FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Orren, DK Dianov, GL Bohr, VA AF Orren, DK Dianov, GL Bohr, VA TI The human CSB (ERCC6) gene corrects the transcription-coupled repair defect in the CHO cell mutant UV61 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CYCLOBUTANE PYRIMIDINE DIMERS; NUCLEOTIDE EXCISION-REPAIR; RNA-POLYMERASE-II; COCKAYNE-SYNDROME CELLS; HAMSTER OVARY CELLS; INDUCED DNA DAMAGE; XERODERMA-PIGMENTOSUM; ACTIVE GENES; ACCURATE INITIATION; DHFR GENE AB The human CSB gene, mutated in Cockayne's syndrome group B (partially defective in both repair and transcription) was previously cloned by virtue of its ability to correct the moderate UV sensitivity of the CHO mutant UV61. To determine whether the defect in UV61 is the hamster equivalent of Cockayne's syndrome, the RNA polymerase II transcription and DNA repair characteristics of a repair-proficient CHO cell line (AA8), UV61 and a CSB transfectant of UV61 were compared, In each cell line, formation and removal of UV-induced cyclobutane pyrimidine dimers (CPDs) were measured in the individual strands of the actively transcribed DHFR gene and in a transcriptionally inactive region downstream of DHFR, AA8 cells efficiently remove CPDs from the transcribed strand, but not from either the non-transcribed strand or the inactive region, There was no detectable repair of CPDs in any region of the genome in UV61, Transfection of the human CSB gene into UV61 restores the normal repair pattern (CPD removal in only the transcribed strand), demonstrating that the DNA repair defect in UV61 is homologous to that in Cockayne's syndrome (complementation group B) cells, However, we observe no significant deficiency in RNA polymerase Ii-mediated transcription in UV61, suggesting that the CSB protein has independent roles in DNA repair and RNA transcription pathways. C1 NIA,GENET MOL LAB,NATL INST HLTH,BALTIMORE,MD 21224. NR 40 TC 27 Z9 27 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 SEP 1 PY 1996 VL 24 IS 17 BP 3317 EP 3322 DI 10.1093/nar/24.17.3317 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VG664 UT WOS:A1996VG66400007 PM 8811084 ER PT J AU Anderson, NB AF Anderson, NB TI The NIH Office of Behavioral Social Science Research: An update on activities SO NURSING OUTLOOK LA English DT Editorial Material RP Anderson, NB (reprint author), NIH,OFF BEHAV & SOCIAL SCI RES,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD SEP-OCT PY 1996 VL 44 IS 5 BP 222 EP 222 PG 1 WC Nursing SC Nursing GA VN526 UT WOS:A1996VN52600004 ER PT J AU Meltzer, AA Everhart, JE AF Meltzer, AA Everhart, JE TI Correlations with self-reported weight loss in overweight US adults SO OBESITY RESEARCH LA English DT Article DE weight loss; risk factors; confounding factors; health surveys ID UNITED-STATES ADULTS; SEX-DIFFERENCES; BODY-WEIGHT; PROGRAM; WOMEN; POPULATION; ACCURACY; DIETARY; OBESITY; HEALTH AB The authors investigated two issues among overweight men and women in the U.S.: 1) what is the influence of the self-expressed intention to lose weight in the presence of other potential predictors of loss and 2) what are easily identifiable predictors of intentional weight loss during a 1-year recall period, The sample consisted of 1996 overweight men (body mass index (BMI greater than or equal to 27.8 kg/m(2)) and 2586 overweight women (BMI greater than or equal to 27.3 kg/m(2)) who answered questions regarding 1-year weight change in a Current Health Topic supplement of the population-based 1989 National Health Interview Survey, Of these overweight persons, 56.8% of men and 72.1% of women attempted to lose weight during the previous year, The most important characteristic associated with weight loss was the expressed intention itself, For any weight loss, the odds ratios (95% confidence intervals) for intention were 4.6 (3.6-5.9) for men and 3.8 (2.8-5.0) for women, Controlling for other factors reduced the odds only slightly, to 4.3 for men and 3.5 for women, Among women, older age, having a greater frequency of blood pressure checks, and being in poorer health reduced the influence of intent as a predictor of loss, To address the second objective, the identification of predictors of intentional 1-year weight loss, analysis was restricted to overweight persons who attempted to lose weight. For both sexes, statistically significant predictors (p < 0.05) included never being married, smoking, higher BMI, being diabetic, and having a higher number of blood pressure checks, Being divorced or separated was predictive of weight loss in men only, Also, men were more likely to achieve weight loss than women, In conclusion, 1-year weight loss among the overweight was primarily a function of the intention to lose weight, although other factors contributed to determine whether weight loss was achieved. C1 NIDDKD,BETHESDA,MD 20892. SOCIAL & SCI SYST INC,BETHESDA,MD 20814. FU NIDDK NIH HHS [N01-DK-1-2282] NR 34 TC 10 Z9 10 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI BATON ROUGE PA 6400 PERKINS RD, BATON ROUGE, LA 70808 SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 1996 VL 4 IS 5 BP 479 EP 486 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA VH353 UT WOS:A1996VH35300008 PM 8885213 ER PT J AU Gracely, RH AF Gracely, RH TI Sensations, feelings, and physical events SO PAIN FORUM LA English DT Editorial Material C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NEUROPATH PAIN & PAIN MEASUREMENT SECT,NIH,BETHESDA,MD 20892. NR 5 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 1058-9139 J9 PAIN FORUM JI Pain Forum PD FAL PY 1996 VL 5 IS 3 BP 162 EP 164 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WH423 UT WOS:A1996WH42300002 ER PT J AU Kenshalo, DR AF Kenshalo, DR TI Pain and the primary somatosensory cortex - Is its role in pain overrated? SO PAIN FORUM LA English DT Editorial Material ID STIMULI; INTENSITY; NEURONS C1 NIDR, NEUROBIOL & ANESTHESIOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1058-9139 J9 PAIN FORUM JI Pain Forum PD FAL PY 1996 VL 5 IS 3 BP 181 EP 183 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WH423 UT WOS:A1996WH42300008 ER PT J AU Wisnewski, AV Olds, GR Johnson, JH Ramirez, B Kresina, TF AF Wisnewski, AV Olds, GR Johnson, JH Ramirez, B Kresina, TF TI Function and expression of a human idiotypic network in Schistosomiasis japonica SO PARASITE IMMUNOLOGY LA English DT Article DE Schistosomiasis japonica; anti-idiotype; major cross-reactive idiotype; idiotypic networks; granulomatous inflammation ID LYMPHOCYTE-T RESPONSIVENESS; IMMUNE-RESPONSES; MONOCLONAL-ANTIBODY; MANSONI; INFECTION; INVITRO; ANTIGEN; PHILIPPINES; VACCINE; CELLS AB The cross-reactive idiotype (Hu-SJ-CRI(M)) is defined by polyclonal human anti-idiotypic antibodies derived from chronically S. japonicum infected patients. The present study shows that serum levels of Hu-SJ-CRI(M) expressed by antibodies to S. japonicum soluble egg antigen (SEA) are associated with acute infection and hepatosplenic disease. Xenogenic anti-idiotypic antisera (anti-Hu-SJ-CRI(M)) suppressed human lymphocyte blastogenesis to SEA in vitro by 47-82% (P < 0.05). These anti-idiotypic antibodies also suppressed in vitro granuloma formation induced by SEA coated beads in a dose dependent manner. This immunosuppression was antigen specific in that mitogen (PHA) or non-related antigen (PPD) induced blastogenic responses were not suppressed. Surprisingly, anti-idiotypic antibodies (anti-SJ-CRI(M)), which describe the mouse correlate CRI(M) were not suppressive in the human blastogenesis or in vitro granuloma formation assays. These data indicate a dichotomy in the function and specificity of the idiotype/anti-idiotype human and murine immune networks in S. japonicum infection. Thus, only the patient derived molecules and serology form the basis for an immunoregulatory network in Schistosomiasis japonica. C1 NIDDKD,DIV DIGEST DIS & NUTR,NIH,BETHESDA,MD. NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. METROGEN HLTH MED CTR,DEPT MED,CLEVELAND,OH. RES INST TROP MED,MANILA,PHILIPPINES. NR 26 TC 5 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD SEP PY 1996 VL 18 IS 9 BP 439 EP 447 DI 10.1111/j.1365-3024.1996.tb01027.x PG 9 WC Immunology; Parasitology SC Immunology; Parasitology GA VH602 UT WOS:A1996VH60200002 PM 9226679 ER PT J AU Krogstad, D Kojima, S James, SL AF Krogstad, D Kojima, S James, SL TI Parasitology research in the USA and Japan SO PARASITOLOGY TODAY LA English DT Editorial Material ID SCHISTOSOMA-MANSONI; IMMUNE-RESPONSE; AEDES-AEGYPTI; ANTIGEN; SUSCEPTIBILITY; MALARIA; MICE C1 TULANE UNIV,DEPT TROP MED,NEW ORLEANS,LA 70112. UNIV TOKYO,INST MED SCI,DEPT PARASITOL,TOKYO 108,JAPAN. NIAID,PARASITOL & INT PROGRAMS BRANCH,NIH,BETHESDA,MD 20892. NR 10 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 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD SEP PY 1996 VL 12 IS 9 BP 332 EP 335 DI 10.1016/0169-4758(96)30012-4 PG 4 WC Parasitology SC Parasitology GA VE715 UT WOS:A1996VE71500002 ER PT J AU Gonzalez, CE Shetty, D Lewis, LL Mueller, BU Pizzo, PA Walsh, TJ AF Gonzalez, CE Shetty, D Lewis, LL Mueller, BU Pizzo, PA Walsh, TJ TI Cryptococcosis in human immunodeficiency virus-infected children SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE pediatric acquired immunodeficiency syndrome; cryptococcosis; amphotericin B; flucytosine ID ACQUIRED-IMMUNODEFICIENCY; EXTRAPULMONARY CRYPTOCOCCOSIS; CEREBROSPINAL-FLUID; AMPHOTERICIN-B; AIDS; FLUCYTOSINE; MENINGITIS; ANTIGEN; SERUM AB Background. Cryptococcosis is a common opportunistic infection in adults with AIDS. Few cases of cryptococcosis complicating pediatric AIDS have been reported. To our knowledge there are no studies that describe the epidemiology, clinical manifestations and outcome of cryptococcosis in a large population of HIV-infected children, Methods. We identified the cases of cryptococcosis through a retrospective review of the hospital records of the 473 HIV-infected children prospectively monitored in the Pediatric Branch of the National Cancer Institute during the 8 years from 1987 to 1995. Results. Pour (0.85%) patients developed cryptococcosis during the study period. All patients had profound depression of the absolute CD4 counts, a history of previous opportunistic infections, and onset of cryptococcosis in the second decade of life. Cryptococcosis developed as a disseminated infection or a localized process of the lungs. Intermittent fever was the most common presenting manifestation. Serum cryptococcal antigen was positive in all patients and gradually declined after the institution of the antifungal therapy. All patients were treated with amphotericin B with or without flucytosine as initial therapy. Suppressive therapy consisted of fluconazole with or without flucytosine, There were no deaths due to Cryptococcus neoformans. Conclusions. Cryptococcosis is an infrequent yet treatable opportunistic infection of advanced pediatric AIDS that may present with subtle manifestations and warrants careful consideration in the evaluation of febrile HIV-infected children. C1 NCI,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD 20892. NR 21 TC 44 Z9 49 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD SEP PY 1996 VL 15 IS 9 BP 796 EP 800 DI 10.1097/00006454-199609000-00012 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA VG538 UT WOS:A1996VG53800011 PM 8878224 ER PT J AU Armand, M Hamosh, M Mehta, NR Angelus, PA Philpott, JR Henderson, TR Dwyer, NK Lairon, D Hamosh, P AF Armand, M Hamosh, M Mehta, NR Angelus, PA Philpott, JR Henderson, TR Dwyer, NK Lairon, D Hamosh, P TI Effect of human milk or formula on gastric function and fat digestion in the premature infant SO PEDIATRIC RESEARCH LA English DT Article ID LONG-CHAIN TRIGLYCERIDES; EXOCRINE PANCREATIC INSUFFICIENCY; GLOBULE SIZE DISTRIBUTION; CARBOXYL ESTER LIPASE; LINGUAL LIPASE; GESTATIONAL-AGE; ENZYME-ACTIVITY; DIETARY-FAT; LIPOLYTIC-ACTIVITY; ACID COMPOSITION AB The effect of diet, human milk or formula, on gastric function (lipase and pepsin activity, pH, and volume) and intragastric digestion of fat was assessed in 28 appropriate for gestational age preterm infants (gestational age, 28.9 +/- 1.4, 29.1 +/- 0.9, 29.5 +/- 0.6 wk; birth weight, 1.00 +/- 0.14 to 1.18 +/- 0.07 kg). The infants were fed either human milk (n = 11), SMA Super Preemie formula (n = 9), or Similac, Special Care formula (n = 8). Fasting and postprandial activity of digestive enzymes, pH, and gastric volume (measured before or during 50 min after gavage feeding) did not differ as a function of diet among the three groups of infants. Gastric lipase output, 23.1 +/- 5.1, 28.3 +/- 6.6, and 22.5 +/- 6.4 (U/kg of body weight) in human milk-, SMA SP-, or Similac SC-fed infants was comparable to the gastric lipase output of healthy adults fed a high fat diet (22.6 +/- 3.0). Pepsin output was, however, significantly lower (597 +/- 77, 743 +/- 97, and 639 +/- 142 U/kg of body weight) in human milk-, SMA SP-, and Similac SC-fed infants) than in healthy adults (3352 +/- 753 U/kg). The hydrolysis of dietary fat was 1.7-2.5-fold higher (p < 0.01) in human milk-fed infants than in infants fed either formula. We conclude that differences in type of feeding, i.e. different fatty acid profiles (long chain or medium chain triglycerides), different emulsions (natural or artificial), and different fat particle sizes do not affect the level of activity of gastric enzymes. However, the triglyceride within milk fat globules appears to be more accessible to gastric lipase than that within formula fat particles. We suggest that the contribution of gastric lipase to overall fat digestion might be greater in the newborn (a period of pancreatic insufficiency) than in the adult. C1 GEORGETOWN UNIV, MED CTR, DEPT PEDIAT, WASHINGTON, DC 20007 USA. GEORGETOWN UNIV, MED CTR, DIV DEV BIOL & NUTR, WASHINGTON, DC 20007 USA. GEORGETOWN UNIV, MED CTR, DIV NEONATOL, WASHINGTON, DC 20007 USA. GEORGETOWN UNIV, MED CTR, DEPT PHYSIOL & BIOPHYS, WASHINGTON, DC 20007 USA. NIDDKD, CELL BIOCHEM & BIOL LAB, SECT LIPID CELL BIOL, BETHESDA, MD 20892 USA. NIH, UNITE RECH TRANSPORT LIPIDES, INSERM, U130, MARSEILLE, FRANCE. RI Armand, Martine/O-5780-2016 NR 61 TC 107 Z9 107 U1 7 U2 47 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD SEP PY 1996 VL 40 IS 3 BP 429 EP 437 DI 10.1203/00006450-199609000-00011 PG 9 WC Pediatrics SC Pediatrics GA VD852 UT WOS:A1996VD85200011 PM 8865280 ER PT J AU Hirschfeld, S Moss, H Dragisic, K Smith, W Pizzo, PA AF Hirschfeld, S Moss, H Dragisic, K Smith, W Pizzo, PA TI Pain in pediatric human immunodeficiency virus infection: Incidence and characteristics in a single-institution pilot study SO PEDIATRICS LA English DT Article DE human immunodeficiency virus; acquired immunodeficiency syndrome; pain; care givers; foster care; cancer ID CHILDREN; PREVALENCE; GENDER AB Objective. Children with human immunodeficiency virus (HIV) infection have multiple complications associated with the disease process. Many of these complications are potentially painful and could affect the patient's quality of life. We examined the incidence and characteristics of the perception of pain in a cohort of families with children with HIV infection. Methodology. A questionnaire was developed and validated with a cohort of families with children with cancer. In a survey of families at the Pediatric Branch of the National Cancer Institute, 61 children with HIV infection and their care givers, along with 19 children with cancer and their care givers, were interviewed to determine the incidence and impact of pain. Results. Fifty-nine percent of the HIV-infected children and 55% of their care givers described pain as a component of their illness that impacted on their lives. Younger children and girls tended to report more pain. There was also a tendency for biological parents to expect and to treat more pain than foster parents, although there was no difference in the incidence of pain that biological and foster parents reported for their children. No differences were found between parents who were HIV positive and those who were not. In addition, no correlations were noted in incidence, expectation, or impact of pain with disease progression or surrogate markers such as CD4 counts. Pain in HIV-infected patients tended to be either in the gastrointestinal tract or limbs and usually responded to nonsteroidal anti-inflammatory therapy. The patients with cancer reported an incidence (47%) and impact of pain similar to those of previously reported studies on pediatric patients with cancer. Conclusion. Pain is common among children infected with HIV and can adversely impact on their lives, and its management should be a component of the general care of these patients. C1 NIDR,PAIN SERV,NIH,BETHESDA,MD. RP Hirschfeld, S (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20904, USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 29 TC 21 Z9 21 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1996 VL 98 IS 3 BP 449 EP 452 PN 1 PG 4 WC Pediatrics SC Pediatrics GA VF506 UT WOS:A1996VF50600017 PM 8784372 ER PT J AU Long, RM AF Long, RM TI News from the National Institute of General Medical Sciences (NIGMS) SO PHARMACEUTICAL RESEARCH LA English DT News Item RP Long, RM (reprint author), NIGMS,PHARMACOL & PHYSIOL SCI BRANCH,PHARMACOL PHYSIOL & BIOL CHEM DIV,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD SEP PY 1996 VL 13 IS 9 BP 1279 EP 1279 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA VL498 UT WOS:A1996VL49800001 ER PT J AU Tirelli, E Witkin, JM AF Tirelli, E Witkin, JM TI Pharmacological characterization of the enhancement of apomorphine-induced gnawing in mice by cocaine SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE apomorphine; (+)-amphetamine; (-)-cocaine; (+)-cocaine; cocaine methiodide; lidocaine; GBR 12909; gnawing; climbing; C57BL/6J mice ID CENTRAL NERVOUS-SYSTEM; DOPAMINE UPTAKE; STEREOTYPED BEHAVIOR; NUCLEUS ACCUMBENS; LOCAL-ANESTHETICS; MOUSE-BRAIN; BINDING; RATS; TRANSPORTERS; INHIBITION AB The present study was designed to provide additional information on the behavioral and pharmacological mechanisms associated with the augmentation of apomorphine-induced gnawing in C57BL/6J mice. (-)-Cocaine enhanced apomorphine-induced gnawing at doses devoid of effects on gnawing when given alone. The effect was stereoselective, with (+)-cocaine devoid of activity in this test. Peripheral synapses may also not be critical to the cocaine enhancement, as cocaine methiodide, a charged species, was also without effect. The local anesthetic actions of cocaine were evaluated with lidocaine, a local anesthetic without prominent dopaminergic actions. Like (-)-cocaine, lidocaine augmented the gnawing response to apomorphine without increasing climbing or gnawing when given alone, (+)-Amphetamine enhanced apomorphine-induced gnawing but only at a high dose that increased gnawing by itself. The selective dopamine uptake blocker, GBR 12909, augmented apomorphine-induced gnawing without increasing gnawing when given alone; however, unlike cocaine or lidocaine, GBR 12909 increased climbing at doses that augmented the gnawing response. These data indicate that the cocaine-augmented gnawing response to apomorphine does not appear to be the result of psychomotor stimulation per se. Rather, this effect may be due to blockade of dopamine uptake and/or the local anesthetic actions of cocaine. C1 NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,DRUG DEV GRP,NIH,BALTIMORE,MD 21224. NR 59 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD SEP PY 1996 VL 55 IS 1 BP 135 EP 140 DI 10.1016/0091-3057(96)00067-6 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA VE050 UT WOS:A1996VE05000019 PM 8870049 ER PT J AU Piscitelli, SC Wells, MJ Metcalf, JA Baseler, M Stevens, R Davey, RT AF Piscitelli, SC Wells, MJ Metcalf, JA Baseler, M Stevens, R Davey, RT TI Pharmacokinetics and pharmacodynamics of subcutaneous interleukin-2 in HIV-infected patients SO PHARMACOTHERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; RECOMBINANT INTERLEUKIN-2; THERAPY AB Study Objectives. To assess the pharmacokinetics and pharmacodynamics of subcutaneously administered interleukin-2 (IL-2) in patients infected with the human immunodeficiency virus (HIV). Design. Open, dose-escalating phase I clinical trial. Setting, Government research hospital. Patients. Eighteen patients infected with HIV. Interventions. Recombinant IL-2 at dosages of 12, 15, or 18 MIU/day was administered subcutaneously once or twice/day for 5 consecutive days every 2 months. A total, of 28 cycles of therapy were included in the analysis. Measurements and Main Results. Concentrations of IL-2 in serum were determined by a commercial enzyme-linked immunosorbent assay. Interleukin-2 was well absorbed, with peak concentrations from 21.9-112.9 IU/ml. Absorption was slow, with mean (+/- SD) time to maximum of 4.4 +/- 1.8 hours and a lag time of 26.9 +/- 13.7 minutes. Elimination half-life was 3.3 +/- 0.9 hours. The concentrations had wide variability both within and among patients. Levels of tumor necrosis faclor-alpha were increased. Maximum body temperature and systemic side effects were associated with peak serum levels. Conclusion. Interleukin-2 is well absorbed after subcutaneous injection in HIV-infected patients, and that route of administration is an alternative to intravenous infusions. C1 NIAID,DEPT CRIT CARE MED,NATL INST HLTH,BETHESDA,MD 20892. NIAID,WARREN G MAGNUSON CLIN CTR,IMMUNOREGULAT LAB,NATL INST HLTH,BETHESDA,MD 20892. SCI APPLICAT INT CORP,FREDERICK,MD. RP Piscitelli, SC (reprint author), NIAID,CTR CLIN,DEPT PHARM,NATL INST HLTH,BLDG 10,ROOM 1N257,BETHESDA,MD 20892, USA. NR 17 TC 22 Z9 22 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD SEP-OCT PY 1996 VL 16 IS 5 BP 754 EP 759 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VJ996 UT WOS:A1996VJ99600004 PM 8888071 ER PT J AU Bilski, P Martinez, LJ Koker, EB Chignell, CF AF Bilski, P Martinez, LJ Koker, EB Chignell, CF TI Photosensitization by norfloxacin is a function of pH SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID INDUCED CUTANEOUS PHOTOTOXICITY; QUINOLONE ANTIBACTERIAL AGENTS; NALIDIXIC-ACID; OXYGEN; MICE AB Norfloxacin is a fluoroquinolone (FQ) antibiotic that has been reported to cause cutaneous photosensitivity in animals and occasionally in humans. We have studied the fluorescence and singlet oxygen (O-I(2))-generating properties of norfloxacin, Upon UV excitation the drug fluoresces in water, and the relative intensities of two major fluorescence bands at ca 420 and 450 mm are affected by pH. The overall quantum yield of fluorescence (Phi(F)) is also strongly pH dependent: Phi(F), is low in 0.2 N HCl solution (0.2), increasing steeply to 0.12 at pH 4, then gradually decreasing to 0.01 at pH 10, The changes in Phi(F) are accompanied by changes in fluorescence lifetime from 0.6 ns at pH 1 to 1.8 ns at pH 4. Norfloxacin exhibits phosphorescence in low temperature glasses, The formation of a triplet state at room temperature is also suggested by O-I(2) phosphorescence in aerobic D2O. This phosphorescence is ''self-quenched'' by norfloxacin itself with an efficiency that is pH dependent: k(q) is 7.9 x 10(6)M(-1)s(-1) at pD 4, decreases to 1.9 X 10(6)M(-1)s(-1) at pD 7.5 but then increases about 20-fold in alkaline D2O solutions, This quenching causes the observed O-I(2), production by norfloxacin (0.1 mM) to show a maximum at around pH 8-9, However, after correction for self-quenching, the quantum yield of O-I(2), production (Phi(50)), measured by using perinaphthenone as a standard, yielded the following values: Phi(50), is about 0.07 in 0.2 1Y DCI solution, 0.08 at pH 7.5 and then increases smoothly to similar to 0.2 in 0.1 M NaOD solution, The relatively high, unquenched O-I(2) production at physiological pH 7.4 (Phi(50) similar to 0.08) suggests that O-I(2) reactions mag play an important role in the cutaneous phototoxicity of norfloxacin and other FQ antibiotics. C1 ELIZABETH CITY STATE UNIV,ELIZABETH CITY,NC. RP Bilski, P (reprint author), NIEHS,MOL BIOPHYS LAB,MAIL DROP 17-05,RES TRIANGLE PK,NC 27709, USA. NR 19 TC 71 Z9 75 U1 0 U2 13 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP PY 1996 VL 64 IS 3 BP 496 EP 500 DI 10.1111/j.1751-1097.1996.tb03096.x PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VG533 UT WOS:A1996VG53300015 PM 8806228 ER PT J AU Spouge, JL Szabo, A Weiss, GH AF Spouge, JL Szabo, A Weiss, GH TI Single-particle survival in gated trapping SO PHYSICAL REVIEW E LA English DT Article ID DYNAMIC TRAP; PASSAGE TIME; DIFFUSION AB Any chemical reaction A* + B --> C whose progress is modulated by another reaction of the form A* reversible arrow A is said to be gated. The eating reaction A* reversible arrow A represents a reversible fluctuation from a active state A* to an inactive state A that does not react with B, Reversibly blocked chemical reactions, conformational fluctuations in proteins, and reactions occurring within biomembranes or involving biological molecules have all been studied recently in contexts related to gating. This paper gives a unified, general formalism for calculating trapping rates and mean survival times of gated reactions. It also presents and solves some gating models. Although most of its explicit formulas are for problems with a single particle moving in the presence of a single gated, static trap, the method of solution is formally applicable to problems involving several particles and several point traps, even when the gating kinetics are non-Markovian. Those cases give integral equations that cannot be solved in closed form, however. This paper's results also include the bimolecular rate constant for a gated ligand binding to a gated protein. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NIH,PHYS SCI LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP Spouge, JL (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. RI Szabo, Attila/H-3867-2012 NR 23 TC 28 Z9 28 U1 1 U2 5 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD SEP PY 1996 VL 54 IS 3 BP 2248 EP 2255 DI 10.1103/PhysRevE.54.2248 PG 8 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA VK265 UT WOS:A1996VK26500018 ER PT J AU Robinson, WP Langlois, S Schuffenhauer, S Horsthemke, B Michaelis, RC Christian, S Ledbetter, DH Schinzel, A AF Robinson, WP Langlois, S Schuffenhauer, S Horsthemke, B Michaelis, RC Christian, S Ledbetter, DH Schinzel, A TI Cytogenetic and age-dependent risk factors associated with uniparental disomy 15 SO PRENATAL DIAGNOSIS LA English DT Article DE Prader-Willi syndrome; uniparental disomy; non-disjunction; t(15q15q); confined placental mosaicism ID PRADER-WILLI-SYNDROME; ANGELMAN-SYNDROME; MOLECULAR DIAGNOSIS; INV DUP(15); PATERNAL AGE; ROBERTSONIAN TRANSLOCATIONS; MILDER PHENOTYPE; HUMAN SPERM; CHROMOSOME-15; ORIGIN AB Prader-Willi syndrome (PWS) results primarily from either a paternal deletion of 15q11-q13 or maternal uniparental disomy (UPD) of chromosome 15. Including the present and published cases, more than 120 patients with maternal UPD of human chromosome 15 have been ascertained. Investigation of chromosome 15 markers indicates that approximately 71 per cent of the additional maternal chromosomes were the result of meiosis I segregation errors, 13 per cent were the result of meiosis II errors, and 16 per cent resulted from post-zygotic duplication of one chromosome 15. An increase in maternal age is associated with UPD cases due to meiotic errors. The age-specific risk for UPD(15) is analysed and shows an exponential increase with maternal age which is similar to that observed for trisomy 21. For women greater than or equal to 40 years of age, the risk for UPD(15) is approximately 1/3400 livebirths. The frequency of chromosome aberrations associated with UPD(IS) is also discussed. Two types of aberrations are at significantly increased risk of fetal UPD(IS): de novo (or inherited) isochromosome 15 and confined placental mosaicism for trisomy 15. Two additional abnormalities, tie novo small marker chromosomes derived from 15, e.g., idic15(pter-q11:q11-pter), and familial Robertsonian translocations involving chromosome 15; appear to have a mildly increased risk of UPD(15). C1 UNIV BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER,BC,CANADA. UNIV MUNICH,KINDERPOLIKLIN,ABT PADIAT GENET,MUNICH,GERMANY. UNIV ESSEN GESAMTHSCH KLINIKUM,INST HUMAN GENET,ESSEN,GERMANY. GREENWOOD GENET CTR,GREENWOOD,SC 29646. NIH,NCHGR,BETHESDA,MD 20892. UNIV ZURICH,INST MED GENET,ZURICH,SWITZERLAND. RI Robinson, Wendy/I-9590-2014 OI Robinson, Wendy/0000-0002-2010-6174 NR 50 TC 40 Z9 41 U1 2 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD SEP PY 1996 VL 16 IS 9 BP 837 EP 844 DI 10.1002/(SICI)1097-0223(199609)16:9<837::AID-PD956>3.0.CO;2-7 PG 8 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA VM820 UT WOS:A1996VM82000008 PM 8905898 ER PT J AU Salive, ME Guralnik, JM Brock, D AF Salive, ME Guralnik, JM Brock, D TI Preventive services for breast and cervical cancer in US office-based practices SO PREVENTIVE MEDICINE LA English DT Article DE breast examination; mammography; breast self-examination counseling; pelvic examination; Papanicolau smear; cancer screening; ambulatory care; medical service delivery ID SCREENING MAMMOGRAPHY; FAMILY PHYSICIANS; PRIMARY CARE; HEALTH; GUIDELINES; QUEBEC AB Background. This study was undertaken to examine patterns of delivery of preventive services for breast and cervical cancer and the bundling of several preventive services. Methods. Data from the National Ambulatory Medical Care Survey on visits by women ages greater than or equal to 45 years to office-based physicians during 1989 and 1990 were analyzed for delivery of clinical breast examination, mammography, breast self-examination counseling, pelvic examination, and Pap smear. Results. An estimated 38.7 million office visits included one or more preventive services for breast and cervical cancer (46.7 visits per 100 women per year). Visits that included clinical breast examination, Pap smear, and mammography together were largely provided by obstetricians and gynecologists, less by general family practice and general internal medicine physicians, and rarely by subspecialists. Twenty-two percent of these visits were periodic preventive visits, lowest for subspecialists and highest for general internists. Major sources of payment included insurance and personal resources at younger ages and Medicare at ages greater than or equal to 65. Conclusions. The periodic preventive visit has received only limited acceptance by physicians who provide preventive care for adult women, Payment for preventive visits changes with age and may affect the appropriate provision of services. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH,BETHESDA,MD 20892. NR 33 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP-OCT PY 1996 VL 25 IS 5 BP 561 EP 568 DI 10.1006/pmed.1996.0090 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VJ934 UT WOS:A1996VJ93400009 PM 8888324 ER PT J AU Elenkov, IJ Papanicolaou, DA Wilder, RL Chrousos, GP AF Elenkov, IJ Papanicolaou, DA Wilder, RL Chrousos, GP TI Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: Clinical implications SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE IL-12; IL-10; norepinephrine; epinephrine; stress ID NECROSIS-FACTOR-ALPHA; CORTICOTROPIN-RELEASING HORMONE; NERVOUS-SYSTEM; BACTERIAL LIPOPOLYSACCHARIDE; IMMUNE-SYSTEM; CYTOKINE; STRESS; SUSCEPTIBILITY; INFLAMMATION; ADRENALINE AB Interleukin-12 (IL-12) is a key inducer of differentiation of uncommitted T helper (TH) cells toward the TH1 phenotype, which regulates cellular immunity, whereas IL-10 inhibits TH1 functions and potentiates TH2-regulated responses (i.e., humoral immunity). To examine the potential effects of stress on TH1/TH2 balance, we studied the ability of three prototype stress hormones-dexamethasone (a synthetic glucocorticoid) and the catecholamines norepinephrine and epinephrine-to alter the production of IL-12 (p70) and IL-10 induced by bacterial lipopolysaccharide (LPS) in human whole blood. Dexamethasone inhibited LPS-induced bioactive IL-12 production in a dose-dependent fashion and at physiologically relevant concentrations; it had no effect on IL-10 secretion. The glucocorticoid-induced reduction of IL-12 production was antagonized by RU 486, a glucocorticoid-receptor antagonist, suggesting that it was mediated by the glucocorticoid receptor. Norepinephrine and epinephrine also suppressed IL-12 production in a dose-dependent fashion and at physiological concentrations; both catecholamines, however, dose-dependently increased the production of IL-10. The effects of either catecholamine on IL-12 or IL-10 secretion were blocked completely by propranolol, a beta-adrenoreceptor antagonist, indicating that they were mediated by the beta-adrenergic receptor. These findings suggest that the central nervous system may regulate IL-12 and IL-10 secretion and, hence, TH1/TH2 balance via the peripheral end-effecters of the stress system. Thus, stress may cause a selective suppression of TH1 functions and a shift toward a TH2 cytokine pattern rather than generalized TH suppression. The TH1-to-TH2 shift may be responsible for the stress-induced susceptibility of the organism to certain infections. Through the same or a reciprocal mechanism, states associated with chronic hyperactivity or hypoactivity of the stress system might influence the susceptibility of an individual to certain autoimmune, allergic, infectious, or neoplastic diseases. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIAMS,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD. NR 36 TC 297 Z9 303 U1 1 U2 4 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD SEP PY 1996 VL 108 IS 5 BP 374 EP 381 PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VP845 UT WOS:A1996VP84500005 PM 8902882 ER PT J AU Walls, R Thibault, A Liu, L Wood, C Kozlowski, JM Figg, WD Sampson, ML Elin, RJ Samid, D AF Walls, R Thibault, A Liu, L Wood, C Kozlowski, JM Figg, WD Sampson, ML Elin, RJ Samid, D TI The differentiating agent phenylacetate increases prostate-specific antigen production by prostate cancer cells SO PROSTATE LA English DT Article DE differentiation therapy; tumor markers; aromatic fatty acid ID ACID-PHOSPHATASE; RADICAL PROSTATECTOMY; PHASE-I; ADENOCARCINOMA; DIAGNOSIS AB The prostatic-specific antigen (PSA) is the tumor marker most widely relied upon for the monitoring of patients with prostate cancer. Recently, declines in the serum concentrations of PSA have been advocated as a surrogate marker of tumor response in clinical trials of investigational antitumor agents. We examined the hypothesis that this postulate may not apply to the evaluation of drugs such as phenylacetate, a differentiating agent endowed with mechanisms of action different from those of classic cytotoxic chemotherapy. Using human prostatic carcinoma LNCaP cells as a model, we show that phenylacetate induces PSA production despite inhibition of tumor cell proliferation. Incubation of LNCaP cultures with cytostatic doses of phenylacetate (3-10 mM) resulted in a three- to fourfold increase in PSA secretion per cell. This appears to result from upregulation of PSA gene expression, as indicated by elevated PSA mRNA steady-state levels in treated cells. The increase in PSA production per cell was confirmed in rats bearing subcutaneous LNCaP tumor implants that were treated systemically with phenylacetate. Further comparative studies indicate that upregulation of PSA is common to various differentiation inducers, including all-trans-retinoic acid, 1,25-dihydroxyvitamin D-3, and butyrate but is not induced by other antitumor agents of clinical interest such as suramin. We conclude that declines in PSA may be treatment specific and that the exclusive use of this criterion as a marker of disease response may mislead the proper evaluation of differentiating agents in prostate cancer patients. (C) 1996 Wiley-Liss, Inc. C1 UNIV VIRGINIA,CTR CANC,CHARLOTTESVILLE,VA 22908. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,DEPT CLIN PATHOL,BETHESDA,MD 20892. NORTHWESTERN UNIV,DEPT UROL,CHICAGO,IL 60611. RI Figg Sr, William/M-2411-2016 NR 22 TC 28 Z9 29 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0270-4137 J9 PROSTATE JI Prostate PD SEP PY 1996 VL 29 IS 3 BP 177 EP 182 PG 6 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA VK288 UT WOS:A1996VK28800006 PM 8827086 ER PT J AU Alexandrov, NN AF Alexandrov, NN TI SARFing the PDB SO PROTEIN ENGINEERING LA English DT Article DE beta-prism architecture; globin fold; non-topological threading; parallel beta-helix; protein structure comparison; WWW ID NONHOMOLOGOUS PROTEINS; STRUCTURAL SIMILARITY; DOMAIN; RESOLUTION; ALIGNMENT; CALCIUM; VISION; MOTIFS; FOLD AB Fast growth of the number of the solved protein structures is increasing the role of their comparative analysis. In this paper I describe a new program, SARF2, for protein structure comparison and discuss new examples of the non-topological structural resemblance. SARF2 is designed to detect ensembles of secondary structure elements, which form similar spatial arrangements with possible different topological connections. The program is available to everyone through the World Wide Web (URL http://www-lmmb.ncifcrf.gov/similar to nicka/sarf2.html). The performance of the program is demonstrated by previously unnoticed cases of the significant similarities. One similarity discussed in this paper, between heme-binding proteins (cytochrome P450 and globin), consists of six alpha-helices, arranged into a globin fold. Another pair of structures (pectate lyase and snowdrop lectin) achieve similar beta-prism architecture through different topologies. The significance of these similarities is validated by (i) the distribution of a similarity score, (ii) the comparison of the aligned contact maps and/or (iii) the location of the active site. The observation of recurrent non-topological structural motifs implies their energetic stability and opens new possibilities for sequence-structure alignment (threading) methods. RP Alexandrov, NN (reprint author), NCI,MATH BIOL LAB,NIH,FREDERICK,MD 21702, USA. NR 25 TC 70 Z9 72 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD SEP PY 1996 VL 9 IS 9 BP 727 EP 732 DI 10.1093/protein/9.9.727 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA VK019 UT WOS:A1996VK01900003 PM 8888137 ER PT J AU Ren, ZJ Lewis, GK Wingfield, PT Locke, EG Steven, AC Black, LW AF Ren, ZJ Lewis, GK Wingfield, PT Locke, EG Steven, AC Black, LW TI Phage display of intact domains at high copy number: A system based on SOC, the small outer capsid protein of bacteriophage T4 SO PROTEIN SCIENCE LA English DT Article DE bacteriophage T4; capsid assembly; human immunodeficiency virus antigens; phage display; protein engineering ID FILAMENTOUS BACTERIOPHAGE; MONOCLONAL-ANTIBODIES; SURFACE LATTICE; EXPRESSION; PEPTIDES; EPITOPE; GENE; IMMUNOGENICITY; NEUTRALIZATION; LOCALIZATION AB Peptides fused to the coat proteins of filamentous phages have found widespread applications in antigen display, the construction of antibody libraries, and biopanning. However, such systems are limited in terms of the size and number of the peptides that may be incorporated without compromising the fusion proteins' capacity to self-assemble. We describe here a system in which the molecules to be displayed are bound to pre-assembled polymers. The polymers are T4 capsids and polyheads (tubular capsid variants) and the display molecules are derivatives of the dispensable capsid protein SOC. In one implementation, SOC and its fusion derivatives are expressed at high levels in Escherichia coli, purified in high yield, and then bound in vitro to separately isolated polyheads. In the other, a positive selection vector forces integration of the modified soc gene into a sec-deleted T4 genome, leading to in vivo binding of the display protein to progeny virions. The system is demonstrated as applied to C-terminal fusions to SOC of (1) a tetrapeptide; (2) the 43-residue V3 loop domain of gp120, the human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein; and (3) poliovirus VP1 capsid protein (312 residues). SOC-V3 displaying phage were highly antigenic in mice and produced antibodies reactive with native gp120. That the fusion protein binds correctly to the surface lattice was attested in averaged electron micrographs of polyheads. The SOC display system is capable of presenting up to similar to 10(3) copies per capsid and >10(4) copies per polyhead of V3-sized domains. Phage displaying SOC-VP1 were isolated from a 1:10(6) mixture by two cycles of a simple biopanning procedure, indicating that proteins of at least 35 kDa may be accommodated. C1 NIAMSD,STRUCT BIOL LAB,NIH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT IMMUNOL & MICROBIOL,BALTIMORE,MD 21201. NIAMSD,PROT EXPRESS LAB,NIH,BETHESDA,MD 20892. NR 45 TC 68 Z9 86 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD SEP PY 1996 VL 5 IS 9 BP 1833 EP 1843 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VG558 UT WOS:A1996VG55800009 PM 8880907 ER PT J AU Chacko, S Silverton, EW SmithGill, SJ Davies, DR Shick, KA Xavier, KA Willson, RC Jeffrey, PD Chang, CYY Sieker, LC Sheriff, S AF Chacko, S Silverton, EW SmithGill, SJ Davies, DR Shick, KA Xavier, KA Willson, RC Jeffrey, PD Chang, CYY Sieker, LC Sheriff, S TI Refined structures of bobwhite quail lysozyme uncomplexed and complexed with the HyHEL-5 Fab fragment SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE avian lysozyme; anti-protein Fab; antibody-antigen complex ID INFLUENZA-VIRUS HEMAGGLUTININ; ANTIBODY-ANTIGEN COMPLEX; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURE; MACROMOLECULAR STRUCTURES; ANGSTROM RESOLUTION; LEAST-SQUARES; PROTEIN; NEURAMINIDASE; IDIOTOPE AB The HyHEL-5 antibody has more than a thousandfold lower affinity for bobwhite quail lysozyme (BWQL) than for hen egg-white lysozyme (HEL). Four sequence differences exist between BWQL and HEL, of which only one is involved in the interface with the Fab. The structure of bobwhite quail lysozyme has been determined in the uncomplexed state in two different crystal forms and in the complexed state with HyHEL-5, an antihen egg-white lysozyme Fab, Similar backbone conformations are observed in the three molecules of the two crystal forms of uncomplexed BWQL, although they show considerable variability in side-chain conformation, A relatively mobile segment in uncomplexed BWQL is observed to be part of the HS HEL-B epitope. No major backbone conformational differences are observed in the lysozyme upon complex formation, but side-chain conformational differences are seen in surface residues that are involved in the interface with the antibody. The hydrogen bonding in the interface between BWQL and Hy HEL-B is similar to that in previously determined lysozyme-HyHEL-5 complexes. (C) 1996 Wiley-Liss, Inc. C1 NIDDK,MOL BIOL LAB,NIH,BETHESDA,MD 20895. NCI,NIH,BETHESDA,MD 20895. UNIV HOUSTON,DEPT CHEM ENGN,HOUSTON,TX 77204. UNIV HOUSTON,DEPT BIOCHEM & BIOPHYS SCI,HOUSTON,TX 77204. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. NR 56 TC 24 Z9 25 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 0887-3585 J9 PROTEINS JI Proteins PD SEP PY 1996 VL 26 IS 1 BP 55 EP 65 DI 10.1002/(SICI)1097-0134(199609)26:1<55::AID-PROT5>3.0.CO;2-F PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VH401 UT WOS:A1996VH40100006 PM 8880929 ER PT J AU Roca, CA Schmidt, PJ Bloch, M Rubinow, DR AF Roca, CA Schmidt, PJ Bloch, M Rubinow, DR TI Implications of endocrine studies of premenstrual syndrome SO PSYCHIATRIC ANNALS LA English DT Article ID CYCLICAL ORAL NORETHISTERONE; HORMONE AGONIST; DEPOT LEUPROLIDE; CONTROLLED TRIAL; CROSSOVER TRIAL; PROGESTERONE; SYMPTOMS; PLACEBO; WOMEN; MANAGEMENT C1 NIMH,BIOL PSYCHIAT BRANCH,SECT BEHAV ENDORINOL,BETHESDA,MD 20892. RP Roca, CA (reprint author), NIMH,BIOL PSYCHIAT BRANCH,REPROD ENDOCRINOL UNIT,BLDG 10,RM 3N238,10 CTR DR,MSC 1276,BETHESDA,MD 20892, USA. NR 36 TC 20 Z9 20 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD SEP PY 1996 VL 26 IS 9 BP 576 EP 580 PG 5 WC Psychiatry SC Psychiatry GA VG546 UT WOS:A1996VG54600007 ER PT J AU Robinson, JK Wenk, GL Wiley, RG Lappi, DA Crawley, JN AF Robinson, JK Wenk, GL Wiley, RG Lappi, DA Crawley, JN TI (192)IgG-Saporin immunotoxin and ibotenic acid lesions of nucleus basalis and medial septum produce comparable deficits on delayed nonmatching to position in rats SO PSYCHOBIOLOGY LA English DT Article ID FOREBRAIN CHOLINERGIC SYSTEM; TO-SAMPLE; ALZHEIMERS-DISEASE; NGF RECEPTOR; MEMORY; MAGNOCELLULARIS; CONSEQUENCES; SCOPOLAMINE; PERFORMANCE; INJECTIONS AB The recently developed immunotoxin, (192)IgG-Saporin (192-SAP), was compared with the standard excitotoxin, ibotenic acid, on two measures: (1) the extent of deficits on performance of a working memory task, delayed nonmatching-to-position (DNMTP), and (2) sensitivity to scopolamine on this task. Rats were extensively pretrained in an operant, spatial DNMTP memory task, then given combined site-specific lesions of the medial septum/diagonal band and nucleus basalis magnocellularis using either ibotenic acid (IBO) or low doses of the selective cholinergic immunotoxin 192-SAP. When compared with sham controls, both IBO and 192-SAP lesioned rats showed significant delay-independent reductions in DNMTP choice accuracy. Both 192-SAP and IBO lesioned rats showed increased sensitivity to a threshold dose of scopolamine, 0.15 mg/kg i.p., on DNMTP, as compared with sham-lesioned controls. When the rats were assessed at 18 weeks postlesioning, levels of choline acetyltransferase were depleted in the hippocampus in both IBO and 192-SAP lesioned groups. These findings suggest that 192-SAP, a cholinergically selective neurotoxin, is as effective as an excitotoxin when microinjected into cholinergic cell bodies of the basal forebrain, producing deficits in behavioral tasks that persist for several weeks. C1 NIMH,BETHESDA,MD 20892. UNIV ARIZONA,TUCSON,AZ. VET ADM MED CTR,NASHVILLE,TN 37203. ADV TARGETING SYST,SAN DIEGO,CA. NR 32 TC 19 Z9 19 U1 0 U2 1 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0889-6313 J9 PSYCHOBIOLOGY JI Psychobiology PD SEP PY 1996 VL 24 IS 3 BP 179 EP 186 PG 8 WC Psychology; Psychology, Multidisciplinary SC Psychology GA VL925 UT WOS:A1996VL92500001 ER PT J AU Waller, NG Putnam, FW Carlson, EB AF Waller, NG Putnam, FW Carlson, EB TI Types of dissociation and dissociative types: A taxometric analysis of dissociative experiences SO PSYCHOLOGICAL METHODS LA English DT Review ID MULTIPLE PERSONALITY-DISORDER; POSTTRAUMATIC STRESS DISORDER; SEXUAL ABUSE; SCALE; VALIDITY; HYPNOTIZABILITY; PSYCHOPATHOLOGY; RELIABILITY; PERSPECTIVE; INDICATORS AB This article examined evidence for dimensional and typological models of dissociation. The authors reviewed previous research with the Dissociative Experiences Scale (DES; E. B. Bernstein-Carlson & F. W. Putnam, 1986) and note that this scale, like other dissociation questionnaires, was developed to measure that so-called dissociative continuum. Next, recently developed taxometric methods for distinguishing typological from dimensional constructs are described and applied to DES item-response data from 228 adults with diagnosed multiple personality disorder and 228 normal controls. The taxometric findings empirically justify the distinction between two types of dissociative experiences. Nonpathological dissociative experiences are manifestations of a dissociative trait, whereas pathological dissociative experiences are manifestations of a latent class variable. The taxometric findings also indicate that there are two types of dissociators. Individuals in the pathological dissociative class (taxon) can be identified with a brief, 8-item questionnaire called the DES-T. Scores on the DES-T and DES are compared in 11 clinical and nonclinical samples. It is concluded that the DES-T is a sensitive measure of pathological dissociation, and the implications of these taxometric results for the identification, treatment, and understanding of multiple personality disorder and allied pathological dissociative states are discussed. C1 NIMH,BETHESDA,MD 20892. BELOIT COLL,DEPT PSYCHOL,BELOIT,WI 53511. RP Waller, NG (reprint author), UNIV CALIF DAVIS,DEPT PSYCHOL,DAVIS,CA 95616, USA. OI Carlson, Eve/0000-0002-4431-2415 NR 106 TC 444 Z9 447 U1 6 U2 35 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 1082-989X J9 PSYCHOL METHODS JI Psychol. Methods PD SEP PY 1996 VL 1 IS 3 BP 300 EP 321 DI 10.1037/1082-989X.1.3.300 PG 22 WC Psychology, Multidisciplinary SC Psychology GA VV661 UT WOS:A1996VV66100007 ER PT J AU Staley, JK Ouyang, Q Pablo, J Hearn, WL Flynn, DD Rothman, RB Rice, KC Mash, DC AF Staley, JK Ouyang, Q Pablo, J Hearn, WL Flynn, DD Rothman, RB Rice, KC Mash, DC TI Pharmacological screen for activities of 12-hydroxyibogamine: A primary metabolite of the indole alkaloid ibogaine SO PSYCHOPHARMACOLOGY LA English DT Article DE ibogaine; 12-hydroxyibogamine; ligand binding; neuroreceptors; neurotransporter; drug dependence ID NMDA RECEPTOR COMPLEX; ANTI-ADDICTIVE DRUG; HUMAN-BRAIN; BINDING-SITES; RAT-BRAIN; RADIOLIGAND-BINDING; INTRAVENOUS COCAINE; NUCLEUS-ACCUMBENS; MK-801 BINDING; OPIOID SYSTEMS AB The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. Ibogaine undergoes first pass metabolism and is O-demethylated to 12-hydroxy-ibogamine (12-OH ibogamine). Radioligand binding assays were conducted to identify the potency and selectivity profiles for ibogaine and 12-OH ibogamine. A comparison of 12-OH ibogamine to the primary molecular targets identified previously for ibogaine demonstrates that the metabolite has a binding profile that is similar, but not identical to the parent drug. Both ibogaine and 12-OH ibogamine demonstrated the highest potency values at the cocaine recognition site on the 5-HT transporter. The same rank order (12-OH ibogamine > ibogaine), but lower potencies were observed for the [H-3]paroxetine binding sites on the 5-HT transporter. Ibogaine and 12-OH ibogamine were equipotent at vesicular monoamine and dopamine transporters. The metabolite demonstrated higher affinity at the kappa-1 receptor and lower affinity at the NMDA receptor complex compared to the parent drug. Quantitation of the regional brain levels of ibogaine and 12-OH ibogamine demonstrated micromolar concentrations of both the parent drug and metabolite in rat brain. Drug dependence results from distinct, but inter-related neurochemical adaptations, which underlie tolerance, sensitization and withdrawal. Ibogaine's ability to alter drug-seeking behavior may be due to combined actions of the parent drug and metabolite at key pharmacological targets that modulate the activity of drug reward circuits. C1 UNIV MIAMI,SCH MED,DEPT NEUROL D45,MIAMI,FL 33101. METRO DADE CTY MED EXAMINERS DEPT,MIAMI,FL 33136. UNIV MIAMI,SCH MED,DEPT MOL & CELLULAR PHARMACOL,MIAMI,FL 33101. NATL INST DRUG ABUSE,ADDICT RES CTR,NIH,CLIN PSYCHOPHARMACOL SECT,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. NIDDK,MED CHEM LAB,SECT DRUG DESIGN & SYNTHESIS,NIH,BETHESDA,MD 20892. FU NIDA NIH HHS [DA09202] NR 66 TC 33 Z9 33 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 1996 VL 127 IS 1 BP 10 EP 18 DI 10.1007/BF02805969 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VJ420 UT WOS:A1996VJ42000002 PM 8880938 ER PT J AU Benjamin, J Greenberg, BD Murphy, DL AF Benjamin, J Greenberg, BD Murphy, DL TI Daily administration of m-chlorophenylpiperazine to healthy human volunteers rapidly attenuates many of its behavioral, hormonal, cardiovascular and temperature effects SO PSYCHOPHARMACOLOGY LA English DT Article DE serotonin; m-CPP; anxiety; tolerance; humans; ACTH; prolactin; cortisol; mydriasis; body temperature; blood pressure ID OBSESSIVE-COMPULSIVE DISORDER; META-CHLOROPHENYLPIPERAZINE; SEROTONIN AGONIST; M-CPP; 1-(2,5-DIMETHOXY-4-IODOPHENYL)-2-AMINOPROPANE DOI; PSYCHOTROPIC-DRUGS; ALZHEIMERS-DISEASE; LOCOMOTOR-ACTIVITY; 5-HT2C RECEPTORS; NEURO-ENDOCRINE AB The serotonergic agent meta-chlorophenyl-piperazine (m-CPP) increases temperature and plasma ACTH and other hormones and decreases social interaction, locomotor activity and food intake in rats, most likely via stimulation of 5-HT2C receptors. Repeated daily administration of m-CPP to rats induces rapid tolerance to these effects of m-CPP. As m-CPP has been used in challenge tests and in preliminary treatment trials in humans, we evaluated the possible development of tolerance to m-CPP in ten healthy human volunteers using a double-blind, random assignment crossover study of placebo versus daily m-CPP infusions. Psychological and physical symptoms of anxiety, temperature, pupil size, diastolic blood pressure, and plasma ACTH, cortisol, and prolactin concentrations were increased by the first administration of m-CPP (0.08 mg/kg) compared to placebo. All of these responses were attenuated on m-CPP days 2 and 3. Plasma m-CPP levels did not differ across the 3 m-CPP days. Repeated m-CPP administration thus appears to induce rapid tolerance to its behavioral and physiological effects in humans. Further investigations of the mechanisms involved in the development of subsensitivity to m-CPP may contribute to increased understanding of the regulation of serotonin-mediated functions and of anxiety disorders. RP Benjamin, J (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D41,10 CTR DR,MSC 1264,BETHESDA,MD 20892, USA. NR 81 TC 33 Z9 34 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 1996 VL 127 IS 2 BP 140 EP 149 DI 10.1007/BF02805987 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VJ421 UT WOS:A1996VJ42100010 PM 8888380 ER PT J AU Simonsick, EM AF Simonsick, EM TI Untitled - Response SO PSYCHOSOMATIC MEDICINE LA English DT Letter RP Simonsick, EM (reprint author), NIA,NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP-OCT PY 1996 VL 58 IS 5 BP 515 EP 516 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA VN538 UT WOS:A1996VN53800015 ER PT J AU Confrey, EA AF Confrey, EA TI The information exchange groups experiment SO PUBLISHING RESEARCH QUARTERLY LA English DT Article AB From 1961 through 1966, the National Institutes of Health operated a facility for the rapid distribution of unevaluated preprints to research workers-an obvious precursor of many of the activities taking place today on the Internet. The experiment began with 32 researchers in a single Information Exchange Group (IEG). It grew to seven IEGs with total membership over 3600. During 1966, more than 1.5 million copies of preprints were produced and distributed. Considerable enthusiasm was generated among researchers who valued the speed of dissemination. Critics charged that the quality of the average preprint deteriorated with increased participation. They also noted that the unplanned burdens on production had often delayed receipt of the preprints until after they had appeared as formally reviewed journal papers. During this period, the Atomic Energy Commission had mounted a similar experimental program of ''written informal communications'' that was limited to theoretical high energy physics. RP Confrey, EA (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 2 TC 2 Z9 2 U1 1 U2 2 PU TRANSACTION PERIOD CONSORTIUM PI NEW BRUNSWICK PA DEPT 3091 RUTGERS-THE STATE UNIV OF NJ, NEW BRUNSWICK, NJ 08903 SN 1053-8801 J9 PUBLISH RES Q JI Publ. Res. Q. PD FAL PY 1996 VL 12 IS 3 BP 37 EP 39 DI 10.1007/BF02680369 PG 3 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA XQ122 UT WOS:A1996XQ12200006 ER PT J AU Boice, JD Lubin, JH AF Boice, JD Lubin, JH TI Lung cancer risks: Comparing radiation with tobacco SO RADIATION RESEARCH LA English DT Letter ID IONIZING-RADIATION C1 NCI,DIV CANC EPIDEMIOL & GENET,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 8 TC 5 Z9 5 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD SEP PY 1996 VL 146 IS 3 BP 356 EP 357 DI 10.2307/3579470 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA VE408 UT WOS:A1996VE40800017 PM 8752318 ER PT J AU Toh, MY Falk, RB Main, JS AF Toh, MY Falk, RB Main, JS TI Interactive brain atlas with the visible human project data: Development methods and techniques SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 1995 Meeting of the Radiological-Society-of-North-America CY NOV 26-DEC 01, 1995 CL CHICAGO, IL SP Radiol Soc N Amer DE brain, anatomy; computers, educational aid; images, display; images, processing ID OBJECTS AB A prototype of an interactive digital brain atlas was developed by using the Visible Human Project data set of the National Library of Medicine, This data set provides corresponding axial magnetic resonance images, computed tomographic images, and cryosections of the brain. The prototype was developed to demonstrate the techniques and methods that will be used throughout the development process of the atlas, The atlas has a graphical user interface, supports user interaction with various representations of the brain tie, two-dimensional and three-dimensional [3D]), and displays multiple images simultaneously. Motion sequences of the 3D brain were incorporated in the atlas to provide an important link between two-dimensional brain slices and volume-rendered 3D anatomic structures. Volume visualization tools were used to interactively render, rotate, and reslice the volumetric brain data, The brain was segmented with manual tracing, thresholding, and morphologic algorithms and then rendered with volume-rendering tools. C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. RP Toh, MY (reprint author), NATL LIB MED,LHNCBC,BLDG 38A,RM B2N-35,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 9 TC 15 Z9 15 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP PY 1996 VL 16 IS 5 BP 1201 EP 1206 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VK251 UT WOS:A1996VK25100019 PM 8888399 ER PT J AU Choyke, PL AF Choyke, PL TI Inherited cystic diseases of the kidney SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID RENAL-CELL CARCINOMA; VONHIPPEL-LINDAU DISEASE; TUBEROUS SCLEROSIS COMPLEX; INTRACRANIAL ANEURYSMS; NATURAL-HISTORY; SPARING SURGERY; LESIONS; ANGIOMYOLIPOMAS; PATHOGENESIS; PREVALENCE AB Great strides have been made in our understanding of hereditary cystic diseases of the kidney. This article reviews the genetic, pathologic, and clinical aspects of autosomal dominant polycystic kidney disease, tuberous sclerosis, and von Hippel-Lindau disease. The role of imaging in screening and management of these diseases is emphasized. Understanding of genetic diseases of the kidney is expected to advance dramatically in the coming decade. C1 NIH,DEPT RADIOL,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT RADIOL,BETHESDA,MD 20814. NR 57 TC 18 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 1996 VL 34 IS 5 BP 925 EP & PG 23 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VF522 UT WOS:A1996VF52200002 PM 8784390 ER PT J AU Summers, RM Feng, DH Holland, SM Sneller, MC Shelhamer, JH AF Summers, RM Feng, DH Holland, SM Sneller, MC Shelhamer, JH TI Virtual bronchoscopy: Segmentation method for real-time display SO RADIOLOGY LA English DT Article DE bronchi, (CT); bronchoscopy; computed tomography (CT), three-dimensional; lung, cavitation ID CT; IMAGES; CONNECTIVITY; COLONOSCOPY AB Computed tomography (CT) data sets obtained in 14 patients were used in a segmentation method for virtual bronchoscopy (VB). The method constrained the distance of propagation of a region-growing algorithm. The resulting three-dimensional bronchial model was a faithful representation of the source CT data and could be manipulated in real time at frame rates of one to two frames per second. Preliminary data showed that 90% of bronchi (up to third order) measurable on multiplanar CT reformations were also measurable at VB. The bronchial diameters measured at VB were within 1 mm of those measured on multiplanar reconstructions of the CT data. C1 NIH, WARREN GRANT MAGNUSON CLIN CTR, HENRY M JACKSON FDN, DEPT CRIT CARE MED, BETHESDA, MD 20892 USA. MED COLL PENN & HAHNEMANN UNIV, SCH MED, PHILADELPHIA, PA 19102 USA. NIAID, NIH, BETHESDA, MD 20892 USA. RP Summers, RM (reprint author), NIH, WARREN GRANT MAGNUSON CLIN CTR, HENRY M JACKSON FDN,DEPT DIAGNOST RADIOL,BLDG 10, RM 1C660, BETHESDA, MD 20892 USA. NR 21 TC 111 Z9 114 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1996 VL 200 IS 3 BP 857 EP 862 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD062 UT WOS:A1996VD06200048 PM 8756944 ER PT J AU Nunez, SB Blye, RP Thomas, PM Reel, JR Barnes, KM Malley, JD Cutler, GB AF Nunez, SB Blye, RP Thomas, PM Reel, JR Barnes, KM Malley, JD Cutler, GB TI Recovery of reproductive function in rats treated with the aromatase inhibitor fadrozole SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE aromatase inhibitor; fadrozole hydrochloride; reproductive toxicology; estrous cycles; fertility; gestational body weight; McCune-Albright syndrome; gynecomastia ID MCCUNE-ALBRIGHT SYNDROME; PRECOCIOUS PUBERTY; POSTMENOPAUSAL WOMEN; SEXUAL-BEHAVIOR; CGS-16949A; TESTOLACTONE AB The aromatase inhibitor, fadrozole hydrochloride (CGS 16949A), was developed for the treatment of breast cancer, and has not been available for pediatric use because of the lack of information about potential reproductive toxicology, To determine the effect of fadrozole on subsequent fertility and reproductive performance in rats, peripubertal male and female Sprague-Dawley rats (10/group) were given fadrozole by oral gavage once a day for 60 consecutive days (age 21 through 80 d) at a dose of 0, 1200, or 6000 mu g/kg/d (dose range in women with breast cancer: 60 to 240 mu g/kg/d). Following a 30-d recovery period (days 81 through 111 of age), cohabitation with untreated rats of the opposite sex was accomplished for 30 d or until positive evidence of mating was obtained (daily vaginal smears), The nonfadrozole-treated males used for cohabitation were proven fertile breeders; the females were virgin with proven 4-d estrous cycles, The duration of pregnancy, number, sex, condition, and body weight of pups were determined, Pregnant rats were weighed on gestational days 7, 14, and 20, There was a profound decrease in the number of estrous cycles at both dose levels of fadrozole compared to the control (P < 0.001), During the 30-d recovery period, estrous cycles were reestablished within a few days in the treated rats and the number and length of estrous cycles were not statistically different between fadrozole-treated and control rats, The gestational body weights of fadrozole-treated and untreated females did not differ significantly, There were no statistically significant differences in the number of matings/number of pairings, gestational length, mean live pups/litter, % pups born alive/litter, and % male pups/litter in the three groups (vehicle-, low-, and high-dose fadrozole-treated females, cohabited with untreated males and fadrozole-treated males, cohabited with untreated females), Thus, young male and female rats treated for 60 d with large doses of fadrozole had no detectable adverse effect on subsequent reproductive function. C1 NICHHD,NIH,CONTRCEPT DEV BRANCH,LAB STAT & MATH METHODOL,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. BIOQUAL INC,ROCKVILLE,MD. RP Nunez, SB (reprint author), NICHHD,NIH,DEV ENDOCRINOL BRANCH,LAB STAT & MATH METHODOL,BLDG 10,RM 10N262,10 CTR DR,MSC 1862,BETHESDA,MD 20892, USA. NR 12 TC 9 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD SEP-OCT PY 1996 VL 10 IS 5 BP 373 EP 377 DI 10.1016/0890-6238(96)00083-4 PG 5 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA VJ224 UT WOS:A1996VJ22400003 PM 8888409 ER PT J AU Willett, WC Colditz, GA Mueller, NE AF Willett, WC Colditz, GA Mueller, NE TI Strategies for minimizing cancer risk SO SCIENTIFIC AMERICAN LA English DT Article ID PREVENTION C1 HARVARD UNIV,SCH PUBL HLTH,SCH MED,CAMBRIDGE,MA 02138. HARVARD UNIV,BRIGHAM & WOMENS HOSP,CAMBRIDGE,MA 02138. HARVARD UNIV,CTR CANC PREVENT,CAMBRIDGE,MA 02138. NATL CANC INST,CAMBRIDGE,MA 02138. RP Willett, WC (reprint author), HARVARD UNIV,DEPT NUTR,CAMBRIDGE,MA 02138, USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 5 TC 23 Z9 24 U1 0 U2 1 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD SEP PY 1996 VL 275 IS 3 BP 88 EP & PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VC941 UT WOS:A1996VC94100029 PM 8701299 ER PT J AU Greenwald, P AF Greenwald, P TI Chemoprevention of cancer SO SCIENTIFIC AMERICAN LA English DT Article ID BREAST-CANCER C1 NEW YORK STATE DEPT HLTH,CANC CONTROL BUR,NEW YORK,NY. NEW YORK STATE DEPT HLTH,DIV EPIDEMIOL,NEW YORK,NY. RP Greenwald, P (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 5 TC 27 Z9 28 U1 0 U2 1 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD SEP PY 1996 VL 275 IS 3 BP 96 EP 99 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VC941 UT WOS:A1996VC94100030 PM 8701300 ER PT J AU Cunnion, RE CottlerFox, M AF Cunnion, RE CottlerFox, M TI Cardiac complications of marrow transplantation SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID HIGH-DOSE CYCLOPHOSPHAMIDE; CARDIOTOXICITY; IFOSFAMIDE; RADIATION; TOXICITY; LEUKEMIA; BUSULFAN; REGIMEN; RISK AB Cardiac complications are common, but usually subclinical, after blood and marrow transplantation. The most frequent causes of serious, life-threatening cardiac complications, such as severe heart failure, effusive pericarditis, and arrhythmias, are regimen-related toxicities due to cyclophosphamide and ifosfamide. These are most common in the presence of pre-existing anthracycline cardiac toxicity. Patients with baseline ejection fractions less than 50% have a higher incidence of cardiac toxicity. Radiation and other transplant-associated agents (etoposide, taxol, etc.) are known to have potential, but less frequent, cardiac toxicities. It may be clinically difficult to distinguish cardiac problems from other processes, such as pulmonary toxicity, volume overload, or sepsis-related myocardial depression. Additionally, pericardial, myocardial, and valvular infections are potential, rare causes of complications and may pose diagnostic challenges. While there is no consensus regarding the pre-transplant evaluation of left ventricular function, general guidelines for management issues, both before and after transplant, can be made. C1 UNIV MARYLAND,CTR CANC,BONE MARROW STEM CELL TRANSPLANTAT LAB,BALTIMORE,MD 21201. RP Cunnion, RE (reprint author), NATL INST HLTH,DEPT CRIT CARE MED,BLDG 10,ROOM 7-D-43,BETHESDA,MD 20892, USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PD SEP PY 1996 VL 17 IS 5 BP 409 EP 415 DI 10.1055/s-2007-1009916 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VN871 UT WOS:A1996VN87100009 ER PT J AU Gaydos, CA Ngeow, YF Lee, HH Canavaggio, M Welsh, LE Johanson, J Quinn, TC AF Gaydos, CA Ngeow, YF Lee, HH Canavaggio, M Welsh, LE Johanson, J Quinn, TC TI Urine as a diagnostic specimen for the detection of Chlamydia trachomatis in Malaysia by ligase chain reaction SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; FIRST-VOID URINE; REACTION ASSAY; ASYMPTOMATIC MEN; ENZYME-IMMUNOASSAY; WOMEN; INFECTION AB Background and Objectives: Noninvasive urine screening for Chlamydia trachomatis infections offers a valuable public health tool, which could be of vast importance in chlamydial control programs. The authors evaluated a new DNA amplification method, ligase chain reaction (LCR). Goals: The goal was to ascertain whether urine testing could be used as screening method to detect C. trachomatis infections in commercial sex workers, patients at sexually transmitted diseases clinic, and asymptomatic patients in Kuala Lumpur, Malaysia. Methods: First-void urine specimens from 300 men and 300 women were tested by LCR, as well as by a commercially available enzyme immunoassay. The LCR assay amplifies specific sequences within the chlamydial plasmid with ligand-labeled probes, and the resultant amplicons are detected by an automated immunoassay. Specimens with discrepant results were confirmed by another LCR of the specimen that targeted the gene for the major outer membrane protein (OMP1). Results: There were 31 LCR-positive male urine and 37 LCR-positive female urine specimens. The resolved sensitivity and specificity for the LCR of the male urine specimens were 100% and 99.6%, respectively, whereas for female urine specimens, the sensitivity and specificity were 100% and 98.5%, respectively. After resolution of discrepant test results by OMP1 LCR, the prevalence was 10% for men and 11% for women. The urine enzyme immunoassay was not useful in diagnosing C. trachomatis infections in either men or women, as the resolved sensitivities were 10% and 15.2%, respectively. The specificities were 99.6% for men and 98.9% for women. Conclusions: Testing first-void urine specimens by LCR is a highly sensitive and specific method to diagnose C. trachomatis infections in men and women, providing health care workers and public health officials with a new molecular amplification assay that uses noninvasive urine specimens for population-based screening purposes. C1 JOHNS HOPKINS UNIV,BALTIMORE,MD. UNIV MALAYA,KUALA LUMPUR,MALAYSIA. ABBOTT LABS,ABBOTT PK,IL. NIAID,BETHESDA,MD 20892. RI Gaydos, Charlotte/E-9937-2010 NR 22 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD SEP-OCT PY 1996 VL 23 IS 5 BP 402 EP 406 DI 10.1097/00007435-199609000-00010 PG 5 WC Infectious Diseases SC Infectious Diseases GA VH395 UT WOS:A1996VH39500010 PM 8885072 ER PT J AU Enright, PL Newman, AB Wahl, PW Manolio, TA Haponik, EF Boyle, PJR AF Enright, PL Newman, AB Wahl, PW Manolio, TA Haponik, EF Boyle, PJR TI Prevalence and correlates of snoring and observed apneas in 5,201 older adults SO SLEEP LA English DT Article DE snoring; observed apneas; daytime sleepiness; cardiovascular disease; older adults ID CARDIOVASCULAR RISK-FACTORS; OBSTRUCTIVE SLEEP-APNEA; SELF-REPORTS; HEALTH; MEN; POPULATION; DISEASE; QUESTIONNAIRE; ASSOCIATION; VALIDITY AB The objectives of this study were to describe the prevalence of snoring, observed apneas, and daytime sleepiness in older men and women, and to describe the relationships of these sleep disturbances to health status and cardiovascular diseases (CVD). A cross-sectional design was employed to study sleep problems, CVD, general health, psychosocial factors, and medication use. The subjects were participants in the Cardiovascular Health Study, which included 5,201 adults, aged 65 and older, who were recruited from a random sample of Medicare enrollees in four U.S. communities. Study measures employed were sleep questions, echocardiography, carotid ultrasound, resting electrocardiogram, cognitive function, cardiopulmonary symptoms and diseases, depression, independent activities of daily living (IADLs), and benzodiazepine use. Thirty-three percent of the men and 19% of the women reported loud snoring, which was less frequent in those over age 75. Snoring was positively associated with younger age, marital status, and alcohol use in men, and obesity, diabetes, and arthritis in women. Snoring was not associated, however, with cardiovascular risk factors or clinical CVD in men or women. Observed apneas were reported much less frequently (13% of men and 4% of women) than snoring, and they were associated with alcohol use, chronic bronchitis, and marital status in men. Observed apneas were associated with depression and diabetes in women. In both men and women, daytime sleepiness was associated with poor health, advanced age, and IADL limitations. The conclusions of the study were that loud snoring, observed apneas, and daytime sleepiness are not associated cross-sectionally with hypertension or prevalent CVD in elderly persons. C1 MED COLL PENN & HAHNEMANN UNIV,DEPT MED,PITTSBURGH,PA. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT MED,WAKE FOREST,NC. RP Enright, PL (reprint author), UNIV ARIZONA,HLTH SCI CTR,RESP SCI CTR,ROOM 2342,1501 N CAMPBELL AVE,TUCSON,AZ 85718, USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85086, N01-HC-85079] NR 42 TC 129 Z9 135 U1 1 U2 10 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 SN 0161-8105 J9 SLEEP JI Sleep PD SEP PY 1996 VL 19 IS 7 BP 531 EP 538 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VM165 UT WOS:A1996VM16500002 PM 8899931 ER PT J AU Lamb, ME AF Lamb, ME TI Divergent realities: The emotional lives of mothers, fathers and adolescents - Larson,R, Richards,MH SO SOCIAL SERVICE REVIEW LA English DT Book Review RP Lamb, ME (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0037-7961 J9 SOC SERV REV JI Soc. Serv. Rev. PD SEP PY 1996 VL 70 IS 3 BP 489 EP 490 PG 2 WC Social Work SC Social Work GA VC958 UT WOS:A1996VC95800010 ER PT J AU Russell, MWW duManoir, S Munroe, DJ Collins, FS Brody, LC AF Russell, MWW duManoir, S Munroe, DJ Collins, FS Brody, LC TI Chromosomal localization of 15 ion channel genes SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID LONG QT SYNDROME; ACTIVATED POTASSIUM CHANNEL; CARDIAC-ARRHYTHMIA; MALIGNANT HYPERTHERMIA; RECEPTOR GENE; CLONING; MUTATIONS; DISEASE; LINKAGE; LOCUS AB Several human Mendelian diseases, including the long-QT syndrome, malignant hyperthermia, and episodic ataxia/myokymia syndrome, have recently been demonstrated to be due to mutations in ion channel genes. Systematic mapping of ion channel genes may therefore reveal candidates for other heritable disorders. in this study, the GenBank and dbEST databases were used to identify members of several ion channel families (voltage-gated calcium and sodium, cardiac chloride, and all classes of potassium channels). Genes and ESTs without prior map localization were identified based on GDB and OWL database information and 15 genes and ESTs were selected for mapping. Of these 15, only the serotonin receptor 5HT3R had been previously mapped to a chromosome. A somatic cell hybrid panel (SCH) was screened with an STS from each gene and if necessary, the results verified by a second SCH panel. For three ESTs, rodent derived PCR products of the same size as the human STS precluded SCH mapping. For these thr-ee, human P1 clones were isolated and the genomic location was determined by metaphase FISH. These genes and ESTs can now be further evaluated as candidate genes for inherited cardiac, neuromuscular; and psychiatric disorders mapped to these chromosomes. Furthermore, the ESTs developed in this study can be used to isolate genomic clones, enabling the determination of each transcript's genomic structure and physical map location. This approach may also be applicable to other gene families and may aid in the identification of candidate genes for groups of related heritable disorders. C1 UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. NIH,LAB GENE TRANSFER,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NIH,DIAGNOST DEV BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. RP Russell, MWW (reprint author), UNIV MICHIGAN,DEPT PEDIAT & COMMUNICABLE DIS,ANN ARBOR,MI 48109, USA. NR 25 TC 2 Z9 2 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD SEP PY 1996 VL 22 IS 5 BP 425 EP 431 DI 10.1007/BF02369898 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA WK593 UT WOS:A1996WK59300007 PM 9039851 ER PT J AU Ashwell, JD King, LB Vacchio, MS AF Ashwell, JD King, LB Vacchio, MS TI Cross-talk between the T cell antigen receptor and the glucocorticoid receptor regulates thymocyte development SO STEM CELLS LA English DT Review DE steroids; thymocyte development; thymocyte selection; T cell receptor; glucocorticoids; glucocorticoid receptor; apoptosis ID POSITIVE SELECTION; TRANSGENIC MICE; NEGATIVE SELECTION; INDUCED APOPTOSIS; FREE CORTICOSTERONE; FAS-LIGAND; ACTIVATION; DEATH; THYMUS; BCL-2 AB The fate of an immature thymocyte, life or death, is largely determined by the ligand-specificity of its T cell antigen receptor (TCR), The default pathway for thymocytes bearing TCRs with subthreshold avidity for self-antigens is death (death by neglect), Thymocytes bearing TCRs with high avidity for self also undergo apoptosis (negative selection), Those thymocytes with intermediate avidities, or that perhaps recognize self-peptides that have partial agonist or antagonist properties, survive and differentiate into mature immunocompetent T cells (positive selection), How TCR avidity is interpreted as a ''rescue'' signal or a death signal is unknown, Based upon a T cell hybridoma model, our laboratory proposed that glucocorticoids, which themselves are potent inducers of thymocyte apoptosis, antagonize TCR-mediated thymocyte deletion and allow positive selection to occur, In fact, epithelial cells in the thymus proved to be a source of steroid production, and interference with steroid synthesis in fetal thymic organ culture resulted in a greatly enhanced sensitivity of thymocytes to TCR-mediated apoptosis, Transgenic mice with reduced glucocorticoid receptor (GR) levels were produced by tissue-specific expression of GR antisense, Thymocytes in these mice had high levels of spontaneous apoptosis, and were exquisitely sensitive to deletion induced by cross-linking the TCR, Moreover, there was a very large (greater than or equal to 90%) loss of CD4(+)CD8(+) thymocytes, signifying a block at the CD4(-)CD8(-) to CD4(+)CD8(+) transition, perhaps due to apoptosis of cells upon engagement of the pre-TCR in the absence of an antagonizing glucocorticoid stimulus, The molecular mechanism of the antagonism is currently being investigated, These data indicate that there is cross-talk in thymocytes between the TCR and glucocorticoid signaling pathways resulting in apoptosis, and that locally produced steroids, in a paracrine fashion, participate in setting the TCR avidity thresholds that determine whether developing thymocytes survive or die, and therefore help to mold the antigen-specific T cell repertoire. C1 US FDA, CTR BIOL EVALUAT & RES, DIV HEMATOL PROD, IMMUNOL LAB, BETHESDA, MD USA. RP Ashwell, JD (reprint author), NIH, NCI, LAB IMMUNE CELL BIOL, ROOM 1B-40, BLDG 10, BETHESDA, MD 20852 USA. NR 58 TC 53 Z9 53 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD SEP PY 1996 VL 14 IS 5 BP 490 EP 500 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA VJ494 UT WOS:A1996VJ49400002 PM 8888490 ER PT J AU Manolio, TA Kronmal, RA Burke, GL OLeary, DH Price, TR AF Manolio, TA Kronmal, RA Burke, GL OLeary, DH Price, TR TI Short-term predictors of incident stroke in older adults - The Cardiovascular Health Study SO STROKE LA English DT Article DE aged; stroke, cerebrovascular disorders; epidemiology; risk factors ID CORONARY HEART-DISEASE; RISK-FACTORS; MEN; MORTALITY; COMMUNITY; COHORT; AGE AB Background and Purpose Risk factors for incident stroke have been examined in middle-aged persons, but less is known about stroke precursors in the elderly, who suffer the highest rates of stroke. Short-term risk factors for incident stroke were examined in a longitudinal, population-based study including extensive measures of subclinical disease. Methods Prospective study of 5201 women and men aged 65 years and older was undertaken in the multicenter Cardiovascular Health Study. Results During an average 3.31-year follow-up, 188 incident strokes occurred. Stroke incidence increased significantly with age and was similar in women and men. Factors associated with increased stroke risk in multivariate analysis included age, aspirin use, diabetes, impaired glucose tolerance, higher systolic blood pressure, increased time needed to walk 15 ft, frequent falls, elevated creatinine level, abnormal left ventricular (LV) wall motion and increased LV mass on echocardiography, ultrasound-defined carotid stenosis, and atrial fibrillation. Increased LV mass and carotid stenosis were associated with twofold and threefold increases in incidences of stroke, respectively (P<.001). Aspirin users had a 52% higher risk of stroke (relative risk, 1.52; 95% confidence interval, 1.1 to 2.0; P<.007) after adjustment for other factors. This association was present only among aspirin users without prior coronary disease, atrial fibrillation, claudication, or transient ischemic attack, who had an 84% higher risk (relative risk, 1.84; 95% confidence interval, 1.2 to 2.8). Conclusions Short-term risk of stroke has a complex relationship with aspirin use and is strongly related to subclinical disease in this sample of older adults. These relationships should be considered in assessing stroke risk in the elderly, in whom recognized and subclinical cardiovascular disease is highly prevalent. C1 UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. TUFTS NEW ENGLAND MED CTR,DEPT RADIOL,BOSTON,MA. UNIV MARYLAND,DEPT NEUROL,BALTIMORE,MD 21201. RP Manolio, TA (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,6701 ROCKLEDGE DR,RM 8160,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85080, N01-HC-85081] NR 47 TC 175 Z9 180 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 1996 VL 27 IS 9 BP 1479 EP 1486 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VF032 UT WOS:A1996VF03200005 PM 8784116 ER PT J AU Herbert, RA Hailey, JR Grumbein, S Chou, BJ Sills, RC Haseman, JK Goehl, T Miller, RA Roycroft, JH Boorman, GA AF Herbert, RA Hailey, JR Grumbein, S Chou, BJ Sills, RC Haseman, JK Goehl, T Miller, RA Roycroft, JH Boorman, GA TI Two-year and lifetime toxicity and carcinogenicity studies of ozone in B6C3F1 mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE hazard identification; chemical carcinogenesis; air pollution; inhalation; lung ID PPM OZONE; STATISTICAL ISSUES; AMBIENT LEVELS; RAT NASAL; EXPOSURE; RESPONSES; INHALATION; EPITHELIUM; BRONCHIOLITIS; CHILDREN AB To evaluate the toxicity and carcinogenic potential of long-term exposure to ozone, B6C3F1 mice were exposed by whole-body inhalation to 0, 0.12, 0.5, or 1.0 ppm and 0, 0.5, or 1.0 ppm ozone for 24 or 30 mo (lifetime), respectively. The incidence of alveolar/bronchiolar adenomas and carcinomas (combined) increased (p < 0.05) in female mice exposed to 1.0 ppm for 24 or 30 mo and marginally increased (p > 0.05) in male mice exposed to concentrations of 0.5 or 1.0 ppm. An increased incidence of nonneoplastic lesions were observed in the nasal cavities and in the centriacinar region of the lung of mice exposed to 0.5 or 1.0 ppm for 24 and 30 mo. Nasal cavity lesions were mild and included hyaline degeneration, hyperplasia, squamous metaplasia, fibrosis and suppurative inflammation of the transitional and respiratory epithelium of the lateral wall, and atrophy of the olfactory epithelium. Lung lesions included replacement of the epithelium of the alveolar ducts and adjacent alveolar septa with epithelium similar to that normally found in terminal bronchioles (metaplasia) and associated alveolar histiocytosis. Based on the results of these studies, we conclude that inhalation exposure of B6C3F1 mice to ozone for 24 or 30 mo (a) is carcinogenic in female B6C3F1 mice exposed to 1.0 ppm of ozone based on an increased incidence of alveolar/bronchiolar adenoma or carcinoma and (b) results in mild, site-specific, nonneoplastic lesions in the nasal cavity and centriacinar lung of male and female mice exposed to 0.5 or 1.0 ppm of ozone for 2 yrs, which persist with continued exposure to 30 mo. It is uncertain whether or not the marginal increase (p > 0.05) of alveolar/bronchiolar neoplasms in male B6C3F1 mice resulted from exposure to ozone. RP Herbert, RA (reprint author), NIEHS,PATHOL BRANCH,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 53 TC 16 Z9 17 U1 1 U2 1 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD SEP-OCT PY 1996 VL 24 IS 5 BP 539 EP 548 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA VR345 UT WOS:A1996VR34500002 PM 8923674 ER PT J AU FernandezSalguero, PM Hilbert, DM Rudikoff, S Ward, JM Gonzalez, FJ AF FernandezSalguero, PM Hilbert, DM Rudikoff, S Ward, JM Gonzalez, FJ TI Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID AH-RECEPTOR; GUINEA-PIGS; RAT STRAIN; TCDD; ACTIVATION; MORPHOLOGY; INDUCTION; EXPOSURE; BINDING; ANIMALS AB Acute exposure of mammals to the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in a diverse set of toxicologic and pathologic effects. The mechanism of some of these effects has been studied extensively in vitro and correlative studies have indicated the involvement of a transcription factor known as the aryl hydrocarbon receptor (AHR), However, a definitive association of the AHR with TCDD-mediated toxicity has been difficult to establish due to the diversity of effects and the ubiquitous expression of this receptor. In an effort to distinguish AHR-mediated TCDD toxicities from those resulting from alternative pathways, we have made use of the recently described AHR-deficient mouse that was generated by locus-specific homologous recombination in embryonic stem cells. Present studies demonstrate that AHR-deficient mice are relatively unaffected by doses of TCDD (2000 mu g/kg) 10-fold higher than that found to induce severe toxic and pathologic effects in littermates expressing a functional AHR, Analyses of liver, thymus, heart, kidney, pancreas, spleen, lymph nodes, and uterus from AHR-deficient mice identified no significant TCDD-induced lesions. The resistance of AHR-deficient mice to TCDD-induced thymic atrophy appears restricted to processes involving AHR since the corticosteroid dexamethasone rapidly and efficiently induced cortical depletion in both AHR-deficient and normal littermate control mice, Taken together these results suggest that the pathological changes induced by TCDD in the liver and thymus are mediated entirely by the AHR. However, it is important to note that at high doses of TCDD, AHR-deficient mice displayed limited vasculitis and scattered single cell necrosis in their lungs and livers, respectively. The mechanism(s) responsible for these apparently receptor-independent processes remain unclear but may involve novel, alternative pathways for TCDD-induced toxicity. (C) 1996 Academic Press, Inc. C1 NCI,GENET LAB,NIH,BETHESDA,MD 20892. NCI,VET & TUMOR PATHOL SECT,OFF LAB ANIM SCI,FREDERICK,MD 21702. RP FernandezSalguero, PM (reprint author), NCI,MOL CARCINOGENESIS LAB,NIH,BLDG 37,BETHESDA,MD 20892, USA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 22 TC 519 Z9 536 U1 3 U2 16 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP PY 1996 VL 140 IS 1 BP 173 EP 179 DI 10.1006/taap.1996.0210 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VG799 UT WOS:A1996VG79900020 PM 8806883 ER PT J AU Fonger, GC AF Fonger, GC TI Toxicological and environmental health information from the National Library of Medicine SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article AB The National Library of Medicine's Toxicology and Environmental Health Information Program is the outgrowth of a 1966 document on ''Handling of Toxicological Information, ''prepared by the Presidents Science Advisory Committee (National Library of Medicine, 1995). The Toxicology and Environmental Health Program is responsible for the creation and deployment of both bibliographic and factual files concerned with toxicology, carcinogenesis, developmental and reproductive effects of chemical substances, toxic chemical releases, and the medical and environmental behavior of chemical substances. The two main computer systems that provide bibliographic and factual data banks are Toxicology Data Network (TOXNET) and ELHILL. A number of the files found in the TOXNET system are built and maintained by other federal agencies such as the National Cancer Institute, the U.S. Environmental Protection Agency, the National Institute for Occupational Safety and Health. RP Fonger, GC (reprint author), NATL LIB MED,DIV SPECIALIZED INFORMAT SERV,TOXICOL & ENVIRONM HLTH INFORMAT PROGRAM,BETHESDA,MD 20894, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD SEP-OCT PY 1996 VL 12 IS 5 BP 639 EP 649 PG 11 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA WB261 UT WOS:A1996WB26100004 PM 8989844 ER PT J AU Mosley, JW Huang, W Stram, DO Nowicki, MJ Hollinger, FB Aach, RD Stevens, CE Barbosa, LH Nemo, GJ AF Mosley, JW Huang, W Stram, DO Nowicki, MJ Hollinger, FB Aach, RD Stevens, CE Barbosa, LH Nemo, GJ TI Donor levels of serum alanine aminotransferase activity and antibody to hepatitis B core antigen associated with recipient hepatitis C and non-B,non-C outcomes SO TRANSFUSION LA English DT Article ID TRANSFUSION-TRANSMITTED VIRUSES; POLYMERASE CHAIN-REACTION; NON-A-HEPATITIS; POSTTRANSFUSION HEPATITIS; BLOOD-DONORS; INFECTION; GENOMES; ASSAYS; RISK AB Background: Hepatitis virus(es) that are neither hepatitis B (HBV) nor hepatitis C (HCV) (non-B,non-C [NBNC]) may be transmitted by transfusion. The present study assessed donor values for alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti-HBc) for their association with HCV and NBNC hepatitis outcomes among allogeneic blood recipients. Study Design and Methods: Data on blood donors and recipients enrolled in the Transfusion-Transmitted Viruses Study in four United States cities from 1974 through 1980 were supplemented by anti-HBc testing of donors and anti-HCV evaluation of recipients. Two statistical approaches estimated the value of these indirect tests in detecting donors associated with HCV seroconversion and NBNC hepatitis in recipients. Results: For HCV cases, donor ALT alone (at greater than or equal to 60 IU/L) had a sensitivity and a specificity of 30 and 96 percent, respectively, and anti-HBc alone (at greater than or equal to 6% inhibition) had a sensitivity and specificity of 53 and 86 percent, respectively. The two markers combined had a sensitivity and a specificity of 69 and 83 percent. For NBNC hepatitis cases, each measure had low sensitivity (2%) that was not improved by using both (2%). Conclusion: The indirect tests proved to be equal in sensitivity to the first-generation anti-HCV tests. The positive predictive power of these indirect tests in the 1980s was sufficient to affect HCV incidence in studies during that period. Improved anti-HCV assays, however, replaced the need for indirect tests. The sensitivity of indirect tests for NBNC hepatitis contributed little. C1 BAYLOR COLL MED,DEPT VIROL & EPIDEMIOL,HOUSTON,TX 77030. NEW YORK BLOOD CTR,LINDSLEY F KIMBALL RES INST,NEW YORK,NY 10021. NHLBI,DIV BLOOD DIS & RESOURCES,TRANSFUS MED SCI RES GRP,NIH,BETHESDA,MD 20892. MT SINAI MED CTR,CLEVELAND,OH 44106. RP Mosley, JW (reprint author), UNIV SO CALIF,SCH MED,DEPT PREVENT MED,EDMONDSON BLDG,ROOM 108,1840 N SOTO ST,LOS ANGELES,CA 90032, USA. FU NHLBI NIH HHS [N01-HB-4-2972] NR 29 TC 16 Z9 17 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1996 VL 36 IS 9 BP 776 EP 781 DI 10.1046/j.1537-2995.1996.36996420752.x PG 6 WC Hematology SC Hematology GA VJ087 UT WOS:A1996VJ08700004 PM 8823449 ER PT J AU Matsuo, K Reid, DM AF Matsuo, K Reid, DM TI Allele-specific restriction analysis of human platelet antigen system 4 SO TRANSFUSION LA English DT Article ID MEMBRANE GLYCOPROTEIN-IIIA; NEONATAL ALLOIMMUNE THROMBOCYTOPENIA; AMINO-ACID POLYMORPHISM; POLYMERASE CHAIN-REACTION; ALLOANTIGEN SYSTEM; ENZYMATIC AMPLIFICATION; POINT MUTATION; IB-ALPHA; DNA; DIAGNOSIS AB Background: Diagnosis, and occasionally treatment, of disorders involving platelet-specific alloimmunization, including neonatal alloimmune thrombocytopenia and posttransfusion purpura, requires platelet allotyping. Allele-specific restriction analyses for convenient genotyping are available for the major human platelet antigen (HPA) systems except HPA-4. Study Design and Methods: An allele-specific restriction analysis for HPA-4 was developed by designing a polymerase chain reaction primer containing a single-base substitution (A for T) at glycoprotein IIIa cDNA position 529. The resulting mismatch did not interfere with DNA amplification. Digestion of the polymerase chain reaction product with Bsml allowed differentiation of HPA-4a and HPA-4b alleles. Results: A 126-bp polymerase chain reaction product was amplified with the novel primer. Bsml endonuclease cleaved product encoding HPA-4a into 104- and 22-bp fragments and left DNA encoding HPA-4b intact. Conclusion: This rapid allele-specific restriction analysis for genotyping the HPA-4 system complements similar methods for other platelet alloantigenic determinants. RP Matsuo, K (reprint author), NIDDKD,CLIN HEMATOL BRANCH,NIH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 4D-51,BETHESDA,MD 20892, USA. NR 35 TC 8 Z9 9 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1996 VL 36 IS 9 BP 809 EP 812 DI 10.1046/j.1537-2995.1996.36996420759.x PG 4 WC Hematology SC Hematology GA VJ087 UT WOS:A1996VJ08700011 PM 8823456 ER PT J AU Pavel, J Morgan, V Leitman, SF AF Pavel, J Morgan, V Leitman, SF TI Design and use of a computer application to search for HLA compatible platelet donors. SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1996 VL 36 IS 9 SU S BP A86 EP A86 PG 1 WC Hematology SC Hematology GA VK089 UT WOS:A1996VK08900345 ER PT J AU ConryCantilena, C Shakil, AO VanRaden, M Melpolder, JC Kleiner, D Hoofnagle, J Alter, HJ Gibble, J Nass, C Ness, P AF ConryCantilena, C Shakil, AO VanRaden, M Melpolder, JC Kleiner, D Hoofnagle, J Alter, HJ Gibble, J Nass, C Ness, P TI Symptoms and liver histology in blood donors with hepatitis C virus infection. SO TRANSFUSION LA English DT Meeting Abstract C1 AMER RED CROSS,BALTIMORE,MD. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1996 VL 36 IS 9 SU S BP S202 EP S202 PG 1 WC Hematology SC Hematology GA VK089 UT WOS:A1996VK08900202 ER PT J AU Gladden, SD Kessel, O Pavel, J Leitman, SF AF Gladden, SD Kessel, O Pavel, J Leitman, SF TI Feasibility and safety of using peripherally inserted central catheters (PICC) for red cell (RBC) SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1996 VL 36 IS 9 SU S BP S183 EP S183 PG 1 WC Hematology SC Hematology GA VK089 UT WOS:A1996VK08900183 ER PT J AU Leiby, DA Yund, J Read, EJ Lenes, BA Dodd, RY AF Leiby, DA Yund, J Read, EJ Lenes, BA Dodd, RY TI Risk factors for Trypanosoma cruzi-infection in seropositive blood donors. SO TRANSFUSION LA English DT Meeting Abstract C1 USUHS,BETHESDA,MD. ARC,ROCKVILLE,MD. NIH,ROCKVILLE,MD. ARC,MIAMI,FL. