEORY FOR NONIDEAL ACQUISITION DEVICES SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Article ID SPLINE; MULTIRESOLUTION; CONVERGENCE; APPROXIMATIONS; REPRESENTATION AB We first describe the general class of approximation spaces generated by translation of a function rho(x), and provide a full characterization of their basis functions. We then present a general sampling theorem for computing the approximation of signals in these subspaces based on a simple consistency principle. The theory puts no restrictions on the system input which can be an arbitrary finite energy signal; bandlimitedness is not required. In contrast to previous approaches, this formulation allows for an independent specification of the sampling (analysis) and approximation (synthesis) spaces. In particular, when both spaces are identical, the theorem provides a simple procedure for obtaining the least squares approximation of a signal. We discuss the properties of this new sampling procedure and present some examples of applications involving bandlimited, and polynomial spline signal representations. We also define a spectral coherence function that measures the ''similarity'' between the sampling and approximation spaces, and derive a relative performance bound for the comparison with the least squares solution. RP UNSER, M (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008; Aldroubi, Akram/J-7186-2012 NR 24 TC 214 Z9 221 U1 2 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 1053-587X J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD NOV PY 1994 VL 42 IS 11 BP 2915 EP 2925 DI 10.1109/78.330352 PG 11 WC Engineering, Electrical & Electronic SC Engineering GA PR274 UT WOS:A1994PR27400003 ER PT J AU WEINSTEIN, PD ANDERSON, AO MAGE, RG AF WEINSTEIN, PD ANDERSON, AO MAGE, RG TI RABBIT IGH SEQUENCES IN APPENDIX GERMINAL-CENTERS - VH DIVERSIFICATION BY GENE CONVERSION-LIKE AND HYPERMUTATION MECHANISMS SO IMMUNITY LA English DT Article ID CHAIN VARIABLE-REGION; HUMORAL IMMUNE-SYSTEM; B-CELL DEVELOPMENT; HEAVY-CHAIN; SOMATIC DIVERSIFICATION; ANTIBODY DIVERSITY; LYMPHOID-TISSUES; EMBRYONIC BURSA; PEYERS-PATCHES; VDJ GENES AB Although the rabbit IgH locus contains approximately 100 VH genes, the majority of B cells rearrange VH1. To produce a primary repertoire containing a sufficient number of protective antibodies, rearranged VH1-DH-JH sequences may diversify within rabbit B cells in an organ that functions like a chicken bursa, sheep ileal Peyer's patch, or both. It was suggested many years ago that the rabbit appendix could be a bursal equivalent. To reexamine this possibility, we analyzed rearranged heavy chain variable region sequences in B cells from light and dark zones of appendix germinal centers from B-week old rabbits. Our findings indicate that antibody diversification occurs by gene conversion-like and somatic hypermutation mechanisms in appendix germinal centers of young rabbits. C1 NIAID, IMMUNOL LAB, BETHESDA, MD 20892 USA. RP WEINSTEIN, PD (reprint author), USA, MED RES INST INFECT DIS, DIV APPL RES, FT DETRICK, FREDERICK, MD 21702 USA. NR 67 TC 121 Z9 122 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 1994 VL 1 IS 8 BP 647 EP 659 DI 10.1016/1074-7613(94)90036-1 PG 13 WC Immunology SC Immunology GA PT930 UT WOS:A1994PT93000003 PM 7600292 ER PT J AU SAMMARITANO, LR LOCKSHIN, MD AF SAMMARITANO, LR LOCKSHIN, MD TI PREGNANCY LOSS IN AUTOIMMUNE-DISEASES SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; CONNECTIVE-TISSUE DISEASE; CONGENITAL HEART-BLOCK; RHEUMATOID-ARTHRITIS; ANTIPHOSPHOLIPID ANTIBODIES; WEGENERS GRANULOMATOSIS; NEONATAL LUPUS; TAKAYASUS-ARTERITIS; ANTICARDIOLIPIN ANTIBODIES; RENAL-DISEASE AB Systemic autoimmune disease varies in organ involvement and degree of inflammation. Interaction of pregnancy-induced immune changes with preexisting immune system disorders may affect disease status and pregnancy outcome. Risk of disease exacerbation and fetal loss depends on the specific disorder, activity of disease, time of onset, and presence of particular autoantibodies. C1 NIAMSD,BETHESDA,MD 20892. CORNELL UNIV,HOSP SPECIAL SURG,COLL MED,NEW YORK,NY. NR 120 TC 3 Z9 3 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD NOV PY 1994 VL 14 IS 4 BP 803 EP 819 PG 17 WC Allergy; Immunology SC Allergy; Immunology GA PR105 UT WOS:A1994PR10500009 ER PT J AU THOMAS, DL MAHLEY, RW BADUR, S PALAOGLU, E QUINN, TC AF THOMAS, DL MAHLEY, RW BADUR, S PALAOGLU, E QUINN, TC TI THE EPIDEMIOLOGY OF HEPATITIS-C IN TURKEY SO INFECTION LA English DT Article ID NON-B-HEPATITIS; VIRUS-INFECTION; RISK GROUPS; UNITED-STATES; BLOOD-DONORS; NON-A; ANTIBODIES; PREVALENCE AB Hepatitis C virus (HCV) and hepatitis E virus (HEV) are the principal causes of non-A, non-B hepatitis worldwide, and in Turkey one-third of the cases of acute hepatitis are non-A, non-B. To explore the epidemiology of HCV in Turkey (including the association of HCV with HEV), a seroprevalence study of HCV was conducted. Sera from residents from five distinct regions of the country were tested for antibodies to HCV (anti-HCV) and HEV (anti-HEV). Anti-HCV was detected in 21 (1.5%) of 1,374 persons and was more common in residents over 54 years of age (p=0.02), with less than primary education (p=0.013), more than two children (p=0.003), and who lived in the regions of Ayvalik (p=0.046) or Trabzon (p=0.038) compared to Istanbul, Anti-HCV was marginally associated with anti-HEV, which was found in 5.9% of residents. However, this association was lost after controlling for age and education (p=0.225). HCV infection occurs in all regions of Turkey and is more common in persons who are older and of low socioeconomic status. As resources permit, efforts to reduce the transmission of HCV in Turkey (such as screening blood donations for anti-HCV) are indicated. C1 NIAID,IMMUNOREGULAT LAB,BALTIMORE,MD. AMER BRISTOL HOSP,GLADSTONE INST,ISTANBUL,TURKEY. ISTANBUL FAC MED,DEPT MICROBIOL,ISTANBUL,TURKEY. RP THOMAS, DL (reprint author), JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,1155 ROSS BLDG,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. NR 15 TC 20 Z9 20 U1 0 U2 1 PU MMW MEDIZIN VERLAG GMBH PI MUNICH 80 PA NEUMARKTER STRASSE 18, W-8000 MUNICH 80, GERMANY SN 0300-8126 J9 INFECTION JI Infection PD NOV-DEC PY 1994 VL 22 IS 6 BP 411 EP 414 DI 10.1007/BF01715499 PG 4 WC Infectious Diseases SC Infectious Diseases GA PY618 UT WOS:A1994PY61800008 PM 7698839 ER PT J AU ARORA, N LEPPLA, SH AF ARORA, N LEPPLA, SH TI FUSIONS OF ANTHRAX TOXIN LETHAL FACTOR WITH SHIGA TOXIN AND DIPHTHERIA-TOXIN ENZYMATIC DOMAINS ARE TOXIC TO MAMMALIAN-CELLS SO INFECTION AND IMMUNITY LA English DT Article ID SYMMETRICAL TETRAALKYLAMMONIUM IONS; PHOSPHOLIPID-BILAYER MEMBRANES; VOLTAGE-DEPENDENT BLOCK; AERUGINOSA EXOTOXIN-A; BACILLUS-ANTHRACIS; ESCHERICHIA-COLI; PROTECTIVE ANTIGEN; ADENYLATE-CYCLASE; CRYSTAL-STRUCTURE; PLASMA-MEMBRANE AB To investigate the ability of anthrax toxin lethal factor (LF) to translocate foreign proteins into the cytosol of eukaryotic cells and to characterize the structural requirements of this process, fusion proteins containing a portion of LF and the catalytic domains of either diphtheria toxin or Shiga toxin were constructed. Previous work showed that residues 1 to 254 of anthrax toxin lethal factor (LF(1-254)) are sufficient for binding to the protective antigen component of the toxin and that portions of Pseudomonas exotoxin A fused to