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1996 VL 36 IS 9 SU S BP S228 EP S228 PG 1 WC Hematology SC Hematology GA VK089 UT WOS:A1996VK08900228 ER PT J AU Kimura, S AF Kimura, S TI Thyroid-specific enhancer-binding protein - Role in thyroid function and organogenesis SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID THYROTROPIN RECEPTOR GENE; TRANSCRIPTION FACTOR-I; GROWTH FACTOR-I; THYROGLOBULIN PROMOTER; PEROXIDASE GENE; NUCLEAR-PROTEIN; EXPRESSION; CELLS; TTF-1; IDENTIFICATION AB Thyroid-specific enhancer-binding protein (T/EBP), also known as thyroid-specific transcription factor-1 (TTF-1), is a trans-activating transcription factor known to be involved in the tissue-specific expression of genes encoding thyroglobulin (TG), thyroid peroxidase (TPO), and thyrotropin receptor (TSHR) in the thyroid, and surfactant proteins A, B, and C, and Clara cell secretory protein in the lung. T/EBP is a homeodomain-containing DNA-binding protein found in the thyroid, lung epithelium, and specific areas of the forebrain during early embryogenesis. A mutant mouse lacking T/EBP expression was recently generated that is missing the thyroid, lung, ventral forebrain, and pituitary. These results clearly establish that T/EBP functions not only as a trans-activating factor to regulate expression of genes in the thyroid and lung, but also is required for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. RP Kimura, S (reprint author), NCI,NIH,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 47 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD SEP PY 1996 VL 7 IS 7 BP 247 EP 252 DI 10.1016/S1043-2760(96)00115-4 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VK445 UT WOS:A1996VK44500004 PM 18406755 ER PT J AU Koonin, EV Mushegian, AR Bork, P AF Koonin, EV Mushegian, AR Bork, P TI Non-orthologous gene displacement SO TRENDS IN GENETICS LA English DT Letter C1 MAX DELBRUCK CTR MOL MED,BERLIN,GERMANY. EUROPEAN MOL BIOL LAB,D-69012 HEIDELBERG,GERMANY. RP Koonin, EV (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894, USA. RI Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 7 TC 184 Z9 193 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD SEP PY 1996 VL 12 IS 9 BP 334 EP 336 DI 10.1016/0168-9525(96)20010-1 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA VF348 UT WOS:A1996VF34800003 PM 8855656 ER PT J AU Vousden, KH AF Vousden, KH TI HPV EG: Ensuring all's well at the end SO TRENDS IN MICROBIOLOGY LA English DT Editorial Material ID HUMAN FORESKIN KERATINOCYTES; HUMAN-CELLS; IMMORTALIZATION; TELOMERASE; E6; ONCOPROTEINS; PROTEIN; P53 C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 12 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD SEP PY 1996 VL 4 IS 9 BP 337 EP 338 DI 10.1016/0966-842X(96)30024-3 PG 2 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA VG686 UT WOS:A1996VG68600001 PM 8885163 ER PT J AU Hackstadt, T AF Hackstadt, T TI Biosafety concerns and Coxiella burnetii SO TRENDS IN MICROBIOLOGY LA English DT Letter ID VIRULENCE; VARIANTS; MODEL C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840. NR 9 TC 21 Z9 23 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD SEP PY 1996 VL 4 IS 9 BP 341 EP 342 DI 10.1016/0966-842X(96)81555-1 PG 2 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA VG686 UT WOS:A1996VG68600004 PM 8885166 ER PT J AU Williams, AO Knapton, AD Geiser, A Letterio, JJ Roberts, AB AF Williams, AO Knapton, AD Geiser, A Letterio, JJ Roberts, AB TI The liver in transforming growth factor-beta-1 (TGF-beta 1) null mutant mice SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE Golgi; inclusions; intracytoplasmic canaliculi; liver; mice; mitochondria; phenotype; TGF-beta 1 ID FACTOR-BETA; MYOGENIC DIFFERENTIATION; GIANT MITOCHONDRIA; CELLS; EXPRESSION; INHIBITOR; DISEASE; LOCALIZATION; HEPATOCYTES; RECEPTOR AB Transforming growth factor-beta-1 (TGF-beta 1) null mutant mice have no gross developmental abnormalities at birth but succumb to multifocal inflammatory lesions that lead to organ failure and death about 20 days after birth. Treatment with anti-inflammatory and immune suppressive agents, such as rapamycin, reduces the severity and extent of inflammatory infiltrates in the liver and can prolong the life of knockout (KO) mice compared to untreated null mice. To determine whether there is an associated hepatic phenotype, livers of ''young'' (<3 weeks), ''old'' (>3 weeks), and age-matched wild-type (WT) mice were studied using light and electronmicroscopy. On light microscopy, old KO mice had foci of mononuclear cells in liver parenchyma in addition to scattered foci of megalocytosis. Intracytoplasmic vacuoles, some of which were juxtanuclear in location, were also seen but these were most prominent in the oldest (10 weeks) rapamycin-treated mouse. In the untreated young KO mice, there were only foci of mononuclear cells in the liver parenchyma and portal tracts and variable numbers of binucleated hepatocytes. Ultrastructurally, there was a significant increase in the number of mitochondria in livers of the old KO mice, when compared either to the age-matched wild-type or to the young KO mice (p > .001). Hepatocytes from all KO mice showed increased numbers of hypertrophied or enlarged Golgi complexes compared to age-matched wild-type mice. Intracytoplasmic canaliculi lined with microvilli were seen in livers of old KO mice, but were absent in the young KO and wild-type mice. Primary cultures of hepatocytes, derived from livers of both young and old KO mice, showed similar changes on phase contrast and electronmicroscopy. These included juxtanuclear vacuoles, intracytoplasmic canaliculi, enlarged Golgi vesicles, and increased numbers of autolysosomes. Phenotypic abnormalities of mitochondria were either minimal or absent in cultured KO hepatocytes. The findings demonstrate, for the first time, that targeted disruption of the TGF-beta 1 gene in mice results in an altered ultrastructural phenotype of hepatocytes. The data suggest that TGF-beta 1 may be required for normal development and regulation of subcellular organelles in hepatocytes and may be essential for physiological functions involving mitochondria and Golgi complex. C1 NCI,CHEMOPREVENT LAB,DIV BASIC SCI,BETHESDA,MD 20892. RP Williams, AO (reprint author), NCI,EXPT PATHOL LAB,DIV BASIC SCI,BLDG 41,ROOM C-105,BETHESDA,MD 20892, USA. NR 46 TC 23 Z9 23 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD SEP-OCT PY 1996 VL 20 IS 5 BP 477 EP 490 PG 14 WC Microscopy; Pathology SC Microscopy; Pathology GA VJ178 UT WOS:A1996VJ17800010 PM 8883333 ER PT J AU Tamano, S Rehm, S Waalkes, MP Ward, JM AF Tamano, S Rehm, S Waalkes, MP Ward, JM TI High incidence and histogenesis of seminal vesicle adenocarcinoma and lower incidence of prostate carcinomas in the Lobund-Wistar prostate cancer rat model using N-nitrosomethylurea and testosterone SO VETERINARY PATHOLOGY LA English DT Article DE carcinoma; histogenesis; male accessory sex glands; prostate; prostatic intraepithelial neoplasia; rat; seminal vesicle; testosterone ID ACCESSORY SEX-ORGANS; L-W RATS; INVASIVE CARCINOMAS; INDUCTION; PROPIONATE; TUMORS; 3,2'-DIMETHYL-4-AMINOBIPHENYL; PREVENTION; GLAND; DIHYDROTESTOSTERONE AB The origin of chemically induced male accessory sex gland tumors was studied in Lobund-Wistar rats. Rats were treated at the age of 3 months with a single intravenous injection of 30 mg N-nitrosomethylurea (NMU)/kg body weight and given subcutaneous silastic implants filled with 40 mg testosterone propionate. Previous reports described a high incidence of prostate carcinomas in these rats with this treatment protocol. Additional animal groups included untreated controls, rats that received only an injection of 30 mg NMU/kg, and rats that were subjected to ablation of the seminal vesicle lobes prior to the treatment with NMU and testosterone. Three to 14 rats per group were sacrificed 4 to 10 months after NMU treatment and all remaining rats after 12 months. Twenty-four additional rats died or became moribund during the study. All rats were necropsied and the dorsolateral and ventral prostate and seminal vesicles with coagulating gland (anterior prostate) were examined histologically according to a standardized protocol. Lesions detected included atypical hyperplasia in all glands (resembling prostate intraepithelial neoplasia of human beings), adenomas in seminal vesicles only, and early carcinomas and adenocarcinomas in seminal vesicles and coagulating gland. Early carcinomas of the seminal vesicle, microscopically small and with invasion of the lamina propria and/or tunica muscularis, were detected as rapidly as 4 months after treatment. The vast majority (>95%) of the grossly visible nodules/masses originated from the seminal vesicles. Testosterone treatment enhanced occurrence and increased the incidence of all lesions, particularly of seminal vesicle adenocarcinomas, from 30% (7/23) to 64% (21/33). Coagulating gland tumors were found in 21% (7/33) of the rats. Ablation of the seminal vesicle lobes reduced the incidence of seminal vesicle adenocarcinomas to 11% (3/29), and these tumors arose from tissues remaining within the parenchyma of the seminal vesicle/prostate complex after ablation. Thus, NMU-induced and testosterone-promoted male sex gland tumors of the Lobund-Wistar rat arise almost exclusively in the seminal vesicles and coagulating gland (anterior prostate), are highly invasive in seminal vesicles before attaining a grossly visible size, and progress rapidly within 4 months, spreading to adjacent tissues and other organs. C1 NCI,FREDERICK CANC RES & DEV CTR,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. NCI,INORGAN CARCINOGENESIS SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 29 TC 26 Z9 26 U1 0 U2 0 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD SEP PY 1996 VL 33 IS 5 BP 557 EP 567 PG 11 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA VJ271 UT WOS:A1996VJ27100011 PM 8885183 ER PT J AU MacLean, PD AF MacLean, PD TI Women: A more balanced brain? SO ZYGON LA English DT Article DE brain disparities in men and women; brain imaging; evolution; hypotheses; limbic system; neuroanatomy ID SEX-DIFFERENCES; ASYMMETRY; CORTEX AB On the basis of knowledge prior to 1988, Ashbrook pointed out that whereas most men are primarily dependent on the left cerebral hemisphere (''dominant hemisphere'') for verbally related functions, women show a greater hemispheric balance in this respect. For men, he argues, their possession of a ''speaking'' and a non-speaking hemisphere'' results in a positive-negative, bipolar way of thinking that may be characterized as dualistic and dialectically hierarchical. In contrast, the greater balance of hemispheric function in women appears to promote greater generalization and synthesis in their thinking. In this article I cite more recent neuroanatomical and brain imaging studies that provide further evidence of disparities in structure and function of the brains of men and women. As background for an attempt to explain these differences, I give a brief review of the triune evolution of the mammalian brain leading up to the human cerebrum. It is of major significance that the female has played a central role in mammalian evolution for more than 180 million years and that the evolutionary transition from reptilian therapsids to mammals is characterized by the development of (1) nursing, conjoined with maternal care; (2) audiovocal communication for aiding mother-offspring contact: and (3) play. In human beings, the infant-carrying hypothesis suggests one means by which, over generations, certain parts of a woman's right hemisphere could undergo functional and eventual anatomical expansion. The mother-infant communication of basic mammalian sounds with vowel and consonant components suggests a basis for the origination of speech. Finally, in an expansion or Ashbrook's original thesis, we arrive at the provocative consideration that, unlike men, with their dialectical reasoning, women, with their more balanced brain, are provided with a trialectial ladder for climbing to achieve knowledge. In terms of quantum mechanics, the particle and wave would correspond to the substance and strength of the sides of the ladder, and the derived psychic information (which is neither matter nor energy) would compare to the rungs in between. RP MacLean, PD (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 34 TC 6 Z9 6 U1 2 U2 6 PU BLACKWELL PUBLISHERS PI CAMBRIDGE PA 350 MAIN STREET, STE 6, CAMBRIDGE, MA 02148-5023 SN 0591-2385 J9 ZYGON JI Zygon PD SEP PY 1996 VL 31 IS 3 BP 421 EP 439 PG 19 WC Social Issues; Religion SC Social Issues; Religion GA VC546 UT WOS:A1996VC54600004 ER PT J AU Scrimgeour, EM Brown, P Monaghan, P AF Scrimgeour, EM Brown, P Monaghan, P TI Disposal of rendered specified offal SO VETERINARY RECORD LA English DT Letter ID BOVINE SPONGIFORM ENCEPHALOPATHY; SCRAPIE; SURVIVAL C1 NINCDS,LAB CENT NERVOUS SYST DIS,NIH,BETHESDA,MD 20892. UNIV GLASGOW,DEPT ZOOL,APPL ORNITHOL UNIT,GLASGOW G12 8QQ,LANARK,SCOTLAND. RP Scrimgeour, EM (reprint author), SULTAN QABOOS UNIV,DEPT MED,POB 35,AL KHOUD 123,MUSCAT,OMAN. RI Monaghan, Pat/E-6810-2015 NR 14 TC 1 Z9 1 U1 0 U2 0 PU BRITISH VETERINARY ASSOC PI LONDON PA 7 MANSFIELD ST, LONDON, ENGLAND W1M 0AT SN 0042-4900 J9 VET REC JI Vet. Rec. PD AUG 31 PY 1996 VL 139 IS 9 BP 219 EP 220 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA VF346 UT WOS:A1996VF34600013 PM 8883342 ER PT J AU Clarke, K Kashiwaya, Y King, MT Gates, D Keon, CA Cross, HR Radda, GK Veech, RL AF Clarke, K Kashiwaya, Y King, MT Gates, D Keon, CA Cross, HR Radda, GK Veech, RL TI The beta/alpha peak height ratio of ATP - A measure of free [Mg2+] using P-31 NMR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CREATINE-KINASE EQUILIBRIUM; INTRAVENOUS LOADING TEST; MAGNETIC-RESONANCE; INTRACELLULAR PH; MAGNESIUM-DEFICIENCY; HEART-DISEASE; FREE MG-2+; SPECTROSCOPY; LIVER; MGATP AB From P-31 NMR measurements made in vitro at 38 degrees C, I = 0.25, pH 5.75-8.5, and calculated free [Mg2+] from 0 to 5 mm, we show that, within the physiological range of cytosolic free [Mg-2+] from 0.25 to 1.5 mM, the chemical shift difference between the alpha- and beta-ATP resonances, delta(alpha beta), changes by only 0.6 ppm. Consequently, we developed new formalisms from known acid and Mg2+ dissociation constants by which the observed chemical shift of P-i, delta(Pi), and the peak height ratio of the beta- and alpha-ATP resonances, (h) over bar(beta/alpha), could be related to free [Mg2+] by simultaneous solution of: [GRAPHICS] We found that (H) over bar(beta/alpha) changed 2.5-fold as free [Mg2+] varied from 0.25 to 1.5 mM, providing a more sensitive and accurate measure of free cytosolic [Mg2+]. In working rat heart perfused with glucose, free [Mg2+] was 1.0 +/- 0.1 from (h) over bar(beta/alpha) and 1.2 +/- 0.03 from measured [citrate]/ [isocitrate] but 0.51 +/- 0.1 from delta(alpha beta). Addition of ketone bodies to the perfusate decreased free [Mg2+] estimated from (h) over bar(beta/alpha) to 0.61 +/- 0.02 and 0.74 +/- 0.11 by [citrate]/ [isocitrate] but the estimate from delta(alpha beta) was unchanged at 0.46 +/- 0.04 mM. Such differences in estimated free [Mg2+] alter the apparent K-eq of the creatine kinase reaction and hence the estimated cytosolic free [Sigma ADP]. C1 NIAAA,DEPT MEMBRANE BIOCHEM & BIOPHYS,ROCKVILLE,MD 20852. UNIV OXFORD,DEPT BIOCHEM,OXFORD OX1 3QU,ENGLAND. NR 51 TC 25 Z9 25 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 30 PY 1996 VL 271 IS 35 BP 21142 EP 21150 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700030 PM 8702884 ER PT J AU Braun, JR Willnow, TE Ishibashi, S Ashwell, G Herz, J AF Braun, JR Willnow, TE Ishibashi, S Ashwell, G Herz, J TI The major subunit of the asialoglycoprotein receptor is expressed on the hepatocellular surface in mice lacking the minor receptor subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; ALPHA-2-MACROGLOBULIN RECEPTOR; MEDIATED ENDOCYTOSIS; LIGAND-BINDING; PROTEIN LRP; LIVER; CELLS; LECTIN; OLIGOSACCHARIDES; SEQUENCE AB The mammalian asialoglycoprotein receptor (ASGPR) is located on the sinusoidal membrane of hepatocytes where it binds and endocytoses galactose-terminated glycoproteins (asialoglycoproteins). ASGPR is composed of two highly homologous subunits, termed hepatic lectin 1 and 2. Despite numerous studies the contribution of both subunits to biosynthesis and functional activity of ASGPR in vivo has remained controversial. Mice lacking the murine hepatic lectin (MHL)-2 subunit are viable and fertile without obvious phenotypic abnormalities. In the absence of MHL-2, knockout mice express MHL-1 protein at reduced levels. Here, we examine the intracellular fate and function of this remaining subunit. The results show that MHL-1 reaches the hepatocellular surface in knockout mice but is unable to effectively remove any one of three different radiolabeled ligands within 30 min. A small but detectable residual ligand clearance in knockout mice at 4 h is apparently not mediated by remaining MHL-1. Serum concentrations of galactose-terminating glycoproteins are not elevated in these ASGPR-deficient mice. However, competitive in vitro degradation experiments suggest that other endogenous ASGPR ligands, the nature of which remain to be determined, accumulate in serum of knockout animals. C1 UNIV TEXAS,SW MED CTR,DEPT MOL GENET,DALLAS,TX 75235. UNIV TOKYO,FAC MED,DEPT INTERNAL MED 3,BUNKYO KU,TOKYO 113,JAPAN. NIDDKD,NIH,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL20948] NR 44 TC 50 Z9 51 U1 3 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 30 PY 1996 VL 271 IS 35 BP 21160 EP 21166 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700032 PM 8702886 ER PT J AU Kim, CG Park, D Rhee, SG AF Kim, CG Park, D Rhee, SG TI The role of carboxyl-terminal basic amino acids in G(q)alpha-dependent activation, particulate association, and nuclear localization of phospholipase C-beta 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-GAMMA-SUBUNITS; PHOSPHOINOSITIDASE-C-BETA; PROTEIN ALPHA-SUBUNIT; BOVINE BRAIN; EXPRESSION SYSTEM; VACCINIA VIRUS; DNA-POLYMERASE; CELLS; PURIFICATION; ISOZYMES AB The phospholipase C (PLC)-beta isozymes differ from the PLC-gamma and PLC-delta isozymes in that they possess a long COOH-terminal sequence downstream of their catalytic domain, are activated by alpha subunits of the G(q) class of G proteins, associate with the particulate subcellular fraction, and are present in the nucleus. Most of the COOH-terminal domain of PLC-beta isozymes is predicted to be helical, and three regions in this domain, PLC-beta 1 residues 911-928 (region 1), 1055-1072 (region 2), and 1109-1126 (region 3), contain a high proportion of basic residues that are highly conserved. Projection of the sequences of these three regions in helical wheels reveals clustering of the basic residues. The role of the COOH terminus and the clustered basic residues in PLC-beta 1 was investigated by either truncating the entire COOH-terminal domain (mutant Delta C) or replacing two or three clustered basic residues with isoleucine (or methionine), and expressing the mutant enzymes in CV-1, Rat-2, or Swiss 3T3 cells. The Delta C mutant no longer showed the ability to be activated by G(q) alpha, to translocate to the nucleus, or to associate with the particulate fraction. Substitution of clusters of basic residues in regions 1 and 2 generally reduced the extent of activation by G(q) alpha, whereas substitution of a basic cluster in region 3 had no effect. Substitution of the cluster of lysine residues 914, 921, and 925 in region 1 had the most marked effect, reducing G(q) alpha-dependent activity to 10% of that of wild type. All substitution mutants, with the exception of that in which lysine residues 1056, 1063, and 1070 in region 2 were substituted with isoleucine, behaved like the wild-type enzyme in showing an approximately equal distribution between cytoplasm and nucleus; only 12% of the region 2 mutant was present in the nucleus. None of the basic clusters appeared critical for particulate association; however, replacement of each cluster reduced the amount of PLC-beta 1 in the particulate fraction by some extent, suggesting that all the basic residues contribute to the association, presumably by interacting with acidic residues in the particulate fraction, Membrane localization of PLC-beta isozymes is therefore likely mediated by both the COOH-terminal domain and the pleckstrin homology domain, the latter of which is known to bind phosphatidylinositol 4,5-biphosphate. C1 NHLBI,LAB CELL SIGNALING,NIH,BETHESDA,MD 20892. NR 41 TC 173 Z9 174 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 30 PY 1996 VL 271 IS 35 BP 21187 EP 21192 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700035 PM 8702889 ER PT J AU Tomic, M Jobin, RM Vergara, LA Stojilkovic, SS AF Tomic, M Jobin, RM Vergara, LA Stojilkovic, SS TI Expression of purinergic receptor channels and their role in calcium signaling and hormone release in pituitary gonadotrophs - Integration of P-2 channels in plasma membrane- and endoplasmic reticulum-derived calcium oscillations SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTRACELLULAR CALCIUM; CHROMAFFIN CELLS; ATP RECEPTORS; CA2+ RELEASE; EXTRACELLULAR ATP; XENOPUS-OOCYTES; SENSORY NEURONS; ION CHANNELS; AR42J CELLS; ADENOSINE AB The role of ATP as a positive feedback element in Ca2+ signaling and secretion was examined in female rat pituitary gonadotrophs. ATP and ADP, but not AMP or adenosine, induced a dose- and extracellular Ca2+-dependent rise in [Ca-2+](i) in identified gonadotrophs in a Mg2+- and suramin-sensitive manner. ATP, adenosine-5'-O-(3-thiotriphosphate), adenosine-5'-O-(1-thiotriphosphate), 2-methylthio-ATP, and 3'-O-(4-benzoyl)benzoyl-ATP. were roughly equipotent in rising [Ca2+](i) in gonadotrophs, while ADP was effective only at submillimolar concentration range, and none of these compounds permeabilized the cells. On the other hand, alpha,beta-methylene-ATP, beta,gamma-methylene-ATP, and UTP were unable to induce any rise in [Ca2+](i). This pharmacological profile is consistent with expression of P2X(2) and/or P2X(5) purinergic receptor channels. Patch-clamp experiments showed that ATP induced an inward depolarizing current in gonadotrophs clamped at -90 mV, associated with an increase in [Ca2+](i). The ATP-induced [Ca2+](i) response was partially inhibited by nifedipine, a blocker of voltage-sensitive Ca2+ channels (VSCC), but was not affected by tetrodotoxin, a blocker of voltage-sensitive Na+ channels. Thus, the P-2-depolarizing current itself drives Ca2+ into the cell, but also activates Ca2+ entry through VSCC. In accord with this, low [ATP] induced plasma membrane-dependent [Ca2+](i) oscillations in quiescent cells, and increased the frequency of spiking in spontaneously active cells. ATP-induced Ca2+ influx also affected agonist-induced and InsP(3)-dependent [Ca2+](i) oscillations by increasing the frequency, base line, and duration of Ca2+ spiking. In addition, ATP stimulated gonadotropin secretion and enhanced agonist-induced gonadotropin release. ATP was found to be secreted by pituitary cells during agonist stimulation and was promptly degraded by ectonucleotidase to adenosine. These observations indicate that ATP represents a paracrine/autocrine factor in the regulation of Ca2+ signaling and secretion in gonadotrophs, and that these actions are mediated by P-2 receptor channels. C1 NICHHD,ERRB,UCS,NIH,BETHESDA,MD 20892. RI Tomic, Melanija/C-3371-2016 NR 58 TC 63 Z9 63 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 30 PY 1996 VL 271 IS 35 BP 21200 EP 21208 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700037 PM 8702891 ER PT J AU Sasner, M Buonanno, A AF Sasner, M Buonanno, A TI Distinct N-methyl-D-aspartate receptor 2B subunit gene sequences confer neural and developmental specific expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROMERIC NMDA RECEPTORS; TRANSGENIC MICE; RAT-BRAIN; MOLECULAR CHARACTERIZATION; NEURONAL MIGRATION; 5'-FLANKING REGION; MAMMALIAN-CELLS; MESSENGER-RNAS; I GENE; CHANNEL AB Expression of the N-methyl-D-aspartate (NMDA) receptor 2B (NR2B) subunit is neural-specific and differentially regulated. It is expressed in the forebrain and in cerebellar granule cells at early postnatal stages and selectively repressed in the cerebellum after the second postnatal week, where it is replaced by the NR2C subunit. This switch confers distinct properties to the receptor. In order to understand the molecular mechanisms that differentially regulate the NR2B gene in the forebrain and cerebellum during development, we have isolated and characterized the promoter region of the NR2B gene. Two 5' noncoding exons and multiple transcription start sites were identified. Transcriptional analysis in transgenic mice reveals that an upstream 800-base pair region, which includes the first exon, is sufficient to direct neural-specific transcription. Developmental repression of the gene in the cerebellum requires additional regulatory elements residing in the first intron or second exon. Sequence elements that may participate in the regulation of the NR2B gene were identified by comparison to other neural genes. These studies provide insight into the molecular mechanisms regulating the switch of NMDA receptor subunit expression in the cerebellum, which ultimately account for the physiological changes in receptor function during development. C1 NICHHD,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. FU NICHD NIH HHS [HD-0-2911] NR 53 TC 52 Z9 52 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 AUG 30 PY 1996 VL 271 IS 35 BP 21316 EP 21322 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700056 PM 8702910 ER PT J AU Gaffen, SL Lai, SY Ha, M Liu, XW Henninghausen, L Greene, WC Goldsmith, MA AF Gaffen, SL Lai, SY Ha, M Liu, XW Henninghausen, L Greene, WC Goldsmith, MA TI Distinct tyrosine residues within the interleukin-2 receptor beta chain drive signal transduction specificity, redundancy, and diversity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID JAK-3 JANUS KINASE; GAMMA-CHAIN; IL-2 RECEPTOR; CELL-PROLIFERATION; STAT PROTEINS; C-FOS; ERYTHROPOIETIN RECEPTOR; FUNCTIONAL COMPONENT; TRANSCRIPTION FACTOR; CYTOPLASMIC DOMAINS AB To explore the basis for interleukin (IL)-2 receptor (IL-2R) signaling specificity, the roles of tyrosine-based sequences located within the cytoplasmic tails of the beta and gamma(c) chains were examined in the murine helper T cell line HT-2, Activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, cellular proliferation, and the induction of various genes were monitored, All four of the cytoplasmic tyrosine residues as well as the distal portion of the gamma(c) proved dispensable for the entire spectrum of IL-2R signaling responses studied. Conversely, select tyrosine residues within the beta chain were essential and differentially required for various signaling events, Specifically, activation of c-fos gene expression was found to occur exclusively through the most membrane proximal tyrosine, Tyr-338, whereas proliferation and the activation of STAT-5 were induced either through Tyr-338 or through the two C-terminal tyrosine residues, Tyr-392 and Tyr-510, These tyrosine residues mediated the induction of two different STAT-5 isoforms, which were found to form heterodimers upon receptor activation, In contrast to the tyrosine dependence of c-fos and STAT-5 induction, bcl-2 gene induction proceeded independently of all IL-2R beta tyrosine residues, Thus, the tyrosine-based modules present within the IL-2R beta cytoplasmic tail play a critical role in IL-2R signaling, mediating specificity, redundancy, and multifunctionality. C1 GLADSTONE INST VIROL & IMMUNOL,SAN FRANCISCO,CA 94141. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT MICROBIOL & IMMUNOL,SAN FRANCISCO,CA 94143. NIDDK,LAB BIOCHEM & METAB,NATL INST HLTH,BETHESDA,MD 20892. RI Gaffen, Sarah/B-1560-2009 FU NIAID NIH HHS [R01 AI36452]; NIGMS NIH HHS [R01 GM54351] NR 53 TC 62 Z9 63 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 30 PY 1996 VL 271 IS 35 BP 21381 EP 21390 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700065 PM 8702919 ER PT J AU Xu, M Chakraborti, PK Garabedian, MJ Yamamoto, KR Simons, SS AF Xu, M Chakraborti, PK Garabedian, MJ Yamamoto, KR Simons, SS TI Modular structure of glucocorticoid receptor domains is not equivalent to functional independence - Stability and activity of the steroid binding domain are controlled by sequences in separate domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THYROID-HORMONE RECEPTOR; HEAT-SHOCK PROTEIN-90; DNA-BINDING; NUCLEAR RECEPTOR; TRANSCRIPTIONAL REGULATION; TYROSINE AMINOTRANSFERASE; CRYSTAL-STRUCTURE; FUSION PROTEINS; GENE-REGULATION; HSP90 BINDING AB A long-standing conundrum of glucocorticoid receptors has been why the steroid binding domain is active in hybrid proteins but not in isolation, For this reason, the precise boundaries of the steroid binding domain have not been de fined. These questions have How been systematically examined with a variety of receptor deletion constructs, Plasmids encoding amino acids 537-673 and 537-795 of the rat receptor did not yield stable proteins, while the fusion of receptor or non-receptor sequences upstream of 537-673 afforded stable proteins that did not bind steroid, Wild type steroid binding affinity could be obtained, however, when proteins such as beta-galactosidase or dihydrofolate reductase were fused upstream of receptor amino acids 531-795, Studies of a series of dhfr/receptor constructs with deletions at the amino- and carboxyl-terminal ends of the receptor sequence localized the boundaries of the steroid binding domain to 550-795, The absence of steroid binding upon deletion of sequences in the carboxyl-terminal half of this domain was consistent with improperly folded receptor sequences. This conclusion was supported by analyses of the proteolysis and thermal stability of the mutant receptors, Thus, three independent regions appear to be required for the generation of the steroid binding form of receptors: 1) a protein sequence upstream of the steroid binding domain, which conveys stability to the steroid binding domain, 2) sequences of the carboxyl-terminal amino acids (674-795), which are required far the correct folding of the steroid binding domain, and 3) amino-terminal sequences (550-673), which may be sufficient for steroid binding after the entire steroid binding domain is properly folded. These results establish that the steroid binding domain of glucocorticoid receptors is not independently functional and illustrate the importance of both protein stability and protein folding when constructing mutant proteins. C1 NIDDK,STEROID HORMONES SECT,LMCB,NATL INST HLTH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM,SAN FRANCISCO,CA 94143. NR 79 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 30 PY 1996 VL 271 IS 35 BP 21430 EP 21438 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700071 PM 8702925 ER PT J AU Ribeiro, CMP Putney, JW AF Ribeiro, CMP Putney, JW TI Differential effects of protein kinase C activation on calcium storage and capacitative calcium entry in NIH 3T3 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN NEUTROPHILS; PHORBOL ESTER; CA2+ ENTRY; ENDOPLASMIC-RETICULUM; CHEMOTACTIC PEPTIDE; RBL-2H3 CELLS; RECEPTOR; ASSOCIATION; PATHWAY; FIBROBLASTS AB In NIH 3T3 cells, treatment with phorbol 12-myristate 13-acetate (PMA) reduced the release of Ca2+ by thapsigargin, but did not activate Ca2+ entry; Ca2+ influx was triggered after the residual pool was emptied by thapsigargin, and this Ca2+ influx was similar to that induced by thapsigargin in control cells. The effect of PMA was clue to decreased Ca2+ storage because 1) Ca2+ release by ionomycin was similarly affected by PMA, and in both control and PMA-treated cells, ionomycin did not release Ca2+ following thapsigargin treatment; 2) PMA reduced Ca-45(2+) accumulation; and 3) studies with Ca2+ indicator compartmentalized into the endoplasmic reticulum indicated that stored Ca2+ was reduced by PMA. Although PMA did not itself activate Ca2+ entry, PMA potentiated Ca2+ entry with low concentrations of cyclopiazonic acid. With a somewhat higher concentration of cyclopiazonic acid, PMA had no effect on calcium entry. Thus, protein kinase C has two apparent actions on calcium signaling in NIH 3T3 cells: 1) reduced intracellular Ca2+ storage capacity and 2) augmented calcium entry with submaximal intracellular Ca2+ pool depletion. These actions indicate a complex and potentially important role for the protein kinase C system in calcium homeostasis in this cell type. RP Ribeiro, CMP (reprint author), NIEHS,NATL INST HLTH,POB 12233,MAIL DROP 7-10,RES TRIANGLE PK,NC 27709, USA. RI Ribeiro, Carla Maria/A-6955-2009 NR 29 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 30 PY 1996 VL 271 IS 35 BP 21522 EP 21528 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700083 PM 8702937 ER PT J AU Neufeld, EB Cooney, AM Pitha, J Dawidowicz, EA Dwyer, NK Pentchev, PG BlanchetteMackie, EJ AF Neufeld, EB Cooney, AM Pitha, J Dawidowicz, EA Dwyer, NK Pentchev, PG BlanchetteMackie, EJ TI Intracellular trafficking of cholesterol monitored with a cyclodextrin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY LIPOPROTEIN; NIEMANN-PICK DISEASE; LEYDIG TUMOR-CELLS; PLASMA-MEMBRANE; CULTURED FIBROBLASTS; GOLGI-APPARATUS; C FIBROBLASTS; BREFELDIN-A; SPHINGOMYELIN DEGRADATION; RAT-LIVER AB The sterol binding agent 2-hydroxypropyl-beta-cyclodextrin is shown to be a convenient and useful experimental tool to probe intracellular pathways of cholesterol transport. Biochemical and cytochemical studies reveal that cyclodextrin specifically removes plasma membrane cholesterol. Depletion of plasma membrane sphingomyelin greatly accelerated cyclodextrin-mediated cholesterol removal. Cholesterol arriving at the plasma membrane from lysosomes and the endoplasmic reticulum was also removed by cyclodextrin. Cellular cholesterol esterification linked to the mobilization of cholesterol from lysosomes was strongly attenuated by cyclodextrin, suggesting that the major portion of endocytosed cholesterol is delivered from lysosomes to the endoplasmic reticulum via the plasma membrane. Evidence for translocation of lysosomal cholesterol to the endoplasmic reticulum by a plasma membrane-independent pathway is provided by the finding that cyclodextrin loses its ability to suppress esterification when plasma membrane sphingomyelin is depleted. The Golgi apparatus appears to play an active role in directing the relocation of lysosomal cholesterol to the plasma membrane since brefeldin A also abrogated cyclodextrin-mediated suppression of cholesterol esterification. Using cyclodextrin we further show that attenuated esterification of lysosomal cholesterol in Niemann-Pick C cells reflects defective translocation of cholesterol to the plasma membrane that may be linked to abnormal Golgi trafficking. C1 NINCDS, DEV & METAB NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. NIA, GERONTOL RES CTR, NIH, BALTIMORE, MD 21224 USA. MARINE BIOL LAB, WOODS HOLE, MA 02543 USA. RP NIDDK, LIPID CELL BIOL SECT,LAB CELL BIOCHEM & BIOL,NIH, BLDG 8,RM 427, 8 CTR DR, BETHESDA, MD 20892 USA. NR 57 TC 281 Z9 283 U1 2 U2 13 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 30 PY 1996 VL 271 IS 35 BP 21604 EP 21613 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700094 PM 8702948 ER PT J AU Vaughan, RA Kuhar, MJ AF Vaughan, RA Kuhar, MJ TI Dopamine transporter ligand binding domains - Structural and functional properties revealed by limited proteolysis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; COCAINE RECEPTORS; CLONING; GLYCOSYLATION; SITES; EXPRESSION; SUBSTRATE; PROGRESS; PROTEINS; COMPLEX AB Dopamine transporters (DATs) are members of the Na+- and Cl--dependent neurotransmitter and amino acid transporter family predicted by hydrophobicity analysis to have 12 transmembrane-spanning helices. The structure of DAT was studied using the photoaffinity compounds [I-125]1-[2-(diphenylmethoxy)-ethyl]-4-[2-(4-azido-3- iodophenyl)ethyl]piperazine ([I-125]DEEP), a 1-(2-diphenylmethoxy)-ethyl-4-(3-phenyl propyl)piperazine (GBR analog), and [I-125]-3 beta-(p-chlorophenyl)tropane-2 beta-carboxylic acid, 4'-azido-3'-idophenylethyl ester ([I-125]RTI 82), a cocaine analog, which had been shown in a previous study to become incorporated into different regions of the DAT primary sequence. The proximity of the photolabeled binding sites to integral membrane structures was investigated by subjecting photolabeled membrane suspensions to limited proteolysis with trypsin and separately analyzing the resulting membranes and supernatants for the presence of photolabeled DAT fragments. Trypsin treatment of [I-125] DEEP-labeled membranes generated labeled 45- and 14-kDa DAT fragments that immunoprecipitated with an epitope-specific antiserum generated against amino acids 42-59 near the first putative transmembrane domain, whereas [I-125]RTI 82 was found in 32- and 16-kDa tryptic fragments that precipitated with an antiserum directed against a sequence near transmembrane domain 4 (amino acids 225-238), All of the photolabeled fragments were recovered in the protease-treated membranes, indicating that they possess integral membrane structures that prevent their release from the membrane as soluble forms. The size of the two smallest fragments in conjunction with their retention in the membrane suggests that incorporation of the photoaffinity ligands occurs in or near membrane spanning regions and delineates the maximum possible distance between the transmembrane structures, incorporated photolabel, and antibody epitopes. Carbohydrate analysis of the fragments identified sialic acids and N-linked oligosaccharides exclusively on the 45 kDa [I-125]DEEP-labeled fragment, which, based on size, would be expected to contain four consensus glycosylation sites between putative transmembrane domains 3 and 4. Photoaffinity labeling after trypsin treatment of membranes showed that the larger but not the smaller fragments retain binding capacity, as the 45- and 32-kDa fragments were capable of becoming photolabeled. Binding of photoaffinity ligands at these fragments was displaced with the same pharmacology as that of intact DATs. These results verify numerous aspects of DAT structure and topology heretofore only predicted from theoretical considerations and extend our knowledge of DAT structure function properties. C1 EMORY UNIV,YERKES REG PRIMATE RES CTR,DIV NEUROSCI,ATLANTA,GA 30322. RP Vaughan, RA (reprint author), NIDA,NEUROSCI BRANCH,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD 21224, USA. NR 41 TC 57 Z9 57 U1 1 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 AUG 30 PY 1996 VL 271 IS 35 BP 21672 EP 21680 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700103 PM 8702957 ER PT J AU Kim, CU McGee, LR Krawczyk, SH Harwood, E Harada, Y Swaminathan, S Bischofberger, N Chen, MS Cherrington, JM Xiong, SF Griffin, L Cundy, KC Lee, A Yu, B Gulnik, S Erickson, JW AF Kim, CU McGee, LR Krawczyk, SH Harwood, E Harada, Y Swaminathan, S Bischofberger, N Chen, MS Cherrington, JM Xiong, SF Griffin, L Cundy, KC Lee, A Yu, B Gulnik, S Erickson, JW TI New series of potent, orally bioavailable, non-peptidic cyclic sulfones as HIV-1 protease inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RETROVIRAL PROTEASES; DESIGN; UREAS C1 NCI,FREDERICK CANC RES & DEV CTR,STRUCT BIOCHEM PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. RP Kim, CU (reprint author), GILEAD SCI INC,353 LAKESIDE DR,FOSTER CITY,CA 94404, USA. NR 14 TC 41 Z9 41 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 AUG 30 PY 1996 VL 39 IS 18 BP 3431 EP 3434 DI 10.1021/jm960340o PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VE546 UT WOS:A1996VE54600001 PM 8784440 ER PT J AU Zhang, Y Williams, W Bowen, WD Rice, KC AF Zhang, Y Williams, W Bowen, WD Rice, KC TI Synthesis and evaluation of aryl-substituted N-(arylethyl)-N-methyl-2-(1-pyrrolidinyl)ethylamines and corresponding arylacetamides for sigma receptor affinity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID H-3 (+)-PENTAZOCINE; BINDING-SITES; RAT-BRAIN; LIGANDS; CELLS; CONTAIN; SUGGEST; POTENT; DRUGS AB A series of aryl-monosubstituted arylacetamides (4-9) and arylethylenediamine (10-18) compounds were synthesized based on the structure of the high-affinity sigma ligand N-[2-(3 ,4-dichlorophenyl)ethyl] -N-nlethyl-2-(1-pyrrolidinyl)ethylamine (2). These compounds were prepared to evaluate the effect of aromatic substitution patterns on sigma-1 and sigma-2 receptor binding affinity and selectivity. The data indicate that 10-18 possessed higher affinity than 4-9 for both sigma sites, especially when substituted with an electron-withdrawing group. The diamine compounds 10-18 were selective for sigma-1 binding sites, whereas the arylacetamide compounds 4-9 generally exhibited an increased selectivity far sigma-2 sites compared to sigma-1. No clear pattern between the orientation of aromatic substituents and the sigma binding activity was observed. C1 NIDDK,MED CHEM LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 31 TC 11 Z9 12 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 30 PY 1996 VL 39 IS 18 BP 3564 EP 3568 DI 10.1021/jm9600813 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VE546 UT WOS:A1996VE54600016 PM 8784455 ER PT J AU Strong, MJ Garruto, RM Joshi, JG Mundy, WR Shafer, TJ AF Strong, MJ Garruto, RM Joshi, JG Mundy, WR Shafer, TJ TI Can the mechanisms of aluminum neurotoxicity be integrated into a unified scheme? SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article; Proceedings Paper CT Research Issues in Aluminum Toxicity Workshop CY JUL, 1995 CL VANCOUVER, CANADA ID INDUCED NEUROFIBRILLARY DEGENERATION; CHOLINE-ACETYLTRANSFERASE ACTIVITY; AVOIDANCE-RESPONSE ACQUISITION; NICTITATING-MEMBRANE RESPONSE; CALCIUM-CHANNEL CURRENTS; CHROMATIN BOUND ALUMINUM; RAT-BRAIN; ALZHEIMERS-DISEASE; PHOSPHOINOSITIDE HYDROLYSIS; PROTEIN-KINASE AB Regardless of the host, the route of administration, or the speciation, aluminum is a potent neurotoxicant. In the young adult or developmentally mature host, the neuronal response to Al exposure can be dichotomized on morphological grounds. In one, intraneuronal neurofilamentous aggregates are formed whereas in the other, significant neurochemical and neurophysiological perturbations are induced without neurofilamentous aggregate formation. Evidence is presented that the induction of neurofilamentous aggregates is a consequence of alterations in the posttranslational processing of neurofilament (NF), particularly with regard to phosphorylation state. Although Al has been reported to impact on gene expression, this does not appear to be critical to the induction of cytoskeletal pathology. In hosts responding to Al exposure without the induction of cytoskeletal pathology, impairments in glucose utilization, agonist-stimulated inositol phosphate accumulation, free radical-mediated cytotoxicity, lipid peroxidation, reduced cholinergic function, and altered protein phosphorylation have been described. The extent to which these neurochemical modifications correlate with the induction of a characteristic neurobehavioral state is unknown. In addition to these paradigms, Al is toxic in the immediate postnatal interval. C1 UNIV WESTERN ONTARIO,DEPT CLIN NEUROL SCI,LONDON,ON N6A 3K7,CANADA. NINCDS,NIH,BETHESDA,MD 20892. UNIV TENNESSEE,DEPT BIOCHEM,KNOXVILLE,TN 37996. US EPA,DIV NEUROTOXICOL,RES TRIANGLE PK,NC 27711. RI Shafer, Timothy/D-6243-2013; Strong, Michael/H-9689-2012; OI Shafer, Timothy/0000-0002-8069-9987 NR 107 TC 48 Z9 52 U1 0 U2 5 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD AUG 30 PY 1996 VL 48 IS 6 BP 599 EP 613 DI 10.1080/009841096161096 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA VE144 UT WOS:A1996VE14400008 PM 8772801 ER PT J AU Lovell, MA Ehmann, WD Markesbery, WR Melethil, S Swyt, CR Zatta, PF AF Lovell, MA Ehmann, WD Markesbery, WR Melethil, S Swyt, CR Zatta, PF TI Standardization in biological analyses of aluminum: What are the needs? SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article; Proceedings Paper CT Research Issues in Aluminum Toxicity Workshop CY JUL, 1995 CL VANCOUVER, CANADA ID NEUTRON-ACTIVATION ANALYSIS; MICROPROBE MASS ANALYSIS; HUMAN BRAIN-TISSUE; ALZHEIMERS-DISEASE; NEUROFIBRILLARY DEGENERATION; PLAQUE CORES; SPECTROMETRY; LAMMA; ACCUMULATION; ABSENCE AB A review of the literature of aluminum (Al)levels in biological samples, particularly Alzheimer's disease (AD) brain, reveals a lack of interlaboratory agreement at both the bulk and microprobe levels. One possible reason for this controversy may be the methods chosen for quantitation and standardization. Currently, the major problem affecting quantitation of Al at the bulk level is the lack of low-Al-concentration, matrix-matched certified standards. Although a number of certified aluminum bulk standards are available, most do not match well in matrix with the samples of interest. A similar situation exists for microprobe standards in which commercially available pure metal foils and thin films of materials, such as metal oxides, are available but again do not match well in matrix. A review of the current status of quantitation of Al levels in biological analyses at the bulk and microprobe level is presented. Future directions to develop standards include the submission of currently used microprobe standards to a central laboratory for critical analysis and selection of the optimum standard, followed by establishment of interlaboratory and intertechnique comparisons. Other future directions include the adaptation of a standard protocol for the selection of tissue for analysis and criteria for data rejection, as well as the development of a standard system for data normalization and reporting. C1 UNIV KENTUCKY,SANDERS BROWN CTR AGING,LEXINGTON,KY 40506. UNIV KENTUCKY,DEPT PATHOL,LEXINGTON,KY 40506. UNIV KENTUCKY,DEPT NEUROL,LEXINGTON,KY 40506. UNIV MISSOURI,PHARMACEUT SCI DIV,KANSAS CITY,KS. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. UNIV PADUA,DEPT BIOL,I-35100 PADUA,ITALY. RP Lovell, MA (reprint author), UNIV KENTUCKY,DEPT CHEM,LEXINGTON,KY 40506, USA. NR 39 TC 10 Z9 10 U1 0 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD AUG 30 PY 1996 VL 48 IS 6 BP 637 EP 648 DI 10.1080/009841096161113 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA VE144 UT WOS:A1996VE14400010 PM 8772803 ER PT J AU Massaquoi, SG Slotine, JJE AF Massaquoi, SG Slotine, JJE TI The intermediate cerebellum may function as a wave-variable processor SO NEUROSCIENCE LETTERS LA English DT Article DE cerebellum; feedback; stability; wave variable; control system; arm movement; delay ID MOVEMENTS; JOINT; MODEL AB A newly developed model suggests that the intermediate cerebellum and spinal cord gray matter may contribute to movement control by processing control signals as wave variables, Within specialized communication systems, wave variables are combinations of forward and return signals that ensure stable exchange between two sites despite transmission delays. The composition of signals transmitted in the ventral spinocerebellar tract appears to be consistent with that of a wave variable, and computer simulations of the model yield signals similar to those observed in the monkey interpositus nucleus. Wave-variable communication may enable the animal motor system to maintain stable, high-performance feedback control in the presence of potentially destabilizing signal transmission delays. C1 MIT,NONLINEAR SYST LAB,CAMBRIDGE,MA 02139. RP Massaquoi, SG (reprint author), NINCDS,NIH,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,10 CTR DR MSC-1430,BETHESDA,MD 20892, USA. NR 29 TC 20 Z9 20 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 AUG 30 PY 1996 VL 215 IS 1 BP 60 EP 64 DI 10.1016/S0304-3940(96)12927-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA VG380 UT WOS:A1996VG38000016 PM 8880754 ER PT J AU Grady, TA Broocks, A Canter, SK Pigott, TA Dubbert, B Hill, JL Murphy, DL AF Grady, TA Broocks, A Canter, SK Pigott, TA Dubbert, B Hill, JL Murphy, DL TI Biological and behavioral responses to D-amphetamine, alone and in combination with the serotonin(3) receptor antagonist ondansetron, in healthy volunteers SO PSYCHIATRY RESEARCH LA English DT Article DE 5-hydroxytryptamine; dopamine; blood pressure; mood; prolactin; cortisol; temperature; growth hormone ID 5-HT3 RECEPTORS; NUCLEUS-ACCUMBENS; NEURO-ENDOCRINE; RAT; RELEASE; PSYCHOPHARMACOLOGY; DEXTROAMPHETAMINE; STIMULATION; ATTENUATION; PROLACTIN AB Evidence that serotonin(3) (5-hydroxytryptamine(3), 5-HT3) antagonists attenuate behavioral responses to D-amphetamine and cocaine suggests that 5-HT3 receptors modulate brain dopamine in animals. This study examined the potential interactions of the 5-HT3 antagonist ondansetron and D-amphetamine in 10 healthy human volunteers. After the subjects were pretreated with placebo or ondansetron (0.15 mg/kg, i.v.), 5-h challenge tests with oral D-amphetamine (0.5 mg/kg) were performed. As animal studies and early clinical studies with ondansetron have suggested nonlinear dose-response relationships, three subjects also underwent pilot studies with three doses of ondansetron (0.15, 0.05, and 0.015 mg/kg) before they received D-amphetamine. Administration of D-amphetamine increased plasma levels of cortisol, prolactin, growth hormone; elevated blood pressure, pulse, and temperature; and tended to increase self-ratings of activation/euphoria and anxiety. Amphetamine-induced increases in plasma prolactin were significantly reduced by ondansetron pretreatment, but the other neuroendocrine responses were unchanged. Diastolic blood pressure elevations were also significantly attenuated after administration of the lower ondansetron doses, but the other physiologic responses were unchanged. In subjects with minimal or moderate activation/euphoria responses, ondansetron pretreatment only minimally affected these effects of D-amphetamine. Preliminary data, however, indicate that those subjects with robust activation-euphoria responses to D-amphetamine had attenuated responses after ondansetron pretreatment. Taken together, these results suggest that some but not most of D-amphetamine's biological and behavioral effects may be modified by a 5-HT3 antagonist in healthy human volunteers. C1 UNIV GOTTINGEN,DEPT PSYCHIAT,D-37075 GOTTINGEN,GERMANY. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. UNIV TEXAS,MED BRANCH,DEPT PSYCHIAT & BEHAV SCI,GALVESTON,TX 77555. GEORGETOWN UNIV,MED CTR,DEPT PSYCHIAT,WASHINGTON,DC 20007. NIDA,ROCKVILLE,MD 20857. RP Grady, TA (reprint author), DUKE UNIV,MED CTR,DEPT PSYCHIAT & BEHAV SCI,BOX 3837,DURHAM,NC 27710, USA. NR 47 TC 28 Z9 28 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD AUG 30 PY 1996 VL 64 IS 1 BP 1 EP 10 DI 10.1016/0165-1781(96)02884-3 PG 10 WC Psychiatry SC Psychiatry GA VJ061 UT WOS:A1996VJ06100001 PM 8888359 ER PT J AU Wolf, SS Jones, DW Knable, MB Gorey, JG Lee, KS Hyde, TM Coppola, R Weinberger, DR AF Wolf, SS Jones, DW Knable, MB Gorey, JG Lee, KS Hyde, TM Coppola, R Weinberger, DR TI Tourette syndrome: Prediction of phenotypic variation in monozygotic twins by caudate nucleus D2 receptor binding SO SCIENCE LA English DT Article ID BASAL GANGLIA; IMAGING AGENT; DISORDER; LINKAGE; ABNORMALITIES; MRI AB Tourette syndrome, a chronic tic disorder with autosomal dominant inheritance, exhibits considerable phenotypic variability even within monozygotic twin pairs. The origins of this variability remain unclear. Recent findings have implicated the caudate nucleus as a locus of pathology, and pharmacological evidence supports dopaminergic involvement. Within monozygotic twins discordant for Tourette syndrome severity, differences in D2 dopamine receptor binding in the head of the caudate nucleus predicted differences in phenotypic severity (r = 0.99); this relation was not observed in putamen. These data may link Tourette syndrome with a spectrum of neuropsychiatric disorders that involve associative striatal circuitry. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,NIH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032. NR 31 TC 175 Z9 176 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 30 PY 1996 VL 273 IS 5279 BP 1225 EP 1227 DI 10.1126/science.273.5279.1225 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VE476 UT WOS:A1996VE47600039 PM 8703056 ER PT J AU Varga, K Lovas, G Palkovits, M Kunos, G AF Varga, K Lovas, G Palkovits, M Kunos, G TI Ethanol inhibition of stress-related tachycardia involves medullary NMDA receptors SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE defense area; perifornical area; GABA (gamma-aminobutyric acid); glutamate; nucleus tractus solitarii ID NUCLEUS-TRACTUS-SOLITARIUS; BARORECEPTOR REFLEX CONTROL; LATERAL HYPOTHALAMIC AREA; GAMMA-AMINOBUTYRIC-ACID; D-ASPARTATE RECEPTORS; BRAIN-STEM; ANATOMICAL ORGANIZATION; CARDIOVASCULAR PRESSOR; BAROREFLEX BRADYCARDIA; GABA(B) RECEPTORS AB In rats, neurons in the perifornical area of the hypothalamus send descending projections to the commissural part of the nucleus tractus solitarii as demonstrated by an anterograde tracer study. In urethane-anaesthetised rats, stimulation of neurons in the perifornical area by microinjection of bicuculline or 6-OH-saclofen causes tachycardia and inhibits baroreflex bradycardia. The effects elicited from the perifornical area are similar in magnitude to those elicited from the adjacent dorsomedial nucleus, also called the hypothalamic defense area. Microinjection into the nucleus tractus solitarii of the NMDA (N-methyl-D-aspartate) receptor antagonist, AP-7 (2-amino-7-phosphonoheptanoic acid), inhibits the tachycardic response to stimulation of the perifornical area. Injection of ethanol intravenously or into the nucleus tractus solitarii also inhibits this tachycardic response, but causes no further inhibition when combined with AP-7. We conclude that the perifornical area is part of the hypothalamic defense area, and it is under strong, tonic GABAergic inhibition mediated by both GABA(A) and GABA(B) receptors. Furthermore, descending input from the perifornical area to the nucleus tractus solitarii is via an NMDA synapse, and ethanol inhibits stress-related tachycardia by inhibiting these NMDA receptors in the nucleus tractus solitarii. C1 VIRGINIA COMMONWEALTH UNIV,SCH MED,DEPT PHARMACOL & TOXICOL,RICHMOND,VA 23298. SEMMELWEIS UNIV MED,SCH MED,NEUROMORPHOL LAB,BUDAPEST,HUNGARY. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 FU NIAAA NIH HHS [AA09719] NR 30 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 29 PY 1996 VL 310 IS 2-3 BP 145 EP 153 DI 10.1016/0014-2999(96)00305-6 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VG697 UT WOS:A1996VG69700008 PM 8884211 ER PT J AU Ijzerman, AP Kunzel, JKVD Kim, J Jiang, QL Jacobson, KA AF Ijzerman, AP Kunzel, JKVD Kim, J Jiang, QL Jacobson, KA TI Site-directed mutagenesis of the human adenosine A(2A) receptor. Critical involvement of Glu(13) in agonist recognition SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE adenosine A(2A) receptor, human; mutation; glutamic acid; CGS21680; XAC; amiloride ID PROTEIN-COUPLED RECEPTORS; BINDING; ANTAGONIST AB A glutamic acid residue in the first transmembrane domain of the human adenosine A(2A) receptor was mutated to glutamine. Radioligand binding studies on COS-7 cell membranes expressing either the wild-type or the mutant receptor revealed that the affinity of the prototypic agonist CGS21680 (2-[4-[(2-carboxyethyl)phenyl]ethylamino]-5'-N-ethylcarboxamidoadenosine) for the mutant receptor was 15-fold lower than for the wild-type receptor. This was confirmed in functional studies with intact cells. The EC(50) values of CGS21680 for the stimulation of cAMP production differed in a similar way. Antagonists of various chemical structure were equally effective on both mutant and wild-type receptors, thus the mutation selectively diminishes agonist affinity, We propose an indirect perturbation of the binding site, perhaps through a proton transfer mechanism as suggested by molecular modelling. C1 NIDDK, MOL RECOGNIT SECT, BIOORGAN CHEM LAB, NIH, BETHESDA, MD 20892 USA. RP Ijzerman, AP (reprint author), LEIDEN AMSTERDAM CTR DRUG RES, DIV MED CHEM, POB 9502, NL-2300 RA LEIDEN, NETHERLANDS. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 11 TC 27 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 29 PY 1996 VL 310 IS 2-3 BP 269 EP 272 DI 10.1016/0014-2999(96)00495-5 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VG697 UT WOS:A1996VG69700023 PM 8884226 ER PT J AU Abenhaim, L Moride, Y Brenot, F Rich, S Benichou, J Kurz, X Higenbottam, T Oakley, C Wouters, E Aubier, M Simonneau, G Begaud, B AF Abenhaim, L Moride, Y Brenot, F Rich, S Benichou, J Kurz, X Higenbottam, T Oakley, C Wouters, E Aubier, M Simonneau, G Begaud, B TI Appetite-suppressant drugs and the risk of primary pulmonary hypertension SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FENFLURAMINE; INFECTION AB Background Recently in France, primary pulmonary hypertension developed in a cluster of patients exposed to derivatives of fenfluramine in appetite suppressants (anorexic agents), which are used for weight control. We investigated the potential role of anorexic agents and other suspected risk factors for primary pulmonary hypertension. Methods In a case-control study, we assessed 95 patients with primary pulmonary hypertension from 35 centers in France, Belgium, the United Kingdom, and the Netherlands and 355 controls recruited from general practices and matched to the patients' sex and age. Results The use of anorexic drugs (mainly derivatives of fenfluramine) was associated with an increased risk of primary pulmonary hypertension (odds ratio with any anorexic-drug use, 6.3; 95 percent confidence interval, 3.0 to 13.2). For the use of anorexic agents in the preceding year, the odds ratio was 10.1 (95 percent confidence interval, 3.4 to 29.9). When anorexic drugs were used for a total of more than three months, the odds ratio was 23.1 (95 percent confidence interval, 6.9 to 77.7). We also confirmed an association with several previously identified risk factors: a family history of pulmonary hypertension, infection with the human immunodeficiency virus, cirrhosis, and use of cocaine or intravenous drugs. Conclusions The use of anorexic drugs was associated with the development of primary pulmonary hypertension. Active surveillance for this disease should be considered, particularly since the use of anorexic drugs is expected to increase in the near future. (C) 1996, Massachusetts Medical Society. C1 MCGILL UNIV,CTR CLIN EPIDEMIOL & COMMUNITY STUDIES,MONTREAL,PQ H3T 1E2,CANADA. ANTOINE BECLERE HOSP,SERV PNEUMOL,CLAMART,FRANCE. UNIV ILLINOIS,DEPT SURG,CARDIOL SECT,CHICAGO,IL 60680. NCI,ROCKVILLE,MD. CHU LIEGE,INST PATHOL,PHARMACOL LAB,LIEGE,BELGIUM. UNIV SHEFFIELD,SECT RESP MED,SHEFFIELD S10 2TN,S YORKSHIRE,ENGLAND. HAMMERSMITH HOSP,DEPT CARDIOL,LONDON,ENGLAND. UNIV HOSP MAASTRICHT,DEPT PULMONOL,MAASTRICHT,NETHERLANDS. HOP XAVIER BICHAT,SERV PNEUMOL,PARIS,FRANCE. PELLEGRIN HOSP,CTR PHARMACOVIGILANCE,BORDEAUX,FRANCE. RP Abenhaim, L (reprint author), SIR MORTIMER B DAVIS JEWISH HOSP,CTR CLIN EPIDEMIOL & COMMUNITY STUDIES,MONTREAL,PQ H3T 1E2,CANADA. NR 27 TC 772 Z9 798 U1 0 U2 12 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 29 PY 1996 VL 335 IS 9 BP 609 EP 616 DI 10.1056/NEJM199608293350901 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VD425 UT WOS:A1996VD42500001 PM 8692238 ER PT J AU Zhou, YF Leon, MB Waclawiw, MA Popma, JJ Yu, ZX Finkel, T Epstein, SE AF Zhou, YF Leon, MB Waclawiw, MA Popma, JJ Yu, ZX Finkel, T Epstein, SE TI Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ENDOTHELIAL-CELLS; ANGIOPLASTY; SURFACE; VIRUS; ATHEROSCLEROSIS; FIBROBLASTS; ADHESION AB Background Restenosis occurs commonly after coronary angioplasty and atherectomy, but the causes of restenosis are poorly understood. Recently, it has been found that cytomegalovirus (CMV) DNA is present in restenotic lesions from atherectomy specimens. This and other evidence suggest that CMV may have a role in the process of restenosis. Methods We prospectively studied 75 consecutive patients undergoing directional coronary atherectomy for symptomatic coronary artery disease. Before atherectomy was performed, we measured blood levels of anti-CMV IgG antibodies to determine whether previous exposure to CMV increased the risk of restenosis, as determined by coronary angiography performed six months after atherectomy. Results After atherectomy, the mean (+/-SD) minimal luminal diameter of the target vessel was greater in the 49 patients who were seropositive for CMV than in the 26 patients who were seronegative (3.18+/-0.51 mm vs. 2.89+/-0.45 mm, P=0.01). After six months, however, the seropositive patients had a greater reduction in the luminal diameter (1.24+/-0.83 mm vs, 0.68+/-0.69 mm, P=0.003), resulting in a significantly higher rate of restenosis in the seropositive patients (43 percent vs. 8 percent, P=0.002). In a multivariable logistic-regression model, CMV seropositivity and the CMV titer were independently predictive of restenosis (odds ratios, 12.9 and 8.1, respectively). There was no evidence of acute infection, since the titer of anti-CMV IgG antibodies did not increase over time and tests for anti-CMV IgM antibodies were negative in all patients. Conclusions Prior infection with CMV is a strong independent risk factor for restenosis after coronary atherectomy. If confirmed, these findings may help identify patients at risk for restenosis. (C) 1996, Massachusetts Medical Society. C1 NHLBI, CARDIOL BRANCH, BETHESDA, MD 20892 USA. WASHINGTON HOSP CTR, WASHINGTON, DC 20010 USA. NR 31 TC 382 Z9 396 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 29 PY 1996 VL 335 IS 9 BP 624 EP 630 DI 10.1056/NEJM199608293350903 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VD425 UT WOS:A1996VD42500003 PM 8687516 ER PT J AU Farci, P Alter, HJ Shimoda, A Govindarajan, S Cheung, LC Melpolder, JC Sacher, RA Shih, JW Purcell, RH AF Farci, P Alter, HJ Shimoda, A Govindarajan, S Cheung, LC Melpolder, JC Sacher, RA Shih, JW Purcell, RH TI Hepatitis C virus-associated fulminant hepatic failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID POLYMERASE CHAIN-REACTION; NON-B HEPATITIS; NON-A; VIRAL-HEPATITIS; LIVER-FAILURE; RNA; DNA AB FULMINANT hepatic failure is a dramatic clinical syndrome characterized by massive necrosis of liver cells.(1) It is most often caused by hepatitis A virus and hepatitis B virus (HBV)(2); whether hepatitis C virus (HCV) can cause it is still controversial.(3,4) Among patients with non-A, non-B fulminant hepatitis, antibodies against HCV (anti-HCV) or serum HCV RNA were found in 40 to 60 percent in Japan(5,6) and Taiwan,(7) but in only 2 percent (range, 0 to 12 percent) in Western countries,(8-13) with one exception: a recent study conducted in California reported a prevalence of 60 percent associated with low socioeconomic status and Hispanic ethnicity.(14) Whether these discrepancies reflect geographic differences in the epidemiology of HCV infection or the pathogenicity of the prevalent viral strains is not known. Furthermore, because of the dramatic course of fulminant hepatic failure, in most patients only a single serum sample, often obtained late in the course of the disease, was studied. In this report, we describe a patient with HCV-associated fulminant hepatitis in whom serial studies were done that provided a unique opportunity to establish a temporal association between the acquisition of HCV infection and the development of fulminant hepatitis and to define the clinical, virologic, and histologic profile of fulminant hepatitis C. C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. UNIV SO CALIF,RANCHO LOS AMIGOS MED CTR,DEPT PATHOL,DOWNEY,CA 90242. GEORGETOWN UNIV,MED CTR,DIV CLIN & LAB SERV,WASHINGTON,DC 20007. NR 28 TC 98 Z9 99 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 29 PY 1996 VL 335 IS 9 BP 631 EP 634 DI 10.1056/NEJM199608293350904 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VD425 UT WOS:A1996VD42500004 PM 8687517 ER PT J AU Winer, KK Yanovski, JA Cutler, GB AF Winer, KK Yanovski, JA Cutler, GB TI Synthetic human parathyroid hormone 1-34 vs calcitriol and calcium in the treatment of hypoparathyroidism - Results of a short-term randomized crossover trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID VITAMIN-D; BONE; 1,25-DIHYDROXYVITAMIN-D3; OSTEOPOROSIS; CHILDREN; FRAGMENT AB Objective.-To test the hypothesis that treatment with human parathyroid hormone 1-34 (PTH 1-34) can maintain normal serum calcium without hypercalciuria in patients with hypoparathyroidism. Design.-Randomized crossover trial lasting 20 weeks. Each 10-week arm consisted of a 2-week inpatient dose-adjustment phase followed by an 8-week outpatient phase. Setting.-Tertiary care center. Patients.-A total of 10 patients with hypoparathyroidism were enrolled consecutively over a 15-month period. Half of the patients were prior National Institutes of Health patients, and the other 5 patients were referred from outside physicians. Interventions.-A dose of PTH 1-34 was administered each morning by subcutaneous injection. Calcitriol was given orally twice daily with supplemental calcium carbonate. Main Outcome Measures.-Serum and urine calcium and phosphorus levels. Results.-Once-daily treatment with PTH 1-34 maintained serum calcium in the normal range with decreased urine calcium excretion (P<.05 at 2 weeks and P<.01 at 10 weeks) compared with calcitriol treatment. Biochemical markers of bone turnover increased significantly (P<.01 at 10 weeks) during PTH 1-34 treatment. Conclusions.-Treatment of hypoparathyroidism with PTH 1-34 reduces urine calcium excretion compared with treatment with calcitriol and calcium. RP Winer, KK (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,SDE,NIH,BLDG 10,ROOM 10N262,10 CTR DR,MSC 1862,BETHESDA,MD 20892, USA. NR 26 TC 83 Z9 87 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 28 PY 1996 VL 276 IS 8 BP 631 EP 636 DI 10.1001/jama.276.8.631 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VC853 UT WOS:A1996VC85300030 PM 8773636 ER PT J AU Hu, JS Bax, A AF Hu, JS Bax, A TI Measurement of three-bond C-13-C-13 J couplings between carbonyl and carbonyl/carboxyl carbons in isotopically enriched proteins SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CALCIUM-FREE CALMODULIN; METHYL-GROUPS; ASSIGNMENT; RESOLUTION; CONSTANTS; RESIDUES; BACKBONE C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 17 TC 62 Z9 62 U1 0 U2 4 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 AUG 28 PY 1996 VL 118 IS 34 BP 8170 EP 8171 DI 10.1021/ja9616239 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA VE266 UT WOS:A1996VE26600046 ER PT J AU Galazka, G Windsor, LJ BirkedalHansen, H Engler, JA AF Galazka, G Windsor, LJ BirkedalHansen, H Engler, JA TI APMA (4-aminophenylmercuric acetate) activation of stromelysin-1 involves protein interactions in addition to those with cysteine-75 in the propeptide SO BIOCHEMISTRY LA English DT Article ID MATRIX METALLOPROTEINASE-3 STROMELYSIN; HUMAN FIBROBLAST COLLAGENASE; LATENT COLLAGENASE; MUTATIONAL ANALYSIS; TISSUE INHIBITOR; RNA-POLYMERASE; PLASMID DNA; ACTIVE-SITE; CELLS; EXPRESSION AB Matrix metalloproteinases (MMPs) can be activated in vitro by multiple mechanisms such as treatment with proteases, organomercurials, oxidants, and detergents. The proposed cysteine switch model for activation suggests that these multiple methods for activation cause the dissociation of the single cysteine residue. In the propeptide from the active site zinc. In particular, it has been suggested that organomercurials such as 3-aminophenylmercuric acetate (APMA) work by directly reacting with the sulfhydryl group of this cysteine residue, resulting in its displacement from the active site. However, recent data by Chen et al. [(1993) Biochemistry 32, 10289-10295] demonstrated that modification of this cysteine residue in the propeptide of stromelysin-l by sulfhydryl reagents did not result in an active enzyme as predicted. To investigate the roles that this cysteine residue and the propeptide salt bridge (R74 to D79) might play in the APMA-induced activation of stromelysin-l, we have changed these residues by site-directed mutagenesis. Wild-type stromelysin-l and the mutants were all expressed at detectable levels using a recombinant vaccinia virus system and determined to be catalytically competent by zymography. The wild-type stromelysin-l and the cysteine mutants (C75S and C75H) underwent APMA-induced activation as determined by the characteristic reduction in molecular weight associated with activation and by their ability to cleave casein only when activated, On the other hand, mutants R74K, D79A, and C75H/D79A did not undergo APMA-induced activation. These results demonstrate that APMA-induced activation of stromelysin-l involves protein interactions in addition to those with cysteine-75 in the propeptide and also suggest that the R74 to D79 salt bridge may play a role. C1 UNIV ALABAMA, ORAL BIOL RES CTR, BIRMINGHAM, AL 35294 USA. UNIV ALABAMA, DEPT BIOCHEM & MOL GENET, BIRMINGHAM, AL 35294 USA. NIDR, NIH, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA-13148]; NIDCR NIH HHS [R01 DE10631, P50 DE08228] NR 42 TC 51 Z9 51 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 27 PY 1996 VL 35 IS 34 BP 11221 EP 11227 DI 10.1021/bi960618e PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE299 UT WOS:A1996VE29900026 PM 8780527 ER PT J AU Marin, C Engber, TM Bonastre, M Chase, TN Tolosa, E AF Marin, C Engber, TM Bonastre, M Chase, TN Tolosa, E TI Effect of long-term haloperidol treatment on striatal neuropeptides: Relation to stereotyped behavior SO BRAIN RESEARCH LA English DT Article DE haloperidol; stereotypy; enkephalin; somatostatin; dynorphin; substance P ID PROENKEPHALIN MESSENGER-RNA; ANTI-SCHIZOPHRENIC DRUGS; NEUROLEPTIC TREATMENT; ENKEPHALIN CONTENT; BASAL GANGLIA; RAT STRIATUM; SUBSTANCE-P; DOPAMINE-RECEPTORS; MOLECULAR-BIOLOGY; BRAIN AB Behavioral and biochemical responses to D-1 and D-2 dopamine (DA) agonists were used to evaluate the participation of striatal peptidergic mechanisms in the motor function alterations that attend chronic neuroleptic :treatment. Rats, given haloperidol (1 mg/kg, s.c.) for 21 consecutive days, were randomly allocated to one of the following treatments: the D-1 agonist SKF 38393, the D-2 agonist quinpirole, their combination or saline. Stereotyped behavior and neuropeptide levels were evaluated after 5 days treatment and 4 days washout. Haloperidol increased most oral behaviors including licking, chewing and biting as well as striatal enkephalin and somatostatin levels. Subsequent treatment with SKF 38393 diminished the haloperidol-induced increase in licking and chewing; quinpirole reduced chewing behavior. The administration of both agonists together decreased chewing and biting. Neither DA agonist alone, nor their combination, reduced the haloperidol-induced increase in enkephalin levels. Both SKF 38393 and quinpirole, when given alone, tended to decrease the haloperidol-induced increase in somatostatin levels; when both the D, and D, agonists were administered together, somatostatin levels declined significantly. These results suggest that somatostatin- but not enkephalin-containing striatal neurons contribute to the expression of haloperidol-induced stereotypies. C1 NINCDS,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. RP Marin, C (reprint author), UNIV BARCELONA,HOSP CLIN,SERV NEUROL,DEPT MED,LAB NEUROL EXPT,VILLARROEL 170,BARCELONA 08036,SPAIN. NR 43 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 26 PY 1996 VL 731 IS 1-2 BP 57 EP 62 DI 10.1016/0006-8993(96)00461-1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA VH448 UT WOS:A1996VH44800007 PM 8883854 ER PT J AU Matsuoka, N Aigner, TG AF Matsuoka, N Aigner, TG TI The glycine/NMDA receptor antagonist HA-966 impairs visual recognition memory in rhesus monkeys SO BRAIN RESEARCH LA English DT Article DE visual recognition memory; delayed nonmatching-to-sample; cognitive impairment; NMDA receptor; glycine receptor; HA-966; MK-801; monkey ID LONG-TERM POTENTIATION; D-ASPARTATE RECEPTOR; EXCITATORY AMINO-ACIDS; NMDA RECEPTOR; D-CYCLOSERINE; ALZHEIMERS-DISEASE; RAT HIPPOCAMPUS; MODULATORY SITE; LEARNING-TASKS; BINDING-SITES AB Recent studies have shown that strychnine-insensitive glycine binding sites positively modulate the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors, which are important in neural pathways involved in cognitive function. We examined the effect of (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), a highly specific antagonist of this glycine modulatory site on the NMDA receptor, on visual recognition memory in four rhesus monkeys performing a computer-automated version of delayed nonmatching-to-sample (DNMS) with a list length of 20 trial-unique graphic symbols. In addition, the effect of HA-966 was compared with that of (+)-5-methyl-10,11-dihydro -5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine; MK-801), a noncompetitive NMDA channel blocker. Administration of HA-966 (0.1-10 mg/kg, i.m.) 30 min before testing impaired DNMS performance dose-dependently, starting at doses of 3.2 mg/kg; the memory deficit following the highest dose (10 mg/kg) was associated with prolonged response latencies. Similar impairments in recognition memory were observed following treatment with MK-801, though at much lower doses (3.2-32 mu g/kg) than those at which HA-966 was effective. Administration of low doses of HA-966 (1 mg/kg) and MK-801 (10 mu g/kg), each of which had no significant effect on performance when given alone, also failed to impair performance when given concurrently. Combined administration of both drugs, each at amnesia-producing doses (3.2 mg/kg of HA-966 plus 32 mu g/kg of MK-801), markedly impaired performance in an additive, not a synergistic, manner. From these results, we propose that the recognition memory impairment observed in our monkeys following HA-966 administration is via an action on the glycine modulatory site of the NMDA receptor complex. C1 NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. NR 47 TC 14 Z9 14 U1 2 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 AUG 26 PY 1996 VL 731 IS 1-2 BP 72 EP 78 DI 10.1016/S0006-8993(96)00463-5 PG 7 WC Neurosciences SC Neurosciences & Neurology GA VH448 UT WOS:A1996VH44800009 PM 8883856 ER PT J AU Cheng, PY Moriwaki, A Wang, JB Uhl, GR Pickel, VM AF Cheng, PY Moriwaki, A Wang, JB Uhl, GR Pickel, VM TI Ultrastructural localization of mu-opioid receptors in the superficial layers of the rat cervical spinal cord: Extrasynaptic localization and proximity to Leu(5)-enkephalin SO BRAIN RESEARCH LA English DT Article DE ultrastructure; anatomy; analgesia; neurotransmitter; afferent ID SUBSTANTIA-GELATINOSA NEURONS; CENTRAL NERVOUS-SYSTEM; DORSAL HORN; OPIATE RECEPTOR; BINDING-SITES; AUTORADIOGRAPHIC LOCALIZATION; IMMUNOCYTOCHEMICAL LOCALIZATION; IMMUNOREACTIVE DYNORPHIN; METHIONINE-ENKEPHALIN; NEUTRAL ENDOPEPTIDASE AB Many of the analgesic effects of opiate drugs and of endogenous opioid ligands, such as Leu(5)-enkephalin (LE) are thought to be mediated in part by mu-opioid receptors (MOR) in the dorsal horn of the spinal cord. To establish the cellular sites for the spinally mediated analgesic effects of MOR activation and the potential anatomical substrates for interactions with LE, we examined the ultrastructural localization of MOR and LE immunoreactivities in the adult rat cervical spiral cord (C3-C5), Anti-MOR sera-recognizing the carboxyl terminal domain of MOR was localized using immunoperoxidase and immunogold-silver methods. CL-opioid receptor-like immunoreactivity (MOR-LI) was observed mainly in the superficial layers of the dorsal horn. Electron microscopy of this region revealed that small unmyelinated axons and axon terminals constituted 48% (91/189) and 15% (TL8/189), respectively, while dendrites comprised 36% (68/189) of the total population of neuronal profiles containing the MOR. MOR-LI was localized mainly along extrasynaptic portions of the plasma membrane in both axons and dendrites. In sections dually labeled, for MOR and LE, 21% (14/68) of the dendrites containing MOR-LI closely apposed or received synaptic contact from axon terminals :exhibiting LE reaction product. The results provide the first ultrastructural evidence that within the dorsal horn of the spinal cord, LE, as well as exogenous opiates may alter both axonal release of neurotransmitters and postsynaptic responsiveness of target neurons to aff:trent input through activation of extrasynaptic MOR. C1 NIDA,INTRAMURAL RES PROGRAM,MOL NEUROBIOL BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. RP Cheng, PY (reprint author), CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,411 E 69TH ST,NEW YORK,NY 10021, USA. FU NHLBI NIH HHS [HL 18974]; NIDA NIH HHS [DA04600]; NIMH NIH HHS [MH00078] NR 73 TC 47 Z9 49 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 26 PY 1996 VL 731 IS 1-2 BP 141 EP 154 DI 10.1016/S0006-8993(96)00492-1 PG 14 WC Neurosciences SC Neurosciences & Neurology GA VH448 UT WOS:A1996VH44800017 PM 8883864 ER PT J AU Maurice, T Lockhart, BP Su, TP Privat, A AF Maurice, T Lockhart, BP Su, TP Privat, A TI Reversion of beta(25-35)-amyloid peptide-induced amnesia by NMDA receptor-associated glycine site agonists SO BRAIN RESEARCH LA English DT Article DE D-cycloserine; milacemide; NMDA/glycine site; beta-amyloid; amnesia ID D-ASPARTATE RECEPTOR; D-CYCLOSERINE; ALZHEIMERS-DISEASE; ENHANCES PERFORMANCE; LEARNING-TASKS; MILACEMIDE; ACTIVATION; BLOCKADE; COMPLEX; PRODRUG AB The effects of D-cycloserine (DCS), a N-methyl-D-aspartate receptor-associated glycine site agonist, and milacemide (MIL), a glycine prodrug, were examined on learning impairments induced by administration of beta(25-35)-amyloid peptide (3 nmol i.c.v.). Mice were examined for spontaneous alternation and step-down passive avoidance, 7 and 14 days after beta(25-35), respectively. The beta(25-35)-induced deficits were reversed by DCS, 1-30 mg/kg i.p., or MIL, 3-100 mg/kg i.p., each drug being ineffective on control mice behaviours. These observations strengthen the therapeutic potential of glycine site agonists against the memory impairments induced by beta-amyloid peptides. C1 NIDA,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD 21224. RP Maurice, T (reprint author), ECOLE NATL SUPER CHIM MONTPELLIER,INSERM U336,8 RUE ECOLE NORMALE,F-34053 MONTPELLIER,FRANCE. NR 23 TC 43 Z9 44 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 26 PY 1996 VL 731 IS 1-2 BP 249 EP 253 DI 10.1016/S0006-8993(96)00710-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA VH448 UT WOS:A1996VH44800034 PM 8883881 ER PT J AU Petralia, RS Wang, YX Zhao, HM Wenthold, RJ AF Petralia, RS Wang, YX Zhao, HM Wenthold, RJ TI Ionotropic and metabotropic glutamate receptors show unique postsynaptic, presynaptic, and glial localizations in the dorsal cochlear nucleus SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE NMDA; AMPA; kainate; delta; auditory ID CENTRAL-NERVOUS-SYSTEM; UNIPOLAR BRUSH CELL; ELECTRON-MICROSCOPIC IMMUNOCYTOCHEMISTRY; SUBUNIT-SPECIFIC ANTIBODIES; RAT CEREBELLAR CORTEX; LONG-TERM DEPRESSION; GUINEA-PIG; INTRACELLULAR-RECORDINGS; BINDING-SITES; MESSENGER-RNA AB The dorsal cochlear nucleus (DCN) is a major brain center for integration of auditory information, and excitatory amino acid neurotransmission plays a central role in the processing of this information. In this study, the distribution of glutamate receptors was examined with preembedding immunocytochemistry. using 14 antibodies to ionotropic (GluR1, GluR2/3, GluR4, GluR5-7, GluR6/7, KA2, NR1, NR2A/B, delta 1/2) and metabotropic (mGluR1 alpha, mGluR2/3, mGluR5) glutamate receptor subtypes. Each of these antibodies produced a specific immunolabeling pattern, including a variety of post-synaptic, presynaptic, and glial localizations, Some antibodies showed widespread distribution patterns, notably the antibodies to the alpha-amiao-3-hydroxy-5-methyl-4-isoxazolepropinate (AMPA) receptor subunits, GluR2 and GluR3, and the N-methyl-D-aspartate (NMDA) receptor subunit, NR1. In contrast, antibodies to other glutamate receptor subunits produced more restricted distribution patterns, especially that to GluR1, which stained the outer neuropil of the DCN, cartwheel cells, and a small population of presumptive interneurons associated with the dorsal acoustic stria, but produced little or no staining in fusiform cells or deep DCN neurons. Staining of the postsynaptic density and membrane of the granule cell-parallel fiber/cartwheel cell spine synapse was most prevalent with delta 1/2 and mGluR1 alpha antibodies, a unique pattern of staining was found with mGluR2/3 antibody-with staining concentrated in Golgi cells and unipolar brush cells of the middle to deep DCN, Distribution of some glutamate receptors in the DCN shows similarities to that of the cerebellum, where delta 2 and mGluR1 alpha may modulate neurotransmission at parallel fiber synapses, while mGluR2 and/or mGluR3 may modulate messy terminal function. (C) 1996 Wiley-Liss, Inc.* RP Petralia, RS (reprint author), NIDCD, NIH,NEUROCHEM LAB,36-5D08,36 CONVENT DR, MSC 4162, BETHESDA, MD 20892 USA. NR 117 TC 109 Z9 109 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 26 PY 1996 VL 372 IS 3 BP 356 EP 383 PG 28 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VD567 UT WOS:A1996VD56700003 PM 8873866 ER PT J AU Burke, RE Glenn, LL AF Burke, RE Glenn, LL TI Horseradish peroxidase study of the spatial and electrotonic distribution of group Ia synapses on type-identified ankle extensor motoneurons in the cat SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE spinal cord; light microscopy; anatomical reconstruction ID LUMBOSACRAL SPINAL-CORD; MOTOR UNIT TYPE; ALPHA-MOTONEURONS; SYNAPTIC POTENTIALS; AFFERENT-FIBERS; MEDIAL GASTROCNEMIUS; TRICEPS SURAE; TIME COURSE; HETERONYMOUS MOTONEURONS; EPSPS AB Eight functionally identified group Ia muscle afferents from triceps surae or plantaris muscles were labeled intraaxonally with horseradish peroxidase (HRP) in seven adult cats. Subsequently, HRP was injected into two to six homonymous or heteronymous alpha-motoneurons per animal (total = 22), each identified by motor unit type and located near the site of afferent injection. The complete trajectories of labeled afferents were reconstructed, and putative synaptic contacts on HRP-labeled motoneurons were identified at high magnification. Dendritic paths from each contact were also mapped and measured. A total of 24 contact systems (the combination of a group Ia afferent and a postsynaptic motoneuron) were reconstructed, of which 17 were homonymous, and seven were heteronymous. Overall, homonymous contact systems had an average of 9.6 boutons, whereas heteronymous contact systems had an average of 5.9 boutons. The average number of boutons found on type S motoneurons in homonymous contact systems was smaller (6.4, range 3-17) than in systems involving types FF or FR motoneurons (FF: 10.4, range 4-18; FR: 11.3, range 4-32). Neither of these differences were statistically significant. In contrast to earlier reports, a majority (15/24) of contact systems included more than one collateral from the same Ia afferent. The complexity (number of branch points) in the arborization pathway leading to each contact (overall mean 8.4 +/- 3.3) was virtually identical in all contact systems, irrespective of the type of the postsynaptic motoneuron. The three-dimensional distribution of group Ia contacts was not coextensive with the radially organized dendrites of motoneurons: Dendrites oriented in the ventromedial to dorsolateral axis had the fewest (8%) contacts, whereas rostrocaudal dendrites had the most (63%) contacts. Nevertheless, contacts were widely distributed on the motoneuron surface, with few on and near the soma (less than or equal to 200 mu m radial distance from the soma) or on the most distal parts of the tree (greater than or equal to 1,000 mu m) The boutons in individual contact systems also showed wide spatial and estimated electrotonic distributions; only 3/24 systems had all contact located within a restricted spatial/electrotonic region. The relations between these anatomical results and existing electrophysiological data on group Ia synaptic potentials are discussed. (C) 1996 Wiley-Liss, Inc. RP Burke, RE (reprint author), NINCDS,NIH,NEURAL CONTROL LAB,BLDG 49,ROOM 3A50,BETHESDA,MD 20892, USA. NR 57 TC 74 Z9 74 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 AUG 26 PY 1996 VL 372 IS 3 BP 465 EP 485 PG 21 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VD567 UT WOS:A1996VD56700009 PM 8873872 ER PT J AU Darden, T Pedersen, L AF Darden, T Pedersen, L TI Use of fast Ewald summation in molecular dynamics simulations SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS,NIH,RES TRIANGLE PK,NC 27709. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 6 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501394 ER PT J AU Rich, RH Kirk, KL AF Rich, RH Kirk, KL TI Preparation of fluorinated dopamine beta-hydroxylase irreversible inhibitors as positron emission tomography agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 6 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91502564 ER PT J AU Johnson, SC Tuinman, A Tagliaferri, F Moyer, JD Baker, DC AF Johnson, SC Tuinman, A Tagliaferri, F Moyer, JD Baker, DC TI 5-deoxy-5-fluoro-1-O-phosphatidylinositol: Evidence for the enzymatic incorporation of a fraudulent cyclitol into the PtdIns cycle. A FAB mass spectrometric study. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV TENNESSEE,DEPT CHEM,KNOXVILLE,TN 37996. NCI,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 11 EP CARB PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500495 ER PT J AU Szeliga, J Amin, S Hilton, BD Chmurny, GN Dipple, A AF Szeliga, J Amin, S Hilton, BD Chmurny, GN Dipple, A TI Identification and characterization of DNA adducts formed by syn and anti 5,6-dimethylchrysene 1,2-dihydrodiol 3,4-epoxide. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC INC,FREDERICK,MD 21702. AMER HLTH FDN,VALHALLA,NY 10595. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 13 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501049 ER PT J AU Brooks, BR AF Brooks, BR TI Macromolecular dynamics: Insights from simulation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 DCRT,STRUCT BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 15 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501403 ER PT J AU Li, G Waltham, M Unsworth, E Treston, A Anderson, NL Weinstein, JN AF Li, G Waltham, M Unsworth, E Treston, A Anderson, NL Weinstein, JN TI Protein identification in 2D-page using MALDI-MS. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. LARGE SCALE BIOL CORP,ROCKVILLE,MD 20850. RI Waltham, Mark/A-1728-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 20 EP PHYS PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VB009 UT WOS:A1996VB00900525 ER PT J AU Zhao, H Neamati, N Mazumder, A Pommier, Y Burke, TR AF Zhao, H Neamati, N Mazumder, A Pommier, Y Burke, TR TI Design, synthesis and structure-activity relationship of HIV-1 integrase inhibitors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 21 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91502579 ER PT J AU Hong, HX Neamati, N Wang, SM Nicklaus, M Pommier, Y Milne, GWA AF Hong, HX Neamati, N Wang, SM Nicklaus, M Pommier, Y Milne, GWA TI Discovery of novel HIV-1 integrase inhibitors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 22 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91502580 ER PT J AU Bansal, M CasasFinet, J Cholody, WM Michejda, CJ AF Bansal, M CasasFinet, J Cholody, WM Michejda, CJ TI Bisimidazoacridone binding to nucleic acids: Thermodynamic, kinetic, spectroscopic, and electrophoretic mobility studies. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 BRP,ABL,FREDERICK,MD 21702. SAIC,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 23 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501059 ER PT J AU Farnsworth, DW Blumenstein, JJ Hernandez, LF Michejda, CJ AF Farnsworth, DW Blumenstein, JJ Hernandez, LF Michejda, CJ TI Haloacyl bistriazenes: Novel potent cytotoxic agents which interact with nucleic acids. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. SAIC,AIDS VACCINE PROGRAM,TITUSVILLE,NJ 08560. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 24 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501060 ER PT J AU Gupta, PK Blumbergs, P Sun, H Varma, RK AF Gupta, PK Blumbergs, P Sun, H Varma, RK TI Synthetic analogs of calanolide A and their antiviral activities SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ASH STEVENS INC,DETROIT,MI 48202. NCI,PHARMACEUT RESOURCES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 24 EP MEDI PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91502582 ER PT J AU Porter, DW Nelson, VC Fivash, MJ Kasprzak, KS AF Porter, DW Nelson, VC Fivash, MJ Kasprzak, KS TI MutT-catalyzed hydrolysis of promutagenic 8-oxo-dGTP is inhibited by Ni(II).1 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 26 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501062 ER PT J AU Milne, GWA AF Milne, GWA TI Mathematics as a basis for chemistry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 33 EP CINF PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501014 ER PT J AU Mathews, JM Garner, CE Matthews, HB AF Mathews, JM Garner, CE Matthews, HB TI Metabolism of diethanolamine and formation of aberrant lipids. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 RES TRIANGLE INST,CTR BIOORGAN CHEM,RES TRIANGLE PK,NC 27709. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 34 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501070 ER PT J AU Pohl, LR AF Pohl, LR TI Immunochemical methods for detecting and characterizing tissue protein adducts of the nonsteroidal antiinflammatory drug diclofenac. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NHLBI,MOL & CELLULAR TOXICOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 36 EP TOXI PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501072 ER PT J AU Schwab, JM Smith, JL Leesong, M Sathyanarayana, BK AF Schwab, JM Smith, JL Leesong, M Sathyanarayana, BK TI Reevaluation of the link between enzyme mechanism and reaction stereochemistry for a dehydratase-allylic isomerase SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 PURDUE UNIV,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907. PURDUE UNIV,DEPT BIOL SCI,W LAFAYETTE,IN 47907. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 37 EP BIOL PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91502872 ER PT J AU Tsao, LI Su, TP AF Tsao, LI Su, TP TI Chromatographic purification of sigma receptors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA,NEUROCHEM UNIT,MOLEC NEUROPSYCHIAT SECT,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 39 EP ANYL PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500285 ER PT J AU Wu, C Brechbiel, MW Gansow, OA Carrasquillo, J Pastan, I AF Wu, C Brechbiel, MW Gansow, OA Carrasquillo, J Pastan, I TI Synthesis and evaluation of the four stereoisomers of 2-(p-nitrobenzyl)-trans-CyDTPA for radiolabeling immunoprotein with yttrium-90 and bismuth-212/213 for radioimmunotherapy. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,RADIAT ONCOL BRANCH,CHEM SECT,NIH,CC,DEPT NUCL MED,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 40 EP NUCL PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91502806 ER PT J AU Bal, W Moudrianakis, EN Lukszo, A Kasprzak, KS AF Bal, W Moudrianakis, EN Lukszo, A Kasprzak, KS TI Binding of carcinogenic nickel to histones. Structural and mechanistic studies. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. NIAID,MOL STRUCT LAB,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 46 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501082 ER PT J AU Gupta, PK Varma, RK AF Gupta, PK Varma, RK TI Synthesis and anticancer activity of dolastatin 10 mimic. Dolaphenine androstane. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ASH STEVENS INC,DETROIT,MI 48202. NCI,PHARMACEUT RESOURCES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 46 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91502604 ER PT J AU Hodosi, G Kovac, P AF Hodosi, G Kovac, P TI Facile access to some rare carbohydrate derivatives via stannylene acetals of free carbohydrates SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,LMC,SC,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 51 EP CARB PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500537 ER PT J AU Bell, DA AF Bell, DA TI Role of N-acetyltransferase polymorphisms (NAT1 and NAT2) in aromatic amine-associated cancers SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 52 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501088 ER PT J AU Dhume, ST Das, PC Klein, JLD Palmantier, R Roberts, JD Olden, K AF Dhume, ST Das, PC Klein, JLD Palmantier, R Roberts, JD Olden, K TI Swainsonine internalization in macrophage, bone marrow progenitor cell and breast cancer cell lines. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 59 EP CARB PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500547 ER PT J AU Wu, C Brechbiel, MW Gansow, OA AF Wu, C Brechbiel, MW Gansow, OA TI An improved generator for the production of Bi-213 from Ac-225 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,CHEM SECT,RADIAT ONCOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 61 EP NUCL PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91502827 ER PT J AU Shibusawa, Y AF Shibusawa, Y TI Purification of lactate dehydrogenase from bovine heart crude extract by countercurrent chromatography. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV TOKYO,SCH PHARM,DEPT ANALYT CHEM,HACHIOJI,TOKYO 19203,JAPAN. NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 4 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 64 EP ANYL PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500309 ER PT J AU Dipple, A AF Dipple, A TI Polycyclic aromatic hydrocarbon-DNA adducts and biological response. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 73 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501109 ER PT J AU Jerina, DM Schwartz, JL Rice, JS Luxon, BA Yeh, HJC Liu, X Sayer, JM Yagi, H Gorenstein, DG AF Jerina, DM Schwartz, JL Rice, JS Luxon, BA Yeh, HJC Liu, X Sayer, JM Yagi, H Gorenstein, DG TI Solution structure of a minor conformer of a benzo[a]-pyrene-DNA adduct SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,NIH,BETHESDA,MD 20892. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77555. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 78 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501114 ER PT J AU Pei, XF Badio, B Daly, JW AF Pei, XF Badio, B Daly, JW TI Tropane derivatives: Syntheses and binding properties to nicotinic and muscarinic receptors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 80 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91502638 ER PT J AU Foster, RS Haberman, CB Hazard, GM AF Foster, RS Haberman, CB Hazard, GM TI Navigating your way through the National Library of Medicines TEHIP files via the Internet. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ORISE,EDUC & TRAINING DIV,OAK RIDGE,TN 37831. NATL LIB MED,DIV SPECIALIZED INFORMAT,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 82 EP ENVR PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501709 ER PT J AU Klausner, RD AF Klausner, RD TI Exploring the biology of transition metals. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 94 EP BIOL PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91500468 ER PT J AU Jacobson, KA vanRhee, AM Jiang, L Ji, XD Karton, Y vonLubitz, DKJE Olah, ME Stiles, GL AF Jacobson, KA vanRhee, AM Jiang, L Ji, XD Karton, Y vonLubitz, DKJE Olah, ME Stiles, GL TI Novel adenosine antagonists: A(3) receptor-selective flavonoid and dihydropyridine derivatives. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BIOORGAN CHEM LAB,NIH,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 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 99 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91502657 ER PT J AU Saavedra, JE Booth, MN Keefer, LK AF Saavedra, JE Booth, MN Keefer, LK TI Design and synthesis of diazeniumdiolates for tissue selective delivery of nitric oxide. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 IRSP,SAIC,FREDERICK,MD 21702. COMEDICUS INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 100 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501136 ER PT J AU Keefer, LK AF Keefer, LK TI Nitric oxide, DNA damage, and cancer. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 103 EP TOXI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501139 ER PT J AU McGee, LR Krawczyk, S Harwood, E Harada, Y Kim, CU Swaminathan, S Krishnamurthy, K Bischofberger, N Mendel, D Moon, K Smith, J Xiong, SF Cherrington, JM Mulato, A Flores, C Chen, MS Griffin, L Oliyai, R Cundy, KC Lee, A Erickson, JW AF McGee, LR Krawczyk, S Harwood, E Harada, Y Kim, CU Swaminathan, S Krishnamurthy, K Bischofberger, N Mendel, D Moon, K Smith, J Xiong, SF Cherrington, JM Mulato, A Flores, C Chen, MS Griffin, L Oliyai, R Cundy, KC Lee, A Erickson, JW TI The discovery of GS2992 and GS3333: Potent, bioavailable carbohydrate-based inhibitors of HIV protease SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 GILEAD SCI INC,FOSTER CITY,CA 94404. FREDERICK CANC RES & DEV CTR,SAIC,STRUCT BIOCH PROG,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 124 EP ORGN PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA VB009 UT WOS:A1996VB00900124 ER PT J AU Chan, CK Hu, Y Takahashi, S Rousseau, DL Eaton, WA Hofrichter, J AF Chan, CK Hu, Y Takahashi, S Rousseau, DL Eaton, WA Hofrichter, J TI Submillisecond protein folding kinetics studied by ultrafast mixing SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. AT&T BELL LABS,MURRAY HILL,NJ 07974. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 149 EP PHYS PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VB009 UT WOS:A1996VB00900652 ER PT J AU Ananthan, S Johnson, CA Porreca, F Davis, P Rice, KC Xu, H Rothman, RB AF Ananthan, S Johnson, CA Porreca, F Davis, P Rice, KC Xu, H Rothman, RB TI Opioid receptor ligands: Synthesis and structure-activity relationships of naltrindole analogues substituted in the indolic benzene moiety. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SO RES INST,BIRMINGHAM,AL 35255. UNIV ARIZONA,COLL MED,DEPT PHARMACOL,TUCSON,AZ 85724. NIDDK,MED CHEM LAB,NIH,BETHESDA,MD 20892. NIDA,CLIN PSYCHOPHARMACOL SECT,DIR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 158 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91502716 ER PT J AU Brooks, BR Eurenius, KP Chatfield, DC AF Brooks, BR Eurenius, KP Chatfield, DC TI Investigation of QM/MM potential energy surfaces. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,STRUCT BIOL LAB,DCRT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 171 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91501556 ER PT J AU Fan, F Pommier, Y Kohn, KW Weinstein, JN AF Fan, F Pommier, Y Kohn, KW Weinstein, JN TI A molecular model for binding of camptothecin and its analogs in the topoisomerase I-DNA cleavable complex SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MOL PHARMACOL LAB,DBS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 203 EP MEDI PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VA915 UT WOS:A1996VA91502760 ER PT J AU Shah, JH Yagi, H Sayer, JM Mah, H Xie, G Jerina, DM AF Shah, JH Yagi, H Sayer, JM Mah, H Xie, G Jerina, DM TI Site-specific incorporation of the potent mutagen 9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene as a trans ring opened-deoxyadenosine adduct into a DNA oligomer SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 219 EP ORGN PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VB009 UT WOS:A1996VB00900219 ER PT J AU Eaton, WA Hagen, SJ Henry, ER Hofrichter, J AF Eaton, WA Hagen, SJ Henry, ER Hofrichter, J TI Conformational dynamics of proteins investigated by time-resolved optical spectroscopy SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,PHYS CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 251 EP PHYS PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VB009 UT WOS:A1996VB00900752 ER PT J AU Ikeda, H Marquez, VE AF Ikeda, H Marquez, VE TI Use of the Mitsunobu reaction for the construction of (beta-CH2-TAD), a metabolically stable analog of the antitumor agent TAD SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,DBS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 25 PY 1996 VL 212 BP 281 EP ORGN PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA VB009 UT WOS:A1996VB00900280 ER PT J AU Kong, LY Wilson, BC McMillian, MK Bing, GY Hudson, PM Hong, JS AF Kong, LY Wilson, BC McMillian, MK Bing, GY Hudson, PM Hong, JS TI The effects of the HIV-1 envelope protein gp120 on the production of nitric oxide and proinflammatory cytokines in mixed glial cell cultures SO CELLULAR IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; CENTRAL-NERVOUS-SYSTEM; NEURONAL INJURY; FACTOR-ALPHA; COAT PROTEIN; MONONUCLEAR-CELLS; CALCIUM-CHANNEL; GENE-EXPRESSION; AIDS DEMENTIA AB Although the neurotoxicity induced by the HIV envelope protein, gp120, has been demonstrated to require the presence of glial cells (microglia/astrocytes), the mechanisms for the gp120-induced neurotoxicity are not well understood. Moreover, the neurotoxic potencies of gp120s obtained from various HIV isolates are different. Since nitric oxide (NO) and proinflammatory cytokines (TNF-alpha, IL-1, IL-6) produced by glial cells have been involved in the neuropathogenesis of various diseases, this study examined the effects of gp120 obtained from two strains, HIV-1(IIIB) and HIV-1(SF2), of the HIV-1 virus on the production of NO, TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6 in murine primary mixed glial cell cultures. The glial cells exposed to HIV-1(IIIB) gp120 released NO, TNF-alpha, and IL-6 in a dose-dependent manner, whereas IL-1 alpha and IL-1 beta were undetectable. The cells exposed to HIV-1(SF2) gp120 increased the release of IL-6 only. The gp120-induced effects were significantly enhanced by priming glial cells with IFN-gamma. To investigate the cellular sources and mechanisms of the gp120-induced IL-6 production, in situ hybridization with mRNA for IL-6 was performed in HIV-1(IIIB) gp120- or HIV-1(SF2) gp120-stimulated microglia-enriched or astrocyte-enriched cultures. HIV-1(IIIB) gp120 or HIV-1(SF2) gp120 induced the expression of IL-6 mRNA in both microglia-enriched and astrocyte-enriched cultures, indicating that both microglia and astrocytes produce IL-6, and that the transcriptional regulation is involved in the gp120-induced IL-6 production. Taken together, these results demonstrate that the production of NO, TNF-alpha, IL-1, or IL-6 from glial cells is differentially regulated by HIV-1(IIIB) gp120 and HIV-1(SF2) gp120. These results may provide insights into the roles of NO and proinflammatory cytokines in the neurotoxicity of gp120s and the neuropathology of different strains of HIV-1 viruses. (C) 1996 Academic Press, Inc. RP Kong, LY (reprint author), NIEHS,NIH,SECT NEUROPHARMACOL,TOXICOL BRANCH,RES TRIANGLE PK,NC 27709, USA. OI Bing, Guoying/0000-0003-0609-8152 NR 53 TC 67 Z9 67 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD AUG 25 PY 1996 VL 172 IS 1 BP 77 EP 83 DI 10.1006/cimm.1996.0217 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA VD598 UT WOS:A1996VD59800010 PM 8806809 ER PT J AU Baskar, P Hildreth, JEK Chrest, FJ Nagel, JE Adler, WH AF Baskar, P Hildreth, JEK Chrest, FJ Nagel, JE Adler, WH TI Anti-HLA Class I antibody inhibits Staphylococcus enterotoxin A (SEA)-induced proliferation of human PBMC SO CELLULAR IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; MONOCLONAL-ANTIBODY; MHC MOLECULES; SIGNAL TRANSDUCTION; ACCESSORY CELLS; LYMPHOCYTES-T; SUPERANTIGEN; RECEPTOR; STIMULATION; MONOCYTES AB The antigen-presenting role of major histocompatibility complex (MHC) Class I molecules in the activation of appropriately restricted T cells is well documented. Now growing evidence indicates that MHC Class I molecules can, in addition, exert a regulatory effect and influence the resulting immune responses. In this report we show that a monoclonal antibody (mAb) directed against a conserved region of the human leukocyte antigens (HLA)-A, -B, and -C was able to inhibit proliferation of human peripheral blood mononuclear cells induced by the superantigen, Staphylococcus enterotoxin A. While anti-HLA inhibition was associated with a decrease in IL-2 receptor (IL-2R) expression, the addition of exogenous IL-2 did not restore the proliferative response in the presence of anti-HLA mAb. The inhibition of DNA synthesis was also associated with a decrease in the expression of the early activation marker CD69. These results suggest a critical role for HLA Class I molecules in the early events of human lymphocyte activation and proliferation as well as in their expression of the IL-2R. (C) 1996 Academic Press, Inc C1 JOHNS HOPKINS SCH MED,DEPT PHARMACOL & MOL SCI,BALTIMORE,MD 21205. RP Baskar, P (reprint author), NIA,NIH,CLIN IMMUNOL SECT,BALTIMORE,MD 21224, USA. FU NIAID NIH HHS [AI 07394, AI 29382, AI 31806] NR 41 TC 1 Z9 2 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD AUG 25 PY 1996 VL 172 IS 1 BP 135 EP 138 DI 10.1006/cimm.1996.0224 PG 4 WC Cell Biology; Immunology SC Cell Biology; Immunology GA VD598 UT WOS:A1996VD59800017 PM 8806816 ER PT J AU Pahor, M Guralnik, JM Ferrucci, L Corti, MC Salive, ME Cerhan, JR Wallace, RB Havlik, RJ AF Pahor, M Guralnik, JM Ferrucci, L Corti, MC Salive, ME Cerhan, JR Wallace, RB Havlik, RJ TI Calcium-channel blockade and incidence of cancer in aged populations SO LANCET LA English DT Article ID CELL-DEATH; DEPENDENT TISSUES; OLDER PERSONS; ANTAGONISTS; MORTALITY; DISEASE; RISK; APOPTOSIS; SURVIVAL; SERUM AB Background Calcium-channel blockers can alter apoptosis, a mechanism for destruction of cancer cells. We examined whether the long-term use of calcium-channel blockers is associated with an increased risk of cancer. Methods Between 1988 and 1992 we carried out a prospective cohort study of 5052 people aged 71 years or more and who lived in three regions of Massachusetts, Iowa, and Connecticut USA. Those taking calcium-channel blockers (n=451) were compared with all other participants (n=4601). The incidence of cancer was assessed by survey of hospital discharge diagnoses and causes of death. These outcomes were validated by the cancer registry in the one region where it was available. Demographic variables, disability, cigarette smoking, alcohol consumption, blood pressure, body-mass index, use of other drugs, hospital admissions for other causes, and comorbidity were all assessed as possible confounding factors. Findings The hazard ratio for cancer associated with calcium-channel blockers (1549 person-years, 47 events) compared with those not taking calcium-channel blockers (17 225 person-years, 373 events) was 1 . 72 (95% CI 1 . 27-2 . 34, p=0 . 0005), after adjustment for confounding factors. A significant dose-response gradient was found. Hazard ratios associated with verapamil, diltiazem, and nifedipine did not differ significantly from each other. The results remained unchanged in community-specific analyses. The association between calcium-channel blockers and cancer was found with most of the common cancers. Interpretation Calcium-channel blockers were associated with a general increased risk of cancer in the study populations, which suggested a common mechanism. These observational findings should be confirmed by other studies. C1 CATHOLIC UNIV,DEPT INTERNAL MED & GERIATR,ROME,ITALY. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. IST NAZL RIC & CURA PER GLI ANZIANI,DEPT GERIATR,FLORENCE,ITALY. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. FU NIA NIH HHS [N01-AG-0-2105, N01-AG-0-2106, N01-AG-0-2107] NR 36 TC 258 Z9 260 U1 0 U2 4 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD AUG 24 PY 1996 VL 348 IS 9026 BP 493 EP 497 DI 10.1016/S0140-6736(96)04277-8 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA VD427 UT WOS:A1996VD42700008 PM 8757150 ER PT J AU Poulter, NR Chang, CL Farley, TMM Meirik, O Marmot, MG DebertRibeiro, M Medina, E Artigas, J Shen, H Zhong, YH Zhang, DW Zhao, WJ Rojas, O Vessey, M Heinemann, L Donnan, S Ho, S Bartfai, G Kisjanto, J Wilks, R Agwanda, R Ruiz, R KozuhNovak, M Dusitsin, N Virutamasen, P Phanthumcinda, K Koetsawang, S PiyaAnant, M Demirovic, J Belkic, K Mwandila, WS Mutale, CM Matenga, J Wilson, A Petitti, D Perlman, J Keleghan, J Lawley, S Smith, S Shipley, M Olsen, J Thorogood, M AF Poulter, NR Chang, CL Farley, TMM Meirik, O Marmot, MG DebertRibeiro, M Medina, E Artigas, J Shen, H Zhong, YH Zhang, DW Zhao, WJ Rojas, O Vessey, M Heinemann, L Donnan, S Ho, S Bartfai, G Kisjanto, J Wilks, R Agwanda, R Ruiz, R KozuhNovak, M Dusitsin, N Virutamasen, P Phanthumcinda, K Koetsawang, S PiyaAnant, M Demirovic, J Belkic, K Mwandila, WS Mutale, CM Matenga, J Wilson, A Petitti, D Perlman, J Keleghan, J Lawley, S Smith, S Shipley, M Olsen, J Thorogood, M TI Ischaemic stroke and combined oral contraceptives: Results of an international, multicentre, case-control study SO LANCET LA English DT Article ID BLOOD-PRESSURE; CEREBROVASCULAR-DISEASE; RISK; AGE AB Background The association between use of oral contraceptives (OCs) and cerebral infarction was established in studies from northern Europe and the USA during the 1960s and 1970s. Since then, the constituents of hormonal OCs have changed and now contain lower doses of oestrogen and progestagen. Current recommendations restrict OC use to younger women who do not have other risk factors for cardiovascular disease, in this international study we assessed the risk of CC-associated first stroke in women from Europe and other countries throughout Vie world. Methods In this hospital-based, case-control study, we assessed the risk of ischaemic stroke in association with current use of combined OCs in 697 cases, aged 20-44 years, and 1962 age-matched hospital controls in 21 centres in Africa, Asia, Europe, and Latin America. The diagnosis of ischaemic stroke was almost exclusively based on computed tomography (CT), magnetic resonance imaging (MRI), or cerebral angiography carried out within 3 weeks of the clinical event. Ail cases and controls were interviewed while in hospital with the same questionnaire, which included information on medical and personal history, details of lifetime contraceptive use, and blood-pressure measurements before the most recent episode of OC use. Findings The overall odds ratio of ischaemic stroke was 2 . 99 (95% CI 1 . 65-5 . 40) in Europe and 2 . 93 (2 . 15-4 . 00) in the non-European (developing) countries, Odds ratios were lower in younger women and those who did not smoke, and less than 2 in women who did not have hypertension and who reported that their blood pressure had been checked before the current episode of OC use. By contrast, among current OC users with a history of hypertension, the odds ratio was 10 . 7 (2 . 04-56 . 6) in Europe and 14 . 5 (5 . 36-39 . 0) in the developing countries. In Europe, the odds ratio associated with current use of low-dose OCs (<50 mu g oestrogen) was 1 . 53 (0 . 71-3 . 31), whereas for higher-dose preparations it was 5 . 30 (2 . 56-11 . 0). In the developing countries, there was no significant difference between overall estimates of risk associated with use of low-dose or higher-dose OCs (3 . 26 [2 . 19-4 . 86] vs 2 . 71 [1 . 75-4 . 19]), This differential effect of dose in Europe and the developing countries is likely to be due to different levels of other risk factors among users of low-dose and higher-dose OCs in the two groups of countries. There was no significant increase in odds ratios with increasing duration of OC use among current users; odds ratios were not significantly increased after cessation of OC use. Interpretation The incidence of ischaemic stroke is low in women of reproductive age and any risk attributable to OC use is small. The risk can be further reduced if users are younger than 35 years, do not smoke, do not have a history of hypertension, and have blood pressure measured before the start of QC use. In such women OC preparations with low oestrogen doses may be associated with even lower risk. C1 WHO, UNDP UNFPA WHO WORLD BANK SPECIAL PROGRAMME RES D, CH-1211 GENEVA 27, SWITZERLAND. ESCOLA PAULISTA MED, DEPT PREVENT MED, SAO PAULO, BRAZIL. UNIV CHILE, ESCUELA SALUD PUBL, SANTIAGO, CHILE. ESCUELA MED, DEPT SALUD PUBL, VALPARAISO, CHILE. NATL RES INST FAMILY PLANNING, BEIJING, PEOPLES R CHINA. SICHUAN FAMILY PLANNING RES INST, CHENGDU, PEOPLES R CHINA. SHANGHAI INST PLANNED PARENTHOOD RES, SHANGHAI, PEOPLES R CHINA. UNIV VALLE, FAC SALUD, CALI, COLOMBIA. UNIV OXFORD, DEPT PUBL HLTH & PRIMARY CARE, OXFORD OX3 7LF, ENGLAND. ZENTRUM EPIDEMIOL & GESUNDHEITSFORSCH, BERLIN, GERMANY. CHINESE UNIV HONG KONG, DEPT COMMUNITY MED, HONG KONG, HONG KONG. ALBERT SZENT GYORGYI MED UNIV, DEPT OBSTET & GYNAECOL, SZEGED, HUNGARY. UNIV INDONESIA, FAC MED, JAKARTA, INDONESIA. UNIV W INDIES, TROP METAB RES UNIT, KINGSTON 7, JAMAICA. KENYA GOVT MED RES CTR, NAIROBI, KENYA. GRP INTERUNIV MEXICANO INVEST EPIDEMIOL SALUD REP, DURANGO, MEXICO. UNIV LJUBLJANA, INST PUBL HLTH, LJUBLJANA, SLOVENIA. CHULALONGKORN HOSP, DEPT OBSTET & GYNAECOL, BANGKOK, THAILAND. SIRIRAJ HOSP, SIRIRAJ FAMILY HLTH RES CTR, BANGKOK, THAILAND. UNIV BELGRADE, SCH MED, BELGRADE, YUGOSLAVIA. UNIV LUSAKA, TEACHING HOSP, LUSAKA, ZAMBIA. UNIV ZIMBABWE, DEPT MED, HARARE, ZIMBABWE. UCL, LONDON MED SCH, DEPT EPIDEMIOL & PUBL HLTH, LONDON, ENGLAND. UNIV OXFORD, DEPT PUBL HLTH & PRIMARY CARE, OXFORD OX3 7LF, ENGLAND. KAISER PERMANENTE, PASADENA, CA USA. NIH, BETHESDA, MD 20892 USA. UNIV AARHUS, DANISH EPIDEMIOL SCI CTR, AARHUS, DENMARK. UNIV LONDON LONDON SCH HYG & TROP MED, LONDON WC1E 7HT, ENGLAND. RP Poulter, NR (reprint author), UCL, SCH MED, DEPT EPIDEMIOL & PUBL HLTH, LONDON WC1E 6BT, ENGLAND. NR 36 TC 241 Z9 244 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD AUG 24 PY 1996 VL 348 IS 9026 BP 498 EP 505 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VD427 UT WOS:A1996VD42700009 ER PT J AU Poulter, NR Chang, CL Farley, TMM Meirik, O Marmot, MG AF Poulter, NR Chang, CL Farley, TMM Meirik, O Marmot, MG TI Haemorrhagic stroke, overall stroke risk, and combined oral contraceptives: Results of an international, multicentre, case-control study SO LANCET LA English DT Article ID CEREBROVASCULAR-DISEASE; SUBARACHNOID HEMORRHAGE; EPIDEMIOLOGY; SMOKING; AGE AB Background The risk of haemorrhagic stroke associated with use of oral contraceptives (OCs) is less well-established than that for ischaemic stroke. We assessed the risk of haemorrhagic stroke associated with current use of modern OCs as now used throughout the world. Methods In this WHO collaborative, case-control study, we assessed the association between risk of haemorrhagic stroke and use of combined OCs in 1068 cases, 20-44 years, and 2910 age-matched controls. We also assessed risks for all strokes combined (haemorrhagic, ischaemic, and unclassified) based on 2198 cases and 6086 controls. Findings Overall, current use of combined OCs was associated with slightly increased risk of haemorrhagic stroke; the increase was significant in the developing countries (odds ratio 1 . 76 [95% CI 1 . 34-2 . 30]) but not in Europe (1 . 38 [0 . 84-2 . 25]). Use of OCs in women younger than 35 years did not affect risk of haemorrhagic stroke in either group of countries, whereas in women aged older than 35 years, odds ratios were greater than 2. Women who were current users of OCs and had a history of hypertension (detected before current episode of OC use, but not during pregnancy) had a substantially increased risk (ten-fold to 15-fold) of haemorrhagic stroke compared with women who did not use OCs and had no history of hypertension. Odds ratios among current OC users who were also current cigarette smokers were greater than 3. In both groups of countries, past use of OCs, dose of oestrogen, and dose and type of progestagen had no effect on risk, and risks were similar for subarachnoid and intracerebral haemorrhage. The odds ratios for any type of stroke associated with current use of low-dose (<50 mu g oestrogen) and higher-dose OCs were 1 . 41 (0 . 90-2 . 20) and 2 . 71 (1 . 70-4 . 32), respectively, in Europe and 1 . 86 (1 . 49-2 . 33) and 1 . 92 (1 . 48-2 . 50) in the developing countries. From these data we estimated that about 13% and 8% of all strokes in women aged 20-44 in Europe and the developing countries, respectively, are attributable to the use of OCs. Interpretation The risk of haemorrhagic stroke attributable to OC use is not increased in younger women and is only slightly increased in older women. The estimated excess risk of all stroke types associated with use of low-oestrogen and higher-oestrogen dose OCs in Europe was about two and eight, respectively, per 100 000 woman-years of OC use. However, findings need to be considered in the context of other risks and benefits associated with OC use, as well as those associated with the use of other forms of contraception. C1 WHO, UNDP UNFPA WHO WORLD BANK SPECIAL PROGRAMME RES D, CH-1211 GENEVA 27, SWITZERLAND. ESCOLA PAULISTA MED, DEPT PREVENT MED, SAO PAULO, BRAZIL. UNIV CHILE, ESCUELA SALUD PUBL, SANTIAGO, CHILE. ESCUELA MED, DEPT SALUD PUBL, VALPARAISO, CHILE. NATL RES INST FAMILY PLANNING, BEIJING, PEOPLES R CHINA. SICHUAN FAMILY PLANNING RES INST, CHENGDU, PEOPLES R CHINA. SHANGHAI INST PLANNED PARENTHOOD RES, SHANGHAI, PEOPLES R CHINA. UNIV VALLE, FAC SALUD, CALI, COLOMBIA. UNIV OXFORD, DEPT PUBL HLTH & PRIMARY CARE, OXFORD OX3 7LF, ENGLAND. ZENTRUM EPIDEMIOL & GESUNDHEITSFORSCH, BERLIN, GERMANY. CHINESE UNIV HONG KONG, DEPT COMMUNITY MED, HONG KONG, HONG KONG. ALBERT SZENT GYORGYI MED UNIV, DEPT OBSTET & GYNAECOL, H-6701 SZEGED, HUNGARY. UNIV INDONESIA, FAC MED, JAKARTA, INDONESIA. UNIV W INDIES, TROP METAB RES UNIT, KINGSTON 7, JAMAICA. KENYA GOVT MED RES CTR, NAIROBI, KENYA. GRP INTERUNIV MEXICANO INVEST EPIDEMIOL SALUD REP, DURANGO, MEXICO. UNIV LJUBLJANA, INST PUBL HLTH, LJUBLJANA, SLOVENIA. CHULALONGKORN HOSP, DEPT OBSTET & GYNAECOL, BANGKOK, THAILAND. SIRIRAJ HOSP, SIRIRAJ FAMILY HLTH RES CTR, BANGKOK, THAILAND. UNIV BELGRADE, SCH MED, BELGRADE, YUGOSLAVIA. UNIV LUSAKA, TEACHING HOSP, LUSAKA, ZAMBIA. UNIV ZIMBABWE, DEPT MED, HARARE, ZIMBABWE. UNIV OXFORD, DEPT PUBL HLTH & PRIMARY CARE, OXFORD OX3 7LF, ENGLAND. KAISER PERMANENTE, PASADENA, CA USA. NIH, BETHESDA, MD 20892 USA. UNIV AARHUS, DANISH EPIDEMIOL SCI CTR, AARHUS, DENMARK. UNIV LONDON LONDON SCH HYG & TROP MED, LONDON WC1E 7HT, ENGLAND. RP Poulter, NR (reprint author), UCL, SCH MED, DEPT EPIDEMIOL & PUBL HLTH, LONDON WC1E 6BT, ENGLAND. NR 32 TC 146 Z9 147 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD AUG 24 PY 1996 VL 348 IS 9026 BP 505 EP 510 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VD427 UT WOS:A1996VD42700010 ER PT J AU Pahor, M Guralnik, JM Salive, ME Corti, MC Havlik, RJ AF Pahor, M Guralnik, JM Salive, ME Corti, MC Havlik, RJ TI Do calcium antagonists cause cancer? Reply SO LANCET LA English DT Letter C1 US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. RP Pahor, M (reprint author), UNIV TENNESSEE,DEPT PREVENT MED,MEMPHIS,TN 38105, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD AUG 24 PY 1996 VL 348 IS 9026 BP 541 EP 542 DI 10.1016/S0140-6736(05)64694-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VD427 UT WOS:A1996VD42700039 ER PT J AU Movsesian, MA Komas, N Krall, J Manganiello, VC AF Movsesian, MA Komas, N Krall, J Manganiello, VC TI Expression and activity of low K-m cGMP-inhibited cAMP phosphodiesterase in cardiac and skeletal muscle SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TROPONIN-I; PHOSPHOLAMBAN; PHOSPHORYLATION; PROTEIN; STIMULATION; MYOCARDIUM; HEARTS; SLOW AB The expression and activity of low K-m, cGMP-inhibited cAMP phosphodiesterase (PDE3)(4) were examined in rabbit and canine cardiac and skeletal muscle. In cardiac muscle, a cDNA probe: whose sequence encompasses the catalytic domain of human myocardial PDE3 (PDE3A) hybridized predominantly with a 7.2-7.4 kb mRNA. No hybridization was observed in preparations from slow or fast twitch skeletal muscle. Likewise, PDE3 activity was present in cytosolic and microsomal fractions of cardiac muscle but was absent from cytosolic and microsomal fractions of slow twitch and fast twitch skeletal muscle. These results, which demonstrate the absence of PDE3 from slow and fast twitch mammalian skeletal muscle, further delineate the differences in beta-adrenergic receptor-mediated signal transduction pathways in cardiac and skeletal muscle. (C) 1996 Academic Press. Inc. C1 UNIV UTAH,SCH MED,SALT LAKE CITY VET AFFAIRS MED CTR,RES SERV,SALT LAKE CITY,UT. UNIV UTAH,SCH MED,DEPT INTERNAL MED,SALT LAKE CITY,UT. UNIV UTAH,SCH MED,DEPT CARDIOL,SALT LAKE CITY,UT. UNIV UTAH,SCH MED,DEPT PHARMACOL,SALT LAKE CITY,UT. NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. NR 23 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 23 PY 1996 VL 225 IS 3 BP 1058 EP 1062 DI 10.1006/bbrc.1996.1294 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VE458 UT WOS:A1996VE45800058 PM 8780733 ER PT J AU Pineau, T Hudgins, WR Liu, L Chen, LC Sher, T Gonzalez, FJ Samid, D AF Pineau, T Hudgins, WR Liu, L Chen, LC Sher, T Gonzalez, FJ Samid, D TI Activation of a human peroxisome proliferator-activated receptor by the antitumor agent phenylacetate and its analogs SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE aromatic fatty acids; phenylacetate; phenylbutyrate; clofibrate; acyl-CoA oxidase; cytochrome P450IV; cytostasis; nuclear receptors ID ACUTE PROMYELOCYTIC LEUKEMIA; ACID OMEGA-HYDROXYLASE; ENZYME GENE-EXPRESSION; TRANS RETINOIC ACID; COA OXIDASE GENE; FATTY-ACIDS; CELL-DIFFERENTIATION; PHENOTYPIC REVERSION; HYPOLIPIDEMIC DRUGS; RESPONSIVE ELEMENTS AB The aromatic fatty acid phenylacetate and its analogs induce tumor cytostasis and differentiation in experimental models. Although the underlying mechanisms of action are not clear, effects un lipid metabolism are evident. We have now examined whether these compounds, structurally similar to the peroxisome proliferator clofibrate, affect the human peroxisome proliferator-activated receptor (hPPAR), a homolog of the rodent PPAR alpha, a transcriptional factor regulating lipid metabolism and cell growth. Gene transfer experiments showed activation of hPPAR, evident by the increased expression of the reporter gene chloramphenicol acetyltransferase linked to PPAR-response element from either the rat acyl-CoA oxidase or rabbit CW4A6 genes. The relative potency of tested drugs in the co-transfection assay was: 4-iodophenylbutyrate > 4-chlorophenylbutyrate > clofibrate > phenylbutyrate > naphthylacetate > 2,4-D > 4-chlorophenylacetate > phenylacetate >> indoleacetate. Phenylacetylglutamine, in which the carboxylic acid is blocked, was inactive. The ability of the aromatic fatty acids to activate PPAR was confirmed in vivo, as CYP4A mRNA levels increased in hepatocytes of treated rats, Further studies using human prostate carcinoma, melanoma, and glioblastoma cell lines showed a eight correlation between drug-induced cytostasis, increased expression of the endogenous hPPAR, and receptor activation documented in the gene-transfer model. These results identify phenylacetate and its analogs as a new class of aromatic fatty acids capable of activating hPPAR, and suggest that this nuclear receptor may mediate tumor cytostasis induced by these drugs. C1 UNIV VIRGINIA,CTR CANC,EXPT THERAPEUT PROGRAM,CHARLOTTESVILLE,VA 22908. NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NR 54 TC 107 Z9 114 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 AUG 23 PY 1996 VL 52 IS 4 BP 659 EP 667 DI 10.1016/0006-2952(96)00340-1 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VA235 UT WOS:A1996VA23500018 PM 8759039 ER PT J AU Linert, W Herlinger, E Jameson, RF Kienzl, E Jellinger, K Youdim, MBH AF Linert, W Herlinger, E Jameson, RF Kienzl, E Jellinger, K Youdim, MBH TI Dopamine, 6-hydroxydopamine, iron, and dioxygen - Their mutual interactions and possible implication in the development of Parkinson's disease SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE Parkinson's disease; dopamine; 6-hydroxydopamine; iron(III); iron(II); manganese(II); Fenton's reagent; nicotine ID SUBSTANTIA-NIGRA; LIPID-PEROXIDATION; CIGARETTE-SMOKING; METAL-IONS; NEUROMELANIN; NEURONS; CATECHOLAMINES; PATHOGENESIS; AUTOXIDATION; FERRITIN AB The reactions of dopamine (1-amino-2-(3,4-dihydroxyphenyl)-ethane DA), 5-hydroxydopamine (5-OHDA), and 6-hydroxydopamine (6-OHDA), with molecular oxygen - with and without the addition of catalytic amounts of iron(III) and other metal ions - have been studied and the implication of these results with respect to the chemistry involved in the progress of Parkinson's disease is discussed, In the presence of O-2 DA reacts spontaneously without the necessity of metal-ion catalysis under the production of stoichiometric amounts of H2O2, to form initially pink dopaminochrome, which is not stable and reacts further (without the consumption of dioxygen) to form the insoluble polymeric material known as 'melanine'. DA reacts with iron(III) yielding an intermediate 1:1 complex, which decomposes releasing Fe(II) and the semiquinone, which reacts further under involvement of both Fr(III) and dioxygen. 6-OHDA reacts without showing the necessity of such an intermediate, and it is shown to be able to release iron as Fe(II) from ferritine. On the other hand, it is shown (in vitro) that Fe(II) reacts in a Fenton type reaction with DA and the present H2O2 producing 5-OHDA and especially 6-OHDA. Based on these mutual interacting reactions a mechanism for the initiation and progress of Parkinson's disease is suggested. The catalytic effects of some other transition-metal ions are presented and an explanation for the peculiarly toxic effects of manganese(II) is put forward. Finally, a possible reason for the effect that nicotine has in the mitigation of Parkinson's disease is discussed. C1 UNIV DUNDEE,DEPT CHEM,DUNDEE DD1 4HN,SCOTLAND. HOSP LAINZ,LUDWIG BOLTZMANN INST CLIN NEUROBIOL,A-1130 VIENNA,AUSTRIA. NIH,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892. RP Linert, W (reprint author), TECH UNIV VIENNA,INST INORGAN CHEM,A-1060 VIENNA,AUSTRIA. NR 47 TC 174 Z9 175 U1 2 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD AUG 23 PY 1996 VL 1316 IS 3 BP 160 EP 168 DI 10.1016/0925-4439(96)00020-8 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VD709 UT WOS:A1996VD70900004 PM 8781534 ER PT J AU Ohgaki, H Sanderson, ND Ton, P Thorgeirsson, SS AF Ohgaki, H Sanderson, ND Ton, P Thorgeirsson, SS TI Molecular analyses of liver tumors in c-myc transgenic mice and c-myc and TGF-alpha double transgenic mice SO CANCER LETTERS LA English DT Article DE c-myc; transforming growth factor alpha; insulin-like growth factor II; liver tumor; transgenic mice ID GROWTH FACTOR-II; H-RAS ONCOGENE; WOODCHUCK HEPATITIS-VIRUS; HEPATOCELLULAR-CARCINOMA; MESSENGER-RNA; EXPRESSION; HEPATOCARCINOGENESIS; MUTATIONS; GENE; OVEREXPRESSION AB It has been demonstrated that co-expression of c-myc and transforming growth factor alpha (TGF-alpha) as transgenes in the mouse liver results in a tremendous acceleration of neoplastic development in this organ as compared to expression of either transgene alone [Murakami, H., et al. (1993) Cancer Res., 53, 1719-1723]. In order to clarify the roles of transgenes and additional other genetic alterations during hepatocarcinogenesis, we analyzed liver tumors developed in albumin/c-myc transgenic mice and albumin/c-myc and MT-1/TGF-alpha double transgenic mice. High expression of TGF-alpha transgene was found in nine of 14 (64%) liver tumors in double transgenic mice, suggesting that TGF-alpha overexpression confers growth advantage during hepatocarcinogenesis. Only one of 14 (7%) liver tumors in double transgenic mice and none of 13 liver tumors in c-myc transgenic mice showed overexpression of insulin-like growth factor II (IGF-II). This result was in contrast to the report by Takagi et al. [Takagi, H., et al. (1992) Cancer Res., 52, 5171-5177] which showed overexpression of IGF-II in 75% of liver tumors in TGF-alpha transgenic mice and suggested that the presence of c-myc transgenes together with TGF-alpha from an early stage of hepatocarcinogenesis may lead to different carcinogenic pathways which are independent of IGF-II overexpression. Expression of c-myc transgene was found in most of the liver tumors, but at lower levels than non-tumorous parts of the liver in c-myc and double transgenic mice. These results suggest that c-myc transgene expression cooperates with TGF-alpha in the early stages of hepatocarcinogenesis but has growth disadvantage in later stages of hepatocarcinogenesis. There was no evidence of mutational activation of the H-ras gene or mutational inactivation of the p53 gene in any liver tumors developed in c-myc or double transgenic mice. C1 NATL CANC INST,EXPT CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NR 31 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 23 PY 1996 VL 106 IS 1 BP 43 EP 49 DI 10.1016/0304-3835(96)04299-1 PG 7 WC Oncology SC Oncology GA VG549 UT WOS:A1996VG54900006 PM 8827045 ER PT J AU Ueda, A Yoshimura, T AF Ueda, A Yoshimura, T TI Characterization of cis-acting elements of the gene for macrophage-stimulating protein from the human - The involvement of positive and negative regulatory elements SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPATOCYTE-GROWTH-FACTOR; CCAAT-BINDING PROTEIN; TRANSCRIPTION FACTOR; TYROSINE KINASE; DNA-BINDING; MOLECULAR-CLONING; EUKARYOTIC TRANSCRIPTION; HETEROLOGOUS SUBUNITS; SEQUENCE IDENTITY; NUCLEAR FACTOR AB To analyze the promotor region of the human macrophage-stimulating protein (MSP) gene, the 5'-flanking region of this gene was cloned. The major initiation site was determined at T located 49 base pairs upstream of the translation initiation site by primer extention with mRNA from HepG2 and Hep3B cells. There was no TATA sequence in this region. Transient transfection assay with 5'-deletion constructs showed that the transcription of this gene was regulated by positive and negative regulatory elements (PRE and NRE). The PRE (-34 to +2) was essential for the maximal transcription of this gene, and the NRE (-141 to -34) appeared to be responsible for the tissue-specific expression of the gene. The PRE contained the CCAAT sequence and a mutation from CCAAT to CTGAT resulted in a significant loss of the transcriptional activity. Electrophoretic mobility shift assay suggested that two different proteins bound to the PRE (MSP-PRE-binding protein-1 (MSP-PREB1) and 2). MSP-PREB1 and 2 were detected in various cell types, and the CCAAT sequence was involved in these bindings. These findings indicate that MSP-PREB1 and 2 are positive regulators. Further characterization also revealed that MSP-PREB2 was identical to CCAAT binding transcription factor, also known as NF-Y. RP Ueda, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21702, USA. NR 51 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 23 PY 1996 VL 271 IS 34 BP 20265 EP 20272 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700011 PM 8702759 ER PT J AU Mould, AP Akiyama, SK Humphries, MJ AF Mould, AP Akiyama, SK Humphries, MJ TI The inhibitory anti-beta 1 integrin monoclonal antibody 13 recognizes an epitope that is attenuated by ligand occupancy - Evidence for allosteric inhibition of integrin function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-BINDING DOMAIN; SITE-DIRECTED MUTAGENESIS; HUMAN-PLASMA FIBRONECTIN; LEUKOCYTE INTEGRINS; ADHESION MOLECULE-1; ENDOTHELIAL-CELLS; DIVALENT-CATIONS; ACTIVATION; ALPHA-5-BETA-1; IDENTIFICATION AB Integrin-ligand binding causes conformational changes in the integrin, as evidenced by the increased expression of epitopes known as ligand-induced binding sites. Some monoclonal antibodies (mAbs) that recognize ligand-induced binding sites stimulate ligand binding, possibly by stabilizing the ligand-occupied conformation of the integrin. Here we have investigated the effect of ligand recognition by alpha 5 beta 1 on the binding of a mAb that inhibits beta 1 integrin function (mAb 13). Ligand (fibronectin fragment or GRGDS peptide) decreased the binding of mAb 13 to alpha 5 beta 1. Analysis of this inhibition showed that at high ligand concentrations, approximately 50% of the total integrin bound mAb 13 with >50-fold lower affinity than in the absence of ligand. The concentration of ligand required for half-maximal inhibition of antibody binding was independent of antibody concentration, suggesting that ligand acts as an allosteric inhibitor of mAb 13 binding. Hence, ligand and mAb 13 did not appear to compete directly for binding to alpha 5 beta 1. The stimulatory anti-beta 1 mAb 9EG7 was found to increase the maximum level of ligand binding similar to 2-fold, indicating that up to 50% of the total integrin could not bind ligand without 9EG7 stimulation. Analysis of mAb 13 binding in the presence of 9EG7 and ligand (i.e. maximal ligand occupancy) demonstrated that essentially all of the integrin bound mAb 13 with very low or zero affinity. Our results demonstrate that mAb 13 recognizes an epitope that is dramatically attenuated in the ligand-occupied form of alpha 5 beta 1. Hence, since mAb 13 preferentially recognizes the unoccupied conformation of the integrin, the antibody may inhibit ligand binding by stabilizing the unoccupied state of alpha 5 beta 1. In addition, we present evidence that the binding of mAb 13 to ligand-occupied alpha 5 beta 1 may also induce a conformational change in the integrin, resulting in the displacement of ligand. C1 NIDR,NIH,DEV BIOL LAB,BETHESDA,MD 20892. RP Mould, AP (reprint author), UNIV MANCHESTER,SCH BIOL SCI,WELLCOME TRUST CTR CELL MATRIX RES,2205 STOPFORD BLDG,MANCHESTER M13 9PT,LANCS,ENGLAND. FU Wellcome Trust NR 46 TC 81 Z9 82 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 23 PY 1996 VL 271 IS 34 BP 20365 EP 20374 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700024 PM 8702772 ER PT J AU Olney, JJ Sellers, JR Cremo, CR AF Olney, JJ Sellers, JR Cremo, CR TI Structure and function of the 10S conformation of smooth muscle myosin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REGULATORY LIGHT-CHAIN; HEAVY-MEROMYOSIN; ACTIVE-SITE; ATPASE ACTIVITY; GIZZARD MYOSIN; PHOSPHORYLATION; FILAMENTS; IDENTIFICATION; CONTRACTION; TRANSITION AB Smooth myosin regulatory light chain (RLC) was exchanged with RLC labeled with benzophenone-4-iodoacetamide at Cys-108. Irradiation under conditions that favor the folded (10 S) conformation resulted in 10 S cross-linked myosin that could not unfold. Purified 10 S cross-linked myosin was cross-linked between the RLC of one head to light meromyosin between leucine 1554 and glutamate 1583, adjacent to a predicted noncoiled region, approximately 60 nn from the tip of the tail. At high ionic strength without actin, product release from one-half of the heads was slow (like 10 S) whereas the other half were activated. This suggests that tail binding to the RLC carboxyl-terminal domain stabilizes ionic interactions important to slow nucleotide release. With actin, product release from both (un)phosphorylated 10 S cross-linked myosin was from one slow population similar to unphosphorylated filaments. 10 S cross-linked myosin weakly bound actin (dissociation constant > 500 mu M) and did not move actin in vitro. Single-headed myosin did not fold or trap nucleotide, These and other data suggest that ''trapping'' occurs only with both heads and the tail binds to a newly formed site, which includes the RLC carboxyl-terminal domain, once trapping has occurred. C1 WASHINGTON STATE UNIV, DEPT BIOCHEM & BIOPHYS, PULLMAN, WA 99164 USA. NHLBI, MOL CARDIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 64 TC 33 Z9 33 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 AUG 23 PY 1996 VL 271 IS 34 BP 20375 EP 20384 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700025 PM 8702773 ER PT J AU Taylor, GA Jeffers, M Largaespada, DA Jenkins, NA Copeland, NG VandeWoude, GF AF Taylor, GA Jeffers, M Largaespada, DA Jenkins, NA Copeland, NG VandeWoude, GF TI Identification of a novel GTPase, the inducibly expressed GTPase, that accumulates in response to interferon gamma SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE PERITONEAL-MACROPHAGES; SIGNAL RECOGNITION PARTICLE; TUMOR-NECROSIS-FACTOR; IFN-GAMMA; TRIPHOSPHATE CONFORMATION; MOLECULAR-CLONING; BINDING PROTEINS; GROWTH-FACTOR; DYNAMIN; GENE AB Interferon gamma is a pleiotropic cytokine that regulates many immune functions, We have identified a novel protein, inducibly expressed GTPase (IGTP), whose expression was regulated by interferon gamma in macrophages. In mouse RAW 264.7 macrophages, IGTP mRNA levels were almost undetectable but increased within 1 h of exposure to interferon gamma, peaked at very high levels within 3 h, and remained at high levels to at least 48 h; pretreatment of the cells with cycloheximide blocked the majority of mRNA accumulation, In the mouse, the mRNA was highly expressed in thymus, spleen, lung, and small intestine. Using interspecific backcross analysis, the Igtp gene was mapped to mouse chromosome 11. The IGTP cDNA encoded a putative polypeptide of M(r) 48,507 and pI 7.79 that contained three consensus GTP binding motifs, GXXXXGK(S/T), DXXG, and NTKXD. Both IGTP that had been immunoprecipitated from RAW cells and a glutathione S-transferase IGTP fusion protein were able to convert GTP to GDP in vitro. Subcellular protein fractionation and Western blotting localized IGTP to the cytosol of RAW cells, In addition, the protein was homologous to proteins encoded by three previously cloned cDNAs, IRG-47, TGTP/Mg21, and LRG-47, and thus may be representative of a new family of interferon gamma-regulated GTPases. C1 NCI,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RI Largaespada, David/C-9832-2014 NR 45 TC 74 Z9 83 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 23 PY 1996 VL 271 IS 34 BP 20399 EP 20405 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700028 PM 8702776 ER PT J AU Piras, G Dittmer, J Radonovich, MF Brady, JN AF Piras, G Dittmer, J Radonovich, MF Brady, JN TI Human T-cell leukemia virus type I tax protein transactivates RNA polymerase III promoter in vitro and in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONG TERMINAL REPEAT; TROPICAL SPASTIC PARAPARESIS; PRIMARY HUMAN-LYMPHOCYTES; RECEPTOR GENE-EXPRESSION; CAMP-RESPONSIVE ELEMENT; 2 FUNCTIONAL COMPONENTS; HORMONE-RELATED PROTEIN; HTLV-I; TRANSCRIPTIONAL ACTIVATION; 21-BASE-PAIR REPEATS AB Tax protein of the human T-cell lymphotropic virus type 1 (HTLV-I) is critical for viral replication and is a potent transcriptional activator of viral and cellular polymerase II (pol II) genes, We report here that Tax is able to transactivate a classical pol III promoter, VA-I. In cotransfection experiments, Tax is shown to increase transcription of the VA-I promoter approximately 25-fold. Moreover, Tax is able to activate VA-I transcription when added exogenously to an in vitro transcription reaction, Using Tax affinity column chromatography, we demonstrate that Tax is able to deplete a HeLa cell extract for components required for transcription of VA-I. The transcriptional activity of the Tax-depleted extract can be restored by the 0.6 M phosphocellulose fraction. Interestingly, a consensus binding site for cAMP-responsive element binding protein (CREB) is located upstream of the VA-I promoter, and deletion of this element results in the loss of Tax responsiveness, When this CREB binding site is replaced by a Gal-4 binding site, the VA-I promoter can be transactivated by a Gal4-Tax fusion protein, Taken together, these results suggest that Tax may activate pol III and pol II promoter through a similar mechanism involving the CREB activation pathway, It is also possible that Tax affects pol III transcription by direct interaction with a component of the pol III transcriptional machinery. C1 NCI,MOL VIROL LAB,NIH,BETHESDA,MD 20892. RI Dittmer, Juergen/G-1160-2011 NR 74 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 23 PY 1996 VL 271 IS 34 BP 20501 EP 20506 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700043 PM 8702791 ER PT J AU Ahuja, SK Murphy, PM AF Ahuja, SK Murphy, PM TI The CXC chemokines growth-regulated oncogene (GRO) alpha, GRO beta, GRO gamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interleukin-8 receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; CHEMOTACTIC CYTOKINES; STIMULATORY ACTIVITY; A RECEPTOR; IL-8; BINDING; CHEMOATTRACTANT; IDENTIFICATION; LYMPHOTACTIN AB Interleukin-8 (IL-8), growth-related oncogene (GRO) alpha, GRO beta, GRO gamma, neutrophil-activating peptide-2 (NAP-2), epithelial cell-derived neutrophil activating peptide-78 (ENA-78), and granulocyte chemoattractant protein-2 are potent neutrophil chemoattractants 40-90% identical in amino acid sequence that comprise a subgroup of human CXC chemokines defined by the conserved sequence motif glutamic acid-leucine-arginine (ELR). Two human chemotactic receptor subtypes for IL-8, named IL-8 receptors (IL8R) A and B, have been cloned. They are 78% identical in amino acid sequence, coexpressed in neutrophils, and distinguished by their different se selectivities for GRO alpha and NAP-2. Their selectivity for other ELR(+) CXC chemokines has not been previously reported. By measuring calcium flux in human embryonic kidney 293 cells transfected with plasmids encoding IL8RA or IL8RB, we have now defined receptor selectivity for GRO beta, GRO gamma, and ENA-78. The rank order of agonist potency, based on inspection of the mean effective concentration values (EC(50)), for IL8RB was GRO gamma (1 nM) > IL-8 (4 nM) similar to GRO alpha (5 nM) similar to GRO beta (4 nM) similar to NAP-2 (7 nM) > ENA-78 (11 nM), and for IL8RA was IL-8 (4 nM) >>> ENA-78 (40 nM) similar to NAP-2 (45 nM) > GRO alpha (63 nM) similar to GRO gamma (65 nM) >> GRO beta. The maximal response of IL8RA to IL-8 was at least a-fold greater than the other five chemokines. All six agonists for IL8RB competed for high affinity I-125-IL-8, -GRO alpha NAP-2, and -ENA-78 binding sites at IL8RB. GRO alpha, GRO beta, GP gamma, NAP-2, and ENA-78 competed weakly for the high affinity IL-8 binding site at IL8RA. Thus, IL8RA and IL8RB are both highly selective for IL-8 and have similar sequences but differ dramatically in their selectivity for all other ELR(+) CXC chemokines tested. These findings have important implications for developing novel neutrophil-specific anti-inflammatory drugs directed against the CXC chemokine signaling system. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 35 TC 268 Z9 272 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 23 PY 1996 VL 271 IS 34 BP 20545 EP 20550 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700050 PM 8702798 ER PT J AU Butcher, BA Turco, SJ Hilty, BA Pimenta, PF Panunzio, M Sacks, DL AF Butcher, BA Turco, SJ Hilty, BA Pimenta, PF Panunzio, M Sacks, DL TI Deficiency in beta 1,3-galactosyltransferase of a Leishmania major lipophosphoglycan mutant adversely influences the Leishmania sand fly interaction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROMASTIGOTES; DONOVANI; IDENTIFICATION; EXPRESSION; VIRULENCE AB To study the function of side chain oligosaccharides of the cell-surface lipophosphoglycan (LPG), mutagenized Leishmania major defective in side chain biosynthesis were negatively selected by agglutination with the monoclonal antibody WIC79,3, which recognizes the galactose-containing side chains of L, major LPG, One such mutant, called Spock, lacked the ability to bind significantly to midguts of the natural L. major vector, Phlebotomus papatasi, and to maintain infection in the sand fly after excretion of the digested bloodmeal, Biochemical characterization of Spock LPG revealed its structural similarity to the LPG of Leishmania donovani, a species whose inability to bind to and maintain infections in P, papatasi midguts has been strongly correlated with the expression of a surface LPG lacking galactose-terminated oligosaccharide side chains, An in vitro galactosyltransferase assay using wild-type or Spock membranes was used to determine that the defect in Spock LPG biosynthesis is a result of defective beta 1,3-galactosyltransferase activity as opposed to a modification of LPG, which would prevent it from serving as a competent substrate for galactose addition, The results of these experiments show that Speck lacks the beta 1,3-galactosyltransferase for side chain addition and that the LPG side chains are required for L, major to bind to and to produce transmissible infection in P, papatasi. C1 UNIV KENTUCKY,MED CTR,DEPT BIOCHEM,LEXINGTON,KY 40536. NIH,PARASIT DIS LAB,INTRACELLULAR PARASITE BIOL SECT,BETHESDA,MD 20892. UNIV ESTADUAL NORTE FLUMINENSE,PARASITOL LAB,CTR BIOCIENCIAS & BITECNOL,RIO JANEIRO,BRAZIL. UNIV BARI,INST MED MICROBIOL,BARI,ITALY. FU NIAID NIH HHS [R37 AI20491] NR 25 TC 59 Z9 60 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 23 PY 1996 VL 271 IS 34 BP 20573 EP 20579 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700054 PM 8702802 ER PT J AU Kutty, RK Kutty, G Kambadur, R Duncan, T Koonin, EV Rodriguez, IR Odenwald, WF Wiggert, B AF Kutty, RK Kutty, G Kambadur, R Duncan, T Koonin, EV Rodriguez, IR Odenwald, WF Wiggert, B TI Molecular characterization and developmental expression of a retinoid- and fatty acid-binding glycoprotein from Drosophila - A putative lipophorin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VON-WILLEBRAND-FACTOR; PROTEIN SECONDARY STRUCTURE; LIPID TRANSPORT; GENE; LIPOPROTEIN; ENCODES; DNA; NITROCELLULOSE; BIOSYNTHESIS; LIPOVITELLIN AB A detailed understanding of the mechanism of Lipid transport in insects has been hampered by the inability to identify the proapolipophorin gene that encodes apolipophorins I and II, the principal protein components of lipophorin, the lipid transport vehicle, Here we provide the first molecular description of the Drosophila gene encoding a retinoid- and fatty acid-binding glycoprotein (RFABG) and present evidence that it is a member of the proapolipophorin gene family, The gene, localized to the chromosome 4 (102 F region), encodes a 3351-amino acid protein that could serve as the precursor for the similar to 70-kDa and > 200-kDa polypeptides associated with RFABG, The N-terminal sequence of the similar to 70-kDa polypeptide and that predicted for the > 200-kDa polypeptide showed high sequence similarity to blowfly apolipophorin II and apolipophorin I, respectively. The RFABG precursor contains a signal peptide and exhibits a multidomain mosaic protein structure, which is typical of extracellular proteins. It has structural domains similar to lipid-binding proteins, namely vitellogenins and apolipoprotein B. The protein also contains a domain similar to the D domain of von Willebrand factor and mucin, The gene is expressed in the Drosophila embryo during development in cells that make up the amnioserosa and fat bodies. Immunolocalizations using specific antibodies against RFABG reveal that the protein is initially dispersed through the embryonic amnioserosa sac and latter concentrated at skeletal muscle-epidermis apodemeal contact junctions during larval development, This novel gene may play an important role in the transport of lipids, including retinoids and fatty acids, in insects. C1 NINCDS,NEUROGENET UNIT,NEUROCHEM LAB,BETHESDA,MD 20892. NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20892. RP Kutty, RK (reprint author), NEI,RETINAL CELL & MOL BIOL LAB,BETHESDA,MD 20892, USA. NR 49 TC 63 Z9 64 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 AUG 23 PY 1996 VL 271 IS 34 BP 20641 EP 20649 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700064 PM 8702812 ER PT J AU Saxena, SK Gravell, M Wu, YN Mikulski, SM Shogen, K Ardelt, W Youle, RJ AF Saxena, SK Gravell, M Wu, YN Mikulski, SM Shogen, K Ardelt, W Youle, RJ TI Inhibition of HIV-1 production and selective degradation of viral RNA by an amphibian ribonuclease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; III REPLICATION INVITRO; ALPHA-A-INTERFERON; CYTOTOXIC RIBONUCLEASES; SYNERGISTIC INHIBITION; MOLECULAR EVOLUTION; P-30 PROTEIN; H9 CELLS; INFECTION; SUPERFAMILY AB Ribonucleases appear to have physiologic roles in host defense against cancer, viruses, and other parasites, Previously it was shown that select ribonucleases added to cells concurrently with virions blocked human immunodeficiency virus, type I (HIV-1) infection of H9 cells, We now report that a ribonuclease homologous to RNase A, named onconase, inhibits virus replication in chronically HIV-1-infected human cells without killing the virally infected cell, Examining the mechanism of this inhibition shows that onconase enters the infected cells and degrades HIV-1 RNA without degrading ribosomal RNA or the three different cellular messenger RNAs analyzed, The homologous human pancreatic RNase lacks anti-viral activity, Comparing recombinant forms of onconase and a onconase-human RNase chimera shows that the N-terminal 9 amino acids and the pyroglutamyl residue of onconase are required for full anti-viral activity. Thus extracellular ribonucleases can enter cells, metabolize select RNAs, and inhibit HIV virion production within viable replicating cells. C1 NINCDS,BIOCHEM SECT,SURG NEUROL BRANCH,NIH,BETHESDA,MD 20892. NINCDS,LAB MOL MED & NEUROSCI,BETHESDA,MD 20892. ALFACELL CORP,BLOOMFIELD,NJ 07003. OI Saxena, Shailendra K/0000-0003-2856-4185 NR 42 TC 66 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 AUG 23 PY 1996 VL 271 IS 34 BP 20783 EP 20788 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700084 PM 8702832 ER PT J AU Weitzmann, MN Woodford, KJ Usdin, K AF Weitzmann, MN Woodford, KJ Usdin, K TI The development and use of a DNA polymerase arrest assay for the evaluation of parameters affecting intrastrand tetraplex formation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TELOMERE-BINDING-PROTEIN; GENE; SEQUENCE; QUADRUPLEX; HAIRPIN; REGION; MODEL; ACID; CHROMOSOME; EXPRESSION AB We show here that a K+-dependent block to DNA synthesis is a sensitive and specific indicator of intrastrand tetraplex formation that can be used, both to identify sequences with tetraplex-forming potential and to examine parameters that affect tetraplex formation, We show that tetraplex formation is determined by a complex combination of factors including the size and base composition of its constituent loops and stems, In the process of carrying out this study we have found that the number of sequences with the ability to form tetraplexes is larger than previously thought, and that such sequences are ubiquitous in eukaryote genomes. C1 NIDDK,NIH,BIOCHEM PHARMACOL LAB,SECT GENOM STRUCT & FUNCT,BETHESDA,MD 20892. NR 37 TC 63 Z9 63 U1 0 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 23 PY 1996 VL 271 IS 34 BP 20958 EP 20964 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700107 PM 8702855 ER PT J AU Romanova, LY Deriagin, GV Mashkova, TD Tumeneva, IG Mushegian, AR Kisselev, LL Alexandrov, IA AF Romanova, LY Deriagin, GV Mashkova, TD Tumeneva, IG Mushegian, AR Kisselev, LL Alexandrov, IA TI Evidence for selection in evolution of alpha satellite DNA: The central role of CENP-B/pJ alpha binding region SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE centromere; alpha satellite; selection; CENP-B; DNA repeats ID HUMAN Y-CHROMOSOME; GENOMIC DISTRIBUTION; SEQUENCE; STERILITY; ORGANIZATION; MUS; KINETOCHORE; CENTROMERES; DISRUPTION; MITOSIS AB Conservation of DNA segments performing sequence-related functions is a landmark of selection and functional significance. Phylogenetic variability of alpha satellite and apparent absence of conserved regions calls its functional significance into question, even though sequence-specific alpha satellite-binding proteins pJ alpha and CENP-B have been discovered. Moreover, the function of pJ alpha is obscure and CENP-B binding satellite DNA, which is thought to participate in centromere formation, is found only in few species and not necessarily in all chromosomes. Analysis of alpha satellite evolution allows us to recognize the order in this variability. Here we report a new alpha satellite suprachromosomal family, which together with the four defined earlier, covers all known alpha satellite sequences. Although each family has its characteristic types of monomers, they all descend from two prototypes, A and B. We show that most differences between prototypes are concentrated in a short region (positions 35 to 51), which exists in two alternative states: it matches a binding site for pJ alpha. in type A and the one for CENP-B in type B. Lower primates have only type A monomers whereas great apes have both A and B. The new family is formed by monomeric types almost identical to A and B prototypes, thus representing a living relic of alpha satellite. Analysis of these data shows that selection-driven evolution, rather than random fixation of mutations, formed the distinction between A and B types. To our knowledge, this is the first evidence for selection in any of the known satellite DNAs. (C) 1996 Academic Press Limited. C1 NATL RES CTR MENTAL HLTH,MOSCOW,RUSSIA. VA ENGELHARDT MOL BIOL INST,LAB MOL BASIS ONCOGENESIS,MOSCOW 117984,RUSSIA. NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20892. NR 33 TC 59 Z9 59 U1 0 U2 2 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 AUG 23 PY 1996 VL 261 IS 3 BP 334 EP 340 DI 10.1006/jmbi.1996.0466 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD432 UT WOS:A1996VD43200006 PM 8780776 ER PT J AU Pascale, A Fortino, I Govoni, S Trabucchi, M Wetsel, WC Battaini, F AF Pascale, A Fortino, I Govoni, S Trabucchi, M Wetsel, WC Battaini, F TI Differential isoform-specific regulation of calcium-independent protein kinase C in rat cerebral cortex SO NEUROSCIENCE LETTERS LA English DT Article DE rat cerebral cortex; protein kinase C; calcium-independent isoforms; phorbol esters; Western blot analysis ID LONG-TERM POTENTIATION; PHORBOL ESTER; HIPPOCAMPUS; ACTIVATION; EXPRESSION; ISOENZYMES; RELEASE; BRAIN; CELLS AB Regulation of the Ca2+-independent protein kinase C (PKC) activity and isoforms by phorbol esters was investigated in rat cerebral cortex. Loss of soluble PKC eta immunoreactivity from the soluble fraction was dramatic with only a small increase in the membrane fraction. The kinetics of PKC epsilon and -delta translocation were slower than that for PKCeta, while phorbol esters had no effect on PKC zeta translocation. Despite the translocation of PKC delta, -epsilon and -eta from the soluble to the membrane fraction, both fractions showed a loss of PKC activity. These data indicate that the rates of translocation, inactivation and/or downregulation appear to be different not only among these Ca2+-independent isozymes, but also from that reported for the Ca2+-dependent PKCs. In addition, these results emphasize the importance of measuring both Ca2+-independent PKC activity and immunoreactivity in evaluating activation of these isoforms. C1 UNIV MILAN,INST PHARMACOL SCI,I-20133 MILAN,ITALY. UNIV PAVIA,INST PHARMACOL,I-27100 PAVIA,ITALY. UNIV ROMA TOR VERGATA,DEPT EXPT MED & BIOCHEM SCI,ROME,ITALY. NIEHS,CELLULAR & MOL PHARMACOL LAB,RES TRIANGLE PK,NC 27709. RI Battaini , Fiorenzo/H-2617-2012; Govoni, Stefano/K-2965-2015 OI Govoni, Stefano/0000-0002-7243-6837 NR 21 TC 16 Z9 16 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 AUG 23 PY 1996 VL 214 IS 2-3 BP 99 EP 102 DI 10.1016/0304-3940(96)12901-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VF281 UT WOS:A1996VF28100007 PM 8878093 ER PT J AU Katsube, N Sunaga, K Chuang, DM Ishitani, R AF Katsube, N Sunaga, K Chuang, DM Ishitani, R TI ONO-1603, a potential antidementia drug, shows neuroprotective effects and increases m(3)-muscarinic receptor mRNA levels in differentiating rat cerebellar granule neurons SO NEUROSCIENCE LETTERS LA English DT Article DE prolyl endopeptidase inhibitor; ONO-1603; antidementia; cerebellar granule cell; neurotrophic; muscarinic receptor; Alzheimer's disease ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; TETRAHYDROAMINOACRIDINE; CELLS AB We have reported that the antidementia drug tetrahydroaminoacridine (THA; 30 mu M) is neuroprotective and neurotrophic and selectively increases m(3)-muscarinic acetylcholine receptor (mAChR) mRNA levels in differentiating cerebellar granule cells. Here, we examined whether novel prolyl endopeptidase inhibitor ONO-1603, a potential antidementia drug, induces similar effects in these cerebellar neurons. Supplement of ONO-1603 (0.03 mu M) to cultures grown in 15 mM KCl-containing media was found to markedly promote neuronal survival and neurite outgrowth and enhance [H-3]N-methylscopolamine binding to mAChRs. Moreover, ONO-1603 increased the level of m(3)-mAChR mRNA and stimulated mAChR-mediated phosphoinositide turnover. The common actions of ONO-1603 and THA suggest that these properties could be related to their putative antidementia activities and that this model system may be used to screen for drugs effective in the treatment for Alzheimer's disease. C1 JOSAI UNIV,GRP CELLULAR NEUROBIOL,SAKADO,SAITAMA 35002,JAPAN. ONO PHARMACEUT CO LTD,MINASE RES INST,OSAKA 618,JAPAN. NIMH,BIOL PSYCHIAT BRANCH,MOL NEUROBIOL SECT,NIH,BETHESDA,MD 20892. NR 19 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD AUG 23 PY 1996 VL 214 IS 2-3 BP 151 EP 154 DI 10.1016/0304-3940(96)12912-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VF281 UT WOS:A1996VF28100020 PM 8878106 ER PT J AU Kondoh, N Noda, M Fisher, RJ Schweinfest, CW Papas, TS Kondoh, A Samuel, KP Oikawa, T AF Kondoh, N Noda, M Fisher, RJ Schweinfest, CW Papas, TS Kondoh, A Samuel, KP Oikawa, T TI The S29 ribosomal protein increases tumor suppressor activity of Krev-1 gene on v-Kras-transformed NIH3T3 cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE S29 ribosomal protein; Krev-1; tumor suppressor ID SIGNAL-TRANSDUCTION; COLON-CARCINOMA; MESSENGER-RNAS; RAF-1; RAS; GROWTH; KINASE; PHOSPHORYLATION; EXPRESSION; RESISTANT AB The human S29 ribosomal protein (S29 rp) cDNA has been isolated from differential hybridization screening of a colon carcinoma cDNA library, Northern blot analysis showed that the level of S29 rp mRNA was higher in undifferentiated HT29 human colon carcinoma cells than in a morphologically differentiated subclone under the same growth condition. Furthermore, the level of S29 rp mRNA was downregulated in rapidly proliferating HT29 cells, as compared to the contact inhibited cells. Interestingly, the amount of It rev-1 mRNA was inversely correlated with respect to the amount of S29 rp mRNA in these cells, To examine a functional link between S29 rp and K rev-1 protein, we co-transfected the expression vectors containing wild-type or mutant S29 rp and mutationally activated K rev-1(63E) cDNAs into the v-Ki-ras-transformed NIH3T3 (DT) cells, and observed the induction of flat revertants. K rev-1(63E) induced a certain amount of flat colonies, while S29 rp alone also induced flat colonies at low frequencies. Interestingly, revertant-inducing activity of K rev-1(63E) was significantly enhanced by S29 rp, We have also demonstrated that a zinc finger-like domain of S29 rp indeed has a zinc binding activity and a derivative, S29 rp(ms), which was unable to bind zinc ion but still retained revertant inducing activity by itself, could not functionally interact with K rev-1(63E) protein. C1 SASAKI INST,DEPT CELL GENET,TOKYO 101,JAPAN. KYOTO UNIV,SCH MED,DEPT MOL ONCOL,SAKYO KU,KYOTO 606,JAPAN. SAIC,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. MED UNIV S CAROLINA,CMSB HOLLINGS CANC CTR,CHARLESTON,SC 29425. RI Fisher, Robert/B-1431-2009 NR 29 TC 16 Z9 19 U1 0 U2 2 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 AUG 21 PY 1996 VL 1313 IS 1 BP 41 EP 46 DI 10.1016/0167-4889(96)00052-3 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VE147 UT WOS:A1996VE14700007 PM 8781548 ER PT J AU Bach, LA Rechler, MM AF Bach, LA Rechler, MM TI Measurement of insulin-like growth factor (IGF)-II binding to purified IGF binding proteins 1-6: Comparison of charcoal adsorption and high performance size exclusion chromatography SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE insulin-like growth factor-II; charcoal adsorption; size exclusion chromatography ID HUMAN-FIBROBLASTS; CARRIER PROTEIN; RAT-LIVER; SERUM; RECEPTOR AB Insulin-like growth factor (IGF) binding to IGF binding proteins is commonly assessed by adsorbing free IGF to albumin-coated charcoal and quantitating bound IGF in the supernatant, but the validity of this technique has been questioned and many variations have been described. We compared the measurement of binding affinity and capacity of purified IGFBPs 1-6 for IGF-II using charcoal adsorption and Superdex G75 high performance size exclusion chromatography (HPSEC) to separate free and bound I-125-IGF-II. Optimal HPSEC recovery and resolution was obtained for IGFBP-1 and IGFBP-6 with low salt buffer (0.1 M sodium phosphate, pH 7.4), whereas phosphate buffer supplemented with 0.5 M NaCl was optimal for IGFBPs 2-5. Measurement of binding of I-125-IGF-II to IGFBPs 3-5 using the charcoal assay was also increased by the use of high salt buffer. Under optimal conditions, charcoal measurements of I-125-IGF-II binding to IGFBPs 1-5 were consistently lower than HPSEC measurements. By competitive binding using unlabeled IGF-II, the binding affinity of each of the IGFBPs for IGF-II was the same using both methods. Similarly, binding affinities as measured by charcoal assay were not affected by buffer composition. Differences in total binding obtained using the two methods and under different conditions were therefore due to differences in binding capacity. Charcoal adsorbs 15% of cross-linked I-125-IGF-II:IGFBP complexes which may partially explain the lower binding capacity for IGFBPs 1-5 determined by charcoal adsorption. Charcoal adsorption and HPSEC, therefore, are both valid methods for the measurement of binding affinities of IGFBPs for IGF-II, but assay conditions must be validated prior to measurement of binding capacity. C1 NIDDKD,GROWTH & DEV SECT,MOL & CELLULAR ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. OI Bach, Leon/0000-0002-9062-1518 NR 25 TC 8 Z9 8 U1 0 U2 1 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 AUG 21 PY 1996 VL 1313 IS 1 BP 79 EP 88 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VE147 UT WOS:A1996VE14700012 PM 8781553 ER PT J AU Schiffmann, R AF Schiffmann, R TI Niemann-Pick disease type C - From bench to bedside SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LIPOPROTEIN-DERIVED CHOLESTEROL; INTRACELLULAR-TRANSPORT; CULTURED FIBROBLASTS; STORAGE; ESTERIFICATION; ACCUMULATION; SPECTRUM RP Schiffmann, R (reprint author), NINCDS,DEV & METAB BRANCH,NIH,BLDG 10,ROOM 3D03,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 23 TC 24 Z9 24 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 21 PY 1996 VL 276 IS 7 BP 561 EP 564 DI 10.1001/jama.276.7.561 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VC101 UT WOS:A1996VC10100033 PM 8709406 ER PT J AU Wiener, EC Auteri, FP Chen, JW Brechbiel, MW Gansow, OA Schneider, DS Belford, RL Clarkson, RB Lauterbur, PC AF Wiener, EC Auteri, FP Chen, JW Brechbiel, MW Gansow, OA Schneider, DS Belford, RL Clarkson, RB Lauterbur, PC TI Molecular dynamics of ion-chelate complexes attached to dendrimers SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PROTON RELAXATION ENHANCEMENT; SPIN-LATTICE RELAXATION; RESONANCE LINE-SHAPES; MR CONTRAST AGENT; GD-DTPA; MAGNETIC-RESONANCE; VANADYL COMPLEXES; WEIGHT; POLYMERS; CONJUGATION AB We studied the molecular dynamics of vanadyl-chelate complexes covalently attached to the surface of cascade polymers, dendrimers. The rotational correlation times of the ion-chelate complex were determined from computer simulations of their EPR spectra. The chelate 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid was covalently attached to ammonia core poly(amidoamine) (PAMAM) cascade polymers via a thiourea (TU) linkage, resulting in PAMAM-TU-DTPA cascade polymers. X-band EPR spectra of their vanadyl complexes were taken, and the A and g matrices were determined from the rigid limit spectra using the SIMPOW program. Spectra were fitted with modification of the slow-motional line-shape theory. Our results indicate that the rotational correlation times of the surface chelate increase with molecular weight and resemble those of ''internal'' segmental motions found in PAMAMs. For this macromolecular system, the rotational correlation times alone cannot account for differences in the relaxivity between high and moderate molecular weight species, These data are consistent with the hypothesis that the differences between linear-based and cascade polymer-based MRI contrast agents in the response of their relaxivity to molecular weight partially result from differing responses of their rotational correlation time to increases in molecular weight. A comparison of isotropic and anisotropic tumbling models indicates anisotropic tumbling of the ion-chelate complex at physiological temperatures, which is consistent with a model that incorporates segmental motions of the dendrimer side chains. C1 BECKMAN INSTRUMENTS INC,URBANA,IL 61801. UNIV ILLINOIS,DEPT VET MED,URBANA,IL 61821. UNIV ILLINOIS,DEPT CHEM,URBANA,IL 61821. CORNELL UNIV,CORNELL THEORY CTR,ITHACA,NY 14853. NCI,NIH,BETHESDA,MD 20892. RP Wiener, EC (reprint author), UNIV ILLINOIS,COLL MED,DEPT MED INFORMAT SCI,BIOMED MAGNET RESONANCE LAB,URBANA,IL 61801, USA. RI Schneider, David/H-2236-2012 OI Schneider, David/0000-0002-2124-8385 NR 56 TC 84 Z9 88 U1 2 U2 18 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 AUG 21 PY 1996 VL 118 IS 33 BP 7774 EP 7782 DI 10.1021/ja9536126 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA VD328 UT WOS:A1996VD32800017 ER PT J AU Hsing, AW AF Hsing, AW TI Hormones and prostate cancer: Where do we go from here? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID SERUM HORMONES; RISK; ESTROGEN; RATS RP Hsing, AW (reprint author), NCI,NIH,DIV CANC EPIDEMIOL & GENET,EPN 415,BETHESDA,MD 20892, USA. NR 22 TC 33 Z9 34 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 AUG 21 PY 1996 VL 88 IS 16 BP 1093 EP 1095 DI 10.1093/jnci/88.16.1093 PG 3 WC Oncology SC Oncology GA VC852 UT WOS:A1996VC85200002 PM 8757182 ER PT J AU Potischman, N Hoover, RN Brinton, LA Siiteri, P Dorgan, JF Swanson, CA Berman, ML Mortel, R Twiggs, LB Barrett, RJ Wilbanks, GD Persky, V Lurain, JR AF Potischman, N Hoover, RN Brinton, LA Siiteri, P Dorgan, JF Swanson, CA Berman, ML Mortel, R Twiggs, LB Barrett, RJ Wilbanks, GD Persky, V Lurain, JR TI Case-control study of endogenous steroid hormones and endometrial cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POST-MENOPAUSAL WOMEN; BODY-FAT DISTRIBUTION; POSTMENOPAUSAL WOMEN; ORAL-CONTRACEPTIVES; BINDING GLOBULIN; INSULIN-RESISTANCE; MENSTRUAL-CYCLE; FREE ESTRADIOL; RISK-FACTORS; ESTROGENS AB Background: It has been suggested that identified risk factors for endometrial cancer operate through a single etiologic pathway, i.e., exposure to relatively high levels of unopposed estrogen (estrogen in the absence of progestins). Only a few studies, however, have addressed this issue directly. Purpose: We assessed the risk of developing endometrial cancer among both premenopausal and postmenopausal women in relation to the circulating levels of steroid hormones and sex hormone-binding globulin (SHBG). The independent effect of hormones was assessed after adjustment for other known risk factors. Methods: The data used in the analysis are from a case-control study conducted in five geographic regions in the United States. Incident cases mere newly diagnosed during the period from June 1, 1987, through May 15, 1990. The case patients, aged 20-74 years, were matched to control subjects by age, race, and geographic region. The community control subjects were obtained by random-digit-dialing procedures (for subjects 20-64 years old) and from files of the Health Care Financing Administration (for subjects greater than or equal to 65 years old). Additional control subjects who were having a hysterectomy performed for benign conditions were obtained from the participating centers. Women reporting use of exogenous estrogens or oral contraceptives within 6 months of interview were excluded, resulting in 68 case patients and 107 control subjects among premenopausal women and 208 case patients and 209 control subjects among postmenopausal women. The hormone analyses were performed on blood samples obtained from case patients or from hysterectomy control subjects before surgery. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of an unconditional logistic regression analysis after we controlled for matching variables and potential confounders. All P values were two-sided. Results: High circulating levels of androstenedione were associated with 3.6-fold and 2.8-fold increased risks among premenopausal and postmenopausal women, respectively, after adjustment for other factors (P for trend = .01 and < .001, respectively). Risks related to other hormone fractions varied by menopausal status. Among postmenopausal women, a reduced risk was associated with high SHBG levels and persisted after adjustment was made for obesity and other factors (OR = 0.51; 95% CI = 0.27-0.95). High estrone levels were associated with increased risk (OR = 3.8; 95% CI = 2.2-6.6), although adjustment for other risk factors (particularly body mass index) diminished the effect (OR = 2.2; 95% CI = 1.2-4.4). Albumin-bound estradiol (E(2)), a marker of the bioavailable fraction, also remained an important risk factor after adjustment was made for other factors (OR = 2.0; 95% CI = 1.0-3.9). In contrast, high concentrations of total, free, and albumin-bound E(2) were unrelated to increased risk in premenopausal women. In both premenopausal and postmenopausal groups, risks associated with obesity and fat distribution were not affected by adjustment for hormones. Conclusion: High endogenous levels of unopposed estrogen are related to increased risk of endometrial cancer, but their independence from other risk factors is inconsistent with being a common underlying biologic pathway through which all risk factors for endometrial cancer operate. Implications: Further research should focus on alternative endocrinologic mechanisms for risk associated with obesity and body fat distribution and for the biologic relevance of the increased risk associated with androstenedione in both premenopausal and postmenopausal disease. C1 NCI,CANC PREVENT STUDIES BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. UNIV CALIF IRVINE,MED CTR,DEPT OBSTET & GYNECOL,IRVINE,CA 92717. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT OBSTET & GYNECOL,HERSHEY,PA 17033. UNIV MINNESOTA,SCH MED,DEPT OBSTET & GYNECOL,MINNEAPOLIS,MN 55455. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT OBSTET & GYNECOL,WINSTON SALEM,NC 27103. RUSH MED COLL,DEPT OBSTET & GYNECOL,CHICAGO,IL 60612. UNIV ILLINOIS,SCH PUBL HLTH,DIV EPIDEMIOL BIOSTAT,CHICAGO,IL. NORTHWESTERN UNIV,SCH MED,DEPT OBSTET & GYNECOL,CHICAGO,IL 60611. RP Potischman, N (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,SUITE 443,BETHESDA,MD 20892, USA. RI Perez , Claudio Alejandro/F-8310-2010; Brinton, Louise/G-7486-2015 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Brinton, Louise/0000-0003-3853-8562 NR 49 TC 184 Z9 193 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 21 PY 1996 VL 88 IS 16 BP 1127 EP 1135 DI 10.1093/jnci/88.16.1127 PG 9 WC Oncology SC Oncology GA VC852 UT WOS:A1996VC85200012 PM 8757192 ER PT J AU Workman, P Fitzsimmons, SA Grever, M Paull, K Camalier, R Lewis, AD AF Workman, P Fitzsimmons, SA Grever, M Paull, K Camalier, R Lewis, AD TI Reductase enzyme expression across the National Cancer Institute tumor cell line panel: Correlation with sensitivity to mitomycin C and EO9 - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID DT-DIAPHORASE ACTIVITY; INDOLOQUINONE EO9 C1 CRC,BEATSON LABS,GLASGOW,LANARK,SCOTLAND. JOHNS HOPKINS UNIV,CTR ONCOL,BALTIMORE,MD 21205. NCI,DIV CANC TREATMENT,INFORMAT TECHNOL BRANCH,BETHESDA,MD 20892. HERIOT WATT UNIV,QUINTILES SCOTLAND LTD,EDINBURGH,MIDLOTHIAN,SCOTLAND. RP Workman, P (reprint author), ZENECA PHARMACEUT,CANC METAB & ENDOCRINE RES DEPT,MERESIDE ALDERLEY PK,MACCLESFIELD SK10 4TJ,CHESHIRE,ENGLAND. NR 14 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 AUG 21 PY 1996 VL 88 IS 16 BP 1161 EP 1163 DI 10.1093/jnci/88.16.1161-a PG 3 WC Oncology SC Oncology GA VC852 UT WOS:A1996VC85200018 ER PT J AU Mule, JJ Custer, M Averbook, B Yang, JC Weber, JS Goeddel, DV Rosenberg, SA Schall, TJ AF Mule, JJ Custer, M Averbook, B Yang, JC Weber, JS Goeddel, DV Rosenberg, SA Schall, TJ TI RANTES secretion by gene-modified tumor cells results in loss of tumorigenicity in vivo: Role of immune cell subpopulations SO HUMAN GENE THERAPY LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; FUNCTIONAL EXPRESSION; HUMAN BASOPHILS; MOLECULAR-CLONING; CYTOKINE RANTES; C CHEMOKINE; LYMPHOCYTES; MONOCYTE; MIP-1-BETA; INVIVO AB An immunogenic murine fibrosarcoma cell line was genetically modified to express and produce the human RANTES chemokine stably, In in vitro chemotaxis assays purified recombinant human RANTES as well as human RANTES secreted by the modified murine tumor cells were strongly chemoattractant for mouse CD8(+)/Thy-1(+) tumor-infiltrating lymphocytes (TIL), RANTES production did not alter the growth of these cytokine gene-modified tumor cells in vitro, but injection of RANTES-secreting cells resulted in the abolition of the ability of those cells to form solid tumors in vivo. The growth of tumors could be restored by co-administration of monoclonal antibodies that inhibit the function of various subsets of immune cells, For example, depletion of CD8(+) T cells by antibody administration resulted in complete restoration of solid tumor formation by RANTES-secreting cells, whereas depletion of the CD4(+) T cell population resulted in a partial restoration of tumor formation, Additionally, administration of an anti-CR3 monoclonal antibody known to inhibit the in vivo migration of macrophages also completely restored the tumorigenicity of RANTES-secreting fibrosarcoma cells, Thus, the human RANTES chemokine can abolish tumorigenicity of an immunogenic fibrosarcoma in an in vivo murine model, and this process is mediated by various subpopulations of immune effector cells. C1 NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. GENENTECH INC,S SAN FRANCISCO,CA 94080. RP Mule, JJ (reprint author), UNIV MICHIGAN,DEPT SURG,MED CTR,MSRB-1,RM 1520C,1150 W MED CTR DR,ANN ARBOR,MI 48103, USA. NR 28 TC 117 Z9 120 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG 20 PY 1996 VL 7 IS 13 BP 1545 EP 1553 DI 10.1089/hum.1996.7.13-1545 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD322 UT WOS:A1996WD32200007 PM 8864755 ER PT J AU McKeon, C Samulski, RJ AF McKeon, C Samulski, RJ TI NIDDK workshop on AAV vectors: Gene transfer into quiescent cells SO HUMAN GENE THERAPY LA English DT Editorial Material C1 UNIV N CAROLINA,GENE THERAPY CTR,CHAPEL HILL,NC 27599. RP McKeon, C (reprint author), NIDDK,METAB DIS & GENE THERAPY RES PROGRAM,NIH,NATCHER BLDG RM 5AN-18B,45 CTR DR MSC 6600,BETHESDA,MD 20892, USA. NR 2 TC 14 Z9 14 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG 20 PY 1996 VL 7 IS 13 BP 1615 EP 1619 DI 10.1089/hum.1996.7.13-1615 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD322 UT WOS:A1996WD32200014 PM 8864762 ER PT J AU Lorenzi, MV Horii, Y Yamanaka, R Sakaguchi, K Miki, T AF Lorenzi, MV Horii, Y Yamanaka, R Sakaguchi, K Miki, T TI FRAG1, a gene that potently activates fibroblast growth factor receptor by C-terminal fusion through chromosomal rearrangement SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE receptor tyrosine kinase; expression cloning; malignant transformation; osteosarcoma; F6FR2 ID EXPRESSION CDNA CLONING; LIGAND-BINDING; SINGLE GENE; ONCOGENE; DOMAIN; PURIFICATION; SPECIFICITY; PROTEINS; FAMILY; MEMBER AB A constitutively active form of fibroblast growth factor 2 (FGFR2) was identified in rat osteosarcoma (ROS) cells by an expression cloning strategy, Unlike other tyrosine kinase receptors activated by N-terminal truncation in tumors, this receptor, FGFR2-ROS, contains an altered C terminus generated from chromosomal rearrangement with a novel gene, designated FGFR activating gene 1 (FRAG1). While the removal of the C terminus slightly activates FGFR2, the presence of the FRAG1 sequence drastically stimulates the transforming activity and autophosphorylation of the receptor. FGFR2-ROS is expressed as a unusually large protein and is highly phosphorylated in NIH 3T3 transfectants. FRAG1 is ubiquitously expressed and encodes a predicted protein of 28 kDa lacking significant structural similarity to known proteins. Epitope-tagged FRAG1 protein showed a perinuclear localization by immunofluorescence staining, The highly activated state of FGFR2-ROS appears to be attributed to constitutive dimer formation and higher phosphorylation level as well as possibly altered subcellular localization. These results indicate a unique mechanism of receptor activation by a C terminus alteration through a chromosomal fusion with FRAG1. C1 NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. NR 26 TC 35 Z9 37 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 20 PY 1996 VL 93 IS 17 BP 8956 EP 8961 DI 10.1073/pnas.93.17.8956 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VD434 UT WOS:A1996VD43400032 PM 8799135 ER PT J AU Vukicevic, S Kopp, JB Luyten, FP Sampath, TK AF Vukicevic, S Kopp, JB Luyten, FP Sampath, TK TI Induction of nephrogenic mesenchyme by osteogenic protein 1 (bone morphogenic protein 7) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE transforming growth factor type beta superfamily; epithelial-mesenchymal interaction; kidney development ID GROWTH FACTOR-I; KIDNEY DEVELOPMENT; RENAL DEVELOPMENT; FACTOR RECEPTOR; MESSENGER-RNA; EXPRESSION; MOUSE; CELLS; METANEPHROS; INVITRO AB The definitive mammalian kidney forms as the result of reciprocal interactions between the ureteric bud epithelium and metanephric mesenchyme, As osteogenic protein 1 (OP-1/bone morphogenetic protein 7), a member of the TGF-beta superfamily of proteins, is expressed predominantly in the kidney, we examined its involvement during metanephric induction and kidney differentiation. We found that OP-1 mRNA is expressed in the ureteric bud epithelium before mesenchymal condensation and is subsequently seen in the condensing mesenchyme and during glomerulogenesis, Mouse kidney metanephric rudiments cultured without ureteric bud epithelium failed to undergo mesenchymal condensation and further epithelialization, while exogenously added recombinant OP-1 was able to substitute for ureteric bud epithelium in restoring the induction of metanephric mesenchyme. This OP-1-induced nephrogenic mesenchyme differentiation follows a developmental pattern similar to that observed in the presence of the spinal cord, a metanephric inducer. Blocking OP-1 activity using either neutralizing antibodies or antisense oligonucleotides in mouse embryonic day 11.5 mesenchyme, cultured in the presence of metanephric inducers or in intact embryonic day 11.5 kidney rudiment, greatly reduced metanephric differentiation. These results demonstrate that OP-1 is required for metanephric mesenchyme differentiation and plays a functional role during kidney development. C1 NIDDKD,NIH,METAB DIS BRANCH,KIDNEY DIS SECT,BETHESDA,MD 20892. NIDR,NIH,BONE RES BRANCH,BETHESDA,MD 20892. CREAT BIOMOL INC,HOPKINTON,MA 01748. RP Vukicevic, S (reprint author), SCH MED,DEPT ANAT,ZAGREB 41000,CROATIA. NR 40 TC 142 Z9 146 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 20 PY 1996 VL 93 IS 17 BP 9021 EP 9026 DI 10.1073/pnas.93.17.9021 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VD434 UT WOS:A1996VD43400044 PM 8799147 ER PT J AU Jakubczak, JL Merlino, G French, JE Muller, WJ Paul, B Adhya, S Garges, S AF Jakubczak, JL Merlino, G French, JE Muller, WJ Paul, B Adhya, S Garges, S TI Analysis of genetic instability during mammary tumor progression using a novel selection-based assay for in vivo mutations in a bacteriophage lambda transgene target SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE middle T antigen; Big Blue; metastasis; transgenic mice; cII ID IN-VIVO; METASTATIC DISEASE; MUTATOR PHENOTYPE; MICE; CANCER; EXPRESSION; INVIVO; MODEL AB Genetic instability is thought to be responsible for the numerous genotypic changes that occur during neoplastic transformation and metastatic progression, To explore the role of genetic instability at the level of point mutations during mammary tumor development and malignant progression, we combined transgenic mouse models of mutagenesis detection and oncogenesis, Bitransgenic mice were generated that carried both a bacteriophage lambda transgene to assay mutagenesis and a polyomavirus middle T oncogene, mammary gland-targeted expression of which led to metastatic mammary adenocarcinomas. We developed a novel assay for the detection of mutations in the lambda transgene that selects for phage containing forward mutations only in the lambda cII gene, using an hfl(-) bacterial host, In addition to the relative ease of direct selection, the sensitivity of this assay for both spontaneous and chemically induced mutations was comparable to the widely used mutational target gene, lambda lacI, making the cII assay an attractive alternative for mutant phage recovery for any lambda-based mouse mutagenesis assay system, The frequencies of lambda cII(-) mutants were not significantly different in normal mammary epithelium, primary mammary adenocarcinomas, and pulmonary metastases, The cII mutational spectra in these tissues consisted mostly of G/C --> A/T transitions, a large fraction of which occurred at CpG dinucleotides, These data suggest that, in this middle T oncogene model of mammary tumor progression, a significant increase in mutagenesis is not required for tumor development or for metastatic progression. C1 NCI,MOL BIOL LAB,DEV GENET SECT,BETHESDA,MD 20892. NCI,MOL BIOL LAB,MOL GENET SECT,BETHESDA,MD 20892. NIEHS,RES TRIANGLE PK,NC 27709. MCMASTER UNIV,HAMILTON,ON L8S 4K1,CANADA. NR 25 TC 175 Z9 178 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 20 PY 1996 VL 93 IS 17 BP 9073 EP 9078 DI 10.1073/pnas.93.17.9073 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VD434 UT WOS:A1996VD43400053 PM 8799156 ER PT J AU Natarajan, K Singh, S Burke, TR Grunberger, D Aggarwal, BB AF Natarajan, K Singh, S Burke, TR Grunberger, D Aggarwal, BB TI Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE tumor necrosis factor; okadaic acid; ceramide; phorbol ester; hydrogen peroxide ID TUMOR-NECROSIS-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; INTACT-CELLS; T-CELLS; PROTEIN; EXPRESSION; BINDING; CAPE; GROWTH; TRANSFORMATION AB Caffeic acid phenethyl ester (CAFE), an active component of propolis from honeybee hives, is known to have antimitogenic, anticarcinogenic, antiinflammatory and immunomodulatory properties. The molecular basis for these! diverse properties is not known. Since the role of the nuclear factor NF-(k)appa B in these responses has been documented,,ve examined the effect of CAPE on this transcription factor, Our results show that the activation of NF-kappa B by tumor necrosis factor (TNF) is completely blocked by CAFE in a dose- and time-dependent manner. Besides TNF, CAFE also inhibited NF-kappa B activation induced by other inflammatory agents including phorbol ester, ceramide, hydrogen peroxide, and okadaic acid, Since the reducing agents reversed the inhibitory effect of CAFE, it suggests the role of critical sulfhydryl groups in NF-kappa B activation, CAFE prevented the translocation of the p65 subunit of NF-kappa B to the nucleus and had no significant effect on TNF-induced I kappa B alpha degradation, but did delay I kappa B alpha resynthesis. The effect of CAFE on inhibition of NF-kappa B binding to the DNA was specific, in as much as binding of other transcription factors including AP-I, Oct-1, and TFIID to their DNA were not affected, When various synthetic structural analogues of CAFE were examined, it was found that a bicyclic, rotationally constrained, 5,6-dihydroxy form was superactive, whereas 6,7-dihydroxy variant was least active. Thus, overall our results demonstrate that CAFE is a potent and a specific inhibitor of NF-kappa B activation and this may provide the molecular basis for its multiple immunomodulatory and antiinflammatory activities. C1 UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT MED ONCOL,CYTOKINE RES SECT,HOUSTON,TX 77030. NCI,DIV BASIC SCI,MED CHEM LAB,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,INST CANC RES,NEW YORK,NY 10032. RI Aggarwal, Bharat/G-3388-2013; Burke, Terrence/N-2601-2014 NR 44 TC 766 Z9 791 U1 2 U2 41 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 20 PY 1996 VL 93 IS 17 BP 9090 EP 9095 DI 10.1073/pnas.93.17.9090 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VD434 UT WOS:A1996VD43400056 PM 8799159 ER PT J AU Jin, F Wienecke, R Xiao, GH Maize, JC DeClue, JE Yeung, RS AF Jin, F Wienecke, R Xiao, GH Maize, JC DeClue, JE Yeung, RS TI Suppression of tumorigenicity by the wild-type tuberous sclerosis 2 (Tsc2) gene and its C-terminal region SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE rat; renal carcinoma; hereditary cancer; inducible expression ID DOMINANTLY INHERITED CANCER; EKER RAT MODEL; RENAL-CARCINOMA; MUTATION; NEUROFIBROMATOSIS; IDENTIFICATION; EXPRESSION; TUMORS; GROWTH; CELLS AB The Tsc2 gene, which is mutationally inactivated in the germ line of some families with tuberous sclerosis, encodes a large, membrane-associated GTPase activating protein (GAP) designated tuberin. Studies of the the Eker rat model of hereditary cancer strongly support the role of Tsc2 as a tumor suppressor gene. In this study, the biological activity of tuberin was assessed by expressing the wild-type Tsc2 gene in tumor cell lines lacking functional tuberin and also in rat fibroblasts with normal levels of endogenous tuberin. The colony forming efficiency of Eker fat-derived renal carcinoma cells was significantly reduced following reintroduction of wild-type Tsc2. Tumor cells expressing the transfected Tsc2 gene became more anchorage-dependent and lost their ability to form tumors in severe combined immunodeficient mice. At the cellular level, restoration of tuberin expression caused morphological changes characterized by enlargement of the cells and increased contact inhibition, As with the full-length Tsc2 gene, a clone encoding only the C terminus of tuberin (amino acids 1049-1809, including the GAP domain) was capable of reducing both colony formation and in vivo tumorigenicity when transfected into the Eker rat tumor cells, In normal Rat1 fibroblasts, conditional over-expression of tuberin also suppressed colony formation and cell growth in vitro, These results provide direct experimental evidence for the tumor suppressor function of Tsc2 and suggest that the tuberin C terminus plays an important role in this activity. C1 FOX CHASE CANC CTR,DIV MED SCI,PHILADELPHIA,PA 19111. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 27 TC 108 Z9 110 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 20 PY 1996 VL 93 IS 17 BP 9154 EP 9159 DI 10.1073/pnas.93.17.9154 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VD434 UT WOS:A1996VD43400067 PM 8799170 ER PT J AU McMillian, MK Pennypacker, KR Thai, L Wu, GC Suh, HH Simmons, KL Hudson, PM Sawin, SBM Hong, JS AF McMillian, MK Pennypacker, KR Thai, L Wu, GC Suh, HH Simmons, KL Hudson, PM Sawin, SBM Hong, JS TI Dexamethasone and forskolin synergistically increase [Met(5)]enkephalin accumulation in mixed brain cell cultures SO BRAIN RESEARCH LA English DT Article DE astrocyte; glia; opioid peptide; neuron-glia interaction; glucocorticoid; cyclic AMP; preproenkephalin ID PROENKEPHALIN MESSENGER-RNA; RAT GLIOMA-CELLS; GENE-EXPRESSION; CARBOXYPEPTIDASE-E; MET-ENKEPHALIN; GLIAL-CELLS; ASTROCYTES; NEURONS; GLUCOCORTICOIDS; TRANSCRIPTION AB Possible synergistic effects of the glucocorticoid dexamethasone (DEX, 10(-7) M) and the adenylate cyclase agonist forskolin (FSK, 10(-5) M) on [Met(5)]enkephalin (ME) accumulation were examined in enriched rat glial cultures and in mixed neuronal/glial cultures. In enriched glial cultures, DEX and FSK each stimulated the accumulation of ME 2-3-fold over basal media levels, but there was little additional stimulation when these agonists were combined. In contrast, mixed neuronal/glial cultures showed only weak responses to DEX or FSK alone, but the combination of these agonists produced a pronounced synergistic effect on media ME accumulation (6-10-fold over basal levels). The DEX effect was mediated via a classical glucocorticoid receptor, since DEX was potent (acting over a concentration range of 10(-11)-10(-7) M), mimicked by corticosterone (10(-6) M), and blocked by the glucocorticoid receptor antagonist RU486. There was a pronounced time lag (2 days) for the synergistic effects of DEX + FSK to develop. In situ hybridization and immunocytochemical studies suggested that astrocytes were the major source for the increased ME production in all mixed neuronal/glial cultures examined. Creating a mixed culture by plating fetal neurons onto confluent, enriched P7 glial cultures inhibited accumulation of ME in the media. DEX + FSK, but neither agonist alone, overcame this neuronal inhibition and increased accumulation of media ME to levels identical to levels in stimulated enriched glial cultures. The net effect was a 6-fold increase in ME accumulation in the mixed neuronal/glial cultures relative to a 2.5-fold increase in the enriched glial cultures. Neuronal inhibition of basal glial ME production could explain the similar synergistic effects of DEX + FSK observed in all mixed neuronal/glial cultures examined, and may be important in suppressing ME production by astrocytes in the brain. RP McMillian, MK (reprint author), NIEHS,MOL & INTEGRAT NEUROSCI LAB,NATL INST HLTH,MD E1-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Pennypacker, Keith/I-5092-2012 NR 37 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 19 PY 1996 VL 730 IS 1-2 BP 67 EP 74 PG 8 WC Neurosciences SC Neurosciences & Neurology GA VH291 UT WOS:A1996VH29100008 PM 8883890 ER PT J AU Schreurs, BG Lester, DS AF Schreurs, BG Lester, DS TI High-resolution fluorescent labeling of living cerebellar slices SO BRAIN RESEARCH LA English DT Article DE cerebellum; slice; fluorescence; microscopy; phospholipid ID PROTEIN-KINASE-C; PURKINJE-CELL DENDRITES; ACID; PROJECTIONS AB In the present study, we extend previous research on staining of living brain slices with fluorescent phospholipids. This new procedure allows high-resolution staining of specific cell types, in particular, Purkinje cells, in the cerebellar slice while not affecting the intrinsic electrical activity of the tissue. Four different nitrobenzoxadiole (NBD)-phospholipids were incorporated into living cerebellar slices via loading from small unilamellar vesicles (SUVs), composed of a carrier and the fluorescent lipid. The labeled acidic phospholipid, NBD-phosphatidic acid (NBD-PA), produced the highest resolution images with exquisite labeling of the dendritic fields. The label was incorporated predominantly into the Purkinje cell body (excluding the nucleus), with more diffuse staining in other cell types, including stellate, basket and granule cells. The labeled lipid concentration and composition of the carrier Lipid were significant in determining the specificity of labeling. Labeling, which was optimal after a 1 h incubation, was present throughout the depth of the slice. This procedure provides a promising approach to fluorescent labeling that will allow simultaneous monitoring of changes in cellular morphology and electrophysiology of living brain slices. C1 US FDA,CDER,DIV RES TESTING,LAUREL,MD 20708. NINCDS,NIH,LAB ADAPT SYST,BETHESDA,MD 20892. OI Schreurs, Bernard/0000-0002-5776-0807 NR 22 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 19 PY 1996 VL 730 IS 1-2 BP 125 EP 132 PG 8 WC Neurosciences SC Neurosciences & Neurology GA VH291 UT WOS:A1996VH29100014 PM 8883896 ER PT J AU Sander, CA Simon, M Puchta, U Raffeld, M Kind, P AF Sander, CA Simon, M Puchta, U Raffeld, M Kind, P TI HHV-8 in lymphoproliferative lesions in skin SO LANCET LA English DT Letter ID KAPOSIS-SARCOMA; DNA-SEQUENCES C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,NIH,BETHESDA,MD 20892. UNIV MUNICH,DEPT DERMATOL,D-8000 MUNICH,GERMANY. NR 4 TC 31 Z9 34 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD AUG 17 PY 1996 VL 348 IS 9025 BP 475 EP 476 DI 10.1016/S0140-6736(05)64569-2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VC673 UT WOS:A1996VC67300048 PM 8709802 ER PT J AU Witt, KL Bishop, JB AF Witt, KL Bishop, JB TI Mutagenicity of anticancer drugs in mammalian germ cells SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE genetic toxicity; spermatocyte; oocyte; mouse; human risk; mutation ID DOMINANT-LETHAL MUTATIONS; CHEMICALLY-INDUCED ANEUPLOIDY; SYNAPTONEMAL COMPLEX DAMAGE; MOUSE BONE-MARROW; STRUCTURAL CHROMOSOME-ABERRATIONS; NATIONAL-TOXICOLOGY-PROGRAM; SPERMATOGONIAL STEM-CELLS; METAPHASE-II OOCYTES; MALE-RAT MEIOSIS; MALE-MICE AB The evidence for mammalian germ cell mutagenicity induced by anticancer drugs is summarized. Primary attention is paid to the three major mouse germ cell mutagenicity tests - the dominant lethal, heritable translocation, and morphological specific locus tests - from which most germ cell mutagenicity data historically have been obtained. Of the 21 anticancer drugs reviewed, 16 have been tested in one or more of these three tests; with all 16 tested in the most common germ cell test, the male dominant lethal test, and 9 of the 16 also tested in the female dominant lethal test. The patterns of germ cell stage specificity for most of the anticancer drugs are similar, and generally resemble the patterns seen with other types of chemicals; however, some of the patterns are unique. For example, 2 of the 8 chemicals shown to induce dominant lethal mutations in female oocytes, do not induce dominant lethal mutations in male germ cells (adriamycin and platinol). Ten of the 16 chemicals tested in the dominant lethal test were positive in post-meiotic stages (spermatids through mature sperm), and seven also induced reciprocal translocations and/or specific locus mutations in post-meiotic stages. This propensity to induce mutations in post-meiotc stages has been observed with most mutagens. However, 5 of the anticancer drugs also induced dominant lethal mutations in spermatocytes (meiotic prophase cells) and one of them, 6-mercaptopurine, uniquely induced dominant lethal mutations exclusively in preleptotene spermatocytes. Finally, three of the anticancer drugs (melphalan, mitomycin C, procarbazine) are members of a very select group of chemicals shown to induce specific locus mutations in spermatogonial stem cells of mice, The implications for human risk are discussed. C1 OAK RIDGE INST SCI & EDUC,OAK RIDGE,TN 37831. RP Witt, KL (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 186 TC 86 Z9 94 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD AUG 17 PY 1996 VL 355 IS 1-2 BP 209 EP 234 DI 10.1016/0027-5107(96)00029-2 PG 26 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA VE166 UT WOS:A1996VE16600011 PM 8781584 ER PT J AU Milstien, S Jaffe, H Kowlessur, D Bonner, TI AF Milstien, S Jaffe, H Kowlessur, D Bonner, TI TI Purification and cloning of the GTP cyclohydrolase I feedback regulatory protein, GFRP SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE SYNTHASE; MESSENGER-RNA EXPRESSION; TETRAHYDROBIOPTERIN LEVELS; COFACTOR BIOSYNTHESIS; INTERFERON-GAMMA; SMOOTH-MUSCLE; RAT; TRIPHOSPHATE; ENZYME; CELLS AB The activity of GTP cyclohydrolase I, the initial enzyme of the de novo pathway for biosynthesis of tetrahydrobiopterin, the cofactor required for aromatic amino acid hydroxylations and nitric oxide synthesis, is sensitive to end-product feedback inhibition by tetrahydrobiopterin. This inhibition by tetrahydrobiopterin is mediated by the GTP cyclohydrolase I feedback regulatory protein GFRP, previously named p35 (Harada, T., Kagamiyama, H., and Hatakeyama, K. (1993) Science 260, 1507-1510), and L-phenylalanine specifically reverses the tetrahydrobiopterin dependent inhibition. As a first step in the investigation of the physiological role of this unique mechanism of regulation, a convenient procedure has been developed to co purify to homogeneity both GTP cyclohydrolase I and GFRP from rat liver, GTP cyclohydrolase I and GFRP exist in a complex which can be bound to a GTP-affinity column from which GTP cyclohydrolase I and GFRP are separately and selectively eluted. GFRP is dissociated from the GTP agarose-bound complex with 0.2 M NaCl, a concentration of salt which also effectively blocks the tetrahydrobiopterin-dependent inhibitory activity of GFRP. GTP cyclohydrolase I is then eluted from the GTP-agarose column with GTP, Both GFRP and GTP cyclohydrolase I were then purified separately to near homogeneity by sequential high performance anion exchange and gel filtration chromatography, GFRP was found to have a native molecular mass of 20 kDa and consist of a homodimer of 9.5-kDa subunits. Based on peptide sequences obtained from purified GFRP, oligonucleotides were synthesized and used to clone a cDNA from a rat liver cDNA library by polymerase chain reaction-based methods. The cDNA contained an open reading frame that encoded a novel protein of 84 amino acids (calculated molecular mass 9665 daltons). This protein when expressed in Escherichia coli as a thioredoxin fusion protein had tetrahydrobiopterin-dependent GTP cyclohydrolase I inhibitory activity. Northern blot analysis indicated the presence of an 0.8-kilobase GFRP mRNA in most rat tissues, the amounts generally correlating with levels of GTP cyclohydrolase I and tetrahydrobiopterin. Thus, mRNA levels were relatively high in liver and kidney and somewhat lower in testis, heart, brain, and lung. These results suggest that GFRP is widely expressed and may play a role in regulating not only phenylalanine metabolism in the liver, but also the production of biogenic amine neurotransmitters as well as nitric oxide synthesis. C1 NINCDS,LNC NINDS PROT PEPTIDE SEQUENCING FACIL,NIH,BETHESDA,MD 20892. NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. RP Milstien, S (reprint author), NIMH,CELL BIOL LAB,36 CONVENT DR,BLDG 36,RM 3A-17,BETHESDA,MD 20892, USA. NR 30 TC 75 Z9 76 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 16 PY 1996 VL 271 IS 33 BP 19743 EP 19751 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900021 PM 8702680 ER PT J AU Gardella, TJ Luck, MD Jensen, GS Usdin, TB Juppner, H AF Gardella, TJ Luck, MD Jensen, GS Usdin, TB Juppner, H TI Converting parathyroid hormone-related peptide (PTHrP) into a potent PTH-8 receptor agonist SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NMR SOLUTION STRUCTURE; HUMORAL HYPERCALCEMIA; EXPRESSION CLONING; ADENYLATE-CYCLASE; PLASMA-MEMBRANE; BINDING DOMAINS; COMMON RECEPTOR; FRAGMENT 1-34; ROS 17/2.8; PROTEIN AB Most of the bone and kidney-related functions of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) are thought to be mediated by the PTH/PTHrP receptor. Recently, a homologous receptor, the PTH-2 receptor, was obtained from rat and human brain cDNA libraries. This receptor displayed the remarkable property of responding potently to PTH, but not to PTHrP. To begin to define residues involved in the ligand specificity of the PTH-2 receptor, we studied the interaction of several PTH/PTHrP hybrid ligands and other related peptide analogs with the human PTH-2 receptor The results showed that two sites in PTH and PTHrP fully account for the different potencies that the tu o ligands exhibited with PTH-2 receptors; residue 5 (His in PTHrP and Ile in PTH) determined signaling capability, while residue 23 (Phe in PTHrP and Trp in PTH) determined binding affinity. By changing these two residues of PTHrP to the corresponding residues of PTH, we were able to convert PTHrP into a ligand that avidly bound to the PTH-2 receptor and fully and potently stimulated cAMP formation, Changing residue 23 alone yielded [Trp(23)]hPTHrP-(1-36), which was an antagonist for the PTH-2 receptor, but a fall agonist for the PTH/PTHrP receptor. Residues 5 and 23 in PTH and PTHrP thus play keg roles in signaling and binding interactions, respectively, with the PTH-2 receptor. Receptor-selective agonists and antagonists derived hom these studies could help to identify the biological role of the PTH-2 receptor and to map specific sites of ligand-receptor interaction. C1 MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CHILDRENS SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. RP Gardella, TJ (reprint author), MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-11794, DK-50708] NR 30 TC 69 Z9 69 U1 1 U2 3 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 AUG 16 PY 1996 VL 271 IS 33 BP 19888 EP 19893 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900042 PM 8702701 ER PT J AU Wolfe, AM Wray, S Westphal, H Radovick, S AF Wolfe, AM Wray, S Westphal, H Radovick, S TI Cell-specific expression of the human gonadotropin-releasing hormone gene in transgenic animals SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMORTALIZED HYPOTHALAMIC NEURONS; GNRH MESSENGER-RNA; POU-DOMAIN; FEMALE RAT; TRANSCRIPTION FACTORS; INSITU HYBRIDIZATION; KALLMANN SYNDROME; ESTROGEN; LHRH; MOLECULES AB We have previously demonstrated that 1131 base pairs (bp) of the human gonadotropin-releasing hormone (hGnRN) gene promoter can target simian virus 40 T antigen expression to GnRH neurons in transgenic mice. In these animals, GnRH neurons were transformed before they migrated to their final location in the rostral hypothalamus, complicating an analysis of cell-specific expression. To localize regions of the hGnRB promoter that are important for cell-specific expression, we created transgenic mice with various 5'-flanking regions of the hGnRH gene fused to the luciferase reporter gene, When 3828 or 1131 bp of the hGnRH promoter 5'-flanking DNA were used (-3828/+5LUC and -1131/+5LUC, respectively), luciferase expression in adult transgenic mice was observed in the rostral hypothalamus and olfactory tissues, regions which have been shown to be loci of GnRH-expressing neurons, Luciferase expression was not observed in other brain or peripheral tissues. Double-labeled in situ hybridization further demonstrated that luciferase expression was invariably colocalized with GnRH expression. When transgenic animals were created with a construct consisting of 484 bp of the hGnRH 5'-flanking DNA fused to the luciferase gene (-484/+5LUC), luciferase expression was not observed in the hypothalamus or in olfactory tissues. This is the first report localizing DNA sequences responsible for cell-specific expression of the GnRH gene in vivo. C1 CHILDRENS HOSP,DIV ENDOCRINOL,BOSTON,MA 02115. NINCDS,NIH,BETHESDA,MD 20892. NICHHD,NIH,BETHESDA,MD 20892. OI wray, susan/0000-0001-7670-3915 FU NICHD NIH HHS [HD30040-02] NR 44 TC 48 Z9 48 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 16 PY 1996 VL 271 IS 33 BP 20018 EP 20023 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900060 PM 8702719 ER PT J AU Itagaki, K Carver, GT Philpot, RM AF Itagaki, K Carver, GT Philpot, RM TI Expression and characterization of a modified flavin-containing monooxygenase 4 from humans SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADULT HUMAN LIVER; ESCHERICHIA-COLI; PRIMARY SEQUENCE; RABBIT LIVER; GUINEA-PIG; FORM-II; CLONING; DISTINCT; LUNG; GENE AB The inability to obtain flavin-containing monooxygenase 4 (FMO4) in heterologous systems lass hampered efforts to characterize this isoform of the FMO gene family. Neither the human nor the rabbit ortholog of FMO4, each of which has been cloned and sequenced, has been expressed. Attempts to achieve expression of FMO4 have beets made with Escherichia coli, baculovirus, yeast, and COS systems. The cDNAs encoding FMO4 have extended coding regions compared with those encoding other FMO isoforms, The derived amino acid sequences of FMO1, -2, -3, and -5 from all species examined contain about the same number of residues (531-535 residues), whereas the derived sequences of human and rabbit FMO4 contain 558 and 555 residues, respectively. We have investigated whether the elongation of the FMO4 coding region is related to the inability to achieve expression, The cDNA encoding human FMO4 has been modified by a single base change that introduces a stop codon at the consensus position. This modification allows for expression in E. coli, Lack of expression of intact FMO4 is caused by a problem that occurs following transcription, a problem that is overcome completely by relocation of the stop codon 81 bases to 5' of its normal position, Truncated FMO4 is expressed as an active enzyme with characteristics typical of an FMO isoform. Possible functional changes resulting from altering the 3'-end of an FMO were investigated with human FMO3. Elongation of the coding region of the FMO3 cDNA to the next available stop codon (FMO3*) resulted in the expression of an enzyme with properties very similar to those of unmodified FMO3. Elongation of FMO3 lowered the level of expression in E. coli but did not eliminate it. As with FMO4, the difference in expression levels between FMO3 and elongated FMO3 (FMO3*) appears to be related to translation rather than transcription, The functional characteristics of FMO3 and FMO3* are not significantly different. C1 NIEHS,MOL PHARMACOL SECT,CELLULAR & MOL PHARMACOL LAB,RES TRIANGLE PK,NC 27709. NR 38 TC 29 Z9 29 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 16 PY 1996 VL 271 IS 33 BP 20102 EP 20107 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900072 PM 8702731 ER PT J AU Segal, RA Bhattacharyya, A Rua, LA Alberta, JA Stephens, RM Kaplan, DR Stiles, CD AF Segal, RA Bhattacharyya, A Rua, LA Alberta, JA Stephens, RM Kaplan, DR Stiles, CD TI Differential utilization of Trk autophosphorylation sites SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NERVE GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; NEURONAL DIFFERENTIATION; SIGNAL-TRANSDUCTION; NEUROTROPHIC FACTOR; PC12 CELLS; MAP KINASE; INSULIN-RECEPTOR; BINDING-SITES; ACTIVATION AB Tyrosine autophosphorylation controls the catalytic and signaling activities of the neurotrophin receptors, the Trks. To analyze the regulation of distinct tyrosine sites, we generated a panel of antibodies that report the phosphorylation state of individual tyrosines within the Trk cytoplasmic domain. Using pheochromocytoma-derived cell lines, we show that individual tyrosines within the nerve growth factor receptor TrkA are phosphorylated in a non-coordinate fashion following receptor activation. The non-coordinate response of these tyrosines reflects their separate functions in regulating the catalytic and signaling activities of Trk receptors. The differential utilization of distinct sites on Trk receptor tyrosine kinases suggests that the receptor can specify both the timing and the nature of neurotrophin-stimulated signal transduction pathways. Moreover, we show that these Trk autophosphorylation sites, which have hitherto been mapped and characterized only in non-neuronal cell lines, are activated in normal neurons in response to ligand stimulation. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 41 TC 98 Z9 100 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 16 PY 1996 VL 271 IS 33 BP 20175 EP 20181 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900084 PM 8702742 ER PT J AU Zhang, SY Coso, OA Collins, R Gutkind, JS Simonds, WF AF Zhang, SY Coso, OA Collins, R Gutkind, JS Simonds, WF TI A C-terminal mutant of the G protein beta subunit deficient in the activation of phospholipase C-beta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADRENERGIC-RECEPTOR KINASE; HETEROTRIMERIC G-PROTEINS; GAMMA-SUBUNITS; BINDING PROTEINS; DICTYOSTELIUM-DISCOIDEUM; LIMITED PROTEOLYSIS; ADENYLYL CYCLASE; IDENTIFICATION; PATHWAY; STIMULATION AB The molecular mechanism by which the G protein py complex modulates multiple mammalian effector pathways is unknown. Homolog-scanning mutagenesis of the G protein beta subunit was employed to identify residues critical for the activation of phospholipase C-beta(2) (PLC-beta(2)). A series of chimeras was made by introducing small segments of the Dictyostelium beta subunit into a background of mammalian beta(1) and tested in COS cell cotransfection assays for their ability ito activate PLC-beta(2), and assemble with mammalian gamma(2). A chimera that contained four Dictyostelium beta substitutions within the C-terminal 14 residues was unable to activate PLC beta(2), when cotransfected with gamma, despite its demonstrable expression in a gamma-dependent manner. Cotransfection of the mutant blocked m2 muscarinic receptor activation of PLC by a pertussis toxin-sensitive pathway. This C-terminal mutant retained the ability, however, to stimulate the mitogen-activated protein kinase pathway. These results imply that activation of different beta gamma-responsive effectors is mediated by distinct domains. C1 NIDDK,METAB DIS BRANCH,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 NR 52 TC 28 Z9 29 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 16 PY 1996 VL 271 IS 33 BP 20208 EP 20212 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900089 PM 8702747 ER PT J AU Winter, H Maeda, Y Mitsuya, H Zemlicka, J AF Winter, H Maeda, Y Mitsuya, H Zemlicka, J TI Phosphodiester amidates of allenic nucleoside analogues: Anti-HIV activity and possible mechanism of action SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ARYL PHOSPHATE DERIVATIVES; INTRACELLULAR DELIVERY; ABSOLUTE-CONFIGURATION; DEOXYCYTIDINE KINASE; ENANTIOSELECTIVITY; AZT; NUCLEOTIDES; CELLS AB Lipophilic phosphodiester amidates 2a, 2b, 4a, 4b, and 6 derived from anti-HIV agent adenallene 1a, 3a, inactive hypoxallene 1b, 3b, and 9-(4-hydroxy-2-butyn-1-yl)adenine (5) were synthesized and studied as inhibitors of HIV-1 in ATH8 cell system. All phosphodiester amidates were more biologically active than their parent nonphosphorylated compounds. Analogues 2a and 4a derived from (+/-)-adenallene 1a and (R)-enantiomer 3a are effective anti-HIV agents with EC(50) approximately 0.88 and 0.21 mu M, respectively. Both analogues are 16 and 28 times more effective than parent-compounds 1a and 3a, respectively. Some anti-HIV activity of hypoxallene derivatives 2b and 4b was noted in the range of 0.1-10 mu M but the dose-response relationship was poor. Phosphodiester amidate analogue 6 also exhibited anti-HIV activity in the range of 0.1-100 mu M, but this effect was accompanied by cytotoxicity. Hydrolytic studies performed at pH 9.8 and with pig liver esterase at pH 7.4 have shown that analogue 2a gives adenallene 4'-phosphoralaninate (10a) as the major product. These results can be interpreted in terms of initial hydrolysis of phosphodiester amidates 2a, 2b, 4a, 4b, and 6 catalyzed by intracellular esterase(s) to give stable phosphomonoester amidate intermediates with a free carboxyl group. The results obtained with hypoxallene phosphoramidates 2b and 4b indicate-that the aminosuccinate-fumarate enzyme system responsible for activation of AIDS drug ddIno (didanosine, Videx) can also, albeit less efficiently, activate hypoxallene 4'-phosphate (9b) and the respective (R)-enantiomer released inside the HIV-infected cells. C1 WAYNE STATE UNIV,SCH MED,BARBARA ANN KARMANOS CANC INST,DEPT CHEM,DETROIT,MI 48201. NCI,EXPT RETROVIROL SECT,MED BRANCH,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA 32779] NR 38 TC 32 Z9 32 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 16 PY 1996 VL 39 IS 17 BP 3300 EP 3306 DI 10.1021/jm960330n PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VC704 UT WOS:A1996VC70400011 PM 8765513 ER PT J AU Shah, JH Kline, RH GeterDouglass, B Izenwasser, S Witkin, JM Newman, AH AF Shah, JH Kline, RH GeterDouglass, B Izenwasser, S Witkin, JM Newman, AH TI (+/-)-3-[4'-(N,N-dimethylamino)cinnamyl]benzazepine analog: Novel dopamine D-1 receptor antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SUBTYPES AB Neurochemical studies and structure-activity relationships of dopamine D-1 receptor ligands suggest that their intrinsic activity may depend on the conformational state or binding site at which they interact on the receptor protein. Important differences in the modes of binding of these ligands may confer their agonist, partial agonist, or antagonist properties. In an effort to develop novel dopamine D-1 antagonists and investigate the D-1 antagonist pharmacophore, a series of (+/-)-(N-alkylamino)benzazepines were prepared in which (+/-)-7-chloro-8-hydroxy-3-[6-(N,N-dimethylamino)hexyl]-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (1) demonstrated the highest binding affinity (K-i = 49.3 nM) and selectivity to dopamine D-1 receptors, This compound inhibited dopamine-stimulated adenylyl cyclase, in rat caudate, confirming a D-1 receptor antagonist profile. From this initial series of N-alkylamino-substituted benzazepines, structure-activity relationships suggested that the terminal amino function was necessary for optimal binding affinity and selectivity at D-1 vs D-2 sites. Further, addition of this side chain to the D-1 agonist pharmacophore (e.g., 7,8-dihydroxy-3-[4-(N,N-dimethylamino)butyl]-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) greatly decreased binding affinity at D-1 receptors. These data suggested that a binding domain that may be unique to the D-1 antagonists may have been identified. In an attempt to exploit an apparent amine-accepting binding domain on the D-1 receptor, a series of (+/-)-3-[4'-(N,N-dimethylamino)cinnamyl]benzazepine analogs was designed and prepared, as D-1 antagonists. In this series, (+/-)-7-chloro-8-hydroxy-3-[4'-(N,N-dimethylamino)cinnamyl]-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (6a) showed the highest binding affinity (K-i = 60.3 nM) for dopamine D-1 receptors. Compound 6a was a potent dopamine D-1 antagonist as evidenced by its ability to block dopamine-stimulated adenylyl cyclase activity in rat caudate (predicted K-i value = 18.4 nM). Molecular modeling studies demonstrated that the mast potent and selective dopamine D-1 antagonists, in both series, contained terminal amino groups 8-9 Angstrom away from the 3-position benzazepine nitrogen. Compounds that lacked a terminal amine function or where this moiety was less than 7 Angstrom away from the benzazepine nitrogen demonstrated significantly lower binding affinities. Therefore, this series of (+/-)-3-[4'-(N,N-dimethylamino)cinnamyl]benzazepines also appears to be identifying an amine-accepting binding domain on the dopamine D-1 receptor protein that may be further explored for the development of novel dopamine D-1 antagonists. C1 NIDA,DIV INTRAMURAL RES,NIH,PSYCHOBIOL SECT,BALTIMORE,MD 21224. RI Izenwasser, Sari/G-9193-2012 NR 24 TC 6 Z9 6 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 AUG 16 PY 1996 VL 39 IS 17 BP 3423 EP 3428 DI 10.1021/jm960143p PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VC704 UT WOS:A1996VC70400026 PM 8765528 ER PT J AU Zhao, RH Pathak, N Jaffe, H Reese, TS Khan, S AF Zhao, RH Pathak, N Jaffe, H Reese, TS Khan, S TI FliN is a major structural protein of the C-ring in the Salmonella typhimurium flagellar basal body SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE macromolecular assembly; chromatography; electron microscopy; molecular motor; protein export ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ESCHERICHIA-COLI; BACTERIAL FLAGELLA; PROTONMOTIVE FORCE; SWITCH COMPLEX; MOTOR; CHEMOTAXIS; PHOSPHORYLATION; ROTATION; MOTILITY AB The Salmonella typhimurium FliN protein has been proposed to form a mutually interacting complex with FIG and FliM, the switch complex, that is required for flagellar morphogenesis and function. We have used affinity chromatography for purification of extended flagellar basal bodies sufficient for quantitative analysis of their protein composition. The belied, extended structure is predominantly comprised of the switch complex proteins; with FliN present in the most copies (111 +/- 13). This explains why single, missense fliN, fliG or fliM mutations, found in many non-motile strains, can alter the belied morphology. Cell lysates from these strains contained the wild-type complement of FliG, FliM and FliN; but the basal bodies lacked the outer, cytoplasmic(C)-ring of the bell and were separated by sedimentation from FliM and FliN. The amount of FliG present in basal bodies from wild-type and one such mutant, FliN100LP, was comparable. These data show that: (1) the mutations define a FliG and FliMFliN multiple contact interface important for motility. (2) FliG is responsible for the increased size of the membrane-embedded MS-ring complex of belied relative to acid-treated basal bodies. (3) FliN, together with FliM, account for most of the C-ring. As a major component of the C-ring, FliN is distinct from the other proteins implicated in axial flagellar protein export. Inner, cytoplasmic rod basal substructure, seen by negative-stain and quick-freeze replica electron microscopy, may gate such export. Lack of connectivity between the cytoplasmic rod and ring substructures places contacts between FliG and FliMFliN at the periphery of the basal body, proximal to the flagellar intramembrane ring particles. This topology is consistent with models where torque results from interaction of circumferential arrays of the switch complex proteins with the ring particles. (C) 1996 Academic Press Limited C1 NINCDS,LNC,PROTEIN SEQUENCING FACIL,NIH,BETHESDA,MD 20892. NINCDS,NEUROBIOL LAB,NIH,BETHESDA,MD 20892. RP Zhao, RH (reprint author), ALBERT EINSTEIN COLL MED,DEPT PHYSIOL & BIOPHYS,BRONX,NY 10461, USA. FU NIGMS NIH HHS [R01-GM36936] NR 54 TC 75 Z9 76 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 16 PY 1996 VL 261 IS 2 BP 195 EP 208 DI 10.1006/jmbi.1996.0452 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC335 UT WOS:A1996VC33500010 PM 8757287 ER PT J AU Daling, JR Brinton, LA Voigt, LF Weiss, NS Coates, RJ Malone, KE Schoenberg, JB Gammon, M AF Daling, JR Brinton, LA Voigt, LF Weiss, NS Coates, RJ Malone, KE Schoenberg, JB Gammon, M TI Risk of breast cancer among white women following induced abortion SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE abortion, induced; breast neoplasms; pregnancy ID YOUNG-WOMEN; REPRODUCTIVE FACTORS; AGE; CARCINOGENESIS; TISSUE; GLAND; TIME AB Some studies (but not all) have suggested that there may be an increase in the risk of breast cancer associated with a prior induced abortion. The risk, if present, may vary according to the duration of the pregnancy in which the abortion occurred, or to a woman's age or parity at that time. The authors conducted a case-control study of breast cancer in white women under age 45 years to address the question of breast cancer risk in relation to induced abortion, with the intention of identifying subgroups of women who might be at particularly increased risk. White women who were diagnosed with breast cancer (n=1,302) from May 1, 1990, through December 31, 1992, in three geographic regions of the United States (Atlanta, Georgia; Seattle/Puget Sound, Washington; and five counties in central New Jersey) were interviewed about their reproductive histories, including the occurrence of induced abortion. Similar information was obtained from control women identified through random digit dialing. Logistic regression analysis was used to estimate the relative risk of breast cancer associated with a history of induced abortion, controlling for the potentially confounding influence of other breast cancer risk factors, Among women who had been pregnant at least once, the risk of breast cancer in those with a prior induced abortion was 20% higher than that in women with no history of abortion (95% confidence interval 1.0-1.5). This small increase in risk varied little according to number of abortions or a woman's current age. The association was present primarily among nulliparous women whose abortions occurred prior to 9 weeks' gestation (estimated relative risk=2.0, 95% confidence interval 1.2-3.3). There was no excess risk of breast cancer associated with induced abortion among parous women. These data support the hypothesis that there may be a small increase in the risk of breast cancer related to a history of induced abortion among young women of reproductive age. However, the data from this study and others do not permit a causal interpretation at this time; neither do the collective results of the studies suggest that there is a subgroup of women in whom the relative risk associated with induced abortion is unusually high. C1 WASHINGTON UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,SEATTLE,WA. NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,ROCKVILLE,MD. EMORY UNIV,ROLLINS SCH PUBL HLTH,DEPT EPIDEMIOL,ATLANTA,GA 30322. NEW JERSEY STATE DEPT HLTH,SPECIAL EPIDEMIOL PROGRAM,TRENTON,NJ 08625. COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY. RP Daling, JR (reprint author), FRED HUTCHINSON CANC RES CTR,DIV PUBL HLTH SCI,1124 COLUMBIA ST,MP 381,SEATTLE,WA 98104, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [N01-CN-05230, N01-CP-95671] NR 25 TC 40 Z9 40 U1 0 U2 5 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 1996 VL 144 IS 4 BP 373 EP 380 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VB181 UT WOS:A1996VB18100006 PM 8712194 ER PT J AU Westhoff, C Gentile, G Lee, J Zacur, H Helbig, D AF Westhoff, C Gentile, G Lee, J Zacur, H Helbig, D TI Predictors of ovarian steroid secretion in reproductive-age women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; estrogens; menarche; obesity; ovary; progestational hormones; smoking ID BREAST-CANCER RISK; CIGARETTE-SMOKING; MENARCHE; ESTROGENS; HORMONES AB During the baseline period (1985-1988) of a prospective study, midcycle and luteal-phase estrogens and progestins were measured in 175 healthy women aged 21-36 years with spontaneous, cyclic menses in Brooklyn, New York. Subjects contributed daily first-morning urine specimens and three blood specimens during a single menstrual cycle monitored by basal body temperature, Hormone levels were compared according to age, race, and levels of known or suspected breast cancer risk factors, Late age at menarche was associated with increased urinary and serum progestin levels, Increased body weight was associated with decreased progestin levels, even in ovulatory women. Neither weight nor age at menarche was related to estrogen levels. Cigarette smoking was associated with decreased midcycle and luteal-phase estradiol levels, No other factors were associated with differences in any of the hormones measured either midcycle or during the luteal phase, despite good statistical power to detect moderate differences, Sources of individual variability in ovarian steroid levels remain unexplained, These data do not support hypotheses that breast cancer risk factors act through an effect on ovarian hormones during the middle reproductive years. C1 SUNY HLTH SCI CTR,BROOKLYN,NY 11203. NICHHD,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT GYNECOL & OBSTET,BALTIMORE,MD. RP Westhoff, C (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,NEW YORK,NY 10027, USA. FU NICHD NIH HHS [N01-HD-52908] NR 18 TC 56 Z9 57 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 1996 VL 144 IS 4 BP 381 EP 388 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VB181 UT WOS:A1996VB18100007 PM 8712195 ER PT J AU Morens, DM Grandinetti, A Davis, JW Ross, GW White, LR Reed, D AF Morens, DM Grandinetti, A Davis, JW Ross, GW White, LR Reed, D TI Evidence against the operation of selective mortality in explaining the association between cigarette smoking and reduced occurrence of idiopathic Parkinson disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Parkinson disease; smoking ID PROTECTION; RISK AB To investigate the association between idiopathic Parkinson disease (IPD) and reduced frequency of prior cigarette smoking, the authors compared the 29-year follow-up mortality rates and IPD incidence rates of men who were either cigarette smokers or nonsmokers at the time of enrollment in the Honolulu Heart Study (1965-1968). Based on IPD cases detected up to June 30, 1994, the age-adjusted incidence rate in smokers was less than half ?hat in nonsmokers: 34.4 versus 94.2 cases per 100,000 person-years of pre-illness follow-up, respectively. When data were stratified by 5-year age group, lower IPD incidence in smokers was observed at all ages between 50 and 90 years. Age-specific mortality trends for smokers and nonsmokers with and without IPD suggested that increased mortality in IPD patients was mostly associated with IPD itself and not with smoking. The slight excess mortality in smokers without IPD, versus nonsmokers without IPD, appeared insufficient to account for the ''missing'' incident IPD cases in smokers. These IPD incidence and mortality data are not highly consistent with the ''selective mortality'' hypothesis, which attributes reduced prior smoking frequency, typically reported by persons with IPD, to accelerated mortality in undiagnosed IPD-affected persons who smoker The ''protective'' association of cigarette smoking with IPD occurrence may thus be real, suggesting the need for further study of biologic mechanisms of protection. C1 UNIV HAWAII,SCH MED,HONOLULU,HI 96822. EAST WEST CTR,HONOLULU,HI 96848. HAWAII OSTEOPOROSIS CTR,HONOLULU,HI. NIA,NIH,HONOLULU ASIA AGING STUDY,HONOLULU,HI. US DEPT VET AFFAIRS,HONOLULU,HI. BUCK CTR RES AGING,NOVATO,CA. RP Morens, DM (reprint author), UNIV HAWAII,SCH PUBL HLTH,PROGRAM EPIDEMIOL,BIOMED D103,1960 EAST WEST RD,HONOLULU,HI 96822, USA. FU NINDS NIH HHS [NS 30371] NR 9 TC 44 Z9 46 U1 0 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 1996 VL 144 IS 4 BP 400 EP 404 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VB181 UT WOS:A1996VB18100009 PM 8712197 ER PT J AU Graham, BS Keefer, MC McElrath, MJ Gorse, GJ Schwartz, DH Weinhold, K Matthews, TJ Esterlitz, JR Sinangil, F Fast, PE Wright, PF Dolin, R Corey, L Belshe, RB Clements, ML Bolognesi, DP Stablein, DM Chernoff, D Duliege, AM Walker, CM AF Graham, BS Keefer, MC McElrath, MJ Gorse, GJ Schwartz, DH Weinhold, K Matthews, TJ Esterlitz, JR Sinangil, F Fast, PE Wright, PF Dolin, R Corey, L Belshe, RB Clements, ML Bolognesi, DP Stablein, DM Chernoff, D Duliege, AM Walker, CM TI Safety and immunogenicity of a candidate HIV-1 vaccine in healthy adults: Recombinant glycoprotein (rgp) 120 - A randomized, double-blind trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE vaccines, synthetic; human immunodeficiency virus-1; acquired immunodeficiency syndrome; HIV envelope protein gp120; human immunodeficiency virus infection ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESPIRATORY SYNCYTIAL VIRUS; T-LYMPHOCYTE ACTIVITY; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSES; GP160 VACCINE; TYPE-1; GP120; INFECTION; CHIMPANZEES AB Objective: To evaluate the safety and immunogenicity of recombinant glycoprotein (rgp) 120, a candidate vaccine for the human immunodeficiency virus (HIV), formulated with a novel adjuvant, MF59, with or without a biological response modifier, MTP-PE. Design: Multicenter, double-blind, randomized trial. Setting: University medical centers. Participants: 49 healthy, HIV-seronegative volunteers 18 to 60 years of age who were at low risk for HIV type 1 (HIV-1) infection. Interventions: In part A of the study, 32 participants were randomly assigned to receive either 15 mu g of rgp120 in MF59, 15 mu g of rgp120 in MF59 plus 50 mu g of MTP-PE, 50 mu g of rgp120 in MF59, or 50 mu g of rgp120 in MF59 plus 50 mu g of MTP-PE. Participants were vaccinated at 0, 1, 6, and 12 to 18 months. In part B, 17 participants were randomly assigned to receive five monthly injections of either 50 mu g of rgp120 in MF59 or MF59 alone followed by a booster injection at 12 to 18 months. Main Outcome Measures: Local and systemic reactions; laboratory measures of hepatic renal, immunologic, and bone marrow toxicity; and HIV-specific serologic and cell-mediated immune responses. Results: 13 patients in part A received 50-mu g doses of rgp120; type-specific neutralizing antibody responses against the SF-2 strain of HIV-1 (HIV-1/SF-2) were induced in ail 13, Nine of the 13 had crossreactive neutralizing activity against the MN strain of HIV-1 (HIV-1/MN), and 2 had crossreactive neutralizing activity against the IIIB strain of HIV-1 (HIV-1/IIIB). Twelve patients had type-specific fusion inhibition activity; only 1 had crossreactive fusion inhibition activity against HIV-1/MN. The monthly vaccination schedule used in part B resulted in decreased antibody titers, indicating that a rest period in the schedule is necessary for maximal immunogenicity, Lymphoproliferative responses against gp120 were induced in all vaccine recipients, The stimulation index to gp120 was persistently greater than 15 for 6 months after the last booster vaccination was given. CD8(+) cytotoxic T-lymphocyte activity was detected in 1 of the 11 participants tested. Vaccine that contained MTP-PE caused a greater number of moderate or severe local and systemic reactions (of 16 participants, 4 had local reactions and 13 had systemic reactions) than did vaccine formulated with MF59 alone (of 16 participants, 7 had local reactions [P <0.01] and 0 had systemic reactions [P < 0.001]). Conclusions: The SF-2 rgp120 vaccine is safe and immunogenic. Three vaccinations with rgp120 in MF59 can induce type-specific and crossreactive neutralizing antibody against B-subtype laboratory strains of HIV-1. Human immunodeficiency virus-specific lymphoproliferative responses were induced in all vaccinated participants, and CD8(+) cytotoxic T-lymphocyte activity was shown in one participant. A trend toward the augmentation of lymphoproliferative and humoral responses by MTP-PE was seen in the participants receiving 15 mu g of rgp120. However, MTP-PE caused a statistically significant increase in the incidence of local and systemic side effects, which was felt to outweigh the small increase in immunogenicity provided by this biological response modifier in an otherwise well-tolerated vaccine. C1 UNIV ROCHESTER,MED CTR,SCH MED & DENT,ROCHESTER,NY 14642. UNIV WASHINGTON,SCH MED,AIDS VACCINE EVALUAT UNIT,SEATTLE,WA 98144. ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63110. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,CTR IMMUNIZAT RES,BALTIMORE,MD 21205. DUKE UNIV,MED CTR,DURHAM,NC 27710. EMMES CORP,POTOMAC,MD 20854. CHIRON BIOCINE CORP,EMERYVILLE,CA 94608. NIAID,BETHESDA,MD 20892. RP Graham, BS (reprint author), VANDERBILT UNIV,SCH MED,A-3310 MCN,NASHVILLE,TN 37232, USA. FU NIAID NIH HHS [N01-AI-05061, N01-AI-05062, N01-AI-82500] NR 37 TC 79 Z9 80 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 15 PY 1996 VL 125 IS 4 BP 270 EP & PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA VB680 UT WOS:A1996VB68000006 PM 8678389 ER PT J AU Stone, MJ Sausville, EA Fay, JW Headlee, D Collins, RH Figg, WD StetlerStevenson, M Jain, V Jaffe, ES Solomon, D Lush, RM Senderowicz, A Ghetie, V Schindler, J Uhr, JW Vitetta, ES AF Stone, MJ Sausville, EA Fay, JW Headlee, D Collins, RH Figg, WD StetlerStevenson, M Jain, V Jaffe, ES Solomon, D Lush, RM Senderowicz, A Ghetie, V Schindler, J Uhr, JW Vitetta, ES TI A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma SO BLOOD LA English DT Article ID RICIN-A-CHAIN; SEVERE COMBINED IMMUNODEFICIENCY; ANTIVIRAL PROTEIN IMMUNOTOXIN; LARGE-SCALE PREPARATION; MONOCLONAL-ANTIBODIES; ANTI-B4-BLOCKED RICIN; ANTITUMOR-ACTIVITY; INVIVO EFFICACY; TRIAL; MICE AB IgG-HD37-SMPT-dgA is a deglycosylated ricin A chain (dgA)containing immunotoxin (IT) prepared by conjugating the monoclonal murine (MoAb) anti-CD19 antibody, HD37, to dgA using the heterobifunctional hindered disulfide linker, N-succinimidyl-oxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio) toluene (SMPT). In this report, we have used two regimens for the administration of IgG-HD37-SMPT-dgA to patients with non-Hodgkin's lymphoma (NHL) in two concomitant phase I trials. One trial examined four intermittent bolus infusions administered at 48-hour intervals. The other studied a continuous infusion (CI) administered over the same 8-day period. In the intermittent bofus regimen, the maximum tolerated dose (MTD) was 16 mg/m(2)/8 d and the dose limiting toxicity (DLT) consisted of vascular leak syndrome (VLS), aphasia, and evidence of rhabdomyolysis encountered at 24 mg/m(2)/8 d. Using the Cl regimen, the MTD was defined by VLS at 19.2 mg/m(2)/8 d. At the MTD of both regimens, a novel toxicity, consisting of acrocyanosis with reversible superficial distal digital skin necrosis in the absence of overt evidence of systemic vasculitis, occurred in 3 patients. Of 23 evaluable patients on the bolus schedule, there was 1 persisting complete response (OR; >40 months) and 1 partial response (PR). Of 9 evaluable patients on the continuous infusion regimen, there was 1 PR. Pharmacokinetic parameters for the bolus regimen at the MTD showed a mean maximum serum concentration (C-max) of 1,209 +/- 430 ng/mL, with a median T(1/2)beta for all courses of 18.2 hours (range, 10.0 to 80.0 hours), a volume of distribution (Vd) of 10.9 L (range, 3.1 to 34.5 L), and a clearance (CL) of 0.45 L/h (range, 0.13 to 2.3 L/h). For the Ci regimen at MTD, the mean C-max was 953 +/- 473 ng/mL, with a median T(1/2)beta for all courses of 22.8 hours (range, 24.1 to 30.6 hours), a Vd of 9.4 L (range, 4.4 to 19.5 L), and a CL of 0.32 L/h (range, 0.12 to 0.55 L/h). Twenty-five percent of the patients on the bolus infusion regimen and 30% on the CI regimen made antibody against mouse Ig (HAMA) and/or ricin A chain antibody (HARA). We conclude that this IT can be administered safely and that both regimens achieve comparable peak serum concentrations at the MTD; these concentrations are similar to those achieved previously using other regimens with IgG-dgA ITs at their respective MTDs. Thus, toxicity is related to the serum level of the IT and does not differ with different targeting MoAbs. (C) 1996 by The American Society of Hematology. C1 UNIV TEXAS, SW MED CTR, CTR CANC IMMUNOBIOL, DALLAS, TX 75235 USA. UNIV TEXAS, SW MED CTR, DEPT MICROBIOL, DALLAS, TX 75235 USA. BAYLOR UNIV, MED CTR, DALLAS, TX USA. CHARLES A SAMMONS CANC CTR, DALLAS, TX USA. NCI, PATHOL LAB, CLIN PHARMACOL BRANCH, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. RI Figg Sr, William/M-2411-2016 FU NCI NIH HHS [CA41081, CA28149] NR 36 TC 128 Z9 129 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1996 VL 88 IS 4 BP 1188 EP 1197 PG 10 WC Hematology SC Hematology GA VC854 UT WOS:A1996VC85400007 PM 8695836 ER PT J AU Rosen, RL Winestock, KD Chen, G Liu, XW Hennighausen, L Finbloom, DS AF Rosen, RL Winestock, KD Chen, G Liu, XW Hennighausen, L Finbloom, DS TI Granulocyte-macrophage colony-stimulating factor preferentially activates the 94-kD STAT5A and an 80-kD STAT5A isoform in human peripheral blood monocytes SO BLOOD LA English DT Article ID TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTORS; GAMMA-INTERFERON; GENE FAMILY; T-CELLS; CYTOKINE; SIGNALS; EXPRESSION; PROTEINS; RECEPTOR AB Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces immediate effects in monocytes by activation of the Janus kinase (JAK2) and STAT transcription factor (STAT5) pathway. Recent studies have identified homo logues of STAT5, STAT5A, and STAT5B, as well as lower molecular weight variants of STAT5. To define the activation of the STAT5 homologues and lower molecular weight variant in human monocytes and monocytes differentiated into macrophages by culture in macrophage-CSF (M-CSF), we measured the GM-CSF induced tyrosine phosphorylation of STAT5A, STAT5B, and any lower molecular weight STAT5 isoforms. Freshly isolated monocytes expressed 94-kD STAT5A, 92-kD STAT5B, and an 80-kD STAT5A molecule. Whereas 94-kD STAT5A was clearly tyrosine phosphorylated and bound to the enhancer element, the gamma response region (GRR), of the Fc gamma RI gene, substantially less tyrosine phosphorylated STAT5B bound to the immobilized GRR element. Macrophages lost their ability to express the 80-kD STAT5A protein, but retained their ability to activate STAT5A. STAT5A-STAT5A homodimers and STAT5A-STAT5B heterodimers formed in response to GM-CSF. Therefore, activation of STAT5A predominates compared to STAT5B when assayed by direct immunoprecipitation and by evaluation of bound STATs to immobilized GRR. Selective activation of STAT5 homologues in addition to generation of lower molecular isoforms may provide specificity and control to genes expressed in response to cytokines such as GM-CSF. C1 US FDA,DIV CYTOKINE BIOL,CTR BIOL RES & EVALUAT,BETHESDA,MD 20892. NIDDKD,BIOCHEM LAB,BETHESDA,MD. NR 27 TC 80 Z9 80 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1996 VL 88 IS 4 BP 1206 EP 1214 PG 9 WC Hematology SC Hematology GA VC854 UT WOS:A1996VC85400009 PM 8695838 ER PT J AU Tuscano, JM Druey, KM Riva, A Pena, J Thompson, CB Kehrl, JH AF Tuscano, JM Druey, KM Riva, A Pena, J Thompson, CB Kehrl, JH TI Bcl-x rather than Bcl-2 mediates CD40-dependent centrocyte survival in the germinal center SO BLOOD LA English DT Article ID CENTER B-CELLS; INDUCED APOPTOSIS; IN-VIVO; DEATH; MICE; INDUCTION; PROTEIN; GENE; LYMPHOCYTES; MATURATION AB Both rapid B-cell proliferation and programmed cell death (PCD) occur during the differentiation and selection of B cells within the germinal center, io help elucidate the role of Bcl-x in B-cell antigen selection and (PCD) within the germinal center, we examined its expression in defined B-cell populations and by immunochemistry of tonsil tissue. Purified B-cell fractions enriched for centrocytes express high amounts of Bcl-x and relatively low amounts of Bcl-2, whereas fractions enriched for centroblasts lack significant levels of both proteins, Consistent with this observation, immunocytochemistry localized Bcl-x within cells scattered throughout the germinal center. Stimulation of tonsil B cells with either CD40 or Staphylococcus aureus Cowan increases bcl-x mRNA and protein levels, Treatment of a cell line with a germinal center phenotype (RAMOS) or the tonsillar B-cell centroblast fraction with CD40 rapidly increased Bcl-x levels and partially rescued B cells from PCD, These data suggest that Bcl-x rather than Bcl-2 may rescue centrocytes during selection in the germinal center. (C) 1996 by The American Society of Hematology. C1 NIAID,IMMUNOREGULAT LAB,B CELL MOL IMMUNOL SECT,NIH,BETHESDA,MD 20892. UNIV CHICAGO,HOWARD HUGHES MED INST,CHICAGO,IL 60637. OI Kehrl, John/0000-0002-6526-159X NR 35 TC 79 Z9 79 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1996 VL 88 IS 4 BP 1359 EP 1364 PG 6 WC Hematology SC Hematology GA VC854 UT WOS:A1996VC85400025 PM 8695854 ER PT J AU Guan, XY Horsman, D Zhang, HE Parsa, NZ Meltzer, PS Trent, JM AF Guan, XY Horsman, D Zhang, HE Parsa, NZ Meltzer, PS Trent, JM TI Localization by chromosome microdissection of a recurrent breakpoint region on chromosome 6 in human B-cell lymphoma SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN-MALIGNANT MELANOMA; FOLLICULAR LYMPHOMA; LONG ARM; CYTOGENETIC ANALYSIS; COMMON REGION; ABNORMALITIES; HETEROZYGOSITY; CARCINOMAS AB Deletion of the long arm of chromosome 6 (6q) is one of the most common chromosomal alterations in human B-cell lymphomas, Conventional cytogenetic banding analysis and loss-of-heterozygosity (LOH) studies have detected several common regions of deletion ranging across the entire long arm (6q), with no defined recurrent breakpoint yet identified, We describe here a strategy combining chromosome microdissection and fluorescence in situ hybridization (Micro-FISH) to determine a minimal region of deletion along chromosome 6. Seven clinical cases and one cell line of follicular lymphoma containing a t(14;18) and one case of diffuse lymphoma, also with a t(14;18), were used for this study, All nine cases had previously defined abnormalities of chromosome 6 determined by cytogenetic analysis. The results of chromosome dissection were unexpected and in contrast to the suggestion of disparate breakpoints by conventional chromosome banding. Specifically, Micro-FISH analysis provided evidence for a common breakpoint at 6q11 in seven of nine cases, After Micro-FISH analysis, all of the presumed simple deletions of chromosome 6 were carefully reanalyzed and shown to actually represent either nonreciprocal translocations (three cases), interstitial deletions (five cases), or isochromosome (one case), The recurrent proximal breakpoint (6q11) was detected in seven of nine cases, with the minimal region of deletion encompassing 6q11 to 6q21. By analogy to other tumor systems, the identification of recurring breakpoints within 6q11 may suggest that a gene(s) important to the genesis or progression of follicular lymphoma can be localized to this band region. C1 NIH,CANC GENET LAB,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. BRITISH COLUMBIA CANC AGCY,DIV LAB MED,VANCOUVER,BC V5Z 4E6,CANADA. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 28 TC 30 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1996 VL 88 IS 4 BP 1418 EP 1422 PG 5 WC Hematology SC Hematology GA VC854 UT WOS:A1996VC85400033 PM 8695862 ER PT J AU Dent, AL Yewdell, J PuvionDutilleul, F Koken, MHM deThe, H Staudt, LM AF Dent, AL Yewdell, J PuvionDutilleul, F Koken, MHM deThe, H Staudt, LM TI LYSP100-associated nuclear domains (LANDs): Description of a new class of subnuclear structures and their relationship to PML nuclear bodies SO BLOOD LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; PRIMARY BILIARY-CIRRHOSIS; RAR-ALPHA; TRANSCRIPTIONAL ADAPTER; DROSOPHILA-TRITHORAX; MOLECULAR-CLONING; PROTEIN P300; COILED BODY; TRANSLOCATION; EXPRESSION AB The PML gene is fused to the retinoic acid receptor alpha (RAR alpha) gene in t(15;17) acute promyelocytic leukemia (APL), creating a PML-RAR alpha fusion oncoprotein. The PML gene product has been localized to subnuclear dot-like structures variously termed PODs, ND10s, Kr bodies, or PML nuclear bodies (PML NBs), The present study describes the cloning of a lymphoid-restricted gene, LYSP100, that is homologous to another protein that localizes to PML NBs, SP100. In addition to SP100 homology regions, one LYSP100 cDNA isoform contains a bromodomain and a PHD/TTC domain, which are present in a variety of transcriptional regulatory proteins. By immunofluorescence, LYSP100 was localized to nuclear dots that were surprisingly largely nonoverlapping with PML NBs. However, a minority of LYSP100 nuclear dots exactly colocalized with PML and SP100. We term the LYSP100 structures ''LANDs,'' for LYSP100-associated nuclear domains, Although LYSP100 is expressed only in lymphoid cells, LANDs could be visualized in HeLa cells by transfection of a LYSP100 cDNA. Immunoelectron microscopy revealed LANDs to be globular, electron-dense structures morphologically distinct from the annular structures characteristic of PML NBs, LANDs were most often found in the nucleoplasm, but were also found at the nuclear membrane and in the cytoplasm, suggesting that these structures may traffic between the cytoplasm and the nucleus. By double-immunogold labeling of PML and LYSP100, some LANDs were shown to contain both PML and LYSP100. Thus, PML is localized to a second subnuclear domain that is morphologically and biochemically distinct from PML NBs. (C) 1996 by The American Society of Hematology. C1 NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. IRSC,CNRS UPR 272,VILLEJUIF,FRANCE. HOP ST LOUIS,DEPT BIOCHEM,PARIS,FRANCE. RI yewdell, jyewdell@nih.gov/A-1702-2012; koken, marcel/J-8154-2012 OI koken, marcel/0000-0002-0839-0125 NR 60 TC 55 Z9 57 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1996 VL 88 IS 4 BP 1423 EP 1436 PG 14 WC Hematology SC Hematology GA VC854 UT WOS:A1996VC85400034 PM 8695863 ER PT J AU Chan, CH Blazar, BR Greenfield, L Kreitman, RJ Vallera, DA AF Chan, CH Blazar, BR Greenfield, L Kreitman, RJ Vallera, DA TI Reactivity of murine cytokine fusion toxin, diphtheria Toxin(390)-murine interleukin-3 (DT390-mIL-3), with bone marrow progenitor cells SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; BINDING DOMAIN SUBSTITUTION; LEUKEMIC BLAST CELLS; GROWTH-FACTOR; GENETIC CONSTRUCTION; GM-CSF; RECEPTOR; PROTEIN; EXPRESSION AB Myeloid leukemias can express interleukin-3 receptors (IL-3R), Therefore, as an antileukemia drug, a fusion immunotoxin was synthesized consisting of the murine IL-3 (mIL-3) gene spliced to a truncated form of the diphtheria toxin (DT390) gene coding for a molecule that retained full enzymatic activity, but excluded the native binding domain. The DT390-mIL-3 hybrid gene was cloned into a vector under the control of an inducible promoter. The fusion protein was expressed in Escherichia coli and then purified from inclusion bodies. The fusion toxin was potent because it inhibited FDC-P1, an IL-3R-expressing murine myelomonocytic tumor line (IC50 = 0.025 nmol/L or 1.5 ng/mL), Kinetics were rapid and cell-free studies showed that DT390-mIL-3 was as toxic as native DT, DT390-mIL-3 was selective because anti-mIL-3 monoclonal antibody, but not irrelevant antibody, inhibited its ability to kill, Cell lines not expressing IL-3R were not inhibited by the fusion protein. Because the use of DT390-mIL-3 as an antileukemia agent could be restricted by its reactivity with committed and/or primitive progenitor cells, bone marrow (BM) progenitor assays were performed. DT390-mIL-3 selectively inhibited committed BM progenitor cells as measured by in vitro colony-forming unit-granulocyte-macrophage and in vivo colony-forming unit-spleen colony assays. To determine if this fusion protein was reactive against BM progenitor cells required to rescue lethally irradiated recipients, adoptive transfer experiments were performed, Eight million DT390-mIL-8-treated C57BL/6 Ly5.2 BM cells, but not 4 million, were able to rescue lethally irradiated congenic C57BL/6 Ly5.1 recipients, suggesting that progenitor cells might be heterogenous in their expression of IL-3R. This idea was supported in competitive repopulation experiments in which DT390-mIL-8-treated C57BL/6 Ly5.2 BM cells were mixed with nontreated C57BL/6 Ly5.1 BM cells and used to reconstitute C57BL/6 Ly5.1 mice, A significant reduction, but not elimination, of Ly5.2-expressing cells 95 days post-BM transplantation and secondary transfer experiments indicated that IL-3R is not uniformly expressed on all primitive progenitor cells, The fact that some early progenitor cells survived DT390-mIL-3 treatment indicates that this fusion toxin may be useful in the treatment of myeloid leukemias that express the IL-3R. (C) 1996 by The American Society of Hematology. C1 UNIV MINNESOTA HOSP & CLIN,DIV BONE MARROW TRANSPLANTAT,DEPT PEDIAT,DEPT THERAPEUT RADIOL,MINNEAPOLIS,MN 55455. ROCHE MOL SYST,ALAMEDA,CA. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [R01-CA36725, R01-CA31618] NR 55 TC 26 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 1996 VL 88 IS 4 BP 1445 EP 1456 PG 12 WC Hematology SC Hematology GA VC854 UT WOS:A1996VC85400036 PM 8695865 ER PT J AU Black, MM Zachrau, RE Hankey, BF Feuer, EJ AF Black, MM Zachrau, RE Hankey, BF Feuer, EJ TI Prognostic significance of in situ carcinoma associated with invasive breast carcinoma - A natural experiment in cancer immunology? SO CANCER LA English DT Article DE antitumor immunity; breast carcinoma; breast carcinoma prognosis; in situ breast carcinoma; second primary breast carcinoma; SEER ID MAMMARY-TUMOR VIRUS; GRAPHICAL REPRESENTATION; CELLULAR-IMMUNITY; SURVIVAL; ANTIGEN AB BACKGROUND. Our previous studies indicate that the in situ phase of mammary carcinogenesis is characteristically associated with cell-mediated immunity (CMI) against an immunogen shared by most breast carcinomas. Such reactivity is inversely correlated with stage and appears to impede in situ-to-invasive progression and lethality from invasive breast carcinoma. If in situ carcinomas are indeed associated with ambient, prognostically favorable immunity against such an immunogen, one would expect lethality from invasive breast carcinoma to be reduced in patients with a diagnosis of a prior, simultaneous, or subsequent in situ breast carcinoma. The present study provides a test of such relationships. METHODS. Patient survival was analyzed for 129,394 female patients with invasive breast carcinoma diagnosed in areas covered by the Surveillance, Epidemiology, and End Results (SEER) Program based at the National Cancer Institute (NCI). Patients were classified according to whether they had a prior, simultaneous, or subsequent in situ breast carcinoma and survival was examined for up to 15 years subsequent to diagnosis using life tables and the Cox regression model. RESULTS. The findings indicate that patients with an invasive breast carcinoma who had a prior, simultaneous, or subsequent in situ breast carcinoma did experience significantly better survival than comparison groups of patients who either did not have an associated cancer of any type, had an associated invasive breast carcinoma, or had an in situ or invasive cancer of non-breast origin. CONCLUSIONS. Our prior and current observations warrant more direct studies of the prognostic, therapeutic, and prophylactic significance of the in situ carcinoma-associated type of specific CMI in breast cancer patients. (C) 1996 American Cancer Society. C1 NEW YORK METHODIST HOSP,DEPT SURG,BROOKLYN,NY. NCI,CANC STAT BRANCH,SURVEILLANCE PROGRAM,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NCI,APPL RES BRANCH,SURVEILLANCE PROGRAM,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP Black, MM (reprint author), NEW YORK MED COLL,INST BREAST DIS,VALHALLA,NY 10595, USA. NR 22 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 1996 VL 78 IS 4 BP 778 EP 788 PG 11 WC Oncology SC Oncology GA VA437 UT WOS:A1996VA43700014 PM 8756372 ER PT J AU Nicholson, HS Blask, AN Markle, BM Reaman, GH Byrne, J AF Nicholson, HS Blask, AN Markle, BM Reaman, GH Byrne, J TI Uterine anomalies in Wilms' tumor survivors SO CANCER LA English DT Article DE Wilms' tumor; survival; uterine anomalies; fertility; magnetic resonance imaging; ultrasound; WT1; genetic epidemiology ID ABDOMINAL IRRADIATION; CHILDHOOD; ULTRASONOGRAPHY; PREGNANCY; CANCER; LOCUS; GENE; WT1 AB BACKGROUND. The association between Wilms' tumor (WT) and genitourinary (GU) anomalies has long been appreciated; however, associated GU anomalies have been described almost exclusively in males. METHODS. To investigate whether females with WT also have an increased prevalence of GU anomalies, the authors evaluated the uterine anatomy of 24 WT survivors using magnetic resonance imaging and ultrasonography. RESULTS. Two of 24 female survivors (8%) had anomalies. One had a septate uterus, and a limited molecular analysis of her constitutional DNA revealed no mutations or deletions of the tumor suppressor gene WT1. Another survivor with the WAGR syndrome (WT, aniridia, GU anomalies, and retardation), with the characteristic 11p13 deletion including WT1, had a uterine anomaly (hypoplastic vs. unicornuate). CONCLUSIONS. Because uterine malformations are rare in the general population, this finding suggests an association between WT and uterine malformations and also may partially explain the fertility deficit previously demonstrated in adult female WT survivors. Pelvic ultrasonography in adult female WT survivors can alert survivors and clinicians to possible fertility problems that may lead to problem pregnancies and adverse pregnancy outcomes. (C) 1996 American Cancer Society. C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT PEDIAT,WASHINGTON,DC 20052. CHILDRENS NATL MED CTR,DEPT DIAGNOST IMAGING & RADIOL,WASHINGTON,DC 20010. NATL CANC INST,GENET EPIDEMIOL BRANCH,NATL INST HLTH,WASHINGTON,DC. RP Nicholson, HS (reprint author), CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. NR 30 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 1996 VL 78 IS 4 BP 887 EP 891 PG 5 WC Oncology SC Oncology GA VA437 UT WOS:A1996VA43700028 PM 8756386 ER PT J AU Wexler, LH DeLaney, TF Tsokos, M Avila, N Steinberg, SM WeaverMcClure, L Jacobson, J Jarosinski, P Hijazi, YM Balis, FM Horowitz, ME AF Wexler, LH DeLaney, TF Tsokos, M Avila, N Steinberg, SM WeaverMcClure, L Jacobson, J Jarosinski, P Hijazi, YM Balis, FM Horowitz, ME TI Ifosfamide and etoposide plus vincristine, doxorubicin, and cyclophosphamide for newly diagnosed Ewing's sarcoma family of tumors SO CANCER LA English DT Article DE Ewing's sarcoma family of tumors (Ewing's sarcoma, peripheral primitive; neuroectodermal tumor, peripheral neuroepithelioma); ifosfamide; etoposide; doxorubicin; cyclophosphamide; vincristine; radiation therapy; local control; prognostic factors ID COMBINED MODALITY THERAPY; TERM FOLLOW-UP; YOUNG-ADULTS; MULTIMODAL THERAPY; RADIATION-THERAPY; SURGICAL RESECTION; INTER-GROUP; BONE; CHILDREN; CHEMOTHERAPY AB BACKGROUND. This study was conducted to determine the feasibility of, and improve outcome by, incorporating ifosfamide and etoposide (IE) into the therapy of newly diagnosed patients with Ewing's sarcoma family of tumors of bone and soft tissue. METHODS. Fifty-four newly diagnosed patients received 7 cycles of vincristine, doxorubicin, and cyclophosphamide (VAdriaC) and 11 cycles of IE. Radiation therapy after the fifth chemotherapy cycle was the primary approach to local control. RESULTS. Actuarial 5-year event-free survival (EFS) and overall survival rates were 42% and 45%, respectively, with a median duration of potential follow-up of 6.8 years. EFS was significantly better for patients with localized tumors than for those with metastatic lesions (64% v. 13%, P < 0.0001). Actuarial local progression-free survival at 5 years was 74%, and did not correlate with primary tumor size or site, histologic subtype, or the presence of metastases. Febrile neutropenia developed after 49% of cycles, and clinical or sub-clinical cardiac dysfunction was common (7% and 40% respectively). There were four toxic deaths and one case of secondary myelodysplastic syndrome. CONCLUSIONS. Despite substantial toxicity, the integration of IE into the front-line, VAdriaC-based therapy of patients with Ewing's sarcoma family of tumors is feasible and appeared to significantly improve the outcome for patients with high risk localized tumors, but had no impact on the poor prognosis of patients with metastatic tumors. Local control can be achieved in the vast majority of patients using radiotherapy exclusively, even among patients with bulky, central axis tumors. Longer follow-up is needed to evaluate the late effects of this intensive therapy. (C) 1996 American Cancer Society. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. RP Wexler, LH (reprint author), NCI,PEDIAT BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 13N240,10 CTR DR,BETHESDA,MD 20892, USA. NR 52 TC 81 Z9 84 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 1996 VL 78 IS 4 BP 901 EP 911 PG 11 WC Oncology SC Oncology GA VA437 UT WOS:A1996VA43700030 PM 8756388 ER PT J AU Schully, RE Henson, DE Nielsen, ML Ruby, SG Creasman, WT Fried, A Gershenson, DM Hart, WR Kempson, RL Page, DL Selvaggi, SM Coppock, DL Farrow, GM Gorstein, F Hammond, ME Hutter, RVP Min, KW Nash, G Oberman, HA Schwartz, IS Schlosnagle, DC Travers, H Webb, JH Weiss, LL Wick, MR AF Schully, RE Henson, DE Nielsen, ML Ruby, SG Creasman, WT Fried, A Gershenson, DM Hart, WR Kempson, RL Page, DL Selvaggi, SM Coppock, DL Farrow, GM Gorstein, F Hammond, ME Hutter, RVP Min, KW Nash, G Oberman, HA Schwartz, IS Schlosnagle, DC Travers, H Webb, JH Weiss, LL Wick, MR TI Practice protocol for the examination of specimens removed from patients with ovarian tumors - A basis for checklists SO CANCER LA English DT Article ID PROGNOSTIC-SIGNIFICANCE; CELL TUMORS; CARCINOMA; CANCER; BORDERLINE; PATHOLOGY; STAGE C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NCI,EARLY DETECT BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. PATHOL CONSULTANTS,WICHITA,KS. HINSDALE HOSP,DEPT PATHOL & LAB MED,HINSDALE,IL. RP Schully, RE (reprint author), MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 37 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 1996 VL 78 IS 4 BP 927 EP 940 PG 14 WC Oncology SC Oncology GA VA437 UT WOS:A1996VA43700033 ER PT J AU Glick, AB Weinberg, WC Wu, IH Quan, W Yuspa, SH AF Glick, AB Weinberg, WC Wu, IH Quan, W Yuspa, SH TI Transforming growth factor beta(1) suppresses genomic instability independent of a G(1) arrest, p53, and Rb SO CANCER RESEARCH LA English DT Article ID MOUSE SKIN CARCINOGENESIS; WILD-TYPE P53; GENE AMPLIFICATION; TGF-BETA; MALIGNANT CONVERSION; HAMSTER-CELLS; CANCER CELLS; II RECEPTOR; HIGH-RISK; PROTEIN AB Alterations in expression of or responsiveness to transforming growth factor beta (TGF-beta) are frequently found in human and animal epithelial cancers and are thought to be important for loss of growth control in the neoplastic cell, We show here that keratinocyte cell lines from mice with a targeted deletion of the TGF-beta 1 gene have significantly increased frequencies of gene amplification in response to the drug N-phosphonacetyl-L-aspartate (PALA) compared to TGF-beta 1-expressing control keratinocyte cell lines, In contrast to the control lines, the PALA-mediated G(1) arrest did not occur in the TGF-beta 1 null keratinocytes despite the presence of wild-type p53 in both genotypes, Exogenous TGF-beta 1 suppresses gene amplification in the null keratinocytes at concentrations that do not cause a G(1) growth arrest and in human tumor cell lines that are insensitive to TGF-beta 1-mediated growth inhibition, The pathway of TGF-beta 1 suppression is independent of the p53 and Rb genes, but requires an intact TGF-beta type II receptor. These studies reveal a novel TGF-beta-mediated pathway regulating genomic stability and suggest that defects in TGF-beta signaling may have profound effects on tumor progression independent of cell proliferation. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,DIV BASIC SCI,BETHESDA,MD 20892. RI Weinberg, Wendy/A-8920-2009 NR 30 TC 80 Z9 83 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1996 VL 56 IS 16 BP 3645 EP 3650 PG 6 WC Oncology SC Oncology GA VB986 UT WOS:A1996VB98600009 PM 8706000 ER PT J AU Wei, SJC Chang, RL Cui, XX Merkler, KA Wong, CQ Yagi, H Jerina, DM Conney, AH AF Wei, SJC Chang, RL Cui, XX Merkler, KA Wong, CQ Yagi, H Jerina, DM Conney, AH TI Dose-dependent differences in the mutational profiles of (-)-(1R,2S,3S,4R)-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phen anthrene and its less carcinogenic enantiomer SO CANCER RESEARCH LA English DT Article ID HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE; DIASTEREOMERIC BENZOPYRENE 7,8-DIOL-9,10-EPOXIDES; DIHYDROFOLATE-REDUCTASE GENE; DIPLOID HUMAN FIBROBLASTS; MURINE TUMOR-MODELS; HAMSTER V-79 CELLS; ADDUCT OPPOSITE DT; OPTICAL ENANTIOMERS; SHUTTLE VECTOR; CODING REGION AB Chinese hamster V-79 cells were treated with high cytotoxic or low noncytotoxic concentrations of the highly carcinogenic and mutagenic (-)-(1R,2S,3S,4R)-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrsbenzo[c]-phenanthrene [(-)-B[c]PhDE; fjord-region diol epoxide] or its biologically less active (+)-(1S,2R,3R,4S) enantiomer [(+)-B[c]PhDE], The benzylic 4-hydroxyl group and the epoxide oxygen are trails in both enantiomers. Independent 8-azaguanine-resistant clones were isolated, The coding region of the hypoxanthine (guanine) phosphoribusyltransferase gene was amplified by reverse transcription-PCR and sequenced, For (-)-B[c]PhDE, mutation frequencies were 10- or 356-fold above background for the low 10.01-0.1 mu M; 97% cell survival) or high (1.0-1.25 mu M; 26% cell survival) doses, respectively, For the high dose group, 20 of 64 base substitutions occurred at GC base pairs (31%) and 44 at AT base pairs (69%), For the low-dose group, 6 of 55 base substitutions were at GC base pairs (11%), and 49 mere at AT base pairs (89%), For the less active (+)-B[c]PhDE, mutation frequencies were 17- or 372-fold above background for the low (0.12-0.5 mu M; 95% cell survival) or high (2.0-3.0 mu M; 31% cell survival) doses, respectively, In contrast to the results with the (-)-B[c]PhDE, both the high- and the low-dose groups for (+)-B[c]PhDE gave a 50:50 distribution of base substitution at GC versus AT base pairs, Our data indicate that: (a) transversions were the predominant base substitutions observed for both the (+)- and (-)-enantiomers of B[c]PhDE; (b) (-)-B[c]PhDE showed high selectivity for causing AT --> TA transversions, whereas considerably less selectivity was observed for (+)-B[c]PhDE; (c) (-)-B[c]PhDE had a different hot spot profile for base substitutions than did (+)-B[c]PhDE, but some common hot spots were observed for both compounds; and (d) decreasing the dose of (-)-B[c]PhDE increased the proportion of mutations at AT base pairs and decreased those at GC base pairs, but this was not observed for (+)B[c]PhDE. C1 NIDDKD,SECT OXIDAT MECH,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. RP Wei, SJC (reprint author), RUTGERS STATE UNIV,COLL PHARM,CANC RES LAB,DEPT BIOL CHEM,POB 789,PISCATAWAY,NJ 08855, USA. FU NCI NIH HHS [CA49756]; NIEHS NIH HHS [ES05022] NR 50 TC 25 Z9 27 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1996 VL 56 IS 16 BP 3695 EP 3703 PG 9 WC Oncology SC Oncology GA VB986 UT WOS:A1996VB98600019 PM 8706010 ER PT J AU Suganuma, M Okabe, S Sueoka, E Iida, N Komori, A Kim, SJ Fujiki, H AF Suganuma, M Okabe, S Sueoka, E Iida, N Komori, A Kim, SJ Fujiki, H TI New process of cancer prevention mediated through inhibition of tumor necrosis factor alpha expression SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; PROTEIN PHOSPHATASE-1; (-)-EPIGALLOCATECHIN GALLATE; CHEMOPREVENTIVE AGENTS; CELL-PROLIFERATION; SODIUM-SALICYLATE; BREAST-CANCER; ACTIVATION; RELEASE; ASPIRIN AB Mechanisms of cancer prevention were studied using structurally different cancer-preventive agents, sarcophytol A, canventol, (-)-epigallocatechin gallate, and tamoxifen, based on our evidence that tumor necrosis factor alpha (TNF-alpha) acts as an endogenous tumor promoter relevant to human carcinogenesis. Pretreatment with the four preventive agents commonly inhibited TNF-alpha mRNA expression and TNF-alpha release in BALB/3T3 cells induced by a tumor promoter, okadaic acid, whereas the expression of early response genes (c-jun, junB, c-fos, and fosB) was enhanced, These results strongly suggest that inhibition of TNF-alpha mRNA expression and its release is a new process of cancer prevention. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. SAITAMA CANC CTR,RES INST,INA,SAITAMA 362,JAPAN. NR 32 TC 100 Z9 103 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 AUG 15 PY 1996 VL 56 IS 16 BP 3711 EP 3715 PG 5 WC Oncology SC Oncology GA VB986 UT WOS:A1996VB98600021 PM 8706012 ER PT J AU Scala, S Wosikowski, K Giannakakou, P Valle, P Biedler, JL Spengler, BA Lucarelli, E Bates, SE Thiele, CJ AF Scala, S Wosikowski, K Giannakakou, P Valle, P Biedler, JL Spengler, BA Lucarelli, E Bates, SE Thiele, CJ TI Brain-derived neurotrophic factor protects neuroblastoma cells from vinblastine toxicity SO CANCER RESEARCH LA English DT Article ID HUMAN NEURO-BLASTOMA; NERVE GROWTH-FACTOR; GLUTAMATE-INDUCED NEUROTOXICITY; ACID-INDUCED DIFFERENTIATION; MULTIDRUG RESISTANCE GENE; DRUG-RESISTANCE; IN-VITRO; EXPRESSION; BDNF; SURVIVAL AB Brain-derived neurotrophic factor (BDNF) and its receptors are necessary for the survival and development of many neuronal cells, Because BDNF and TrkB are expressed in many poor-prognosis neuroblastoma (NB) tumors, we evaluated the role of BDNF in affecting sensitivity to chemotherapeutic agents. We investigated the effects of activation of the BDNF-TrkB signal transduction pathway in two NB cell lines, 15N and SY5Y, 15N cells lack the high-affinity receptor p145TrkB and express BDNF; 15N cells were used along with 15N-TrkB cells, a subline transfected with a TrkB expression vector. In cytotoxicity assays, 15N-TrkB cells were consistently 1.4-2-fold more resistant to vinblastine than 15N cells, Drug accumulation assays showed a 50% reduction in [H-3]vinblastine accumulation in 15N-TrkB cells compared with control 15N cells. Addition of 30 ng/ml BDNF resulted in a reduction to 46% of control in 15N cells and a reduction to 28% of control in 15N-TrkB cells. SY5Y cells were chosen as a second model because they lack both endogenous BDNF and TrkB expression, p145TrkB expression is induced by 1 nm retinoic acid, Vinblastine accumulation was not significantly affected by 1 nM retinoic acid in SY5Y cells. Addition of 30 ng/ml BDNF decreased [H-3]vinblastine accumulation to 58% of control in SY5Y cells and decreased [H-3]vinblastine accumulation to 62% of control in TrkB-expressing SY5Y cells. Although an increase in BDNF expression is seen in multidrug-resistant sublines of SY5Y and BE(2)-C NE cells, the protective effect of BDNF in vinblastine toxicity may be unrelated to mdr-1, because the activity of other agents transported by P-glycoprotein was not affected. There was no increase in mdr-1 expression in 1 nM RA SY5Y cells and 15N-TrkB cells, as assessed by Northern blot analysis. In addition to the effects of BDNF on vinblastine cytotoxicity and accumulation, there was an inhibition in the ability of vinblastine to depolymerize tubulin in BDNF-treated cells, Thus, BDNF and TrkB may partially rescue NE cells from vinblastine toxicity and thereby may contribute to a more chemoresistant phenotype. C1 NCI,CELL & MOL BIOL SECT,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,DIV CANC TREATMENT,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,LAB CELL & BIOCHEM GENET,NEW YORK,NY 10021. RI Scala, Stefania/K-1380-2016; Lucarelli, Enrico/G-3588-2015 OI Scala, Stefania/0000-0001-9524-2616; Lucarelli, Enrico/0000-0002-6681-6374 NR 49 TC 50 Z9 53 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1996 VL 56 IS 16 BP 3737 EP 3742 PG 6 WC Oncology SC Oncology GA VB986 UT WOS:A1996VB98600026 PM 8706017 ER PT J AU Kobayashi, H Yoo, TM Kim, IS Kim, MK Le, N Webber, KO Pastan, I Paik, CH Eckelman, WC Carrasquillo, JA AF Kobayashi, H Yoo, TM Kim, IS Kim, MK Le, N Webber, KO Pastan, I Paik, CH Eckelman, WC Carrasquillo, JA TI L-lysine effectively blocks renal uptake of I-125- or Tc-99m-labeled anti-Tac disulfide-stabilized Fv fragment SO CANCER RESEARCH LA English DT Article ID SINGLE-CHAIN-FV; AMINO-ACID INFUSION; MONOCLONAL-ANTIBODIES; IMMUNOGLOBULIN FORMS; SOMATOSTATIN ANALOG; TUBULAR FUNCTION; NUDE-MICE; PROTEIN; RADIOIMMUNOTHERAPY; BINDING AB In this study, me investigated the ability of L-lysine to block renal uptake of I-125-, Tc-99m- labeled Fv fragments. Anti-Tac disulfide-stabilized Fv fragment (dsFv) was derived from a murine monoclonal antibody that recognizes the alpha subunit of the interleukin-2 receptor (IL-2R alpha). The I-125- or Tc-99m-labeled dsFv was injected i.v. into non-tumor-hearing nude mice or into nude mice hearing SP2/Tac (IL-2R alpha positive) and SP2/0 (IL-2R alpha negative) tumor. We then evaluated the pharmacokinetics of L-[H-3]lysine and the effect of L-lysine dose, timing of administration, and route of delivery on catabolism and biodistribution of i.v. dsFv. Peak renal uptake of i.v. or i.p. injected L-[H-3]lysine occurred within 5 and 15 min, respectively. The kidney uptake of L-lysine exhibited a dose-response effect. When L-lysine was coinfused or injected shortly before dsFv, renal uptake of dsFv was blocked to <5% of the control, but longer intervals were less effective. Aminosyn II and Travasol 10% (parenteral amino acid solutions) also blocked renal uptake of radiolabeled dsFv. Administration of L-lysine did not alter the blood kinetics and slightly increased the tumor uptake of dsFv, but it did prevent catabolism in the kidney and resulted in lower amounts of catabolites In the serum and urine. In conclusion, we have shown that a blocking dose of lysine, injected with or immediately before the injection of radiolabeled dsFv, is most effective in blocking the renal uptake of dsFv. This is consistent with the rapid uptake of L-[H-3]lysine by the kidney and is further substantiated by the relative ineffectiveness of lysine injected immediately after the radiolabeled dsFv injection. C1 NCI, NIH, DEPT NUCL MED, BETHESDA, MD 20892 USA. NCI, NIH, POSITRON EMISS TOMOG DEPT, BETHESDA, MD 20892 USA. NCI, NIH, WARREN G MAGNUSON CLIN CTR, BETHESDA, MD 20892 USA. NCI, NIH, MOL BIOL LAB, DIV BASIC SCI, BETHESDA, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 45 TC 72 Z9 72 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1996 VL 56 IS 16 BP 3788 EP 3795 PG 8 WC Oncology SC Oncology GA VB986 UT WOS:A1996VB98600034 PM 8706025 ER PT J AU Duverger, N Kruth, H Emmanuel, F Caillaud, JM Viglietta, C Castro, G Tailleux, A Fievet, C Fruchart, JC Houdebine, LM Denefle, P AF Duverger, N Kruth, H Emmanuel, F Caillaud, JM Viglietta, C Castro, G Tailleux, A Fievet, C Fruchart, JC Houdebine, LM Denefle, P TI Inhibition of atherosclerosis development in cholesterol-fed human apolipoprotein A-I-transgenic rabbits SO CIRCULATION LA English DT Article DE apolipoproteins; atherosclerosis; cholesterol ID HIGH-DENSITY-LIPOPROTEIN; ESTER TRANSFER PROTEIN; HEPATIC LIPASE; MONOCLONAL-ANTIBODIES; HEART-DISEASE; HUMAN-PLASMA; LESIONS; MICE; EFFLUX; TRIGLYCERIDE AB Background Prospective epidemiological studies support the hypothesis that high levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein (ape) A-I limit atherosclerosis development. However; more data from studies with animal models of atherosclerosis that resemble the human disease are required to demonstrate the effect of apo A-I in the inhibition of atherogenesis. The rabbit is a good animal model for human atherosclerosis. Methods and Results Human apo A-I-transgenic rabbits have been produced, and we have evaluated the effect of apo A-I on the development of atherosclerosis in transgenic rabbits fed a cholesterol-rich diet for 14 weeks. Plasma cholesterol levels of atherogenic apo B-containing lipoproteins were similar for transgenic and control rabbits (>1000 mg/dL), while plasma levels of HDL cholesterol in the transgenic group were always about twice that of the control group (68+/-11 versus 37+/-3 mg/dL at 14 weeks; P <.001). At the end of the experiment, the amount of aortic surface area covered by lesions as well as the amount of lipid accumulation in the aorta were significantly less in transgenic rabbits compared with the control group (15+/-12% versus 30+/-8%, P <.0027 for the surface area of the thoracic aorta; 116+/-31 versus 247+/-39 mu mol/g aorta, P <.006 for cholesterol content in total aorta). Conclusions Overexpression of human apo A-I in rabbits inhibits the development of atherosclerosis in this animal model that resembles, in many respects, human atherosclerosis. C1 NHLBI,SECT EXPTL ATHEROSCLEROSIS,BETHESDA,MD 20892. INRA,JOUY EN JOSAS,FRANCE. INST PASTEUR,INSERM 325,F-59019 LILLE,FRANCE. RP Duverger, N (reprint author), CTR RECH VITRY ALFORTVILLE,ATHEROSCLEROSIS DEPT,RHONE POULENC RORER GENCELL DIV,F-94403 VITRY SUR SEINE,FRANCE. NR 38 TC 171 Z9 180 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 15 PY 1996 VL 94 IS 4 BP 713 EP 717 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VC360 UT WOS:A1996VC36000026 PM 8772693 ER PT J AU Kaplan, G Totsuka, A Thompson, P Akatsuka, T Moritsugu, Y Feinstone, SM AF Kaplan, G Totsuka, A Thompson, P Akatsuka, T Moritsugu, Y Feinstone, SM TI Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus SO EMBO JOURNAL LA English DT Article DE HAV; integral membrane glycoprotein; mucin; picornavirus; virus receptor ID A-VIRUS; MOLECULAR-CLONING; MONOCLONAL-ANTIBODY; IMMUNE-COMPLEXES; XENOPUS-LAEVIS; GENE; CULTURE; PROTEIN; LINES; CDNA AB Very little is known about the mechanism of cell entry of hepatitis A virus (HAV), and the identification of cellular receptors for this picornavirus has been elusive. Here we describe the molecular cloning of a cellular receptor for HAV using protective monoclonal antibodies raised against susceptible African green monkey kidney (AGMK) cells as probes, Monoclonal antibodies 190/4, 235/4 and 263/6, which reacted against similar epitopes, specifically protected AGMK cells against HAV infection by blocking the binding of HAV, Expression; cloning and nucleotide sequence analysis of the cDNA coding for epitope 190/4 revealed a novel mucin-like class I integral membrane glycoprotein of 451 amino acids, the HAV cellular receptor 1 (HAV cr-1). Immunofluorescence anal;sis indicated that mouse Ltk(-) cells transfected with HAV cr-1 cDNA gained Limited susceptibility to HAV infection, which was blocked by treatment with monoclonal antibody 190/4, Our results demonstrate that the HAV cr-1 polypeptide is an attachment receptor for HAV and strongly suggest that it is also a functional receptor which mediates HAV infection, This report constitutes the first identification of a cellular receptor for HAV. C1 NATL INST HLTH,DEPT VIRAL DIS & VACCINE CONTROL,TOKYO 208,JAPAN. RP Kaplan, G (reprint author), NIH,US FDA,CTR BIOL EVALUAT & RES,LAB HEPATITIS RES,OFF VACCINE REVIEW & RES,DIV VIRAL PROD,BETHESDA,MD 20892, USA. NR 57 TC 152 Z9 163 U1 0 U2 8 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 15 PY 1996 VL 15 IS 16 BP 4282 EP 4296 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VE353 UT WOS:A1996VE35300021 PM 8861957 ER PT J AU Vaughan, KT Mikami, A Paschal, BM Holzbaur, ELF Hughes, SM Echeverri, CJ Moore, KJ Gilbert, DJ Copeland, NG Jenkins, NA Vallee, RB AF Vaughan, KT Mikami, A Paschal, BM Holzbaur, ELF Hughes, SM Echeverri, CJ Moore, KJ Gilbert, DJ Copeland, NG Jenkins, NA Vallee, RB TI Multiple mouse chromosomal loci for dynein-based motility SO GENOMICS LA English DT Article ID OUTER ARM DYNEIN; ACTIN-RELATED PROTEIN; LEFT RIGHT ASYMMETRY; CYTOPLASMIC DYNEIN; INTERMEDIATE CHAIN; HEAVY-CHAIN; DROSOPHILA-MELANOGASTER; RETROGRADE TRANSPORT; MOLECULAR-CLONING; VESICLE MOTILITY AB Dyneins are multisubunit mechanochemical enzymes capable of interacting with microtubules to generate force. Axonemal dyneins produce the motive force for ciliary and flagellar beating by inducing sliding between adjacent microtubules within the axoneme. Cytoplasmic dyneins translocate membranous organelles and chromosomes toward the minus ends of cytoplasmic microtubules. Dynactin is an accessory complex implicated in tethering cytoplasmic dynein to membranous organelles and mitotic kinetochores. In the studies described here, we have identified a number of new dynein genes and determined their mouse chromosomal locations by interspecific backcross analysis. We have also mapped several dynein and dynactin genes cloned previously. Our studies provide the first comprehensive attempt to map dynein and dynactin genes in mammals and provide a basis for the further analysis of dynein function in development and disease. (C) 1996 Academic Press, Inc. C1 WORCESTER FDN EXPT BIOL INC,CELL BIOL GRP,SHREWSBURY,MA 01545. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 65 TC 61 Z9 66 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 AUG 15 PY 1996 VL 36 IS 1 BP 29 EP 38 DI 10.1006/geno.1996.0422 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VD246 UT WOS:A1996VD24600004 PM 8812413 ER PT J AU Sun, DS Chang, AC Jenkins, NA Gilbert, DJ Copeland, NG Chang, NCA AF Sun, DS Chang, AC Jenkins, NA Gilbert, DJ Copeland, NG Chang, NCA TI Identification, molecular characterization, and chromosomal localization of the cDNA encoding a novel leucine zipper motif-containing protein SO GENOMICS LA English DT Article ID TRANSCRIPTIONAL REGULATORY PROTEINS; 3' UNTRANSLATED REGION; DNA-BINDING PROTEINS; GENETIC-LINKAGE MAP; NUCLEAR-LOCALIZATION; DOMAINS; CLONING; ORGANIZATION; GENOME; KINASE AB cDNA clones encoding a novel protein (LUZP) with three leucine zipper motifs were first identified from a murine bone marrow cDNA library. After screening two additional cDNA libraries of activated peritoneal exudate cells, 32 positive clones were obtained from 1.3 x 10(7) phage plaques. Four overlapping clones constituting a total of 7399 bp were sequenced on both strands. The complete open reading frame of LUZP is 1067 amino acids. In addition to three leucine zipper motifs located at the NH2 terminus, there are three nuclear localization signals and a large number of putative Ser/Thr phosphorylation sites. Western blot analyses indicate that LUZP is predominantly expressed in brain, whereas immunocytochemistry data clearly reveal its presence in the nucleus of neurons. Interspecific backcross analyses have mapped Luzp to mouse chromosome 4 in proximity to Gpcr14. Comparative mapping data suggest that the human homolog of Luzp will map to human chromosome 1p36. (C) 1996 Academic Press, Inc. C1 NATL YANG MING UNIV,INST MICROBIOL & IMMUNOL,CTR NEUROSCI,TAIPEI 112,TAIWAN. NATL YANG MING UNIV,INST NEUROSCI,CTR NEUROSCI,TAIPEI 112,TAIWAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-46000] NR 32 TC 10 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 15 PY 1996 VL 36 IS 1 BP 54 EP 62 DI 10.1006/geno.1996.0425 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VD246 UT WOS:A1996VD24600007 PM 8812416 ER PT J AU Pras, E Sood, R Raben, N Aksentijevich, I Chen, XA Kastner, DL AF Pras, E Sood, R Raben, N Aksentijevich, I Chen, XA Kastner, DL TI Genomic organization of SLC3A1, a transporter gene mutated in cystinuria SO GENOMICS LA English DT Article ID AMINO-ACID TRANSPORTER; IN-SITU HYBRIDIZATION; EXPRESSION CLONING; CHROMOSOMAL LOCALIZATION; KIDNEY CDNA; RAT-KIDNEY; MUTATIONS; RBAT; HETEROGENEITY; ASSIGNMENT AB The SLC3A1 gene encodes a transport protein for cystine and the dibasic amino acids. Recently mutations in this gene have been shown to cause cystinuria. We report the genomic structure and organization of SLC3A1, which is composed of 10 exons and spans nearly 45 kb. Until now screening for mutations in SLC3A1 has been based on RT-PCR amplification of illegitimate mRNA transcripts from white blood cells. In this report we provide primers for amplification of exons from genomic DNA, thus simplifying the process of screening for SLC3A1 mutations in cystinuria. (C) 1996 Academic Press, Inc. C1 NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. RP Pras, E (reprint author), CHAIM SHEBA MED CTR,DEPT MED C,IL-52621 TEL HASHOMER,ISRAEL. NR 20 TC 15 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 0888-7543 J9 GENOMICS JI Genomics PD AUG 15 PY 1996 VL 36 IS 1 BP 163 EP 167 DI 10.1006/geno.1996.0437 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VD246 UT WOS:A1996VD24600019 PM 8812428 ER PT J AU Inoue, I Taniuchi, I Kitamura, D Jenkins, NA Gilbert, DJ Copeland, NG Watanabe, T AF Inoue, I Taniuchi, I Kitamura, D Jenkins, NA Gilbert, DJ Copeland, NG Watanabe, T TI Characteristics of the mouse genomic histamine H1 receptor gene SO GENOMICS LA English DT Article ID MOLECULAR-CLONING; H-1 RECEPTOR; EXPRESSION; LOCALIZATION AB We report here the molecular cloning of a mouse histamine H1 receptor gene. The protein deduced from the nucleotide sequence is composed of 488 amino acid residues with characteristic properties of GTP binding protein-coupled receptors. Our results suggest that the mouse histamine H1 receptor gene is a single locus, and no related sequences were detected. Interspecific backcross analysis indicated that the mouse histamine H1 receptor gene (Hrh1) is located in the central region of mouse Chromosome 6 linked to microphthalmia (Mitfmi), ras-related fibrosarcoma oncogene 1 (Raf1), and ret proto-oncogene (Ret) in a region of homology with human chromosome 3p. (C) 1996 Academic Press, Inc. C1 KYUSHU UNIV,MED INST BIOREGULAT,DEPT MOL IMMUNOL,HIGASHI KU,FUKUOKA 812,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RI Taniuchi, Ichiro/N-6399-2015 OI Taniuchi, Ichiro/0000-0002-9853-9068 NR 12 TC 25 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 15 PY 1996 VL 36 IS 1 BP 178 EP 181 DI 10.1006/geno.1996.0441 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VD246 UT WOS:A1996VD24600023 PM 8812432 ER PT J AU Nichols, RC Blinder, J Pai, SI Ge, Q Targoff, IN Plotz, PH Liu, P AF Nichols, RC Blinder, J Pai, SI Ge, Q Targoff, IN Plotz, PH Liu, P TI Assignment of two human autoantigen genes - Isoleucyl-tRNA synthetase locates to 9q21 and lysyl-tRNA synthetase locates to 16q23-q24 SO GENOMICS LA English DT Article ID TRANSFER-RNA-SYNTHETASE; MESSENGER-RNA; AUTOANTIBODIES; DOMAIN; DNA C1 NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892. OKLAHOMA MED RES FDN,ARTHRITIS IMMUNOL SECT,OKLAHOMA CITY,OK 73106. RP Nichols, RC (reprint author), NIAMSD,CTR CLIN,ARTHRITIS & RHEUMATISM BRANCH,NIH,9N244,BETHESDA,MD 20892, USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 19 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 15 PY 1996 VL 36 IS 1 BP 210 EP 213 DI 10.1006/geno.1996.0449 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VD246 UT WOS:A1996VD24600031 PM 8812440 ER PT J AU Rabkin, CS Corbin, DOC Felton, S Barker, H Davison, D Dearden, C Blattner, WA Evans, AS AF Rabkin, CS Corbin, DOC Felton, S Barker, H Davison, D Dearden, C Blattner, WA Evans, AS TI Human T-cell lymphotropic virus type I infection in Barbados: Results of a 20-year follow-up study SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE follow-up study; chronic infection; household contact; adult T-cell leukemia; dermatitis ID HTLV-I; TRANSMISSION; CHILDREN; ANTIBODY; SEROPREVALENCE; JAMAICA; OKINAWA; JAPAN AB Forty-one human T-cell lymphotropic virus type I (HTLV-1)-seropositive individuals were identified among 1,012 subjects with stored serum samples from a health and seroepidemiological survey conducted in Barbados in 1972. These 41 subjects plus 79 HTLV-1 seronegative household, members were targeted in a follow-up study 20 years later. Sixteen seropositive subjects and 22 seronegative subjects were interviewed, examined, and phlebotomized. There were no changes in HTLV-1 serostatus between the 1972 and follow-up serum samples. Three (19%) of the seropositive subjects had HTLV-1-associated disorders: two with dermatitis and one with ''smoldering'' adult T-cell leukemia. Neurologic and immunologic function was similar in HTLV-1-seropositive and HTLV-1-seronegative subjects. HTLV-1 antibodies persist over many years, and the risk for seroconversion of household contacts is low. C1 RES TRIANGLE INST,WASHINGTON,DC. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. RP Rabkin, CS (reprint author), NCI,VIROL EPIDEMIOL BRANCH,6130 EXECUT BLVD,EPN-434,ROCKVILLE,MD 20852, USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD AUG 15 PY 1996 VL 12 IS 5 BP 519 EP 522 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VC622 UT WOS:A1996VC62200013 PM 8757431 ER PT J AU Zeng, GY Quon, MJ AF Zeng, GY Quon, MJ TI Insulin-stimulated production of nitric oxide is inhibited by wortmannin - Direct measurement in vascular endothelial cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE hypertension; insulin resistance; diabetes; obesity ID MUSCLE BLOOD-FLOW; RAT ADIPOSE-CELLS; RELAXING FACTOR; GLUCOSE-UPTAKE; RESISTANCE; RECEPTOR; PRESSURE; KINASE; TRANSLOCATION; HYPERTENSION AB Hypertension is associated with insulin-resistant states such as diabetes and obesity, Nitric oxide (NO) contributes to regulation of blood pressure, To gain insight into potential mechanisms linking hypertension with insulin resistance we directly measured and characterized NO production from human umbilical vein endothelial cells (HUVEC) in response to insulin using an amperometric NO-selective electrode. Insulin stimulation of HUVEC resulted in rapid, dose-dependent production of NO with a maximal response of similar to 100 nM NO (200,000 cells in 2 ml media; ED(50) similar to 500 nM insulin), Although HUVEC have many more IGF-1 receptors than insulin receptors (similar to 400,000, and similar to 40,000 per cell respectively), a maximally stimulating dose of IGF-1 generated a smaller response than insulin (40 nM NO; ED(50) similar to 100 nM IGF-1), Stimulation of HUVEC with PDGF did not result in measurable NO production. The effects of insulin and IGF-1 were completely blocked by inhibitors of either tyrosine kinase (genestein) or nitric oxide synthase (L-NAME). Wortmannin (an inhibitor of phosphatidylinositol 3-kinase [PI S-kinase]) inhibited insulin-stimulated production of NO by similar to 50%, Since PI 3-kinase activity is required for insulin-stimulated glucose transport, our data suggest that NO is a novel effector of insulin signaling pathways that are also involved with glucose metabolism. C1 NHLBI,NIH,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 37 TC 519 Z9 544 U1 0 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 15 PY 1996 VL 98 IS 4 BP 894 EP 898 DI 10.1172/JCI118871 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VE490 UT WOS:A1996VE49000004 PM 8770859 ER PT J AU Mandon, B Chou, CL Nielsen, S Knepper, MA AF Mandon, B Chou, CL Nielsen, S Knepper, MA TI Syntaxin-4 is localized to the apical plasma membrane of rat renal collecting duct cells: Possible role in aquaporin-2 trafficking SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE syntaxin; collecting duct; vesicle-targeting receptors; water channel; aquaporin ID WATER CHANNEL; MESSENGER-RNA; KIDNEY; VASOPRESSIN; EXPRESSION; PROTEIN; SPECIFICITY; RECEPTORS; VESICLES; COMPLEX AB To evaluate the possible role of a putative vesicle-targeting protein, syntaxin-4, in vasopressin-regulated trafficking of aquaporin-2 water channel vesicles to the apical plasma membrane of renal collecting duct cells, we have carried out immunoblotting, immunocytochemistry, and reverse transcription (RT)-PCR experiments in rat kidney. Immunochemical studies used an affinity-purified, peptide-directed polyclonal antibody to rat syntaxin-4. Immunoblots using membrane fractions from inner medullary collecting duct (IMCD) cell suspensions revealed a solitary protein of 36 kD, the expected molecular mass of syntaxin-4. This protein was enriched in a plasma membrane-enriched membrane fraction from IMCD cells, Immunoperoxidase immunocytochemistry in 0.85-mu m cryosections from rat inner medulla revealed discrete labeling of the apical plasma membrane of IMCD cells. RT-PCR demonstrated the presence of syntaxin-4 mRNA in microdissected IMCD segments, confirmed by direct sequencing of the PCR product. In addition, RT-PCR experiments demonstrated syntaxin-4 mRNA in glomeruli, vasa recta, connecting tubules, and thin descending limbs of Henle's loops. The demonstrated localization of syntaxin-4 in the apical plasma membrane of collecting duct principal cells, coupled with previous demonstration of syntaxin-4's putative cognate receptor VAMP2 in aquaporin-2-containing vesicles, supports the view that these proteins could play a role of aquaporin-2 vesicle targeting to the apical plasma membrane. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BETHESDA,MD 20892. UNIV AARHUS,INST ANAT,DEPT CELL BIOL,AARHUS,DENMARK. FU NHLBI NIH HHS [ZO1-HL-01282-KE] NR 33 TC 105 Z9 107 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 15 PY 1996 VL 98 IS 4 BP 906 EP 913 DI 10.1172/JCI118873 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VE490 UT WOS:A1996VE49000006 PM 8770861 ER PT J AU Chamberlin, ME Ubagai, T Mudd, SH Wilson, WG Leonard, JV Chou, JY AF Chamberlin, ME Ubagai, T Mudd, SH Wilson, WG Leonard, JV Chou, JY TI Demyelination of the brain is associated with methionine adenosyltransferase I/III deficiency SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE methionine adenosyltransferase deficiency; genetic mutations; brain demyelination ID S-ADENOSYLMETHIONINE SYNTHETASE; RAT-LIVER; EXPRESSION; HYPERMETHIONINEMIA; PURIFICATION; CLONING; KIDNEY; MUTATION; CREATINE; PATHWAY AB Individuals deficient in hepatic methionine adenosyltransferase (MAT) activity (MAT I/III deficiency) have been demonstrated to contain mutations in the gene (MATA1) that encodes the major hepatic forms, MAT I and III, MAT I/III deficiency is characterized by isolated persistent hypermethioninemia and, in some cases, unusual breath odor. Most individuals with isolated hypermethioninemia have been free of major clinical difficulties. Therefore a definitive diagnosis of MAT I/III deficiency, which requires hepatic biopsy, is not routinely made, However, two individuals with isolated hypermethioninemia have developed abnormal neurological problems, including brain demyelination, suggesting that MAT I/III deficiency can be deleterious, In the present study we have examined the MATA1 gene of eight hypermethioninemic individuals, including the two with demyelination of the brain, Mutations that abolish or reduce the MAT activity were detected in the MATA1 gene of all eight individuals, Both patients with demyelination are homozygous for mutations that alter the reading frame of the encoded protein such that the predicted MAT alpha 1 subunits are truncated and enzymatically inactive, The product of MAT, S-adenosylmethionine (AdoMet), is the major methyl donor for a large number of biologically important compounds including the two major myelin phospholipids, phosphatidylcholine and sphingomyelin, Both are synthesized primarily in the liver, Our findings demonstrate that isolated persistent hypermethioninemia is a marker of MAT I/III deficiency, and that complete lack of MAT I/III activity can lead to neurological abnormalities. Therefore, a DNA-based diagnosis should be performed for individuals with isolated hypermethioninemia to assess if therapy aimed at the prevention of neurological manifestations is warranted. C1 NICHHD,NIH,HERITABLE DISORDERS BRANCH,BETHESDA,MD 20892. NIMH,NIH,LAB GEN & COMPARAT BIOCHEM,BETHESDA,MD 20892. UNIV VIRGINIA,CHILDRENS MED CTR,CHARLOTTESVILLE,VA 22908. INST CHILD HLTH,LONDON,ENGLAND. NR 34 TC 74 Z9 76 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 15 PY 1996 VL 98 IS 4 BP 1021 EP 1027 DI 10.1172/JCI118862 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VE490 UT WOS:A1996VE49000020 PM 8770875 ER PT J AU Oravecz, T Pall, M Norcross, MA AF Oravecz, T Pall, M Norcross, MA TI beta-chemokine inhibition of monocytotropic HIV-1 infection - Interference with a postbinding fusion step SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; LEUKOCYTE CHEMOATTRACTANT RECEPTORS; T-CELL ACTIVATION; HEPARAN-SULFATE; REPLICATION; BINDING; MIP-1-BETA; RANTES; CD26 AB The beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta have potent suppressive effects on HIV-1 infection resulting from an early postbinding block in virus fusion and entry, inhibition was observed only with monocytotropic isolates and mapped to the V3 region of the HIV-1 envelope. RANTES did not inhibit virus expression in chronically infected cells or reduce initial virus attachment to the cell membrane. Inhibitory activity required RANTES binding to the target cell but not G protein-mediated signaling or protein tyrosine kinase activity. The results are consistent with a reversible competitive mechanism of virus inhibition that prevents a V3-associated postbinding step in membrane fusion. The data support a role for a RANTES chemokine receptor as a coreceptor for monocytotropic HIV-1. C1 NIH,DIV HEMATOL PROD,CTR BIOL EVALUAT & RES,US FDA,BETHESDA,MD 20892. NR 29 TC 129 Z9 130 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1996 VL 157 IS 4 BP 1329 EP 1332 PG 4 WC Immunology SC Immunology GA VH124 UT WOS:A1996VH12400001 PM 8759710 ER PT J AU Chused, TM Apasov, S Sitkovsky, M AF Chused, TM Apasov, S Sitkovsky, M TI Murine T lymphocytes modulate activity of an ATP-activated P-2z-type purinoceptor during differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOSOLIC FREE CALCIUM; PAROTID ACINAR-CELLS; EXTRACELLULAR ATP; MOUSE MACROPHAGES; PLASMA-MEMBRANE; XENOPUS-OOCYTES; ION-CHANNEL; THYMOCYTES; RECEPTOR; RESPONSES AB Murine T, but not B, lymphocytes constitutively express a membrane receptor for adenosine nucleotides that opens a nonspecific pore that admits Ca2+ and ethidium (314 Da), but not propidium (415 Da) ions. ATP, ADP, and AMP show decreasing potency; UTP and adenosine are inactive. Nonhydrolyzable ATP analogues are completely ineffective, Oxidized ATP inhibits the response. Activity is detectable at ATP concentrations of 125 mu M and peaks at 1 mM. The intracellular free Ca2+ ([Ca2+](i)) rise is not reversed by removing ATP by centrifugation or apyrase. The kinetics, agonist and antagonist profiles, and the passage of ions as large as ethidium are the characteristics of a P-2Z-type purinoceptor. No expression of classical P-2X-, P-2U-, or P-2Y-type purinoceptors can be detected. The [CA(2+)](i) elevating activity of the ATP receptor is modulated during T cell differentiation. CD4(+)8(+) double-positive thymocytes are the least responsive. CD4(-)8(+) single-positive thymocytes, CD8(+) splenic T cells, CD4(+)8(-) single-positive thymocytes, and CD4(+) splenic T cells show increasing reactivity. Measurement of P-2Z expression by the rate of ethidium ion uptake correlates with the [Ca2+](i). The trimodal expression of P-2Z by splenic CD4(+) T cells correlates with the subsets defined by CD44 and CD45RB, differentiation Ags that distinguish memory cells: P-2Z(low) cells are CD44(bright)CD45RB(bright); P-2Z(int) are CD44(dull)CD45RB(int); P-2Z(high) are CD44(bright)CD45RB(dull). It is suggested that P-2Z receptor-mediated signaling could be involved in the regulation of differentiation and cell death in the thymus and peripheral T lymphocytes. RP Chused, TM (reprint author), NIAID,IMMUNOBIOL LAB,NIH,TWI 2,ROOM 205,ROCKVILLE,MD 20852, USA. NR 42 TC 58 Z9 59 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1996 VL 157 IS 4 BP 1371 EP 1380 PG 10 WC Immunology SC Immunology GA VH124 UT WOS:A1996VH12400007 PM 8759716 ER PT J AU Ding, L Shevach, EM AF Ding, L Shevach, EM TI Activated B cells express CD28/B7-independent costimulatory activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CTLA-4 COUNTER-RECEPTOR; HEAT-STABLE ANTIGEN; CD4(+) T-CELLS; LYMPHOCYTES-T; CD40 LIGAND; CD28-DEFICIENT MICE; SOLUBLE FORM; CD28; INDUCTION; SIGNAL AB Resting and activated B cells display distinct phenotypes and functional properties. Resting B cells are incompetent accessory cells whereas activated B cells are capable of triggering T cell activation, The up-regulation of expression of the B7 family of molecules has been considered to be the primary reason for this functional conversion of activated B cells. We report here that activation of B cells induces a novel costimulatory activity for induction of T cell proliferation, which is independent of the CD28/B7 costimulatory pathway. B cells activated by different stimuli expressed comparable levels of many of the known counter-receptors for costimulation and intercellular adhesion (B7-1, B7-2, HSA, ICAM-1), but differed markedly in their capacity to activate CD4(+) T cells from CD28-deficient (-/-) mice. Activation of B cells via CD40, and to a lesser extent with LPS, induced potent B7/CD28-independent costimulatory activity that resulted in marked augmentation of IL-2-mediated proliferative responses of CD4(+) T cells from CD28 -/- mice. The B7/CD28-independent costimulatory pathway was capable of triggering the activation of naive CD4(+) T cells, as both sorted CD45RB(high) and isolated high density naive CD4(+) T cells from CD28 -/- mice responded vigorously to the costimulation provided by CD40L-activated B cells. RP Ding, L (reprint author), NIAID,IMMUNOL LAB,NIH,BLDG 10,RM 11N315,10 CTR DR-MSC 1892,BETHESDA,MD 20892, USA. NR 54 TC 21 Z9 22 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1996 VL 157 IS 4 BP 1389 EP 1396 PG 8 WC Immunology SC Immunology GA VH124 UT WOS:A1996VH12400009 PM 8759718 ER PT J AU Ehrhardt, RO Gray, B Duchmann, R Inman, JK Strober, W AF Ehrhardt, RO Gray, B Duchmann, R Inman, JK Strober, W TI Reciprocal regulation of mucosal surface IgA(+) B cells by Ig receptor cross-linking and CD40 ligand SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GERMINAL-CENTERS; DENDRITIC CELLS; EXPRESSION; ACTIVATION; CTLA-4; MICE; PROLIFERATION; LYMPHOCYTES; ANTIGEN; IL-5 AB In the present study, we analyze the role of Ig receptor cross-linking in T cell-dependent stimulation of both preswitch surface IgM(+) (sIgm(+)/sIgD(+)) B cells and postswitch (sIgA(+)) B cells. We demonstrate that purified sIgA(+) B cells pretreated with anti-Iga-dextran at low concentrations (10 and 100 ng/ml) exhibited an increased response to activated T cells, whereas pretreatment with higher doses (1 and 10 mu g/ml) led to a profound suppression of IgA secretion (greater than or equal to 90%). The suppressive effect of anti-IgA-dextran was accentuated in the presence of IL-2 and attenuated in the presence of IL-4. Anti-IgA-dextran pretreatment had no effect on sIgA(+) B cell survival. sIgM(+)/sIgD(+) B cells pretreated with anti-IgD-dextran or anti-IgM-dextran did not show significant inhibition. The increased susceptibility of sIgA(+) B cells, but not of sIgM(+)/sIgD(+) B cells, to Ig cross-linking-mediated suppression was confirmed in cross-linking studies with the same Ab (anti-kappa-dextran) Importantly, anti-IgA-dextran-mediated suppression could be reversed by stimulation of sIgA(+) B cells with fibroblasts expressing CD40L; such a reversal required persistent exposure to cells expressing high levels of CD40L. These studies imply that Ig receptor cross-linking renders postswitch sIga(+) B cells unresponsive to subsequent stimulation via activated T cells, but this unresponsiveness is overcome by a persistent high level CD40L signal. RP Ehrhardt, RO (reprint author), NIAID,MUCOSAL IMMUN SECT,CLIN INVEST LAB,NIH,BLDG 10,ROOM 11N228,BETHESDA,MD 20892, USA. NR 34 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1996 VL 157 IS 4 BP 1397 EP 1405 PG 9 WC Immunology SC Immunology GA VH124 UT WOS:A1996VH12400010 PM 8759719 ER PT J AU Baumgartner, RA Hirasawa, N Ozawa, K Gusovsky, F Beaven, MA AF Baumgartner, RA Hirasawa, N Ozawa, K Gusovsky, F Beaven, MA TI Enhancement of TNF-alpha synthesis by overexpression of G(alpha z) in a mast cell line SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GTP-BINDING PROTEIN; PERTUSSIS TOXIN; HUMAN-PLATELETS; RBL-2H3 CELLS; SIGNAL-TRANSDUCTION; REGULATORY PROTEINS; GZ-ALPHA; SUBUNIT; SITE; PHOSPHORYLATION AB Ag stimulation of mast cells via the IgE receptor (Fc epsilon RI) elicits production and release of numerous cytokines. This activation of Fc epsilon RI initiates various tyrosine kinase-dependent signaling cascades, which ultimately result in the de novo synthesis of cytokines, To date, no heterotrimeric G proteins have been implicated in this process, Here we report that the alpha subunit of the heterotrimeric G protein, G(2), can regulate production of the cytokine, TNF-alpha. The alpha subunit was overexpressed in a cultured mast cell line (RBL-2H3) known to contain G(alpha z). In stimulated cells, overexpression of G(alpha z) significantly enhanced the production of TNF-alpha. This effect of G(alpha z) appeared to be restricted in that constitutive synthesis of the cytokine, TGF-beta, and Ag-stimulation of the phosphoinositide-dependent secretory pathway were not significantly affected, Thus, G(alpha z), a heterotrimeric G protein, appeared to modulate the stimulatory pathways for induction of TNF-alpha synthesis in RBL-2H3 cells. C1 NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. RP Baumgartner, RA (reprint author), NHLBI,LAB MOL IMUNOL,NIH,RM 8N109,BLDG 10,BETHESDA,MD 20892, USA. NR 32 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1996 VL 157 IS 4 BP 1625 EP 1629 PG 5 WC Immunology SC Immunology GA VH124 UT WOS:A1996VH12400039 PM 8759748 ER PT J AU Dombrowicz, D Brini, AT Flamand, V Hicks, E Snouwaert, JN Kinet, JP Koller, BH AF Dombrowicz, D Brini, AT Flamand, V Hicks, E Snouwaert, JN Kinet, JP Koller, BH TI Anaphylaxis mediated through a humanized high affinity IgE receptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FC-EPSILON-RI; EPIDERMAL LANGERHANS CELLS; IMMUNOGLOBULIN-E; ALPHA-CHAIN; EXPRESSION; GENE; GENERATION; ANTIBODY AB Mast cells and basophils, which are activated by IgE and allergens through the high affinity IgE receptor (Fc epsilon RI), play a prominent role in anaphylaxis in the mouse, Mice deficient in this receptor become resistant to passive anaphylaxis. As a first step in developing an in vivo model that more closely mimics the IgE-mediated responses in man, we used a combination of transgenic and embryonic stem cell technology to generate a mouse line in which the murine Fc epsilon RI alpha-chain has been replaced with its human homologue, We demonstrate here that these mice express a tetrameric high affinity IgE receptor, in which the human cw-chain associates with the murine beta- and gamma-chains, and that upon triggering with relevant Ag, this receptor mediates the initiation of the expected intracellular events. In addition, we show that the human alpha-chain restores an anaphylactic response to the nonresponsive alpha-deficient parental mouse line. This ''humanized'' mouse represents a potentially important model system, not only for studying the role of IgE in human immune responses, but also for testing potential therapeutic reagents that can interfere with responses mediated through the human Fc epsilon RI receptor. C1 UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. UNIV MILAN,DEPT PHARMACOL,MILAN,ITALY. UNIV MILAN,DEPT CHEMOTHERAPY,MILAN,ITALY. UNIV MILAN,DEPT MED TOXICOL,MILAN,ITALY. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NIAID,MOL ALLERGY & IMMUNOL SECT,NIH,BETHESDA,MD 20892. RI Dombrowicz, David/F-7044-2013; OI Dombrowicz, David/0000-0002-0485-8923; Brini, Anna Teresa/0000-0002-7848-8099 FU NIDDK NIH HHS [DK38103, R01DK46003-01]; Telethon [D.014] NR 27 TC 56 Z9 57 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1996 VL 157 IS 4 BP 1645 EP 1651 PG 7 WC Immunology SC Immunology GA VH124 UT WOS:A1996VH12400042 PM 8759751 ER PT J AU Nilsson, G Johnell, M Hammer, CH Tiffany, HL Nilsson, K Metcalfe, DD Siegbahn, A Murphy, PM AF Nilsson, G Johnell, M Hammer, CH Tiffany, HL Nilsson, K Metcalfe, DD Siegbahn, A Murphy, PM TI C3a and C5a are chemotaxins for human mast cells and act through distinct receptors via a pertussis toxin-sensitive signal transduction pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMPLEMENT ACTIVATION; CHEMOTACTIC RECEPTOR; ANAPHYLATOXIN C3A; MEDIATOR RELEASE; HUMAN BASOPHILS; BONE-MARROW; LINE; STIMULATION; MIGRATION; LEUKEMIA AB Mast cells are known to accumulate at sites of inflammation, however, the chemotaxins involved are undefined. Since most natural leukocyte secretagogues also induce cell migration, and since the anaphylatoxins C3a and C5a are mast cell secretagogues, we hypothesized that both C3a and C5a are also mast cell chemotaxins. Here we report that C3a and C5a are, in fact, potent chemotaxins for the human mast cell line HMC-1. The optimal concentrations, half-maximal effective concentrations (a measure of agonist potency) and the efficacy (response at the optimal concentration) compared with medium control were, for C3a: 10 nM, 0.5 nM, and 256%, respectively; for C5a: 1 nM, 10 pM and 145%. Chemotaxis of HMC-1 cells to both C3a and C5a was blocked by pertussis toxin, suggesting that G(i)-coupled receptors are involved in signal transduction. C3a and C5a also induced transient pertussis toxin-inhibitable increases in [Ca2+](i) (ED(50) = 1 nM for both) that could be homologously but not heterologously desensitized, suggesting that the receptors for C3a and C5a are distinct. These results make C3a the most effective mast cell chemotaxin identified to date. The chemotactic potency described here for C3a is also 100- to 1000-fold greater than for all of its previously described cellular actions. Direct chemoattraction of mast cells by C3a and C5a may help explain the rapid accumulation of mast cells at sites of inflammation. C1 UNIV UPPSALA HOSP,DEPT PATHOL,S-75185 UPPSALA,SWEDEN. UNIV UPPSALA HOSP,DEPT CLIN CHEM,S-75185 UPPSALA,SWEDEN. NIAID,MOL STRUCT LAB,NIH,BETHESDA,MD 20892. NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NIAID,LAB ALLERG DIS,NIH,BETHESDA,MD 20892. NR 50 TC 170 Z9 172 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1996 VL 157 IS 4 BP 1693 EP 1698 PG 6 WC Immunology SC Immunology GA VH124 UT WOS:A1996VH12400048 PM 8759757 ER PT J AU SuriPayer, E Kehn, PJ Cheever, AW Shevach, EM AF SuriPayer, E Kehn, PJ Cheever, AW Shevach, EM TI Pathogenesis of post-thymectomy autoimmune gastritis - Identification of anti-H/K adenosine triphosphatase-reactive T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NONOBESE DIABETIC MICE; NEONATAL THYMECTOMY; INTRATHYMIC INJECTION; MOLECULAR TARGETS; CELLULAR EVENTS; PARIETAL-CELLS; SELF-TOLERANCE; BETA-SUBUNIT; OOPHORITIS; EFFECTOR AB Autoimmune gastritis spontaneously develops following thymectomy of 3-day-old BALB/c mice (d3Tx). These mice develop autoantibodies to the gastric parietal cell proton pump, H/K ATPase, and aberrant expression of the H/K ATPase in the neonatal thymus prevents the induction of disease post-thymectomy, To characterize the effector cells mediating autoimmune gastritis, we isolated H/K ATPase-enriched preparations of parietal cell microsomes and further purified the enzyme by lectin affinity chromatography. Both preparations induced significant proliferative responses of gastric lymph node cells, which were mediated by CD4(+), MHC class II-restricted T cells, Surprisingly, T cells reactive to the Ag could only be demonstrated in lymph nodes in the immediate proximity of the stomach; little or no response was seen when mesenteric or peripheral lymph nodes were tested. It is likely that the H/K ATPase-reactive T cells are actually the effector cells in this disease, as they could only be detected in mice that developed gastritis, as indicated by anti-parietal cell Ab, gastric inflammation, and the presence of cells capable of transferring disease into nu/nu mice, H/K ATPase-specific T cell proliferative responses could first be detected 5 wk post-thymectomy and were accompanied by high background responses at this time point, These latter responses may represent enhanced syngeneic MLRs, which we have previously shown to be elevated in d3Tx mice, Characterization of the H/K ATPase-reactive and self-reactive T cell populations may reveal the factors that break peripheral T cell tolerance and lead to the development of organ-specific autoimmune disease. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NR 27 TC 74 Z9 74 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1996 VL 157 IS 4 BP 1799 EP 1805 PG 7 WC Immunology SC Immunology GA VH124 UT WOS:A1996VH12400061 PM 8759770 ER PT J AU VanBockstaele, EJ Colago, EEO Cheng, P Moriwaki, A Uhl, GR Pickel, VM AF VanBockstaele, EJ Colago, EEO Cheng, P Moriwaki, A Uhl, GR Pickel, VM TI Ultrastructural evidence for prominent distribution of the mu-opioid receptor at extrasynaptic sites on noradrenergic dendrites in the rat nucleus locus coeruleus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE norepinephrine; drug abuse; enkephalin; opiate; morphine; excitatory amino acid ID ADENYLATE-CYCLASE; CERULEUS NEURONS; CATECHOLAMINERGIC NEURONS; IMMUNOREACTIVE TERMINALS; POTASSIUM CHANNELS; CHRONIC MORPHINE; AREA POSTREMA; BRAIN; ENKEPHALIN; ASTROCYTES AB Physiological studies have indicated that agonists at the mu-opioid receptor (mu OR), such as morphine or the endogenous peptide methionine(5)-enkephalin, can markedly decrease the spontaneous activity of noradrenergic neurons in the locus coeruleus (LC). Messenger RNA and protein for mu OR are also densely expressed by LC neurons. During opiate withdrawal, increased discharge rates of LC neurons coincide with the expression of behavioral features associated with the opiate withdrawal syndrome. To better define the cellular sites for the physiological activation of mu OR in the LC and its relation to afferent terminals, we examined the ultrastructural localization of mu OR immunoreactivity in sections dually labeled for the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH). Immunogold-silver labeling for mu OR (i-mu OR) was localized to parasynaptic and extrasynaptic portions of the plasma membranes of perikarya and dendrites, many of which also contained immunolabeling for TH. The dendrites containing exclusively i-mu OR were more numerous in the rostral pole of the LC. The i-mu OR in dendrites with and without detectable TH immunoreactivity were usually postsynaptic to unlabeled axon terminals containing heterogeneous types of synaptic vesicles and forming asymmetric synaptic specializations characteristic of excitatory-type synapses. These results provide the first direct ultrastructural evidence that mu OR is strategically localized to modulate the postsynaptic excitatory responses of catecholamine-containing neurons in the LC. C1 NIDA,ADDICT RES CTR,DIV INTRAMURAL RES PROGRAMS,BALTIMORE,MD 21224. RP VanBockstaele, EJ (reprint author), CORNELL UNIV,COLL MED,DIV NEUROBIOL,DEPT NEUROL & NEUROSCI,411 E 69TH ST,ROOM KB410,NEW YORK,NY 10021, USA. FU NIDA NIH HHS [R29 DA09082]; NIMH NIH HHS [MH00078, MH40342] NR 52 TC 49 Z9 49 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 15 PY 1996 VL 16 IS 16 BP 5037 EP 5048 PG 12 WC Neurosciences SC Neurosciences & Neurology GA VB324 UT WOS:A1996VB32400020 PM 8756434 ER PT J AU Miller, EK Erickson, CA Desimone, R AF Miller, EK Erickson, CA Desimone, R TI Neural mechanisms of visual working memory in prefrontal cortex of the macaque SO JOURNAL OF NEUROSCIENCE LA English DT Article DE inferior temporal cortex; memory; macaque; vision; neurophysiology; attention ID INFERIOR TEMPORAL CORTEX; SHORT-TERM-MEMORY; LATERAL INTRAPARIETAL AREA; POSTERIOR PARIETAL CORTEX; SACCADE-RELATED ACTIVITY; UNIT-ACTIVITY; DELAYED-RESPONSE; RECOGNITION MEMORY; RHESUS-MONKEYS; VISUOMOTOR ACTIVITY AB Prefrontal (PF) cells were studied in monkeys performing a delayed matching to sample task, which requires working memory. The stimuli were complex visual patterns and to solve the task, the monkeys had to discriminate among the stimuli, maintain a memory of the sample stimulus during the delay periods, and evaluate whether a test stimulus matched the sample presented earlier in the trial. PF cells have properties consistent with a role in all three of these operations. Approximately 25% of the cells responded selectively to different visual stimuli. Half of the cells showed heightened activity during the delay after the sample and, for many of these cells, the magnitude of delay activity was selective for different samples. Finally, more than half of the cells responded differently to the test stimuli depending on whether they matched the sample. Because inferior temporal (IT) cortex also is important for working memory, we compared PF cells with IT cells studied in the same task, Compared with IT cortex, PF responses were less often stimulus-selective but conveyed more information about whether a given test stimulus was a match to the sample. Furthermore, sample-selective delay activity in PF cortex was maintained throughout the trial even when other test stimuli intervened during the delay, whereas delay activity in IT cortex was disrupted by intervening stimuli. The results suggest that PF cortex plays a primary role in working memory tasks and may be a source of feedback inputs to IT cortex, biasing activity in favor of behaviorally relevant stimuli. C1 NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. MIT, DEPT BRAIN & COGNIT SCI, CAMBRIDGE, MA 02139 USA. NR 57 TC 810 Z9 818 U1 4 U2 38 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 15 PY 1996 VL 16 IS 16 BP 5154 EP 5167 PG 14 WC Neurosciences SC Neurosciences & Neurology GA VB324 UT WOS:A1996VB32400030 PM 8756444 ER PT J AU Chu, E Cogliati, T Copur, SM Borre, A Voeller, DM Allegra, CJ Segal, S AF Chu, E Cogliati, T Copur, SM Borre, A Voeller, DM Allegra, CJ Segal, S TI Identification of in vivo target RNA sequences bound by thymidylate synthase SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; COLON-CANCER CELLS; MESSENGER-RNA; PROTEIN INTERACTIONS; OXIDATION-REDUCTION; BINDING-SITE; P53; MYC; IMMUNOPRECIPITATION; AMPLIFICATION AB We developed an immunoprecipitation-RNA-random PCR (rPCR) method to isolate cellular RNA sequences that bind to the folate-dependent enzyme thymidylate synthase (TS). Using this approach, nine different cellular RNAs that formed a ribonucleoprotein (RNP) complex with thymidylate synthase (TS) in human colon cancer cells were identified. RNA binding experiments revealed that seven of these RNAs bound TS with relatively high affinity (IC50 values ranging from 1.5 to 6 nM). One of the RNAs was shown to encode the interferon (IFN)-induced 15 kDa protein. Western immunoblot analyses demonstrated that the level of IFN-induced 15 kDa protein was significantly decreased in human colon cancer H630-R10 cells compared with parent H630 cells. While the level of IFN-induced 15 kDa mRNA expression was the same in parent and TS-overexpressing cell lines, the level of IFN-induced 15 kDa RNA bound to TS in the form of a RNP complex was markedly higher in H630-R10 cells relative to parent H630 cells. These studies begin to define a number of cellular target RNA sequences with which TS interacts and suggest that these TS protein-cellular RNA interactions may have a biological role. C1 NCI,NAVY MED ONCOL BRANCH,NATL INST HLTH,BETHESDA,MD 20889. NR 45 TC 39 Z9 40 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 15 PY 1996 VL 24 IS 16 BP 3222 EP 3228 DI 10.1093/nar/24.16.3222 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE820 UT WOS:A1996VE82000015 PM 8774904 ER PT J AU Brown, PC Silverman, JA AF Brown, PC Silverman, JA TI Characterization of the rat mdr2 promoter and its regulation by the transcription factor Sp1 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID P-GLYCOPROTEIN GENE; MULTIDRUG-RESISTANCE GENE; HOMOZYGOUS DISRUPTION; METABOLIC-ACTIVATION; HEPATOCYTE CULTURES; LIVER; EXPRESSION; CELLS; BINDING; DNA AB The mdr2 gene encodes a P-glycoprotein that transports phospholipids across the canalicular membrane in hepatocytes. In this report we describe the isolation, sequencing and first functional characterization of the promoter of mdr2. Analysis of 1.6 kb of DNA upstream of the initiation of translation revealed that this sequence has a high GC content, lacks a TATA element and contains a number of putative transcription factor binding sites. We observed that transcription initiates at several sites between -290 and -463 and that this region was critical for promoter activity. Gel mobility shift assays indicated that Sp1 protein binds to a Sp1 consensus site located at -263. Go-expression of Sp1 protein with a reporter construct containing the -263 GC box demonstrated that Sp1 regulates transcription of this promoter. Expression of a non-functional Sp1 protein did not increase transcription from the mdr2 promoter. Mutation of the -263 GC box diminished the response of the promoter to Sp1 protein. Mutation of this site also decreased expression of this promoter in cells which normally express this gene. These data show that Sp1 has a role in the regulation of mdr2 expression. RP Brown, PC (reprint author), NCI,EXPT CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 38 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 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 15 PY 1996 VL 24 IS 16 BP 3235 EP 3241 DI 10.1093/nar/24.16.3235 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE820 UT WOS:A1996VE82000017 PM 8774906 ER PT J AU Gibson, L Holmgreen, SP Huang, DCS Bernand, O Copeland, NG Jenkins, NA Sutherland, GR Baker, E Adams, JM Cory, S AF Gibson, L Holmgreen, SP Huang, DCS Bernand, O Copeland, NG Jenkins, NA Sutherland, GR Baker, E Adams, JM Cory, S TI bcl-w, a novel member of the bcl-2 family, promotes cell survival SO ONCOGENE LA English DT Article DE bcl-2; bcl-w; apoptosis; survival; oncogene; chromosome 14 ID CHROMOSOMAL BREAKPOINT; CAENORHABDITIS-ELEGANS; PROTEIN IDENTIFICATION; ENDOPLASMIC-RETICULUM; PROTOONCOGENE BCL-2; SEQUENCE SIMILARITY; CONSERVED DOMAINS; MOLECULAR-CLONING; NUCLEAR-ENVELOPE; HOMOLOG BAK AB The prototypic mammalian regulator of cell death is bcl-2, the oncogene implicated in the development of human follicular lymphoma. Several homologues of bcl-2 are now known. Using a PCR-based strategy we cloned a novel member of this gene family, denoted bcl-w. The gene, which is highly conserved between mouse and human, resides near the T-cell antigen receptor a gene within the central portion of mouse chromosome 14 and on human chromosome 14 at band q11. Enforced expression of bcl-w rendered lymphoid and myeloid cells refractory to several (but not all) cytotoxic conditions. Thus, like Bcl-2 and Bcl-x, the Bcl-w protein promotes cell survival, in contrast to other close homologues, Bar and Bak, which facilitate cell death. Comparison of the expected amino acid sequence of Bcl-w with that of these relatives helps to delineate residues likely to convey survival or anti-survival function. While expression of bcl-w was uncommon in B or T lymphoid cell lines, the mRNA was observed in almost all murine myeloid cell lines analysed and in a wide range of tissues. These findings suggest that bcl-w participates in the control of apoptosis in multiple cell types. Its functional similarity to bcl-2 also makes it an attractive candidate proto-oncogene. C1 ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,MELBOURNE,VIC 3050,AUSTRALIA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. ADELAIDE CHILDRENS HOSP INC,DEPT CYTOGENET & MOL GENET,ADELAIDE,SA 5006,AUSTRALIA. RI Sutherland, Grant/D-2606-2012; Huang, David/C-7586-2013; Adams, Jerry/E-1199-2013; Cory, Suzanne/E-1642-2013 OI Cory, Suzanne/0000-0002-6818-3451 NR 73 TC 216 Z9 227 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 15 PY 1996 VL 13 IS 4 BP 665 EP 675 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VD433 UT WOS:A1996VD43300001 PM 8761287 ER PT J AU Theile, M Seitz, S Arnold, W Jandrig, B Frege, R Schlag, PM Haensch, W Guski, H Winzer, KJ Barrett, JC Scherneck, S AF Theile, M Seitz, S Arnold, W Jandrig, B Frege, R Schlag, PM Haensch, W Guski, H Winzer, KJ Barrett, JC Scherneck, S TI A defined chromosome 6q fragment (at D6S310) harbors a putative tumor suppressor gene for breast cancer SO ONCOGENE LA English DT Article DE breast cancer; tumor suppressor genes; chromosome 6q; LOH analysis; microcell-mediated chromosome transfer; estrogen receptor ID ESTROGEN-RECEPTOR GENE; IMMORTAL HUMAN FIBROBLASTS; HUMAN OVARIAN CARCINOMAS; HUMAN-MALIGNANT MELANOMA; 2 DISTINCT REGIONS; FREQUENT LOSS; LINKAGE MAP; CELL-LINES; HUMAN GENOME; WILD-TYPE AB Recent evidence obtained by cytogenetic and molecular studies indicates that in breast cancer chromosome 6q is often affected by genetic changes suggesting the existence of putative tumor suppressor genes (TSGs). However the function of gene(s) on this chromosome in breast cancer suppession is not understood. To substantiate further the presence of breast cancer related TSGs at 60 and to define their location, we first performed microcell-mediated transfer of chromosome 6 to CAL51 breast cancer cells for studying possible suppression of malignant phenotype and secondly, we analysed DNAs from 46 primary breast cancers for loss of constitutive heterozygosity (LOH) using 24 polymorphic microsatellite markers, The chromosome transfer resulted in loss of tumorigenicity and reversion of other neoplastic properties of the microcell hybrids. Polymorphism analysis of single hybrids revealed that they harbored only a small donor chromosome fragment defined by the marker D6S310 (6q23.3-q25) and flanked by D65292 and D6S311, The LOH data suggest that four tumor suppressor gene loci mapped to the central and distal portion of 6q may be independently deleted in breast cancer. One of these regions corresponds to the region identified by chromosome transfer. C1 MAX DELBRUCK CTR MOL MED,FORSCH GRP ONKOL & TUMORIMMUNOL,D-13122 BERLIN,GERMANY. FREE UNIV BERLIN,ROBERT ROSSLE KLIN,ABT CHIRURG & CHIRURG ONKOL,D-13122 BERLIN,GERMANY. HUMBOLDT UNIV BERLIN,KLINIKUM CHARITE,D-10117 BERLIN,GERMANY. NIEHS,MOL CARCINOGENESIS LAB,NIH,RES TRIANGLE PK,NC 27709. RP Theile, M (reprint author), MAX DELBRUCK CTR MOL MED,ARBEITSGRP TUMORGENET,ROBERT ROSSLE STR 10,D-13122 BERLIN,GERMANY. NR 60 TC 110 Z9 110 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 15 PY 1996 VL 13 IS 4 BP 677 EP 685 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VD433 UT WOS:A1996VD43300002 PM 8761288 ER PT J AU Li, WQ Michieli, P Alimandi, M Lorenzi, MV Wu, YM Wang, LH Heidaran, MA Pierce, JH AF Li, WQ Michieli, P Alimandi, M Lorenzi, MV Wu, YM Wang, LH Heidaran, MA Pierce, JH TI Expression of an ATP binding mutant of PKC-delta inhibits Sis-induced transformation of NIH3T3 cells SO ONCOGENE LA English DT Article DE Sis; transformation; PKC-delta ID PROTEIN-KINASE-C; SIMIAN SARCOMA-VIRUS; ALPHA-PDGF RECEPTOR; GROWTH-FACTOR; SIGNALING PATHWAYS; 3T3 CELLS; H-RAS; ACTIVATION; LOCALIZATION; SEQUENCE AB In an effort to determine the role of protein kinase C-delta (PKC-delta) in cellular transformation mediated by the sis proto-oncogene, we cotransfected expression vectors containing cDNAs that encode for c-sis with an ATP binding mutant of PKC-delta (PKC-delta K376R) or wild type PKC-delta (PKC-delta WT) into NTH3T3 cells, Our results showed that expression of PKC-delta K376R severely impaired Sis-induced focus formation, whereas cotransfection of PKC-delta WT cDNA had no effect on Sis-mediated transformation, Consistent with this result, PKC-delta K376R expression also inhibited PDGF-BB-mediated anchorage-independent colony While cotransfection of a vector containing a dominant negative mutant of uas (N17 ras) cDNA potently inhibited Sis-induced transformation, the expression of PKC-delta K376R did not block transformation mediated by v-H-Ras or v-Raf, In addition, PDGF-BB-induced Raf and mitogen-activated protein kinase activation, which are known to be downstream molecules in the Ras cascade, were not affected by the expression of PKC-delta K376R, indicating that PKC-delta and Ras are segregated in mediating Sis-induced transformation. Interestingly, expression of PKC-delta K376R strongly reduced TPA responsive element (TRE) transactivation induced by PDGF stimulation, suggesting that activation of TRE-containing genes, which may be involved in Sis-mediated transformation, are negatively regulated by expression of PKC-delta K376R. C1 NIDR,IMMUNOL LAB,BETHESDA,MD 20892. CUNY MT SINAI SCH MED,DEPT MICROBIOL,NEW YORK,NY 10029. RP Li, WQ (reprint author), NCI,CELLULAR & MOL BIOL LAB,BLDG 37,ROOM 1E24,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Michieli, Paolo/A-2588-2011 NR 38 TC 47 Z9 47 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 15 PY 1996 VL 13 IS 4 BP 731 EP 737 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VD433 UT WOS:A1996VD43300008 PM 8761294 ER PT J AU Juan, TSC McNiece, IK Jenkins, NA Gilbert, DJ Copeland, NG Fletcher, FA AF Juan, TSC McNiece, IK Jenkins, NA Gilbert, DJ Copeland, NG Fletcher, FA TI Molecular characterization of mouse and rat CPP32 beta gene encoding a cysteine protease resembling interleukin-1 beta converting enzyme and CED-3 SO ONCOGENE LA English DT Article DE cysteine protease; apoptosis, CED-3; gene structure ID PROGRAMMED CELL-DEATH; IL-1-BETA-CONVERTING ENZYME; C-ELEGANS; POLY(ADP-RIBOSE) POLYMERASE; CAENORHABDITIS-ELEGANS; MAMMALIAN HOMOLOG; MICE DEFICIENT; APOPTOSIS; IDENTIFICATION; INDUCTION AB Interleukin-1 beta converting enzyme (ICE) defines a new class of mammalian cysteine protease that shares strong homology with the Caenorhabditis elegans death gene ced-3, Both ICE and CED-3, when introduced into cultured cells, induce apoptosis, indicating that this type of cysteine protease may play an important role in the process of programmed cell death, Here, we report the cloning of a mouse and rat gene encoding a novel cysteine protease. The putative proteins encoded by these cDNAs contain the conserved sequence (QACRG) necessary for covalent linkage to the substrate as well as the three amino acids responsible for substrate binding and catalysis in ICE, Amino acid sequence analysis indicates that this rodent cysteine protease is the homolog of human CPP32 beta, Mouse CPP32 beta mRNA is highly expressed in spleen, and to a lesser degree in brain, lung, liver, and kidney, The mouse CPP32 beta genomic locus spans a region of approximately 20 kb, including seven exons and six introns, Mouse interspecific backcross mapping allowed localization of CPP32 beta to the central region of mouse chromosome 8, linked to Scvr, Lpl, Jund1 and Mlr. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP Juan, TSC (reprint author), AMGEN INC,DEPT DEV HEMATOL,1840 DEHAVILLAND DR,THOUSAND OAKS,CA 91320, USA. NR 36 TC 47 Z9 50 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 15 PY 1996 VL 13 IS 4 BP 749 EP 755 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VD433 UT WOS:A1996VD43300010 PM 8761296 ER PT J AU Jeffers, M Rong, S Anver, M VandeWoude, GF AF Jeffers, M Rong, S Anver, M VandeWoude, GF TI Autocrine hepatocyte growth factor scatter factor-Met signaling induces transformation and the invasive/metastastic phenotype in C127 cells SO ONCOGENE LA English DT Article DE hepatocyte growth factor scatter factor; Met; transformation; invasion; metastasis ID FACTOR/SCATTER FACTOR; EPITHELIAL-CELLS; CARCINOMA-CELLS; TYROSINE KINASE; PROTOONCOGENE; RECEPTOR; TUMORIGENICITY; EXPRESSION; INDUCTION; INVASION AB Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector of cells expressing the Met tyrosine kinase receptor. C127 is a non-tumorigenic mouse cell line which expresses negligible levels of HGF/SF and Met proteins. In the present report we have generated C127 cells which overexpress HGP/SF and/or Met proteins, and have analysed the effect of HGF/SF-Met signaling in these cells. We show that this signaling pathway stimulates the growth and invasiveness of C127 cells in vitro and that cells overexpressing both HGF/SF and Met proteins (but neither alone) are phenotypically transformed and highly tumorigenic and metastatic in vivo. Our data unequivocally demonstrates the autocrine dependency of HGF/SF-Met-induced transformation and metastasis in this system and supports the theory that the inappropriate expression of HGF/SF and Met proteins could play a role in the development and spread of human tumors. In addition, this system may be useful for identifying metastasis-associated genes that are activated by HGF/SF-Met signaling. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK,MD 21702. NR 49 TC 110 Z9 112 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 15 PY 1996 VL 13 IS 4 BP 853 EP 861 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VD433 UT WOS:A1996VD43300021 PM 8761307 ER PT J AU Boguna, M Porra, JM Masoliver, J Weiss, GH AF Boguna, M Porra, JM Masoliver, J Weiss, GH TI Isotropization time for non-Markovian CTRWs SO PHYSICA A LA English DT Article ID RANDOM-WALK AB We calculate the mean-squared displacement, [r(2)(t)], for a CTRW taking into account effects of anisotropic turn angles. When the pausing-time density is a negative exponential one finds a simple expression for [r(2)(t)] which allows an exact determination of the transition time from ballistic to diffusive motion. In the non-Markovian case an exact expression is obtained for the Laplace transform of [r(2)(t)]. The results are useful in the analysis of photon migration in a turbid medium. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. UNIV BARCELONA,DEPT FIS FONAMENTAL,BARCELONA 08028,SPAIN. RI Boguna, Marian/B-7795-2011; Masoliver, Jaume/F-7198-2016 OI Boguna, Marian/0000-0001-7833-3487; Masoliver, Jaume/0000-0002-5810-879X 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 0378-4371 J9 PHYSICA A JI Physica A PD AUG 15 PY 1996 VL 230 IS 1-2 BP 149 EP 155 DI 10.1016/0378-4371(96)00101-X PG 7 WC Physics, Multidisciplinary SC Physics GA VC044 UT WOS:A1996VC04400009 ER PT J AU Werner, MH AF Werner, MH TI Stopping death cold SO STRUCTURE LA English DT Article ID APOPTOTIC CELL-DEATH; ENDOPLASMIC-RETICULUM; CRYSTAL-STRUCTURE; DIPHTHERIA-TOXIN; BCL-2; PROTEIN; BAX; HETERODIMERIZATION; EXPRESSION; REGULATOR AB The three-dimensional structure of Bcl-x(L), an inhibitor of apoptosis, suggests how different combinations of proteins in the same family might be utilized to control apoptosis. C1 NIDDK,PHYS CHEM LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 23 TC 8 Z9 8 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD AUG 15 PY 1996 VL 4 IS 8 BP 879 EP 883 DI 10.1016/S0969-2126(96)00094-9 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VC266 UT WOS:A1996VC26600001 PM 8805578 ER PT J AU Komurasaki, Y Nagineni, CN Wang, Y Hooks, JJ AF Komurasaki, Y Nagineni, CN Wang, Y Hooks, JJ TI Virus RNA persists within the retina in coronavirus-induced retinopathy SO VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MOUSE HEPATITIS-VIRUS; PIGMENT EPITHELIAL-CELLS; MURINE CORONAVIRUS; STRAIN JHM; EXPRESSION; MICE; DEMYELINATION; HYBRIDIZATION; DISEASE AB The murine coronavirus, mouse hepatitis virus (MHV), JHM strain, induces a biphasic retinal disease in adult BALB/c mice. In the early phase, Day 1 to Day 7, a retinal vasculitis is noted which is associated with the presence of viral proteins and infectious virus. In the late phase, Day 10 to Day 140, a retinal degeneration is associated with the absence of viral proteins, infectious virus, and inflammatory cells. The purpose of this study was to determine if viral RNA persists within the retina during the retinal degenerative phase of the disease. BALB/c mice were inoculated by the intravitreal route with 10(4.0) TCID50/5 mu l of virus. The presence of viral RNA was detected by in situ hybridization with a viral cDNA probe and viral proteins were identified by immunocytochemical staining. During the acute phase of the infection, viral RNA was found in the retina, RPE, ciliary body epithelium, and the iris epithelium. During the late phase of the infection, viral RNA was almost exclusively found within the retina and RPE and not in the anterior segment of the eye. Within the retina, viral RNA was detected in the ganglion cell layer, the inner retina, the outer retina, and the RPE cell. Immunocytochemical staining identified viral protein within the retina only from Day 1 to Day 8, This ocular disease was also associated with a persistent systemic infection. Both viral RNA and viral proteins were identified within the liver during the first 8 days. However, only viral RNA was detected in the liver from Day 8 to Day 60. These studies demonstrate that MHV established an acute infection (Day 1-8) where infectious virus and viral proteins were identified. This was followed by a persistent infection within the retina and liver where only viral RNA were detected by in situ hybridization. (C) 1996 Academic Press, Inc. C1 NEI,IMMUNOL & VIROL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 32 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 15 PY 1996 VL 222 IS 2 BP 446 EP 450 DI 10.1006/viro.1996.0442 PG 5 WC Virology SC Virology GA VD707 UT WOS:A1996VD70700016 PM 8806529 ER PT J AU Natoli, C Iacobelli, S Kohn, L AF Natoli, C Iacobelli, S Kohn, L TI The immune stimulatory protein 90K increases major histocompatibility complex class I expression in a human breast cancer cell line SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TUMOR-GROWTH; ANTIGENS; SUPERFAMILY; CLONING; SERUM AB 90K is a widely expressed, secreted 90 kDa human serum protein found both in normal individuals and al elevated levels in the serum of cancer patients. Functional characterization revealed stimulatory effects of 90K on immune defense systems, such as natural killer and lymphokine-activated killer cell activity. Recently, experiments have shown that 90K expression in several tumor cell lines inversely correlates with tumor formation in athymic mice. The mechanism of this tumor suppressive effect is unknown. In the present study, we evaluated the ability of 90K to affect the expression of MHC class I molecules in the human breast cancer cell line EVSA-T. Treatment with 90K (1-50 mu g/ml) caused the levels of MHC class I expression to increase approximately sixfold above control levels, as measured by flow cytometry. IFN-gamma was used as a positive control and yielded increased expression of MHC class I molecules approximately 8 times over control levels. These data demonstrate that 90K can directly affect the expression of molecules that are engaged in protective antitumor response. (C) 1996 Academic Press, Inc. C1 NIDDKD,NIH,METAB DIS BRANCH,CELL REGULAT SECT,BETHESDA,MD 20892. RP Natoli, C (reprint author), UNIV G DANNUNZIO,SCH MED,DEPT MED ONCOL,I-66100 CHIETI,ITALY. RI Natoli, Clara/E-1378-2013 OI Natoli, Clara/0000-0001-7295-0230 NR 18 TC 17 Z9 17 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 14 PY 1996 VL 225 IS 2 BP 617 EP 620 DI 10.1006/bbrc.1996.1219 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VD344 UT WOS:A1996VD34400044 PM 8753808 ER PT J AU Grzesiek, S Stahl, SJ Wingfield, PT Bax, A AF Grzesiek, S Stahl, SJ Wingfield, PT Bax, A TI The CD4 determinant for downregulation by HIV-1 Nef directly binds to Nef. Mapping of the Nef binding surface by NMR SO BIOCHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DOWN-REGULATION; TYPE-1 NEF; CELL-SURFACE; CYTOPLASMIC DOMAIN; MUTATIONAL ANALYSIS; NEGATIVE FACTOR; SH3 DOMAINS; IN-VIVO; PROTEIN AB Using heteronuclear NMR spectroscopy, we demonstrate that a 13-residue peptide (MSQIKRLLSEKKT) from the cytoplasmic tail of CD4 binds to Nef protein. This part of CD4 is critical for downregulation of CD4 by HIV-1 Nef [Aiken el al. (1994) Cell 76, 853-864]. We show that a control peptide without the central dileucine does not bind to Nef. The dependence of Nef H-1 and N-15 amide chemical shifts on peptide concentration indicates that the binding is in the fast chemical exchange limit, with a dissociation constant K-d of similar to 1 mM, The peptide binding site has been mapped onto the previously determined solution structure of HIV-1 Nef [Grzesiek ct al. (1996) Nat. Struct. Biol. 3, 340-345] on the basis of peptide-induced chemical shift changes. It comprises amino acids W57, L58, E59, G95, G96, L97, R106, and L110. When Nef is complexed to the SH3 domain of Hck tyrosine protein kinase, the peptide binds to the same site on Nef but with slightly higher affinity (K-d similar to 0.5 mM). This indicates that the binding of CD4 and Hck SH3 to Nef are two compatible and slightly cooperative events. C1 NIAID,PROT EXPRESS LAB,NIH,BETHESDA,MD 20892. RP Grzesiek, S (reprint author), NIDDKD,CHEM PHYS LAB,NIH,BLDG 5,BETHESDA,MD 20892, USA. NR 47 TC 257 Z9 259 U1 0 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 13 PY 1996 VL 35 IS 32 BP 10256 EP 10261 DI 10.1021/bi9611164 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC341 UT WOS:A1996VC34100002 PM 8756680 ER PT J AU Wolberg, AS Li, LP Cheung, WF Hamaguchi, N Pedersen, LG Stafford, DW AF Wolberg, AS Li, LP Cheung, WF Hamaguchi, N Pedersen, LG Stafford, DW TI Characterization of gamma-carboxyglutamic acid residue 21 of human factor IX SO BIOCHEMISTRY LA English DT Article ID HUMAN PROTEIN-C; CALCIUM-DEPENDENT BINDING; SITE-SPECIFIC MUTAGENESIS; FACTOR-LIKE DOMAINS; VITAMIN-K; PHOSPHOLIPID-VESICLES; MEMBRANE-BINDING; PROTHROMBIN FRAGMENT-1; MONOCLONAL-ANTIBODIES; FACTOR-XIA AB We investigated the functional role of gamma-carboxyglutamic acid (Gla) residue 21 of human factor IX, using site-directed mutagenesis to change the glutamic acid residue to aspartic acid (FIX21D). FIX21D had reduced activity in an activated partial thromboplastin time (aPTT) assay and was activated by factor XIa more slowly than wild-type factor IX (FIXwt). FIX21D underwent normal, two-stage calcium-dependent intrinsic fluorescence quenching, indicating that a folding event similar to that seen in FIXwt occurred upon the addition of calcium ions. Antibody A-7, which recognizes factor IX-specific residues at positions 33-40, bound FIX21D as well as FIXwt; however, the calcium-specific monoclonal antibody, JK-IX-2, whose epitope includes residues 1 and 22, did not recognize FIX21D. FIX21D bound phosphatidylserine/phosphatidylcholine (PS/PC) vesicles with K-d approximately 10-fold greater than FIXwt, as measured by a fluorescence light scattering assay. Finally, although FIXwt binds endothelial cells with a K-d of 2.8 nM, FIX21D did not bind endothelial cells. Molecular modeling simulations of FIXwt and FIX21D indicate that mutating Gla 21 to Asp causes structural changes in residues 3-5 and 8-10, as well as in two exposed calcium ions, consistent with the reduced function of FIX21D. Immunological and intrinsic fluorescence quenching assays and the molecular dynamics simulations suggest normal folding in the C-terminal region of the cia domain. Thus we hypothesize that FIX21D has reduced JK-IX-2 and phospholipid and endothelial cell binding due to localized structural changes in residues 3-10 and the exposed calcium ions. Our study suggests that the Gla 21 to Asp mutation disrupts function in the N-terminal region of the Gla domain without affecting structure in the C-terminal Gla domain region. C1 UNIV N CAROLINA,DEPT BIOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CTR THROMBOSIS & HEMOSTASIS,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. NIEHS,RES TRIANGLE PK,NC 27709. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [R01 HL38973] NR 55 TC 5 Z9 5 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 13 PY 1996 VL 35 IS 32 BP 10321 EP 10327 DI 10.1021/bi960502i PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC341 UT WOS:A1996VC34100009 PM 8756687 ER PT J AU Mefford, IN Kincl, L Dykstra, KH Simpson, JT Markey, SP Dietz, S Wightman, RM AF Mefford, IN Kincl, L Dykstra, KH Simpson, JT Markey, SP Dietz, S Wightman, RM TI Facile oxidative decarboxylation of 3,4-dihydroxyphenylacetic acid catalyzed by copper and manganese ions SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE 3,4-dihydroxyphenylacetic acid; 3,4-dihydroxybenzyl alcohol; 3,4-dihydroxybenzaldehyde; oxidative decarboxylation; copper; manganese ID 3,4-DIHYDROXYMANDELIC ACID; IDENTIFICATION; INTERMEDIATE; METABOLITES; TYROSINASE; MECHANISM AB Under physiological conditions, we observed the rapid, pH- and temperature-dependent, oxidative decarboxylation and hydration of 3,4-dihydroxyphenylacetic acid (DOPAC) to form 3,4-dihydroxybenzyl alcohol (DBAlc). This product was oxidized and underwent tautomerization to form 3,4-dihydroxybenzaldehyde (DBAld). This reaction did not occur in the presence of EDTA, was catalyzed by copper (Cu-I, Cu-II) and manganese (Mn-II) and was oxygen dependent. A variety of mono- and dihydroxyphenyl carboxylic acids were tested and the reaction producing DBAlc as an intermediate was observed to be unique to DOPAC. 3,4-Dihydroxymandelic acid (DOMA) was rapidly oxidatively decarboxylated to form DBAld directly. The substrate and catalyst selectivity of this reaction suggest that this may have physiological relevance in the neurotoxic consequences of manganese and copper to the dopaminergic system in man. C1 NIH,NCRR,CLIN PHARMACOL SECT,BETHESDA,MD 20892. NIMH,NCRR,ANALYT BIOCHEM SECT,NIH,BETHESDA,MD 20892. NIH,NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. NR 23 TC 10 Z9 10 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD AUG 13 PY 1996 VL 1290 IS 3 BP 224 EP 230 DI 10.1016/0304-4165(96)00017-7 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VD349 UT WOS:A1996VD34900004 PM 8765124 ER PT J AU Sassaman, MB AF Sassaman, MB TI Indirect monoalkylation of primary and secondary amines by reductive decyanation of alpha-aminonitriles with sodium cyanoborohydride-mercury bis(trifluoroacetate) SO TETRAHEDRON LA English DT Article AB Secondary and tertiary amines are prepared from alpha-aminonitriles by selective reductive cleavage of the cyanide moiety. The alpha-aminonitriles in this case, function as ''masked'' imine or iminium ions and are ''unmasked'' by mercury (II) in the presence of sodium cyanoborohydride to obtain the reduced product. Secondary amines may be prepared indirectly from primary amines in good yield without danger of over alkylation. RP NIH, WARREN G MAGNUSON CLIN CTR, POSITRON EMISS TOMOG DEPT, BETHESDA, MD 20892 USA. NR 13 TC 12 Z9 12 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD AUG 12 PY 1996 VL 52 IS 33 BP 10835 EP 10840 DI 10.1016/0040-4020(96)00631-X PG 6 WC Chemistry, Organic SC Chemistry GA VB815 UT WOS:A1996VB81500002 ER PT J AU Dickie, P Gazzinelli, R Chang, LJ AF Dickie, P Gazzinelli, R Chang, LJ TI Models of HIV type 1 proviral gene expression in wild-type HIV and MLV/HIV transgenic mice SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; NF-KAPPA-B; T-CELL; DISEASE SPECIFICITY; NERVOUS-SYSTEM; RNA EXPRESSION; MESSENGER-RNA; HTLV-III; REPLICATION AB Two proviral HIV transgenic mouse models, one bearing wild-type HIV proviral DNA and the other a modified provirus in which the viral LTRs contained the core enhancer of the Moloney murine leukemia virus (MLV), were compared, The MLV/HIV chimeric LTR, in which the MLV enhancer replaced the NF-kappa B-binding motifs, was transcriptionally active in human and murine cells in vitro and virus containing the chimeric LTR was replication competent in human cell cultures, Transgenic mice derived from microinjections of chimeric MLV/HIV proviral DNA transcribed HIV genes at a greater frequency and at higher levels than wild-type HIV proviral transgenic mice, MLV/HIV mice were also more apt to develop disease; wasting, periocular infections, and a degenerative myopathy characterized the most predominant phenotype, The tissue specificities of the wild-type and chimeric LTRs in transgenic mice were remarkably similar, but a significant difference was apparent in lymphoid cells, Basal level and LPS-inducible HIV gene expression occurred in peritoneal and bone marrow-derived macrophages from wild-type HIV transgenic mice, In contrast, HIV gene expression in macrophages from MLV/HIV mice was undetectable, even following LPS induction, However, cultured splenocytes from MLV/HIV mice supported HN proviral gene transcription better than splenocytes from HIV mice, particularly after induction with LPS or anti-IgD antibody but not with concanavalin A, These data suggest that in transgenic mice, the HIV and MLV/HIV LTRs display a differential tropism for macrophages and B cells, respectively, HIV and MLV/HIV transgenic mice represent alternative models amenable to in vivo studies of HIV gene regulation in lymphoid cells, the induction of HIV-related disease and the evaluation of anti-HN therapies. C1 NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. RP Dickie, P (reprint author), UNIV ALBERTA,HERITAGE MED RES CTR,DEPT MED MICROBIOL & IMMUNOL,650D HMRC,EDMONTON,AB T6G 2S2,CANADA. NR 56 TC 18 Z9 18 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 AUG 10 PY 1996 VL 12 IS 12 BP 1103 EP 1116 DI 10.1089/aid.1996.12.1103 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VD032 UT WOS:A1996VD03200004 PM 8844015 ER PT J AU Safai, BJ Huang, JL Boeri, E Farid, R Raafat, J Schutzer, P Ahkami, R Franchini, G AF Safai, BJ Huang, JL Boeri, E Farid, R Raafat, J Schutzer, P Ahkami, R Franchini, G TI Prevalence of HTLV type I infection in Iran: A serological and genetic study SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; LYMPHOMA VIRUS; UNITED-STATES; C RETROVIRUS; NATION-WIDE; ANTIBODIES; RISK; REGION AB Several publications describe the presence of the human T cell lymphotropic virus type I (HTLV-I) in Jewish individuals born in Mash-had, Iran, We report here the results of HTLV-I serological and genetic studies in the non-Jewish population of Mash-had as well as a neighboring area: Gonbad-Kavous. Seven hundred and seven serum samples from Mash-had (694 healthy individuals and 13 patients with lymphoma) and 90 from Gonbad-Kavous mere tested for HTLV antibodies by gelatin particle agglutination assay (PA) and confirmatory Western blots (WBs). Seropositive rates of 3.0% (21 of 694) in Mash-had, 0% (0 of 90) in Gonbad-Kavous, and 100% (13 of 13) in lymphoma cases mere observed. HTLV-I DNA sequence were amplified by polymerase chain reaction directly from the fresh PBMCs of seropositive individuals, Phylogenetic analysis of the viral DNA sequence indicated that the HTLV-I present in Mash-had belong to the HTLV-I cosmopolitan clade, Altogether, these data indicate that Mash-had, located in northeastern Iran, is a newly recognized endemic center for HTLV-I. C1 NCI, TUMOR CELL BIOL LAB, NIH, BETHESDA, MD 20892 USA. OSPED SAN RAFFAELE, CTR S LUIGI, VIROL LAB, I-20127 MILAN, ITALY. MASHHAD UNIV MED SCI, MASHHAD 91734, IRAN. UNIV TEHRAN, SCH MED, DEPT ONCOL, TEHRAN, IRAN. ALBANY MED COLL, ALBANY, NY 12208 USA. RP Safai, BJ (reprint author), NEW YORK MED COLL, DEPT DERMATOL, VALHALLA, NY 10595 USA. NR 40 TC 36 Z9 36 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG 10 PY 1996 VL 12 IS 12 BP 1185 EP 1190 DI 10.1089/aid.1996.12.1185 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VD032 UT WOS:A1996VD03200012 PM 8844023 ER PT J AU Stanwell, C Ye, B Yuspa, SH Burke, TR AF Stanwell, C Ye, B Yuspa, SH Burke, TR TI Cell protein cross-linking by erbstatin and related compounds SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE erbstatin; lavendustin A; herbimycin A; protein-tyrosine kinase; cross-link; oxidation ID TYROSINE KINASE INHIBITORS; ANALOGS AB The protein-tyrosine kinase inhibitor and stable erbstatin analogue methyl 2,5-dihydroxycinnamate (4) cross-links cell proteins by a non-physiological chemical mechanism (Stanwell er al., Cancer Res 55: 4950-4956, 1995). To determine the structural requirements for this effect, erbstatin (1) and fifteen related compounds, including caffeic acid phenylethyl ester (9) were synthesized and examined for their ability to induce cross-linking of cellular protein at concentrations ranging from low micromolar up to 1000 mu M. Tests were conducted in NIH3T3 fibroblasts as well as mouse keratinocytes. Potent cross-linking of cellular protein was observed for a number of analogues, including erbstatin, at concentrations as low as 10-50 mu M. The inactivity of methoxy and fluoro as compared with their corresponding dihydroxylated counterparts indicated that free aromatic hydroxyls were essential for cross-linking. Additionally, compounds containing phenyl rings with I,di-dihydroxy substituents were more potent than those having 1,2-dihydroxylated patterns. As with the prototype compound 4, cross-linking was induced at both 37 degrees and 4 degrees, suggesting a chemical rather than physiological mechanism. Consistent with the data, a mechanism of action is proposed which involves initial oxidation to reactive quinone intermediates that subsequently cross-link protein nucleophiles via multiple 1,4-Michael-type additions. Similar alkylation of protein by protein-tyrosine kinase inhibitors, such as herbimycin A, has been invoked. While the latter benzoquinoid ansamycin antibiotics contain performed quinone moieties, results of the present study suggest that other hydroxylated kinase inhibitors can potentially participate in similar phenomena. A large number of potential therapeutics, including HIV integrase inhibitors, possess polyhydroxylated nuclei. The non-specific nature of the protein cross-linking reaction demonstrated for these erbstatin analogues, and the fact that cross-linking can occur at micromolar concentrations, may limit the therapeutic usefulness of such compounds to specific applications. C1 NCI,NIH,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NCI,NIH,MED CHEM LAB,DIV BASIC SCI,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 NR 21 TC 42 Z9 43 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 AUG 9 PY 1996 VL 52 IS 3 BP 475 EP 480 DI 10.1016/0006-2952(96)00250-X PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UU196 UT WOS:A1996UU19600012 PM 8687502 ER PT J AU Wang, TW Li, BY Danielson, PD Shah, PC Rockwell, S Lechleider, RJ Martin, J Manganaro, T Donahoe, PK AF Wang, TW Li, BY Danielson, PD Shah, PC Rockwell, S Lechleider, RJ Martin, J Manganaro, T Donahoe, PK TI The immunophilin FKBP12 functions as a common inhibitor of the TGF beta family type I receptors SO CELL LA English DT Article ID TRANSFORMING GROWTH-FACTOR; SERINE-THREONINE KINASE; PEPTIDYL-PROLYL ISOMERASE; ACTIVIN RECEPTOR; IMMUNOSUPPRESSANT FK506; EXPRESSION CLONING; MAMMALIAN PROTEIN; COMPLEX; CALCINEURIN; RAPAMYCIN AB The immunophilin FKBP12 is an evolutionarily conserved abundant protein; however, its physiological roles remain poorly defined. Here we report that FKBP12 is a common cytoplasmic interactor of TGF beta family type I receptors. FKBP12 binds to ligand-free TGF beta type I receptor, from which it is released upon a ligand-induced, type II receptor mediated phosphorylation of the type I receptor. Blocking FKBP12/type I receptor interaction with FK506 nonfunctional derivatives enhances the ligand activity, indicating that FKBP12 binding is inhibitory to the signaling pathways of the TGF beta family ligands. Overexpression of a myristylated FKBP12 in Mv1Lu cell specifically inhibits two separate pathways activated by TGF beta, and two point mutations on FKBP12 (G89P, 190K) abolish the inhibitory activity of FKBP12, suggesting that FKBP12 may dock a cytoplasmic protein to the type I receptors to inhibit TGF beta family mediated signaling. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP Wang, TW (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT SURG,PEDIAT SURG RES LAB,BOSTON,MA 02114, USA. FU NICHD NIH HHS [P-30 HD07396, HD 32112]; NIGMS NIH HHS [R29 GM53710] NR 47 TC 259 Z9 264 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 9 PY 1996 VL 86 IS 3 BP 435 EP 444 DI 10.1016/S0092-8674(00)80116-6 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC309 UT WOS:A1996VC30900011 PM 8756725 ER PT J AU Zheng, Y Zangrilli, D Cerione, RA Eva, A AF Zheng, Y Zangrilli, D Cerione, RA Eva, A TI The pleckstrin homology domain mediates transformation by oncogenic Dbl through specific intracellular targeting SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; BETA-GAMMA-SUBUNITS; PH DOMAIN; SIGNALING PROTEINS; CRYSTAL-STRUCTURE; BINDING; RAS; IDENTIFICATION; PRODUCT; KINASE AB The pleckstrin homology (PH) domain is an similar to 100 amino acid structural motif found in many cellular signaling molecules, including the Dbl oncoprotein and related, putative guanine nucleotide exchange factors (GEFs). Here we have examined the role of the Dbl PH (dPH) domain in the activities of oncogenic Dbl. We report that the dPH domain is not involved in the interaction of Dbl with small GTP-binding proteins and is incapable of transforming NIH 3T3 fibroblasts. On the other hand, co-expression of the dPH domain with on cogenic Dbl inhibits Dbl-induced transformation. A deletion mutant of Dbl that lacks a significant portion of the PH domain retains full GEF activity, but is completely inactive in transformation assays. Replacement of the PH domain by the membrane-targeting sequence of Ras is not sufficient for the recovery of transforming activity. However, subcellular fractionations of Dbl and Dbl mutants revealed that the PH domain is necessary and sufficient for the association of Dbl with the Triton X-100-insoluble cytoskeletal components. Thus, our results suggest that the dPH domain mediates cellular transformation by targeting the Dbl protein to specific cytoskeletal locations to activate Rho-type small GTP-binding proteins. C1 CORNELL UNIV,DEPT PHARMACOL,ITHACA,NY 14853. NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. RI Zheng, Yi/J-7235-2015; Eva, Alessandra/J-8268-2016 OI Zheng, Yi/0000-0001-7089-6074; Eva, Alessandra/0000-0003-2949-078X FU NIGMS NIH HHS [GM47458] NR 33 TC 102 Z9 104 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 9 PY 1996 VL 271 IS 32 BP 19017 EP 19020 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB684 UT WOS:A1996VB68400003 PM 8702569 ER PT J AU Mitchell, DC Lawrence, JTR Litman, BJ AF Mitchell, DC Lawrence, JTR Litman, BJ TI Primary alcohols modulate the activation of the G protein-coupled receptor rhodopsin by a lipid-mediated mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHAIN PHOSPHATIDYLCHOLINE VESICLES; HIGHER-ORDER ANALYSIS; METARHODOPSIN-II; ACETYLCHOLINE-RECEPTOR; RECOMBINANT MEMBRANES; GENERAL-ANESTHETICS; ANISOTROPY DECAY; EQUILIBRIUM; BOVINE; CHOLESTEROL AB The visual pigment rhodopsin is a prototypical member of the G protein-coupled receptor superfamily. In this study, we have investigated the effect of a series of n-alcohols on the formation of metarhodopsin II (MII), the photoactivated conformation of rhodopsin, which binds and activates transducin. When rhodopsin was photolyzed in the presence of several n-alcohols, increased MII formation was observed in the order ethanol > butanol > hexanol, whereas longer chain n-alcohols inhibited MII formation with decanol > octanol, The magnitude of the stimulatory effects was greater in a more highly unsaturated phospholipid, Alcohols, which enhanced MII formation also increased phospholipid acyl chain packing free volume, while those that decreased this bilayer property inhibited MII formation, An apparent discontinuity in the effect of these alcohols results when their potency is calculated in terms of the total aqueous alcohol concentration. In sharp contrast, a continuous variation in their behavior is observed, when their potency is calculated in terms of the amount of alcohol partitioned in the membrane, Our findings strongly support a lipid-mediated mechanism of action for alcohols on rhodopsin and, by analogy, for other G protein-coupled receptors. C1 NIAAA,SECT FLUORESCENCE STUDIES,LAB MEMBRANE BIOCHEM & BIOPHYS,DIV INTRAMURAL CLIN & BIOL RES,BETHESDA,MD 20892. NR 34 TC 58 Z9 58 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 9 PY 1996 VL 271 IS 32 BP 19033 EP 19036 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB684 UT WOS:A1996VB68400007 PM 8702573 ER PT J AU Sechi, S Roller, PP WilletteBrown, J Kinet, JP AF Sechi, S Roller, PP WilletteBrown, J Kinet, JP TI A conformational rearrangement upon binding of IgE to its high affinity receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FC-EPSILON-RI; BOUND IMMUNOGLOBULIN-E; ALPHA-CHAIN; MAST-CELLS; CIRCULAR-DICHROISM; MEMBRANE-SURFACE; SITE; PROTEIN; COMPLEX; DOMAIN AB One of the critical steps in the allergic reaction is the binding of immunoglobulin E (IgE) to its high affinity receptor (Fc epsilon RI), Fc epsilon RI is a tetrameric complex composed of an a chain, a beta-chain, and a dimeric gamma-chain. The extracellular paction of the alpha-chain (alpha-t) is sufficient for the binding of IgE. The Fe portion of IgE contains two copies of the Fc epsilon RI binding sites, In contrast, the binding stoichiometry is 1:1, Previously, it was hypothesized that the binding of Fc epsilon EI to IgE results in a conformational change ill IgE that precludes the binding of a second molecule (Presta, L., Shields, R., O'Connel, L., Lahr, S., Porter, J., German, C., and Jardieu, P. (1994) J. Biol. Chem. 269, 26568-26313), Here we characterize the secondary structure of IgE and alpha-t and analyze their interaction by circular dichroism spectroscopy, Binding experiments show that when IgE interacts with alpha-t there is a 15-26% decrease of the negative ellipticity at 217 nm, Together, the absence of all alpha-helix element in alpha-t and the small contribution of alpha-t to the spectra of the complex indicate that upon binding, a major conformational rearrangement must occur oil IgE, In addition, we analyze the thermal unfolding of alpha-t, IgE, and their complex. Despite the several domains that constitute IgE and alpha-t. these molecules unfold cooperatively with two-state kinetics. C1 NIAID,MOL ALLERGY & IMMUNOL SECT,NIH,ROCKVILLE,MD 20852. NCI,DIV BASIC SCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA 02215. NR 43 TC 27 Z9 27 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 9 PY 1996 VL 271 IS 32 BP 19256 EP 19263 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB684 UT WOS:A1996VB68400041 PM 8702607 ER PT J AU Karnieli, E Werner, H Rauscher, FJ Benjamin, LE LeRoith, D AF Karnieli, E Werner, H Rauscher, FJ Benjamin, LE LeRoith, D TI The IGF-I receptor gene promoter is a molecular target for the Ewing's sarcoma Wilms' tumor 1 fusion protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROUND-CELL TUMOR; GROWTH-FACTOR RECEPTOR; ZINC FINGER PROTEIN; CHROMOSOME-TRANSLOCATION; TRANSCRIPTION FACTOR; PERIPHERAL NEUROEPITHELIOMA; CHIMERIC TRANSCRIPTS; SUPPRESSOR WT1; BINDING; PRODUCT AB Desmoplastic small round cell tumor (DSRCT) is an abdominal malignancy in children which is characterized by a recurrent chromosomal translocation, t(11; 22)(p13;q12). This rearrangement results in the fusion of the ubiquitously expressed EWS1 gene to the Wilms' tumor suppressor (WT1) gene. The chimeric protein contains the N-terminal domain of EWS1 fused to the DNA-binding domain of WT1, including zinc fingers 2-4, Because WT1 has been shown previously to bind and repress the insulin-like growth factor I (IGF-I-R) promoter, we investigated whether this promoter is, in addition, a target for the aberrant EWS/WT1 transcription factor. EWS/WT1 activated the ICF-I-R. promoter similar to 340%, whereas a fusion protein containing a three-amino acid insert (KTS) between zinc fingers 3 and 4 had no effect. On the other hand, expression vectors encoding either WT1 or EWS1 reduced the activity of the promoter to 46 and 58% of control values, respectively. Results of gel shift assays indicate that the binding affinity of EWS/WT1 to a fragment of the 5'-flanking region of the receptor promoter was higher than the affinity of WT1 itself. Consistent with the results of functional assays, the binding of EWS/WT1(+KTS) was significantly reduced. Due to the central role of the IGF-I-R in tumorigenesis, activation of the receptor promoter by EWS/WT1 may constitute a potential mechanism for the etiology and/or progression of DSRCT. C1 NIDDK,DIABET BRANCH,SECT MOL & CELLULAR PHYSIOL,NIH,BETHESDA,MD 20892. TECHNION ISRAEL INST TECHNOL,BRUCE RAPPAPORT FAC MED,IL-31096 HAIFA,ISRAEL. TECHNION ISRAEL INST TECHNOL,RAMBAM MED CTR,INST ENDOCRINOL & METAB,IL-31096 HAIFA,ISRAEL. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. FU NCI NIH HHS [CA52009, CA10815]; NIDDK NIH HHS [DK49210] NR 45 TC 56 Z9 60 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 9 PY 1996 VL 271 IS 32 BP 19304 EP 19309 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB684 UT WOS:A1996VB68400048 PM 8702614 ER PT J AU Yu, PY Eisner, GM Yamaguchi, I Mouradian, MM Felder, RA Jose, PA AF Yu, PY Eisner, GM Yamaguchi, I Mouradian, MM Felder, RA Jose, PA TI Dopamine D-1A receptor regulation of phospholipase C isoform SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-GAMMA-SUBUNITS; PROTEIN-KINASE-C; SPONTANEOUSLY HYPERTENSIVE RATS; ALPHA-SUBUNIT; PHOSPHOINOSITIDE HYDROLYSIS; TYROSINE PHOSPHORYLATION; ADENYLATE-CYCLASE; MUSCLE CELLS; TUBULE CELLS; K+-ATPASE AB In LTK(-) cells stably transfected with rat D-1A receptor cDNA, fenoldopam, a D-1 agonist, increased phosphatidylinositol 4,5-bisphosphate hydrolysis in a time-dependent manner. In the cytosol, phospholipase C (PLC) activity increased (50 +/- 7%) in 30 s, returned to basal level at 4 h, and decreased below basal values by 24 h; in the membrane, PLC activity also increased (36 +/- 13%) in 30 s, returned to basal level at 10 min, and decreased below basal value at 4 and 24 h. Fenoldopam also increased PLC-gamma protein in a time-dependent manner. The latter was blocked by the D-1 antagonist SKF83742 and by a D-1A antisense oligodeoxynucleotide, indicating involvement of the D-1A receptor. The fenoldopam-induced increase in PLC-gamma and activity was mediated by protein kinase A (PKA) since it was blocked by the PKA antagonist R(p)-8-CTP-adenosine cyclic 3':5'-monophosphorothioate (R(p)-8-CTP-cAMP-S) and mimicked by direct stimulation of adenylyl cyclase with forskolin or by a PKA agonist, S-p-cAMP-S. Protein kinase C (PKC) was also involved, since the fenoldopam-induced increase in PLC-gamma protein was blocked by two different PKC inhibitors, calphostin C and chelerythrine; calphostin C also blocked the fenoldopam-induced increase in PLC activity. In addition, forskolin and a PKA agonist, S-p-8-CTP-cAMP-S, increased PKC activity, and direct stimulation of PKC with phorbol 12-myristate 13-acetate increased PLC-gamma protein and activity, effects that were blocked by calphostin C. We suggest that the D-1A-mediated stimulation of PLC occurs as a result of PKA activation. PKA then stimulates PLC-gamma in cytosol and membrane via activation of PKC. C1 GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. GEORGETOWN UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. UNIV VIRGINIA,SCH MED,DEPT PATHOL,CHARLOTTESVILLE,VA 22908. NINCDS,GENET PHARMACOL UNIT,NIH,BETHESDA,MD 20892. OI Mouradian, M. Maral/0000-0002-9937-412X FU NIDDK NIH HHS [DK42185, DK44756, DK39308] NR 52 TC 56 Z9 58 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 9 PY 1996 VL 271 IS 32 BP 19503 EP 19508 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB684 UT WOS:A1996VB68400075 PM 8702641 ER PT J AU Janini, GM Muschik, GM Issaq, HJ AF Janini, GM Muschik, GM Issaq, HJ TI Micellar electrokinetic chromatography in zero-electroosmotic flow environment SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article; Proceedings Paper CT 6th Annual Frederick Conference on Capillary Electrophoresis CY OCT 23-25, 1995 CL FREDERICK, MD DE reversed-flow micellar electrokinetic chromatography; polynuclear aromatic hydrocarbons; aflatoxins; amino acids, dns derivatives ID CAPILLARY ZONE ELECTROPHORESIS; INDUCED FLUORESCENCE DETECTION; COATED CAPILLARIES; AMINO-ACIDS; SEPARATION; PERFORMANCE; ELUTION; MIGRATION; MOLECULES; BEHAVIOR AB Micellar electrokinetic chromatography (MEKC) is conducted in polyacrylamide-coated-capillaries under almost complete suppression of electroosmotic flow, The equations of migration and resolution for neutral solutes in this mode of MEKC operation are presented. The technique is termed reversed-flow MEKC (RF-MEKC) because, in contrast to MEKC in bare-silica capillaries (N-MEKC), solute migration order is reversed and solute migration time is inversely proportional to micelle concentration. This presents an advantage for the high-efficiency separation of extremely and moderately hydrophobic solutes in a short analysis time. Examples of the separation of polycyclic aromatic hydrocarbons, aflatoxins and dansylated-amino acids are presented using sodium dodecyl sulfate (SDS) surfactant. Polycyclic aromatic hydrocarbons are separated using a relatively low micelle concentration. The detection sensitivity for these compounds is enhanced in two ways, First, the peaks are sharp because of the short analysis time and the inertness of the column surface, Second, the fluorescence background and Joule's heating are minimal because of the low concentration of SDS and other additives needed to affect the separation. While N-MEKC is mainly conducted with basic buffers, RF-MEKC can be conducted in basic as well as acidic media as illustrated in the separation of 15 dansylated-amino acids at pH 4.2. RP Janini, GM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,POB B,FREDERICK,MD 21702, USA. NR 30 TC 30 Z9 31 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD AUG 9 PY 1996 VL 683 IS 1 BP 29 EP 35 DI 10.1016/0378-4347(96)00130-2 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VD586 UT WOS:A1996VD58600004 PM 8876436 ER PT J AU Valadon, P Nussbaum, G Boyd, LF Margulies, DH Scharff, MD AF Valadon, P Nussbaum, G Boyd, LF Margulies, DH Scharff, MD TI Peptide libraries define the fine specificity of anti-polysaccharide antibodies to Cryptococcus neoformans SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE antibody; Cryptococcus; peptide library; phage; polysaccharide ID MONOCLONAL-ANTIBODIES; ANTIIDIOTYPIC ANTIBODIES; FILAMENTOUS PHAGE; EPITOPE LIBRARY; BINDING; LIGANDS; INFECTION; GLUCURONOXYLOMANNAN; AFFINITY; IMMUNIZATION AB Cryptococcus neoformans is an encapsulated fungus that causes life-threatening meningoencephalitis in patients with AIDS. Monoclonal antibodies to the capsular glucuronoxylomannan can modulate the infection in mice, but the epitopes on this complex polysaccharide recognized by protective and non-protective antibodies have not been defined. We have used 2H1, one of our most protective antibodies, to screen phage display peptide libraries for peptide mimotopes that would allow us to explore the fine specificity of anti-cryptococcal polysaccharide antibodies. Hexa- and decapeptides have been identified with sequence homologies that define four motifs: 1, (E)TPXWM/LM/L; 2, W/YXWM/LYE; 3, DWXDW; and 4, (Ar)WDGQ(Ar). Peptides representing these motifs compete with each other for a shared binding site that overlaps the polysaccharide binding site. Motifs 1 and 2 confer high affinity binding, and PA1, which displays a motif I peptide with the sequence LQYTPSWMLV, binds to 2H1 with a K-d Of 295 nM. Analysis of the interaction between the 2H1 binding peptides and 24 structurally related anti-polysaccharide antibodies reveals a complex pattern of reactivity that strongly suggests binding to or close to the complementary determining regions. Furthermore, those antibodies that have been shown to have different specificity, and in some cases different protective potential, do not bind any of the peptides selected by the protective 2H1 antibody. This study shows that peptide mimotopes for a complex microbial polysaccharide can be identified by screening phage peptide Libraries and demonstrates the usefulness of such peptides in analyzing closely related interactive sites of proteins in general and of antibodies in particular. (C) 1996 Academic Press Limited C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT CELL BIOL,BRONX,NY 10461. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU NCI NIH HHS [CA39838]; NIAID NIH HHS [P01AI33184]; NIGMS NIH HHS [T32GM07288] NR 38 TC 117 Z9 118 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 AUG 9 PY 1996 VL 261 IS 1 BP 11 EP 22 DI 10.1006/jmbi.1996.0438 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB428 UT WOS:A1996VB42800002 PM 8760499 ER PT J AU Carmona, GN Baum, I Schindler, CW Goldberg, SR Jufer, R Cone, E Slaughter, E Belendiuk, GW Gorelick, DA AF Carmona, GN Baum, I Schindler, CW Goldberg, SR Jufer, R Cone, E Slaughter, E Belendiuk, GW Gorelick, DA TI Plasma butyrylcholinesterase activity and cocaine half-life differ significantly in rhesus and squirrel monkeys SO LIFE SCIENCES LA English DT Article DE butyrylcholinesterase; rhesus monkeys; squirrel monkeys; cocaine ID HUMAN-SERUM CHOLINESTERASE; HYDROLYSIS; ENZYME; BLOOD AB In vitro studies have implicated butyrylcholinesterase (BChE, E.C.3.1.1.8) as the major enzyme for metabolizing cocaine in humans, but little is known about endogenous BChE activity in monkeys and other animals often used in preclinical studies of cocaine. We compared BChE activity in 18 rhesus and 11 squirrel monkeys, using the colorimetric method of Ellman with butyrylthiocholine as substrate, and in vitro cocaine half-life in pooled plasma samples measuring cocaine concentrations over 60 minutes by GC-MS. Rhesus monkeys had a significantly higher plasma BChE activity than squirrel monkeys (8.2 +/- 0.5 U/L vs. 2.8 +/- 0.5 U/L), and a three-fold shorter in vitro cocaine half-life (20.1 min vs. 60.2 min). BChE activity in rhesus monkeys was comparable to the activity reported in humans. There was no significant influence of age, weight, or prior cocaine exposure. These results indicate that BChE level can vary between species of non-human primates, a factor that should be taken into account when studying drugs such as cocaine which are metabolized by BChE. C1 NIDA,PRECLIN PHARMACOL LAB,BALTIMORE,MD 21224. NIDA,TREATMENT BRANCH,BALTIMORE,MD 21224. NIDA,OFF DIRECTOR,BALTIMORE,MD 21224. NIDA,CHEM & DRUG METAB SECT,DIV INTRAMURAL RES,BALTIMORE,MD 21224. PHARMAVENE INC,ROCKVILLE,MD 20850. NR 21 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 0024-3205 J9 LIFE SCI JI Life Sci. PD AUG 9 PY 1996 VL 59 IS 11 BP 939 EP 943 DI 10.1016/0024-3205(96)00392-X PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VB941 UT WOS:A1996VB94100007 PM 8795705 ER PT J AU Cole, NB Smith, CL Sciaky, N Terasaki, M Edidin, M LippincottSchwartz, J AF Cole, NB Smith, CL Sciaky, N Terasaki, M Edidin, M LippincottSchwartz, J TI Diffusional mobility of Golgi proteins in membranes of living cells SO SCIENCE LA English DT Article ID HUMAN KDEL RECEPTOR; ENDOPLASMIC-RETICULUM; BREFELDIN-A; ELECTRON-MICROSCOPY; RETROGRADE TRANSPORT; LATERAL DIFFUSION; COMPLEX; RETENTION; APPARATUS; FLUORESCENCE AB The mechanism by which Golgi membrane proteins are retained with in the Golgi complex in the midst of a continuous flow of protein and lipid is not yet understood. The diffusional mobilities of mammalian Golgi membrane proteins fused with green fluorescent protein from Aequorea victoria were measured in living HeLa cells with the fluorescence photobleaching recovery technique. The diffusion coefficients ranged from 3 x 10(-9) square centimeters per second to 5 x 10(-9) square centimeters per second, with greater than 90 percent of the chimeric proteins mobile. Extensive lateral diffusion of the chimeric proteins occurred between Golgi stacks. Thus, the chimeras diffuse rapidly and freely in Golgi membranes, which suggests that Golgi targeting and retention of these molecules does not depend on protein immobilization. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. NINCDS,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. UNIV CONNECTICUT,CTR HLTH,DEPT PHYSIOL,FARMINGTON,CT 06032. FU NIAID NIH HHS [R37 AI14584] NR 36 TC 352 Z9 357 U1 2 U2 19 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 9 PY 1996 VL 273 IS 5276 BP 797 EP 801 DI 10.1126/science.273.5276.797 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VB429 UT WOS:A1996VB42900043 PM 8670420 ER PT J AU Senkevich, TG Bugert, JJ Sisler, JR Koonin, EV Darai, G Moss, B AF Senkevich, TG Bugert, JJ Sisler, JR Koonin, EV Darai, G Moss, B TI Genome sequence of a human tumorigenic poxvirus: Prediction of specific host response-evasion genes SO SCIENCE LA English DT Article ID MOLLUSCUM-CONTAGIOSUM VIRUS; EPIDERMAL GROWTH-FACTOR; VACCINIA VIRUS; NUCLEOTIDE-SEQUENCE; RING FINGER; ZINC-FINGER; DNA; PROTEIN; VARIOLA; HOMOLOG AB Molluscum contagiosum virus (MCV) commonly causes asymptomatic cutaneous neoplasms in children and sexually active adults as well as persistent opportunistic acquired immunodeficiency syndrome (AIDS)-associated disease. Sequencing the 190-kilobase pair genome of MCV has now revealed that the virus potentially encodes 163 proteins, of which 103 have homologs in the smallpox virus. MCV lacks counterparts to 83 genes of the smallpox virus, including those important in suppression of host responses to infection, nucleotide biosynthesis, and cell proliferation. MCV possesses 59 genes that are predicted to encode previously uncharacterized proteins, including major histocompatibility complex class I, chemokine, and glutathione peroxidase homologs, which suggests that there are MCV-specific strategies for coexistence with the human host. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20892. UNIV HEIDELBERG,INST MED VIROL,D-69120 HEIDELBERG,GERMANY. RI Bugert, Joachim/D-1705-2012 OI Bugert, Joachim/0000-0002-0556-3211 NR 58 TC 231 Z9 246 U1 4 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 AUG 9 PY 1996 VL 273 IS 5276 BP 813 EP 816 DI 10.1126/science.273.5276.813 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VB429 UT WOS:A1996VB42900048 PM 8670425 ER PT J AU Layer, RT Skolnick, P Bertha, CM Bandarage, UK Kuehne, ME Popik, P AF Layer, RT Skolnick, P Bertha, CM Bandarage, UK Kuehne, ME Popik, P TI Structurally modified ibogaine analogs exhibit differing affinities for NMDA receptors SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE NMDA receptor; ibogaine; O-desmethylibogaine; morphine; naloxone ID ANTI-ADDICTIVE DRUG; MORPHINE-TOLERANCE; RADIOLIGAND-BINDING; MK-801 BINDING; ANTAGONIST; RATS; WITHDRAWAL; CONGENERS; MECHANISMS; METABOLITE AB Based on both preclinical findings and anecdotal evidence in man, the psychoactive indole alkaloid ibogaine has been suggested to have anti-addictive properties. Previous studies indicate that blockade of NMDA receptors may mediate at least some of the putative anti-addictive actions of ibogaine. The potencies of a series of ibogaine analogs to inhibit (+)-[3-H-3]5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine ([H-3]MK-801) binding to NMDA receptors were examined. This series of analogs included the putative ibogaine metabolite O-desmethylibogaine, its metabolism resistant analog O-t-butyl-O-desmethylibogaine, the iboga alkaloids (+/-)-ibogamine, (+/-)-coronaridine, tabernanthine, harmaline, and the indolotropanes endo-3-(1-methylindol-2-yl)-8-methyl-8-azabicyclo[3.2.1]octane (RS 075194-190), exo-3-(1-methylindol-2-yl)-8-methyl-8-azabicyclo[3.2.1]octane (RS 075237-190) and endo-3-(indol-2-yl)-8-methyl-8-azabicyclo[3.2.1]octane (RS 025989-190). Among these compounds, ibogaine was the most potent inhibitor of [H-3]MK-801 binding (K-i = similar to 1.2 mu M), whilst the compounds with the greatest structural similarity to ibogaine, O-desmethylibogaine and O-t-butyl-O-desmethylibogaine were less potent (K-i = similar to 5.5 and 179.0 mu M, respectively). In morphine-dependent mice, ibogaine, but not O-desmethylibogaine or O-t-butyl-O-desmethylibogaine, attenuated naloxone precipitated withdrawal jumping. These findings are consistent with the hypothesis that inhibition of the expression of morphine dependence by ibogaine is related to its NMDA receptor antagonist properties. C1 NIDDK,NIH,MED CHEM LAB,BETHESDA,MD. UNIV VERMONT,DEPT CHEM,BURLINGTON,VT. POLISH ACAD SCI,INST PHARMACOL,KRAKOW,POLAND. RP Layer, RT (reprint author), NIDDK,NIH,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. RI Popik, Piotr/R-5383-2016 OI Popik, Piotr/0000-0003-0722-1263 NR 42 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 8 PY 1996 VL 309 IS 2 BP 159 EP 165 DI 10.1016/0014-2999(96)00304-4 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VD075 UT WOS:A1996VD07500006 PM 8874134 ER PT J AU Bartosova, Z Pirsel, M Reinhold, W StetlerStevenson, M Zajac-Kaye, M May, A Horak, ID Bohr, VA AF Bartosova, Z Pirsel, M Reinhold, W StetlerStevenson, M Zajac-Kaye, M May, A Horak, ID Bohr, VA TI Gene-specific repair in human CD4(+) lymphocytes reflects transcription and proliferation SO MUTATION RESEARCH-DNA REPAIR LA English DT Article DE gene-specific repair; CD4+ lymphocyte ID DNA-REPAIR; EXCISION-REPAIR; PYRIMIDINE DIMERS; CELL-CYCLE; C-MYC; MAMMALIAN-CELLS; DHFR GENE; STRAND; HETEROGENEITY; INDUCTION AB We have measured the gene-specific repair of ultraviolet irradiation (UV)-induced cyclobutane pyrimidine dimers (CPD) in freshly isolated human peripheral blood CD4(+) T-lymphocytes. Two populations of CD4(+) lymphocytes were assayed: resting and proliferating cells. DNA repair was assessed in the essential gene dihydrofolate reductase (DHFR) as well as in each of its strands, in the proliferation inducible c-myc gene and in the inactive delta-globin gene. Transcription rates in these genes were determined by nuclear run-on assay in the two cell populations. The rate of DHFR transcription increased 10-fold from resting to proliferating lymphocytes. Transcripts from c-myc were present only in proliferating cells, and we detected no delta-globin transcripts in either cell population. During the 24-h period after UV irradiation, there was little or no repair in any of the genes in the resting cells; there was some repair in the transcribed strand of the DHFR gene, but no repair in its nontranscribed strand. In the proliferating cells where the transcription of DHFR was much increased, the repair was efficient. The delta-globin gene was not expressed in either cell population, but it was more efficiently repaired in the proliferating than in the resting cells. We suggest that the gene-specific repair activity in CD4(+) lymphocytes can reflect the proliferative state of the cells as well as the transcriptional state of the gene. C1 NIA, GENET MOL LAB, NIH, BALTIMORE, MD 21224 USA. NCI, PATHOL LAB, DCBDC, NIH, BETHESDA, MD 20892 USA. NCI, METAB BRANCH, NIH, BETHESDA, MD 20892 USA. NCI, BIOL CHEM LAB, NIH, BETHESDA, MD 20892 USA. RI Pirsel, Miroslav/A-9996-2008 NR 38 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD AUG 8 PY 1996 VL 363 IS 3 BP 191 EP 199 DI 10.1016/0921-8777(96)00011-0 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA VD354 UT WOS:A1996VD35400005 PM 8765160 ER PT J AU Nakagawa, T Sawada, M Gonzalez, FJ Yokoi, T Kamataki, T AF Nakagawa, T Sawada, M Gonzalez, FJ Yokoi, T Kamataki, T TI Stable expression of human CYP2E1 in Chinese hamster cells: High sensitivity to N,N-dimethylnitrosamine in cytotoxicity testing SO MUTATION RESEARCH-ENVIRONMENTAL MUTAGENESIS AND RELATED SUBJECTS LA English DT Article DE NADPH-cytochrome P450 reductase; 7-ethoxycoumarin O-deethylase; 3-amino-1,2,4-triazole ID METABOLIC-ACTIVATION; N-NITROSODIMETHYLAMINE; CHL CELLS; CDNA; CYTOCHROME-P-450; ENZYME; DNA; RAT AB Involvement of human CYP2E1 expressed in genetically engineered cells in the metabolic activation of promutagens and procarcinogens was studied, An expression plasmid containing an insert of CYP2E1 cDNA and SR alpha promoter was constructed and transfected into the cultured cell line CR-119 which had previously been established by introducing a cDNA coding for NADPH-cytochrome P450 reductase. Among newly established cell lines, ER-181 showed the highest expression of CYP2E1 mRNA. Production of the CYP2E1 protein was confirmed by Western blot analysis using anti-rat CYP2E1 antibodies. Assay of 7-ethoxycoumarin O-deethylase activity demonstrated that ER-181 cells acquired the catalytic function of CYP2E1. ER-181 cells showed higher sensitivity to N,N-dimethylnitorosamine (DMN) in cytotoxicity assays as compared to parental CR-119 cells. Hypersensitivity to DMN of ER-181 cells was completely suppressed by 3-amino-1,2,4-triazole, a known inhibitor of CYP2E1. These results indicate that ER-181 cells which express human CYP2E1 are a useful tool to investigate toxicological functions of the cytochrome. C1 HOKKAIDO UNIV,FAC PHARMACEUT SCI,DIV DRUG METAB,KITA KU,SAPPORO,HOKKAIDO 060,JAPAN. NIH,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. RI yokoi, tsuyoshi/I-7115-2014 NR 24 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1161 J9 MUTAT RES-ENVIR MUTA JI Mutat. Res.-Environ. Mutagen. Rel. Subj. PD AUG 8 PY 1996 VL 360 IS 3 BP 181 EP 186 DI 10.1016/S0165-1161(96)90015-1 PG 6 WC Environmental Sciences; Genetics & Heredity SC Environmental Sciences & Ecology; Genetics & Heredity GA UY697 UT WOS:A1996UY69700004 PM 8692217 ER PT J AU Boice, JD Doody, MM Mandel, JS AF Boice, JD Doody, MM Mandel, JS TI Breast cancer among radiologic technologists - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. RP Boice, JD (reprint author), NCI,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 7 PY 1996 VL 276 IS 5 BP 369 EP 370 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UZ776 UT WOS:A1996UZ77600008 ER PT J AU Henson, DE AF Henson, DE TI Loss of p53-immunostaining intensity in breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID IMMUNOHISTOCHEMISTRY; STANDARDIZATION C1 NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,BETHESDA,MD 20892. NR 8 TC 21 Z9 21 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 AUG 7 PY 1996 VL 88 IS 15 BP 1015 EP 1016 DI 10.1093/jnci/88.15.1015 PG 2 WC Oncology SC Oncology GA VA550 UT WOS:A1996VA55000001 PM 8683628 ER PT J AU Merrill, R AF Merrill, R TI Stat bite - Trends in corpus uteri cancer incidence SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material RP Merrill, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 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 AUG 7 PY 1996 VL 88 IS 15 BP 1019 EP 1019 PG 1 WC Oncology SC Oncology GA VA550 UT WOS:A1996VA55000003 ER PT J AU Wang, YX Freedberg, DI Yamazaki, T Wingfield, PT Stahl, SJ Kaufman, JD Kiso, Y Torchia, DA AF Wang, YX Freedberg, DI Yamazaki, T Wingfield, PT Stahl, SJ Kaufman, JD Kiso, Y Torchia, DA TI Solution NMR evidence that the HIV-1 protease catalytic aspartyl groups have different ionization states in the complex formed with the asymmetric drug KNI-272 SO BIOCHEMISTRY LA English DT Article ID INHIBITOR; ALLOPHENYLNORSTATINE; RESIDUES AB In order to improve the design of HIV-1 protease inhibitors, it is essential to understand how they interact with active site residues, particularly the catalytic Asp25 and Asp125 residues, KNI-272 is a promising, potent HIV-1 protease inhibitor (K-i approximate to 5 pM), currently undergoing phase 1 clinical trials. Because KNI-272 is asymmetric, the complex it forms with the homodimeric HIV-1 protease also lacks symmetry, and the two protease monomers can have distinct NMR spectra. Monomer specific signal assignments were obtained for amino acid residues in the drug binding site as well as for six of the eight Asp residues in the protease/KNI-272 complex. Using these assignments, the ionization states of the Asp carboxyl groups were determined from measurements of (a) the pD dependence of the chemical shifts of the Asp carboxyl carbons and (b) the H/D isotope effect upon the Asp carboxyl carbon chemical shifts. The results of these measurements indicate that the carboxyl of Asp25 is protonated while that of Asp125 is not protonated. These findings provide not only the first experimental evidence regarding the distinct protonation states of Asp25/125 in HIV-1 protease/drug complexes, but also shed light on interactions responsible for inhibitor binding that should form the basis for improved drug designs. C1 NIDR,STRUCT MOL BIOL UNIT,NIH,BETHESDA,MD 20892. NIAMSD,PROT EXPRESS LAB,NIH,BETHESDA,MD 20892. KYOTO PHARMACEUT UNIV,DEPT MED CHEM,YAMASHIMA KU,KYOTO 607,JAPAN. NR 19 TC 119 Z9 120 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 6 PY 1996 VL 35 IS 31 BP 9945 EP 9950 DI 10.1021/bi961268z PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB211 UT WOS:A1996VB21100001 PM 8756455 ER PT J AU Ciotti, M Owens, IS AF Ciotti, M Owens, IS TI Evidence for overlapping active sites for 17 alpha-ethynlestradiol and bilirubin in the human major bilirubin UDPglucuronosyltransferase SO BIOCHEMISTRY LA English DT Article ID NAJJAR TYPE-I; UGT1 GENE-COMPLEX; UDP-GLUCURONOSYLTRANSFERASE; COS-1 CELLS; LIVER; EXPRESSION; PATIENT; GLUCURONIDATION; DEFICIENCY; ENZYMES AB The human major bilirubin UDPglucuronosyltransferase (transferase), HUG-Brl, and its mutants were expressed in the COS-1 cells using cDNA-based pSVL expression units to generate isoforms for the comparison of relative activities with 17 alpha-ethynlestradiol (17 alpha-EE) and bilirubin, its natural substrate, In comparison to bilirubin, 17 alpha-EE was a good substrate for HUG-Br1 under typical assay conditions of pH 7.2, confirming published studies [Ebner, T., et al. (1993) Mel. Pharmacol. 43, 649-654], It was further shown that the estrogen derivative is 1.2-2-fold more effective as a substrate at pH 6.4 than at pH 7.2. The k(m) for 17 alpha-EE was 40 mu M under both pH conditions, while the V-max values were 400 and 200 pmol per hour per 300 mu g of protein at pH 6.4 and 7.2, respectively, The pattern of glucuronidation was similar for both bilirubin and 17 alpha-EE, Previously, a ratio of 2-3-fold more activity for bilirubin glucuronidation at pH 6.4 versus 7.6 was established, and k(m) values of 2.5 mu M at both pH conditions were determined [Ritter, J. K., et al. (1993) J. Biol. Chem. 268, 23573-23579], In this study, the generation of 17 alpha-EE and bilirubin beta-glucuronides under both pH conditions was confirmed by the sensitivity of the products to beta-glucuronidase treatment, Concurrent glucuronidation reaction mixtures containing equal amounts of wild-type and mutant proteins demonstrated the following. P270G, V273D, and five different G276 mutants nearly or completely inactivated all,glucuronidation at both pH levels. V273Q generated 81-94% of the normal activity for 17 alpha-EE and 42% of the normal activity for bilirubin turnover; H173R gave 37-60% of the normal turnover with both substrates, and V275I produced 15-24% of the normal level of glucuronide with both compounds. The most distinguishing amino acid tested was P176G which was approximately 50% normal for 17 alpha-EE at both pH conditions but was totally inactive for bilirubin, A second substitution, P285G, did not affect 17 alpha-EE turnover but was 50% normal for bilirubin, The parallel effects on the metabolism of both substrates by some mutants and the opposite results from two mutants are evidence for a common set of amino acids for their catalysis with the recruitment of additional amino acids to depend upon the substrate to be metabolized, Hence, amino acid substitutions in the protein are not necessarily universally inactivating. C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. NR 23 TC 24 Z9 24 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 AUG 6 PY 1996 VL 35 IS 31 BP 10119 EP 10124 DI 10.1021/bi960584a PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB211 UT WOS:A1996VB21100021 PM 8756475 ER PT J AU Leroy, MJ Degerman, E Taira, M Murata, T Wang, LH Movsesian, MA Meacci, E Manganiello, VC AF Leroy, MJ Degerman, E Taira, M Murata, T Wang, LH Movsesian, MA Meacci, E Manganiello, VC TI Characterization of two recombinant PDE3 (cGMP-Inhibited cyclic nucleotide phosphodiesterase) isoforms, RcGIP1 and HcGIP2, expressed in NIH 3006 murine fibroblasts and Sf9 insect cells SO BIOCHEMISTRY LA English DT Article ID INSULIN-SENSITIVE PHOSPHODIESTERASE; RAT ADIPOSE-TISSUE; AMP PHOSPHODIESTERASE; CAMP-PHOSPHODIESTERASE; SELECTIVE INHIBITORS; GEL-ELECTROPHORESIS; CARDIOTONIC AGENT; MOLECULAR-CLONING; BOVINE BRAIN; PURIFICATION AB CDNAS encoding PDE3 [cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI PDE)] isoforms, cGIP1 and cGIP2, have been cloned from rat (R) and human (II) cDNA libraries. The deduced amino acid sequences of RcGIP1 and HcGIP2 are very similar in their conserved catalytic domains but differ in their N-terminal regulatory domains [Meacci, E., et al. (1992) Pi;oc. Natl. Acad. Sci. U.S.A. 89, 3721-3725; Taira, M., ct al. (1993) J. Biol. Chem. 268, 18573-18579]. cDNAs encoding both rat adipocyte RcGIP1 and human myocardial HcGIP2 (full-length forms and truncated forms lacking much of the putative N-terminal domain) were expressed in NIH 3006 fibroblasts and in Sf9 insect cells. The recombinant proteins exhibited the expected subunit molecular mass, immunologic reactivities, and characteristics of native membrane-associated forms of the enzymes, e.g., high affinity for cAMP (K-m), sensitivity to the selective cGI PDE Inhibitors OPC 3689 and OPC 3911 and to cGMP. The full-length recombinants were predominantly particulate, whereas the truncated HcGIP2 forms were cytosolic suggesting that N-terminal domains contain structural determinants important for membrane association. Both fibroblast RcGIP1 and authentic adipocyte cGI PDE were phosphorylated ii vitro by cAMP-dependent protein kinase; tryptic [P-32]peptides released from rat adipocyte P-32-cGI PDE and P-32-RcGIP1 exhibited identical electrophoretic profiles suggesting that the same peptides are phosphorylated in both. C1 NHLBI,PULM & CRIT CARE MED BRANCH,SECT BIOCHEM PHYSIOL,NIH,BETHESDA,MD 20892. LUND UNIV,DEPT CELL & MOL BIOL,SECT MOL SIGNALLING,S-22100 LUND,SWEDEN. VET ADM MED CTR,RES SERV,SALT LAKE CITY,UT 84148. UNIV UTAH,SCH MED,DEPT INTERNAL MED,SALT LAKE CITY,UT 84112. UNIV UTAH,SCH MED,DEPT PHARMACOL,SALT LAKE CITY,UT 84112. NR 46 TC 47 Z9 48 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 6 PY 1996 VL 35 IS 31 BP 10194 EP 10202 DI 10.1021/bi952711t PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB211 UT WOS:A1996VB21100030 PM 8756484 ER PT J AU Tan, DP Shao, XP Pu, LP Guo, V Nirenberg, M AF Tan, DP Shao, XP Pu, LP Guo, V Nirenberg, M TI Sequence and expression of the murine Hoxd-3 homeobox gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Hoxa-3; Hoxb-3; embryonic development; Src homology 3 binding sites ID TARGETED DISRUPTION; RETINOIC ACID; MICE; TRANSFORMATIONS; TRANSCRIPTS; ASSIGNMENT; VERTEBRAE; CLONING; REGION AB Murine Hoxd-3 (Hox 4.1) genomic DNA and cDNA and Hoxa-3 (Hox 1.5) cDNA were cloned and sequenced, The homeodomains of Hoxd-3 and Hoxa-3 and regions before and after the homeodomain are highly conserved. Both Hoxd-3 and Hoxa-3 proteins have a proline-rich region that contains consensus amino acid sequences for binding to Src homology 3 domains of some signal transduction proteins, Northern blot analysis of RNA from 8- to 11-day-old mouse embryos revealed a 4.3-kb species of Hoxd-3 RNA, whereas a less abundant 3.0-kb species of Hoxd-3 RNA was found in RNA from 9- to 11-day-old embryos. Two species of Hoxd-3 poly(A)(+) RNA, 4.3 and 6.0 kb in length, were found in poly(A)(+) RNA from adult mouse kidney, but not in RNA from other adult tissues tested, Hoxd-3 mRNA was detected by in situ hybridization in 12-, 14-, and 17-day-old mouse embryos in the posterior half of the myelencephalon, spinal cord, dorsal root ganglia, first cervical vertebra, thyroid gland, kidney tubules, esophagus, stomach, and intestines. C1 NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. RP Tan, DP (reprint author), NHLBI,LAB BIOCHEM GENET,BLDG 36,ROOM 1C-06,BETHESDA,MD 20892, USA. NR 22 TC 9 Z9 11 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 6 PY 1996 VL 93 IS 16 BP 8247 EP 8252 DI 10.1073/pnas.93.16.8247 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VB325 UT WOS:A1996VB32500018 PM 8710855 ER PT J AU Werner, H Karnieli, E Rauscher, FJ LeRoith, D AF Werner, H Karnieli, E Rauscher, FJ LeRoith, D TI Wild-type and mutant p53 differentially regulate transcription of the insulin-like growth factor I receptor gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INITIATOR-MEDIATED TRANSCRIPTION; TUMOR-SUPPRESSOR GENE; TATA-BINDING PROTEIN; IGF-I; CELLULAR ASPECTS; PROMOTER REGION; CELLS; DNA; MUTATIONS; SEQUENCE AB The insulin-like growth factor I receptor (IGF-I-R) plays a critical role in transformation events. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Tumor suppressor p53 p53 is a nuclear transcription factor that blocks cell cycle progression and induces apoptosis, p53 is the most frequently mutated gene in human cancer. Cotransfection of Saos-2 (osteosarcoma-derived cells) and PD (rhabdomyosarcoma-derived cells) cells with IGF-I-R promoter constructs driving luciferase reporter genes and with wild-type p53 expression vectors suppressed promoter activity in a dose-dependent manner. This effect of p53 is mediated at the level of transcription and it involves interaction with TBP, the TATA hox-binding component of TFIID. On the other hand, three tumor-derived mutant forms of p53 (mut 143, mut 248, and mut 273) stimulated the activity of the IGF-I-R promoter and increased the levels of IGF-I-R/luciferase fusion mRNA. These results suggest that wild-type p53 has the potential to suppress the IGF-I-R promoter in the postmitotic, fully differentiated cell, thus resulting in low levels of receptor gene expression in adult tissues. Mutant versions of p53 protein, usually associated with malignant states, can derepress the IGF-I-R promoter, with ensuing mitogenic activation by locally produced or circulating IGFs. C1 NIDDKD,SECT MOL & CELLULAR PHYSIOL,DIABET BRANCH,NIH,BETHESDA,MD 20892. TECHNION ISRAEL INST TECHNOL,RAMBAM MED CTR,INST ENDOCRINOL & METAB,IL-31096 HAIFA,ISRAEL. TECHNION ISRAEL INST TECHNOL,BRUCE RAPPAPORT FAC MED,IL-31096 HAIFA,ISRAEL. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. NR 49 TC 268 Z9 274 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 6 PY 1996 VL 93 IS 16 BP 8318 EP 8323 DI 10.1073/pnas.93.16.8318 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VB325 UT WOS:A1996VB32500031 PM 8710868 ER PT J AU Blagosklonny, MV Toretsky, J Bohen, S Neckers, L AF Blagosklonny, MV Toretsky, J Bohen, S Neckers, L TI Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mutated p53; geldanamycin; chaperone; conformational recognition ID HEAT-SHOCK PROTEIN; DIOXIN RECEPTOR FUNCTION; HELIX-LOOP-HELIX; WILD-TYPE P53; GLUCOCORTICOID RECEPTOR; HETEROPROTEIN COMPLEX; MONOCLONAL-ANTIBODY; FUNCTION MUTATIONS; SUPPRESSOR; GENE AB The p53 mutant, 143(ala), was translated in vitro in either rabbit reticulocyte lysate (RRL) or wheat germ extract (WGE). In RRL, p53-143(ala) protein of both mutant and wild-type conformation, as detected immunologically with conformation-specific antibodies, was translated. The chaperone protein HSP90, present in RRL, was found to coprecipitate only with the mutated conformation of p53. Geldanamycin, shown previously to bind to HSP90 and destabilize its association with other proteins, decreased the amount of immunologically detectable mutated p53 and increased the amount of detectable wild-type protein, without affecting the total translation of p53. When translated in WGE, known to contain functionally deficient HSP90, p53-143(ala) produced p53 protein, which was not recognized by a mutated conformation-specific antibody. In contrast, the synthesis of conformationally detectable wild-type p53 in this system was not compromised, Reconstitution of HSP90 function in WGE permitted synthesis of conformationally detectable mutated p53, and this was abrogated by geldanamycin. Finally, when p53-143(ala) was stably transfected into yeast engineered to be defective for HSP90 function, conformational recognition of mutated p53 was impaired. When stable transfectants of p53-143(ala) were prepared in yeast expressing wildtype HSP90, conformational recognition of mutated p53 was antagonized by macbecin I, a geldanamycin analog also known to bind HSP90. Taken together, these data demonstrate a role for HSP90 in the achievement and/or stabilization of the mutated conformation of p53-143(ala). Furthermore, we show that the mutated conformation of p53 can be pharmacologically antagonized by drugs targeting HSP90. C1 NCI,CLIN PHARMACOL BRANCH,NIH,BETHESDA,MD 20892. NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NR 39 TC 219 Z9 232 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 6 PY 1996 VL 93 IS 16 BP 8379 EP 8383 DI 10.1073/pnas.93.16.8379 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VB325 UT WOS:A1996VB32500042 PM 8710879 ER PT J AU SussToby, E Zimmerberg, J Ward, GE AF SussToby, E Zimmerberg, J Ward, GE TI Toxoplasma invasion: The parasitophorous vacuole is formed from host cell plasma membrane and pinches off via a fission pore SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell capacitance; intracellular parasite; endocytosis ID MALARIA-INFECTED ERYTHROCYTES; PLASMODIUM-FALCIPARUM; PARASITE INVASION; NERVE-TERMINALS; MAST-CELLS; MEROZOITES; SECRETION; GONDII; LIPIDS; PENETRATION AB Most intracellular pathogens avoid lysing their host cells during invasion by wrapping themselves in a vacuolar membrane, This parasitophorous vacuole membrane (PVM) is often retained, serving as a critical transport interface between the parasite and the host cell cytoplasm, To test whether the PVM formed by the parasite Toxoplasma gondii is derived from host cell membrane or from lipids secreted by the parasite, we used time-resolved capacitance measurements and video microscopy to assay host cell surface area during invasion. We observed no significant change in host cell surface area during PVM formation, demonstrating that the PVM consists primarily of invaginated host cell membrane, Pinching off of the PVM from the host cell membrane occurred after an unexpected delay (34-305 sec) and was seen as a 0.219 +/- 0.006 pF drop in capacitance, which corresponds well to the predicted surface area of the entire PVM (30-33 mu m(2)). The formation and closure of a fission pore connecting the extracellular medium and the vacuolar space was detected as the PVM pinched off, This final stage of parasite entry was accomplished without any breach in cell membrane integrity. C1 NICHHD,THEORET & PHYS BIOL LAB,NIH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NR 36 TC 172 Z9 181 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 AUG 6 PY 1996 VL 93 IS 16 BP 8413 EP 8418 DI 10.1073/pnas.93.16.8413 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VB325 UT WOS:A1996VB32500048 PM 8710885 ER PT J AU Raynal, P Pollard, HB Cushman, SW GuerreMillo, M AF Raynal, P Pollard, HB Cushman, SW GuerreMillo, M TI Unique subcellular distribution of five annexins in resting and insulin-stimulated rat adipose cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-KINASE-C; GLUCOSE-TRANSPORTER; BINDING PROTEINS; CHROMAFFIN GRANULES; ADIPOCYTES; CALCIUM; GLUT4; EXOCYTOSIS; MEMBRANE; CALPACTIN AB Several lines of evidence suggest that annexins, a family of phospholipid-binding proteins, play a role in cellular trafficking. Five annexins (I, II, V, VI, VII) were detected in rat adipose cells. They were primarily associated with the plasma membrane in a calcium-dependent manner, None of them redistributed with insulin treatment of the cells, in contrast to the glucose transporter GLUT4, which moved from intracellular membranes to the plasma membrane. Although the actual function of annexins in adipose cells remains to be determined, our data indicate that insulin-stimulated GLUT I trafficking does not rely on a change in subcellular location of any of the five annexins detected so far in these cells. (C) 1996 Academic Press, Inc. C1 NIDDKD,CELL BIOL & GENET LAB,DIABET BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,EXPT DIABET METAB & NUTR SECT,DIABET BRANCH,NIH,BETHESDA,MD 20892. NR 35 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 5 PY 1996 VL 225 IS 1 BP 116 EP 121 DI 10.1006/bbrc.1996.1139 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VE983 UT WOS:A1996VE98300019 PM 8769103 ER PT J AU Kong, LY McMillian, MK Maronpot, R Hong, JS AF Kong, LY McMillian, MK Maronpot, R Hong, JS TI Protein tyrosine kinase inhibitors suppress the production of nitric oxide in mixed glia, microglia-enriched or astrocyte-enriched cultures SO BRAIN RESEARCH LA English DT Article DE lipopolysaccharide; protein tyrosine kinase inhibitor; nitric oxide; inducible nitric oxide synthase; microglia; astrocyte ID SIGNAL-TRANSDUCTION; BACTERIAL LIPOPOLYSACCHARIDE; ACTIVATED MICROGLIA; SYNTHASE ACTIVITY; MOUSE-BRAIN; INDUCTION; CELLS; MACROPHAGES; EXPRESSION; INTERFERON AB Nitric oxide (NO) produced bq glial cells has been implicated in the neuropathogenesis of various diseases. However, the signaling transduction pathway(s) for the production of NO in these cells is not well understood, To test whether protein tyrosine kinases (PTKs) are required for signaling events of NO production in glial cells, this study examined the effects of genistein and tyrphostin A25, two potent inhibitors of PTKs, on the production of NO in mouse primary mixed glia, microglia-enriched or astrocyte-enriched cultures exposed to lipopolysaccharide (LPS) ora combination of LPS and interferon-gamma (IFN gamma). LPS induced a dose-dependent increase in NO production from the mixed glia cultures. The LPS-induced NO production was significantly enhanced by stimulating the cells with IFN gamma. Genistein or tyrphostin A25 inhibited the production of NO in both LPS- and LFN gamma/LPS-stimulated mixed glia cultures. The production of NO in the stimulated microglia-enriched or astrocyte-enriched cultures was also inhibited by tyrphostin A25. To verify the cellular sources of NO, immunocytochemical staining of inducible NO synthase (iNOS) was followed by staining with the microglia marker Mac-1 or the astrocyte marker glial fibrillary acid protein (GFAP) in microglia-enriched or astrocyte-enriched cultures. The expression of iNOS and the production of NO in microglia-enriched cultures were significantly higher than those in the identically stimulated astrocyte-enriched cultures. These results demonstrate that PTKs are involved in the signaling events of LPS-induced NO production in microglia and astrocytes, and that microglia are more responsive than astrocytes to stimuli which induce NO. These results may provide insights into therapeutic interventions In the pathway for NO production in the brain. C1 NIEHS,NIH,TOXICOL BRANCH,SECT NEUROPHARMACOL,RES TRIANGLE PK,NC 27709. NIEHS,NIH,LAB EXPT PATHOL,RES TRIANGLE PK,NC 27709. NR 35 TC 63 Z9 64 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 5 PY 1996 VL 729 IS 1 BP 102 EP 109 DI 10.1016/0006-8993(96)00417-9 PG 8 WC Neurosciences SC Neurosciences & Neurology GA VE467 UT WOS:A1996VE46700011 PM 8874881 ER PT J AU Liang, BC Hays, L AF Liang, BC Hays, L TI Mitochondrial DNA copy number changes in human gliomas SO CANCER LETTERS LA English DT Article DE glioblastoma; neoplasm; gene amplification; subtractive hybridization ID COMPARATIVE GENOMIC HYBRIDIZATION; INDUCED RAT HEPATOMAS; GENE AMPLIFICATION; INCREASED EXPRESSION; MALIGNANT GLIOMAS; GROWTH; CELLS; MECHANISMS; TUMORS; CANCER AB Gene amplification has been found to be biologically important in cancer, We report a complementary DNA sequence obtained using a subtractive hybridization approach which is frequently and highly amplified in human gliomas. 39/45 (87%) glial tumor specimens (of pathologically low and high grade) revealed increases in copy number of this clone from 5- to 25-fold; erb-b amplification was found in 8/45 (18%). This clone revealed homology to non-continuous mitochondrial DNA positions 1679-1948 and 2017-2057, with the interspersed sequences deleted, A non-mitochondrial genomic addition of 15 bases at the 5' end of the clone and a 7 base insertion adjacent: to position 1948 were also present. Evaluation of the entire mitochondrial genome in a subset of 11 tumors showed maximal amplification between mitochondrial positions 748 and 5882, and a lower degree of amplification elsewhere, with a recurrent deletion of a 1.2 kb EcoRI fragment noted in 5/11 (46%) tumors. The mitochondrial genome is frequently affected in human gliomas, and warrants further study to determine its role in glial malignancy. C1 NCI,CLIN PHARMACOL BRANCH,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. RP Liang, BC (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT NEUROL,4200 E 9TH AVE,BOX B182,DENVER,CO 80262, USA. NR 23 TC 35 Z9 39 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 2 PY 1996 VL 105 IS 2 BP 167 EP 173 DI 10.1016/0304-3835(96)04276-0 PG 7 WC Oncology SC Oncology GA UZ585 UT WOS:A1996UZ58500006 PM 8697440 ER PT J AU Szallasi, Z Bogi, K Gohari, S Biro, T Acs, P Blumberg, PM AF Szallasi, Z Bogi, K Gohari, S Biro, T Acs, P Blumberg, PM TI Non-equivalent roles for the first and second zinc fingers of protein kinase C delta - Effect of their mutation on phorbol ester-induced translocation in NIH 3T3 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYSTEINE-RICH DOMAIN; DIFFERENTIAL REGULATION; BINDING; PHOSPHOLIPIDS; ACTIVATION; ISOZYMES; REGION; GAMMA AB Classical and novel protein kinase C (PKC) isozymes contain two, so-called cysteine-rich zinc finger domains that represent the binding sites for phorbol esters and the diacylglycerols, X-ray crystallographic, mutational, and modeling studies are providing detailed understanding of the interactions between the phorbol esters and individual PKC zinc fingers, In the present study, we explore the roles of the individual zinc fingers in the context of the intact enzyme, Our approach was to mu tate either the first, the second, or both zinc fingers of PKC delta, to express the mutated enzyme in NIH 3T3 cells, and to monitor the effect of the mutations on the dose-response curve for translocation induced by phorbol 12-myristate 13-acetate. The introduced mutations change into glycine the consensus proline in the phorbol ester binding loop of the zinc finger; in the isolated zinc finger, this mutation causes a 125-fold decrease in phorbol ester binding affinity, We observed that mutation in the first zinc finger caused almost no shift in the dose-response curve for translocation; mutation in the second zinc finger caused a al-fold shift, whereas mutation in both zinc fingers caused a 138-fold shift, We conclude that the zinc fingers in the intact PRC are not equivalent and that the second zinc finger plays the predominant role in translocation of protein kinase C gamma in response to phorbol 12-myristate 13-acetate, Our findings have important implications for the understanding and design of PKC inhibitors targeted to the zinc finger domains. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOL MECHANISMS TUMOR PROMOT SECT,NIH,BETHESDA,MD 20892. NR 16 TC 115 Z9 116 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 2 PY 1996 VL 271 IS 31 BP 18299 EP 18301 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB683 UT WOS:A1996VB68300002 PM 8702464 ER PT J AU Ferraris, JD Williams, CK Jung, KY Bedford, JJ Burg, MB GarciaPerez, A AF Ferraris, JD Williams, CK Jung, KY Bedford, JJ Burg, MB GarciaPerez, A TI ORE, a eukaryotic minimal essential osmotic response element - The aldose reductase gene in hyperosmotic stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RENAL MEDULLARY CELLS; EXTRACELLULAR NACL; TRANSPORTER GENE; TRANSCRIPTION; INDUCTION; CLONING; RNA; PROMOTER AB Organisms, almost universally, adapt to hyperosmotic stress through increased accumulation of organic osmolytes but the molecular mechanisms have only begun to be addressed, Among mammalian tissues, renal medullary cells are uniquely exposed to extreme hyperosmotic stress. Sorbitol, synthesized through aldose reductase, is a predominant osmolyte induced under hyperosmotic conditions in renal cells, Using a rabbit renal cell line, we originally demonstrated that hyperosmotic stress induces transcription of the aldose reductase gene, Recently, we cloned the rabbit aldose reductase gene, characterized its structure, and found the first evidence of an osmotic response region in a eukaryotic gene, Now, we have progressively subdivided this 3221-base pair (bp) region into discrete fragments in reporter gene constructs. Thereby, we have functionally defined the smallest sequence able to confer hyperosmotic response on a downstream gene independent of other putative cis-elements, that is, a minimal essential osmotic response element (ORE). The sequence of the ORE is CGGAAAATCAC(C) (bp -1105/-1094). A 17-bp fragment (-1108/-1092) containing the ORE used as a probe in electrophoretic mobility shift assays suggests hyperosmotic induction of a slowly migrating band. Isolation of trans-acting factor(s) and characterization of their interaction with the ORE should elucidate the basic mechanisms for regulation of gene expression by hyperosmotic stress. RP Ferraris, JD (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BLDG 10,RM 6N307,10 CTR DR MSC 1598,BETHESDA,MD 20892, USA. NR 24 TC 142 Z9 144 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 AUG 2 PY 1996 VL 271 IS 31 BP 18318 EP 18321 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB683 UT WOS:A1996VB68300007 PM 8702469 ER PT J AU Hwang, SC Jhon, DY Bae, YS Kim, JH Rhee, SG AF Hwang, SC Jhon, DY Bae, YS Kim, JH Rhee, SG TI Activation of phospholipase C-gamma by the concerted action of tau proteins and arachidonic acid SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STIMULATES PHOSPHOINOSITIDE HYDROLYSIS; PLACENTAL-LACTOGEN RELEASE; UNSATURATED FATTY-ACIDS; CYTOSOLIC PHOSPHOLIPASE-A2; INTERFACIAL CATALYSIS; SIGNAL-TRANSDUCTION; PHOSPHATIDIC-ACID; KINASE-C; DOMAIN; CELLS AB Phospholipase C-gamma (PLC-gamma) isozymes are thought to be activated by receptor-induced tyrosine phosphorylation. Proteins that activate PLC-gamma 1 have now been purified from bovine brain and identified as members of the tan family of microtubule-associated proteins. Activation of PLC-gamma by tau was enhanced in the presence of unsaturated fatty acids such as arachidonic acid, saturated fatty acids being ineffective. Maximal (15-20-fold) activation was apparent in the presence of 0.15 mu M tau and 25 mu M arachidonic acid (AA). The effect of tau and AA was specific to PLC-gamma isozymes in the presence of submicromolar concentrations of Ca2+ and was markedly inhibited by phosphatidylcholine. These results suggest that in cells that express tau, receptor to cytosolic phospholipase A, may activate PLC-gamma isozymes indirectly in the absence of tyrosine phosphorylation through the hydrolysis of phosphatidylcholine to generate AA. C1 NHLBI,LAB CELL SIGNALING,NIH,BETHESDA,MD 20892. OI Hwang, Sung Chul/0000-0003-2401-619X NR 41 TC 152 Z9 158 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 2 PY 1996 VL 271 IS 31 BP 18342 EP 18349 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB683 UT WOS:A1996VB68300013 PM 8702475 ER PT J AU Magnuson, P Lehnherr, H Mukhopadhyay, G Yarmolinsky, MB AF Magnuson, P Lehnherr, H Mukhopadhyay, G Yarmolinsky, MB TI Autoregulation of the plasmid addiction operon of bacteriophage P1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REPRESSOR-OPERATOR COMPLEX; AMINO-ACID-SEQUENCE; ESCHERICHIA-COLI; ARC REPRESSOR; F-PLASMID; SECONDARY-STRUCTURE; CRYSTAL-STRUCTURE; CLONING VECTORS; GEL RETARDATION; DNA RECOGNITION AB The P1 plasmid addiction operon increases the apparent stability of a plasmid that carries it by killing plasmid-free (cured) segregants. The operon consists of a gene encoding an endotoxin responsible for death on curing (dec), preceded by a gene encoding a relatively unstable antidote that can prevent host death (phd). When the copy number of the operon was increased, expression of a lacZ reporter fused to the promoter of the operon decreased, indicating that expression of the operon was stabilized by an autoregulatory circuit. Transcription of the lacZ reporter was repressed about 10-fold when phd, without dec, was expressed from an exogenous promoter, DNase I footprinting showed that Phd binds a perfect 10-base pair palindromic DNA sequence and, at higher concentrations, an adjacent, imperfect palindrome. The palindromic sites are located between the -10 region of the putative promoter and the start codon of phd. Electrophoretic mobility of DNA containing the promoter region was retarded in the presence of Phd and further retarded in the presence of Phd and Dec. When doc was co-expressed with phd, repression of the lacZ fusion was enhanced more than 100-fold. Thus, both products of the addiction operon participate in its autoregulation. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NR 44 TC 21 Z9 21 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 2 PY 1996 VL 271 IS 31 BP 18705 EP 18710 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB683 UT WOS:A1996VB68300063 ER PT J AU Hernandez, VJ Hsu, LM Cashel, M AF Hernandez, VJ Hsu, LM Cashel, M TI Conserved region 3 of Escherichia coli sigma(70) is implicated in the process of abortive transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LAC UV5 PROMOTER; RNA-POLYMERASE; INITIATION; DNA; PURIFICATION; BINDING; SUBUNIT; COMPLEXES; INVITRO AB Multiple-round in vitro transcription assays were performed using purified Escherichia coli RNA polymerase reconstituted with either wild-type or mutant sigma(70) proteins, These mutants, sigma(70)(P504L) and sigma(70)(S506F), bear single amino acid changes in conserved protein region 3, Behavior of the mutant enzymes on three test templates, bearing either the T7 Al, T5 N25, or T5 N25(antiDSR) promoter, were characterized, Transcription of all three promoter templates produced a pattern of specific abortive RNA species, which was qualitatively different for the mutants compared to the wild-type sigma(70) enzyme. Short abortive RNAs were produced at similar levels for mutant and wild-type enzymes, The production of longer abortive species was either reduced or increased by the mutant enzymes in a systematic manner that appears promoter specific, and could be RNA length- or promoter distance-dependent. The process of abortive RNA transcription is thought to be tightly associated with that of promoter clearance, However, promoter clearance from these templates appears only slightly affected by the mutant enzymes, These mutants implicated region 3 of sigma(70) in the process of abortive transcription and suggest that the sequence of enzymatic events leading to the production of abortive or full-length RNA may be separable. C1 MT HOLYOKE COLL, PROGRAM BIOCHEM, S HADLEY, MA 01075 USA. RP Hernandez, VJ (reprint author), NICHHD, NIH,LMG,9000 ROCKVILLE PIKE,BLDG 6B, RM 316, BETHESDA, MD 20892 USA. NR 27 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 2 PY 1996 VL 271 IS 31 BP 18775 EP 18779 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB683 UT WOS:A1996VB68300072 PM 8702534 ER PT J AU Mo, JY Schaaper, RM AF Mo, JY Schaaper, RM TI Fidelity and error specificity of the alpha catalytic subunit of Escherichia coli DNA polymerase III SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPONTANEOUS MUTATION; REVERSE-TRANSCRIPTASE; BASE SUBSTITUTION; MISMATCH REPAIR; LACI GENE; PRONE REPLICATION; HOLOENZYME; EXONUCLEASE; MUTAGENESIS; MECHANISMS AB Escherichia coli DNA polymerase III holoenzyme is the replicative enzyme primarily responsible for the duplication of the E. coli chromosome. This process occurs with high accuracy, less than 10(-9) to 10(-10) errors being committed per base pair per round of replication. As a first step in understanding the mechanisms responsible for the high fidelity of this process, we have purified the polymerase III alpha catalytic subunit, free of exonuclease activity, and analyzed its fidelity in vitro. We employed a newly developed gap-filling assay using the N-terminal 250 bases of the loci gene as a forward mutational target. When synthesizing across this target, alpha subunit produced mutations at a frequency of 0.6%. DNA sequencing revealed that the mutants created in vitro consisted mostly of frameshift mutations, although some base substitutions were also observed, The frameshifts, occurring at more than 120-fold above the background, consisted largely of -1 deletions. Among them, about 80% were the deletion of a purine template base with a pyrimidine 5'-neighbor, These results suggest that the alpha subunit (i) has a relatively low ability to extend from misincorporated bases, accounting for the low level of observed base substitutions, and (ii) has a relatively high capability of extension after misalignment of a misincorporated base on the next (complementary) template base, accounting for the high level of frameshift mutations. This model is supported by an experiment in which alpha subunit was required to initiate DNA synthesis from a terminal mispair in a sequence context that allowed slippage on the next template base. Among the products of this reaction, frameshifts outnumbered base pair substitutions by greater than 70-fold. A comparison to in vivo mutational spectra suggests that the pol III accessory factors may play a major role in modulating the fidelity of DNA synthesis. C1 NIEHS, MOL GENET LAB, NIH, RES TRIANGLE PK, NC 27709 USA. NR 58 TC 38 Z9 38 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 AUG 2 PY 1996 VL 271 IS 31 BP 18947 EP 18953 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB683 UT WOS:A1996VB68300096 PM 8702558 ER PT J AU Cushman, M Golebiewski, WM Graham, L Turpin, JA Rice, WG FliakasBoltz, V Buckheit, RW AF Cushman, M Golebiewski, WM Graham, L Turpin, JA Rice, WG FliakasBoltz, V Buckheit, RW TI Synthesis and biological evaluation of certain alkenyldiarylmethanes as anti-HIV-1 agents which act as non-nucleoside reverse transcriptase inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIGHLY SELECTIVE INHIBITORS; ANTI-HIV ACTIVITY; NONNUCLEOSIDE INHIBITORS; TYPE-1 HIV-1; OXATHIIN CARBOXANILIDE; ANTIVIRAL ACTIVITY; RESISTANT VIRUS; DERIVATIVES; POTENT AB Several novel alkenyldiarylmethane (ADAM) non-nucleoside HIV-1 reverse transcriptase inhibitors were synthesized. The most potent of these proved to be 3',3''-dibromo-4',4 ''-dimethoxy-5',5 ''-bis(methoxycarbonyl)-1,1-diphenyl-1-heptene (8). ADAM 8 inhibited the cytopathic effect of HIV-1 in CEM cell culture with an EC(50) value of 7.1 mu M and was active against an array of laboratory strains of HIV-1 in CEM-SS and MT-4 cells, but was inactive as an inhibitor of HIV-2. In common with the other known non-nucleoside reverse transcriptase inhibitors, ADAM 8 was an effective inhibitor of HIV-1 reverse transcriptase (IC50 1 mu M) with poly(rC). oligo(dG), but not with poly(rA). oligo(dT), as the template/primer. ADAM 8 was inactive against HIV-1 reverse transcriptases containing non-nucleoside reverse transcriptase inhibitor resistance mutations at residues 101, 106, 108, 139, 181, 188, and 236, while it remained active against enzymes with mutations at residues 74, 98, 100, 103, and at 103/181. An AZT-resistant virus having four mutations in reverse transcriptase was more sensitive to inhibition by ADAM 8 than the wild-type HIV-1. In addition, ADAM 8 displayed synergistic activity with AZT, but lacked synergy with ddI. ADAM 8 or a structurally related analog may therefore be useful as an antiviral agent in combination with AZT or with other NNRTIs that are made ineffective by mutations at residues which do not confer resistance to ADAM 8. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB ANTIVIRAL DRUG MECH,SAIC FREDERICK,FREDERICK,MD 21702. SO RES INST,FREDERICK RES CTR,VIROL RES GRP,FREDERICK,MD 21701. RP Cushman, M (reprint author), PURDUE UNIV,SCH PHARM & PHARMACAL SCI,DEPT MED CHEM & MOLEC PHARMACOL,W LAFAYETTE,IN 47907, USA. FU NCI NIH HHS [N01-CM-17513, N01-CM-37818]; NIAID NIH HHS [R01-AI-36624] NR 69 TC 46 Z9 47 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 2 PY 1996 VL 39 IS 16 BP 3217 EP 3227 DI 10.1021/jm960082v PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VA564 UT WOS:A1996VA56400023 PM 8759644 ER PT J AU Cerritelli, ME Wall, JS Simon, MN Conway, JF Steven, AC AF Cerritelli, ME Wall, JS Simon, MN Conway, JF Steven, AC TI Stoichiometry and domainal organization of the long tail-fiber of bacteriophage T4: A hinged viral adhesin SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE adhesin; bacteriophage tail-fiber; molecular stoichiometry; scanning transmission electron microscopy; compute image processing ID TRANSMISSION ELECTRON-MICROSCOPY; MOLECULAR-STRUCTURE; PECTATE LYASE; COILED COILS; DISTAL HALF; PROTEIN; SEQUENCE; DNA; GENES; PRECURSORS AB The long-tail fibers (LTFs) form part of bacteriophage T4's apparatus for host cell recognition and infection, being responsible for its initial attachment to susceptible bacteria. The LTF has two parts, each similar to 70 to 75 nm long; gp34 (140 kDa) forms the proximal half-fiber, while the distal half-fiber is composed of gp37 (109 kDa), gp36 (23 kDa) and gp35 (30 kDa). LTFs have long been thought to be dimers of gp34,gp37 and gp36, with one copy of gp,35. We have used mass mapping by scanning transmission electron microscopy (STEM), quantitative SDS-PAGE, and computational sequence analysis to study the structures of purified LTFs and half-fibers of both kinds. These data establish that the LTF is, in fact, trimeric, with a stoichiometry of gp34: gp37: gp36: gp35 = 3:3:3:1. Averaged images of stained and unstained molecules resolve the LTF into a linear stack of 17 domains. At the proximal end is a globular domain of similar to 145 kDa that becomes incorporated into the baseplate. It is followed by a rod-like shaft (33 x 4 nm; 151 kDa) which correlates with a cluster of seven quasi repeats, each 34 to 39 residues long. The proximal half-fiber terminates in three globular domains. The distal half-fiber consists of ten globular domains of variable size and spacing, preceding a needle-like end domain (15 x 2.5 nm; 31 kDa). The LTF is rigid apart from hinges between the two most proximal domains, and between the proximal and distal half-fibers. The latter hinge occurs at a site of local non-equivalence (the ''kneecap'') at which density, correlated with the presence of gp35, bulges asymmetrically out on one side. Several observations indicate that gp34 participates in the sharing of conserved structural modules among coliphage tail-fiber genes to which gp37 was previously noted to subscribe. Two adjacent globular domains in the proximal half-fiber match a pair of domains in the distal half-fiber, and the rod domain in the proximal half-fiber resembles a similar domain in the T4 short tail-fiber (gp12). Finally, possible structures are considered; combining our data with earlier observations, the most likely conformation for most of the LTF is a three-stranded beta-helix. (C) 1996 Academic Press Limited C1 NIAMSD,NIH,STRUCT BIOL LAB,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 51 TC 65 Z9 70 U1 0 U2 2 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 AUG 2 PY 1996 VL 260 IS 5 BP 767 EP 780 DI 10.1006/jmbi.1996.0436 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VA248 UT WOS:A1996VA24800012 PM 8709154 ER PT J AU Hyman, SE AF Hyman, SE TI Shaking out the cause of addiction SO SCIENCE LA English DT Article RP Hyman, SE (reprint author), NIMH,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 8 TC 26 Z9 27 U1 0 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 AUG 2 PY 1996 VL 273 IS 5275 BP 611 EP 612 DI 10.1126/science.273.5275.611 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VA249 UT WOS:A1996VA24900036 PM 8701316 ER PT J AU Bulte, JWM Laughlin, PG Jordan, EK Tran, VA Vymazal, J Frank, JA AF Bulte, JWM Laughlin, PG Jordan, EK Tran, VA Vymazal, J Frank, JA TI Tagging of T cells with superparamagnetic iron oxide: Uptake kinetics and relaxometry SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Symposium CY JUN 17-22, 1995 CL NAANTALI, FINLAND ID DEXTRAN-MAGNETITE PARTICLES; MR; LYMPHOCYTES C1 NINCDS,NEUROIMAGING BRANCH,NIH,BETHESDA,MD 20892. RP Bulte, JWM (reprint author), NIH,LAB DIAGNOST RADIOL RES,OFF INTRAMURAL RES,BLDG 10,RM B1N256,10 CTR DR,MSC 1074,BETHESDA,MD 20892, USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 8 TC 37 Z9 37 U1 0 U2 3 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S301 EP S303 DI 10.1016/S1076-6332(96)80564-2 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700043 PM 8796587 ER PT J AU Dean Laubenberger Kawamura Brasch Lipton Wolf Kormano Unger Albrecht Blomley Moreau Mattay Mattrey deHaen Frank Maly AF Dean Laubenberger Kawamura Brasch Lipton Wolf Kormano Unger Albrecht Blomley Moreau Mattay Mattrey deHaen Frank Maly TI Perfusion imaging - Discussion 12 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 FUKUI MED SCH,FUKUI 91011,JAPAN. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. HAMMERSMITH HOSP,LONDON,ENGLAND. BRACCO SPA,MILAN,ITALY. NIH,BETHESDA,MD 20892. UNIV CHICAGO,MED CTR,CHICAGO,IL 60637. MGH,CIPR,CHARLESTOWN,MA. HOP NECKER ENFANTS MALAD,PARIS,FRANCE. UNIV CALIF SAN DIEGO,MED CTR,SAN DIEGO,CA 92103. MALMO GEN HOSP,S-21401 MALMO,SWEDEN. RP Dean (reprint author), UNIV TURKU,TURKU,FINLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S389 EP S391 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700072 ER PT J AU Dean Revel Adamzli Cavagna Li Wendland Blomley deHaen Frank Higgins AF Dean Revel Adamzli Cavagna Li Wendland Blomley deHaen Frank Higgins TI Advances in cardiac imaging - Discussion 13 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 MALLINCKRODT MED INC,ST LOUIS,MO. HAMMERSMITH HOSP,LONDON,ENGLAND. BRACCO SPA,MILAN,ITALY. NIH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. MD ANDERSON CANC CTR,HOUSTON,TX. HOP CARDIOVASC & PNEUMOL LOUIS PRADEL,LYON,FRANCE. RP Dean (reprint author), UNIV TURKU,TURKU,FINLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S407 EP S408 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700078 ER PT J AU Frank, JA Bash, C Stone, L Petrella, J Maloni, H McFarland, H AF Frank, JA Bash, C Stone, L Petrella, J Maloni, H McFarland, H TI Evaluation of magnetic resonance imaging sensitivity in patients with relapsing remitting multiple sclerosis: Baseline versus Betaseron treatment trials SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Symposium CY JUN 17-22, 1995 CL NAANTALI, FINLAND ID DISEASE-ACTIVITY; MRI C1 NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. HOSP UNIV PENN,PHILADELPHIA,PA 19104. RP Frank, JA (reprint author), NINCDS,LAB DIAGNOST RADIOL RES,OFF INTRAMURAL RES,NIH,BLDG 10,RM B1N256,10 CTR DR,MSC 1074,BETHESDA,MD 20854, USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S173 EP S175 DI 10.1016/S1076-6332(96)80525-3 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700004 PM 8796554 ER PT J AU Koenig Miyazawa McLachlan Li, C Muller Frija Bulte Adams Mattrey Davis Brady Saini AF Koenig Miyazawa McLachlan Li, C Muller Frija Bulte Adams Mattrey Davis Brady Saini TI Superparamagnetic contrast media - Discussion 7 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 MALLINCKRODT MED INC,ST LOUIS,MO. MASSACHUSETTS GEN HOSP,NMR CTR,CHARLESTOWN,MA. NIH,BETHESDA,MD 20892. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. FAC MED NECKER ENFANTS MALAD,PARIS,FRANCE. MD ANDERSON CANC CTR,HOUSTON,TX 77030. UNIV CALIF SAN DIEGO,MED CTR,SAN DIEGO,CA 92103. ADV MAGNET INC,PRINCETON,NJ. NIHON SCHERING KK,OSAKA,JAPAN. UNIV MONS HAINAUT,MONS,BELGIUM. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GUERBET SA,ROISSY,FRANCE. RP Koenig (reprint author), RELAXOMETRY INC,MAHOPAC,NY 10541, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S304 EP S307 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700044 ER PT J AU Koenig Siegle Frank Davis Grabowski Unger Kawamura Bulte Schlief Alexander Mattrey Bettman Muller Miyazawa Sovak AF Koenig Siegle Frank Davis Grabowski Unger Kawamura Bulte Schlief Alexander Mattrey Bettman Muller Miyazawa Sovak TI Development of new contrast agents - Discussion 11 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 NIH,BETHESDA,MD 20892. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FUKUI MED SCH,FUKUI 91011,JAPAN. UNIV UTAH,SALT LAKE CITY,UT. DARTMOUTH HITCHCOCK MED CTR,LEBANON,NH 03766. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. SCHERING AG,D-1000 BERLIN,GERMANY. UNIV CALIF SAN DIEGO,MED CTR,SAN DIEGO,CA 92103. UNIV MONS,B-7000 MONS,BELGIUM. NIHON SCHERING KK,OSAKA,JAPAN. BIOPHYSICA,LA JOLLA,CA. RP Koenig (reprint author), RELAXOMETRY INC,MAHOPAC,NY 10541, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S373 EP S375 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700067 ER PT J AU Lasser Adams Grabowski Kallio Albrecht Jakobsen Moreau MetzgerRose Mattrey Bettmann Schlief Unger Schneider Mulvagh Witter LaFrance Thomsen AF Lasser Adams Grabowski Kallio Albrecht Jakobsen Moreau MetzgerRose Mattrey Bettmann Schlief Unger Schneider Mulvagh Witter LaFrance Thomsen TI Progress in contrast enhanced ultrasonic imaging - Discussion 8 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 MALLINCKRODT MED INC,ST LOUIS,FRANCE. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. TURKU UNIV HOSP,FIN-20520 TURKU,FINLAND. HAMMERSMITH HOSP,LONDON,ENGLAND. DARTMOUTH HITCHCOCK MED CTR,LEBANON,NH 03766. BRACCO DIAGNOST INC,PRINCETON,NJ. UNIV OSLO,NATL HOSP,OSLO,NORWAY. UNIV ARIZONA,TUCSON,AZ. HOP NECKER ENFANTS MALAD,PARIS,FRANCE. NIH,BETHESDA,MD 20892. BRACCO RES SA,GENEVA,SWITZERLAND. SCHERING AG,D-1000 BERLIN,GERMANY. MAYO CLIN,ROCHESTER,MN. UNIV COPENHAGEN,HERLEV HOSP,DK-2730 HERLEV,DENMARK. RP Lasser (reprint author), UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S325 EP S327 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700051 ER PT J AU Mattay, VS Frank, JA Duyn, JH Kotrla, KJ Santha, AKS Esposito, G Sexton, RH Barker, P Sunderland, T Moonen, CTW Weinberger, DR AF Mattay, VS Frank, JA Duyn, JH Kotrla, KJ Santha, AKS Esposito, G Sexton, RH Barker, P Sunderland, T Moonen, CTW Weinberger, DR TI Three-dimensional ''BURST'' functional magnetic resonance imaging: Initial clinical applications SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Symposium CY JUN 17-22, 1995 CL NAANTALI, FINLAND ID POSITRON EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; ALZHEIMERS-DISEASE; BOLUS TRACKING; BLOOD-FLOW; MRI; SPECT C1 NIMH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIH,IN VIVO NMR RES CTR,BEIP,NCRR,BETHESDA,MD 20892. NIMH,SECT GERIATR PSYCHIAT,LCS,BETHESDA,MD 20892. RP Mattay, VS (reprint author), NIH,LAB DIAGNOST RADIOL RES,OIR,OD,BLDG 10,B1N 256,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 18 TC 4 Z9 4 U1 1 U2 1 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S379 EP S383 DI 10.1016/S1076-6332(96)80590-3 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700069 PM 8796608 ER PT J AU Abulafia, O Sherer, D AF Abulafia, O Sherer, D TI Longstanding ovarian serous cystadenofibroma sonographically mimicking a urachal cyst SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE magnetic resonance imaging; serous cystadenofibroma of the ovary; ultrasonography; urachal cyst ID ULTRASOUND DIAGNOSIS; ADULT C1 GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,NICHD,DIV INTRAMURAL,PERINATOL RES BRANCH,WASHINGTON,DC 20007. MARSHALL UNIV,DEPT OBSTET & GYNECOL,HUNTINGTON,WV. NR 12 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD AUG PY 1996 VL 75 IS 7 BP 685 EP 687 DI 10.3109/00016349609054701 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VG496 UT WOS:A1996VG49600021 PM 8822669 ER PT J AU Bilato, C Crow, MT AF Bilato, C Crow, MT TI Atherosclerosis and the vascular biology of aging SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE aging; atherosclerosis; endothelium; smooth muscle cell; vasculature ID SMOOTH-MUSCLE CELLS; AMERICAN-HEART-ASSOCIATION; AGE-RELATED-CHANGES; CONVERTING ENZYME-INHIBITION; ADHESION MOLECULE-1 VCAM-1; GLYCOSYLATION END-PRODUCTS; AORTIC ENDOTHELIAL-CELLS; FIBROBLAST GROWTH-FACTOR; NITRIC-OXIDE; CORONARY-ARTERY AB With advancing age, a series of struc tural, architectural and compositional modifications take place in the vasculature. The diameter of the vessels tends to increase, and thickening of intimal and medial layers is often observed. In the subendothelial space, blood-derived leukocytes and an increased amount of ''activated'' smooth muscle cells are present. Extracellular matrix accumulates and becomes particularly rich in glycosaminoglycans. Collagen content increases, while elastin fibers appear progressively disorganized, thinner, and frequently fragmented. These changes in the normal architecture of the vessel wall, that could be referred to as ''the vasculopathy of aging'', are likely to be the consequence of adaptive mechanisms to maintain normal conditions of flow, mechanical stress and/or wall tension. Although many of these features are similar to the histological findings of the atherosclerotic vessels, atherosclerosis and age-related ''vasculopathy'' are two distinct phenomena. Nonetheless, several experimental observations in animal models suggest a special link between ''the vasculopathy of aging'' and atherosclerosis disease, and suggest a particular predisposition of the old vessel to develop the atherosclerotic lesion. Compared to vessels from young animals, older ones show a greater reactivity to mechanical injury and to chronic insults. This may reflect changes in the biology of the vessels that are ''intrinsic'' to the aging process. Indeed, aging affects the function and responsiveness of the endothelium and vascular smooth muscle cells. Endothelial per meability is increased with age, while ability to produce vasoactive substances declines. Smooth muscle cells from old individuals show a growth advantage over the young ones, and display an increased ability to migrate toward chemoattractants. Moreover, the accumulation of advanced glycation end products (AGEs) occurring with aging can trigger a series of cellular events, such as cellular oxidative stress, expression of leukocyte adhesion molecules, endothelial transmigration of monocytes, and smooth muscle cell chemotaxis, all considered important prelesional events in the atherogenesis process. Taken together, the changes occurring with aging, while unproven to initiate lesion formation per se, are likely to accelerate the development of the atherosclerotic plaque and contribute to increased severity of this disease in the elderly. (C)1996, Editrice Kurtis RP Bilato, C (reprint author), NIA,VASC BIOL UNIT,CARDIOVASC SCI LAB,GERONTOL RES CTR,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 131 TC 68 Z9 69 U1 0 U2 6 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD AUG PY 1996 VL 8 IS 4 BP 221 EP 234 PG 14 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA VK199 UT WOS:A1996VK19900002 PM 8904951 ER PT J AU Chougnet, CA Margolis, D Landay, AL Kessler, HA Shearer, GM AF Chougnet, CA Margolis, D Landay, AL Kessler, HA Shearer, GM TI Contribution of prostaglandin E(2) to the interleukin-12 defect in HIV-infected patients SO AIDS LA English DT Letter ID PROLIFERATIVE RESPONSE; CYTOKINE SECRETION; LYMPHOCYTE-T; CELLS; MODULATION; MONOCYTES; INDUCTION; TH1 C1 UNIV MARYLAND,INST BIOTECHNOL,CTR MED BIOTECHNOL,BALTIMORE,MD 21201. RUSH MED COLL,DEPT IMMUNOL MICROBIOL,CHICAGO,IL 60612. RUSH MED COLL,DEPT MED,CHICAGO,IL 60612. RP Chougnet, CA (reprint author), NCI,EXPT IMMUNOL BRANCH,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 16 TC 7 Z9 7 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD AUG PY 1996 VL 10 IS 9 BP 1043 EP 1045 DI 10.1097/00002030-199610090-00018 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VA502 UT WOS:A1996VA50200018 PM 8853741 ER PT J AU Seelig, MS Elin, RJ AF Seelig, MS Elin, RJ TI Is there a place for magnesium in the treatment of acute myocardial infarction? SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Symposium on Cardiovascular Medicine-Acute Myocardial Infarction - The Importance of Magnesium as a Pharmacological Agent, at the 5th European Magnesium Congress CY JUN 16, 1995 CL VIENNA, AUSTRIA ID ISCHEMIC-HEART-DISEASE; INTRAVENOUS-MAGNESIUM; RANDOMIZED TRIALS; ARRHYTHMIAS; SULFATE; THERAPY; REPERFUSION; INFUSION; MODEL; MORTALITY AB Infusions of solutions of magnesium sulfate for patients with acute myocardial infarction were shown by a meta-analysis of seven small studies and a larger study of 2316 patients (LIMIT-2) to have clinical efficacy. However, the ISIS-4 study of 58,050 patients found no improvement in short-term mortality rates with magnesium therapy in patients with acute myocardial infarction. In this article we explore the following four differences between the ISIS-4 study and the earlier studies: (1) Time of initiation of magnesium treatment after acute myocardial infarction and thrombolytic therapy; (2) dosage of magnesium in the first 24 hours after acute myocardial infarction; (3) duration of magnesium infusion after acute myocardial infarction; and (4) differences in patient risks in control and treatment groups. These four differences may explain the different outcomes among these studies and indicate the type of additional studies that are needed to define the clinical utility of magnesium infusion in the treatment of patients with acute myocardial infarction. C1 NIH,DEPT CLIN PATHOL,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. UNIV N CAROLINA,SCH PUBL HLTH,CHAPEL HILL,NC. NR 73 TC 16 Z9 17 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 AUG PY 1996 VL 132 IS 2 BP 471 EP 477 DI 10.1016/S0002-8703(96)90338-5 PN 2 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VA492 UT WOS:A1996VA49200003 PM 8694006 ER PT J AU Smetana, R Laggner, A Antman, EM Balkin, J Charbon, G Dienstl, F Elin, RJ Glogar, D McGuigan, JAS Kunert, M Seelig, MS Shechter, M Tzivoni, D Weglicki, WB Wester, P AF Smetana, R Laggner, A Antman, EM Balkin, J Charbon, G Dienstl, F Elin, RJ Glogar, D McGuigan, JAS Kunert, M Seelig, MS Shechter, M Tzivoni, D Weglicki, WB Wester, P TI Consensus on future regimen of therapeutic strategies in acute myocardial infarction? Discussion SO AMERICAN HEART JOURNAL LA English DT Editorial Material C1 UNIV VIENNA,SCH MED,DEPT EMERGENCY MED,VIENNA,AUSTRIA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV CARDIOVASC,SAMUEL A LEVINE CARDIAC UNIT,BOSTON,MA 02115. SHAARE ZEDEK MED CTR,DEPT CARDIOL,JERUSALEM,ISRAEL. UNIV CLIN INNSBRUCK,INNSBRUCK,AUSTRIA. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. UNIV VIENNA,SCH MED,DEPT CARDIOL,CLIN INTERNAL MED,INVAS & INTERVENT CARDIOL UNIT,VIENNA,AUSTRIA. UNIV BERN,INST PHYSIOL,BERN,SWITZERLAND. UNIV WITTEN HERDECKE,HEART CTR WUPPERTAL,DEPT CARDIOL,WUPPERTAL,GERMANY. EMORY UNIV,ATLANTA,GA 30322. UNIV N CAROLINA,CHAPEL HILL,NC. TEL AVIV UNIV,TEL HASHOMER & SACKLER SCH MED,CHAIM SHEBA MED CTR,INST HEART,IL-69978 TEL AVIV,ISRAEL. GEORGE WASHINGTON UNIV,DEPT PHYSIOL,WASHINGTON,DC. RP Smetana, R (reprint author), UNIV VIENNA,SCH MED,CLIN INTERNAL MED,AUSTRIAN SOC MAGNESIUM RES,WAEHRINGER GUERTEL 18-20,A-1090 VIENNA,AUSTRIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 1996 VL 132 IS 2 BP 496 EP 502 PN 2 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VA492 UT WOS:A1996VA49200007 ER PT J AU Losonczy, KG Harris, TB Havlik, RJ AF Losonczy, KG Harris, TB Havlik, RJ TI Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: The established populations for epidemiologic studies of the elderly SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE vitamin E; antioxidants; supplements; elderly persons; coronary heart disease; mortality ID ANTIOXIDANT VITAMINS; CARDIOVASCULAR-DISEASE; IMMUNE-RESPONSE; SERUM SELENIUM; DIETARY-INTAKE; E CONSUMPTION; FOLLOW-UP; ATHEROSCLEROSIS; CANCER; WOMEN AB We examined vitamin E and vitamin C supplement use in relation to mortality risk and whether vitamin C enhanced the effects of vitamin E in 11 178 persons aged 67-105 y who participated in the Established Populations for Epidemiologic Studies of the Elderly in 1984-1993. Participants were asked to report all nonprescription drugs currently used, including vitamin supplements. Persons were defined as users of these supplements if they reported individual vitamin E and/or vitamin C use, not part of a multivitamin. During the follow-up period there were 3490 deaths. Use of vitamin E reduced the risk of all-cause mortality [relative risk (RR) = 0.66; 95% CI: 0.53, 0.83] and risk of coronary disease mortality (RR = 0.53; 95% CI: 0.34, 0.84). Use of vitamin E at two points in time was also associated with reduced risk of total mortality compared with that in persons who did not use any vitamin supplements. Effects were strongest for coronary heart disease mortality (RR = 0.37; 95% CI: 0.15, 0.90). The RR for cancer mortality was 0.41 (95% CI: 0.15, 1.08). Simultaneous use of vitamins E and C was associated with a lower risk of total mortality (RR = 0.58; 95% CI: 0.42, 0.79) and coronary mortality (RR = 0.47; 95% CI: 0.25, 0.87). Adjustment for alcohol use, smoking history, aspirin use, and medical conditions did not substantially alter these findings. These findings are consistent with those for younger persons and suggest protective effects of vitamin E supplements in the elderly. RP Losonczy, KG (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,GATEWAY BLDG,ROOM 3C-309,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 48 TC 255 Z9 260 U1 1 U2 8 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 1996 VL 64 IS 2 BP 190 EP 196 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UZ129 UT WOS:A1996UZ12900010 PM 8694019 ER PT J AU Sandlund, JT Miser, JS Miser, AW AF Sandlund, JT Miser, JS Miser, AW TI Sweet syndrome in a patient with osteosarcoma SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE neutrophilic dermatosis; sweet syndrome AB Neutrophilic dermatosis (Sweet syndrome) is a rare condition characterized by painful indurated cutaneous plaques infiltrated with mature neutrophils and may be accompanied by fever, granulocytosis, arthritis, and conjunctivitis. It is associated with various malignant and preneoplastic states, the most common being leukemia and myeloproliferative disorders. Its association with solid tumors is infrequent. The case described here represents, to our knowledge, the first report of Sweet syndrome in a patient with osteogenic sarcoma, a primary tumor of bone arising from mesenchymal cells. C1 NCI, PEDIAT BRANCH, WASHINGTON, DC USA. RP Sandlund, JT (reprint author), ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, 332 N LAUDERDALE ST, MEMPHIS, TN 38105 USA. FU NCI NIH HHS [CA 20180, CA 21765] NR 5 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD AUG PY 1996 VL 19 IS 4 BP 349 EP 350 DI 10.1097/00000421-199608000-00005 PG 2 WC Oncology SC Oncology GA UW941 UT WOS:A1996UW94100005 PM 8677902 ER PT J AU Bellissant, E Benichou, J Chastang, C AF Bellissant, E Benichou, J Chastang, C TI The group sequential triangular test for phase II cancer clinical trials SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE oncology; phase II noncomparative trials; group sequential method; triangular test ID CHEMOTHERAPY; PLANS AB In cancer, phase II clinical trials are usually noncomparative. Their purpose Is to determine whether a new chemotherapy is effective enough to warrant further evaluation in phase III. Therefore, in order to meet ethical requirements, decisionmaking methods must allow for early termination when inefficacy (or efficacy) is clear. We previously extended the Triangular Test, a group sequential method initially proposed for phase III trials, to phase II trials and demonstrated its advantages (i.e., type I error rate alpha and power close to the nominal values, reduction of the sample size) over other methods. The aim of this paper is to present the Triangular Test from a practical standpoint that will facilitate its application to phase II clinical trials in oncology. After summarizing the minimal theoretical knowledge required to use the method appropriately, we discuss its use in the design and analysis of a phase II cancer trial. C1 HOP ST LOUIS,DEPT BIOSTAT & INFORMAT MED,PARIS,FRANCE. NCI,BETHESDA,MD 20892. RP Bellissant, E (reprint author), CTR HOSP REG & UNIV RENNES PONTCHAILLOU,LAB PHARMACOL CLIN,AVE PROF LEON BERNARD,F-35043 RENNES,FRANCE. NR 25 TC 8 Z9 8 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD AUG PY 1996 VL 19 IS 4 BP 422 EP 430 DI 10.1097/00000421-199608000-00021 PG 9 WC Oncology SC Oncology GA UW941 UT WOS:A1996UW94100021 PM 8677918 ER PT J AU Folsom, AR Jacobs, DR Wagenknecht, LE Winkhart, SP Yunis, C Hilner, JE Savage, PJ Smith, DE Flack, JM AF Folsom, AR Jacobs, DR Wagenknecht, LE Winkhart, SP Yunis, C Hilner, JE Savage, PJ Smith, DE Flack, JM TI Increase in fasting insulin and glucose over seven years with increasing weight and inactivity of young adults - The CARDIA study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE exercise; glucose; insulin; longitudinal studies; obesity ID CORONARY HEART-DISEASE; UNITED-STATES POPULATION; DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE; RESISTANCE SYNDROME; PHYSICAL-ACTIVITY; FOLLOW-UP; HYPERINSULINEMIA; RISK; NIDDM AB To characterize 7-year changes in fasting serum insulin and glucose concentrations, the authors analyzed population-based data on 3,095 nondiabetic black and white men and women who were initially aged 18-30 years in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Measurements were made of fasting insulin (by an assay with little cross-reactivity to proinsulin) and fasting glucose on frozen samples from baseline and Year 7 examinations. Over the 7-year period, mean fasting insulin increased 10-25%, mean fasting glucose increased 7-10%, and mean body mass increased 7-12% across the four race-, sex-groups. The strongest predictor of both insulin increase and glucose increase was an increase in body mass over the 7 years. Adjusted for age and examination time period in race-, sex-specific repeated measures analyses, fasting insulin increased longitudinally by approximately 5 mu U/mL per 5 kg/m(2) increase in body mass index (p < 0.05). Adjusted for age and time period, fasting insulin increased over the 7 years by approximately 2.5 mu U/mL per 0.08 unit increase in waist/hip ratio (p < 0.05), although this association was much stronger cross-sectionally. In a similar model, each 100 unit decrease in physical activity longitudinally predicted a 0.1-0.2 mu U/mL increase in fasting insulin (p < 0.05 in black men only); this association was stronger and statistically significant in all race-, sex-groups cross-sectionally. Fasting insulin was not associated with energy intake either cross-sectionally or longitudinally, but age- and time-adjusted associations of insulin change with change in several nutrients (e.g., energy from fat) were statistically significant in whites. The authors conclude that marked increase in weight in young adulthood adversely alters glucose and insulin metabolism, and that, if not reversed, this may lead to harmful health consequences in later life. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV MINNESOTA,SCH MED,DEPT MED,DIV GEN & PREVENT MED,MINNEAPOLIS,MN 55455. UNIV ALABAMA,CARDIA COORDINATING CTR,BIRMINGHAM,AL. NHLBI,NIH,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV ALABAMA,DIV PREVENT MED,BIRMINGHAM,AL. BOWMAN GRAY SCH MED,HYPERTENS CTR,WINSTON SALEM,NC. RP Folsom, AR (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,SUITE 300,1300 S 2ND ST,MINNEAPOLIS,MN 55454, USA. FU NHLBI NIH HHS [N01-HC-48049, N01-HC-48047, N01-HC-48048] NR 46 TC 75 Z9 75 U1 0 U2 3 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 1 PY 1996 VL 144 IS 3 BP 235 EP 246 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UZ754 UT WOS:A1996UZ75400004 PM 8686692 ER PT J AU Lewis, CE Funkhouser, E Raczynski, JM Sidney, S Bild, DE Howard, BV AF Lewis, CE Funkhouser, E Raczynski, JM Sidney, S Bild, DE Howard, BV TI Adverse effect of pregnancy on high density lipoprotein (HDL) cholesterol in young adult women - The CARDIA study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE lipoproteins; lipoproteins, HDL cholesterol; parity; reproduction; women ID CORONARY HEART-DISEASE; DEPENDENT DIABETES-MELLITUS; REPRODUCTIVE HISTORY; DEHYDROEPIANDROSTERONE-SULFATE; POSTPARTUM LACTATION; LIPID-METABOLISM; 1ST PREGNANCY; INSULIN; PARITY; RISK AB The authors analyzed data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study in order to examine associations between parity and lipoproteins. Of 2,787 women recruited in 1985-1986, 2,534 (91%) returned in 1987-1988 and 2,393 (86%) returned in 1990-1991 for repeat evaluations, Two-year change (1987-1988 to 1985-1986) in high density lipoprotein (HDL) cholesterol was significantly different among the parity groups, HDL cholesterol decreased in women who had their first pregnancy of at least 28 weeks duration during follow-up (mean +/- standard error, -3.5 +/- 1.2 mg/dl), and this change was significantly different from the increase in women parous at baseline who had no further pregnancies (2.5 +/- 0.3 mg/dl) and in nullipara (2.4 +/- 0.3 mg/dl). There was a nonsignificant trend for a greater decrease in HDL(2) cholesterol fraction in the primipara compared with the other groups. The HDL cholesterol decrease remained significant after controlling for race, age, education, oral contraceptive use, and changes in body mass index, waist-hip ratio, physical activity, smoking status, and alcohol intake. Change in HDL cholesterol was also significantly different among the parity groups in analyses of pregnancies that occurred during the subsequent 3 years of follow-up, There were no differences for change in LDL cholesterol or triglycerides. Potential mechanisms for a detrimental effect of pregnancy on HDL cholesterol include hormonal, body composition, or life-style/behavioral changes. C1 UNIV ALABAMA,SCH PUBL HLTH,DEPT EPIDEMIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,SCH PUBL HLTH,DEPT HLTH BEHAV,BIRMINGHAM,AL 35294. KAISER PERMANENTE,DIV RES,OAKLAND,CA. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. MEDLANT RES INST,WASHINGTON,DC. RP Lewis, CE (reprint author), UNIV ALABAMA,DIV PREVENT MED,BEHAV MED UNIT,1717 11TH AVE S,ROOM 734,BIRMINGHAM,AL 35205, USA. FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049] NR 54 TC 35 Z9 35 U1 0 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 1 PY 1996 VL 144 IS 3 BP 247 EP 254 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UZ754 UT WOS:A1996UZ75400005 PM 8686693 ER PT J AU Ruttledge, MH Andermann, AA Phelan, CM Claudio, JO Han, FY Chretien, N Rangaratnam, S MacCollin, M Short, P Parry, D Michels, V Riccardi, VM Weksberg, R Kitamura, K Bradburn, JM Hall, BD Propping, P Rouleau, GA AF Ruttledge, MH Andermann, AA Phelan, CM Claudio, JO Han, FY Chretien, N Rangaratnam, S MacCollin, M Short, P Parry, D Michels, V Riccardi, VM Weksberg, R Kitamura, K Bradburn, JM Hall, BD Propping, P Rouleau, GA TI Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; TUMOR-SUPPRESSOR GENE; UNITED-KINGDOM; LENS OPACITIES; CHROMOSOME-22; DIAGNOSIS; INDIVIDUALS; ASSOCIATION; NEUROMAS; MARKERS AB The gene predisposing to neurofibromatosis type 2 (NF2) on human chromosome 22 has revealed a wide variety of different mutations in NF2 individuals. These patients display a marked variability in clinical presentation, ranging from very severe disease with numerous tumors at a young age to a relatively mild condition much later in life. To investigate whether this phenotypic heterogeneity is determined by the type of mutation in NF2, we have collected clinical information on 111 NF2 cases from 73 different families on whom we have performed mutation screening in this gene. Sixty-seven individuals (56.2%) from 41 of these kindreds revealed 36 different putative disease-causing mutations. These include 26 proposed protein-truncating alterations (frameshift deletions/insertions and nonsense mutations), 6 splice-site mutations, 2 missense mutations, 1 base substitution in the 3' UTR of the NF2 cDNA, and a single 3-bp in-frame insertion. Seventeen of these mutations are novel, whereas the remaining 19 have been described previously in other NF2 individuals or sporadic tumors. When individuals harboring protein-truncating mutations are compared with cases with single codon alterations, a significant correlation (P < .001) with clinical outcome is observed. Twenty-four of 28 patients with mutations that cause premature truncation of the NF2 protein, schwannomin, present with severe phenotypes. In contrast, all 16 cases from three families with mutations that affect only a single amino acid have mild NF2. These data provide conclusive evidence that a phenotype/genotype correlation exists for certain NF2 mutations. C1 MCGILL UNIV,UNIV DIV MED GENET,MONTREAL,PQ,CANADA. KAROLINSKA HOSP,DEPT MOL MED,ENDOCRINE TUMOR UNIT,S-10401 STOCKHOLM,SWEDEN. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA. NATL CANC INST,GENET EPIDEMIOL BRANCH,BETHESDA,MD. MAYO CLIN,DEPT GENET,ROCHESTER,MN. NEUROFIBROMATOSIS INST,LA CRESCENTA,CA. HOSP SICK CHILDREN,GENET CLIN,TORONTO,ON M5G 1X8,CANADA. JICHI MED SCH,DEPT OTOLARYNGOL,MINAMI KAWACHI,TOCHIGI,JAPAN. UNIV KENTUCKY,KENTUCKY CLIN,DEPT PEDIAT GENET,LEXINGTON,KY. UNIV BONN,INST HUMAN GENET,D-5300 BONN,GERMANY. RP Ruttledge, MH (reprint author), MONTREAL GEN HOSP,RES INST,CTR RES NEUROSCI,7TH FLOOR,LIVINGSTON HALL,1650 CEDAR AVE,MONTREAL,PQ H3G 1A4,CANADA. NR 24 TC 171 Z9 176 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 1996 VL 59 IS 2 BP 331 EP 342 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA VM288 UT WOS:A1996VM28800008 PM 8755919 ER PT J AU Shimkets, R Gailani, MR Siu, VM YangFeng, T Pressman, CL Levanat, S Goldstein, A Dean, M Bale, AE AF Shimkets, R Gailani, MR Siu, VM YangFeng, T Pressman, CL Levanat, S Goldstein, A Dean, M Bale, AE TI Molecular analysis of chromosome 9q deletions in two Gorlin syndrome patients SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CELL CARCINOMA SYNDROME; BASAL; GENE; RETINOBLASTOMA AB Gorlin syndrome is an autosomal dominant disorder characterized by multiple basal cell carcinomas, medulloblastomas, ovarian fibromas, and a variety of developmental defects. All affected individuals share certain key features, but there is significant phenotypic variability within and among kindreds with respect to malformations. The gene (NBCCS) maps to chromosome 9q22, and allelic loss at this location is common in tumors from Gorlin syndrome patients. Two recessive cancer-predisposition syndromes, xeroderma pigmentosum group A (XPAC) and Fanconi anemia group C (FACC), map to the NBCCS region; and unusual, dominant mutations in these genes have been proposed as the cause of Gorlin syndrome. This study presents cytogenetic and molecular characterization of germ-line deletions in one patient with a chromosome 9q22 deletion and in a second patient with a deletion of 9q22-q31. Both have typical features of Gorlin syndrome plus additional findings, including mental retardation, conductive hearing loss, and failure to thrive. That Gorlin syndrome can be caused by null mutations (deletions) rather than by activating mutations has several implications. First, in conjunction with previous analyses of allelic loss in tumors, this study provides evidence that associated neoplasms arise with homozygous inactivation of the gene. In addition, dominant mutations of the XPAC and FACC1 genes can be ruled out as the cause of Gorlin syndrome, since the two patients described have null mutations. Finally, phenotypic features that show variable expression must be influenced by genetic background, epigenetic effects, somatic mutations, or environmental factors, since these two patients with identical alterations (deletions) of the Gorlin syndrome gene have somewhat different manifestations of Gorlin syndrome. C1 YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06520. UNIV WESTERN ONTARIO,LONDON,ON,CANADA. NATL CANC INST,GENET EPIDEMIOL BRANCH,BETHESDA,MD. NATL CANC INST,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [K11 CA 60199, R01 CA57605] NR 28 TC 47 Z9 48 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 1996 VL 59 IS 2 BP 417 EP 422 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA VM288 UT WOS:A1996VM28800018 PM 8755929 ER PT J AU Strass, E McCabe, ERB Biesecker, L Cassidy, S Chakravarti, A Grody, W Juengst, E Khory, M Knoppers, BM Motulsky, A Phillips, JA Spence, MA AF Strass, E McCabe, ERB Biesecker, L Cassidy, S Chakravarti, A Grody, W Juengst, E Khory, M Knoppers, BM Motulsky, A Phillips, JA Spence, MA TI ASHG REPORT - Statement on informed consent for genetic research SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,SCH MED,CTR HUMAN GENET,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,DEPT GENET,CLEVELAND,OH 44106. UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL & LAB MED,LOS ANGELES,CA 90024. CASE WESTERN RESERVE UNIV,SCH MED,CTR BIOMED ETH,CLEVELAND,OH 44106. CTR DIS CONTROL,DIV BIRTH DEFECTS & DEV DISABIL,ATLANTA,GA 30333. UNIV MONTREAL,SCH LAW,CTR RES PUBL LAW,MONTREAL,PQ H3C 3J7,CANADA. UNIV WASHINGTON,DEPT GENET,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. VANDERBILT UNIV,MED CTR,DIV GENET,NASHVILLE,TN. UNIV CALIF IRVINE,MED CTR,DEPT PEDIAT,IRVINE,CA 92717. RP Strass, E (reprint author), AMER SOC HUMAN GENET,9650 ROCKVILLE PIKE,BETHESDA,MD 20814, USA. NR 6 TC 98 Z9 98 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 1996 VL 59 IS 2 BP 471 EP 474 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VM288 UT WOS:A1996VM28800025 ER PT J AU Ward, EM Ruder, AM Suruda, A Smith, AB FesslerFlesch, CA Zahm, SH AF Ward, EM Ruder, AM Suruda, A Smith, AB FesslerFlesch, CA Zahm, SH TI Acute and chronic liver toxicity resulting from exposure to chlorinated naphthalenes at a cable manufacturing plant during World War II SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE chlorinated naphthalenes; chloracne; cirrhosis; cohort mortality study; epidemiology; occupational health ID TABLE ANALYSIS SYSTEM; POLYCHLORINATED-BIPHENYLS; CHEMICAL WORKERS; CANCER MORTALITY; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; CIRRHOSIS; ALCOHOL; FEMALE; COHORT; RATS AB Historical records were used to reconstruct an outbreak of chloracne and acute liver toxicity due to chlorinated naphthalene exposure at a New York State plant which manufactured ''Navy cables'' during World War II. A cohort mortality study was conducted of the population (n = 9,028) employed at the plant from 1940 to 1944. Vital status was followed through December 31, 1985. The study found an excess of deaths from cirrhosis of the liver [observed (OBS) = ISO; standardized mortality ratio (SMR) = 1.84; 95% confidence interval (CI) = 1.56-2.16]; cirrhosis deaths were elevated to a similar degree in the 460 individuals who had chloracne (OBS = 8; SMR = 1.51; CI = 0.65-2.98). The SMR for ''non-alcoholic cirrhosis'' (OBS = 83; SMR = 1.67; CI = 1.33-2.07) was similar to the SMR for ''alcoholic cirrhosis'' (OBS = 59; SMR = 1.96; CI = 1.49-2.53). There was no evidence for increased alcoholism in the overall cohort based on mortality from alcohol-related causes of death other than cirrhosis (SMR for esophageal cancer = 1.01 and for deaths from alcoholism = 0.99). We conclude that the excess mortality from cirrhosis of the liver observed in this cohort is due to the chronic effect of chlorinated naphthalene exposure. (C) 1996 Wiley-Liss, Inc. C1 NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,BETHESDA,MD 20892. RP Ward, EM (reprint author), NIOSH,DIV SURVEILLANCE HAZARD EVALUAT & FIELD STUDIES,INDUSTRYWIDE STUDIES BRANCH,CINCINNATI,OH 45226, USA. RI Ruder, Avima/I-4155-2012; Zahm, Shelia/B-5025-2015 OI Ruder, Avima/0000-0003-0419-6664; NR 27 TC 6 Z9 6 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD AUG PY 1996 VL 30 IS 2 BP 225 EP 233 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VA198 UT WOS:A1996VA19800015 PM 8844054 ER PT J AU Striker, GE AF Striker, GE TI NIDDK releases 1996 Renal Data report SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article RP Striker, GE (reprint author), NIDDKD,DIV KIDNEY UROL & HEMATOL DIS,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 1996 VL 28 IS 2 BP 305 EP 306 DI 10.1016/S0272-6386(96)90319-4 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA VA600 UT WOS:A1996VA60000023 ER PT J AU Link, CJ Reed, E Sarosy, G Kohn, EC AF Link, CJ Reed, E Sarosy, G Kohn, EC TI Borderline ovarian tumors SO AMERICAN JOURNAL OF MEDICINE LA English DT Review ID MALIGNANT POTENTIAL BORDERLINE; GYNECOLOGIC-ONCOLOGY-GROUP; EPITHELIAL TUMORS; PERITONEAL IMPLANTS; SEROUS TUMORS; DNA CONTENT; PROGNOSTIC-SIGNIFICANCE; HISTOLOGIC FEATURES; NUCLEAR MORPHOLOGY; LOW-GRADE AB Borderline tumor of the ovary (BOT) is an epithelial tumor with a low rate of growth and a low potential to invade or metastasize. This tumor often is associated with a significantly better prognosis than epithelial ovarian cancer. Most tumors are either serous or mucinous in histology and present as early stage lesions. However, stage III lesions with peritoneal implants are not uncommon. Patients with early stage lesions have an excellent prognosis. Patients with higher stage lesions have a worse prognosis. Long-term follow-up of patients with BOT is required since the tumor can recur up to 20 years after the initial diagnosis. Recently, investigators have begun to identify subsets of patients with a worse prognosis, such as patients with aneuploid tumors. Treatment for early stage lesions is surgical and conservative surgery can be accomplished successfully in younger patients who desire to maintain fertility. Treatment for later stage lesions has been approached in a variety of ways. All approaches initially begin with maximal cytoreductive surgery. Studies suggest that early stage disease should be managed with surgery alone. Conflicting results on the usefulness of adjuvant therapy for patients with later stage disease have been obtained. At this time, the usefulness of adjuvant therapy for advanced disease remains undetermined. Further understanding of the basis of the disease and analysis of specific higher risk subsets might identify patients in whom adjuvant therapy could be tested in the setting of controlled clinical trials. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RP Link, CJ (reprint author), CENT IOWA HLTH SYST,HGTRI,GENE THERAPY PROGRAM,1417 WOODLAND AVE,DES MOINES,IA 50325, USA. NR 70 TC 47 Z9 47 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 AUG PY 1996 VL 101 IS 2 BP 217 EP 225 DI 10.1016/S0002-9343(96)80079-9 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA VC319 UT WOS:A1996VC31900014 PM 8757363 ER PT J AU Berry, SM Romero, R Bianchi, DW AF Berry, SM Romero, R Bianchi, DW TI Activation of the fetal immune system: Marker of imminent delivery or of intrauterine infection? Reply SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 NICHHD,PERINATOL RES BRANCH,WASHINGTON,DC 20007. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02125. TUFTS UNIV,SCH MED,BOSTON,MA 02125. RP Berry, SM (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 1996 VL 175 IS 2 BP 501 EP 502 DI 10.1016/S0002-9378(96)70171-0 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VF643 UT WOS:A1996VF64300063 ER PT J AU SantoniRugiu, E Nagy, P Jensen, MR Factor, VM Thorgeirsson, SS AF SantoniRugiu, E Nagy, P Jensen, MR Factor, VM Thorgeirsson, SS TI Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-alpha SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HEPATITIS-B VIRUS; HUMAN HEPATOCELLULAR-CARCINOMA; BETA MESSENGER-RNA; CELL DYSPLASIA; PLASMINOGEN-ACTIVATOR; EPITHELIAL-CELLS; RAT-LIVER; CHEMICAL HEPATOCARCINOGENESIS; REGRESSING LIVER; ELEVATED LEVELS AB We have previously shown that co-expression of c-myc and transforming growth factor (TGF)-alpha as transgenes in mouse liver results in major enhancement of neoplastic development in this organ as compared with expression of either of these transgenes alone. In this report we describe in detail the progression from liver cell dysplasia to hepatocellular carcinomas (HCCs) occurring in the liver of c-myc/TGF-alpha and c-myc transgenic mice. Despite morphological similarities in the sequence of events between the two transgenic lines, the dramatic acceleration, extent, and severity of hepatic lesions in c-myc/TGF-alpha mice clearly demonstrated the synergistic effects of this transgenic combination. Although c-myc/TGP-alpha and c-myc females displayed longer latency and lower tumor incidence, the pathological changes were the same as those seen in the male mice, including the formation of HCCs, which are absent in TGF-alpha single-transgenic females. Tumors in single- and double-transgenic mice showed induction of the endogenous c-myc and TGF-alpha and, most frequently, unchanged or decreased epidermal growth factor receptor, further indicating the collaborative role of c-myc and TGF-alpha in providing a selective growth advantage to tumor cells independently of the epidermal growth factor receptor levels. To identify Possible tumor precursors, we focused particularly on the dysplastic changes Preceding and accompanying the appearance of preneoplastic and neoplastic lesions in the double-transgenic mice. Early on, these changes were characterized by the appearance of large dysplastic hepatocytes, mostly pericentrally, expressing high levels of TGF-alpha and uPA, as wed as TGF-beta 1, particularly in apoptotic cells. After a short period of replication and expansion into the liver parenchyma, as well as penetration into the central veins, these cells underwent apoptotic cea death while preneoplastic and neoplastic lesions were forming. The peritumorous tissues also contained small dysplastic hepatocytes and oval-like cells, similar to those found in the tumors. Transplantation of the transgenic liver tissues harboring only dysplasia with or without vascular lesions onto nude mice was able to yield HCCs composed of small diploid cells, suggesting that initiated cells are generated during the early dysplastic phase and can progress to HCC. It is therefore likely that large dysplastic hepatocytes undergo apoptosis, which may be closely associated with the up-regulation of TGF-beta 1 and uPA, whereas other cells evolve into the precursor population for HCC. Due to the simultaneous presence of c-myc, TGF-alpha, and dysplasia in premalignant human liver diseases, our transgenic mouse system appears to be an appropriate model for studying human hepatocarcinogenesis. C1 NCI,EXPTL CARCINOGENESIS LAB,DIV BASIC SCI,NATL INST HLTH,BETHESDA,MD 20892. RI Jensen, Michael/E-9677-2011 NR 81 TC 97 Z9 99 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1996 VL 149 IS 2 BP 407 EP 428 PG 22 WC Pathology SC Pathology GA UZ763 UT WOS:A1996UZ76300007 PM 8701981 ER PT J AU Guinee, D Fleming, M Hayashi, T Woodward, M Zhang, J Walls, J Koss, M Ferrans, V Travis, W AF Guinee, D Fleming, M Hayashi, T Woodward, M Zhang, J Walls, J Koss, M Ferrans, V Travis, W TI Association of p53 and WAF1 expression with apoptosis in diffuse alveolar damage SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; TUMOR-SUPPRESSOR GENE; ACUTE LUNG INJURY; FREE-RADICALS; INTERSTITIAL PNEUMONIA; OXYGEN PNEUMONITIS; G(1) ARREST; DNA-DAMAGE; IN-VIVO; RADIATION AB Little is known about alterations in cell cycle regulatory proteins such as p53 and WAF1 in diffuse alveolar damage (DAD). We hypothesized that upregulation of p53 and WAF1 in type II pneumocytes in DAD is associated with underlying DNA damage and apoptosis. Twenty cases of DAD and twenty control specimens of lung adjacent to resected tumors were studied Immunohistochemical stains with antibodies recognizing p53 and WAF1 were performed, and apoptosis was assessed in sixteen cases by the nick end-labeling method. We identified p53 expression and apoptosis in all cases of DAD but not in any of the control lungs We detected WAF1 expression at nineteen of twenty cases of DAD and in sixteen of twenty control lungs. In general the distribution and intensity of WAF1 staining were greater in DAD than in control lungs. Staining for both p53 and WAF1 and labeling of apoptotic cells in DAD were usually focal (<10% of cells) and predominantly localized in type II pneumocytes. We conclude that increased p53 and WAF1 expression in DAD reflects normal physiological up-regulation in response to cellular and DNA damage and is associated with apoptosis of type II pneumocytes. p53-dependent apoptosis may contribute to the pathogenesis of this disease. C1 ARMED FORCES INST PATHOL,DEPT PULM & MED PATHOL,WASHINGTON,DC. NIH,BETHESDA,MD 20892. UNIV CALIF DAVIS,DEPT PATHOL,DAVIS,CA 95616. RP Guinee, D (reprint author), UNIV UTAH,MED CTR,DEPT PATHOL,50 N MED DR,SALT LAKE CITY,UT 84132, USA. NR 62 TC 79 Z9 79 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1996 VL 149 IS 2 BP 531 EP 538 PG 8 WC Pathology SC Pathology GA UZ763 UT WOS:A1996UZ76300018 PM 8701992 ER PT J AU Martinez, A Treston, AM Saldise, L Montuenga, LM Linnoila, RI AF Martinez, A Treston, AM Saldise, L Montuenga, LM Linnoila, RI TI Expression of peptidyl-glycine alpha-amidating mono-oxygenase (PAM) enzymes in morphological abnormalities adjacent to pulmonary tumors SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID LUNG-CANCER; FUNCTIONAL EXPRESSION; BRONCHIAL EPITHELIUM; MESSENGER-RNA; ADENOCARCINOMA; HYPERPLASIA; CELL; MONOOXYGENASE; LOCALIZATION; ASSOCIATION AB Carboxyl-terminal amidated peptide hormones are known to be autocrine growth factors for lung tumors and tumor cell lines. Expression of the enzymes necessary for the biosynthesis of active amidated peptide hormones is therefore necessary for autocrine growth stimulation in lung tumors and possibly in the early proliferative stages of lung carcinogenesis. The peptidyl amidating enzymes have previously been identified in cell lines of all histological types of lung cancer and in lung tumors by immunohistochemistry and in situ hybridization. In this study we analyzed the expression of the peptidyl amidating enzymes in histological abnormalities found in the proximity of pulmonary tumors from a series of 59 patients. Most of the lesions in both the proximal airways (basal cell hyperplasia, carcinoma in situ, and some squamous metaplasia) and the alveoli (type II cell hyperplasia, bronchiolization of the alveoli, atypical alveolar hyperplasia, and isolated atypias) had a high proportion of cells strongly positive for the peptidyl amidating enzymes. The intense expression of peptidyl amidating enzymes in type II cell hyperplasia and atypical alveolar cells, together with the high frequency of these abnormalities in the alveoli, which is an area that does not express these enzymes in normal lung, points to the involvement of peptide hormones in the growth biology of pulmonary tumors. These findings suggest that peptide hormone stimulation of mitogenesis is an early event in tumor progression and merits additional investigation as a target for early detection and chemo-intervention of lung carcinogenesis. C1 UNIV NAVARRA,DEPT HISTOL & PATHOL,E-31080 PAMPLONA,SPAIN. RP Martinez, A (reprint author), NCI,BIOMARKERS & PREVENT RES BRANCH,DIV CLIN SCI,NIH,9610 MED CTR DR,ROOM 300,ROCKVILLE,MD 20850, USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 43 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1996 VL 149 IS 2 BP 707 EP 716 PG 10 WC Pathology SC Pathology GA UZ763 UT WOS:A1996UZ76300034 PM 8702008 ER PT J AU Etgen, GJ Wilson, CM Jensen, J Cushman, SW Ivy, JL AF Etgen, GJ Wilson, CM Jensen, J Cushman, SW Ivy, JL TI Glucose transport and cell surface GLUT-4 protein in skeletal muscle of the obese Zucker rat SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin; insulin resistance; diabetes; muscle contraction; glycogen ID INSULIN RESISTANCE; PLASMA-MEMBRANES; EXERCISE; TRANSLOCATION; CONTRACTION; INCREASES; MECHANISM; DISTINCT; INVITRO; NUMBER AB The relationship between 3-O-methyl-D-glucose transport and 2-N-4-(1-azi-2,2,2-trifluoroethyl)-benzoyl-1,3-bis-(D-mannos-4-yloxy)-2-propylamine (ATB-BMPA)-labeled cell surface GLUT-4 protein was assessed in fast-twitch (epitrochlearis) and slow-twitch (soleus) muscles of lean and obese (f alpha/f alpha) Zucker rats. In the absence of insulin, glucose transport as well as cell surface GLUT-4 protein was similar in both epitrochlearis and soleus muscles of lean and obese rats. In contrast, insulin-stimulated glucose transport rates were significantly higher far lean than obese rats in both soleus (0.74 +/- 0.05 vs. 0.40 +/- 0.02 mu mol . g(-1) . 10 min(-1)) and epitrochlearis (0.51 +/- 0.05 vs. 0.17 +/- 0.02 mu mol . g(-1) . 10 min(-1)) muscles. The ability of insulin to enhance glucose transport in fast- and slow-twitch muscles from both lean and obese rats corresponded directly with changes in cell surface GLUT-4 protein. Muscle contraction elicited similar increases in glucose transport in lean and obese rats, with the effect being more pronounced in fast-twitch (0.70 +/- 0.07 and 0.77 +/- 0.04 mu mol . g(-1) . 10 min(-1) for obese and lean, respectively) than in slow-twitch muscle (0.36 +/- 0.03 and 0.40 +/- 0.02 mu mol . g(-1) . 10 min(-1) for obese and lean, respectively). The contraction-induced changes in glucose transport directly corresponded with the observed changes in cell surface GLUT-4 protein. Thus the reduced glucose transport response to insulin in skeletal muscle of the obese Zucker rat appears to result directly from an inability to effectively enhance cell surface GLUT-4 protein. C1 UNIV TEXAS, DEPT KINESIOL, EXERCISE PHYSIOL & METAB LAB, AUSTIN, TX 78712 USA. NIDDKD, EXPT DIABET METAB & NUTR SECT, DIABET BRANCH, BETHESDA, MD 20892 USA. RI Jensen, Jorgen/O-2245-2013 NR 35 TC 72 Z9 74 U1 0 U2 0 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 AUG PY 1996 VL 271 IS 2 BP E294 EP E301 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA VD647 UT WOS:A1996VD64700012 PM 8770023 ER PT J AU Sherman, A AF Sherman, A TI Contributions of modeling to understanding stimulus-secretion coupling in pancreatic beta-cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Review DE glucose metabolism; bursting electrical activity; insulin; gap junctions; endoplasmic reticulum; muscarinic receptors; inositol 1,4,5-trisphosphate ID BURSTING ELECTRICAL-ACTIVITY; SENSITIVE K+ CHANNELS; B-CELLS; INSULIN-SECRETION; CA2+ OSCILLATIONS; CALCIUM INFLUX; IN-SITU; MOUSE; GLUCOSE; ISLETS AB Mechanisms of ionic control of insulin secretion in beta-cells of the pancreatic islets of Langerhans are reviewed. The focus is on aspects that have been treated by mathematical models, especially those related to bursting electrical activity. The study of these mechanisms is difficult because of the need to consider ionic fluxes, calcium handling, metabolism, and Electrical coupling with other cells in the islet. The data came either from islets, where experimental maneuvers tend to have multiple effects, or from isolated cells, which have degraded electrical activity and secretory sensitivity. Modeling aids in the process by integrating data on individual components such as channels and calcium handling and testing hypotheses for coherence and quantitative plausibility. The study of a variety of models has led to some general mathematical results that have yielded qualitative model-independent insights. RP Sherman, A (reprint author), NIDDK, NIH,MRB BSA BLDG,SUITE 350,9190 WISCONSIN AVE, MSC 269, BETHESDA, MD 20892 USA. NR 70 TC 48 Z9 48 U1 0 U2 0 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 AUG PY 1996 VL 271 IS 2 BP E362 EP E372 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA VD647 UT WOS:A1996VD64700021 PM 8770032 ER PT J AU Tataranni, PA Larson, DE Snitker, S Young, JB Flatt, JP Ravussin, E AF Tataranni, PA Larson, DE Snitker, S Young, JB Flatt, JP Ravussin, E TI Effects of glucocorticoids on energy metabolism and food intake in humans SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE hypothalamic-pituitary-adrenal axis; obesity; methylprednisolone; appetite; sympathetic nervous system ID SYMPATHETIC NERVOUS-SYSTEM; CORTICOTROPIN-RELEASING FACTOR; NEUROPEPTIDE-Y; DIETARY-FAT; EXPENDITURE; OBESITY; BALANCE; TISSUE; MEN; CATECHOLAMINES AB The effect of glucocorticoid administration on energy metabolism and food intake was studied in 20 healthy, nondiabetic Caucasian male volunteers [27 +/- 5 (SD) yr, 72 +/- 9 kg, 20 +/- 7% body fat] randomly and blindly assigned to glucocorticoid (methylprednisolone, METH; n = 10) or placebo (PLAC; n = 10) treatment. Each subject was studied twice: during a weight maintenance diet and during ad libitum food intake. Energy metabolism was measured by indirect calorimetry and food intake by an automated food-selection system. Twenty-four-hour urinary norepinephrine excretion (24-h NE) was used as an estimate of sympathetic nervous system activity. During weight maintenance, METH intravenous infusion (125 mg/30 min) increased energy expenditure compared with PLAC, and after 4 days of oral therapy, METH (40 mg/day) decreased 24-h NE and increased energy expenditure compared with PLAC. During ad libitum food intake, after 4 days of METH (40 mg/day) or PLAC oral therapy, both groups increased their energy intake over weight maintenance, but the increase was significantly larger in the METH group compared with the PLAC group (4,554 +/- 1,857 vs. 2,867 +/- 846 kcal/day; P = 0.04). Our data suggest that therapeutic doses of glucocorticoids induce obesity mostly by increasing energy intake, an effect which may be related to the ability of glucocorticoids to act directly or indirectly on the central regulation of appetite. C1 NW MED SCH, CHICAGO, IL 60611 USA. UNIV MASSACHUSETTS, SCH MED, DEPT BIOCHEM & MOL BIOL, WORCESTER, MA 01655 USA. RP Tataranni, PA (reprint author), NIDDKD, CLIN DIABET & NUTR SECT, NIH, 4212 N 16TH ST, PHOENIX, AZ 85016 USA. FU NIDDK NIH HHS [DK-33214] NR 44 TC 230 Z9 230 U1 3 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 1996 VL 271 IS 2 BP E317 EP E325 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA VD647 UT WOS:A1996VD64700015 PM 8770026 ER PT J AU Terris, J Ecelbarger, CA Nielsen, S Knepper, MA AF Terris, J Ecelbarger, CA Nielsen, S Knepper, MA TI Long-term regulation of four renal aquaporins in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE loop of Henle; collecting duct; water permeability; water channels; vasopressin; urinary concentrating mechanism ID KIDNEY COLLECTING DUCT; INSENSITIVE WATER CHANNEL; MOLECULAR-CLONING; VASOPRESSIN; PERMEABILITY; EXPRESSION; PROTEIN; MEMBRANE; GLYCEROL; CAMP AB The aquaporins are molecular water channels expressed in the kidney and other organs. To investigate long-term regulation of renal expression of these water channels, we carried out immunoblotting studies using membrane fractions from rat renal cortex and medulla. Both 48-h water restriction in Sprague-Dawley rats and 5-day arginine vasopressin (AVP) infusion in Brattleboro rats caused significant increases in the expression levels of two aquaporins, aquaporin-2 and aquaporin-3, while the levels of aquaporin-1 and aquaporin-4 were unchanged. The increases in aquaporin-2 and aquaporin-3 expression were seen in inner and outer medulla as well as cortex. Ablation of the corticomedullary interstitial osmotic gradient with an infusion of furosemide did not eliminate the upregulatory response to AVP infusion in Brattleboro rats. Furthermore, 5-day furosemide infusion to Sprague-Dawley rats did not decrease expression levels of the collecting duct aquaporins, but rather increased them. We conclude that the expression of aquaporin-2 and aquaporin-3, but not aquaporin-1 or aquaporin-4, is increased in response to elevated circulating AVP. Because regulation of aquaporin-2 and aquaporin-3 levels was observed in the cortex and because osmotic gradient ablation did not abrogate the increase, we conclude that changes in interstitial osmolality are not necessary for the AVP-induced upregulation of aquaporin-2 and aquaporin-3 expression. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT PHYSIOL, BETHESDA, MD 20814 USA. UNIV AARHUS, INST ANAT, DEPT CELL BIOL, DK-8000 AARHUS, DENMARK. NR 37 TC 308 Z9 312 U1 2 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD AUG PY 1996 VL 271 IS 2 BP F414 EP F422 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA VD635 UT WOS:A1996VD63500022 PM 8770174 ER PT J AU Leibenluft, E AF Leibenluft, E TI Sex is complex SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID PSYCHIATRIC-DISORDERS; DIFFERENTIATION; PREVALENCE; LIFETIME; NEURONS C1 NIMH,UNIT RAPID CYCLING BIPOLAR DISORDER,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. NR 20 TC 8 Z9 9 U1 4 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1996 VL 153 IS 8 BP 969 EP 972 PG 4 WC Psychiatry SC Psychiatry GA UZ550 UT WOS:A1996UZ55000001 PM 8678191 ER PT J AU Rubinow, DR Schmidt, PJ AF Rubinow, DR Schmidt, PJ TI Androgens, brain, and behavior SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID PLASMA TESTOSTERONE LEVELS; SEXUALLY DIMORPHIC NUCLEUS; HYPOGONADAL MALE-PATIENTS; AGGRESSIVE-BEHAVIOR; SERUM TESTOSTERONE; FEMALE RATS; REPLACEMENT THERAPY; STEROID-HORMONES; RHESUS-MONKEYS; DEPRESSED MEN AB Objective: This article defines androgens (and anabolic steroids), describes their mechanisms of action, and summarizes their behavioral effects and relevance in animals and humans. Method: A MEDLINE-derived review of the literature on androgens and behavior was performed; pivotal earlier publications were also obtained and included in the review. Results: In animals, the effects of androgens on brain structure and function are well-established and profound with behavioral implications extending far beyond reproduction. Androgens play a prominent role in the organization or programming of brain circuits, which are subsequently activated by gonadal steroids. In humans, roles for androgens have been described albeit inconsistently, in the regulation of sexuality, aggression, cognition, emotion, and personality. The relevance of androgens for psychiatry is further suggested by gender-related differences in pharmacokinetics/pharmacodynamics and in the prevalence, course, and treatment response characteristics of several psychiatric disorders. Direct psychoactive effects of exogenously administered androgens have been described for many years, most recently in reports of the psychotoxic effects of anabolic steroids. Conclusions: Data from both animals and humans suggest that the biological and behavioral responses to androgens are context-dependent. RP Rubinow, DR (reprint author), NIMH,BLDG 10,ROOM 3N238,10 CTR DR,MSC 1276,BETHESDA,MD 20892, USA. NR 179 TC 268 Z9 269 U1 7 U2 27 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1996 VL 153 IS 8 BP 974 EP 984 PG 11 WC Psychiatry SC Psychiatry GA UZ550 UT WOS:A1996UZ55000003 PM 8678193 ER PT J AU Schwartz, PJ Brown, C Wehr, TA Rosenthal, NE AF Schwartz, PJ Brown, C Wehr, TA Rosenthal, NE TI Winter seasonal affective disorder: A follow-up study of the first 59 patients of the National Institute of Mental Health Seasonal Studies Program SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BRIGHT LIGHT THERAPY; CIRCADIAN PHASE; MOOD DISORDERS; EVENING LIGHT; DEPRESSION; PHOTOTHERAPY; ANTIDEPRESSANT; RELIABILITY; MELATONIN; PATTERNS AB Objective: The purpose of this study was to characterize the long-term course of patients with seasonal affective disorder. Method: The first 59 patients with winter seasonal affective disorder who had entered winter protocols were retrospectively followed up after a mean interval of 8.8 years. Detailed life charts were constructed through use of a semistructured interview and collateral records. Results: The disorder of 25 patients (42%) remained purely seasonal, with regular recurrences of winter depression and no depression or treatment through any summer. The course of illness was complicated by varying degrees of nonseasonal depression in 26 patients (44%). The disorders of eight patients (14%) had fully remitted. Certain features of the group with complicated seasonal affective disorder suggested that they were more severely ill. Twenty-four patients (41%) continued to use light treatment regularly throughout the follow-up period. Light treatment was preferred to medication for winter recurrences, although antidepressants had been used in the winter by most (63%) of the patients who still used lights at follow-up. Conclusions: The pattern of winter depressions and summer remissions remained fairly persistent over time in this group of patients. The temporal distribution of depressive episodes both within and across individual patients was consistent with the results of several recent follow-up studies of seasonal affective disorder, providing support for the predictive and construct validity of the Rosenthal et al. diagnosis of winter seasonal affective disorder. Light treatment, while remaining a safe and satisfactory treatment for many, may be insufficient for more severely ill patients. The appearance of nonseasonal depressions in patients with winter seasonal affective disorder may be associated with greater severity of illness and less responsiveness to light treatment. RP Schwartz, PJ (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,RM 4S-239,BETHESDA,MD 20892, USA. RI Schwartz, Peter/J-4267-2016 OI Schwartz, Peter/0000-0003-0367-1048 NR 50 TC 49 Z9 49 U1 0 U2 4 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1996 VL 153 IS 8 BP 1028 EP 1036 PG 9 WC Psychiatry SC Psychiatry GA UZ550 UT WOS:A1996UZ55000010 PM 8678171 ER PT J AU Malhotra, AK Goldman, D Ozaki, N Breier, A Buchanan, R Pickar, D AF Malhotra, AK Goldman, D Ozaki, N Breier, A Buchanan, R Pickar, D TI Lack of association between polymorphisms in the 5-HT2A receptor gene and the antipsychotic response to clozapine SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ALLELIC VARIATION; MECHANISM AB Objective: The authors' goal was to determine whether either of two 5-HT2A receptor polymorphisms, 102-T/C and 452-His/Tyr, are associated with clozapine response. Method: Brief Psychiatric Rating Scale (BPRS) ratings were obtained for 70 patients with schizophrenia or schizoaffective disorder to determine their response to clozapine compared with a typical neuroleptic. Patients were genotyped with the polymerase chain reaction and restriction fragment length polymorphism analysis. Results: Neither 102-T/C nor 452-His/Tyr was associated with clozapine response. There were no significant differences in BPRS scores among patients with different 5-HT2A genotypes at week 10 of clozapine administration. Conclusions: Allelic variation in the 5-HT2A gene is not associated with individual differences in clozapine response. C1 NIAAA,NEUROGENET LAB,ROCKVILLE,MD. UNIV MARYLAND,SCH MED,DEPT PSYCHIAT,MARYLAND PSYCHIAT RES CTR,BALTIMORE,MD 21201. RP Malhotra, AK (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BLDG 10,RM 4N212,BETHESDA,MD 20892, USA. RI Ozaki, Norio/M-8908-2014; Goldman, David/F-9772-2010 OI Ozaki, Norio/0000-0002-7360-4898; Goldman, David/0000-0002-1724-5405 NR 13 TC 90 Z9 92 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1996 VL 153 IS 8 BP 1092 EP 1094 PG 3 WC Psychiatry SC Psychiatry GA UZ550 UT WOS:A1996UZ55000020 PM 8678181 ER PT J AU Nair, S Caspi, RR Nelson, LM AF Nair, S Caspi, RR Nelson, LM TI Susceptibility to murine experimental autoimmune oophoritis is associated with genes outside the major histocompatibility complex (MHC) SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 07-12, 1995 CL SEATTLE, WA SP Amer Soc Reproduct Med DE autoimmunity; H-2; mouse; neonatal thymectomy; oophoritis ID PREMATURE OVARIAN FAILURE; CLASS-II AB PROBLEM: Neonatal thymectomy induces experimental autoimmune oophoritis in certain strains of mice, and this serves as a model for human autoimmune oophoritis. Because strong MHC associations have been noted in human autoimmune conditions, we investigated the role of MHC in determining susceptibility to murine experimental autoimmune oophoritis. Strain A mice are highly susceptible to post-thymectomy autoimmunity, whereas strain B10 mice are relatively resistant. The availability of congenic strains of mice makes it possible to separate the effects of genetic background and specific H-2 haplotype. METHODS: We neonatally thymectomized A and B10 background female mice, and their H-2 congenic counterparts, and then evaluated the resulting ovarian disease at age 6 weeks. RESULTS: A.By mice, which have the A background and the H-2(b) haplotype, developed severe disease equivalent to strain A mice. Similarly, B10.A mice, which have the B background and the H-2(a) haplotype, failed to develop disease. Thus, H-2(a) haplotype did not convey disease susceptibility. CONCLUSIONS: Our findings suggest that immune-regulatory regions outside the H-2 locus play an important role in determining susceptibility to murine post-thymectomy autoim mune oophoritis. This is in accord with our previous findings in women that showed no association between MHC and premature ovarian failure. Thus, in this respect this model is similar to human autoimmune ovarian failure. This suggests that the non-MHC genes conveying susceptibility to autoimmune oophoritis in mice might represent similar predisposing genes for premature ovarian failure in women. C1 NICHHD,SECT GYNECOL RES,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 16 TC 9 Z9 9 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD AUG PY 1996 VL 36 IS 2 BP 107 EP 110 PG 4 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA UZ064 UT WOS:A1996UZ06400008 PM 8862255 ER PT J AU Chrousos, GP Castro, M Leung, DYM Webster, E Kino, T Bamberger, C Elliot, S Stratakis, C Karl, M AF Chrousos, GP Castro, M Leung, DYM Webster, E Kino, T Bamberger, C Elliot, S Stratakis, C Karl, M TI Molecular mechanisms of glucocorticoid resistance hypersensitivity potential clinical implications SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Meeting on Corticosteroid Action and Resistance in Asthma CY OCT, 1995 CL DANESFIELD HOUSE, ENGLAND SP Astra Draco ID NF-KAPPA-B; CORTISOL RESISTANCE; STEROID-RECEPTOR; IN-VIVO; HSP90; ASTHMA; CORTICOSTERONE; ASSOCIATION; THERAPY; BINDING C1 UNIV COLORADO,HLTH SCI CTR,DENVER,CO. RP Chrousos, GP (reprint author), NICHHD,NIH,DEPT ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,10 CTR DR,MSC 1862,BETHESDA,MD 20892, USA. RI Castro, Margaret/A-4918-2009 FU NHLBI NIH HHS [HL-36577] NR 28 TC 21 Z9 21 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG PY 1996 VL 154 IS 2 SU S BP S39 EP S43 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VC105 UT WOS:A1996VC10500016 PM 8756786 ER PT J AU Levine, SJ Benfield, T Shelhamer, JH AF Levine, SJ Benfield, T Shelhamer, JH TI Corticosteroids induce intracellular interleukin-1 receptor antagonist type I expression by a human airway epithelial cell line SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; BRONCHOALVEOLAR LAVAGE FLUID; ALVEOLAR MACROPHAGES; HUMAN KERATINOCYTES; SYMPTOMATIC ASTHMA; GUINEA-PIGS; CYTOKINES; GLUCOCORTICOIDS; INFLAMMATION; IL-1-BETA AB Interleukin-1 (IL-1) is an important proinflammatory cytokine which may contribute to the pathogenesis of inflammatory airway disorders, such as asthma and cystic fibrosis. Interleukin-1 receptor antagonist (IL-1ra) is a naturally occurring IL-1 inhibitor which binds to IL-1 receptors without inducing agonist activity. Three IL-1ra isoforms have been identified: secreted IL-1ra (sIL-1ra), which is preferentially expressed by inflammatory cells; intracellular IL-1ra (iIL-1ra) type I, which lacks a signal peptide and is preferentially expressed by epithelial cells; and ilL-1ra type II, which is identical to iIL-1ra type I except for the insertion of an additional 21 amino acids. The goal of this study was to assess whether airway epithelial cell iIL-1ra type I production can be regulated by corticosteroids. First, using reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting, we confirm that normal human bronchial epithelial (NHBE) cells and a human pulmonary mucoepidermoid carcinoma cell line (NCI-H292) express intracellular IL-1ra type I messenger RNA (mRNA) and protein. Second, using immunoblotting and ELISA, we report that dexamethasone induces time- and concentration-dependent increases in iIL-1ra type I protein within NCI-H292 cell lysates. Lastly, utilizing a ribonuclease protection assay, we report that dexamethasone induces concentration-dependent increases in iIL-1ra type I mRNA levels in NCI-H292 cells. These data suggest that corticosteroid-mediated induction of iIL-1ra type I mRNA and protein by human bronchial epithelial cells represents a novel mechanism by which IL-1-mediated airway inflammatory events might be regulated. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 41 TC 41 Z9 42 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 AUG PY 1996 VL 15 IS 2 BP 245 EP 251 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA VB696 UT WOS:A1996VB69600012 PM 8703481 ER PT J AU Avila, NA Skarulis, M Rubino, DM Doppman, JL AF Avila, NA Skarulis, M Rubino, DM Doppman, JL TI Oncogenic osteomalacia: Lesion detection by MR skeletal survey SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID RICKETS C1 NIDDKD,DIV INTRAMURAL RES,NIH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. RP Avila, NA (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,HENRY M JACKSON FDN,DEPT DIAGNOST RADIOL,BLDG 10,RM 1C660,BETHESDA,MD 20892, USA. NR 8 TC 40 Z9 45 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 1996 VL 167 IS 2 BP 343 EP 345 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UY821 UT WOS:A1996UY82100012 PM 8686600 ER PT J AU Ostrowski, ML Merino, MJ AF Ostrowski, ML Merino, MJ TI Tall cell variant of papillary thyroid carcinoma - A reassessment and immunohistochemical study with comparison to the usual type of papillary carcinoma of the thyroid SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE papillary thyroid carcinoma; tall cell variant; immunohistochemistry ID EPITHELIAL MEMBRANE ANTIGEN; CARCINOEMBRYONIC ANTIGEN; MONOCLONAL-ANTIBODIES; HURTHLE CELL; LEU-M1 ANTIGEN; EXPRESSION; NEOPLASMS; GLAND; VIMENTIN; TISSUE AB A review of 92 consecutive cases of papillary thyroid carcinoma diagnosed at The Methodist Hospital revealed 11 tall cell variant (TCV) cases in nine women and two men. There was a greater average age and larger tumor diameter of TCV cases compared with papillary thyroid carcinoma of the usual type (UPTC), but these differences were not statistically significant. Extrathyroidal extension of tumor was noted in nine of 11 TCV cases and was intraoperatively evident in five cases. The presence of extrathyroidal extension represented a statistically significant difference between TCV and UPTC (p = 0.0001) in a multivariate stepwise logistic regression analysis, with controls for variables of age, sex, tumor size, and lymph node metastases. In 11 TCV patients, tumor recurrence was present in two cases, and there was one tumor-associated death with 1 to 4 years of follow-up. Immunohistochemical stains for thyroglobulin, vimentin, keratins, and Leu-7 were positive in all TCV cases and in 16 of 16 UPTC. Immunoreactivity with antibodies to Leu M1 antigen, a myelomonocytic marker included in cluster designation group (CD 15), which is present in many adenocarcinomas, was present diffusely in all TCV, in contrast to UPTC (with sparse immunostaining in only one of 16 cases). Immunoreactivity with antibodies to ZC-23, an anti-carcinoembryonic antigen (CEA) monoclonal antibody with cross-reactivity to nonspecific cross-reacting antigen and biliary glycoprotein antigen, was present in all TCV but was not present in UPTC. COL-1, a CEA-specific monoclonal antibody, was nonimmunoreactive with all TCV and UPTC cases. Epithelial membrane antigen (EMA) was present in all TCV but was also present focally in eight of 16 UPTC, sometimes in a membranous pattern in epithelium surrounding cystic or hemorrhagic spaces. Strong immunoreactivity with antibodies to Leu M1 and EMA in papillary carcinomas of the thyroid has been associated with advanced stages of disease and tumor-associated mortality. The pattern of immunoreactivity in TCV is dissimilar to that in UPTC and is supportive evidence that TCV is a neoplasm that is distinct from papillary thyroid carcinoma of the usual type. C1 BAYLOR COLL MED,HOUSTON,TX 77030. NCI,BETHESDA,MD 20892. RP Ostrowski, ML (reprint author), METHODIST HOSP,DEPT PATHOL,6565 FANNIN,HOUSTON,TX 77030, USA. NR 51 TC 71 Z9 74 U1 1 U2 1 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 AUG PY 1996 VL 20 IS 8 BP 964 EP 974 DI 10.1097/00000478-199608000-00005 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA UZ126 UT WOS:A1996UZ12600005 PM 8712296 ER PT J AU Fears, TR Benichou, J Gail, MH AF Fears, TR Benichou, J Gail, MH TI A reminder of the fallibility of the wald statistic SO AMERICAN STATISTICIAN LA English DT Article DE ANOVA; F test; hypothesis tests; maximum likelihood estimate; one-way random effects model; power; Wald test AB Computer programs often produce a parameter estimate <(theta)over cap> and estimated variance (var) over cap(<(theta)over cap>). Thus it is easy to compute a Wald statistic (<(theta)over cap> - theta(0)){(var) over cap(<(theta)over cap>)}(-1/2) to test the null hypothesis theta = theta(0). Hauck and Donner and Vaeth have identified situations in which the Wald statistic has poor power. We consider another example that is not in the classes discussed by those authors. We present data from a balanced one-way random effects analysis of variance (ANOVA) that illustrate the poor power of the Wald statistic compared to the usual F test, In this example the parameter of interest is the variance of the random effect. The power of the Wald test depends on the parameterization used, however, and a whole family of Wald statistics with p values ranging from 0 to 1 can be generated with power transformations of the random effect parameter. RP Fears, TR (reprint author), NCI,BIOSTAT BRANCH,ROCKVILLE,MD 20892, USA. NR 10 TC 32 Z9 32 U1 0 U2 7 PU AMER STATIST ASSN PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0003-1305 J9 AM STAT JI Am. Stat. PD AUG PY 1996 VL 50 IS 3 BP 226 EP 227 DI 10.2307/2684659 PG 2 WC Statistics & Probability SC Mathematics GA VV331 UT WOS:A1996VV33100005 ER PT J AU Vaneechoutte, M Cartwright, CP Williams, EC Jager, B Tichy, HV DeBaere, T DeRouck, A Verschraegen, G AF Vaneechoutte, M Cartwright, CP Williams, EC Jager, B Tichy, HV DeBaere, T DeRouck, A Verschraegen, G TI Evaluation of 16S rRNA gene restriction analysis for the identification of cultured organisms of clinically important Clostridium species SO ANAEROBE LA English DT Article DE Clostridium; 16S rRNA-gene; restriction analysis; identification; diagnostics ID AMPLIFIED RIBOSOMAL DNA; ENDONUCLEASE SITE DIFFERENCES; FRAGMENT-LENGTH-POLYMORPHISM; ANAEROBE IDENTIFICATION; RAPID IDENTIFICATION; RNA GENE; PCR; BACTERIA; SYSTEM; REPRODUCIBILITY AB In order to evaluate the usefulness of restriction analysis of the amplified 16S rRNA gene for the genotypic identification of cultured Clostridium organisms, a collection of a total of 52 isolates belonging to the following 19 species was studied: Clostridium bifermentans (n=4), C. butyricum (3), C. cadaveris (3), C. clostridioforme (2), C. difficile (3), C. ghonii (2), C. glycolicum (3), C. histolyticum (3), C. innocuum (3), C. novyi A (1), C. paraputrificum (3), C. perfringens (3), C. ramosum (3), C. septicum (3), C. tetani (3), C. sordelli (3), C. sporogenes (3), C. subterminale (1), and C. tertium (3). Restriction analysis was carried out for all species with the enzymes AluI, CfoI, RSaI, BfaI and MboI. Restriction digestion with AluI alone enabled differentiation between all of the species, except for C. bifermentans, C. ghonii and C. sordelli, which could not be differentiated from each other by any of these enzymes or by restriction with BstUI, HaeIII or HinfI. Finally, one C. histolyticum isolate could not be identified with this method since it yielded a 1000 bp fragment after amplification (instead of the expected 1500 bp fragment), most probably due to a reproducible mispriming event. (C) 1996 Academic Press. C1 NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20982. TUV SUDW DLG,D-79108 FREIBURG,GERMANY. RP Vaneechoutte, M (reprint author), STATE UNIV GHENT,DEPT CLIN CHEM MICROBIOL & IMMUNOL,BLOK A,B-9000 GHENT,BELGIUM. RI Vaneechoutte, Mario/A-6189-2009 NR 25 TC 8 Z9 9 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1075-9964 J9 ANAEROBE JI Anaerobe PD AUG PY 1996 VL 2 IS 4 BP 249 EP 256 DI 10.1006/anae.1996.0034 PG 8 WC Microbiology SC Microbiology GA VH342 UT WOS:A1996VH34200009 ER PT J AU Lehman, TA Scott, F Seddon, M Kelly, K Dempsey, EC Wilson, VL Mulshine, JL Modali, R AF Lehman, TA Scott, F Seddon, M Kelly, K Dempsey, EC Wilson, VL Mulshine, JL Modali, R TI Detection of K-ras oncogene mutations by polymerase chain reaction-based ligase chain reaction SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID LUNG-CANCER; POINT MUTATIONS; HUMAN CARCINOMA; REACTION LCR; CELL-LINES; GENE; ADENOCARCINOMA; DIAGNOSIS; ASSAY AB To evaluate a rapid multiplexed assay to detect three common K-ras codon 12 mutations, primer pairs complementary to the wild-type and mutant loci were developed and tested with lung cancer cell lines with previously identified mutation status. The sensitivity of detection of mutations was determined to be at least 1% using spiked samples containing K-ras codon 12 mutations. This assay was then used to evaluate prospectively K-ras status in airways of individuals at high risk of lung cancer by analysis of bronchoalveolar lavage (BAL) specimens from patients who have been previously treated for lung cancer. DNA was extracted from BAL specimen cell pellets, and PCR-based ligase chain reaction was performed for mutations in the first position of codon 12 of K-ras, with positive and negative controls. Of 10 BAL samples, 4 contained 1 mutation (GGT --> TGT), 1 contained 2 mutations (GGT --> TGT and GGT --> AGT), and the rest were wild-type. The BAL mutations were validated by cloning and screening with mutant-specific probes followed by confirmation sequencing. (C) 1996 Academic Press, Inc. C1 BIOSERVE BIOTECHNOL LTD,LAUREL,MD 20707. NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD. VET ADM MED CTR,DENVER,CO 80262. LOUISIANA STATE UNIV,INST ENVIRONM STUDIES,BATON ROUGE,LA 70803. FU NIAID NIH HHS [1R43AI37401-01] NR 19 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 1 PY 1996 VL 239 IS 2 BP 153 EP 159 DI 10.1006/abio.1996.0310 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VA593 UT WOS:A1996VA59300005 PM 8811898 ER PT J AU Mentis, SW AF Mentis, SW TI Tangier disease SO ANESTHESIA AND ANALGESIA LA English DT Article ID PATHOLOGY RP Mentis, SW (reprint author), NIH,DEPT ANESTHESIOL,ANESTHESIA SECT,10-2C624,10 CTR DR MSC 1512,BETHESDA,MD 20892, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD AUG PY 1996 VL 83 IS 2 BP 427 EP 429 PG 3 WC Anesthesiology SC Anesthesiology GA UZ991 UT WOS:A1996UZ99100040 PM 8694332 ER PT J AU Arbuck, SG AF Arbuck, SG TI Workshop on phase I study design - Ninth NCI/EORTC New Drug Development Symposium, Amsterdam, March 12, 1996 SO ANNALS OF ONCOLOGY LA English DT Editorial Material DE cancer drug development; dose; dose escalation; dose-limiting toxicity; phase I trials; response; toxicity; toxicology AB Many of the methods currently used in phase I trial design date back to the 1970's. Recently, some investigators have considered whether it might be possible to perform more efficient phase I trials that minimize the number of patients treated at biologically ineffective doses, maximize the precision of recommended phase II doses, and maintain patient safety. The objective of this Workshop was to examine aspects of phase I trial design, with consideration of both standard and novel approaches. Topics included choice of starting dose level, definition of dose-limiting toxicity, development and incorporation of non-toxicity endpoints, use of alternate dose escalation schemes, and definitions of tumor response and clinical benefit, including consideration of whether these determinations from phase I studies should alter the decision to proceed to phase II drug evaluation. For each topic, this summary includes a description of the standard approach, a summary of the speaker's presentation, and commentary. The Workshop initiated discussion and reassessment that are expected to lead to testing of some of the suggested alternate approaches. RP Arbuck, SG (reprint author), NATL CANC INST,INVESTIGAT DRUG BRANCH,CTEP,DIV CANC TREATMENT,DIAG & CTR,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 8 TC 48 Z9 48 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 1996 VL 7 IS 6 BP 567 EP 573 PG 7 WC Oncology SC Oncology GA VG534 UT WOS:A1996VG53400011 PM 8879369 ER PT J AU King, CD Green, MD Rios, GR Coffman, BL Owens, IS Bishop, WP Tephly, TR AF King, CD Green, MD Rios, GR Coffman, BL Owens, IS Bishop, WP Tephly, TR TI The glucuronidation of exogenous and endogenous compounds by stably expressed rat and human UDP-glucuronosyltransferase 1.1 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE UDP-glucuronosyltransferase; glucuronidation; UGT1.1; opioids; buprenorphine; Crigler-Najjar syndrome ID HUMAN-LIVER; SUBSTRATE-SPECIFICITY; GENE-COMPLEX; I PATIENT; BILIRUBIN; CLONING; CELLS AB Rat and human UDP-glucuronosyltransferase (UGT)1.1 share >70% identity in their deduced primary amino acid sequences. We have previously shown that rat UGT1.1, stably expressed in human embryonic kidney 293 cells, catalyzes the glucuronidation of bilirubin and the mixed opioid agonist/antagonist buprenorphine with high efficiency. The present study was designed to characterize the reactivity of expressed human UGT1.1 with opioid compounds and compare its substrate specificity for opioids to that of the expressed rat enzyme. The results show that both rat and human UGT1.1 catalyze the glucuronidation of opioids with a relative reactivity of buprenorphine much greater than nalorphine approximate to naltrexone. Comparison of glucuronidation activities in livers from Crigler-Najjar type 1 patients and normal patients indicates that UGT1.1 catalyzes at least 75% of buprenorphine conjugation in normal human liver. In separate studies, the reactivity of expressed rat UGT1.1 was characterized toward various xeno- and endobiotics of various compound classes. It was found that both rat and human UGT1.1 exhibited comparable substrate specificities and efficiencies (V-max/K-m) of glucuronide formation for anthraquinones, coumarins, estrogens, flavonoids, and phenolic compounds. Neither rat nor human UTGT1.1 catalyzed the glucuronidation of amines, monoterpenoid alcohols, androgens, or progestins. In general, these data indicate that rat and human UGT1.1 are functionally identical and can be considered orthologous enzymes. (C) 1996 Academic Press, Inc. C1 UNIV IOWA,DEPT PHARMACOL,IOWA CITY,IA 52242. UNIV IOWA,DEPT PEDIAT,IOWA CITY,IA 52242. NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM-26221] NR 25 TC 147 Z9 152 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD AUG 1 PY 1996 VL 332 IS 1 BP 92 EP 100 DI 10.1006/abbi.1996.0320 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VA614 UT WOS:A1996VA61400012 PM 8806713 ER PT J AU Clarkin, JF Pilkonis, PA Magruder, KM AF Clarkin, JF Pilkonis, PA Magruder, KM TI Psychotherapy of depression - Implications for reform of the health care system SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID COLLABORATIVE RESEARCH-PROGRAM; COGNITIVE THERAPY; MAJOR DEPRESSION; FOLLOW-UP; INTERPERSONAL PSYCHOTHERAPY; MAINTENANCE TREATMENT; GERIATRIC DEPRESSION; RECURRENT DEPRESSION; PHARMACOTHERAPY; EFFICACY AB This article reviews the empirical evidence supporting the role of psychotherapy and psychosocial interventions in the treatment of patients with depression. Treatment models and the evidence for their effectiveness in the acute- and maintenance-treatment phases are reviewed. Whereas the sophistication of research designs and data analysis for the study of psychotherapy have substantially improved, the review highlights current gaps in our knowledge. Most important for reform of the health care system is the need for studies of efficacy to lead to large-scale investigations of effectiveness. C1 UNIV PITTSBURGH, SCH MED, WESTERN PSYCHIAT INST & CLIN, DEPT PSYCHIAT, PITTSBURGH, PA USA. NIMH, OFF RURAL MENTAL HLTH, BETHESDA, MD 20892 USA. RP Clarkin, JF (reprint author), CORNELL UNIV, NEW YORK HOSP,MED CTR,DEPT PSYCHIAT, WESTCHESTER DIV, 21 BLOOMINGDALE RD, WHITE PLAINS, NY 10605 USA. NR 69 TC 21 Z9 21 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1996 VL 53 IS 8 BP 717 EP 723 PG 7 WC Psychiatry SC Psychiatry GA VC004 UT WOS:A1996VC00400008 PM 8694685 ER PT J AU Horn, VJ Redman, RS Ambudkar, IS AF Horn, VJ Redman, RS Ambudkar, IS TI Response of rat salivary glands to mastication of pelleted vitamin A-deficient diet SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE rat; Ca2+ signalling; salivary gland; secretion; vitamin A ID MATERNAL ETHANOL INGESTION; FETAL ALCOHOL SYNDROME; RETINOIC ACID; PAROTID-GLAND; ACINAR-CELLS; LIQUID DIET; PROTEIN; SECRETION; RECEPTORS; DIFFERENTIATION AB Interpretation of previous studies of the effects of hypovitaminosis A on salivary glands is confounded by the atrophic effects of liquid or powdered diets. The purpose of this study was to re-evaluate the effects of vitamin A deficiency on the morphology and function of rat salivary glands using a pelleted diet that promotes physiological levels of masticatory stimulation. Profound vitamin A deficiency resulted in a marked decrease in stimulated parotid secretion. Histological evaluation demonstrated the development of squamous metaplasia in the ducts of parotid, submandibular and sublingual salivary glands; however, atrophy was observed only in serous salivary glands. In the parotid gland the degree of atrophy corresponded to the decrease in stimulated secretion. Mild hypovitaminosis A (before the development of squamous metaplasia in ducts) was associated with distinctly different effects. The parotid gland was moderately enlarged. There was also a significant increase in stimulated secretion, which was not explained by changes in gland size, muscarinic receptor number or affinity, or receptor mediated calcium signalling. Copyright (C) 1996 Published by Elsevier Science Ltd. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20205. RP Horn, VJ (reprint author), DEPT VET AFFAIRS MED CTR,ORAL PATHOL RES LAB,50 IRVING ST NW,WASHINGTON,DC 20422, USA. NR 37 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD AUG-SEP PY 1996 VL 41 IS 8-9 BP 769 EP 777 DI 10.1016/S0003-9969(96)00069-6 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WE636 UT WOS:A1996WE63600007 PM 9022914 ER PT J AU Garber, SL Rintala, DH Rossi, CD Hart, KA Fuhrer, MJ AF Garber, SL Rintala, DH Rossi, CD Hart, KA Fuhrer, MJ TI Reported pressure ulcer prevention and management techniques by persons with spinal cord injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID RISK-FACTORS; SORES; PREVALENCE AB Objective: The purpose of this study was to identify factors that resulted in severe pressure ulcers in a community-based sample of 23 persons with spinal cord injury (SCI). Design: A correlational design was used. Subjects: Twenty men and three women, 57% with tetraplegia and 43% with paraplegia, participated. Adult participants with an ulcer of 12 weeks' duration or less were recruited from the plastic surgery clinic of a regional SCI center. Measures: A structured survey assessed demographic, SCI, and ulcer characteristics; detection method; immediacy and appropriateness of action; time from detection to clinic visit; number of prior ulcers; and knowledge and practice of ulcer prevention techniques. Ulcer characteristics (ie, location, size, and stage) were assessed by examination and compared with participants' descriptions of their ulcers. Results: Severe ulcers and ulcers that progressed in severity after initial detection were less accurately described by participants. Individuals who waited longer to come to the clinic presented with more severe ulcers. Taking immediate or appropriate action when an ulcer was detected was related to reported performance of more preventive behaviors. Contrary to expectation, immediacy and appropriateness of action, and knowledge and practice of preventive behaviors were unrelated to severity, progression of severity, and time from detection to the clinic visit. The findings suggest that educational programs should emphasize more strongly immediate visits to a physician upon detection of an ulcer. Furthermore, such educational models should be assessed for their effectiveness in reducing ulcers and preventing progression in severity once persons with SCI return to the community. (C) 1996 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 NICHHD,NATL CTR MED REHABIL RES,NIH,BETHESDA,MD 20892. RP Garber, SL (reprint author), BAYLOR COLL MED,DEPT PHYS MED & REHABIL,1333 MOURSUND AVE,SUITE A221,HOUSTON,TX 77030, USA. NR 26 TC 25 Z9 25 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD AUG PY 1996 VL 77 IS 8 BP 744 EP 749 DI 10.1016/S0003-9993(96)90251-8 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA VA965 UT WOS:A1996VA96500002 PM 8702366 ER PT J AU Kataoka, S Robbins, DC Cowan, LD Go, O Yeh, JLL Devereux, RB Fabsitz, RR Lee, ET Welty, TK Howard, BV AF Kataoka, S Robbins, DC Cowan, LD Go, O Yeh, JLL Devereux, RB Fabsitz, RR Lee, ET Welty, TK Howard, BV TI Apolipoprotein E polymorphism in American Indians and its relation to plasma lipoproteins and diabetes - The strong heart study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE lipoprotein; apolipoprotein E; diabetes cholesterol; American Indians ID HIGH-DENSITY-LIPOPROTEIN; ESTER TRANSFER PROTEIN; E GENOTYPE INFLUENCE; CARDIOVASCULAR-DISEASE; GENETIC-VARIATION; LIPID-METABOLISM; RISK-FACTORS; E PHENOTYPE; POPULATION; CHOLESTEROL AB Apo E is an important genetic factor in the development of cardiovascular disease, which is the leading cause of death among American Indians. We investigated the occurrence of the apo E alleles and the relation between apo E polymorphism and blood lipoproteins and apoproteins in members of 13 American Indian communities in three geographic areas. The frequencies of the epsilon 2 alleles in American Indians are significantly lower than those in white Americans, with the lowest frequencies of epsilon 2 in American Indians who reside in Arizona. Levels of LDL cholesterol and apo B were highest in those with epsilon 4 and lowest in those with epsilon 2. Concentrations of HDL cholesterol and apo A-I, however, tended to be lowest in epsilon 4 and highest in epsilon 2. Concentrations of total and VLDL triglycerides were lowest in the epsilon 3 group and higher in groups epsilon 2 and epsilon 4. Differences in concentrations of LDL cholesterol, HDL cholesterol, apo B, and apo A-I with apo E polymorphism were greater in women than in men, and differences in total and VLDL triglyceride concentrations by apo E phenotype were greater in men. Relations of total and VLDL triglycerides with apo E phenotype were stronger in women after menopause. In addition, differences in nearly all lipid and apoprotein concentrations between postmenopausal women and premenopausal women were greater if they had epsilon 2. Relations between apo E phenotype and lipoproteins were seen in individuals with diabetes mellitus as well as in nondiabetics. Apo E was significantly related to glucose control in diabetic women; those with epsilon 3 had higher glucose and hemoglobin A(1c) concentrations. Our findings show that (1) American Indians have low frequencies of apo epsilon 2; (2) apo E phenotype can influence levels of VLDL, LDL, HDL, apo B, and apo A-I; (3) the associations of apo E polymorphisms with lipid parameters differ between men and women; and (4) the associations in women of apo E polymorphisms with lipid parameters are modified by menopausal status. C1 MEDLANT RES INST,WASHINGTON,DC 20010. HIROSHIMA UNIV,SCH MED,DEPT INTERNAL MED 2,HIROSHIMA,JAPAN. UNIV OKLAHOMA,HLTH SCI CTR,CTR EPIDEMIOL RES,OKLAHOMA CITY,OK. CORNELL MED CTR,NEW YORK,NY. NHLBI,BETHESDA,MD 20892. ABERDEEN AREA INDIAN HLTH SERV,RAPID CITY,SD. FU NHLBI NIH HHS [U01-HL-41642, U01-HL-41652, UL01-HL-41654] NR 42 TC 55 Z9 58 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 1996 VL 16 IS 8 BP 918 EP 925 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA VB383 UT WOS:A1996VB38300003 PM 8696954 ER PT J AU Gaynor, PM Zhang, WY Weiss, JS Skarlatos, SI Rodrigues, MM Kruth, HS AF Gaynor, PM Zhang, WY Weiss, JS Skarlatos, SI Rodrigues, MM Kruth, HS TI Accumulation of HDL apolipoproteins accompanies abnormal cholesterol accumulation in Schnyder's corneal dystrophy SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE cholesterol; Schnyder's corneal dystrophy; apolipoproteins; lipoproteins; atherosclerosis ID HIGH-DENSITY LIPOPROTEIN; CRYSTALLINE STROMAL DYSTROPHY; HUMAN ATHEROSCLEROTIC LESIONS; CULTURED-CELLS; E DEFICIENCY; ASSOCIATION; HYPERLIPOPROTEINEMIA; FIBROBLASTS; MACROPHAGES; METABOLISM AB Schnyder's corneal dystrophy is an autosomal dominant disorder that results in clouding of the central cornea and premature development of peripheral arcus in the cornea. Previous studies showed that abnormal lipid accumulation is the basis for the corneal clouding. We examined whether apolipoproteins are involved in this disorder and characterized the lipid accumulation in the central portion of corneas removed from patients with Schnyder's dystrophy. Our findings show that cholesterol and phospholipid contents increased greater than 10-fold and 5-fold, respectively, in affected compared with normal corneas. In addition, the percentage of cholesterol that was unesterified (63% versus 50%) and the molar ratio of unesterified cholesterol to phospholipid (1.5 versus 0.5) were higher in affected compared with normal corneas. Large multilamellar vesicles and electron-dense granules (100 to 300 nm in diameter) as well as cholesterol crystals accumulated in the extracellular matrix of affected corneas. Immunohistochemical analysis showed that apolipoprotein constituents of HDL (apoA-I, apoA-II, and apoE), but not apoB, a marker of LDL, accumulated in the affected cornea. Western blot analysis confirmed the increased amounts of these HDL apolipoproteins in affected corneas and showed that the apparent molecular weights of the apolipoproteins were normal. Our findings show for the first time that HDL apolipoproteins accumulate in the corneas of patients with Schnyder's corneal dystrophy. Thus, this disorder influences the metabolism of HDL in the corneas of these patients. C1 NHLBI,SECT EXPT ATHEROSCLEROSIS,NIH,BETHESDA,MD 20892. UNIV MASSACHUSETTS,MED CTR,DEPT OPHTHALMOL,WORCESTER,MA. UNIV MARYLAND,SCH MED,DEPT OPHTHALMOL,BALTIMORE,MD 21201. NR 45 TC 22 Z9 22 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 1996 VL 16 IS 8 BP 992 EP 999 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA VB383 UT WOS:A1996VB38300013 PM 8696964 ER PT J AU Sannerud, CA Kaminski, BJ Griffiths, RR AF Sannerud, CA Kaminski, BJ Griffiths, RR TI Intravenous self-injection of four novel phenethylamines in baboons SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE abuse liability; baboons; cocaine; self-administration; stimulants ID RHESUS-MONKEYS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE ECSTASY; METHYLENEDIOXYMETHYLAMPHETAMINE MDMA; SEROTONIN NEUROTOXICITY; REINFORCING PROPERTIES; STIMULUS PROPERTIES; SQUIRREL-MONKEYS; N,N-DIMETHYLAMPHETAMINE; BRAIN; DRUG AB The present study evaluated the intravenous self-administration of four substituted phenethylamines, using a substitution procedure in baboons, Baboons were trained to self-inject 0.32 mg/kg/injection cocaine under a fixed-ratio (FR) schedule, with a 3 h timeout following each injection. Doses of (+/-)-N-ethyl-3,4-methylenedioxyamphetamine HCI (MDE), (+/-)-N-hydroxy-3,4-methylenedioxyamphetamine HCI (N-OH-MDA), (+)-N-N-dimethylamphetamine HCI (NDMA), and 4-bromo-2,5-dimethyoxy-beta-phenethylamine (BDMPEA) and their vehicles were substituted for cocaine for 15 or more successive days, High doses of MDE and N-OH-MDA maintained self-injection; however, NNDMA and BDMPEA self-injection was less consistent. NNDMA did not reliably maintain self-injection, whereas one or more doses of BDMPEA maintained self-injection in each of three baboons. Intermediate to high doses of all four compounds decreased food pellet intake maintained under a FR schedule of reinforcement on a different lever, In some baboons, high doses of N-OH-MDA, NNDMA and BDMPEA produced signs of behavioral toxicity (e.g. cyclic pattern of self-injection, behavioral agitation, stereotypical movements) that were similar to those previously observed after administration of high doses of classic psychomotor stimulants such as d-amphetamine; however, the severity and profile of this behavioral toxicity differed between compounds. Thus, the present study documents both similarities and differences in the behavioral profiles of these four phenethylamines. C1 NIDA,BEHAV PHARMACOL & GENET LAB,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NR 35 TC 7 Z9 7 U1 1 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD AUG PY 1996 VL 7 IS 4 BP 315 EP 323 DI 10.1097/00008877-199608000-00002 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA VD266 UT WOS:A1996VD26600002 ER PT J AU McDowell, G Isogai, T Tanigami, A Hazelwood, S Ledbetter, D Polymeropoulos, MH LichterKonecki, U Konecki, D Town, MM VantHoff, W Weissenbach, J Gahl, WA AF McDowell, G Isogai, T Tanigami, A Hazelwood, S Ledbetter, D Polymeropoulos, MH LichterKonecki, U Konecki, D Town, MM VantHoff, W Weissenbach, J Gahl, WA TI Fine mapping of the cystinosis gene using an integrated genetic and physical map of a region within human chromosome band 17p13 SO BIOCHEMICAL AND MOLECULAR MEDICINE LA English DT Article ID NEPHROPATHIC CYSTINOSIS; CYSTEAMINE THERAPY; YAC CLONES; INSUFFICIENCY; TRANSPORT; FRACTIONS; DEPLETION; CHILDREN; DISEASE AB The cystinosis gene has been reported to reside in a 3.1 cM region of chromosome 17p13 flanked by markers D17S1828 and D17S1798. We created a yeast artificial chromosome (YAC) contig between these markers and report here an integrated genetic and physical map which will aid in the identification of other genes in this area. Using one pertinent YAC clone, 898A10, we identified new polymorphic markers in the cystinosis gene region, One such marker, D17S2167, was localized by radiation hybrid analysis to within 10.2 cR(8000) Of D17S1828, Haplotype analysis in two separate informative families revealed recombination events which placed the cystinosis gene between markers D17S1828 and D17S2167, an area estimated to be 187-510 kb in size, This dramatic narrowing of the cystinosis gene region permits the creation of a P1 or cosmid contig across the area of interest. The ultimate cloning of the cystinosis gene should eventually reveal how a functional lysosomal transport protein is synthesized, targetted, processed, and integrated into the lysosomal membrane. (C) 1996 Academic Press, Inc. C1 FUJISAWA PHARMACEUT CO LTD, TSUKUBA, IBARAKI 30026, JAPAN. NIH, DIAGNOST DEV BRANCH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. NIH, HOWARD HUGHES MED INST, RES SCHOLAR PROGRAM, BETHESDA, MD 20892 USA. NIH, LAB GENET DIS RES, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. MARSHFIELD MED RES FDN, CTR GENET MED, MOL & CELLULAR BIOL LAB, MARSHFIELD, WI 54449 USA. UNIV HEIDELBERG, CHILDRENS HOSP, D-6900 HEIDELBERG, GERMANY. UNITED MED & DENT SCH, GUYS HOSP, DIV MED & MOL GENET, LONDON SE1 9RT, ENGLAND. INST CHILD HLTH, LONDON WC1N 1EH, ENGLAND. GENETHON SA, HUMAN GENOME RES CTR, CNRS, URA 1922, F-91002 EVRY, FRANCE. RP NICHHD, SECT HUMAN BIOCHEM GENET, HERITABLE DISORDERS BRANCH, NIH, BETHESDA, MD 20892 USA. NR 35 TC 23 Z9 23 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1077-3150 J9 BIOCHEM MOL MED JI Biochem. Mol. Med. PD AUG PY 1996 VL 58 IS 2 BP 135 EP 141 DI 10.1006/bmme.1996.0041 PG 7 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA VB361 UT WOS:A1996VB36100001 PM 8812732 ER PT J AU Laue, L Wu, SM Kudo, M Hsueh, AJW Cutler, GB Jelly, DH Diamond, FB Chan, WY AF Laue, L Wu, SM Kudo, M Hsueh, AJW Cutler, GB Jelly, DH Diamond, FB Chan, WY TI Heterogeneity of activating mutations of the human luteinizing hormone receptor in male-limited precocious puberty SO BIOCHEMICAL AND MOLECULAR MEDICINE LA English DT Article ID CHORIONIC-GONADOTROPIN; SEXUAL PRECOCITY; POINT MUTATION; GENE; CELLS; TESTOTOXICOSIS; EXPRESSION; CDNA; RAT; LH AB Male-Limited precocious puberty (MPP) is a gonadotropin-independent disorder that occurs sporadically or is inherited in an autosomal dominant, male-limited pattern, Recent studies have identified constitutively activating missense mutations in the human luteinizing hormone receptor (hLHR) gene leading to Leydig cell activation and precocious puberty. Patients with sporadic MPP (SMPP) or with different ethnic backgrounds appear to have a greater likelihood of having novel mutations, In the current study we examined genomic DNA from two unrelated cases of SMPP of African-American descent for novel mutations of the hLHR gene. A heterozygous A to C transversion at nucleotide 1723 resulting in substitution of Leu for lle575 in transmembrane helix 6 was identified. Human embryonic kidney cells transfected with cDNA for the mutant hLHR-I575L, created by polymerase chain reaction-based mutagenesis of the wild-type (hLHR-wt) cDNA, exhibited increased basal levels of cAMP production in the absence of agonist, indicating constitutive activation. Surface expression of hLHR-I575L, as reflected by human chorionic gonadotropin binding, was diminished compared to hLHR-wt, while agonist affinity was unaffected. With the exception of two polymorphic bases, no mutation was identified within the coding sequence of the hLHR in the second case of SMPP, We conclude that I575L is a unique constitutively activating mutation that impairs cell surface expression of the receptor but does not alter agonist affinity. Furthermore, mutations of the hLHR gene causing SMPP are highly heterogeneous and may be found in regions other than exon 11 of the hLHR. Last, patients with MPP from different ethnic backgrounds are likely to have novel mutations. (C) 1996 Academic Press, Inc. C1 GEORGETOWN UNIV, MED CTR, DEPT PEDIAT, WASHINGTON, DC 20007 USA. GEORGETOWN UNIV, MED CTR, DEPT BIOCHEM & CELL BIOL, WASHINGTON, DC 20007 USA. STANFORD UNIV, MED CTR, DEPT GYNECOL & OBSTET, STANFORD, CA 94305 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. WARREN CLIN DIABET CTR, TULSA, OK 74136 USA. UNIV S FLORIDA, TAMPA, FL USA. FU NICHD NIH HHS [HD01109, HD31553] NR 29 TC 33 Z9 36 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 1077-3150 J9 BIOCHEM MOL MED JI Biochem. Mol. Med. PD AUG PY 1996 VL 58 IS 2 BP 192 EP 198 DI 10.1006/bmme.1996.0048 PG 7 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA VB361 UT WOS:A1996VB36100008 PM 8812739 ER PT J AU Breitman, TR Takahashi, N AF Breitman, TR Takahashi, N TI Retinoylation of proteins in mammalian cells SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 658th Meeting of the Biochemical-Society CY APR 16-19, 1996 CL UNIV LIVERPOOL, LIVERPOOL, ENGLAND SP Biochem Soc HO UNIV LIVERPOOL ID TRANS-RETINOIC ACID; ADENOSINE 3'-5'-MONOPHOSPHATE-INDUCING AGENTS; ACUTE PROMYELOCYTIC LEUKEMIA; EMBRYONAL CARCINOMA-CELLS; REGULATORY SUBUNITS; DIBUTYRYL-CAMP; HL-60 CELLS; C-JUN; DIFFERENTIATION; KINASE RP Breitman, TR (reprint author), NCI,BIOL CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892, USA. NR 48 TC 34 Z9 35 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD AUG PY 1996 VL 24 IS 3 BP 723 EP 727 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VF683 UT WOS:A1996VF68300024 PM 8878834 ER PT J AU Cvekl, A Piatigorsky, J AF Cvekl, A Piatigorsky, J TI Lens development and crystallin gene expression: Many roles for Pax-6 SO BIOESSAYS LA English DT Review ID RETINOIC ACID RECEPTORS; HOMEOBOX-CONTAINING GENE; BOX-CONTAINING GENE; DNA-BINDING; PAIRED DOMAIN; TRANSACTIVATION PROPERTIES; ANTERIOR NEUROECTODERM; SEQUENCE RECOGNITION; VERTEBRATE EYE; EYELESS GENE AB The vertebrate eye lens has been used extensively as a model for developmental processes such as determination, embryonic induction, cellular differentiation, transdifferentiation and regeneration, with the crystallin genes being a prime example of developmentally controlled, tissue-preferred gene expression. Recent studies have shown that Pax-6, a transcription factor containing both a paired domain and homeodomain, is a key protein regulating lens determination and crystallin gene expression in the lens. The use of Pax-6 for expression of different crystallin genes provides a new link at the developmental and transcriptional level among the diverse crystallins and may lead to new insights into their evolutionary recruitment as refractive proteins. RP Cvekl, A (reprint author), NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD 20892, USA. RI Cvekl, Ales/B-2427-2013 NR 72 TC 212 Z9 215 U1 1 U2 14 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD AUG PY 1996 VL 18 IS 8 BP 621 EP 630 DI 10.1002/bies.950180805 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA VC442 UT WOS:A1996VC44200004 PM 8760335 ER PT J AU Prien, RF Rush, AJ AF Prien, RF Rush, AJ TI National Institute of Mental Health workshop report on the treatment of bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE NIMH workshop; bipolar disorder; research; treatment C1 UNIV TEXAS,SW MED CTR,DEPT PSYCHIAT,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,MENTAL HLTH CLIN RES CTR,DALLAS,TX 75235. RP Prien, RF (reprint author), NIMH,CLIN TREATMENT RES BRANCH,PARKLAWN BLDG,ROOM 18-105,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. OI Rush, Augustus/0000-0003-2004-2382 NR 8 TC 40 Z9 40 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 1 PY 1996 VL 40 IS 3 BP 215 EP 220 DI 10.1016/0006-3223(95)00379-7 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UW573 UT WOS:A1996UW57300008 PM 8830955 ER PT J AU Lee, JW Lewin, NE Blumberg, PM Marquez, VE AF Lee, JW Lewin, NE Blumberg, PM Marquez, VE TI Synthesis of bis-gamma-butyrolactones containing conformationally constrained (S)- and (R)-diacylglycerol structures SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID RIGID DIACYLGLYCEROL ANALOGS; PROTEIN-KINASE-C; SKELETON AB The synthesis of two sets of rigid diacylglycerol (DAG) analogues with either the (S)-DAG or (R)-DAG enantiomer embedded into a bis-gamma-butyrolactone template was accomplished stereoselectively from di-O-isopropylidene-alpha-D-apiose. The key step in both syntheses was the assemblage of the bicyclic perhydrofuro[3,4-b]furan ring system via a radical exo-dig intramolecular cyclization. A lipophilic undecanyl alkyl chain attached at C-3 of the fully assembled perhydrofuro[3,4-b]furan-2,4-dione (bis-gamma-butyrolactone) template can adopt two orientations with the one directed away from the concave face of the bicyclic system favored by a 4 to 1 ratio in each case. Evaluation of the final target pairs of enantiomers as PK-C alpha ligands revealed that the template containing an embedded (R)-DAG structure was more effective. The difference in binding affinity was also modulated by the direction of the alkyl chain. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 13 TC 5 Z9 5 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD AUG PY 1996 VL 4 IS 8 BP 1299 EP 1305 DI 10.1016/0968-0896(96)00116-2 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA VG136 UT WOS:A1996VG13600015 PM 8879551 ER PT J AU Wallqvist, A Covell, DG AF Wallqvist, A Covell, DG TI On the origins of the hydrophobic effect: Observations from simulations of n-dodecane in model solvents SO BIOPHYSICAL JOURNAL LA English DT Article ID EFFECTIVE PAIR POTENTIALS; MONTE-CARLO SIMULATION; MOLECULAR-DYNAMICS; FREE-ENERGY; COMPUTER-SIMULATION; NORMAL-BUTANE; HYDRATION FORCES; AQUEOUS-SOLUTION; WATER; LIQUIDS AB The importance of the small size of a water molecule as contributing to the hydrophobic effect is examined from simulations of n-dodecane in different solvents. The earlier observations of the origin of hydrophobicity, derived from cavity formations by Pratt and Pohorille (1992, Proc. Natl. Acad. Sci. USA. 89:2995-2999) and Madan and Lee (1994, Biophys. Chem. 51:279-289), are shown to be largely consistent for a hydrocarbon-induced water pocket. In effect, the small size of a water molecule limits the probability (and hence free energy) of finding an appropriate void in the fluid that will accommodate a solute. In this work a simulated collapse of an n-dodecane molecule in H2O, CCl4, and a water-like Lennard-Jones solvent indicates that the induced entropy and enthalpy changes are qualitatively similar for hydrogen-bonded and Lennard-Jones water solvents. These results suggest that a large part of the hydrophobic response of solutes in aqueous solutions is due to the small size of the solvent. Important quantitative differences between the studied water solvents indicate that the hydrogen-bonded properties for water are still needed to determine the overall hydrophobic response. RP NCI, FREDERICK CANC RES & DEV CTR, SCI APPLICAT INT CORP, POB B, FREDERICK, MD 21702 USA. NR 51 TC 43 Z9 43 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD AUG PY 1996 VL 71 IS 2 BP 600 EP 608 PG 9 WC Biophysics SC Biophysics GA VA410 UT WOS:A1996VA41000010 PM 8842199 ER PT J AU Ehrenstein, D Iwase, KH AF Ehrenstein, D Iwase, KH TI Viscoelastic relaxation in the membrane of the auditory outer hair cell SO BIOPHYSICAL JOURNAL LA English DT Article ID ELECTROKINETIC SHAPE CHANGES; GUINEA-PIG COCHLEA; MECHANICAL RESPONSES; FORCE GENERATION; MOTOR MODEL; MOTILITY; WALL AB The outer hair cell (OHC) in the mammalian ear has a unique membrane potential-dependent motility, which is considered to be important for frequency discrimination (tuning), The OHC motile mechanism is located at the cell membrane and is strongly influenced by its passive mechanical properties. To study the viscoelastic properties of OHCs, we exposed cells to a hypoosmotic solution for varying durations and then punctured them, to immediately release the osmotic stress. Using video records of the cells, we determined both the imposed strain and the strain after puncturing, when stress was reset to zero. The strain data were described by a simple rheological model consisting of two springs and a dashpot, and the fit to this model gave a time constant of 40 +/- 19 s for the relaxation (reduction) of tension during prolonged strain. For time scales much shorter or longer than this, we would expect essentially elastic behavior. This relaxation process affects the membrane tension of the cell, and because it has been shown that membrane tension has a modulatory role in the OHC's motility, this relaxation process could be part of an adaptation mechanism, with which the motility system of the OHC can adjust to changing conditions and maintain optimum membrane tension. RP Ehrenstein, D (reprint author), NIDCD,LAB CELLULAR BIOL,BIOPHYS SECT,NIH,BLDG 9,RM 1E114,MSC 0922,BETHESDA,MD 20892, USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 35 TC 20 Z9 20 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 1996 VL 71 IS 2 BP 1087 EP 1094 PG 8 WC Biophysics SC Biophysics GA VA410 UT WOS:A1996VA41000056 PM 8842245 ER PT J AU Vesole, DH Tricot, G Jagannath, S Desikan, KR Siegel, D Bracy, D Miller, L Cheson, B Crowley, J Barlogie, B AF Vesole, DH Tricot, G Jagannath, S Desikan, KR Siegel, D Bracy, D Miller, L Cheson, B Crowley, J Barlogie, B TI Autotransplants in multiple myeloma: What have we learned? SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; AUTOLOGOUS BONE-MARROW; HIGH-DOSE MELPHALAN; ACUTE LYMPHOBLASTIC-LEUKEMIA; INTENSIVE THERAPY; COMBINATION CHEMOTHERAPY; MYELOABLATIVE THERAPY; PROGNOSTIC FACTORS; FIRST REMISSION; SINGLE-CENTER AB Of 496 consecutive patients with multiple myeloma (MM) enrolled in clinical trials of tandem transplants with peripheral blood stem cells support, 470 (95%) completed the first autotransplant with melphalan 200 mg/m(2) (MEL 200) and 363 (73%) completed the second transplant with either MEL 200 (40%), MEL 140 mg/m(2) (MEL 140) with total-body irradiation (17%), or a combination of alkylating agents (16%), depending on the response status prior to the second transplant; 31 patients up to age 60 years received an allograft as the second transplant. The median interval from first to second transplant was 5 months, Treatment-related mortality during the first year after transplantation was 7%, and complete remission (CR) was obtained in 36%; the median durations of event-free survival (EFS) and overall survival (OS) after transplant were 26 and 41 months, respectively. Low beta(2)-microglobulin ([B2M] less than or equal to 2.5 mg/L) and C-reactive protein ([CRP] less than or equal to 0.4 mg/dL) were the most significant standard parameters associated with both prolonged EFS and OS. Median OS exceeded 5.5 years in the one third of patients with both low B2M and CRP. When cytogenetics were included in the analysis, the presence of 11q abnormalities and/or complete or partial deletion of chromosome 13 (''unfavorable karyotype'') became a dominant negative feature for both EFS and OS. In addition to these pretransplant parameters, attainment of CR and application of two transplants within 6 months both significantly extended EFS and OS. The group of patients (7%) with high B2M and CRP with either IgA isotype or unfavorable karyotype had the worst prognosis (EFS, less than or equal to 10 months; median OS, less than or equal to 12 months) and will require novel therapy. We conclude that tandem transplants are feasible in the majority of patients up to age 70 years, effecting CR in one third of all patients. Median OS was greater than 5.5 years, regardless of pretransplant features, if the first transplant was applied within 12 months of initial treatment and the second transplant no more than 6 months later. (C) 1996 by The American Society of Hematology. C1 UNIV ARKANSAS MED SCI HOSP,DIV HEMATOL ONCOL,LITTLE ROCK,AR. UNIV ARKANSAS MED SCI HOSP,ARKANSAS CTR RES CTR,LITTLE ROCK,AR. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [CA 55819] NR 53 TC 147 Z9 149 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1996 VL 88 IS 3 BP 838 EP 847 PG 10 WC Hematology SC Hematology GA VB323 UT WOS:A1996VB32300010 PM 8704239 ER PT J AU Keller, JR Gooya, JM Ruscetti, FW AF Keller, JR Gooya, JM Ruscetti, FW TI Direct synergistic effects of leukemia inhibitory factor on hematopoietic progenitor cell growth: Comparison with other hematopoietins that use the gp130 receptor subunit SO BLOOD LA English DT Article ID FACTOR HUMAN INTERLEUKIN; STEM-CELLS; DA CELLS; STIMULATING FACTOR; MOLECULAR-CLONING; ONCOSTATIN-M; FACTOR LIF; MURINE; DIFFERENTIATION; PURIFICATION AB Because leukemia inhibitory factor (LIF) has little or no effect on murine hematopoietic progenitor cell growth yet enhances hematopoiesis in vivo, we sought to determine whether the effects of LIF were directly or indirectly mediated, or a combination of both. Although LIF alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) has no effect on colony formation of unfractionated bone marrow cells (BMCs), it enhances M-CSF-induced colony formation. In comparison, LIF synergizes with IL-3, GM-CSF, M-CSF, and Steel Factor (SLF) to promote the colony formation of partially purified lineage-negative (Lin(-)) BM progenitors without altering their differentiation. These effects were directly mediated since identical results were observed in single-cell assays. Comparing the effect of LIF with other members of this subclass of hematopoietins (IL-6, oncostatin M [OSM], and ciliary neurotrophic factor [CNTF]), we found that while LIF and IL-6 equally synergize with M-CSF and SLF to promote the colony formation of Lin(-) BMCs, OSM, and CNTF have no effect. In agreement with OSMs ability to directly bind gp130, preincubation of BMCs with OSM inhibits progenitor cell growth stimulated by the combination of LIF or IL-6 plus SLF. LIF can also directly enhance the growth of further purified more primitive Lin(-) c-kit(+) progenitor cells in the presence of IL-3, GM-CSF, or SLF. Thus, LIF can directly synergize with growth factors to promote the proliferation of purified hematopoietic progenitors, suggesting that the direct effects of LIF on hematopoietic cell growth can, in part, explain the observed hematopoietic effects in vivo. C1 SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. RP Keller, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LAB LEUKOCYTE BIOL,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-56000] NR 30 TC 17 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1996 VL 88 IS 3 BP 863 EP 869 PG 7 WC Hematology SC Hematology GA VB323 UT WOS:A1996VB32300013 PM 8704242 ER PT J AU Okazaki, IJ Kim, HJ McElvaney, NG Lesma, E Moss, J AF Okazaki, IJ Kim, HJ McElvaney, NG Lesma, E Moss, J TI Molecular characterization of a glycosylphosphatidylinositol-linked ADP-ribosyltransferase from lymphocytes SO BLOOD LA English DT Article ID SKELETAL-MUSCLE CELLS; AERUGINOSA EXOTOXIN-A; ACTIVE-SITE MUTATIONS; DIPHTHERIA-TOXIN; PSEUDOMONAS-AERUGINOSA; GLUTAMIC ACID-553; PERTUSSIS TOXIN; ASPARTIC-ACID; NAD-BINDING; RIBOSYLATION AB Mono-ADP-ribosyltransferases catalyze the transfer of the ADP-ribose moiety of nicotinamide adenine dinucleotide (NAD) to proteins. It was reported by Wang et al (J Immunol 153:4048, 1994) that incubation of mouse cytotoxic T lymphocytes (CTL) with NAD resulted in the ADP-ribosylation of membrane proteins and inhibition of cell proliferation and cytotoxicity. Treatment of CTL with phosphatidylinositol-specific phospholipase C (PI-PLC) before incubation with NAD prevented the inhibitory effects of NAD on the cells, consistent with the removal of a glycosylphosphatidylinositol (GPI)-anchored ADP-ribosyltransferase on the lymphocyte surface. We have identified and cloned a GPI-linked ADP-ribosyltransferase from Yac-l mouse T-cell lymphoma cells. The deduced amino acid sequence of the Yac-l transferase was 70% and 41% identical to those of the rabbit skeletal muscle and chicken heterophil, respectively, it contained three noncontiguous sequences similar to those found in several of the bacterial toxin and vertebrate ADP-ribosyltransferases. Based on crystallography of the bacterial toxins, these regions are believed to form, in part, the catalytic site consistent with a common mechanism for the ADP-ribose transfer reaction, In rat mammary adenocarcinoma (NMU) cells transformed with the Yac-l transferase cDNA, transferase activity was present on the cell surface and was released into the medium by treatment of cells with PI-PLC, Thus, we have cloned a novel gene that has properties identical to the transferase detected in CTL, and may be involved in the NAD-dependent regulation of proliferation and cytotoxicity. RP Okazaki, IJ (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,NIH,10 CTR DR,MSC 1434,BLDG 10,ROOM 5N307,BETHESDA,MD 20892, USA. RI McElvaney, Noel/A-6809-2010 NR 39 TC 41 Z9 42 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1996 VL 88 IS 3 BP 915 EP 921 PG 7 WC Hematology SC Hematology GA VB323 UT WOS:A1996VB32300020 PM 8704249 ER PT J AU Rafferty, SP Domachowske, JB Malech, HL AF Rafferty, SP Domachowske, JB Malech, HL TI Inhibition of hemoglobin expression by heterologous production of nitric oxide synthase in the K562 erythroleukemic cell line SO BLOOD LA English DT Article ID IRON-RESPONSIVE ELEMENT; MESSENGER-RNA; TRANSFERRIN RECEPTOR; BINDING-PROTEIN; 5-AMINOLEVULINATE SYNTHASE; ERYTHROID-DIFFERENTIATION; INTERFERON-GAMMA; ACONITASE; FERRITIN; IDENTIFICATION AB Recent studies have indicated that nitric oxide may affect iron metabolism through disruption of the iron-sulfur complex of iron regulatory protein-1, a translational regulator. in the present study, we report that heterologous expression of murine macrophage nitric oxide synthase (NOS-2) in the human erythroleukemic K562 cell line results in constitutive production of nitric oxide associated with inhibition of hemoglobin expression. K562 cells were transfected with an episomally-maintained, hygromycin-selectable expression vector bearing the coding region of NOS-2. Constitutive NOS expression was detected by Western blotting Of cell lysates and by the accumulation of nitrite in the culture media. Although NOS-transfected cells grew more slowly than control cells, they were able to maintain constitutive expression of NOS and production of nitric oxide for more than 1 month following transfection. The hemoglobin content of NOS-transfected K562 cells was less than one-fifth that of control cells, but increased markedly if NOS inhibitor was included in the culture media. The nitric oxide-mediated inhibition of hemoglobin expression was reversed by supplementing the culture media with 20 mu mol/L hemin or 0.5 mmol/L 5-aminolevulinate, indicating that nitric oxide did not directly inhibit hemoglobin synthesis, but likely acted on a step in heme synthesis. mRNA levels for globin and erythroid aminolevulinic acid synthase (eALAS) were the same in both NOS-transfected and control cells. Our observations indicate that hemoglobin expression is inhibited by nitric oxide in NOS-transfected K562 cells by posttranscriptional repression of eALAS, the first enzyme of the heme biosynthetic pathway. The most likely mechanism is a nitric oxide-mediated translational repression of eALAS, as was recently demonstrated for ferritin synthesis. These observations further illustrate the potential for endogenously produced nitric oxide to regulate cellular posttranscriptional events. In particular, our observations may be relevant to the role of nitric oxide in anemia and lowered blood hemoglobin concentrations that are associated with chronic infections, such as tuberculosis or parasitic disease. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 35 TC 40 Z9 43 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1996 VL 88 IS 3 BP 1070 EP 1078 PG 9 WC Hematology SC Hematology GA VB323 UT WOS:A1996VB32300039 PM 8704216 ER PT J AU Sekhsaria, S Fleisher, TA Vowells, S Brown, M Miller, J Gordon, I Blaese, RM Dunbar, CE Leitman, S Malech, HL AF Sekhsaria, S Fleisher, TA Vowells, S Brown, M Miller, J Gordon, I Blaese, RM Dunbar, CE Leitman, S Malech, HL TI Granulocyte colony-stimulating factor recruitment of CD34(+) progenitors to peripheral blood: Impaired mobilization in chronic granulomatous disease and adenosine deaminase-deficient severe combined immunodeficiency disease patients SO BLOOD LA English DT Article ID HUMAN-BONE-MARROW; STEM-CELL TRANSPLANTATION; FLOW CYTOMETRIC ANALYSIS; HIGH-DOSE CHEMOTHERAPY; MEDIATED GENE-TRANSFER; HEMATOPOIETIC PROGENITORS; G-CSF; LYMPHOMA; THERAPY; GROWTH AB Peripheral blood (PB] CD34(+) cells mobilized by granulocyte colony-stimulating factor (G-CSF) administration are potentially useful for transplantation and as a target of gene transfer for therapy of hematopoietic disorders. Efficient harvest and planning for clinical use of PB CD34(+) cells ideally requires foreknowledge of the expected mobilization kinetics and yield. We developed a sensitive flow cytometric assay for accurately enumerating CD34(+) cells throughout the range seen at baseline to peak mobilization. We used this assay to assess the kinetics of G-CSF-mediated mobilization of CD34(+) cells to PB in normal volunteers and in patients with chronic granulomatous disease (CGD) or adenosine deaminase (ADA)-deficient severe combined immunodeficiency disease (SCID). Two dose levers of G-CSF were examined (5 and 10 mu g/kg/d for 7 days). Both doses were well tolerated. For normal subjects and patients an increase in PB CD34 + cells was first detected only preceding the third dose of G-CSF (day 3), peaked transiently on day 5 or 6, and then decreased thereafter despite additional doses of G-CSF. With 32 normal volunteers mean peak CD34(+) cell counts were 57 and 76 cells/mm(3) of blood (5 and 10 mu g doses, respectively), whereas for 18 CGD patients the mean peaks were 31 and 40 cells/mm(3) of blood. For 2 ADA-deficient SCID patients studied at a G-CSF dose of 5 mu g/kg/d, the average peak was 16 cells/mm(3) of blood. For both of these patient groups mobilization of CD34(+) cells to PB was impaired compared with similarly treated normal subjects (P < .05). By contrast to the kinetics of the CD34(+) cell mobilization, the absolute neutrophil count (ANC) increased markedly by 6 hours after the first dose of G-CSF and then increased steadily through day 8. At days 5 and 6 (peak mobilization of CD34(+) cells) the mean ANC of CGD and ADA patients was only Slightly lower (less than or equal to 15%) than that seen with normal subjects, whereas the difference in CD34(+) cell mobilization was >48%. Thus, ANC is not a reliable surrogate to predict peak PB CD34(+) cell counts and direct enumeration of PB CD34(+) counts should be undertaken in decisions regarding timing and duration of apheresis to harvest a specific number of these cells. Finally, unexpected, but significant differences in the PB CD34(+) cell mobilization between normal subjects and patients with inherited disorders can occur and underscores the importance of establishing the expected mobilization of PB CD34(+) cells in the planning of treatment approaches using these cells. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,SERV IMMUNOL,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 47 TC 51 Z9 51 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 AUG 1 PY 1996 VL 88 IS 3 BP 1104 EP 1112 PG 9 WC Hematology SC Hematology GA VB323 UT WOS:A1996VB32300044 PM 8704221 ER PT J AU Couriel, D Canosa, J Engler, H Collins, A Dunbar, C Barrett, AJ AF Couriel, D Canosa, J Engler, H Collins, A Dunbar, C Barrett, AJ TI Early reactivation of cytomegalovirus and high risk of interstitial pneumonitis following T-depleted BMT for adults with hematological malignancies SO BONE MARROW TRANSPLANTATION LA English DT Article DE CMV; interstitial pneumonitis; T cell depletion; allogeneic bone marrow transplantation ID BONE-MARROW TRANSPLANTATION; PERIPHERAL-BLOOD LEUKOCYTES; POLYMERASE CHAIN-REACTION; VIRUS INFECTION; GANCICLOVIR; DISEASE; RECIPIENTS; ANTIGENEMIA; RECOVERY; THERAPY AB Reactivation of cytomegalovirus (CMV) is a major cause of morbidity and mortality following allogeneic bone marrow transplantation (BMT) and early reactivation with increased risk of interstitial pneumonia (IF) has been reported in T cell-depleted BMT. In 21 patients at risk for CMV reactivation following T cell-depleted BMT for hematological malignancies, CMV reactivation was the main cause of transplant-related mortality: 19 (90.5%) reactivated CMV and five (26% actuarial) developed fatal IF. Median reactivation time post-BMT was 22 days for IP and 39.5 days for non-IF patients (P = 0.04), Patients developing IP showed no increase in lymphocyte count following CMV reactivation, There was a trend for higher pp65 antigen load at reactivation in patients who relapsed with CMV or progressed to IP. Donor lymphocyte transfusions (DLT) were given to pre-empt leukemic relapse and viral infection (15 patients) or to treat UP in two, Nine of 19 patients reactivated CMV before receiving DLT on day 30 post-BMT and DLT were ineffective in established IF. However DLT from seropositive donors did not cause IF. These results confirm the relationship of donor T cell function,vith CMV reactivation following BMT, They suggest that patients receiving T cell-depleted BMT should be protected from CMV disease with prophylactic rather than pre-emptive treatments. C1 NHLBI,HEMATOL BRANCH,BONE MARROW TRANSPLANT UNIT,BETHESDA,MD 20892. NIH,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,HOSP EPIDEMIOL SERV,BETHESDA,MD 20892. NR 30 TC 65 Z9 65 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 1996 VL 18 IS 2 BP 347 EP 353 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA VD053 UT WOS:A1996VD05300013 PM 8864445 ER PT J AU Benson, JR Wakefield, LM Baum, M Colletta, AA AF Benson, JR Wakefield, LM Baum, M Colletta, AA TI Synthesis and secretion of transforming growth factor beta isoforms by primary cultures of human breast tumour fibroblasts in vitro and their modulation by tamoxifen SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; growth factor; paracrine mechanism; tamoxifen ID MESSENGER-RNA; CANCER-CELLS; EXPRESSION; LOCALIZATION; INDUCTION; TISSUE AB Tamoxifen may mediate its effect in early breast cancer in part via an oestrogen receptor (ER)-independent pathway by directly stimulating fibroblasts to produce the negative paracrine growth factor transforming growth Factor (TGF)-beta. We have previously shown that secretion of this factor is induced 3- to 30-fold in human fetal fibroblasts in vitro, and by stromal fibroblasts in vivo following tamoxifen treatment of ER-positive and ER-negative breast cancer patients. Primary cultures of breast tumour fibroblasts have been exposed to tamoxifen for 48 h, and rates of secretion of TGF-beta(1) and TGF-beta(2) measured using a quantitative immunoassay. Fibroblast strains derived from malignant and benign tumours produced and secreted similar amounts of TGF-beta(1), but benign breast tumour fibroblasts secreted significantly higher levels of TGF-beta(2) compared with fibroblasts of malignant origin. Tamoxifen did not induce any consistent increase in TGF-beta secretion into the conditioned medium, but immunofluorescence analysis for the intracellular form of TGF-beta(1) revealed evidence of increased immunoreactive protein in tamoxifen-treated fibroblasts, which is localised to the nucleus. Therefore synthesis of TGF-beta(1) appears to be stimulated by tamoxifen, but increased secretion may be abrogated in vitro. Furthermore, using immunocytochemistry and transient transfection with an ER-responsive reporter construct, no ER was demonstrable in these fibroblasts supporting the proposed ER-independent paracrine pathway. C1 NATL CANC INST,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP Benson, JR (reprint author), ROYAL MARSDEN HOSP,INST CANC RES,SECT ACAD SURG,HARTWELL LAB,FULHAM RD,LONDON SW3 6JJ,ENGLAND. NR 38 TC 36 Z9 37 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD AUG PY 1996 VL 74 IS 3 BP 352 EP 358 DI 10.1038/bjc.1996.365 PG 7 WC Oncology SC Oncology GA UZ039 UT WOS:A1996UZ03900004 PM 8695348 ER PT J AU Boyer, JL Siddiqi, S Fischer, B RomeroAvila, T Jacobson, KA Harden, TK AF Boyer, JL Siddiqi, S Fischer, B RomeroAvila, T Jacobson, KA Harden, TK TI Identification of potent P-2Y-purinoceptor agonists that are derivatives of adenosine 5'-monophosphate SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE P-2Y-purinoceptors; cyclic AMP accumulation; inositol phosphate formation; adenylyl cyclase inhibition; activation of phospholipase C; C6 rat glioma cells; turkey erythrocytes; 2-thioether derivatives of adenosine monophosphate ID PHOSPHOLIPASE-C; ADENYLYL-CYCLASE; 2-THIOETHER DERIVATIVES; PURINERGIC RECEPTOR; ATP RECEPTOR; G-PROTEIN; EXPRESSION; NUCLEOTIDES; CLONING; ACTIVATION AB 1 A series of chain-extended 2-thioether derivatives of adenosine monophosphate were synthesized and tested as agonists for activation of the phospholipase C-linked P-2Y-purinoceptor of turkey erythrocyte membranes, the adenylyl cyclase-linked P-2Y-purinoceptor of C6 rat glioma cells, and the cloned human P-2U-receptor stably expressed in 1321N1 human astrocytoma cells. 2 Although adenosine monophosphate itself was not an agonist in the two P-2Y-purinoceptor test systems, eleven different 2-thioether-substituted adenosine monophosphate analogues were full agonists. The most potent of these agonists, 2-hexylthio AMP, exhibited an EC(50) value of 0.2 nM for activation of the C6 cell receptor. This potency was 16,000 fold greater than that of ATP and was only 10 fold less than the potency of 2-hexylthio ATP in the same system. 2-hexylthio adenosine was inactive. 3 Monophosphate analogues that were the most potent activators of the C6 cell P-2Y-purinoceptor were also the most potent activators of the turkey erythrocyte P-2Y-purinoceptor. However, agonists were in general more potent at the C6 cell receptor, and potency differences varied between 10 fold and 300 fold between the two receptors. 4 Although 2-thioether derivatives of adenosine monophosphate were potent P-2Y-purinoceptor agonists no effect of these analogues on the human P-2U-purinoceptor were observed. 5 These results support the view that a single monophosphate is sufficient and necessary for full agonist activity at P-2Y-purinoceptors, and provide insight for strategies for development of novel P-2Y-purinoceptor agonists of high potency and selectivity. C1 UNIV N CAROLINA,SCH MED,DEPT PHARMACOL,CHAPEL HILL,NC 27599. NIDDK,NIH,MOL RECOGNIT SECT,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999]; NHLBI NIH HHS [HL 32322]; NIGMS NIH HHS [GM38213] NR 23 TC 42 Z9 43 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD AUG PY 1996 VL 118 IS 8 BP 1959 EP 1964 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VC660 UT WOS:A1996VC66000014 PM 8864529 ER PT J AU Boumpas, DT AF Boumpas, DT TI A novel action of glucocorticoids - NF-kappa B inhibition SO BRITISH JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID FUNCTIONAL ANTAGONISM; TRANSCRIPTION FACTORS; T-CELLS; C-JUN; RECEPTOR; INTERFERENCE; IMMUNOSUPPRESSION; MECHANISM; HORMONE; AP-1 RP Boumpas, DT (reprint author), NIH,BLDG 10,RM 9S209,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 18 TC 22 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0263-7103 J9 BRIT J RHEUMATOL JI Br. J. Rheumatol. PD AUG PY 1996 VL 35 IS 8 BP 709 EP 710 PG 2 WC Rheumatology SC Rheumatology GA VC659 UT WOS:A1996VC65900002 PM 8761180 ER PT J AU Lamb, ME AF Lamb, ME TI Effects of nonparental child care on child development: An update SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Review DE day care; nursery school; infants; preschoolers; nonparental care ID INFANT DAY-CARE; NATIONAL LONGITUDINAL SURVEY; LOW-INCOME FAMILIES; MATERNAL EMPLOYMENT; SOCIAL COMPETENCE; SOCIOEMOTIONAL DEVELOPMENT; SUBSTITUTE CAREGIVERS; SWEDISH PRESCHOOLERS; HOME CARE; ATTACHMENT AB Objective: To review the published literature on the effects of nonparental and out-of-home care on infants, toddlers, and preschoolers. Method: Narrative literature review. Results: Although substantial controversy persists, the accumulated evidence suggests that nonparental care does no necessarily have either beneficial or detrimental effects on infants and children, although it can have such effects. In some circumstances, careproviders establish relationships with children that have significant effects on development, and this increases the importance of ensuring that careproviders are well trained, behave sensitively, and are stable rather than ephemeral figures in children's lives. Nonparental care is associated with behaviour problems (including aggression and noncompliance) when the care is of poor quality and opportunities for meaningful relationships with stable careproviders are not available, however. Conclusion: The effects of out-of-home care vary depending on the quality of care as well as the characteristics of individual children, including their age, temperaments, and individual backgrounds. RP Lamb, ME (reprint author), NICHHD,SECT SOCIAL & EMOT DEV,9190 ROCKVILLE PIKE,BETHESDA,MD 20814, USA. NR 149 TC 15 Z9 15 U1 3 U2 6 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA SUITE 200, 237 ARGYLE AVE, OTTAWA ON K2P 1B8, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD AUG PY 1996 VL 41 IS 6 BP 330 EP 342 PG 13 WC Psychiatry SC Psychiatry GA VC581 UT WOS:A1996VC58100003 PM 8862852 ER PT J AU Blaney, SM Phillips, PC Packer, RJ Heideman, RL Berg, SL Adamson, PC Allen, JC Sallan, SE Jakacki, RL Lange, BJ Reaman, GH Horowitz, ME Poplack, DG Balis, FM AF Blaney, SM Phillips, PC Packer, RJ Heideman, RL Berg, SL Adamson, PC Allen, JC Sallan, SE Jakacki, RL Lange, BJ Reaman, GH Horowitz, ME Poplack, DG Balis, FM TI Phase II evaluation of topotecan for pediatric central nervous system tumors SO CANCER LA English DT Article DE topotecan; phase II trial; topoisomerase I; brain tumors ID DOSE INTENSITY; SOLID TUMORS; 9-DIMETHYLAMINOMETHYL-10-HYDROXYCAMPTOTHECIN; CHEMOTHERAPY; XENOGRAFTS; CHILDREN; MODEL; ADULT AB BACKGROUND. Topotecan is a topoisomerase I inhibitor that has good penetration across the blood-brain barrier and significant antitumor activity against human brain tumor xenografts. In a Phase I trial in children with refractory cancer, topotecan was well tolerated when administered as a 24-hour infusion. The maximum tolerated dose was 5.5 mg/m(2) and the dose-limiting toxicity was myelosuppression. This Phase II study of topotecan was performed to assess the activity of topotecan against childhood brain tumors. METHODS, Forty-five children with either a previously treated primary brain tumor that was refractory to standard therapy, or an untreated brain stem glioma or glioblastoma multiforme, received topotecan administered as a 24-hour intravenous infusion every 21 days. The initial dose was 5.5 mg/m(2) with escalation to 7.5 mg/m(2) on the second and subsequent doses in patients who did not experience dose-limiting toxicity. RESULTS, There were no complete or partial responses in the patients with high grade glioma (n = 9), medulloblastoma (n = 9), or brain stem glioma (n = 14). One of 2 patients with a low grade glioma had a partial response lasting more than 17 months; 3 patients with a brain stem glioma had stable disease for 12 to 28 weeks; and 1 patient with a malignant neuroepithelial tumor and 1 patient with an optic glioma had stable disease for 41 weeks and 22 weeks, respectively. Dose escalation from 5.5 mg/m(2) to 7.5 mg/m(2) was well tolerated in the first 11 patients enrolled on this study who had not received prior craniospinal radiation therapy. The starting dose was subsequently increased to 7.5 mg/m(2) for patients without prior craniospinal radiation. CONCLUSIONS, Topotecan administered as a 24-hour infusion every 21 days is inactive in high grade gliomas, medulloblastomas, and brain stem tumors. (C) 1996 American Cancer Society. C1 NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. CHILDRENS HOSP PHILADELPHIA, DIV NEUROL & HEMATOL ONCOL, PHILADELPHIA, PA 19104 USA. CHILDRENS NATL MED CTR, DEPT HEMATOL ONCOL, WASHINGTON, DC 20010 USA. ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38105 USA. NYU, MED CTR, DEPT NEUROL, NEW YORK, NY USA. DANA FARBER CANC INST, DIV PEDIAT HEMATOL ONCOL, BOSTON, MA 02115 USA. JAMES WHITCOMB RILEY HOSP CHILDREN, DIV PEDIAT HEMATOL ONCOL, INDIANAPOLIS, IN 46202 USA. TEXAS CHILDRENS HOSP, SERV HEMATOL, HOUSTON, TX 77030 USA. RP Blaney, SM (reprint author), TEXAS CHILDRENS CANC CTR, 6621 FANNIN MC 3-3320, HOUSTON, TX 77030 USA. NR 17 TC 60 Z9 60 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD AUG 1 PY 1996 VL 78 IS 3 BP 527 EP 531 PG 5 WC Oncology SC Oncology GA UY254 UT WOS:A1996UY25400021 PM 8697400 ER PT J AU Fraumeni, JF AF Fraumeni, JF TI An interdisciplinary approach to populations at high risk of cancer SO CANCER LA English DT Article ID LI-FRAUMENI SYNDROME; SOFT-TISSUE SARCOMA; LUNG-CANCER; BLADDER-CANCER; UNITED-STATES; P53 MUTATIONS; AIR-POLLUTION; FAMILY; EMPLOYMENT; PRONE RP Fraumeni, JF (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N,ROOM 543,BETHESDA,MD 20892, USA. NR 53 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1996 VL 78 IS 3 BP 548 EP 552 PG 5 WC Oncology SC Oncology GA UY254 UT WOS:A1996UY25400024 PM 8697403 ER PT J AU Kinsella, TJ Sindelar, WF AF Kinsella, TJ Sindelar, WF TI Intraoperative radiotherapy for pancreatic carcinoma - Experimental and clinical studies SO CANCER LA English DT Article; Proceedings Paper CT Symposium on Cancer of the Pancreas - Challenge of the Nineties CY JUN, 1994 CL NEWPORT, RI SP Eli Lilly & Co ID LARGE ANIMAL-MODEL; RADIATION-THERAPY; BEAM IRRADIATION; EXTERNAL BEAM; CANCER; IORT; RETROPERITONEAL; TOLERANCE; ADJUVANT; AORTA AB Intraoperative radiotherapy (IORT) is an innovative treatment approach that has been tested in several Phase I-II studies and small Phase III trials in patients with resectable and unresectable pancreatic cancer. The technical approach and dose guidelines for adjacent normal tissues have been established in a series of experiments using a large animal (canine) model. This article reviews the experimental and clinical studies of IORT in cancer of the pancreas. (C) 1996 American Cancer Society. C1 NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. RP Kinsella, TJ (reprint author), UNIV WISCONSIN,CTR COMPREHENS CANC,DEPT HUMAN ONCOL,SCH MED,CLIN SCI CTR K4312,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 36 TC 18 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1996 VL 78 IS 3 SU S BP 598 EP 604 PG 7 WC Oncology SC Oncology GA UY778 UT WOS:A1996UY77800004 PM 8681298 ER PT J AU Pluda, JM Parkinson, DR AF Pluda, JM Parkinson, DR TI Clinical implications of tumor-associated neovascularization and current antiangiogenic strategies for the treatment of malignancies of pancreas SO CANCER LA English DT Article; Proceedings Paper CT Symposium on Cancer of the Pancreas - Challenge of the Nineties CY JUN, 1994 CL NEWPORT, RI SP Eli Lilly & Co ID FIBROBLAST GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; PLATELET FACTOR-IV; MATRIX METALLOPROTEINASE INHIBITOR; ENDOTHELIAL-CELL PROLIFERATION; INVASIVE BREAST-CARCINOMA; ANGIOGENESIS INHIBITOR; PENTOSAN POLYSULFATE; MICROVESSEL DENSITY; PROSTATE CARCINOMA AB There is now a substantial body of evidence that tumor growth is angiogenesis-dependent, and that neovascularization is also necessary for tumor invasion and metastasis. In addition, the assessment of microvessel count or density in a primary tumor may ultimately prove to be a significant and independent prognostic parameter for clinical outcome with respect to tumor recurrence, metastasis, and ultimately, overall patient survival. As our knowledge of the pathways, steps, and factors involved in the underlying pathogenesis of tumor-associate angiogenesis increases, therapeutic agents and modalities aimed at inhibiting angiogenesis by blocking one or more of these steps or factors may be devised and evaluated for their potential to inhibit cancer growth and spread. Ultimately, the inhibition of tumor-associated angiogenesis and associated processes could conceivably form the foundation upon which the treatment of aggressive malignancies is based. (C) 1996 American Cancer Society. RP Pluda, JM (reprint author), NCI,INVEST DRUG BRANCH,CTEP,DCTDC,6130 EXECUT BLVD,EXECUT PLAZA N,ROOM 715,ROCKVILLE,MD 20852, USA. NR 88 TC 35 Z9 35 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1996 VL 78 IS 3 SU S BP 680 EP 687 PG 8 WC Oncology SC Oncology GA UY778 UT WOS:A1996UY77800013 PM 8681307 ER PT J AU Bird, CL Ingles, SA Frankl, HD Lee, ER Longnecker, MP Haile, RW AF Bird, CL Ingles, SA Frankl, HD Lee, ER Longnecker, MP Haile, RW TI Serum lipids and adenomas of the left colon and rectum SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY HEART-DISEASE; SELF-DEFENSE OFFICIALS; COLORECTAL ADENOMAS; BLOOD-CHOLESTEROL; PHYSICAL-ACTIVITY; LARGE-BOWEL; CANCER; POLYPS; PLASMA AB Levels of serum lipids are partially determined by several established risk factors for colorectal cancer and are themselves potential risk factors for the disease, However, evaluating serum lipids as risk factors has proved problematic because metabolic events associated with malignant transformation or progression appear to alter serum lipid concentrations, Serum lipid concentrations are less likely to have altered in individuals with precancerous lesions, such as colorectal adenomas, During 1991-1993, we collected fasting blood samples from and provided questionnaires to men and women 50-75 years old, who visited sigmoidoscopy clinics at a health maintenance organization, Serum lipid concentrations from 486 cases with adenomas and 520 controls were analyzed, Compared to subjects in the lowest quintile of serum triglyceride concentrations, subjects in the highest quintile had an adjusted odds ratio of 1.5 (95% confidence interval, 1.0-2.2), The corresponding odds ratio for total cholesterol was 1.3 (0.9-1.9); for high-density lipoprotein cholesterol, it was 1.1 (0.7-1.6); and for low-density lipoprotein cholesterol, it was 1.1 (0.7-1.6), Further adjustment for potential confounding did not alter these results substantively, although determinants of serum triglycerides and high-density lipoprotein cholesterol (e.g., obesity, physical activity, and refined carbohydrate and alcohol intake) in this and other studies may not be sufficiently well measured to avoid residual confounding, Higher levels of serum triglycerides are associated with an increased risk of adenomatous polyps. Consistent with previous studies, serum cholesterol was not inversely related to the risk of colorectal polyps. C1 UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. KAISER PERMANENTE MED CTR,DIV GASTROENTEROL,LOS ANGELES,CA 90027. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. SUNSET MED CTR,DIV GASTROENTEROL,LOS ANGELES,CA 90027. BELLFLOWER MED CTR,DIV GASTROENTEROL,LOS ANGELES,CA 90027. OI Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [CA 42710, CA 49565, CA 51923] NR 40 TC 46 Z9 46 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 1996 VL 5 IS 8 BP 607 EP 612 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VC074 UT WOS:A1996VC07400004 PM 8824362 ER PT J AU Zhang, L Blot, WJ You, WC Chang, YS Kneller, RW Jin, ML Li, JY Zhao, L Liu, WD Zhang, JS Ma, JL Samloff, IM Correa, P Blaser, MJ Xu, GW Fraumeni, JF AF Zhang, L Blot, WJ You, WC Chang, YS Kneller, RW Jin, ML Li, JY Zhao, L Liu, WD Zhang, JS Ma, JL Samloff, IM Correa, P Blaser, MJ Xu, GW Fraumeni, JF TI Helicobacter pylori antibodies in relation to precancerous gastric lesions in a high-risk Chinese population SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SERUM PEPSINOGENS; STOMACH-CANCER; EPIDEMIOLOGY; INFECTION; CHILDHOOD; CHILDREN; MARKERS; AREAS AB Helicobacter pylori infection is a major cause of gastritis and may be a key risk factor for stomach cancer, but its role in the process of gastric carcinogenesis is not well understood. Herein, we examine H. pylori prevalence in relation to demographic and lifestyle factors and to severity of precancerous lesions in an area of China with one of the highest rates of stomach cancer in the world. H. pylori serum IgG antibody positivity was assayed among 2646 adults, ages 35-64, participating in a population-based gastroscopic screening survey in the high-risk area. The prevalence of positivity was evaluated according to gastric histology, environmental and lifestyle variables determined by interviews during the screening, and level of serum pepsinogens. The odds of advanced precancerous lesions (intestinal metaplasia and dysplasia) of the stomach among those with antibody positivity were estimated by logistic regression. Seventy-two % of the population was H. pylori antibody-positive, with nonsignificant variation by sex, age, income, education, family size, and cigarette smoking habits. H. pylori positivity was higher among those who ate sour pancakes, a fermented indigenous staple that is a risk factor for gastric dysplasia and stomach cancer in this population. The prevalence of H. pylori varied most notably, however, with gastric pathology. The percent of H. pylori positivity increased from 55 to 60 to 87% among those with superficial (nonatrophic) gastritis, mild chronic atrophic gastritis, and severe chronic atrophic gastritis, respectively, before falling to 78% among those with intestinal metaplasia or dysplasia. H. pylori antibody positivity also was strongly correlated with serum pepsinogen concentrations, particularly pepsinogen II, but knowledge of H. pylori status did not markedly improve serological identification of advanced precancerous lesions above that provided by pepsinogen ratios alone. The findings suggest that H. pylori infection contributes to the process of gastric carcinogenesis, particularly during the early stages, in this high-risk area. C1 NCI,BETHESDA,MD 20892. BEIJING MED UNIV,BEIJING INST CANC RES,BEIJING 100083,PEOPLES R CHINA. BEIJING MED UNIV,SCH ONCOL,BEIJING 100083,PEOPLES R CHINA. INT EPIDEMIOL INST LTD,ROCKVILLE,MD 20850. WEIFANG MED INST,SHANDONG 261041,PEOPLES R CHINA. DEPT VET AFFAIRS MED CTR,SEPULVEDA,CA 91343. LOUISIANA STATE UNIV,NEW ORLEANS,LA 70112. VANDERBILT UNIV,NASHVILLE,TN 37232. VET ADM MED CTR,NASHVILLE,TN 37232. FU NCI NIH HHS [N01-CA-21009, N01-CA-15620, N01-CA-05631] NR 24 TC 75 Z9 84 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 1996 VL 5 IS 8 BP 627 EP 630 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VC074 UT WOS:A1996VC07400007 PM 8824365 ER PT J AU Kelloff, GJ Fay, JR Steele, VE Lubet, RA Boone, CW Crowell, JA Sigman, CC AF Kelloff, GJ Fay, JR Steele, VE Lubet, RA Boone, CW Crowell, JA Sigman, CC TI Epidermal growth factor receptor tyrosine kinase inhibitors as potential cancer chemopreventives SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID SQUAMOUS-CELL CARCINOMA; CERVICAL INTRAEPITHELIAL NEOPLASIA; ANTICANCER DRUG DEVELOPMENT; HUMAN BREAST-CANCER; FACTOR-ALPHA; SIGNAL-TRANSDUCTION; TGF-ALPHA; EGF-RECEPTOR; MONOCLONAL-ANTIBODIES; HUMAN PAPILLOMAVIRUS AB Among the most important targets for chemopreventive intervention and drug development are deregulated signal transduction pathways, and protein tyrosine kinases are key components of these pathways. Loss of tyrosine kinase regulatory mechanisms has been implicated in neoplastic growth; indeed, many oncogenes code for either receptor or cellular tyrosine kinases. Because of its deregulation in many cancers (bladder, breast, cervix, colon, esophagus, head and neck, lung, and prostate), the epidermal growth factor receptor (EGFR) has been selected as a potential target for chemoprevention. Because growth factor networks are redundant, selective inhibition of signaling pathways activated in precancerous and cancerous cells should be possible. Requirements for specific EGFR inhibitors include specificity for EGFR, high potency, activity in intact cells, and activity in vivo. Inhibition of autophosphorylation is preferred, because it should result in total blockade of the signaling pathway. Inhibitors that compete with substrate rather than at the ATP-binding site are also preferable, because they are not as likely to inhibit other ATP-using cellular enzymes. Several classes of specific EGFR inhibitors have been synthesized recently, including structures such as benzylidene malononitriles, dianilinophthalimides quinazolines, pyrimidines, [(alkylamino)methyl]-acrylophenones, enollactones, dihydroxybenzyl-aminosalicylates, 2-thioindoles, aminoflavones, and tyrosine analogue-containing peptides. A possible testing strategy for the development of these and other EGFR inhibitors as chemopreventive agents includes the following steps: (a) determine EGFR tyrosine kinase inhibitory activity in vitro; (b) evaluate EGFR specificity and selectivity (relative to other tyrosine kinases and other protein kinases); (c) determine inhibition of EGFR-mediated effects in intact cells; (d) determine inhibition of EGFR-mediated effects in vivo (e.g., in nude mouse tumor xenografts); and (e) determine chemopreventive efficacy in vivo (e.g., in the hamster buccal pouch or mouse or rat bladder). C1 CCS ASSOCIATES,MT VIEW,CA 94043. RP Kelloff, GJ (reprint author), NCI,CHEMOPREVENT BRANCH,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,SUITE 201,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 108 TC 85 Z9 88 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 1996 VL 5 IS 8 BP 657 EP 666 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VC074 UT WOS:A1996VC07400012 PM 8824370 ER PT J AU Lietzau, J AF Lietzau, J TI Teaching symptom management of HIV/AIDS using algorithms SO CANCER NURSING LA English DT Article DE human immunodeficiency virus; acquired immunodeficiency syndrome; patient education; symptom management; algorithm ID PATIENT EDUCATION AB Management of patients infected with the human immunodeficiency virus (HIV) or with acquired immunodeficiency syndrome (AIDS) presents a complex set of challenges to the health-care professional, especially in the area of patient education. Lack of resources, time constraints, and/or patients' willingness to learn about the disease are all factors that can impact the teaching/learning process. Creative and effective teaching strategies must br implemented so that adequate information and support is provided to the patient and/or the caregiver. Algorithms were developed for the patient and/or caregiver to use as a quick reference for decision making regarding symptom management of common manifestations of HIV/AIDS. RP Lietzau, J (reprint author), NCI,NIH,BETHESDA,MD 20892, USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD AUG PY 1996 VL 19 IS 4 BP 263 EP 268 DI 10.1097/00002820-199608000-00001 PG 6 WC Oncology; Nursing SC Oncology; Nursing GA UY561 UT WOS:A1996UY56100001 PM 8768683 ER PT J AU Rao, CV Rivenson, A Zang, E Steele, V Kelloff, G Reddy, BS AF Rao, CV Rivenson, A Zang, E Steele, V Kelloff, G Reddy, BS TI Inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced lymphoma formation by oltipraz SO CANCER RESEARCH LA English DT Article ID NON-HODGKINS-LYMPHOMA; MALE F344 RATS; COLON CARCINOGENESIS; MULTIPLE-MYELOMA; AZOXYMETHANE; INDUCTION; SMOKING; RISK AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine present in pyrolysate products of meat and fish and has been shown to induce tumors in the colon, mammary gland, and possibly lymphatic system. Experiments were designed to examine the lymphoma-inducing capacity of PhIP and to test the inhibitory effects of oltipraz on PhIP-induced lymphomas in male F344 rats. Beginning at 5 weeks of age, groups of rats were fed the diets containing 0, 200, and 400 ppm oltipraz with or without 100-400 ppm PhIP. All animals were continued on this regimen until the 58th week. The results indicate that administration of PhIP produced lymphomas in 75% of rats. Most of the large lymphomas were thymomas (65%), and these lymphomas developed in less than 6 months. Death of animals during the course of the study was due to suffocation produced by a large lymphoma that filled the entire thoracic cavity, resulting in collapse of the lungs. Administration of 200-400 ppm oltipraz significantly protected rats from PhIP-induced toxicity; most of the rats survived until termination of the experiments. It is noteworthy that the addition of oltipraz at 200 and 400 ppm in the diet suppressed the PhIP-induced lymphomas to 90-100%. In conclusion, PhIP-induced lymphomas in the laboratory rat appears to be a very useful model to analyze the genesis of lymphomas, and oltipraz serves as a potential chemopreventive agent for lymphomas. C1 AMER HLTH FDN,DIV PATHOL & TOXICOL,VALHALLA,NY 10595. AMER HLTH FDN,DIV EPIDEMIOL,VALHALLA,NY 10595. NCI,BETHESDA,MD 20892. RP Rao, CV (reprint author), AMER HLTH FDN,DIV NUTR CARCINOGENESIS,1 DANA RD,VALHALLA,NY 10595, USA. RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [CN85095-07, CA17613] NR 20 TC 34 Z9 35 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1996 VL 56 IS 15 BP 3395 EP 3398 PG 4 WC Oncology SC Oncology GA UZ288 UT WOS:A1996UZ28800003 PM 8758900 ER PT J AU Tanner, MM Tirkkonen, M Kallioniemi, A Isola, J Kuukasjarvi, T Collins, C Kowbel, D Guan, XY Trent, J Gray, JW Meltzer, P Kallioniemi, OP AF Tanner, MM Tirkkonen, M Kallioniemi, A Isola, J Kuukasjarvi, T Collins, C Kowbel, D Guan, XY Trent, J Gray, JW Meltzer, P Kallioniemi, OP TI Independent amplification and frequent co-amplification of three nonsyntenic regions on the long arm of chromosome 20 in human breast cancer SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; DNA AMPLIFICATION; SEQUENCES; TUMORS AB DNA amplification at 20q13.2 is common in breast cancer, correlates with poor prognosis, and may reflect location of an important oncogene. Recently, other regions along 20q were also found to undergo amplification. Here, amplification levels and patterns of co-amplification were analyzed by interphase fluorescence in situ hybridization at 14 loci along 20q in 146 uncultured breast carcinomas and 14 cell lines. Three regions were independently amplified in uncultured tumors: RMC20C001 region at 20q13.2 (highly amplified in 9.6% of the cases), PTPN1 region 3 Mb proximal (6.2%), and AIB3 region at 20q11 (6.2%), Co-amplifications involving two or three of these regions were seen in 11 of the 19 highly amplified tumors. The results suggest that three distinct nonsyntenic regions along 20q may be important and that complex chromosomal rearrangements underlie their frequent co-amplification in breast cancer. C1 TAMPERE UNIV, FIN-33101 TAMPERE, FINLAND. NIH, CANC GENET LAB, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. UNIV CALIF BERKELEY, LAWRENCE BERKELEY LAB, DIV LIFE SCI, BERKELEY, CA 94720 USA. UNIV CALIF SAN FRANCISCO, DEPT LAB MED, DIV MOL CYTOMETRY, SAN FRANCISCO, CA 94143 USA. RP Tanner, MM (reprint author), TAMPERE UNIV HOSP, INST MED TECHNOL, CANC GENET LAB, BOX 607, FIN-33101 TAMPERE, FINLAND. RI Guan, Xin-Yuan/A-3639-2009; Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012; OI Guan, Xin-Yuan/0000-0002-4485-6017; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Anne/0000-0003-3552-8158 FU NCI NIH HHS [CA58207] NR 20 TC 168 Z9 168 U1 1 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 AUG 1 PY 1996 VL 56 IS 15 BP 3441 EP 3445 PG 5 WC Oncology SC Oncology GA UZ288 UT WOS:A1996UZ28800012 PM 8758909 ER PT J AU Guan, XY Xu, J Anzick, SL Zhang, HE Trent, JM Meltzer, PS AF Guan, XY Xu, J Anzick, SL Zhang, HE Trent, JM Meltzer, PS TI Hybrid selection of transcribed sequences from microdissected DNA: Isolation of genes within an amplified region at 20q11-q13.2 in breast cancer SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CHROMOSOME MICRODISSECTION; AMPLIFICATION AB In human breast carcinomas, increased copy number of DNA sequences derived from the long arm of chromosome 20 (20q) has been commonly observed by both chromosome microdissection and comparative genomic hybridization. This chromosomal region is likely to contain one or more genes that are the biological targets of this amplification event. We describe here the utilization of a chromosome microdissection-hybrid selection strategy to isolate transcribed sequences from microdissected homogeneously staining regions encompassing 20q. Using this strategy, we have isolated three novel amplified genes (termed AIB1, AIB3, and AIB4) from a cDNA library constructed from the 20q amplified breast cancer cell line BT-474. These three genes were mapped to 20q11 (AIB3 and AIB4) and 20q12 (AIB1) by fluorescence in situ hybridization. Our results indicate an unsuspected complexity to the amplification pattern of 20q in breast cancer and provide probes that will be useful for further characterization of tumor specimens. C1 NIH,CANC GENET LAB,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 15 TC 124 Z9 128 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1996 VL 56 IS 15 BP 3446 EP 3450 PG 5 WC Oncology SC Oncology GA UZ288 UT WOS:A1996UZ28800013 PM 8758910 ER PT J AU Guyton, KZ Gorospe, M Kensler, TW Holbrook, NJ AF Guyton, KZ Gorospe, M Kensler, TW Holbrook, NJ TI Mitogen-activated protein kinase (MAPK) activation by butylated hydroxytoluene hydroperoxide: Implications for cellular survival and tumor promotion SO CANCER RESEARCH LA English DT Article ID QUINONE METHIDE; SIGNAL-TRANSDUCTION; MOUSE SKIN; HA-RAS; CELLS; CARCINOGENESIS; TOXICITY; DIFFERENTIATION; TRANSFORMATION; INVOLVEMENT AB The mitogen-activated protein kinase (MAPK) cascade plays an important role in carcinogenic development. Herein, we show that the skin tumor promoter butylated hydroxytoluene hydroperoxide (BHTOOH) stimulates a rapid and potent (14- to 20-fold) activation of extracellular signal-regulated kinase (ERK) in vivo and in cultured mouse keratinocytes. BHTOOH also moderately (5-fold) activated c-jun-N-terminal kinase and 38-kDa MBPK-related protein in these same cells. N-acetylcysteine and o-phenanthroline abolished ERK activation by BHTOOH, consistent with a requirement for metal-dependent formation of reactive intermediates. Indeed, 4-CD3-BHTOOH, an analogue that generates less of the metabolite BHT-quinone methide (2,6-di-terl-butyl-4-methylene-2,5-cyclohexadienone) and fewer tumors in vivo, accordingly exhibited diminished potency for activating ERK. ERK activation by BHTOOH was inhibited by suramin, and by expression of dominant-negative Ras-N-17 in PC12 cells, suggesting overlap between the pathways for BHTOOH and growth factor signaling. Induction of MAPK-dependent genes c-fos and MAPK phosphatase-1 by BHTOOH was also blocked by Ras-N-17 expression. Moreover, expression of Ras-N-17 or kinase-defective MAPK kinase (MEK) diminished cell survival following BHTOOH exposure, Similarly, pretreatment with suramin or the MEK inhibitor PD098059 also potentiated the toxicity of BHTOOH. On the other hand, expression of constitutively active MEK enhanced cell survival. Thus, we demonstrate that the MAPK cascade is critical to the cellular response to BHTOOH. This study suggests a functional role for MAPK activation in tumor promotion stimulated by oxidants and other agents. C1 NIA,GENE EXPRESS & AGING SECT,CTR GERONTOL RES,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DIV TOXICOL SCI,BALTIMORE,MD 21205. RI Kensler, Thomas/D-8686-2014 OI Kensler, Thomas/0000-0002-6676-261X FU NCI NIH HHS [CA44530] NR 44 TC 79 Z9 79 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 AUG 1 PY 1996 VL 56 IS 15 BP 3480 EP 3485 PG 6 WC Oncology SC Oncology GA UZ288 UT WOS:A1996UZ28800018 PM 8758915 ER PT J AU Zia, H Hida, T Jakowlew, S Birrer, M Gozes, Y Reubi, JC Fridkin, M Gozes, I Moody, TW AF Zia, H Hida, T Jakowlew, S Birrer, M Gozes, Y Reubi, JC Fridkin, M Gozes, I Moody, TW TI Breast cancer growth is inhibited by vasoactive intestinal peptide (VIP) hybrid, a synthetic VIP receptor antagonist SO CANCER RESEARCH LA English DT Article ID FUNCTIONAL EXPRESSION; CELL-LINE; POLYPEPTIDE; LUNG; PACAP; CARCINOMA; SURVIVAL; CLONING; INVITRO AB Breast cancer vasoactive intestinal peptide (VIP) receptors were characterized. Using in vitro autoradiographic techniques, I-125-labeled VIP bound with high affinity to breast biopsy sections. I-125-labeled VIP bound specifically to five breast cancer cell lines examined using receptor-binding techniques. Specific I-125-labeled VIP binding to MDA-MB-231 cells was inhibited with high affinity by VIP and pituitary adenylate cyclase-activating polypeptide (IC50 = 2 nM) and with moderate affinity by the VIP hybrid (IC50 = 0.5 mu M). VIP elevated the cAMP in a dose-dependent manner, and VIP hybrid (10 mu M) inhibited the increase in cAMP caused by VIP. Using Northern blot analysis, VIP (10 nM) stimulated c-fos and c-myc mRNA, and the increase caused by VIP was reversed by the VIP hybrid. The VIP hybrid inhibited breast cancer growth in vitro and 62 vivo using nude mice bearing breast cancer xenografts. These data suggest that the VIP hybrid is a breast cancer VIP receptor antagonist. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. ISRAEL INST BIOL RES,IL-70450 NESS ZIONA,ISRAEL. UNIV BERN,INST PATHOL,DIV CELL BIOL & EXPT CANC RES,BERN,SWITZERLAND. WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-76100 REHOVOT,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,DEPT CHEM PATHOL,TEL AVIV,ISRAEL. NR 36 TC 80 Z9 80 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1996 VL 56 IS 15 BP 3486 EP 3489 PG 4 WC Oncology SC Oncology GA UZ288 UT WOS:A1996UZ28800019 PM 8758916 ER PT J AU Webber, MM Bello, D Kleinman, HK Wartinger, DD Williams, DE Rhim, JS AF Webber, MM Bello, D Kleinman, HK Wartinger, DD Williams, DE Rhim, JS TI Prostate specific antigen and androgen receptor induction and characterization of an immortalized adult human prostatic epithelial cell line SO CARCINOGENESIS LA English DT Article ID EXPRESSION; GROWTH; LNCAP; TRANSFORMATION; ESTABLISHMENT; PROLIFERATION; TRANSFECTION AB Progress in prostate cancer research has been hindered by the lack of well characterized, immortalized, human prostatic epithelial cell lines that express markers of normal prostatic epithelial cells and mimic normal growth and differentiation responses to androgens, The objectives of this study were to: (i) establish immortalized cell lines from non-neoplastic, adult human prostatic epithelium using adenovirus-12/simian virus-40 (Ad12-SV40) hybrid virus; () establish their prostatic epithelial origin; (iii) demonstrate androgen responsiveness; and (iv) examine response to growth factors, Primary epithelial cell cultures derived from a non-neoplastic, adult human prostate were infected with the Ad12-SV40 virus, Several immortalized clones were isolated, Single cell cloning of one clone, free of cytopathic effects, gave rise to the PWR-1E cell line, An immortalized cell line PWR-1E, which expresses many characteristics of normal prostatic epithelial cells was established, Immunostaining showed that cells express cytokeratins 8 and 18 normally expressed by differentiated, secretory prostatic epithelial cells, The most remarkable characteristics of PWR-1E cells are growth stimulation, increased expression of androgen receptor and induction of prostate specific antigen (PSA) expression in response to androgens, which indisputably establish their prostatic epithelial origin, They are positive for SV40 large-T antigen and show strong nuclear staining for p53, Cells from passages 23 and 40 were not tumorigenic in nude mice even when co-injected with Matrigel. They grow in a serum-free defined medium and respond to EGF, bFGF and TGF-P, Passage 42-cells showed a human male (XY), hyperdiploid karyotype, The PWR-1E cell line is the only known Ad12-SV40-immortalized human prostatic epithelial cell line, PWR-1E cells can be used to study (i) the etiology and the multistep process of carcinogenesis and tumor progression in the human prostate; (ii) normal prostate physiology and differentiation; and (iii) potential prostate cancer chemopreventive agents. C1 MICHIGAN STATE UNIV,DEPT ZOOL,E LANSING,MI 48824. NIDR,DEV BIOL & ANOMALIES LAB,NIH,BETHESDA,MD 20892. MICHIGAN STATE UNIV,DEPT OSTEOPATH MED,E LANSING,MI 48824. NCI,MOL ONCOL LAB,FREDERICK,MD. RP Webber, MM (reprint author), MICHIGAN STATE UNIV,DEPT MED,S-350 PLANT BIOL BLDG,E LANSING,MI 48824, USA. NR 27 TC 50 Z9 53 U1 0 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 AUG PY 1996 VL 17 IS 8 BP 1641 EP 1646 DI 10.1093/carcin/17.8.1641 PG 6 WC Oncology SC Oncology GA VD875 UT WOS:A1996VD87500014 PM 8761420 ER PT J AU Giurgiovich, AJ Diwan, BA Lee, KB Anderson, LM Rice, JM Poirier, MC AF Giurgiovich, AJ Diwan, BA Lee, KB Anderson, LM Rice, JM Poirier, MC TI Cisplatin-DNA adduct formation in maternal and fetal rat tissues after transplacental cisplatin exposure SO CARCINOGENESIS LA English DT Article ID CIS-DIAMMINEDICHLOROPLATINUM; COORDINATION-COMPLEXES; PLATINUM; CHEMOTHERAPY; CIS-DIAMMINEDICHLOROPLATINUM(II); PREGNANCY; BINDING; OVARY; MOUSE; TRANS-DIAMMINEDICHLOROPLATINUM(II) AB Cis-diamminedichloroplatinum (II) (cisplatin), given to pregnant rats at 5 mg/kg body weight (bw) is a trans placental carcinogen for fetal liver, kidney, nervous system and lung, resulting in tumor incidences of 22.5, 10.5, 6.1 and 7.5% respectively, in offspring grown to adulthood (B.A, Diwan ef al., 1995, Toxicol, Appl. Pharm., 132, 115), In this study, the capacity of cisplatin to pass through the placental barrier and bind covalently to DNA in maternal and fetal tissues was evaluated, Pregnant F344/NCr rats were injected i.p. with single doses of 5, 10 or 15 mg cisplatin/kg bw at 18 days of gestation and sacrificed 24 h later, Cisplatin-DNA adducts were determined by dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) using both High (90 pmol/mu g DNA) and Low (0.50 pmol/mu g DNA) Modified cisplatin-DNA standards and atomic absorbance spectrometry (AAS), The adduct quantities determined by the two DELFIAs varied in concert, but the DELFIA with Low Modified standard gave actual values similar to those observed with AAS, In maternal and fetal tissues, with the exception of placenta in one experiment and maternal kidney in another experiment, the extent of cisplatin-DNA adduct formation increased with dose. In maternal kidney, the low adduct levels observed at the 15 mg/kg dose may reflect kidney toxicity, Fetal kidney, liver and lung contained fewer cisplatin-DNA adducts than the corresponding maternal tissues, In contrast, at 5 and 15 mg/kg, fetal brain DNA contained higher adduct levels than maternal brain DNA, This study demonstrates the presence of DNA damage induced by cisplatin in multiple maternal and fetal rat tissues at tumorigenic doses of drug; the results are therefore consistent with the hypothesis that genotoxic mechanisms play an important role in the drug-induced tumor incidence. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BETHESDA,MD 20892. SAIC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NCI,CLIN PHARMACOL BRANCH,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 33 TC 10 Z9 11 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 AUG PY 1996 VL 17 IS 8 BP 1665 EP 1669 DI 10.1093/carcin/17.8.1665 PG 5 WC Oncology SC Oncology GA VD875 UT WOS:A1996VD87500017 PM 8761423 ER PT J AU Donnelly, PJ Devereux, TR Foley, JF Maronpot, RR Anderson, MW Massey, TE AF Donnelly, PJ Devereux, TR Foley, JF Maronpot, RR Anderson, MW Massey, TE TI Activation of K-ras in aflatoxin B-1-induced lung tumors from AC3F1 (A/JxC3H/HeJ) mice SO CARCINOGENESIS LA English DT Article ID STRAIN-A MICE; MOUSE LUNG; LIVER-TUMORS; HUMAN-CELLS; DNA; MUTATIONS; SUSCEPTIBILITY; CANCER; GENE; ONCOGENES AB In addition to being a potent hepatocarcinogen, aflatoxin B-1 (AFB(1)) is a pulmonary carcinogen in experimental animals and epidemiological studies have shown an association between AFB(1) exposure and lung cancer in humans, Since point mutations at codons 12, 13 and 61 of the K-ms protooncogene are often implicated in chemically induced mouse lung tumors and in human lung adenocarcinomas, we undertook an investigation of the role of K-ras activation in AFB(1)-induced pulmonary carcinogenesis, Female AC3F1 (A/J x C3H/HeJ) mice were treated with AFB(1) (150 mg/kg i.p., divided into 24 doses over 8 weeks), and 6-14 months after the completion of dosing mice were killed and pulmonary adenomas and carcinomas removed, Of the 76 AFB(1)-induced lung tumors analyzed by single strand conformation polymorphism (SSCP) and direct sequencing, 75 possessed K-ras codon 12 mutations (46 GTT, 14 GAT, 13 TGT and 2 TTT; normal, GGT) and one had a GGC-->CGC mutation in codon 13, The observation that K-ras mutations occurred only at G:C base pairs is in agreement with N-7-guanine being the primary site of AFB(1)-DNA adduct formation and with guanine residues being targets for AFB(1)-induced oxidative DNA damage via formation of 8-hydroxydeoxyguanosine (8-OHdG). The AFB(1)-specific nature of the observed K-ras mutation spectrum and the fact that 100% of the tumor samples examined contained K-ras mutations is consistent with K-ras activation being an early, critical event in AFB(1)-induced pulmonary carcinogenesis in AC3F1 mice, The parental origin of the observed K-ras mutations was determined by allele-specific PCR amplification of AFB(1)-induced lung tumor DNA followed by SSCP analysis, In the vast majority of tumors (73/76), the mutated K-ras allele was derived from the lung tumor susceptible A/J parent, This finding supports the existence of a link between K-ras and differences in mouse lung tumor susceptibility. C1 QUEENS UNIV, DEPT PHARMACOL & TOXICOL, KINGSTON, ON K7L 3N6, CANADA. QUEENS UNIV, DEPT MED, KINGSTON, ON K7L 3N6, CANADA. NIEHS, RES TRIANGLE PK, NC 27709 USA. ST MARYS HOSP, INST CANC RES, GRAND JCT, CO 81502 USA. NR 39 TC 31 Z9 33 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 1996 VL 17 IS 8 BP 1735 EP 1740 DI 10.1093/carcin/17.8.1735 PG 6 WC Oncology SC Oncology GA VD875 UT WOS:A1996VD87500028 PM 8761434 ER PT J AU Agarwal, R Yagi, H Jerina, DM Dipple, A AF Agarwal, R Yagi, H Jerina, DM Dipple, A TI Benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide adducts in native and denatured DNA SO CARCINOGENESIS LA English DT Article ID REGION DIOL-EPOXIDES; SNAKE-VENOM PHOSPHODIESTERASE; EMBRYO CELL-CULTURES; DEOXYADENOSINE ADDUCTS; SOLUTION CONFORMATION; DIHYDRODIOL-EPOXIDE; OPPOSITE DT; 3,4-DIOL-1,2-EPOXIDES; BENZO(C)PHENANTHRENE; CONFIGURATION AB High performance liquid chromatography/UV-absorption and P-32-postlabeling were used to quantitate adducts generated by reaction of the four configurationally isomeric benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxides with native or denatured DNA in vitro. For both the 4R,3S-dihydrodiol 2S,1R-epoxide and the 4S,3R-dihydrodiol 2S,1R-epoxide, the amount of product resulting from trans-opening of the epoxide ring by the exocyclic amino group of deoxyadenosine in denatured DNA was much less than the level found in native DNA, indicating that the native DNA structure probably intercalates the hydrocarbon residue in a fashion that promotes adenine reaction for 2S,1R-epoxides. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 25 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 1996 VL 17 IS 8 BP 1773 EP 1776 DI 10.1093/carcin/17.8.1773 PG 4 WC Oncology SC Oncology GA VD875 UT WOS:A1996VD87500036 PM 8761442 ER PT J AU Lenfant, C Roccella, EJ AF Lenfant, C Roccella, EJ TI The development of public policies for the primary prevention of hypertension SO CARDIOVASCULAR RISK FACTORS LA English DT Article DE public policy; hypertension; primary prevention; health education; lifestyle changes ID POPULATION; PREVALENCE; HEALTH AB For nearly 25 years, the National High Blood Pressure Education Program has designed and implemented strategies to increase the detection, treatment, and control of high blood pressure. Several types of evidence show that these strategies are succeeding, Yet, hypertension remains an health problem. strategies focus on disease detection and treatment, but these strategies do not prevent cardiovascular/renal disease related to blood pressure because blood pressure complications occur prior to the onset of established hypertension. The relationship between blood pressure and cardiovascular risk is continuous and progressive even within the normotensive blood pressure range, Although hypertension treatment is important, it can never be a sufficient response to the burden of high blood pressure on society. Primary prevention of hypertension can be accomplished within populations through lifestyle changes designed to reduce mean arterial pressures. Public policies must be established to permit the desired lifestyle changes to be potentially feasible. RP Lenfant, C (reprint author), NHLBI,NATL HIGH BLOOD PRESSURE EDUC PROGRAM,31 CTR DR,MSC 2480,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1130-7501 J9 CARDIOVASC RISK FACT JI Cardiovasc. Risk Factors PD AUG PY 1996 VL 6 IS 4 BP 199 EP 202 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VB515 UT WOS:A1996VB51500004 ER PT J AU Sussman, MA Ito, M Daniels, MP Flucher, B Buranen, S Kedes, L AF Sussman, MA Ito, M Daniels, MP Flucher, B Buranen, S Kedes, L TI Chicken skeletal muscle tropomodulin: Novel localization and characterization SO CELL AND TISSUE RESEARCH LA English DT Article DE tropomodulin; muscle; Z-disc; localization; actin filaments; chicken ID TROPOMYOSIN-BINDING PROTEIN; THIN FILAMENT LENGTH; ACTIN-FILAMENTS; Z-LINE; POINTED ENDS; STRIATED-MUSCLE; CARDIAC-MUSCLE; MESSENGER-RNA; Z-DISKS; NEBULIN AB Tropomodulin is a 40.6-kDa isoform-specific tropomyosin-binding protein which inhibits actin filament elongation from the slow-growing (pointed) end and Idealizes at or near the pointed ends of thin filaments in rat skeletal muscle. Immunofluorescent localization using affinity-purified anti-tropomodulin antibodies in avian myofibril preparations demonstrates novel immunoreactivity at the Z-disc in addition to the previously reported localization at the periphery of I-Z-I brushes where actin filaments terminate. Identical results were obtained using antibody preparations generated against either bacterially expressed tropomodulin or human erythrocyte tropomodulin. Chicken muscle preparations contain M(r) 43000 polypeptides which bind antibodies generated against tropomodulin in Western blot analysis, as well as I-125-labeled tropomyosin in blot overlays. Tropomodulin mRNA expression in adult muscle was confirmed by RNase protection assays, and the sequence of our tropomodulin cDNA amplified from chicken muscle mRNA preparations by polymerase chain reaction closely matches clones selected by chicken muscle cDNA library screening. The novel immunolocalization we report raises new possibilities for the role of tropomodulin in the organization of avian skeletal muscle at the Z-disc. We conclude that tropomodulin is likely to be important in striated muscle biology as a structural component in the Z-disc region which participates in the process of thin filament organization and assembly. C1 UNIV SO CALIF,SCH MED,DEPT BIOCHEM & MOLEC BIOL,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,INST MED GENET,LOS ANGELES,CA 90033. NIH,LAB BIOCHEM GENET,BETHESDA,MD 20892. NIH,NEUROBIOL LAB,BETHESDA,MD 20892. NR 45 TC 8 Z9 9 U1 0 U2 2 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 AUG PY 1996 VL 285 IS 2 BP 287 EP 296 DI 10.1007/s004410050646 PG 10 WC Cell Biology SC Cell Biology GA UY856 UT WOS:A1996UY85600013 PM 8766165 ER PT J AU Cheng, H Lederer, MR Xiao, RP Gomez, AM Zhou, YY Ziman, B Spurgeon, H Lakatta, EG Lederer, WJ AF Cheng, H Lederer, MR Xiao, RP Gomez, AM Zhou, YY Ziman, B Spurgeon, H Lakatta, EG Lederer, WJ TI Excitation-contraction coupling in heart: New insights from Ca2+ sparks SO CELL CALCIUM LA English DT Review ID CARDIAC SARCOPLASMIC-RETICULUM; SODIUM-CALCIUM EXCHANGE; SKELETAL-MUSCLE; VENTRICULAR MYOCYTES; DIHYDROPYRIDINE RECEPTORS; SPATIAL NONUNIFORMITIES; RELEASE; CELLS; PROPAGATION; RELAXATION AB Ca2+ sparks, the elementary units of sarcoplasmic reticulum (SR) Ca2+ release in cardiac, smooth and skeletal muscle are localized (2-4 mu m) increases in intracellular Ca2+ concentration, [Ca2+](i), that last briefly (30-100 ms). These Ca2+ sparks arise from the openings of a single SR Ca2+ release channel (ryanodine receptor, RyR) or a few RyRs acting in concert. In heart muscle, Ca2+ sparks can occur spontaneously in quiescent cells at a low rate (100 s(-1) per cell). Identical Ca2+ sparks are also triggered by depolarization because the voltage-gated sarcolemmal L-type Ca2+ channels (dihydropyridine receptors, DHPRs) locally increase [Ca2+](i) and thereby activate the RyRs by Ca2+-induced Ca2+ release (CICR). The exquisite responsiveness of this process, reflected by the ability of even a single DHPR to activate a Ca2+ spark, is perhaps due to the large local increase in [Ca2+](i) in the vicinity of the RyR that is a consequence of the close apposition of the DHPRs and the RyRs. in this review we examine our current understanding of cardiac excitation-contraction (EC) coupling in light of recent studies on the elementary Ca2+ release events or Ca2+ sparks. In addition, we further characterized Ca2+ spark properties in rat and mouse heart cells. Specifically we have determined that: (i) Ca2+ sparks occur at the junctions between the transverse-tubules and the SR in both species; (ii) Ca2+ sparks are asymmetric, being 18% longer in the longitudinal direction than in the transverse direction; and (iii) Ca2+ sparks individually do not produce measurable sarcomere shortening (< 1%). These results are discussed with respect to local activation of the RyRs, the stability of CICR, Ca2+ diffusion, and the theory of EC coupling. C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. UNIV MARYLAND,SCH MED,DEPT MOL BIOL & BIOPHYS,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201. RI Lederer, William/B-1285-2010 FU NHLBI NIH HHS [HL25679, HL36974] NR 45 TC 139 Z9 140 U1 0 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD AUG PY 1996 VL 20 IS 2 BP 129 EP 140 DI 10.1016/S0143-4160(96)90102-5 PG 12 WC Cell Biology SC Cell Biology GA VH529 UT WOS:A1996VH52900005 PM 8889204 ER PT J AU Brown, PH Kim, SH Wise, SC Sabichi, AL Birrer, MJ AF Brown, PH Kim, SH Wise, SC Sabichi, AL Birrer, MJ TI Dominant-negative mutants of cJun inhibit AP-1 activity through multiple mechanisms and with different potencies SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TRANSCRIPTION FACTOR AP-1; RAT EMBRYO CELLS; C-JUN; INDUCED TRANSFORMATION; DELETION MUTANT; PROTO-ONCOGENE; FOS PROTEINS; V-JUN; ACTIVATION; PROMOTER AB We have previously described a dominant-negative mutant of cJun that lacks the transactivation domain (TAD) of cJun and prevents AP-1-mediated transcriptional activation by quenching endogenous Jun or Fos proteins, We now report the development of a panel of cJun mutants that have inactivating mutations in the TAD, DNA-binding domain (DBD), or leucine zipper domain, These mutants are all unable to activate transcription, but only TAD and DBD mutants function in a dominant-negative fashion by inhibiting both cJun-induced transcriptional activation and transformation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate in ras-transfected rat embryo cells, Although the TAD and DBD mutants both function as transdominant inhibitors, they work through different mechanisms and with different inhibitory potencies, The DBD mutants, which function by inhibiting DNA binding, are relatively weak inhibitors, whereas the TAD mutants inhibit by quenching and are much more potent, Dimerization assays demonstrate that mutations in the DBD decrease the dimerization affinity of these mutants with cJun, These results demonstrate that the most potent dominant-negative mutants of cJun are proteins that have intact DBDs and quench the activity of the endogenous transcription factors. C1 NCI,DIV CLIN SCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NR 45 TC 60 Z9 60 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD AUG PY 1996 VL 7 IS 8 BP 1013 EP 1021 PG 9 WC Cell Biology SC Cell Biology GA VB917 UT WOS:A1996VB91700006 PM 8853897 ER PT J AU Park, CS Gianotti, C Park, R Krishna, G AF Park, CS Gianotti, C Park, R Krishna, G TI Neuronal isoform of nitric oxide synthase is expressed at low levels in human retina SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE neuronal NO synthase; human retina; RT-PCR; RFLP; genetic polymorphism; CHO-K1 cell ID CULTURED ASTROCYTOMA-CELLS; SOLUBLE GUANYLATE-CYCLASE; MOLECULAR-CLONING; NADPH-DIAPHORASE; MESSENGER-RNA; NERVOUS-SYSTEM; GLIAL-CELLS; RAT; BRAIN; INDUCTION AB 1. The expression of neuronal isoform of nitric oxide synthase (nNOS) was studied in human retinal tissues. The cDNA sequence was cloned in human retinal poly (A)(+) RNA by the RT-PCR method and encompassed an open-reading frame of 4,302 bp encoding 1,434 amino acids. This sequence showed a possibility of genetic polymorphism in comparison to human brain form. 2. Restriction fragment length polymorphism (RFLP) patterns of a partial cDNA fragment suggest that there is genetic polymorphism in the neuronal form of NOS, Important differences were observed in a certain region between human retinal and brain forms, This region is a result of frame shift by the addition of three cytidines. In this study, regions from human brain (cerebellum) and skeletal muscle as well as retina were sequenced to confirm the difference in this region, The sequences from these tissues were completely identical, This indicated that genetic polymorphism of nNOS gene was due to single base substitution and not frame shift phenomenon by addition or deletion of bases. 