LF(1-254) are efficiently translocated to the cytosol of eukaryotic cells (N. Arora and S. H. Leppla, J. Biol, Chem. 268:3334-3341, 1993). In this study, it was found that fusion proteins containing the ADP-ribosylation domain of diphtheria toxin fused at either the amino end or the carboxyl end of LF(1-254) are highly toxic to Chinese hamster ovary (CHO) cells, indicating that translocation does not strictly require that the amino terminus of LF be free. A fusion protein containing the ribosome-inactivating A1 subunit of Shiga toxin fused to the carboxyl terminus of LF(1-254) was also highly toxic for CHO cells. All fusion proteins were toxic only when administered with the anthrax toxin protective antigen component. The data show that the combination of protective antigen and LF fusion proteins can efficiently import polypeptides from diverse bacterial sources to the cytosol of eukaryotic cells and that LF fusion proteins mag have the passenger polypeptides fused at either the amino terminus or the carboxyl terminus of LF(1-254). These LF fusion proteins could potentially be used as components of a therapeutic agent when the destruction of certain types of cells is desired (e.g., in treating cancer). C1 NIDR, MICROBIAL ECOL LAB, BETHESDA, MD 20892 USA. NR 54 TC 76 Z9 78 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1994 VL 62 IS 11 BP 4955 EP 4961 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PN304 UT WOS:A1994PN30400037 PM 7927776 ER PT J AU KONADU, E ROBBINS, JB SHILOACH, J BRYLA, DA SZU, SC AF KONADU, E ROBBINS, JB SHILOACH, J BRYLA, DA SZU, SC TI PREPARATION, CHARACTERIZATION, AND IMMUNOLOGICAL PROPERTIES IN MICE OF ESCHERICHIA-COLI O157 O-SPECIFIC POLYSACCHARIDE-PROTEIN CONJUGATE VACCINES SO INFECTION AND IMMUNITY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; SHIGELLA-DYSENTERIAE TYPE-1; SHIGA-LIKE TOXINS; HEMORRHAGIC COLITIS; SERUM ANTIBODIES; SEROLOGICAL IDENTIFICATION; CLINICAL-EVALUATION; 0157-H7 INFECTIONS; NURSING-HOME; VERO TOXIN AB Escherichia coli O157 causes severe enteritis and the extraintestinal complication of hemolytic-uremic syndrome, with their highest incidence occurring in children. We postulated that serum immunoglobulin G (IgG) antibodies to the O-specific polysaccharide of lipopolysaccharide (LPS) may confer protective immunity to enteric pathogens by inducing bactericidal reactions against the ingested organisms in the jejunum (J. B. Bobbins, C. Chu, and R. Schneerson, Clin. Infect. Dis. 15:346-361, 1992; S. C. Szu, R. Gupta, and J. B. Robbins, p. 381-394, in I. K. Wachsmuth, P. A. Blake, and O. Olsvik, ed., Vibrio cholerae, 1994). Because polysaccharide-protein conjugates induce serum IgG antibodies in infants, we bound the O-specific polysaccharide of coil O157 to proteins. E. coli O157 LPS, treated with acetic acid or hydrazine, was derivatized with adipic acid dihydrazide and bound to proteins by carbodiimide-mediated condensation. Conjugates of these adipic hydrazide derivative were prepared with bovine serum albumin, formalin-treated exotoxin C of Clostridium welchii (Pig Bel toroid), or Pseudomonas aeruginosa recombinant exoprotein A. The conjugates had low levels of endotoxin and elicited serum antibodies with bactericidal activity to the O157 LPS. The largest increase in LPS antibodies was of the IgG class. Clinical evaluation of E. coli O157-toxoid conjugates is planned. C1 NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. NIDDKD,BIOTECHNOL UNIT,BETHESDA,MD 20892. NR 61 TC 41 Z9 43 U1 0 U2 1 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 NOV PY 1994 VL 62 IS 11 BP 5048 EP 5054 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PN304 UT WOS:A1994PN30400050 PM 7927787 ER PT J AU ROSCOE, DM JUNG, SH BENHAR, I PAI, L LEE, BK PASTAN, I AF ROSCOE, DM JUNG, SH BENHAR, I PAI, L LEE, BK PASTAN, I TI PRIMATE ANTIBODY-RESPONSE TO IMMUNOTOXIN - SEROLOGICAL AND COMPUTER-AIDED ANALYSIS OF EPITOPES ON A TRUNCATED FORM OF PSEUDOMONAS EXOTOXIN SO INFECTION AND IMMUNITY LA English DT Article ID MONOCLONAL-ANTIBODIES; AERUGINOSA EXOTOXIN; SYNTHETIC PEPTIDES; DIPHTHERIA-TOXIN; PROTEIN; BINDING; DOMAINS; CANCER; SITE; NAD AB NLysPE38 is a 38-kDa derivative of Pseudomonas exotoxin (PE) in which domain Ia (amino acids 1 to 252) and pert of domain Ib (365 to 380) are deleted and an 11-amino-acid N-terminal peptide is added. LMB-1 is an immunotoxin in which the monoclonal antibody B3 is coupled to NLysPE38 near its N terminus. LMB-7 is a single-chain immunotoxin in which the Fv fragment of B3 is fused to PE38. To identify the antigenic regions of PE38, 12 polyclonal serum samples from monkeys immunized with the immunotoxins LMB-1 (six monkeys) and LMB-7 (six monkeys) were tested for their reactivity to a panel of 120 synthetic, overlapping peptides representing the amino acid sequence of NLysPE38. The antibody responses to peptides were similar among the 12 serum specimens, identifying several major immunodominant B-cell epitopes. Predominant reactivity was seen in six locations: amino acids 272 to 287, 341 to 359, 504 to 516, 540 to 564, and 573 to 591 and the C-terminal amino acids 591 to 613. The sera did not react with approximately 75% of the peptides. Furthermore, a computer-aided analysis was done to predict the immunologically relevant areas and revealed the same antigenic regions defined by serum reactivity to peptides. Competition enzyme-linked immunosorbent assays and neutralization assays were performed with domain II, III, or III plus Ib of PE38 and confirmed the immunodominance of domain III. To analyze the role of specific amino acids in antibody binding, individual amino acids of PE38 with large accessible surface areas were altered by site-directed mutagenesis. These results also show that the predicted areas of immunogenicity agree with the reactivity of the anti-PE38 antibodies to peptides and to the mutants of PE. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 30 TC 24 Z9 24 U1 0 U2 1 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 NOV PY 1994 VL 62 IS 11 BP 5055 EP 5065 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PN304 UT WOS:A1994PN30400051 PM 7927788 ER PT J AU CORSINI, E LUSTER, MI MORGAN, DL CRAIG, WA ROSENTHAL, GJ AF CORSINI, E LUSTER, MI MORGAN, DL CRAIG, WA ROSENTHAL, GJ TI STYRENE INHALATION AND IMMUNE FUNCTION IN MICE SO INHALATION TOXICOLOGY LA English DT Article ID CELL-ACTIVITY; INTERFERON AB Short-term inhalation studies were conducted to evaluate the potential effects of styrene on the immune system. Female B6C3F1 mice were exposed by inhalation to 0, 125, 250, or 500 ppm styrene, 6 h/day for 14 consecutive days. Thymus and spleen weights in styrene-exposed mice were decreased in the high-dose animals, and a marked decrease in spleen cellularity occurred in all chemically treated groups. Cytometric analysis of spleen cells revealed a slight increase in the percentage of B cells and a decrease in the absolute number of CD4(+) cells. This latter change was responsible for a shift in the CD4/CD8 ratio observed in the high dose group. Corresponding increases in the proliferative response to the B-lymphocyte mitogen lipopolysaccharide as well as an increase in the primary antibody response to sheep erythrocytes were observed. Cell-mediated immunity was unaffected by styrene inhalation as demonstrated by normal cytotoxic T-lymphocyte and mixed leukocyte responses. Changes in spleen cellularity were not reflected at the level of the stem cell, as bone marrow cellularity was unaffected by styrene treatment. Styrene slightly suppressed spleen natural killer (NK) cell activity without affecting lung NK cell activity. These studies indicate that the primary immune effect of styrene is splenic hypocellularity. Although an imbalance in the B and T spleen lymphocyte subpopulations and a decrease in spleen NK cell activity were observed, the magnitudes of these effects were minimal. C1 NIEHS,LBRA,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. NIEHS,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RI Corsini, Emanuela/B-5602-2011 NR 17 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD NOV-DEC PY 1994 VL 6 IS 6 BP 647 EP 654 DI 10.3109/08958379409003045 PG 8 WC Toxicology SC Toxicology GA QA455 UT WOS:A1994QA45500008 ER PT J AU CUNNION, RE NATANSON, C AF CUNNION, RE NATANSON, C TI ECHOCARDIOGRAPHY, PULMONARY-ARTERY CATHETERIZATION, AND RADIONUCLIDE CINEANGIOGRAPHY IN SEPTIC SHOCK SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID VENTRICULAR-FUNCTION; REAL-TIME; THERMODILUTION METHOD; CARDIAC-OUTPUT; QUANTIFICATION; SEPSIS RP CUNNION, RE (reprint author), NIH,DEPT CRIT CARE MED,BLDG 10,ROOM 7-D-43,BETHESDA,MD 20892, USA. NR 25 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD NOV PY 1994 VL 20 IS 8 BP 535 EP 537 DI 10.1007/BF01705715 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA PU433 UT WOS:A1994PU43300001 PM 7706562 ER PT J AU POSTAN, M CORREA, R FERRANS, VJ TARLETON, RL AF POSTAN, M CORREA, R FERRANS, VJ TARLETON, RL TI IN-VITRO CULTURE OF CARDIAC MAST-CELLS FROM MICE EXPERIMENTALLY INFECTED WITH TRYPANOSOMA-CRUZI SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE CARDIAC MAST CELL CULTURE; CHAGAS DISEASE; MAST CELLS; MYOCARDITIS; TRYPANOSOMA CRUZI ID CHAGAS-DISEASE; IFN-GAMMA; MYOCARDITIS; HETEROGENEITY AB In this study we describe a mast cell population obtained by in vitro culture of hearts of Trypanosoma-cruzi-infected mice. Heart tissue was placed in culture and observed daily for the efflux of cells. Mast cells appeared in the medium during the 1st week of culture in the area immediately surrounding the tissues and increased in numbers over time. The cells were identified as mast cells by electron microscopy and by positive staining of granules with Giemsa, toluidine blue, and berberine sulfate techniques. Histopathological analysis of the cultured heart fragments from infected mice showed numerous mast cells, located mostly in areas where the histologic structure was abnormal and surrounded by fibrous connective tissue. This is the first report on in situ proliferation and migration of mast cells form inflamed heart tissues. In situ grown mast cells might be useful in developing in vitro models to study the role of these cells in T. cruzi-induced and other myocardiopathies. C1 NHLBI,BETHESDA,MD 20892. RP POSTAN, M (reprint author), UNIV GEORGIA,DEPT ZOOL,ATHENS,GA 30602, USA. FU NIAID NIH HHS [AI-22070] NR 35 TC 11 Z9 12 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. PD NOV PY 1994 VL 105 IS 3 BP 251 EP 257 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA PP375 UT WOS:A1994PP37500007 PM 7920027 ER PT J AU STGEORGIEV, V AF STGEORGIEV, V TI TREATMENT AND DEVELOPMENTAL THERAPEUTICS OF MYCOBACTERIUM-AVIUM COMPLEX (MAC) INFECTIONS SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Review DE MYCOBACTERIUM AVIUM; MYCOBACTERIUM INTRACELLULARE; MYCOBACTERIUM AVIUM COMPLEX (MAC); MAC, UPTAKE BY CELLS; MAC, CONVENTIONAL THERAPIES; QUINOLONES; MACROLIDES; ANTIMYCOBACTERIAL ANTIBIOTICS; FOLATE ANTAGONISTS; CELL WALL SYNTHESIS, INHIBITORS OF; IN VITRO/IN VIVO MODELS; IMMUNOTHERAPY; HOST DEFENSE ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; LIPOSOME-ENCAPSULATED STREPTOMYCIN; COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; IMMUNE-DEFICIENCY-SYNDROME; MULTIPLY RESISTANT MYCOBACTERIA; HUMAN ALVEOLAR MACROPHAGES; INTRACELLULARE COMPLEX; BEIGE MICE; INVITRO ACTIVITY AB Opportunistic infections associated with AIDS pose very serious problems because of their exceedingly high morbidity and mortality. For their part, Mycobacterium avium and M. intracellulare, two organisms belonging to M. avium complex (MAC), are the most often isolated bacteria from AIDS patients. Although in recent years, some progress has been made, by and large, there is no viable drug and/or combinations of drugs effective against MAC, especially in AIDS patients. Conventional therapies with multiple drug combinations involving isoniazid, rifampin, ethambutol, streptomycin, ethionamide, and cycloserine are still widely used, as well as prophylactic treatment with rifabutin. The use of clofazimine and ciprofloxacin has also been reported. Studies on new quinolones (sparfloxacin, difloxacin, WIN 57273), macrolides, folate antagonists and antimycobacterial antibiotics are being actively pursued along with novel strategies involving drugs inhibiting mycobacterial cell wall biosynthesis. The role of various cytokines in enhancing host immune defenses against MAC infections is also discussed. RP STGEORGIEV, V (reprint author), NIAID, SOLAR BLDG, ROOM 4C-04, BETHESDA, MD 20892 USA. NR 228 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 EI 1872-7913 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD NOV PY 1994 VL 4 IS 4 BP 247 EP 270 PG 24 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA PQ773 UT WOS:A1994PQ77300002 ER PT J AU DAY, GL BLOT, WJ MCLAUGHLIN, JK FRAUMENI, JF AF DAY, GL BLOT, WJ MCLAUGHLIN, JK FRAUMENI, JF TI CARCINOGENIC RISK OF DARK VS LIGHT LIQUOR SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ORAL CAVITY; ALCOHOLIC BEVERAGE; CANCER; ESOPHAGUS; DRINKING; PHARYNX; SMOKING AB A previous report suggested that the cancer risk associated with hard liquor is greater among users of dark liquors, which may contain more potentially carcinogenic compounds than light liquors. To test this hypothesis, we examined alcohol consumption data obtained by interview with 921 cases and 900 controls who participated in 1984-1985 in a population-based case-control study of oral and pharyngeal cancer conducted in 4 areas of the United States. Among heavy liquor drinkers (30+ drinks/week), odds ratios were 13.2 (95% CI = 5.2-33.5) for those who usually drank light liquors vs. 4.6 (95% CI = 2.7-7.9) for those who usually drank dark liquors, with higher risks for light vs. dark liquors at each anatomical subsite. This analysis provides no support for the notion that dark liquors are more carcinogenic than light liquors or that non-ethanolic ingredients of alcoholic beverages are major contributors to the excess risk of oral and pharyngeal cancer. (C) 1994 Wiley-Liss, Inc. RP DAY, GL (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,RM 535,BETHESDA,MD 20892, USA. NR 12 TC 14 Z9 14 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 1994 VL 59 IS 3 BP 319 EP 321 DI 10.1002/ijc.2910590305 PG 3 WC Oncology SC Oncology GA PP776 UT WOS:A1994PP77600004 PM 7927935 ER PT J AU STRASSMANN, G DALESSANDRO, F FONG, M NORDAN, RP NICKEL, P CHIZZONITE, R AF STRASSMANN, G DALESSANDRO, F FONG, M NORDAN, RP NICKEL, P CHIZZONITE, R TI SURAMIN BLOCKS THE BINDING OF INTERLEUKIN-1 TO ITS RECEPTOR AND NEUTRALIZES IL-1 BIOLOGICAL-ACTIVITIES SO INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY LA English DT Article DE IL-1; IL-1 RECEPTOR; SURAMIN ID EXPERIMENTAL CANCER CACHEXIA; GROWTH-FACTOR; REVERSE-TRANSCRIPTASE; CELLS; INHIBITION; MECHANISMS; PRODUCTS; INVITRO; AGENT AB This report demonstrates the ability of the anti-cancer drug suramin to interfere with the binding of interleukin (IL)-1 to its receptor and to inhibit IL-1-induced biological activities. In a radioreceptor cell based assay, suramin inhibits the binding of IL-1 alpha to several murine fell lines expressing predominantly type I and type II IL-1 receptors. Affinity cross-linking experiments using IL-1 alpha and EL-4.6.1 cells confirms that suramin inhibits the binding of the ligand to the 80 kDaIL-1 type I receptor. In contrast, suramin fails to displace significantly prebound IL-1. In a cell-free system, suramin prevents the binding of IL-1 alpha and IL-1 beta to murine and human recombinant soluble type I IL-1 receptors. For example, the IC50 for suramin inhibiting IL-1 alpha and IL-1 beta binding to soluble human IL-1 receptor were 204 mu M and 186 mu M, respectively. The suramin analogues, NF-058 and NF-103 (which bear the same number of sulfate groups as suramin), are between three- and ten-fold less active than suramin in inhibiting IL-1 binding to EL-4.6.1 cells, and to recombinant soluble IL-1 receptor. Furthermore, in a dose-dependent manner suramin prevents several IL-1 mediated biological responses, including thymocyte proliferation, PGE-2 synthesis and IL-6 production. The inhibitory effect of the drug can be significantly reversed by the addition of excess cytokine. Taken together, the results indicate that suramin is a competitive IL-1 receptor antagonist. Because IL-1 participates in a broad range of immunological and inflammatory functions, the data suggest that suramin administration may influence important activities beyond those associated strictly with tumor inhibition. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. UNIV BONN,INST PHARMACEUT,W-5300 BONN,GERMANY. HOFFMANN LA ROCHE INC,DEPT INFLAMMAT & AUTOIMMUNE DIS,NUTLEY,NJ 07110. RP STRASSMANN, G (reprint author), OTSUKA AMER PHARMACEUT INC,DEPT IMMUNOL,9900 MED CTR DR,ROCKVILLE,MD 20850, USA. NR 28 TC 14 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0192-0561 J9 INT J IMMUNOPHARMACO JI Int. J. Immunopharmacol. PD NOV PY 1994 VL 16 IS 11 BP 931 EP 939 DI 10.1016/0192-0561(94)00054-9 PG 9 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA PT150 UT WOS:A1994PT15000006 PM 7868298 ER PT J AU SORKIN, JD MULLER, D ANDRES, R AF SORKIN, JD MULLER, D ANDRES, R TI BODY-MASS INDEX AND MORTALITY IN SEVENTH-DAY-ADVENTIST MEN - A CRITIQUE AND REANALYSIS SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE BMI; BODY MASS INDEX; MORTALITY; SEVENTH-DAY-ADVENTISTS ID WEIGHT AB The aim of this work was to determine if the relationship between weight-adjusted-for-height (expressed as body mass index or BMI) using the BMI-at-entry and age-at-entry as opposed to BMI at entry and age-at-event (i.e. death, loss to follow-up, or end of the study) would alter the results previously reported from a population of Seventh-day Adventist men. The subjects were 8828 non-smoking, non-drinking Seventh-day Adventist men, ages 30-89 and older on entry, mean follow-up 15 years (maximum 26 years). The BMI and age reported by subjects when they were enrolled into the study were used to calculate the relationship between BMI and mortality. Mortality rates in each of five BMI quintiles were computed by dividing the number of deaths in each quintile by the number of person years of follow-up in the quintile. Rate ratios were computed by dividing each mortality rate by the rate in the reference quintile. The mortality rate ratios were then adjusted for the age difference between each quintile and the reference quintile. Calculations based upon age-at-enrollment rather than 'age-at-event' (as used in the original paper) demonstrate no increase in mortality until a BMI of 27.5 kg/m(2) or greater is reached rather than a progressive increase in mortality with increasing BMI. C1 NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,BALTIMORE,MD 21224. RP SORKIN, JD (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,GATEWAY BLDG,SUITE 3C309,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 13 TC 17 Z9 17 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD NOV PY 1994 VL 18 IS 11 BP 752 EP 754 PG 3 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA PN754 UT WOS:A1994PN75400006 PM 7866475 ER PT J AU ESPOSITODELPUENTE, A LILLIOJA, S BOGARDUS, C MCCUBBIN, JA FEINGLOS, MN KUHN, CM SURWIT, RS AF ESPOSITODELPUENTE, A LILLIOJA, S BOGARDUS, C MCCUBBIN, JA FEINGLOS, MN KUHN, CM SURWIT, RS TI GLYCEMIC RESPONSE TO STRESS IS ALTERED IN EUGLYCEMIC PIMA-INDIANS SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE STRESS; PIMA INDIAN; HYPERGLYCEMIA; DIABETES; SYMPATHETIC NERVOUS SYSTEM ID OB-OB MICE; LIPOPROTEIN METABOLISM; INSULIN RESISTANCE; HYPERGLYCEMIA; GLUCOSE; CATECHOLAMINES; RELAXATION AB The aim of this work was to study the effects of a computer-driven mental arithmetic task on blood glucose in a group of four male and four female euglycemic Caucasians and a group of seven male and six female euglycemic Pima Indians. Approximately 60% of euglycemic Pima Indian Native Americans eventually develop type 2 diabetes, while only 5% of Caucasians develop the disease. All subjects had normal glucose tolerance. Subjects were given a standard breakfast; 2 h later, they were given a computerized mental arithmetic stress test for 10 min. Before, during and after the test, several variables were analyzed, including serum concentrations of glucose, insulin, glucagon and plasma cortisol and catecholamines. Heart rate, systolic and diastolic blood pressure and all the stress hormones increased during stress and decreased during recovery in all subjects. Blood glucose consistently declined one hour after the meal in all subjects. However, while it continued to decline following stress in seven out of eight Caucasian subjects, it consistently increased during and following stress in 10 out of 13 Pima Indians. Pasting serum glucose in Pima Indians and Caucasians was respectively 5.07 + 0.08 mM and 5.04 + 0.09 mM. Two-hour post-prandial values were 5.63 + 0.22 mM and 5.48 + 0.19 mM respectively, whereas post-stress values were 6.15 + 0.19 mM for Pima Indians and 5.22 + 0.20 mM for Caucasians. Both serum glucose means following stress (t = 3.1, P < 0.005) and the direction of change in serum glucose in response to mental arithmetic (chi(2) = 8.2, P < 0.01) clearly differentiated Pimas from Caucasians. These data suggest that abnormal glycemic responsiveness to stress, even in the absence of impaired glucose tolerance, may be present in subjects at high risk of developing diabetes and may therefore be related in some way to the chain of events leading to the development of the disease. C1 NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. UNIV KENTUCKY,HLTH SCI CTR,DEPT BEHAV SCI,LEXINGTON,KY. DUKE UNIV,MED CTR,DEPT PSYCHIAT,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. RP ESPOSITODELPUENTE, A (reprint author), UNIV NAPLES FEDERICO II,CATTEDRA NUTR CLIN IST MED INTERNA MALATTIE DISME,I-80131 NAPLES,ITALY. RI Lillioja, Stephen/A-8185-2012; OI Lillioja, Stephen/0000-0001-5333-5240 FU NIDDK NIH HHS [R01 DK 43106]; NIMH NIH HHS [K05 MH00303] NR 25 TC 17 Z9 17 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD NOV PY 1994 VL 18 IS 11 BP 766 EP 770 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA PN754 UT WOS:A1994PN75400009 PM 7866478 ER PT J AU DEBIECRYCHTER, M ZUKOWSKI, K TADA, M POIRIER, MC WANG, CY AF DEBIECRYCHTER, M ZUKOWSKI, K TADA, M POIRIER, MC WANG, CY TI REMOVAL OF ARYLAMINE-DNA ADDUCTS IN CULTURED EPITHELIAL-CELLS OF RAT AND HUMAN URINARY-BLADDER AND MAMMARY-GLAND SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE ARYLAMINE-DNA; URINARY BLADDER; MAMMARY GLAND ID CHRONICALLY FED 2-ACETYLAMINOFLUORENE; HUMAN UROTHELIAL CELLS; N-HYDROXY METABOLITES; REPAIR SYNTHESIS; CARCINOGENIC ARYLAMINES; NONTARGET TISSUES; LIVER; INDUCTION; 3,2'-DIMETHYL-4-AMINOBIPHENYL; INVIVO AB Primary mammary and urinary bladder epithelial cells of the rat, and the human urothelial cell line HCV-29 and mammary cell line MCF-10A were incubated for 3 h with 10 mM hydroxyurea and N-hydroxy-N-acetyl-2-aminofluorene, N-hydroxy-N-acetyl-4-aminobiphenyl or N-hydroxy-3,2'-dimethyl-4-aminobiphenyl. DNA adducts of these carcinogens were detected in the nuclei of all cells, except MCF-10A, semi-quantitatively with a novel immunohistochemical-microdensitometric method. The loss of these adducts in these cells was biphasic and was relatively greater between 0 and 24 h than between 24 and 48 h. The half-life of the adducts of all 3 carcinogens was approximately 20 h. The adduct loss is consistent with repair detected by an unscheduled DNA synthesis system reported previously. These results demonstrate that nonacetylated aromatic amine-DNA adducts can be repaired in the target cells for aromatic amine-induced carcinogenesis. C1 MICHIGAN CANC FDN,DEPT CHEM CARCINOGENESIS,DETROIT,MI 48201. AICHI CANC CTR,RES INST,BIOCHEM LAB,NAGOYA,AICHI 464,JAPAN. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 38 TC 1 Z9 1 U1 0 U2 2 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 1994 VL 5 IS 5 BP 997 EP 1002 PG 6 WC Oncology SC Oncology GA PL931 UT WOS:A1994PL93100001 PM 21559671 ER PT J AU HELSON, C ZAHN, Z HELSON, L AF HELSON, C ZAHN, Z HELSON, L TI REVERSION OF P-GLYCOPROTEIN MEDIATED MULTIDRUG-RESISTANCE TO VINCRISTINE AND ADRIAMYCIN BY PSC-833, A CYCLOSPORINE DERIVATIVE IN HUMAN NEUROBLASTOMA CELL-LINES SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE VINCRISTINE; ADRIAMYCIN; PSC-833; SK-N-DZ; SK-N-AS; SK-N-FI; NEUROBLASTOMA ID HUMAN NEURO-BLASTOMA AB We evaluated the effect of PSC-833 a cyclosporine derivative for its MDR1 reversing activity on vincristine and adriamycin resistance in human neuroblastoma cell lines. The cell lines have high, intermittent and low MDR1 expression. Resistance to vincristine and adriamycin was inverse to the degree of MDR1 expression. Resistance could be lowered with longer exposures to drug in all three cell lines. PSC-833 was able to reverse resistance in the SK-N-FI cells to a greater degree than in the two cell lines with lower expression of MDR1. These data suggest that MDR1 may play a protective role against vincristine and adriamycin in human neuroblastoma cells, and PSC-833 can reverse this protection. The duration of exposure to drug alters the response and the effect of PSC-833 on reversal of resistance. Where MDR1 is minimally expressed, PSC-833 is ineffective. Overall activity of vincristine and its modulation by PSC-833 were more consistent than that of adriamycin. Multiple drug resistance mechanisms are complex and vary among different cell lines when challenged with MDR1 drugs and reversing agents. C1 NCI,BETHESDA,MD 20892. RP HELSON, C (reprint author), NEW YORK MED COLL,DEPT MED,DIV HEMATOL ONCOL,VALHALLA,NY 10595, USA. NR 12 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 NOV PY 1994 VL 5 IS 5 BP 1037 EP 1042 PG 6 WC Oncology SC Oncology GA PL931 UT WOS:A1994PL93100007 PM 21559677 ER PT J AU RYBAK, SM LIN, JJ NEWTON, DL KUNG, HF MONKS, A CHEN, HC HUANG, PL LEEHUANG, S AF RYBAK, SM LIN, JJ NEWTON, DL KUNG, HF MONKS, A CHEN, HC HUANG, PL LEEHUANG, S TI IN-VITRO ANTITUMOR-ACTIVITY OF THE PLANT RIBOSOME-INACTIVATING PROTEINS MAP-30 AND GAP-31 SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE ANTI-TUMOR/ANTI-HIV PROTEINS; RIBOSOME-INACTIVATION; DNA TOPOISOMERASE-POISON ID CELL-LINES; DRUG; IMMUNOTOXINS AB MAP 30 and GAP 31 are plant proteins isolated from Momordica charantia and Gelonium multiflorum, respectively. They have recently been shown to inhibit HIV-1 infection and replication. These proteins also possess a novel DNA topoisomerase-poison-like activity as well as ribosome inactivation. They were submitted to the Anti-Cancer Drug Screening Program of the National Cancer Institute and found to have potent anti-tumor activity against certain human tumor cell lines. The most sensitive cell lines responded to MAP 30 and GAP 31 with GI(50) that ranged from 0.01 to 10 mu g/ml and were unrelated to tumor type. These included cell lines from renal, non-small cell lung, and breast cancer. Targeted immunofusions made with MAP 30 or GAP 31 may be most effective toward these types of tumors. C1 PROGRAM RESOURCES INC,DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NYU,SCH MED,DEPT BIOCHEM,NEW YORK,NY 10016. AMER BIOSCI,NEW YORK,NY 10021. RP RYBAK, SM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOCHEM PHYSIOL LAB,BLDG 560,RM 31-76,FREDERICK,MD 21702, USA. NR 21 TC 11 Z9 12 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 1994 VL 5 IS 5 BP 1171 EP 1176 PG 6 WC Oncology SC Oncology GA PL931 UT WOS:A1994PL93100026 PM 21559696 ER PT J AU OREN, DA TEICHER, MH SCHWARTZ, PJ GLOD, C TURNER, EH ITO, YN SEDWAY, J ROSENTHAL, NE WEHR, TA AF OREN, DA TEICHER, MH SCHWARTZ, PJ GLOD, C TURNER, EH ITO, YN SEDWAY, J ROSENTHAL, NE WEHR, TA TI A CONTROLLED TRIAL OF CYANOCOBALAMIN (VITAMIN-B-12) IN THE TREATMENT OF WINTER SEASONAL AFFECTIVE-DISORDER SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE CYANOCOBALAMIN; SEASONAL AFFECTIVE DISORDER; DEPRESSION ID LIGHT THERAPY; DEFICIENCY; CLOCK AB To test the hypothesis that cyanocobalamin (Vitamin B-12) is an effective treatment for winter seasonal affective disorder (SAD). 2 weeks of double-blind placebo washout, followed by random assignment to parallel treatments for 2 weeks with cyanocobalamin vs. placebo. Observations were made during weekly outpatient visits. All subjects met criteria for SAD. 27 patients were studied. After the washout period, 14 were randomly assigned to 1.5 mg cyanocobalamin (3 x /day) and 13 remained on placebo on the same schedule. 29 item SIGH-SAD scores were used to determine antidepressant efficacy. No significant differences were found in the responses between the two groups. Cyanocobalamin does not appear to be an effective short-term treatment for depression in SAD patients. The usefulness as a treatment for SAD of the methylated form of Vitamin B-12, which has been used extensively in related studies, remains to be explored. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. MCLEAN HOSP,BELMONT,MA 02178. RP OREN, DA (reprint author), NIMH,MSC1390,BLDG 10,ROOM 4S-239,10 CTR DR,BETHESDA,MD 20892, USA. RI Turner, Erick/A-4848-2008; Schwartz, Peter/J-4267-2016 OI Turner, Erick/0000-0002-3522-3357; Schwartz, Peter/0000-0003-0367-1048 NR 22 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV PY 1994 VL 32 IS 3 BP 197 EP 200 DI 10.1016/0165-0327(94)90018-3 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PR825 UT WOS:A1994PR82500007 PM 7852661 ER PT J AU SHECHTMAN, O TALAN, MI AF SHECHTMAN, O TALAN, MI TI EFFECT OF EXERCISE ON COLD TOLERANCE AND METABOLIC HEAT-PRODUCTION IN ADULT AND AGED C57BL/6J MICE SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE BODY TEMPERATURE; DIURNAL; HEAT CONSERVATION; THERMOGENESIS ID OXYGEN-CONSUMPTION; DIURNAL PATTERNS; RATS; THERMOREGULATION; TEMPERATURE; RESPONSES; STRESS; YOUNG; OLD AB Two groups of adult (12-mo-old) and two groups of aged (24-mo-old) C57BL/6J male mice were subjected to a standardized cold stress test (3-h partial restraint at 6 degrees C). One group from each age group was tested in the morning, and the other was tested in the afternoon. Half of the mice were subjected to running exercise on a treadmill during 1 h before the cold stress test. The other half were placed on a nonoperational treadmill for 1 h before the cold stress test. One hour of exercise resulted in improvement of cold tolerance during the subsequent cold exposure in both age groups but only during afternoon testing. Improvement in cold tolerance was not accompanied by an elevation of cold-induced metabolic heat production in adult mice. Metabolic heat production in aged mice showed only modest elevation. The discrepancy between improvement in cold tolerance and lack of elevation of metabolic heat production suggests that the primary mechanism for augmentation of cold tolerance after exercise in the afternoon is an improvement in cold-induced vasoconstriction of skin vessels, which is probably normally compromised in the afternoon. C1 NIA,GERONTOL RES CTR,BEHAV SCI LAB,BALTIMORE,MD 21224. NR 33 TC 6 Z9 6 U1 2 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 1994 VL 77 IS 5 BP 2214 EP 2218 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA PQ375 UT WOS:A1994PQ37500023 PM 7868436 ER PT J AU EICHACKER, PQ WAISMAN, Y NATANSON, C FARESE, A HOFFMAN, WD BANKS, SM MACVITTIE, TJ AF EICHACKER, PQ WAISMAN, Y NATANSON, C FARESE, A HOFFMAN, WD BANKS, SM MACVITTIE, TJ TI CARDIOPULMONARY EFFECTS OF GRANULOCYTE-COLONY-STIMULATING FACTOR IN A CANINE MODEL OF BACTERIAL SEPSIS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE NEUTROPHIL; SEPSIS-ASSOCIATED TISSUE INJURY; CARDIOPULMONARY INJURY; SEPTIC SHOCK; ENDOTOXIN; TUMOR NECROSIS FACTOR ID RESPIRATORY-DISTRESS SYNDROME; TUMOR-NECROSIS-FACTOR; HUMAN SEPTIC SHOCK; GRAM-NEGATIVE SEPSIS; ACUTE LUNG INJURY; HUMAN-NEUTROPHILS; HOST DEFENSE; DRUG-THERAPY; FACTOR-ALPHA; ENDOTOXEMIA AB We investigated the effects of recombinant granulocyte colony-stimulating factor (G-CSF) in a canine model of septic shock. Awake 2-yr-old beagles were studied before and after intraperitoneal placement of an Escherichia coli-infected clot. Nine days before and until 3 days after clot placement, animals received daily high-dose G-CSF (5 mu g/kg body wt; n = 17), low-dose G-CSF (0.1 mu g/kg body wt; n = 17), or a control protein (5 mu g/kg body wt; n = 20). Survival rate was greater (P < 0.04, Wilcoxon test) in the high-dose G-CSF group (14/17) than in the low-dose G-CSF (10/17) and control (12/20) groups. High-dose G-CSF improved cardiovascular function, as evidenced by increased left ventricular ejection fraction (day 1 after clot; P < 0.001) and mean arterial pressure (day 2; P < 0.02) compared with low-dose G-CSF and control groups. High-dose G-CSF increased (P < 0.001) mean peripheral neutrophils before (-3 days) and after (2 h to 4 days) clot and produced a more rapid (P < 0.001) rise (day 2) and fall (day 4) in mean alveolar neutrophil numbers compared with the low-dose G-CSF and control groups. High-dose G-CSF decreased mean serum endotoxin (2-8 h; P < 0.002) and tumor necrosis factor (2 h; P < 0.02) levels and lowered blood bacteria counts (2-6 h; P < 0.04) compared with the low-dose G-CSF and control groups. Thus, in this canine model, G-CSF sufficient to increase peripheral neutrophils before and during peritonitis and septic shock enhances host defense, reduces cytokine (tumor necrosis factor) levels, and improves cardiovascular function and survival. C1 ARMED FORCES RADIOBIOL RES INST,DEF NUCL AGCY,BETHESDA,MD 20814. RP EICHACKER, PQ (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BLDG 10,RM 7D43,BETHESDA,MD 20892, USA. NR 44 TC 70 Z9 71 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 1994 VL 77 IS 5 BP 2366 EP 2373 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA PQ375 UT WOS:A1994PQ37500045 PM 7532649 ER PT J AU BORZELLECA, JF EGLE, JL HARRIS, LS JOHNSON, DN TERRILL, JB BELLEVILLE, JAN AF BORZELLECA, JF EGLE, JL HARRIS, LS JOHNSON, DN TERRILL, JB BELLEVILLE, JAN TI TOXICOLOGICAL EVALUATION OF MU-AGONISTS .1. ASSESSMENT OF TOXICITY FOLLOWING 30 DAYS OF REPEATED ORAL DOSING OF MALE AND FEMALE RATS WITH LEVO-ALPHA-ACETYLMETHADOL HCL (LAAM) SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE LAAM; TOXICITY; ACUTE; REPEAT DOSE; RATS; DEPENDENCE; TOLERANCE; MU-AGONIST; OPIATES, MORPHINE TYPE ID METHADONE AB This study evaluated levo-alpha-acetylmethadol hydrochloride (LAAM), a long-acting morphine-like (mu) agonist approved in 1993 to treat opiate dependence. Sprague-Dawley rate (20/sex/group) were gavaged with doses of 3.0-33.5 mg kg(-1) for 30 days followed by a 14-day drug-free recovery period. Treatment-related effects included dose-dependent CNS depression, decreased food consumption and body weight gain, reddish urine and abdominal staining. Tolerance developed by day 7. Mortality was dose-dependent; deaths occurred predominantly during the first week. Increased alanine aminotransferase (SGOT, AST) and lactate dehydrogenase (LDH), observed only in high-dose males, were associated with findings in liver. Decreases in spleen/brain weight and increases in brain/body weight ratios were seen in both sexes. Decreases in weights of heart, liver and kidney achieved statistical significance only for high-dose groups. Kidneys of mid- and high-dose groups displayed intertubular mineral/crystal deposition, focal corticomedullary mineralization and focal regenerative tubular epithelium. Centrilobular hypertrophy was observed in livers of high-dose males and mid- and high-dose females. Following the recovery period, decreased body weights and increased brain/body weight ratios occurred in mid-dose males and low-dose females. Weights of liver and kidney and organ/brain weight ratios were decreased in mid-dose males. Histopathological findings observed in kidneys and livers had abated. In summary, acute and repeated administration of LAAM produced a spectrum of activity consistent with its profile as a long-acting pure mu-agonist which stimulates microsomal enzymes in rodents. Renal and hepatic effects seen in initially drug-naive rats treated with morphine-type agonists are not observed in tolerant individual stabilized on mu-agonists to treat opiate dependence. C1 NIDA,DIV MED DEV,ROCKVILLE,MD 20857. NB ASSOCIATES INC,ROCKVILLE,MD 20853. RP BORZELLECA, JF (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,RICHMOND,VA 23298, USA. NR 62 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD NOV-DEC PY 1994 VL 14 IS 6 BP 435 EP 446 DI 10.1002/jat.2550140609 PG 12 WC Toxicology SC Toxicology GA PW364 UT WOS:A1994PW36400008 PM 7884149 ER PT J AU MARGOLIS, N HOGAN, D TILLY, K ROSA, PA AF MARGOLIS, N HOGAN, D TILLY, K ROSA, PA TI PLASMID LOCATION OF BORRELIA PURINE BIOSYNTHESIS GENE HOMOLOGS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; ENCODING GMP SYNTHETASE; NUCLEOTIDE-SEQUENCE; OSPC GENE; IMP DEHYDROGENASE; CIRCULAR-PLASMID; BURGDORFERI; PROTEIN; AGENT; ESCHERICHIA-COLI-K12 AB The Lyme disease spirochete Borrelia burgdorferi must survive in both its tick vector and its mammalian host to be maintained in nature. We have identified the B. burgdorferi guaA gene encoding GMP synthetase, an enzyme involved in de novo purine biosynthesis that is important for the survival of bacteria in mammalian blood. This gene encodes a functional product that will complement an Escherichia coli GMP synthetase mutant. The gene is located on a 26-kb circular plasmid, adjacent to and divergent from the gene encoding the outer surface protein C (OspC). The guaB gene homolog encoding IMP dehydrogenase, another enzyme in the purine biosynthetic pathway, is adjacent to guaA. In Borrelia hermsii, a tick-borne relapsing fever spirochete, the guaA and guaB genes are located on a linear plasmid. These are the first genes encoding proteins of known function to be mapped to a borrelial plasmid and the only example of genes encoding enzymes involved in the de novo purine biosynthesis pathway to be mapped to a plasmid in any organism. The unique plasmid location of these and perhaps other housekeeping genes may be a consequence of the segmented genomes in borreliae and reflect the need to adapt to both the arthropod and mammalian environments. C1 NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. NR 42 TC 78 Z9 81 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 1994 VL 176 IS 21 BP 6427 EP 6432 PG 6 WC Microbiology SC Microbiology GA PN644 UT WOS:A1994PN64400003 PM 7961392 ER PT J AU SHARMA, M HINTON, DM AF SHARMA, M HINTON, DM TI PURIFICATION AND CHARACTERIZATION OF THE SEGA PROTEIN OF BACTERIOPHAGE-T4, AN ENDONUCLEASE RELATED TO PROTEINS ENCODED BY GROUP-I INTRONS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID THYMIDYLATE SYNTHASE GENE; APOCYTOCHROME-B-GENE; RIBOSOMAL-RNA GENE; YEAST MITOCHONDRIA; DNA ENDONUCLEASE; SACCHAROMYCES-CEREVISIAE; RECOGNITION SITE; FLANKING EXONS; SEQUENCE; RECOMBINATION AB Although not encoded by an intron, the bacteriophage T4 SegA protein shares common amino acid motifs with a family of proteins found within mobile group I introns present in fungi and phage. Each of these intron encoded proteins is thought to initiate the homing of its own intron by cleaving the intronless DNA at or near the site of insertion. Previously, we have found that SegA also cleaves DNA. In this report, we have purified the SegA protein and characterized this endonuclease activity extensively. SegA protein cleaved circular and linear plasmids, DNA containing unmodified cytosines, and wild-type T4 DNA containing hydroxymethylated, glucosylated cytosines. In all cases, certain sites on the DNA were highly preferred for cleavage, but with increasing protein concentration or time of incubation, cleavage occurred at many sites. SegA cleaving activity was stimulated by the presence of ATP or ATP gamma S. Sequence analysis of three highly preferred cleavage sites did not reveal a simple consensus sequence, suggesting that even among highly preferred sites, SegA tolerates many different sequences. A T4 segA amber mutant that we constructed had no phenotype, and PCR analyses indicated that several T-even-related phages lack the segA gene. Taken together, our results show that SegA is an endonuclease with a hierarchy of site specificity, and these results are consistent with the insertion of segA DNA into the T4 genome some time after the divergence of the closely related T-even phages. C1 NIDDKD,CELLULAR & MOLEC BIOL LAB,NUCLE ACID BIOCHEM SECT,BETHESDA,MD 20892. NR 60 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 1994 VL 176 IS 21 BP 6439 EP 6448 PG 10 WC Microbiology SC Microbiology GA PN644 UT WOS:A1994PN64400005 PM 7961394 ER PT J AU BHUSHAN, R CRAIGIE, R MURPHY, TF AF BHUSHAN, R CRAIGIE, R MURPHY, TF TI MOLECULAR-CLONING AND CHARACTERIZATION OF OUTER-MEMBRANE PROTEIN-E OF MORAXELLA-(BRANHAMELLA)-CATARRHALIS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID FATTY-ACID TRANSPORT; ESCHERICHIA-COLI; DNA-SEQUENCE; GENE; SPECIFICITY; PATHOGEN; SURFACE AB Outer membrane protein E (OMP E) is a 50-kDa protein of Moraxella (Branhamella) catarrhalis. It is a potential vaccine antigen because it is expressed on the surface of the bacterium and has antigenic determinants which are conserved among most strains of M. catarrhalis. To clone the gene encoding OMP E, an EMBL-3 genomic library of strain 25240 was screened with a family of degenerate oligonucleotides based on the amino-terminal protein sequence. The OMP E gene was identified in one of the six positive clones by Southern blot analysis. An open reading frame of 1,377 bp encoding a protein of 460 amino acids was identified. The calculated molecular mass of the mature protein of 436 amino acid residues was 47.03 kDa, which correlated well with the results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein product of the OMP E gene had a leader peptide of 25 amino acids and a signal peptidase 1 cleavage site similar to those of known OMPs of Escherichia coli. The transcription initiation site of the OMP E gene was mapped by primer extension to be 78 nucleotides upstream of the ATG start codon. Borderline homology was found to the FadL protein off. coli (49.1% similarity and 25.6% identity), which is involved in the binding and transport of fatty acids. Analysis of restriction fragment length polymorphisms of the OMP E genes of 19 different strains of M. catarrhalis showed that the OMP E gene is highly conserved. The high degree of conservation of sequences of the OMP E genes of M. catarrhalis from diverse sources, along with earlier observations that the protein contains antigenic determinants on the bacterial surface, indicates that OMP E should be studied further as a potential vaccine antigen. C1 DEPT VET AFFAIRS MED CTR,BUFFALO,NY 14215. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. SUNY BUFFALO,DEPT MICROBIOL,BUFFALO,NY. SUNY BUFFALO,DEPT MED,DIV INFECT DIS,BUFFALO,NY. FU NIAID NIH HHS [AI28304] NR 25 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 1994 VL 176 IS 21 BP 6636 EP 6643 PG 8 WC Microbiology SC Microbiology GA PN644 UT WOS:A1994PN64400029 PM 7961416 ER PT J AU CLARK, AJ SATIN, L CHU, CC AF CLARK, AJ SATIN, L CHU, CC TI TRANSCRIPTION OF THE ESCHERICHIA-COLI RECE GENE FROM A PROMOTER IN TN5 AND IS50 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TRANSPOSON-INDUCED MUTATIONS; EXONUCLEASE-VIII; RAC PROPHAGE; AFFECT EXPRESSION; LINKAGE MAP; K-12; SUPPRESSION; DNA; RECOMBINATION; INSERTION AB Six sbc::Tn5 insertions and one sbc:IS50 insertion, which cause recE expression in Escherichia coli, have been cloned, and their DNA sequences have been determined. The sites of insertion are found at three positions in a 10-bp region: 58, 63, and 68 bp upstream of recE. Primer extension experiments with the cloned Tn5 insertions demonstrate that recE transcripts start adjacent to the insertion elements of five of these mutations and both adjacent and one nucleotide within the insertion element for the sixth mutation. This supports the hypothesis that these mutations have inserted a promoter, and PCR analysis reveals an outward promoter within the distal 69 nucleotides of Tn5. Primer extension analysis of RNA from the uncloned Tn5 and IS50 mutants reveals three additional insertion sites dose to the others. Because all the insertions lie in the spacer region between racC and recE, transcribed in sbcA6 and sbc-23 strains, we propose that these insertions be renamed recEs::Tn5 and recEs::IS50. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP CLARK, AJ (reprint author), UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,MCB,410 BARKER HALL,BERKELEY,CA 94720, USA. FU NIAID NIH HHS [AI05371]; NIGMS NIH HHS [GM07127] NR 38 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 1994 VL 176 IS 22 BP 7024 EP 7031 PG 8 WC Microbiology SC Microbiology GA PQ984 UT WOS:A1994PQ98400033 PM 7961467 ER PT J AU BALASUNDARAM, D DINMAN, JD TABOR, CW TABOR, H AF BALASUNDARAM, D DINMAN, JD TABOR, CW TABOR, H TI SPE1 AND SPE2 - 2 ESSENTIAL GENES IN THE BIOSYNTHESIS OF POLYAMINES THAT MODULATE +1-RIBOSOMAL FRAMESHIFTING IN SACCHAROMYCES-CEREVISIAE SO JOURNAL OF BACTERIOLOGY LA English DT Note ID ORNITHINE DECARBOXYLASE; PROTEIN-SYNTHESIS; ESCHERICHIA-COLI; YEAST; SPERMIDINE; EXPRESSION; SLIPPAGE AB We previously showed that a mutant of Saccharomyces cerevisiae, which cannot make spermidine as a result of a deletion in the SPE2 gene (spe2 Delta), exhibits a marked elevation in +1 ribosomal frameshifting efficiency in response to the Ty1 frameshift sequence, CUU AGG C. In the present study, we found that spermidine deprivation alone does not result in increased +1 ribosomal frameshifting efficiency. The high level of +1 ribosomal frameshifting efficiency in spe2 Delta cells is the result of the combined effects of both spermidine deprivation and the large increase in the level of intracellular putrescine resulting from the derepression of the gene for ornithine decarboxylase (SPE1) in spermidine deficient strains. RP BALASUNDARAM, D (reprint author), NIDDK,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 24 TC 31 Z9 31 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 1994 VL 176 IS 22 BP 7126 EP 7128 PG 3 WC Microbiology SC Microbiology GA PQ984 UT WOS:A1994PQ98400051 PM 7961484 ER PT J AU TUMMINIA, SJ RUSSELL, P AF TUMMINIA, SJ RUSSELL, P TI ALPHA-B-CRYSTALLIN ACCUMULATION IN HUMAN ASTROGLIOMA CELL-LINE U373MG IS STRESS-DEPENDENT AND PHOSPHORYLATION-INDEPENDENT SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE ALPHA-B-CRYSTALLIN; HEAT SHOCK; INDUCTION; OXIDATIVE STRESS; PHOSPHORYLATION ID HEAT-SHOCK PROTEIN; ALEXANDERS DISEASE BRAIN; NON-LENTICULAR TISSUES; IMMUNOREACTIVE ALPHA; MOLECULAR CHAPERONE; EXPRESSION; BINDING; LENS; GENE; LOCALIZATION AB alpha B-crystallin, a major lens protein, is present in non-lenticular tissues. Although alpha B-crystallin possesses chaperone-like activity, its physiological significance outside the lens is unclear. Recent studies suggest that stress-induced mechanisms of alpha B-crystallin accumulation are dependent upon the type of insult. To further investigate this possibility, the response of alpha B-crystallin to different stress conditions was examined in the human astroglioma U373MG cell line which constitutively expresses alpha B-crystallin. Exposure of this cell line to 25 mu M cobalt chloride and heat stress resulted in increased accumulation of alpha B-crystallin. Exposure to cobalt chloride resulted in a 6-fold (water-soluble) and 5-fold (water-insoluble) increase in alpha B-crystallin, 4 h after the initial exposure to cobalt. The water-soluble fraction of U373 cells subjected to heat shock at 42 degrees C for 30 min and harvested after 1 h exhibited a 4.5-fold increase in the level of alpha B-crystallin over the control levels. Approximately 2 h after the removal of the cells from the heat stress, the level of alpha B-crystallin in the urea-soluble fraction increased 3-fold. Although alpha B-crystallin accumulation initially increased in response to both the cobalt and heat shock challenges, analysis of the pattern of protein accumulation indicates that there are differences in the mechanism of alpha B-crystallin induction which are dependent on the type of stress. The concentration of alpha B-crystallin in both the water-soluble and water-insoluble fractions of heat-stressed cells showed that alpha B-crystallin concentrations returned to basal levels within 4 h after the initial shock, while levels of alpha B-crystallin remained high in the water-soluble fraction of cobalt-stressed cells 72 h after the initial stress. Since the role of phosphorylation in chaperone function is controversial, U373 cells were examined for induced forms of phosphorylated alpha B-crystallin. Isoelectric focusing gel electrophoresis followed by Western analysis indicated that the predominant form of alpha B-crystallin was unphosphorylated although small amounts of the phosphorylated form were found in all conditions. The phosphorylation state of alpha B-crystallin did not change after exposure to stress conditions indicating that the protective role of alpha B-crystallin is phosphorylation-independent under these conditions. RP TUMMINIA, SJ (reprint author), NEI,MECH OCULAR DIS LAB,BETHESDA,MD 20892, USA. NR 60 TC 10 Z9 10 U1 0 U2 0 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F 25-16 HONGO-5-CHOME, TOKYO TOKYO 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD NOV PY 1994 VL 116 IS 5 BP 973 EP 979 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ969 UT WOS:A1994PQ96900008 PM 7896758 ER PT J AU TERAJIMA, M MATSUI, Y COPELAND, NG GILBERT, DJ JENKINS, NA OBINATA, M AF TERAJIMA, M MATSUI, Y COPELAND, NG GILBERT, DJ JENKINS, NA OBINATA, M TI STRUCTURAL ORGANIZATION OF THE MOUSE GLYCOPHORIN-A GENE SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE CHROMOSOME MAPPING; GLYCOPHORIN A GENE; MOUSE ID HUMAN-ERYTHROCYTE GLYCOPHORIN; AMINO-ACID SEQUENCE; MURINE ERYTHROLEUKEMIA-CELLS; PROMOTING PHORBOL ESTER; NUCLEOTIDE-SEQUENCE; CDNA CLONES; EXPRESSION; IDENTIFICATION; MEMBRANE; REGION AB The human glycophorin gene has been extensively studied, but information on the homologous gene from other species has been unavailable. Here, we determined the structural organization of mouse glycophorin A gene and compared it with the human gene. The mouse glycophorin gene is a single copy gene while in humans, there are two highly related genes (A and B) that were generated by homologous recombination. Chromosomal mapping indicated that the mouse gene is located in the central region of the mouse chromosome 8, which is syntenic with human chromosomes 4q(28-31) where the human glycophorin A gene has been mapped. The mouse gene consists of 8 exons, while the human gene consists of 7 exons and the length of each exon is quite short except for the last exon. The last 4 exons showed extensive homology between the mouse and human genes but divergence in the 5'-exons of the two genes was high. The results suggest that glycophorin genes of mouse and human may have been generated from the same ancestor, but diverged greatly during evolution. The upstream regulatory region of the mouse gene consists of multiple motifs for DNA binding factors that may be required for its erythroid-specific expression. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD. RP TERAJIMA, M (reprint author), TOHOKU UNIV,INST DEV AGING & CANC,DEPT CELL BIOL,AOBA KU,SENDAI,MIYAGI 980,JAPAN. FU NCI NIH HHS [N01-CO-74101] NR 29 TC 13 Z9 13 U1 0 U2 0 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F 25-16 HONGO-5-CHOME, TOKYO TOKYO 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD NOV PY 1994 VL 116 IS 5 BP 1105 EP 1110 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ969 UT WOS:A1994PQ96900027 PM 7896738 ER EF