3. The nNOS mRNA of similar to 12 kb was detected by northern blot analysis. The lower level of the expression was distinguished in comparison to those of human brain and skeletal muscle. The cDNA transiently transfected into CHO-K1 cells expressed a protein which contained a significant level of NOS activity. The size of the nNOS was found to be similar to 160 kDa by both in vitro and in vivo translation systems, This NOS was calcium dependent and the K-m for arginine was 4.4 mu M. 4. The Ca++, L-arginine and NADPH dependency along with the inhibitory effect of N-nitro-L-arginine on NOS activity were evaluated, The finding of a constitutive form of NOS in human retina, which is calcium-NADPH dependent, gives further credence to the possible role of nitric oxide in retinal function and neuronal diseases. C1 NHLBI, SECT CHEM PHARMACOL, LAB MOL IMMUNOL, NIH, ROCKVILLE, MD 20892 USA. NR 46 TC 14 Z9 15 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD AUG PY 1996 VL 16 IS 4 BP 499 EP 515 DI 10.1007/BF02150230 PG 17 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA VH436 UT WOS:A1996VH43600005 PM 8879752 ER PT J AU Curran, PK Fishman, PH AF Curran, PK Fishman, PH TI Endogenous beta(3)- but not beta(1)-adrenergic receptors are resistant to agonist mediated regulation in human SK-N-MC neurotumor cells SO CELLULAR SIGNALLING LA English DT Article DE beta-adrenergic receptors; desensitization; adenylyl cyclase; down regulation; sequestration ID HUMAN BETA-1-ADRENERGIC RECEPTOR; HUMAN BETA-3-ADRENERGIC RECEPTOR; MESSENGER RIBONUCLEIC-ACIDS; HUMAN NEUROBLASTOMA-CELLS; C6 GLIOMA-CELLS; ADRENERGIC-RECEPTOR; BETA-2-ADRENERGIC RECEPTORS; CYCLIC-AMP; BETA(3)-ADRENERGIC RECEPTOR; FUNCTIONAL BETA(3)-ADRENOCEPTOR AB Although there is considerable interest in the regulation of the different beta-adrenergic receptor (AR) subtypes, most previous studies have utilized stably transfected cells expressing recombinant receptors under the control of viral promoters. Human SK-N-MC neurotumor sells appear to be novel, since they express both endogenous beta(1)AR and beta(3)AR based on radioligand binding and on functional response. Saturation binding of either the hydrophilic ligand (-)-[H-3]CGP-12177 or the more hydrophobic (-)-[I-125] iodocyanopindolol indicated the presence of two populations of binding sites with high and low affinities. With either ligand, the beta(1)AR antagonist CGP-20712A preferentially inhibited binding to the high-affinity sites. This is consistent with the latter representing beta(1)AR whereas the low-affinity sites represent beta(3)AR. Both subtypes appeared to be functional on the basis of isoproterenol stimulation of cyclic adenosine monophosphate (cAMP) in intact cells and adenylyl cyclase activity in cell membranes in the absence and presence of CGP-20712A. SK-N-MC-IXC cells, derived by twice subcloning the parental cells, also expressed both beta AR subtypes, indicating that they so-exist in the same cell. SK-N-MC cells exposed to isoproterenol exhibited a rapid sequestration and a slower downregulation of beta(1)AR. The latter subtype also underwent desensitization, as indicated by a rightward shift to less sensitivity in the EC(50) for isoproterenol stimulation of adenylyl cyclase activity. In contrast, the beta(3)AR subtype was resistant to agonist-mediated sequestration, downregulation, and desensitization. Thus, when endogenously expressed in the same cell line, human beta(1)AR and beta(3)AR display differences in their ability to be regulated by agonist. C1 NINCDS,MEMBRANE BIOCHEM SECT,CELLULAR & MOL NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 46 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 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD AUG PY 1996 VL 8 IS 5 BP 355 EP 364 DI 10.1016/0898-6568(96)00068-X PG 10 WC Cell Biology SC Cell Biology GA VL540 UT WOS:A1996VL54000005 PM 8911684 ER PT J AU Damast, AM TamisLeMonda, CS Bornstein, MH AF Damast, AM TamisLeMonda, CS Bornstein, MH TI Mother-child play: Sequential interactions and the relation between maternal beliefs and behaviors SO CHILD DEVELOPMENT LA English DT Article ID 1ST 2 YEARS; UNITED-STATES; PRETEND PLAY; INFANTS; STABILITY; KNOWLEDGE; SPEECH; FRANCE; JAPAN; GAMES AB This investigation of mother and toddler play had 2 goals, The primary goal was to examine the types of play mothers introduce in direct response to their toddlers' play. A secondary and exploratory goal was to examine the relation between maternal knowledge about child play and actual maternal play behaviors. 50 mothers and their 21-month-old toddlers were observed at home during free play. Mother and child exploratory, nonsymbolic, and symbolic play were coded. Sequential analyses revealed that mothers adjusted their play to their children's play level by responding to their children with play that was either at the same level or at a higher level than their children's play. Furthermore, mothers who were more knowledgeable about early play development more often responded to their children's play by introducing higher level play. These findings suggest that mothers tend to play with their toddlers in ways that might promote their child's development, and that mothers with more knowledge about play development provide their children with appropriately challenging play interactions. C1 ALBERT EINSTEIN COLL MED,BRONX,NY 10461. NICHHD,BETHESDA,MD 20892. RP Damast, AM (reprint author), NYU,DEPT APPL PSYCHOL,239 GREENE ST,5TH FLOOR,NEW YORK,NY 10012, USA. FU NICHD NIH HHS [HD20807, HD20559]; NIMH NIH HHS [MH48915] NR 61 TC 51 Z9 55 U1 1 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD AUG PY 1996 VL 67 IS 4 BP 1752 EP 1766 DI 10.1111/j.1467-8624.1996.tb01825.x PG 15 WC Psychology, Educational; Psychology, Developmental SC Psychology GA VP344 UT WOS:A1996VP34400029 PM 8890505 ER PT J AU Mai, S Fluri, M Siwarski, D Huppi, K AF Mai, S Fluri, M Siwarski, D Huppi, K TI Genomic instability in MycER-activated Rat1A-MycER cells SO CHROMOSOME RESEARCH LA English DT Article ID MAMMALIAN GENE AMPLIFICATION; SYRIAN-HAMSTER CELLS; WILD-TYPE P53; C-MYC; CHROMOSOMAL TRANSLOCATIONS; DIHYDROFOLATE-REDUCTASE; CYCLIN D1; CAD GENES; EXPRESSION; ONCOPROTEIN AB The deregulated expression of c-Myc protein is associated with the non-random locus-specific amplification of the dihydrofolate reductase (DHFR) gene. This study was performed to determine whether additional chromosomal aberrations occur when c-Myc protein levels are up-regulated for prolonged periods. To this end, we have used Rat1A-MycER cells, which allow the experimental regulation of Myc protein levels. We examined the genomic stability of Rat1A-MycER cells cultivated in either the absence or the presence of estrogen, which reportedly activates the chimeric MycER protein in these cells. Following prolonged periods of MycER activation, Rat1A-Mycer cells exhibited irreversible chromosomal aberrations. The aberrations included numerical changes, chromosome breakage, the formation of circular chromosomal structures, chromosome fusions, and extrachromosomal elements. C1 BASEL INST IMMUNOL,CH-4005 BASEL,SWITZERLAND. NCI,NIH,GENET LAB,MOL GENET SECT,BETHESDA,MD 20892. RP Mai, S (reprint author), MANITOBA INST CELL BIOL,100 OLIVIA ST,WINNIPEG,MB R3E 0V9,CANADA. RI Mai, Sabine/E-5667-2017 OI Mai, Sabine/0000-0002-5797-2201 NR 32 TC 61 Z9 62 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD AUG PY 1996 VL 4 IS 5 BP 365 EP 371 DI 10.1007/BF02257272 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA VC373 UT WOS:A1996VC37300006 PM 8871825 ER PT J AU Lenfant, C AF Lenfant, C TI Acknowledgment of your research sponsor - It pays to advertise SO CIRCULATION LA English DT News Item RP Lenfant, C (reprint author), NHLBI,BLDG 31,ROOM 5A52,31 CTR DR,MSC 2486,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 1 PY 1996 VL 94 IS 3 BP 234 EP 235 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UZ051 UT WOS:A1996UZ05100002 PM 8759057 ER PT J AU Schulman, SP Fleg, JL Goldberg, AP BusbyWhitehead, J Hagberg, JM OConnor, FC Gerstenblith, G Becker, LC Katzel, LI Lakatta, LE Lakatta, EG AF Schulman, SP Fleg, JL Goldberg, AP BusbyWhitehead, J Hagberg, JM OConnor, FC Gerstenblith, G Becker, LC Katzel, LI Lakatta, LE Lakatta, EG TI Continuum of cardiovascular performance across a broad range of fitness levels in healthy older men SO CIRCULATION LA English DT Article DE aging; exercise; cardiac volume ID EXERCISE; AGE; RESPONSES; DECLINE; VO2MAX; WOMEN; YOUNG; REST AB Background Although it has become clear that habitual exercise in older individuals can partially offset age-associated cardiovascular declines, it is not known whether the beneficial effects of exercise training in older individuals depend on their prior fitness level. Methods and Results Ten sedentary men (S), age 60.0 +/- 1.6 years (mean +/- SEM), who were carefully screened to exclude cardiac disease underwent exercise training for 24 to 32 weeks, and eight age-matched endurance-trained men (ET) stopped their exercise training for 12 weeks. All underwent treadmill exercise and rest and maximal cycle exercise upright gated blood pool scans at baseline and after the lifestyle intervention. Before the intervention, the treadmill maximum rate of oxygen consumption (Vo(2max)) was 49.9 +/- 1.9 and 32.1 +/- 1.4 mL . kg(-1). min(-1) in ET and S, respectively. During upright cycle exercise at exhaustion, although heart rate did not differ between groups, cardiac index, stroke volume index, ejection fraction, and left ventricular contractility index (systolic blood pressure/end-systolic volume index) all were significantly higher, and end-systolic volume index, diastolic blood pressure, and total systemic vascular resistance all were significantly lower in ET versus S. After the partial deconditioning of ET men, Vo(2max) fell to 42 +/- 2.2 mL . kg(-1). min(-1), and training of S increased Vo(2max) to 36.2 +/- 1.6 mL . kg(-1). min(-1). Training of S had effects on cardiovascular function that were similar in magnitude but directionally opposite those of detraining ET. All initial differences in cardiovascular performance at peak work rate between S and ET were abolished with the intervention. Across the broad range of fitness levels encountered before and after change in training status (Vo(2max) of 26 to 58 mL . kg(-1). min(-1)), cardiac index, stroke volume index, end-systolic volume index, ejection fraction, and the left ventricular contractility index were all linearly correlated with Vo(2max). Conclusions Exercise training or detraining of older men results in changes in left ventricular performance that are qualitatively and quantitatively similar, regardless of the initial level of fitness before the intervention. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. UNIV MARYLAND,SCH MED,DIV GERONTOL,BALTIMORE,MD 21201. VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,BALTIMORE,MD 21218. JOHNS HOPKINS MED INST,DIV GERIATR MED & GERONTOL,COLLEGE PK,MD. JOHNS HOPKINS MED INST,DIV CARDIOL,COLLEGE PK,MD. UNIV MARYLAND,CTR AGING,COLLEGE PK,MD 20742. FU NIA NIH HHS [5K08-AG-00497, P01-AG-04402, R01-AG-07660] NR 27 TC 55 Z9 57 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 1 PY 1996 VL 94 IS 3 BP 359 EP 367 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UZ051 UT WOS:A1996UZ05100022 PM 8759077 ER PT J AU Tsutsui, M Milstien, S Katusic, ZS AF Tsutsui, M Milstien, S Katusic, ZS TI Effect of tetrahydrobiopterin on endothelial function in canine middle cerebral arteries SO CIRCULATION RESEARCH LA English DT Article DE NO; NO synthase; superoxide anion; superoxide dismutase ID NITRIC-OXIDE SYNTHASE; SUPEROXIDE ANION; RELAXING FACTOR; MOLECULAR-CLONING; BINDING-KINETICS; L-ARGININE; CELLS; CALMODULIN; MECHANISM; MACROPHAGES AB Tetrahydrobiopterin is an essential cofactor required for activation of NO synthase. However, in intact arteries, the exact role of tetrahydrobiopterin in the regulation of NO synthase activity is not fully understood. The present study was designed to determine the effect of increasing intracellular tetrahydrobiopterin levels on endothelial function in isolated canine middle cerebral arteries. The arterial segments were incubated in MEM for 24 hours at 37 degrees C in the presence or absence of a tetrahydrobiopterin precursor, sepiapterin (10(-4) mol/L), and/or superoxide dismutase (150 U/mL). The rings were suspended for isometric tension recording. Tetrahydrobiopterin levels were assayed by high-performance liquid chromatography. Production of cGMP was measured by radioimmunoassay. Incubation with sepiapterin markedly increased intracellular tetrahydrobiopterin levels. In sepiapterin-treated arteries, endothelium-dependent relaxations to calcium ionophore A23187 and intracellular cGMP levels were significantly reduced. Superoxide dismutase alone did not affect either relaxation to A23187 or production of cGMP. However, when arteries were incubated with superoxide dismutase plus sepiapterin, endothelium-dependent relaxations to A23187, as well as cGMP production, were significantly augmented. The augmentation of cGMP was observed in rings with (but not without) endothelium. Incubation of arteries in calcium-free medium almost abolished the synergistic effect of tetrahydrobiopterin and superoxide dismutase on cGMP production. These results demonstrate that increased availability of tetrahydrobiopterin may activate endothelial NO synthase. This effect appears to be critically dependent on the presence of superoxide dismutase. C1 MAYO CLIN,DEPT ANESTHESIOL & PHARMACOL,ROCHESTER,MN 55905. NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL-53542] NR 46 TC 81 Z9 82 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG PY 1996 VL 79 IS 2 BP 336 EP 342 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA VC257 UT WOS:A1996VC25700023 PM 8756013 ER PT J AU Shindo, M Mullin, GE BraunElwert, L Bergasa, NV Jones, EA James, SP AF Shindo, M Mullin, GE BraunElwert, L Bergasa, NV Jones, EA James, SP TI Cytokine mRNA expression in the liver of patients with primary biliary cirrhosis (PBC) and chronic hepatitis B (CHB) SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE cytokines; mRNA; liver biopsy; primary biliary cirrhosis; hepatitis B ID TUMOR-NECROSIS-FACTOR; POLYMERASE CHAIN-REACTION; CHRONIC ACTIVE HEPATITIS; BLOOD MONONUCLEAR-CELLS; II MHC ANTIGENS; INTERFERON-GAMMA; T-CELLS; PERIPHERAL-BLOOD; VIRUS-INFECTION; MESSENGER-RNA AB The expression of cytokine mRNA species was determined in liver biopsies from six normal subjects, Is patients with PBC and 14 patients with hepatitis B e antigen (HBeAg)-positive CHB using a reverse transcriptase-polymerase chain reaction (RT-PCR) technique. cDNA, obtained by reverse transcription using oligo d(T) primers, was amplified by PCR using primers specific for the coding region of seven different cytokines (IL-1, IL-2, IL-4, IL-5, IL-6, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha)). The abundance of some cytokines (IL-2, IL-4, IL-5 and IFN-gamma) was also estimated by semiquantitative RT-PCR, using as standards dilutions of synthetic cytokine mRNA transcripts, that could be distinguished electrophoretically from respective native cytokine mRNAs. Hepatic inflammation was assessed by a semiquantitative histologic score and by amplification of mRNA for T cell receptor (TCR)-alpha. mRNAs for IL-1 and IL-6 were detected in only one control liver. In CHB, mRNAs for IL-1, IL-2, IL-4, IL-5 and IFN-gamma were detected in 43%, 60%, 80%, 20%, and 54% of biopsies, respectively. mRNA for IFN-gamma and IL-4, but not IL-1, tended to be associated with severe inflammation. In five biopsies semiquantitative analyses revealed increased levels of mRNA for TCR-alpha and, when transcripts were detectable, high levels of mRNA for IFN-gamma and IL-4. In PBC, mRNA for IFN-gamma was detected in 60% of biopsies, but no mRNAs for IL-1, IL-2, IL-4, IL-5, or IL-6, or for TNF-alpha, were detected. Semiquantitative analyses revealed that absolute levels of mRNA for IFN-gamma tended to correlate with the severity of hepatic inflammation. The results suggest that: (i) there may be fundamental differences in the roles that cytokines play in the hepatic inflammatory processes of PBC and CHB; and (ii) while hepatic IFN-gamma mRNA expression is not specific for PBC, IFN-gamma may play a prominent role in the immunopathogenesis of PBC. C1 UNIV AMSTERDAM,ACAD MED CTR,DEPT GASTROINTESTINAL & LIVER DIS,NL-1105 AZ AMSTERDAM,NETHERLANDS. NIDDK,LIVER DIS SECT,BETHESDA,MD 20505. NIAID,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. OI Mullin, Gerard/0000-0001-5317-6788 NR 38 TC 66 Z9 68 U1 0 U2 2 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 AUG PY 1996 VL 105 IS 2 BP 254 EP 259 DI 10.1046/j.1365-2249.1996.d01-759.x PG 6 WC Immunology SC Immunology GA UZ369 UT WOS:A1996UZ36900010 PM 8706330 ER PT J AU Axelrod, FB Goldstein, DS Holmes, C Berlin, D Kopin, IJ AF Axelrod, FB Goldstein, DS Holmes, C Berlin, D Kopin, IJ TI Pattern of plasma levels of catecholamines in familial dysautonomia SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE dihydroxyphenylglycol; dopamine; noradrenaline; orthostatic hypotension; monoamine oxidase ID ORTHOSTATIC HYPOTENSION; AUTONOMIC DYSFUNCTION; POSTURAL CHANGE; RESPONSES AB This report extends previous investigations of endogenous catecholamine levels in patients with orthostatic hypotension due to familial dysautonomia (FD), to define better the neurochemical phenotype and elucidate possible pathophysiological mechanisms. Ten FD patients (age 26.1 +/- 2.6 (SEM) years) and eight control subjects (age 29.5 +/- 3.7 years) were studied. Heart rate, blood pressure and venous blood samples were obtained while supine and after 5 min in the upright position. Plasma levels of dihydroxyphenylalanine (DOPA), noradrenaline (NA), adrenaline (A), dopamine (DA), dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) were measured. When supine, the FD group had greater NA and DOPA levels, and lower DHPG levels. Plasma NA did not increase with erect posture in FD patients. Individual FD mean blood pressures were correlated positively with plasma NA levels when supine and with plasma DA and DOPAC when upright. In FD, DOPA:DHPG ratios were above the range found in normal subjects or that reported in patients with acquired forms of dysautonomia regardless of posture, whereas DOPAC:DHPG ratios remained normal. Thus FD patients have a characteristic neurochemical pattern which probably reflects either decreased vesicular storage of catecholamines or limited oxidative deamination despite normal or increased tyrosine hydroxylation. C1 NYU,MED CTR,DEPT PEDIAT,NEW YORK,NY 10016. NYU,MED CTR,DEPT NEUROL,NEW YORK,NY 10016. NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NR 16 TC 23 Z9 23 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD AUG PY 1996 VL 6 IS 4 BP 205 EP 209 DI 10.1007/BF02291135 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VL768 UT WOS:A1996VL76800003 PM 8902316 ER PT J AU Levine, PH Dale, JK BensonGrigg, E Fritz, S Grufferman, S Straus, SE AF Levine, PH Dale, JK BensonGrigg, E Fritz, S Grufferman, S Straus, SE TI A cluster of cases of chronic fatigue and chronic fatigue syndrome: Clinical and immunologic studies SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID DEFINITION C1 NCI,DIV CANC ETIOL,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. SCI APPLICAT INT CORP FREDERICK,FREDERICK,MD. UNIV PITTSBURGH,PITTSBURGH,PA. NR 11 TC 6 Z9 6 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1996 VL 23 IS 2 BP 408 EP 409 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VA554 UT WOS:A1996VA55400042 PM 8842294 ER PT J AU Rosse, RB Kendrick, K FayMcCarthy, M Prell, GD Rosenberg, P Tsui, LC Wyatt, RJ Deutsch, SI AF Rosse, RB Kendrick, K FayMcCarthy, M Prell, GD Rosenberg, P Tsui, LC Wyatt, RJ Deutsch, SI TI An open-label study of the therapeutic efficacy of high-dose famotidine adjuvant pharmacotherapy in schizophrenia: Preliminary evidence for treatment efficacy SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE famotidine; schizophrenia; adjuvant therapy ID SYMPTOMS AB Histaminergic projections innervate brain areas implicated in the pathophysiology of schizophrenia. In a previous open-label study, there was the suggestion that famotidine, an H-2 histamine-receptor antagonist, possessed adjuvant therapeutic properties when added to the stable neuroleptic medication regimens of 10 treatment-refractory patients. In that study, the maximal dosage of famotidine was limited to 40 mg/day, the recommended maximal dosage for the treatment of peptic ulcer disease. In this study, we examined 18 patients fulfilling DSM-III-R criteria for schizophrenia and schizoaffective disorder who had famotidine (100 mg/day) added to their stable neuroleptic medication regimen. Patients were rated on baseline, weekly thereafter, and 1 week after famotidine discontinuation, by using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Assessment of Negative Symptoms (SANS), and the Clinical Global Impression (CGI). On all of these outcome measures, statistically significant improvements suggestive of a beneficial adjunctive effect of famotidine were found. Famotidine (100 mg/day) was well tolerated by the study subjects. There was a wide range of famotidine blood levels achieved at the end of 3 weeks of famotidine adjunctive treatment, but these blood levels did not correlate with BPRS or SANS score changes. However, the patients with the greatest improvement in BPRS scores (and without concomitant deterioration in SANS scores) had some of the higher famotidine levels found in the study. Double-blind studies further assessing the potential adjunctive benefit of famotidine in the treatment of schizophrenia are indicated. C1 DEPT VET AFFAIRS MED CTR,PSYCHIAT SERV,WASHINGTON,DC 20422. GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC. MT SINAI SCH MED,DEPT PHARMACOL,NEW YORK,NY. NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. RI Tsui, Lap-chee/A-1081-2010 NR 15 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD AUG PY 1996 VL 19 IS 4 BP 341 EP 348 DI 10.1097/00002826-199619040-00007 PG 8 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA UY221 UT WOS:A1996UY22100007 PM 8828997 ER PT J AU Levav, M Mirsky, AF Koby, M Cruz, ME AF Levav, M Mirsky, AF Koby, M Cruz, ME TI The neuropsychological effects of neurocysticercosis (NCC) in children. SO CLINICAL NEUROPSYCHOLOGIST LA English DT Meeting Abstract C1 NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD AUG PY 1996 VL 10 IS 3 BP 324 EP 324 PG 1 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA UY848 UT WOS:A1996UY84800029 ER PT J AU Egan, GJ Kilts, CD Gideon, DA Hoffman, JM Faber, T AF Egan, GJ Kilts, CD Gideon, DA Hoffman, JM Faber, T TI PET analysis of hemispheric involvement in human face emotion perception. SO CLINICAL NEUROPSYCHOLOGIST LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD AUG PY 1996 VL 10 IS 3 BP 335 EP 335 PG 1 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA UY848 UT WOS:A1996UY84800082 ER PT J AU Hoffman, E Gold, J Blaxton, T AF Hoffman, E Gold, J Blaxton, T TI Conceptual transfer on off- and on-line priming tasks in memory-impaired patient groups. SO CLINICAL NEUROPSYCHOLOGIST LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD AUG PY 1996 VL 10 IS 3 BP 338 EP 338 PG 1 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA UY848 UT WOS:A1996UY84800098 ER PT J AU Zhou, LX Pihlstrom, B Hardwick, JP Park, SS Wrighton, SA Holtzman, JL AF Zhou, LX Pihlstrom, B Hardwick, JP Park, SS Wrighton, SA Holtzman, JL TI Metabolism of phenytoin by the gingiva of normal humans: The possible role of reactive metabolites of phenytoin in the initiation of gingival hyperplasia SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID MONOCLONAL-ANTIBODIES; CLINICAL REPORT; CYCLOSPORINE-A; OVERGROWTH; MICROSOMES; SEVERITY; PROTEINS; CYTOCHROME-P-450; HEPATOTOXICITY; ENLARGEMENT AB Gingival hyperplasia is a well-known complication of therapy with cyclosporine, calcium channel blockers, and phenytoin, It is characterized by the presence of inflammation and a marked fibrotic response. The mechanism of this adverse reaction is unknown, We propose that it may be initiated by the metabolic activation of these drugs to form reactive metabolites, These then cause cellular injury and lead to the gingival hyperplasia, To evaluate this hypothesis we examined phenytoin metabolism and the cytochrome P450 contents of gingival tissues from 10 patients undergoing surgery for various periodontal conditions, We found that microsomes obtained from the gingiva show significant phenytoin hydroxylase activity as determined by the production of 5-(4'-hydroxyphenyl)-5-phenylhydantoin (HPPH) (range, 12.8 pmol HPPH/min . mg microsomal protein to 276.9 pmol HPPH/min . mg microsomal protein; rat control, 133.7+/-11.5 pmol HPPH/min . mg microsomal protein), We also found that CYP1A1, CYP1A2, CYP2C9, CYP2E1, and CYP3A4 were present in these microsomes, We detected no CYP2B6 or CYP2D6. We believe that these data support our hypothesis that the proliferative inflammation observed with drugs such as phenytoin, nifedipine, and cyclosporine may be initiated by the formation of reactive metabolites and that the formation of these metabolites may be catalyzed by one or more CYPs found in the gingiva, These metabolites may then cause cellular injury and induce a reactive inflammatory response, followed by fibroblastic proliferation, This proliferation leads to the excess collagen deposition observed with gingival hyperplasia. C1 VET AFFAIRS MED CTR,SECT THERAPEUT 111T,MED SERV,MINNEAPOLIS,MN 55417. UNIV MINNESOTA,SCH MED,DEPT MED,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH MED,DEPT PHARMACOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH DENT,ORAL HLTH CLIN RES CTR,MINNEAPOLIS,MN 55455. NE OHIO UNIV,COLL MED,ROOTSTOWN,OH 44272. ELI LILLY & CO,INDIANAPOLIS,IN 46285. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NIDCR NIH HHS [P30 DE09737]; NIEHS NIH HHS [R01 ES 03731] NR 53 TC 20 Z9 20 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 1996 VL 60 IS 2 BP 191 EP 198 DI 10.1016/S0009-9236(96)90135-6 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VJ969 UT WOS:A1996VJ96900010 PM 8823237 ER PT J AU Strain, EC Preston, KL Liebson, IA Bigelow, GE AF Strain, EC Preston, KL Liebson, IA Bigelow, GE TI Opioid antagonist effects of dezocine in opioid-dependent humans SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID METHADONE-MAINTAINED VOLUNTEERS; POSTOPERATIVE PAIN; PRECIPITATED WITHDRAWAL; INTRAVENOUS DEZOCINE; AGONIST-ANTAGONIST; DOUBLE-BLIND; MORPHINE; BUPRENORPHINE; BUTORPHANOL; PLACEBO AB Dezocine is an opioid mu-partial agonist recently approved for use as an analgesic in the United States. This study characterized the relative agonist versus antagonist effects of dezocine in comparison to naloxone (an opioid antagonist), hydromorphone (an opioid mu-agonist), and placebo (saline solution) in opioid-dependent volunteers. In a residential laboratory, six volunteer male oploid abusers maintained on 30 mg/day oral methadone underwent pharmacologic challenges two to three times per week, 20 hours after the last dose of methadone. Challenges consisted of a double-blind intramuscular injection of dezocine (dose range, 7.5 to 60 mg), hydromorphone (5 and 10 mg), naloxone (0.1 and 0.2 mg), or saline solution. Measures included physiologic indexes, self-reports of drug effects, and observer ratings of drug effects. Naloxone and hydromorphone produced characteristic antagonist-like and agonist-like effects, respectively. Dezocine acted as an opioid antagonist, precipitating a withdrawal syndrome only slightly different from that produced by naloxone. Dezocine's antagonist effects were not directly dose related, but peaked at intermediate doses and declined at higher doses. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BEHAV PHARMACOL RES UNIT,BALTIMORE,MD 21205. NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU NIDA NIH HHS [R01 DA08045, K20 DA00166, K05 DA00050] NR 36 TC 9 Z9 24 U1 0 U2 5 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 1996 VL 60 IS 2 BP 206 EP 217 DI 10.1016/S0009-9236(96)90137-X PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VJ969 UT WOS:A1996VJ96900012 PM 8823239 ER PT J AU Clarke, EJ Waclawiw, MA AF Clarke, EJ Waclawiw, MA TI Probabilistic rule induction from a medical research study database SO COMPUTERS AND BIOMEDICAL RESEARCH LA English DT Article ID KNOWLEDGE AB This paper describes and applies the ITRULE algorithm, a generalized rule induction algorithm of Smyth and Goodman, for the exploratory analysis of a subset of data from the National Heart, Lung, and Blood Institute Growth and Health Study. The ITRULE algorithm is used as an effective, parsimonious method for detecting informative relationships in a large set of study variables. The potential complexity of the search among many variables is controlled by applying an information theoretic rule preference measure, the J-measure, to limit rule specialization. (C) 1996 Academic Press, Inc. C1 NHLBI,BETHESDA,MD 20892. RP Clarke, EJ (reprint author), MARYLAND MED RES INST,600 WYNDHURST AVE,BALTIMORE,MD 21210, USA. FU NHLBI NIH HHS [N01-HC-55023-26] NR 13 TC 3 Z9 3 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 0010-4809 J9 COMPUT BIOMED RES JI Comput. Biomed. Res. PD AUG PY 1996 VL 29 IS 4 BP 271 EP 283 DI 10.1006/cbmr.1996.0020 PG 13 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA VF943 UT WOS:A1996VF94300003 PM 8812074 ER PT J AU Miththapala, S Seidensticker, J OBrien, SJ AF Miththapala, S Seidensticker, J OBrien, SJ TI Phylogeographic subspecies recognition in leopards (Panthera pardus): Molecular genetic variation SO CONSERVATION BIOLOGY LA English DT Article ID MITOCHONDRIAL-DNA; HETEROZYGOSITY; HYBRIDIZATION; CONSERVATION; DIVERSITY; CHEETAH; NUMBER; WOLF AB The incorporation of precise definitions for taxonomic units into wildlife legislation has necessitated the reevaluation of the taxonomy of endangered and threatened species. We used the subspecies recognition criteria proposed by Avise and Ball (1990) and O'Brien and Mayr (1991) to examine the infraspecific taxonomy of the leopard, Panthera pardus, a geographically widespread species with 27 currently recognized trinomial designations. Samples from named subspecies revealed appreciable genetic diversity using three molecular methods: allozymes, mitochondrial DNA restriction sites, and feline-specific minisatellites. Continental populations and subspecies from Africa and Asia possessed the highest amount of molecular genetic variation, whereas relatively lower amounts of diversity were present in island populations. Molecular data were analyzed using three phylogenetic methods (distance-matrix, maximum parsimony, and maximum likelihood) to resolve genetic differentiation below the species level. The combined results revealed phylogenetic distinction of six geographically isolated groups of leopards: (1) African (2) central Asian, (3) Indian, (4) Sir Lankan, (5) Javan, and (6) east Asian. Based on the combined molecular analyses and supporting morphological data (Miththapala 1992), we recommend that subspecific leopard taxonomy be revised to comprise eight subspecies: (1) P. p. pardus, Africa; (2) P. p. saxicolor, central Asia; (3) P. p. fusca, Indian subcontinent; (4) P. p. kotiya, Sri Lanka; (5) P. p. melas, Java; (6) P. p. orientalis, Amur; (7) P. p. japonensis, northern China; and (8) P. p. delacouri, southern China. In most cases, designated subspecies conform to historic geological barriers that would have facilitated allopatric genetic divergence. C1 NCI, FREDERICK CANC RES & DEV CTR, BIOL CARCINOGENESIS & DEV PROGRAM, PROGRAM RESOURCES INC, FREDERICK, MD 21702 USA. SMITHSONIAN INST, NATL ZOOL PK, WASHINGTON, DC 20008 USA. NCI, NIH, VIRAL CARCINOGENESIS LAB, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. NR 80 TC 45 Z9 55 U1 0 U2 38 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0888-8892 EI 1523-1739 J9 CONSERV BIOL JI Conserv. Biol. PD AUG PY 1996 VL 10 IS 4 BP 1115 EP 1132 DI 10.1046/j.1523-1739.1996.10041115.x PG 18 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA VC103 UT WOS:A1996VC10300029 ER PT J AU Andreassen, C Bornstein, MH AF Andreassen, C Bornstein, MH TI Relating events in narrative: A crosslinguistic developmental study - Berman,RA, Slobin,DI SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP Andreassen, C (reprint author), NICHHD,CHILD & FAMILY RES SECT,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD AUG PY 1996 VL 41 IS 8 BP 835 EP 836 PG 2 WC Psychology, Multidisciplinary SC Psychology GA VA971 UT WOS:A1996VA97100060 ER PT J AU Kusek, JW Lee, JY Charleston, J Faulkner, M Levell, B Milligan, S Norris, K AF Kusek, JW Lee, JY Charleston, J Faulkner, M Levell, B Milligan, S Norris, K TI Participant satisfaction in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study SO CONTROLLED CLINICAL TRIALS LA English DT Article DE AASK Pilot Study; hypertension; kidney disease AB Seventy-one of the 94 eligible participants of the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study completed a self-administered questionnaire at the end of the study to determine their satisfaction with the study, difficulties encountered during participation, and willingness to join a similar study in the future. Nearly all of the participants (97%) believed that they would directly benefit from the study; treatment and information from physicians (94%), and more knowledge (92%) and closer monitoring (90%) of their physical condition were often cited as the ways in which the AASK Pilot Study helped. The two most commonly reported problems in the study were side effects from antihypertensive drugs (27%) and travel to and from the clinic (25%). Eighty-two percent of those who completed the survey indicated that they would volunteer for a similar study in the future. We conclude that AASK Pilot Study participants believed that they would benefit directly from the trial and that medical aspects of the trial were of major importance. Side effects from antihypertensive drugs and difficulties in travel to and from the clinic were commonly encountered problems and may hinder long-term participation in the AASK Full-Scale Trial. C1 UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT BIOSTAT,BIRMINGHAM,AL 35294. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. MEHARRY MED COLL,DEPT MED,NASHVILLE,TN 37208. MOREHOUSE SCH MED,ATLANTA,GA 30310. CASE WESTERN RESERVE UNIV,MANDEL SCH APPL SCI,CLEVELAND,OH 44106. CHARLES R DREW UNIV MED & SCI,DEPT MED,LOS ANGELES,CA 90059. RP Kusek, JW (reprint author), NIDDK,NIH,NATCHER BLDG,ROOM 6AS-13,45 CTR DR,MSC 6600,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1996 VL 17 IS 4 SU S BP S47 EP S54 DI 10.1016/S0197-2456(97)82682-7 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VL293 UT WOS:A1996VL29300006 PM 8889354 ER PT J AU Kusek, JW Lee, JY Smith, DE Milligan, S Faulkner, M Cornell, CE Kopple, JD Greene, PG AF Kusek, JW Lee, JY Smith, DE Milligan, S Faulkner, M Cornell, CE Kopple, JD Greene, PG TI Effect of blood pressure control and antihypertensive drug regimen on quality of life: The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study SO CONTROLLED CLINICAL TRIALS LA English DT Article DE AASK Pilot Study; hypertension; kidney disease AB The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of carrying out a randomized, multicenter, 7-year clinical trial to determine the effects of two goal levels of blood pressure control and three antihypertensive drug regimens on decline in glomerular filtration rate in African Americans with clinically diagnosed hypertensive nephrosclerosis. Participants were randomized to either a usual mean arterial blood pressure (MAP) goal group (102-107 mm Hg) or a low-MAP goal group (less than or equal to 92 mm Hg) and to a drug regimen (initial therapy with either atenolol, amlodipine, or enalapril). Quality of life was assessed by the Medical Outcomes Short-Form 36 (MOS SF-36) at baseline and the last follow-up visit for 84 of the 94 participants of the AASK Pilot Study. Symptoms were assessed at baseline and throughout the course of therapy by participant self-report. Mean SF-36 scores increased significantly on physical functioning (9.2), role limitations (physical) (19.0), social functioning (9.0), and vitality dimensions (5.6) from baseline to the last follow-up visit in the usual MAP goal group. Scores for the eight health dimensions assessed by the MOS SF-36 did not change significantly during the same time period either in the low-MAP goal group or in any of the drug regimens. The mean score for general health perception was significantly lower at the last follow-up visit in the enalapril drug regimen (49.9) compared to drug regimens with atenolol (65.4) or amlodipine (63.9). Physical functioning, role limitations (emotional), social functioning, mental health, vitality, and general health perception scores were negatively correlated with self-reported symptoms during treatment. We conclude that selected dimensions of quality of life improved during the AASK Pilot Study only in participants randomized to the usual MAP goal group. Significant differences between MAP goal groups and drug regimens at the end of follow-up were observed for only a few health dimensions. C1 UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT BIOSTAT,BIRMINGHAM,AL 35294. UNIV ALABAMA,DIV PREVENT MED,BIRMINGHAM,AL. CASE WESTERN RESERVE UNIV,MANDEL SCH APPL SCI,CLEVELAND,OH 44106. MEHARRY MED COLL,DEPT MED,NASHVILLE,TN 37208. UNIV CALIF LOS ANGELES,HARBOR MED CTR,DIV NEPHROL & HYPERTENS,TORRANCE,CA 90509. RP Kusek, JW (reprint author), NIDDK,NIH,NATCHER BLDG,ROOM 6AS-13J,45 CTR DR,MSC 6600,BETHESDA,MD 20892, USA. NR 0 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1996 VL 17 IS 4 SU S BP S40 EP S46 DI 10.1016/S0197-2456(97)82681-5 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VL293 UT WOS:A1996VL29300005 PM 8889353 ER PT J AU Kusek, JW Agodoa, LY Glassock, R Wright, JT Kirk, KA Lee, JY AF Kusek, JW Agodoa, LY Glassock, R Wright, JT Kirk, KA Lee, JY TI The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study - Overview SO CONTROLLED CLINICAL TRIALS LA English DT Editorial Material ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; BLOOD-PRESSURE CONTROL; VENTRICULAR DYSFUNCTION SOLVD; CALCIUM-CHANNEL BLOCKER; HEALTH SURVEY SF-36; ANTIHYPERTENSIVE THERAPY; SOCIAL SUPPORT; RACIAL-DIFFERENCES; MEDICAL OUTCOMES C1 UNIV KENTUCKY, DEPT MED, LEXINGTON, KY 40506 USA. UNIV ALABAMA, DEPT MED, BIRMINGHAM, AL 35294 USA. UNIV ALABAMA, DEPT BIOSTAT, BIRMINGHAM, AL 35294 USA. CASE WESTERN RESERVE UNIV, SCH MED, DIV HYPERTENS, CLEVELAND, OH USA. RP Kusek, JW (reprint author), NIDDKD, NIH, BETHESDA, MD 20892 USA. NR 150 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 EI 1879-050X J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1996 VL 17 IS 4 SU S BP S1 EP + DI 10.1016/S0197-2456(96)90370-0 PG 0 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VL293 UT WOS:A1996VL29300001 ER PT J AU Lee, JY Greene, PG Douglas, M Grim, C Kirk, KA Kusek, JW Milligan, S Smith, DE Whelton, PK AF Lee, JY Greene, PG Douglas, M Grim, C Kirk, KA Kusek, JW Milligan, S Smith, DE Whelton, PK TI Appointment attendance, pill counts, and achievement of goal blood pressure in the African American Study of Kidney Disease and Hypertension Pilot Study SO CONTROLLED CLINICAL TRIALS LA English DT Article DE AASK Pilot Study; hypertension; kidney disease AB The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of conducting a 7-year clinical trial to assess the effect of two levels of blood pressure control based on mean arterial pressure (MAP) (low goal less than or equal to 92 mm Hg or usual goal of 102-107 mm Hg) and three antihypertensive drug regimens (atenolol, amlodipine, or enalapril) as initial therapy in slowing the decline of renal function in African Americans with clinically diagnosed hypertensive nephrosclerosis. Ninety-four African American men and women between 18 and 70 years of age were randomized and followed for an average of 4.6 months. On average, participants attended 87.5% of the scheduled monthly follow-up visits and achieved an acceptable level of medication adherence (80%-100% of prescribed doses by pill count) at 65.4% of those visits. Blood pressure levels within goal were observed in 17.5% and 25.6% of the participants in the low- and usual MAP goal groups, respectively. Neither attendance nor medication adherence by pill count was associated with attainment Of goal blood pressure. Although AASK Pilot Study participants maintained excellent attendance, their pill counts were lower than previously reported among clinical trial participants and goal blood pressure levels were difficult to achieve during the short period of follow-up. C1 NIDDK,NIH,BETHESDA,MD 20892. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT BIOSTAT,BIRMINGHAM,AL 35294. UNIV ALABAMA,DIV PREVENT MED,BIRMINGHAM,AL. EMORY UNIV,HYPERTENS RES CTR,ATLANTA,GA 30322. CHARLES R DREW UNIV MED & SCI,DEPT MED,LOS ANGELES,CA 90059. CASE WESTERN RESERVE UNIV,MANDEL SCH APPL SCI,CLEVELAND,OH 44106. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,WELCH CTR PREVENT EPIDEMIOL & CLIN RES,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NR 0 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1996 VL 17 IS 4 SU S BP S34 EP S39 DI 10.1016/S0197-2456(97)82680-3 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VL293 UT WOS:A1996VL29300004 PM 8889352 ER PT J AU Whelton, PK Lee, JY Kusek, JW Charleston, J DeBruge, J Douglas, M Faulkner, M Greene, PG Jones, CA Kiefer, S Kirk, KA Levell, B Norris, K Powers, SN Retta, TM Smith, DE Ward, H AF Whelton, PK Lee, JY Kusek, JW Charleston, J DeBruge, J Douglas, M Faulkner, M Greene, PG Jones, CA Kiefer, S Kirk, KA Levell, B Norris, K Powers, SN Retta, TM Smith, DE Ward, H TI Recruitment experience in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study SO CONTROLLED CLINICAL TRIALS LA English DT Article DE AASK Pilot Study; hypertension; kidney disease; renal insufficiency AB Several approaches for recruitment of African American adults with renal insufficiency due to hypertension (glomerular filtration rate between 25 and 70 ml/min/1.73 m(2)) were explored in the Pilot Study for the African American Study of Kidney Disease and Hypertension (AASK). Over a period of 42 weeks, prescreening information was obtained on 2880 individuals, of whom 498 (17%) were evaluated at a screening visit. Two hundred and twenty-five (8%) had an I-125-iothalamate assessment of glomerular filtration rate. Ninety-four of 97 participants who met all the study eligibility criteria were enrolled in the trial. The most common reasons for ineligibility during screening were absence of renal insufficiency or hypertension, presence of diabetes mellitus, and a body mass index above the acceptable level. Overall, an average of 31 prescreen contacts and 8 screening visits were conducted for every randomization (3.3% yield from prescreening to randomization). Screening in clinical practice was the most efficient method for recruitment (12.6% yield from prescreen contact to randomization compared to 1.1% from mass mailing campaigns, 1.3% from mass media campaigns, and 1.7% from referrals by patients with end-stage renal disease). Randomization yields increased with progressively higher age ranges (2.4%, 3.3%, and 6.0% prescreen to randomization yields for those aged less than or equal to 50, 51-60, and 61-70, respectively). A slight majority (51%) of the prescreen contacts were women, but 75% of the randomized participants were men. Our results suggest that clinic-based screening is an effective approach for recruitment of African Americans with hypertension and renal insufficiency into clinical trials. They also suggest that enrollment of African American women in such studies is a special challenge. C1 NIDDK,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,WELCH CTR PREVENT EPIDEMIOL & CLIN RES,DEPT EPIDEMIOL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT BIOSTAT,BIRMINGHAM,AL 35294. EMORY UNIV,HYPERTENS RES CTR,ATLANTA,GA 30322. MEHARRY MED COLL,DEPT MED,NASHVILLE,TN 37208. UNIV ALABAMA,DIV PREVENT MED,BIRMINGHAM,AL. NIDDKD,NIH,BETHESDA,MD 20892. UNIV SO CALIF,DEPT MED NEPHROL,LOS ANGELES,CA. MOREHOUSE SCH MED,ATLANTA,GA 30310. CHARLES R DREW UNIV MED & SCI,DEPT MED,LOS ANGELES,CA 90059. VANDERBILT UNIV,DEPT MED,NASHVILLE,TN. HOWARD UNIV,DEPT MED,WASHINGTON,DC 20059. NR 0 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1996 VL 17 IS 4 SU S BP S17 EP S33 DI 10.1016/S0197-2456(96)00087-6 PG 17 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VL293 UT WOS:A1996VL29300003 PM 8889351 ER PT J AU Wright, JT Kusek, JW Toto, RD Lee, JY Agodoa, LY Kirk, KA Randall, OS Glassock, R AF Wright, JT Kusek, JW Toto, RD Lee, JY Agodoa, LY Kirk, KA Randall, OS Glassock, R TI Design and baseline characteristics of participants in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study SO CONTROLLED CLINICAL TRIALS LA English DT Article DE AASK Pilot Study; hypertension; kidney disease AB Hypertension and end-stage renal disease (ESRD) are major causes of morbidity and mortality in the United States, especially among African Americans. The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of conducting a long-term clinical trial to compare the effects of two levels of blood pressure control and three different antihypertensive drug regimens on the rate of decline in glomerular filtration rate (GFR) in African Americans with clinically diagnosed hypertensive renal disease. African American men and women aged 18-70 years with a GFR of 25-70 ml/min/1.73m(2) and hypertension were randomized in a 3 x 2 factorial design to initial treatment with either an angiotensin-converting enzyme inhibitor (enalapril), a calcium channel blocker (amlodipine), or a beta blocker (atenolol) and to a mean arterial blood pressure (goal MAP) of either 102-107 mm Hg or less than or equal to 92 mm Hg. Furosemide, doxazosin, clonidine, hydralazine, and minoxidil were added sequentially until goal MAP was achieved. To compare the pathologic diagnosis with the clinical diagnosis of renal disease, study participants without contraindication were also asked to undergo a renal biopsy. The goals of the AASK Pilot Study were to evaluate recruitment techniques, adherence to prescribed antihypertensive drug regimens, ability of the antihypertensive regimens to achieve blood pressure goals, rates of participation in scheduled clinic visits and procedures, and variability of GFR measurements. A further goal was to obtain renal biopsy data in at least 75% of the randomized study participants. Compared to the ESRD patient population whose renal disease is caused by hypertension, women were underrepresented in the AASK Pilot Study. AASK Pilot Study participants had higher unemployment rates and lower income levels than African Americans in the general U.S. population. C1 NIDDK,NIH,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,SCH MED,DIV HYPERTENS,CLEVELAND,OH. UNIV TEXAS SW,DEPT MED,DALLAS,TX. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT BIOSTAT,BIRMINGHAM,AL 35294. NIDDKD,NIH,BETHESDA,MD 20892. HOWARD UNIV,DEPT MED,WASHINGTON,DC 20059. UNIV KENTUCKY,DEPT MED,LEXINGTON,KY 40506. NR 0 TC 67 Z9 69 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 1996 VL 17 IS 4 SU S BP S3 EP S16 DI 10.1016/S0197-2456(96)00081-5 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VL293 UT WOS:A1996VL29300002 PM 8889350 ER PT J AU Lansbury, PT Caughey, B AF Lansbury, PT Caughey, B TI The double life of the prion protein SO CURRENT BIOLOGY LA English DT Article C1 HARVARD UNIV,SCH MED,LMRC,BOSTON,MA 02115. NIAID,ROCKY MT LABS,NIH,HAMILTON,MT 59840. RP Lansbury, PT (reprint author), BRIGHAM & WOMENS HOSP,CTR NEUROL DIS,BOSTON,MA 02115, USA. NR 12 TC 13 Z9 13 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 1 PY 1996 VL 6 IS 8 BP 914 EP 916 DI 10.1016/S0960-9822(02)00624-3 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VB225 UT WOS:A1996VB22500006 PM 8805340 ER PT J AU Uhl, GR Vandenbergh, DJ Miner, LL AF Uhl, GR Vandenbergh, DJ Miner, LL TI Drug addiction: Knockout mice and dirty drugs SO CURRENT BIOLOGY LA English DT Article ID RECEPTOR MUTANT MICE; 6-HYDROXYDOPAMINE LESIONS; COCAINE; TRANSPORTERS AB Recent studies with knockout mice implicate the dopamine transporter as the target of the locomotor effects of the addictive psychomotor drugs cocaine and amphetamine; studies of reward in these animals are eagerly awaited. RP Uhl, GR (reprint author), NIDA,ADDICT RES CTR,DEPT HLTH & HUMAN SERV,NATL INST HLTH,POB 5180,BALTIMORE,MD 21224, USA. NR 15 TC 21 Z9 21 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 1 PY 1996 VL 6 IS 8 BP 935 EP 936 DI 10.1016/S0960-9822(02)00630-9 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VB225 UT WOS:A1996VB22500012 PM 8805320 ER PT J AU Tumminia, SJ Chambers, C Qin, C Zigler, JS Russell, P AF Tumminia, SJ Chambers, C Qin, C Zigler, JS Russell, P TI A comparison of antioxidant enzyme activities in organ-cultured Rhesus monkey lenses following peroxide challenge SO CURRENT EYE RESEARCH LA English DT Article DE oxidative stress; ocular lens; catalase; glutathione peroxidase; superoxide dismutase; rhesus monkey ID GLUTATHIONE REDOX CYCLE; OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; RABBIT LENS; EPITHELIAL-CELLS; POSITIVE CONTROL; H2O2; CATALASE; DETOXIFICATION; GENES AB Purpose. To analyze the activities of catalase, glutathione peroxidase and superoxide dismutase, three enzymes involved in the detoxification of reactive oxygen species in organ-cultured Rhesus monkey lenses. Methods. Lenses freshly obtained from Rhesus monkeys were incubated at 37 degrees C for 2 h and assessed for lens integrity. Lenses were then oxidatively stressed by exposure to a bolus of hydrogen peroxide. The three enzyme activities were assayed 2, 4 and 24 h after exposure to the peroxide challenge. Results. Freshly dissected lenses placed in organ culture exhibited a 20% decrease in catalase activity within 2 h. During the course of a 24 h incubation, catalase activity continued to decrease to a level 58% below that of freshly dissected monkey lenses. In contrast, the activity levels of both glutathione peroxidase and superoxide dismutase increased dramatically within the first 2 h of organ culture, with superoxide dismutase being most affected. Although glutathione peroxidase activity declined with incubation time, its level at the end of 24 h was still 36% greater than that of the fresh lenses. Superoxide dismutase activity remained elevated throughout the 24 h incubation period. The addition of a bolus of 0.25 mM H2O2 to monkey lenses in culture had no effect on catalase activity. Two h after the peroxide insult, glutathione peroxidase activity decreased in comparison to control levels while the activity of superoxide dismutase increased by 43%. After 24 h, superoxide dismutase activity returned to values equivalent to the controls. In lenses challenged with 0.50 mM H2O2, catalase and glutathione peroxidase activities decreased at 2 h, while superoxide dismutase activity increased 67% above control levels. At subsequent timepoints, catalase activity increased and reached control levels. In contrast, glutathione peroxidase activity continued to decrease with time eventually reaching fresh lens levels. Superoxide dismutase activity levels remained elevated and were equivalent to control values at 24 h. Conclusions. The data indicate that placement of monkey lenses into an organ culture system represents an environmental change sufficient to cause a response in antioxidant enzyme levels. The addition of H2O2 to this environment caused only superoxide dismutase to be stimulated above control lens levels. RP Tumminia, SJ (reprint author), NEI,LAB MECHANISMS OCULAR DIS,NIH,BLDG 6,RM 228,6 CTR DR MSC 2735,BETHESDA,MD 20892, USA. NR 32 TC 5 Z9 5 U1 0 U2 1 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 AUG PY 1996 VL 15 IS 8 BP 845 EP 851 DI 10.3109/02713689609017625 PG 7 WC Ophthalmology SC Ophthalmology GA VE511 UT WOS:A1996VE51100005 PM 8921227 ER PT J AU Baxevanis, AD Makalowski, W Ouellette, BFF Recipon, H AF Baxevanis, AD Makalowski, W Ouellette, BFF Recipon, H TI Web alert - Protein engineering SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Article C1 NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP Baxevanis, AD (reprint author), NIH,NATL CTR HUMAN GENOME RES,BLDG 49,ROOM 2C-75,BETHESDA,MD 20892, USA. RI Makalowski, Wojciech/I-2843-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD AUG PY 1996 VL 7 IS 4 BP 462 EP 462 DI 10.1016/S0958-1669(96)80125-X PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA VA970 UT WOS:A1996VA97000017 PM 8829488 ER PT J AU Nagineni, CN Kutty, RK Detrick, B Hooks, JJ AF Nagineni, CN Kutty, RK Detrick, B Hooks, JJ TI Inflammatory cytokines induce intercellular adhesion molecule-1 (ICAM-1) mRNA synthesis and protein secretion by human retinal pigment epithelial cell cultures SO CYTOKINE LA English DT Article DE ICAM-1 inflammation; retinal pigment epithelial cells; uveitis ID TUMOR-NECROSIS-FACTOR; ENDOTHELIAL-CELLS; RHEUMATOID-ARTHRITIS; CIRCULATING ICAM-1; INTERFERON-GAMMA; UVEITIS PATIENTS; GENE-EXPRESSION; FACTOR-ALPHA; DISEASE; ANTIGEN AB Retinal inflammatory diseases in man are associated with an upregulation in the expression of intercellular adhesion molecule-1 (ICAM-1) in cells within the retina and with an increase in soluble ICAM-1 within the vitreous, These studies suggest that this protein may contribute to immunopathological processes within the eye, The effects of inflammatory mediators on the regulation of the expression and secretion of ICAM-1 by human retinal pigment epithelial cell cultures (HRPE) were investigated in order to identity the possible source of soluble ICAM-1 and the conditions which enhance its production, Immunofluorescence studies on TNF-alpha and/or IFN-gamma treated HRPE cells demonstrated cellular expression of ICAM-1 which was predominantly localized to intercellular junctions, Moreover, treatment of HRPE for 24 h with tumour necrosis factor alpha (TNF-alpha) (10 ng/ml), interferon gamma (IFN-gamma) (500 u/ml), interleukin 1 alpha (IL-1 alpha) (10 ng/ml) and IL-1 beta (10 ng/ml) results in the secretion of ICAM-1, ranging from 9 to 13 ng per 10(6) cells, IFN-gamma acts synergistically with (TNF-alpha) and IL-1 in the secretion of ICAM-1 by HRPE. Only 1.75 ng of soluble ICAM-1 was detected in untreated HRPE cells, In contrast, lipopolysaccharide (LPS), IL-6, IFN-alpha or TGF-beta did not exhibit any influence on ICAM-1 secretion by these cells, Northern blot analysis reveals an increased expression of ICAM-1 mRNA in HRPE stimulated with IFN-gamma, TNF-alpha or IL-1 for 24 h, In untreated cells, ICAM-1 mRNA is not detectable, There is a progressive increase in ICAM-1 mRNA levels in cytokine-treated HRPE, that reaches steady state by 12 h, Furthermore, a close correlation is noted between ICAM-1 mRNA levels and the secretion of ICAM-1 protein, suggesting regulation at the level of gene transcription, ICAM-1 secretion by RPE might actively participate in the immune reactions in the retina, by recruiting and activating lymphocytes, and contribute to the immunopathological processes in inflammatory diseases. (C) 1996 Academic Press Limited C1 NEI,IMMUNOL LAB,IMMUNOL & VIROL SECT,NIH,BETHESDA,MD 20892. NEI,RETINAL CELL & MOL BIOL LAB,NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. NR 57 TC 29 Z9 29 U1 0 U2 0 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 AUG PY 1996 VL 8 IS 8 BP 622 EP 630 DI 10.1006/cyto.1996.0083 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA VH273 UT WOS:A1996VH27300005 PM 8894437 ER PT J AU OConnell, ML Rebbert, ML Dawid, IB AF OConnell, ML Rebbert, ML Dawid, IB TI Isolation of the Xenopus nrp-1 gene and analysis of its expression following the midblastula transition in injected Xenopus embryos SO DEVELOPMENT GROWTH & DIFFERENTIATION LA English DT Article DE midblastula transition; neural gene; RNA-binding protein; transcription; Xenopus ID NEURON-SPECIFIC EXPRESSION; SODIUM-CHANNEL GENE; ELONGATION-FACTOR 1-ALPHA; ACHAETE-SCUTE; DEVELOPMENTAL REGULATION; PRESUMPTIVE MESODERM; SILENCER ELEMENT; MOLECULAR-BASIS; TRANSCRIPTION; DROSOPHILA AB During embryogenesis the differentiation of distinct tissues is marked by the expression of tissue-specific genes. In Xenopus, the neural-specific gene nrp-1 is activated following the midblastula transition (MET), and is then expressed exclusively in developing neural tissue. To pursue an investigation of the transcriptional regulation of nrp-1, the genomic DNA encoding nrp-1 was isolated and its structure analyzed. Nrp-1 lacks a canonical TATA box proximal to the start site of transcription, but the 5' flanking sequence is highly GC-rich. Injection studies with nrp-1/chloramphenicol acetyltransferase and luciferase constructs demonstrate that in Xenopus embryos, 200 nt of the 5' flanking sequence of nrp-1 are sufficient to drive the expression of reporter genes soon after the MET, albeit not in a tissue-specific manner. This expression is enhanced by the inclusion of larger regions of the nrp-1 gene. C1 NICHHD,GENET MOLEC LAB,NIH,BETHESDA,MD 20892. TRENTON STATE COLL,DEPT BIOL,TRENTON,NJ 08650. NR 62 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0012-1592 J9 DEV GROWTH DIFFER JI Dev. Growth Diff. PD AUG PY 1996 VL 38 IS 4 BP 439 EP 448 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA UZ172 UT WOS:A1996UZ17200012 ER PT J AU Relaix, F Weng, X Marazzi, G Yang, E Copeland, N Jenkins, N Spence, SE Sassoon, D AF Relaix, F Weng, X Marazzi, G Yang, E Copeland, N Jenkins, N Spence, SE Sassoon, D TI Pw1, a novel zinc finger gene implicated in the myogenic and neuronal lineages SO DEVELOPMENTAL BIOLOGY LA English DT Article ID REGULATORY FACTORS; MESSENGER-RNA; CO-REPRESSOR; EXPRESSION; DNA; TRANSCRIPTION; PROTEINS; LOCALIZATION; DOMAINS; BINDING AB The cellular and molecular processes leading to the establishment of the skeletal muscle lineage in the vertebrate are not well understood. The MyoD-related family of myogenic regulatory factors (MRFs) are expressed during somitogenesis although cells with myogenic capacity are present prior to gastrulation. We propose that regulatory genes exist that guide the skeletal muscle lineage during early development. In an effort to identify these regulatory genes, we performed a differential screening to isolate transcripts that are present in myogenic cells and in the embryo prior to MRF expression but absent in nonmyogenic fibroblasts. We report here the identification of Pw1. The Pw1 transcript is similar to 8.5 kb long and encodes a large protein containing 12 widespread C2H2 zinc fingers and 3 motifs containing periodic prolines and acidic residues. Consistent with the possibility that Pw1 is a transcription factor, we observe nuclear localization of the protein. Pw1 is strongly expressed upon gastrulation and subsequently becomes restricted to skeletal muscle and subregions of the central nervous system. Pw1 is initially expressed in all mesodermal cells early in development; however, its maintained expression in adult differentiated muscle suggests a specific role in the skeletal muscle lineage. Pw1 expression is cell cycle specific with levels highest during late M-phase. The gene is intronless which may facilitate transcription during cell division. At present, the precise function of Pw1 is not understood; however, we note that Pw1 maps to the proximal region of chromosome 7 near the axial segmentation mutant pudgy which shows severe perturbation of axial skeletal and muscle structures. (C) 1996 Academic Press, Inc. C1 MILLENNIUM PHARMACEUT INC,CAMBRIDGE,MA 02139. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP Relaix, F (reprint author), CUNY MT SINAI SCH MED,BROOKDALE CTR MOL BIOL,1 GUSTAVE LEVY PL,NEW YORK,NY 10029, USA. NR 46 TC 85 Z9 87 U1 0 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 1996 VL 177 IS 2 BP 383 EP 396 DI 10.1006/dbio.1996.0172 PG 14 WC Developmental Biology SC Developmental Biology GA VA829 UT WOS:A1996VA82900002 PM 8806818 ER PT J AU Xu, J Liu, LZ Deng, XF Timmons, L Hersperger, E Steeg, PS Veron, M Shearn, A AF Xu, J Liu, LZ Deng, XF Timmons, L Hersperger, E Steeg, PS Veron, M Shearn, A TI The enzymatic activity of Drosophila AWD/NDP kinase is necessary but not sufficient for its biological function SO DEVELOPMENTAL BIOLOGY LA English DT Article ID NUCLEOSIDE DIPHOSPHATE KINASE; TUMOR-METASTASIS; LETHAL INTERACTION; HUMAN-ERYTHROCYTES; CRYSTAL-STRUCTURE; NM23 GENE; MUTATIONS; KILLER; PRUNE; DICTYOSTELIUM AB The Drosophila abnormal wing discs (awd) gene encodes the subunit of a protein that has nucleoside diphosphate kinase (NDP kinase) activity. Null mutations of the awd gene cause lethality after puparium formation. Larvae homozygous for such mutations have small imaginal discs, lymph glands, and brain lobes. Neither the imaginal discs nor the ovaries from such null mutant larvae are capable of further growth or normal differentiation when transplanted into suitable host larvae. This null mutant phenotype can be entirely rescued by one copy of a transgene that has 750 bp of awd upstream regulatory DNA fused to a full-length awd cDNA. Tissue-specific expression of AWD protein from this rescue transgene is identical to tissue-specific expression of beta-galactosidase from a reporter transgene that has the same regulatory region fused to the bacterial Iac Z gene. However, this rescue transgene or reporter transgene expression pattern is only a subset of the endogenous pattern of expression detected by either in situ hybridization or immunohistochemistry. This suggests that awd is normally expressed in some tissues where it is not required. The null mutant phenotype cannot be rescued at all by a transgene that has 750 bp of awd upstream regulatory DNA fused to a full-length awd cDNA with a mutation that eliminates NDP kinase activity by replacement of the active site histidine with alanine. This suggests that the enzymatic activity of the AWD protein is necessary for its biological function. The human genes nm23-H1 and nm23-H2 encode NDP kinase A and B subunits, respectively, The protein subunit encoded by either human nm23 gene is 78% identical to that encoded by the Drosophila awd gene. Transgenes that have the 750-bp awd upstream regulatory DNA fused to human nm23-H2 cDNA but not to nm23-H1 cDNA can rescue the imaginal disc phenotype and the zygotic lethality caused by homozygosis for an awd null mutation as efficiently as an awd transgene. However, rescue of female sterility requires twice as much nm23-H2 expression as awd expression. This implies that the enzymatic activity of the AWD protein is not sufficient for its biological function. The biological function may require nonconserved residues of the AWD protein that allow it to interact with other proteins. (C) 1996 Academic Press, Inc. C1 JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. NCI,WOMENS CANC SECT,PATHOL LAB,BETHESDA,MD 20892. INST PASTEUR,DEPT CELLULAR BIOCHEM,F-75724 PARIS 15,FRANCE. NR 30 TC 56 Z9 59 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 1996 VL 177 IS 2 BP 544 EP 557 DI 10.1006/dbio.1996.0184 PG 14 WC Developmental Biology SC Developmental Biology GA VA829 UT WOS:A1996VA82900014 PM 8806830 ER PT J AU Tomarev, SI Sundin, O BanerjeeBasu, S Duncan, MK Yang, JM Piatigorsky, J AF Tomarev, SI Sundin, O BanerjeeBasu, S Duncan, MK Yang, JM Piatigorsky, J TI Chicken homeobox gene Prox 1 related to Drosophila prospero is expressed in the developing lens and retina SO DEVELOPMENTAL DYNAMICS LA English DT Article DE eye; lens; retina; Prox 1; homeodomain protein; development; prospero; evolution ID A-CRYSTALLIN GENE; ASYMMETRIC SEGREGATION; HOMEODOMAIN PROTEINS; VERTEBRATE EYE; EYELESS GENE; HOX GENES; C-ELEGANS; PAX-6; TRANSCRIPTION; EVOLUTION AB Prox 1 is the vertebrate homolog of Drosophila prospero, a gene known to be expressed in the lens-secreting cone cells of fly ommatidia. Chicken Prox 1 cDNAs were isolated from 14 day embryonic chicken lenses, and a complete open reading frame encoding an 83 kDa protein was elucidated. The homeodomains of chicken and mouse Prox 1 are identical at the amino acid level and are 65-67% similar to the homeodomains of Drosophila and C. elegans prospero. The homology between these proteins extends beyond the homeodomain. There is 56% identity between chicken Prox 1 and Drosophila prospero in the C-terminal region downstream of the homeodomain, whereas there is little similarity upstream of the homeodomain. Prox 1 is expressed most actively in the developing lens and midgut; and at lower levels in the developing brain, heart, muscle, and retina. cDNA sequencing has established that there are alternatively spliced forms of the single Prox 1 gene, which probably account for the two abundant RNAs of about 2 and 8 kb and two less abundant RNAs close to 3.5 kb in length in the lens. In the lens fibers, only the shortest mRNA was present, whereas, in the epithelial cells, both short and long mRNAs were detected. By using in situ hybridization, expression of the Prox 1 gene was first detected at stage 14 in the early lens placode and slightly preceded the expression of delta 1-crystallin, the first crystallin gene expressed in the developing chicken lens. At later stages of development, Prox 1 mRNA was observed throughout the lens, but it appeared more abundant around the bow region of the equator than in the anterior epithelium or the fibers. In the retina, expression of the Prox 1 gene was detected mainly in the inner nuclear layer during later stages of histogenesis. The conserved pattern of Prox 1/prospero gene expression in vertebrates and Drosophila suggests that Prox 1, like Pax-6, may be essential for eye development in different systematic groups. (C) 1996 Wiley-Liss, Inc.* C1 JOHNS HOPKINS UNIV,SCH MED,WILMER EYE INST,BALTIMORE,MD 21287. RP Tomarev, SI (reprint author), NEI,MOL & DEV BIOL LAB,NIH,BLDG 6,ROOM 203,6 CTR DR,MSC 2730,BETHESDA,MD 20892, USA. NR 55 TC 102 Z9 106 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD AUG PY 1996 VL 206 IS 4 BP 354 EP 367 DI 10.1002/(SICI)1097-0177(199608)206:4<354::AID-AJA2>3.0.CO;2-H PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA VA079 UT WOS:A1996VA07900002 PM 8853985 ER PT J AU Nagi, DK McCormack, LJ MohamedAli, V Yudkin, JS Grant, PJ Knowler, WC AF Nagi, DK McCormack, LJ MohamedAli, V Yudkin, JS Grant, PJ Knowler, WC TI Plasminogen activator inhibitor (PAI-1) activin, its promoter (4G/5G) genotype and diabetic retinopathy in subjects with NIDDM. SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIH,PHOENIX,AZ. UNIV LEEDS,DIV MED,DIABET & THROMBOSIS RES GRP,LEEDS,W YORKSHIRE,ENGLAND. UCLMS,DEPT MED,LONDON,ENGLAND. RI Yudkin, John/C-1988-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 94 EP 94 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300094 ER PT J AU LevyMarchal, C Pettitt, DJ Pratley, RE Bogardus, C AF LevyMarchal, C Pettitt, DJ Pratley, RE Bogardus, C TI Insulin-resistance without insulin secretion defect is associated with low birth weight in young adults at risk for NIDDM SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDKD,PHOENIX,AZ 85016. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 190 EP 190 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300191 ER PT J AU Seissler, J Morgenthaler, NG Lan, MS Notkins, AL Scherbaum, WA AF Seissler, J Morgenthaler, NG Lan, MS Notkins, AL Scherbaum, WA TI Autoantibodies to tyrosine phosphatases IA-2 and IA-2 beta in insulin-dependent diabetes mellitus SO DIABETOLOGIA LA English DT Meeting Abstract C1 UNIV LEIPZIG,DEPT INTERNAL MED 3,D-7010 LEIPZIG,GERMANY. NIH,ORAL MED LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 317 EP 317 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300315 ER PT J AU Perfetti, R Wang, Y Egan, JM AF Perfetti, R Wang, Y Egan, JM TI Is the age-dependent decline of pancreatic islet function a reversible phenomenon? SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIA,DIABET UNIT,LCP,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 475 EP 475 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300471 ER PT J AU Wertheimer, E Tennenbaum, T Graham, DE Barth, K Yuspa, SH Taylor, SI AF Wertheimer, E Tennenbaum, T Graham, DE Barth, K Yuspa, SH Taylor, SI TI The role of the insulin receptor in cellular growth and tumorigenesis. SO DIABETOLOGIA LA English DT Meeting Abstract C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT PATHOL,IL-69978 TEL AVIV,ISRAEL. BAR ILAN UNIV,DEPT LIFE SCI,IL-52100 RAMAT GAN,ISRAEL. NIDDK,DIABET BRANCH,NIH,BETHESDA,MD. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 627 EP 627 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300624 ER PT J AU Hohman, TC Jacot, JL Glover, JP Basso, MD Robison, WG AF Hohman, TC Jacot, JL Glover, JP Basso, MD Robison, WG TI Early and late intervention therapy for diabetic retinopathy with an aldose reductase inhibitor SO DIABETOLOGIA LA English DT Meeting Abstract C1 WYETH AYERST RES,PRINCETON,NJ 08543. NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 928 EP 928 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300923 ER PT J AU Lan, MS Modi, WS Xie, H Notkins, AL AF Lan, MS Modi, WS Xie, H Notkins, AL TI Assignment of the IA-2 gene encoding an autoantigen in IDDM to chromosome 2q35 SO DIABETOLOGIA LA English DT Letter ID PROTEIN-TYROSINE-PHOSPHATASE; CLONING; TYPE-1 RP Lan, MS (reprint author), NIDR,ORAL MED LAB,NIH,BLDG 30,ROOM 124,30 CONVENT DR,MSC 4322,BETHESDA,MD 20892, USA. NR 11 TC 13 Z9 14 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 IS 8 BP 1001 EP 1002 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA076 UT WOS:A1996VA07600018 PM 8858226 ER PT J AU Abati, A Cajigas, A Holland, SM Solomon, D AF Abati, A Cajigas, A Holland, SM Solomon, D TI Chronic granulomatous disease of childhood: Respiratory cytology SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE chronic granulomatous disease; cytology; microbiology ID INTERFERON-GAMMA; INFECTION; PATIENT AB Chronic granulomatous disease (CGD) of childhood is a rare inherited disease in which phagocytic cells fail to produce the normal respiratory burst in response to infectious stimuli, leaving the patient particularly susceptible to infections with bacteria and fungi that produce catalase. Between 1988 and 1993 at the NIH, 58 pulmonary cytology specimens were obtained on 24 CGD patients. The number of specimens per patient ranged from one to 13 with an average of 2.4. The 58 specimens included: 33 bronchoalveolar lavages; one bronchial brushing; 20 lung or pleural mass fine-needle aspirates; three pleural fluids, and one sputum. Two lung aspirates with insufficient material, five bronchoalveolar lavages performed post-treatment to confirm clinical resolution of disease, and two bronchoalveolar lavages not submitted for culture were excluded from further analysis. Of the 49 remaining specimens obtained from patients clinically suspected of having a pulmonary infection, cytology demonstrated a pathogenic organism in nine (18%). Microbiologic cultures were positive in 19/49 (39%). Cytology identified fungus in 8/13 (62%) of documented fungal infections, including four cases where microbiology was negative. Bacterial and mixed bacterial/ fungal infections were usually not detected by cytology even with appropriate stains. No organisms were identified by cytology in the four cases of nocardia or the three cases of pseudomonas infection. The combination of cytology and microbiology provided the greatest diagnostic sensitivity, yielding a diagnosis in 22/49 cases (45%). Of the 27 cases with negative cytology and microbiology, an infectious agent was identified in eight upon submission of additional material: three cytology specimens and five tissue specimens. In the remaining 19 cases, no organisms were identified, however, the patients were treated presumptively. Characteristic pathologic features of granulomatous inflammation, necrosis, and giant cells were present in fine-needle aspirates, often when no organisms could be identified but were not seen in other types of respiratory specimens, (C) 1996 Wiley-Liss, Inc.* RP Abati, A (reprint author), NIH,PATHOL LAB,CYTOPATHOL SECT,BLDG 10,ROOM 2A19,BETHESDA,MD 20892, USA. NR 17 TC 11 Z9 11 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD AUG PY 1996 VL 15 IS 2 BP 98 EP 102 DI 10.1002/(SICI)1097-0339(199608)15:2<98::AID-DC3>3.0.CO;2-L PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA VF201 UT WOS:A1996VF20100003 PM 8872429 ER PT J AU Thompson, DC Perera, K London, R AF Thompson, DC Perera, K London, R TI Metabolism and toxicity of 4-hydroxyphenylacetone in rat liver slices: Comparison with acetaminophen SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID QUINONE METHIDE FORMATION; P-BENZOQUINONE IMINE; HEPATOTOXICITY; MECHANISM; OXIDATION; ACTIVATION; REACTIVITY; CYTOCHROME-P-450; SUBSTITUENTS; PARACETAMOL AB Acetaminophen is oxidized by cytochrome P450 to a reactive quinone imino, N-acetyl-p-benzoquinone imine, which is thought to be responsible for its hepatatoxic effects. 4-Hydroxyphenylacetone (4-HPA) is a structural analog of acetaminophen in which the amine group is replaced by a methylene group, Following a similar metabolic pathway, 4-HPA would be oxidized to form a reactive quinone methide intermediate. We compared the metabolism and toxicity of 4-HPA and acetaminaphen in liver microsomes and precision-cut liver slices from male Sprague-Dawley rats, Both 4-HPA and acetaminophen formed glutathione conjugates in microsomal incubations, 4-HPA formed diastereomeric glutathione conjugates, Which is consistent with the formation of an intermediate quinone methide, The rate of conjugate formation with 4-HPA was 8.5-foId greater than that with acetaminophen. In rat liver slices a concentration of 5 mM 4-HPA killed approximately 50% of hepatocytes after 6 hr of incubation, whereas acetaminophen was not toxic at concentrations up to 50 mM, N-Acetylcysteine protected slices from 4-HPA-induced toxicity, whereas phenobarbital enhanced metabolism and toxicity, In summary, 4-HPA is more hepatotoxic than acetaminophen, and this may be the result of differences in the metabolic rate and/or the type of reactive intermediate formed. C1 NIEHS,MOL BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RP Thompson, DC (reprint author), TEXAS A&M UNIV,CTR HLTH SCI,COLL MED,DEPT MED PHARMACOL & TOXICOL,COLLEGE STN,TX 77843, USA. FU NIEHS NIH HHS [ES06016] NR 31 TC 8 Z9 8 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD AUG PY 1996 VL 24 IS 8 BP 866 EP 871 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VC412 UT WOS:A1996VC41200008 PM 8869821 ER PT J AU McCann, UD Slate, SO Ricaurte, GA AF McCann, UD Slate, SO Ricaurte, GA TI Adverse reactions with 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') SO DRUG SAFETY LA English DT Review ID CENTRAL SEROTONERGIC NEURONS; METHYLENEDIOXYMETHAMPHETAMINE MDMA; RAT-BRAIN; (+/-)3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; SUBSTITUTED AMPHETAMINES; SEVERE COMPLICATIONS; CEREBRAL INFARCTION; CEREBROSPINAL-FLUID; RECREATIONAL USERS; NONHUMAN-PRIMATES AB 3,4-Methylenedioxymethamphetamine (MDMA;'ecstasy') is an increasingly popular recreational drug in the US, Western Europe and Australia. In animals, including nonhuman primates, MDMA is known to damage brain serotonin (5-hydroxytryptamine; 5-HT) neurons. It is not known whether MDMA damages serotonin neurons in the human brain but there is some indication that it may. Although the large majority of individuals who have used MDMA recreationally do not develop acute complications, as the popularity of MDMA has increased, so have reports of adverse nonpsychiatric and psychiatric consequences associated with use of the drug. Further, since manifestations of MDMA-induced serotonin injury might only become apparent with age, or under periods of stress, it is possible that some individuals with no apparent abnormalities might develop complications over time. C1 NIMH,UNIT ANXIETY,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 88 TC 87 Z9 87 U1 0 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PD AUG PY 1996 VL 15 IS 2 BP 107 EP 115 DI 10.2165/00002018-199615020-00003 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA VD375 UT WOS:A1996VD37500003 PM 8884162 ER PT J AU Polis, MA AF Polis, MA TI Cidofovir - A viewpoint SO DRUGS LA English DT Editorial Material RP Polis, MA (reprint author), NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PD AUG PY 1996 VL 52 IS 2 BP 231 EP 231 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VA081 UT WOS:A1996VA08100008 ER PT J AU Weiss, GH Sokoloff, H Zakharov, SF Chrambach, A AF Weiss, GH Sokoloff, H Zakharov, SF Chrambach, A TI Interpretation of electrophoretic band shapes by a partition chromatographic model SO ELECTROPHORESIS LA English DT Article DE peak asymmetry; Gaussian peak shape; non-Markovian diffusion; conalbumin; phycoerythrin ID GEL-ELECTROPHORESIS; DNA; APPARATUS AB Measurements of the shape of electrophoretic bands of phycoerythrin and conalbumin have been made at regular intervals during migration in agarose gels. Analysis of the peak shapes suggests the existence of a significant degree of asymmetry. This is to be contrasted with the symmetry around the peak associated with the generally assumed Gaussian band. The degree of asymmetry of the bands decreased as a function of time and increased with agarose concentration. A similar experiment on DNA indicated constancy of the degree of asymmetry as a function of time. These results' can be interpreted as, but do not prove the validity of, a nonlocal diffusion equation which generalizes a theory originally put forth by Giddings and Eyring (J. Am. Chem. Sec. 1955, 59, 416-420). The results may be significant in framing a measure of the resolvability of electrophoretic peaks. C1 NICHHD,NIH,THEORET & PHYS BIOL LAB,MACROMOL ANAL SECT,BETHESDA,MD 20892. NICHHD,NIH,THEORET & PHYS BIOL LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. NR 16 TC 21 Z9 21 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD AUG PY 1996 VL 17 IS 8 BP 1325 EP 1332 DI 10.1002/elps.1150170809 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VG699 UT WOS:A1996VG69900008 PM 8874058 ER PT J AU Chen, YJ Smith, MR Thirumalai, K Zychlinsky, A AF Chen, YJ Smith, MR Thirumalai, K Zychlinsky, A TI A bacterial invasin induces macrophage apoptosis by binding directly to ICE SO EMBO JOURNAL LA English DT Article DE apoptosis; inflammation; interleukin-1 beta converting enzyme; macrophage; Shigella ID DEATH GENE CED-3; SHIGELLA-FLEXNERI; EPITHELIAL-CELLS; INTERLEUKIN-1-BETA-CONVERTING ENZYME; IL-1-BETA-CONVERTING ENZYME; MURINE MACROPHAGES; INTRACELLULAR ROLE; MAMMALIAN HOMOLOG; IPAC INVASINS; PROTEASE AB Shigella, the etiological agent of dysentery, kills macrophages by inducing apoptosis. Deletion mutants in the invasion plasmid antigen B (ipaB) of Shigella flexneri are not cytotoxic. Here, we localized IpaB to the cytoplasm of macrophages infected with S.flexneri. Purified IpaB induced apoptosis when microinjected into macrophages, indicating that IpaB is sufficient to induce apoptosis. Using a GST-IpaB fusion protein as a ligand in affinity purification, we isolated four IpaB binding proteins from macrophages which were identified as the precursor and the mature polypeptides of interleukin-1 beta converting enzyme (ICE) or a highly homologous protease. We found that IpaB binds directly to ICE and this enzyme is activated during S.flexneri infection. Furthermore, specific inhibitors of ICE prevented Shigella-induced apoptosis. C1 NYU,SCH MED,DEPT MICROBIOL,SKIRBALL INST,NEW YORK,NY 10016. NYU,SCH MED,KAPLAN CANC CTR,NEW YORK,NY 10016. NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. FU NIAID NIH HHS [AI37720] NR 46 TC 260 Z9 268 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 1 PY 1996 VL 15 IS 15 BP 3853 EP 3860 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC667 UT WOS:A1996VC66700010 PM 8670890 ER PT J AU Sledjeski, DD Gupta, A Gottesman, S AF Sledjeski, DD Gupta, A Gottesman, S TI The small RNA, DsrA, is essential for the low temperature expression of RpoS during exponential growth in Escherichia coli SO EMBO JOURNAL LA English DT Article DE DsrA; H-NS; RNA; RpoS; temperature regulation ID PROTEIN H-NS; DNA-BINDING PROTEIN; STATIONARY-PHASE; SIGMA-FACTOR; GENE-EXPRESSION; KATF; POLYMERASE; SUBUNIT; TRANSFORMATION; STARVATION AB dsrA encodes a small, untranslated RNA. When overexpressed, DsrA antagonizes the H-NS-mediated silencing of numerous promoters. Cells devoid of DsrA grow normally and show little change in the expression of a number of H-NS-silenced genes. Expression of a transcriptional fusion of lacZ to dsrB, the gene next to dsrA, is significantly lower in cells carrying mutations in dsrA. All expression of beta-galactosidase from the dsrB::lacZ fusion is also dependent on the stationary phase sigma factor, RpoS. DsrA RNA was found to regulate dsrB::lacZ indirectly, by modulating RpoS synthesis, Levels of RpoS protein are substantially lower in a dsrA mutant, both in stationary and exponential phase cells. Mutations in dsrA decrease the expression of an RpoS::LacZ translational fusion, but not a transcriptional fusion, suggesting that DsrA is acting after transcription initiation. While RpoS expression is very low in exponential phase at temperatures of 30 degrees C and above, at 20 degrees C there is substantial synthesis of RpoS during exponential growth, all dependent on DsrA RNA, dsrA expression is also increased at low temperatures. These results suggest a new role for RpoS during exponential growth at low temperatures, mediated by DsrA. C1 NCI,MOL BIOL LAB,BETHESDA,MD 20892. OI Sledjeski, Darren/0000-0001-9882-6625 NR 42 TC 248 Z9 255 U1 2 U2 11 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 1 PY 1996 VL 15 IS 15 BP 3993 EP 4000 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC667 UT WOS:A1996VC66700024 PM 8670904 ER PT J AU Zhou, LX Norman, AW AF Zhou, LX Norman, AW TI Characterization of the second messengers involved in 1 alpha,25-dihydroxyvitamin D-3 stimulated intestinal calcium absorption (transcaltachia) SO ENDOCRINE LA English DT Article DE 1 alpha,25(OH)(2) vitamin D-3; intestinal Ca2+ absorption; transcaltachia; G-proteins ID PROTEIN-KINASE-C; MEMBRANE PHOSPHOINOSITIDE TURNOVER; BINDING-PROTEIN; REGULATORY PROTEINS; DEPENDENT PROCESSES; RAPID ACTION; HL-60 CELLS; WASP VENOM; 1,25-DIHYDROXYVITAMIN-D3; TRANSPORT AB 1 alpha,25-Dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3] has been shown to generate biological responses via both genomic and nongenomic pathways. In the nongenomic process, 1 alpha,25(OH)(23) stimulates the rapid transport of Ca2+ across the chick intestinal epithelial cell, a process termed transcaltachia. In previous studies, the involvement of Ca2+-channels, protein kinase C, and cAMP-dependent kinase in the 1 alpha,25(OH)(2)D-3 stimulated transcaltachic response have been implicated. To further characterize the elements involved in mediating the transcaltachic effect, H7, an inhibitor of protein kinase C, U73122, an inhibitor of phospholipase C, and mastoparan, an activator of C-proteins, were employed. Both H7 and U73122 suppressed 1 alpha,25(OH)(2)D-3 stimulated intestinal Ca2+ transport. Mastoparan was found to mimic the effect of 1 alpha,25(OH)(2)D-3 to stimulate transcaltachia. Collectively, these results suggest that 1 alpha,25(OH)(2)D-3 activations of C-proteins, phospholipase C and protein kinases are essential steps in the rapid stimulation of intestinal Ca2+ transport. C1 UNIV CALIF RIVERSIDE, DEPT BIOCHEM, RIVERSIDE, CA 92521 USA. NIDDK, NIH, BETHESDA, MD USA. NR 33 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD AUG PY 1996 VL 5 IS 1 BP 47 EP 50 DI 10.1007/BF02738655 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VF516 UT WOS:A1996VF51600007 PM 21153093 ER PT J AU Laglia, G Zeiger, MA Leipricht, A Caturegli, P Levine, MA Kohn, LD Saji, M AF Laglia, G Zeiger, MA Leipricht, A Caturegli, P Levine, MA Kohn, LD Saji, M TI Increased cyclic adenosine 3',5'-monophosphate inhibits G protein-coupled activation of phospholipase C in rat FRTL-5 thyroid cells SO ENDOCRINOLOGY LA English DT Article ID GROWTH FACTOR-I; ADENOSINE-3',5'-MONOPHOSPHATE SIGNAL ACTION; INOSITOL PHOSPHATE ACCUMULATION; RECEPTOR GENE-EXPRESSION; THYROTROPIN RECEPTOR; CHOLERA-TOXIN; CA-2+ MOBILIZATION; IODIDE TRANSPORT; ANGIOTENSIN-II; TSH RECEPTOR AB Thyroid cell growth and function are regulated by several hormones and growth factors that bind to cell surface receptors coupled via G proteins, G(s) and G(q), to stimulation of adenylyl cyclase and phospholipase C (PLC), respectively. We created a permanently transfected FRTL-5 cell line (TG8) in which the thyroglobulin gene promoter directs expression of the cholera toxin (CT) A1 subunit (CTA1). CTA1 catalyzes ADP ribosylation of G(s) alpha, which results in persistent activation of G(s) alpha. Activated G(s) alpha causes constitutive stimulation of adenylyl cyclase and increases levels of intracellular cAMP. Because G protein-coupled signaling pathways exhibit cross-talk, we compared TG8 cells to FRTL-5 cells transfected with the neomycin resistance gene (TG4) to determine whether constitutive stimulation of adenylyl cyclase influences the PLC pathway. PLC activity was assessed by measuring levels of total inositol phosphates (IPs) in TG4 and TG8 cells that had been preincubated with myo-[H-3]inositol for 2 days. Baseline values of [H-3]IP production were similar for the two cell lilies. Incubation of TG4 control cells with 10(-8) M TSH, 300 mu M ATP, and 100 mu M norepinephrine for 60 min stimulated 2.5-, 8.1-, and 3.4-fold increases, respectively, in [H-3]IP production over the control value. By contrast, there was no [H-3]IP response to any of these ligands in TG8 cells. TG8 cells exhibit a decrease in [S-35]adenosine 5'-(gamma-thio)triphosphate binding to their cell surface compared to TG4 control cells counterparts, but no decrease in [(125)]TSH binding. Treatment of TG4 cells with 100 ng/ml CT, 50 mu M forskolin, or 1 mM 8-bromo-cAMP for 2 days reproduced the loss of ligand-stimulated [H-3]IP synthesis present in TG8 cells. Although levels of immunoreactive G(q) alpha and G(q) alpha(11) were normal in TG8 cells, sodium fluoride-induced [H-3]IP production was also inhibited. Levels of immunoreactive PLC beta 3, the dominant subtype of PLC beta in FRTL-5 cells, were not altered in TG8 cells or by CT treatment of TG4 cells. These data indicate that elevated levels of cAMP can inhibit the activity of G protein-coupled PLC. Further study of this model will elucidate our understanding of the exact mechanism responsible for this interaction. C1 NIDDKD, CELL REGULAT SECT, BIOCHEM & METAB LAB, NIH, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, DEPT SURG, BALTIMORE, MD 21287 USA. JOHNS HOPKINS UNIV, DEPT PATHOL, BALTIMORE, MD 21287 USA. JOHNS HOPKINS UNIV, DEPT MED, DIV ENDOCRINOL & METAB, BALTIMORE, MD 21287 USA. RI Saji, Motoyasu/E-4007-2011; OI Levine, Michael/0000-0003-0036-7809 FU NIDDK NIH HHS [R01-DK-34281]; NIEHS NIH HHS [3T32ESO7141] NR 48 TC 27 Z9 27 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1996 VL 137 IS 8 BP 3170 EP 3176 DI 10.1210/en.137.8.3170 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UY111 UT WOS:A1996UY11100004 PM 8754735 ER PT J AU Byers, S Pishvaian, M Crockett, C Peer, C Tozeren, A Sporn, M Anzano, M Lechleider, R AF Byers, S Pishvaian, M Crockett, C Peer, C Tozeren, A Sporn, M Anzano, M Lechleider, R TI Retinoids increase cell-cell adhesion strength, beta-catenin protein stability, and localization to the cell membrane in a breast cancer cell line: A role for serine kinase activity SO ENDOCRINOLOGY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; E-CADHERIN; GROWTH-FACTOR; CARCINOMA-CELLS; EXPRESSION; PHOSPHORYLATION; DIFFERENTIATION; PLAKOGLOBIN; RECEPTOR; WNT-1 AB In this study we show that a breast cancer cell line (SKBR3) that expresses no E-cadherin and very low levels of beta-catenin protein and exhibits a poorly adhesive phenotype in Matrigel responds to retinoic acid (RA) by a marked increase in epithelial differentiation. Specifically, treatment of cells with all-trans-RA, 9-cis-RA, or a RA receptor alpha-specific ligand resulted in a large increase in cell-cell adhesive strength and stimulated the formation of fused cell aggregates in Matrigel. A retinoid X receptor-specific ligand was ineffective. Exposure of cells to 9-cis-RA for as little as 4 h was sufficient to maintain the adhesive phenotype for at least 4 days. The effects of 9-cis-RA required protein and RNA synthesis, but were not mediated by factors secreted by stimulated cells or by direct cell contact and did not require serum. These 9-cis-RA-induced morphological effects were completely reversed by growing cells in 50 mu M Ca2+, suggesting a mechanism involving a 9-cis-RA-induced increase in Ca2+-dependent adhesion. Consistent with this, beta-catenin protein levels were markedly elevated in the 9-cis-RA-treated cells, and beta-catenin became localized to a Triton-insoluble pool at regions of cell-cell contact. No change could be detected in beta-catenin steady state messenger RNA levels, but 9-cis-RA did increase beta-catenin protein stability. Treat ment of cells with low calcium medium did not prevent the 9-cis-RA-induced increase in total beta-catenin protein, but did prevent its movement to a Triton-insoluble pool at the cell membrane. Among several kinase inhibitors, only the broad spectrum kinase inhibitor staurosporine and the protein kinase C inhibitor bisindoylmaleimide reversed the morphological changes induced by 9-cis-RA. Like treatment with low calcium medium, these inhibitors did not prevent the 9-cis-RA-induced increase in total beta-catenin protein levels, but completely prevented the movement of beta-catenin to the cell membrane. These results point to a role for beta-catenin and serine kinase activity in mediating the action of 9-cis-RA in epithelial differentiation. C1 GEORGETOWN UNIV, MED CTR, LOMBARDI CANC CTR, WASHINGTON, DC 20007 USA. CATHOLIC UNIV AMER, DEPT MECH ENGN, WASHINGTON, DC 20064 USA. NCI, CHEMOPREVENT LAB, NIH, BETHESDA, MD 20892 USA. RP Byers, S (reprint author), GEORGETOWN UNIV, MED CTR, DEPT CELL BIOL, 3900 RESERVOIR RD NW, WASHINGTON, DC 20007 USA. NR 45 TC 51 Z9 52 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1996 VL 137 IS 8 BP 3265 EP 3273 DI 10.1210/en.137.8.3265 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UY111 UT WOS:A1996UY11100018 PM 8754749 ER PT J AU Dallas, JS Cunningham, SJ Patibandla, SA Seetharamaiah, GS Morris, JC Tahara, K Kohn, LD Prabhakar, BS AF Dallas, JS Cunningham, SJ Patibandla, SA Seetharamaiah, GS Morris, JC Tahara, K Kohn, LD Prabhakar, BS TI Thyrotropin (TSH) receptor antibodies (TSHrAb) can inhibit TSH-mediated cyclic adenosine 3',5'-monophosphate production in thyroid cells by either blocking TSH binding or affecting a step subsequent to TSH binding SO ENDOCRINOLOGY LA English DT Article ID EXTRACELLULAR DOMAIN; AUTOIMMUNE-THYROIDITIS; GONADOTROPIN RECEPTORS; ADENYLYL-CYCLASE; PRIMARY MYXEDEMA; IMMUNOGLOBULIN-G; PEPTIDES; FRTL-5; DISEASE; HYPOTHYROIDISM AB In the present study, rabbit antibodies that possess thyroid stimulation-blocking activity were used to investigate potential mechanisms by which TSH receptor antibodies can inhibit thyroid cell function. The antibodies were produced against two synthetic peptides corresponding to amino acids 357-372 (p357) and 367-386 (p367) of the human TSHr (hTSHr). By enzyme-linked immunosorbent assay, both antisera (alpha 357 and alpha 367) had high titers (>1:100,000) of IgG against their respective peptides and recombinant extracellular TSHr protein (ETSHr); alpha 357 had a low IgG titer to p367 (1:800), and alpha 367 had a low IgG titer to p357 (<1:200). Based on competitive inhibition studies, alpha 357 and alpha 367 displayed similar relative binding affinities for their respective peptides and for recombinant ETSHr. When tested by commercial RRA, alpha 357 did not block (TSH binding inhibition index, -3.7%), whereas alpha 367 blocked TSH binding to TSHr (TSH binding inhibition index, 53.9%). The blocking effect of alpha 367 could be reversed by incubating the antiserum with p367 before assay. When applied alone to FRTL-5 cells, IgG from alpha 357 inhibited [compared to normal rabbit IgG (NRI); P < 0.01] basal cAMP production by the cells, whereas IgG from alpha 367 did not. IgG from both alpha 357 and alpha 367, however, were able to inhibit (P < 0.001) TSH-mediated cAMP production by FRTL-5 cells [bovine (b) TSH, 2.5 x 10(-10) M; cAMP (mean +/- SD; picomoles per ml): NRI, 62.5 +/- 6.1; alpha 357, 12.2 +/- 2.4; alpha 367, 36.2 +/- 3.5]. alpha 357 continued to inhibit (P < 0.05) cAMP production by FRTL-5 cells in 10(-8) M bTSH, whereas alpha 367 no longer inhibited cAMP production at bTSH concentrations above 5 x 10(-10) at. Compared to NRI, both alpha 357 and alpha 367 were also able to inhibit (P < 0.001) Graves' IgG-mediated cAMP production by FRTL-5 cells. When IgG were tested on FRTL-5 cells in the presence of 10(-7) M forskolin, only alpha 357 inhibited (P < 0.001) cAMP production (NRI, 75.1 +/- 4.8; alpha 357, 52.3 +/- 4.5; alpha 367, 77.2 +/- 1.4). To determine whether the inhibitory effect of alpha 357 on forskolin-mediated stimulation was thyroid cell dependent, IgG were tested on Chinese hamster ovary (CHO) cells transfected with the complementary DNA of the hTSHr (CHO-R). Again, alpha 357 inhibited (P < 0.005) cAMP production mediated by forskolin (at 10(-7) M; NRI, 68.7 +/- 4.4; alpha 357, 36.8 +/- 5.7; alpha 367, 64.6 +/- 8.5). alpha 357 did not inhibit forskolin-mediated cAMP production by untransfected CHO cells (CHO-N), indicating that the inhibitory effect of alpha 357 on forskolin stimulation was TSHr dependent. In addition, alpha 357 inhibited (P < 0.01) basal cAMP production by CHO-R cells, but not by CHO-N cells. alpha 367 had no effect on the basal cAMP production in either CHO-R or CHO-N cells. Neither alpha 357 nor alpha 367 inhibited cholera toxin-mediated cAMP production in FRTL-6 cells. In all relevant bioassays, the inhibitory effects of alpha 357 and alpha 367 could be reversed by preincubating the IgG with the respective peptides. From these data, we conclude that 1) alpha 367 binds to the ETSHr and blocks TSH-mediated cAMP production by inhibiting TSH from binding to its receptor; 2) alpha 357 binds to the TSHr and, without blocking TSH binding, inhibits TSH-mediated cAMP production at a step(s) subsequent to ligand binding that affects adenylate cyclase activity; and 3) forskolin-mediated cAMP production by thyroid cells can be inhibited by IgG that bind directly to the TSHr. C1 UNIV TEXAS, MED BRANCH, DEPT IMMUNOL & MICROBIOL, GALVESTON, TX 77555 USA. MAYO CLIN & MAYO FDN, DEPT MED, DIV ENDOCRINOL, ROCHESTER, MN 55905 USA. NIAID, NIH, CELL REGULAT SECT, BETHESDA, MD 20892 USA. UNIV TEXAS, MED BRANCH, DEPT PEDIAT, GALVESTON, TX 77555 USA. FU NICHD NIH HHS [5P30-HD-27841-02]; NIDDK NIH HHS [DK-47417] NR 37 TC 16 Z9 16 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1996 VL 137 IS 8 BP 3329 EP 3339 DI 10.1210/en.137.8.3329 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UY111 UT WOS:A1996UY11100028 PM 8754759 ER PT J AU Kavlock, RJ Daston, GP DeRosa, C FennerCrisp, P Gray, LE Kaattari, S Lucier, G Luster, M Mac, MJ Maczka, C Miller, R Moore, J Rolland, R Scott, G Sheehan, DM Sinks, T Tilson, HA AF Kavlock, RJ Daston, GP DeRosa, C FennerCrisp, P Gray, LE Kaattari, S Lucier, G Luster, M Mac, MJ Maczka, C Miller, R Moore, J Rolland, R Scott, G Sheehan, DM Sinks, T Tilson, HA TI Research needs for the risk assessment of health and environmental effects of endocrine disruptors: A report of the US EPA-sponsored workshop SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE endocrine disruptors; hormones; risk assessment; carcinogenesis; reproductive toxicity; developmental toxicity; immunotoxicity; neurotoxicity; exposure assessment; research needs ID FISH-EATING BIRDS; CONTAMINANT BIOMONITORING PROGRAM; TROUT ONCORHYNCHUS-MYKISS; BREAST-CANCER INCIDENCE; LAWRENCE BELUGA WHALES; MINK MUSTELA-VISON; FRESH-WATER FISH; POLYCHLORINATED-BIPHENYLS; GREAT-LAKES; RAINBOW-TROUT AB The hypothesis has been put forward that humans and wildlife species have suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity--as well as along the risk assessment paradigm--hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, the group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research. C1 PROCTER & GAMBLE CO,MIAMI VALLEY LABS,CINCINNATI,OH. AGCY TOX SUBST & DIS REGISTRY,ATLANTA,GA. US EPA,OFF PREVENT PESTICIDES & TOX SUBST,WASHINGTON,DC 20460. COLL WILLIAM & MARY,VIRGINIA INST MARINE SCI,WILLIAMSBURG,VA. NIEHS,RES TRIANGLE PK,NC 27709. NATL BIOL SERV,WASHINGTON,DC 20240. NATL RES COUNCIL,WASHINGTON,DC 20418. DOW CHEM CO USA,MIDLAND,MI 48674. INST EVALUATING HLTH RISKS,WASHINGTON,DC. WORLD WILDLIFE FUND,WASHINGTON,DC 20037. NATL MARINE FISHERIES SERV,CHARLESTON,SC. US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. RP Kavlock, RJ (reprint author), US EPA,NATL HLTH & ENVIRONM EFFECTS RES LAB,RES TRIANGLE PK,NC 27711, USA. OI gray jr, leon earl/0000-0002-1111-4754 NR 193 TC 693 Z9 743 U1 30 U2 219 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 1996 VL 104 SU 4 BP 715 EP 740 DI 10.2307/3432708 PG 26 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA VC106 UT WOS:A1996VC10600002 PM 8880000 ER PT J AU Portier, CJ Lyles, CM AF Portier, CJ Lyles, CM TI Practicing safe modeling: GLP for biologically based mechanistic models SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. 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 8 Z9 8 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 1996 VL 104 IS 8 BP 806 EP 806 DI 10.2307/3432921 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA VE696 UT WOS:A1996VE69600001 PM 8875144 ER PT J AU Holladay, SD Luster, MI AF Holladay, SD Luster, MI TI Alterations in fetal thymic and liver hematopoietic cells as indicators of exposure to developmental immunotoxicants SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE developmental immunotoxicity; immunotoxicant biomarker; fetal liver; fetal thymus ID TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE; PRENATAL CHLORDANE EXPOSURE; HUMORAL IMMUNE-RESPONSES; GLYCOL MONOMETHYL ETHER; BONE-MARROW; ANTIGEN EXPRESSION; MATERNAL EXPOSURE; DIOXIN TCDD; MICE; MOUSE AB Recent studies indicate that immune development in humans and other species may be altered after perinatal exposure to immunotoxic environmental contaminants. However, limited information is available regarding appropriate tests that may adequately detect developmental immunotoxic compounds. Experiments in which pregnant laboratory rodents were exposed to a variety of immunotoxic environmental agents indicate that fetal thymus and liver immune cells may be quantitatively and qualitatively altered by immunotoxicant exposure and, thus, may serve as sensitive markers of developmental immunotoxicant exposure: In particular, depression of fetal thymic cell counts appears to be a common event following gestational exposure to immunotoxicants that produce this response in adult animals. Total hematopoietic cell counts in fetal liver, however, may be a poor indicator of immunotoxicant exposure. Altered marker expression in both fetal thymus and liver appears to be a highly sensitive indicator of gestational immunotoxicant exposure. Together, these reports suggest that immune tests with high predictability for immunosuppression in adults may also be appropriate for the detection of developmental immunotoxic agents. C1 NIEHS,ENVIRONM IMMUNOL & MICROBIOL SECT,RES TRIANGLE PK,NC 27709. RP Holladay, SD (reprint author), VIRGINIA POLYTECH INST & STATE UNIV,VIRGINIA MARYLAND REG COLL VET MED,DEPT BIOMED SCI,BLACKSBURG,VA 24061, USA. NR 34 TC 24 Z9 24 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 1996 VL 104 SU 4 BP 809 EP 813 DI 10.2307/3432711 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA VC106 UT WOS:A1996VC10600005 PM 8880003 ER PT J AU Thomas, RS Yang, RSH Morgan, DG Moorman, MP Kermani, HRS Sloane, RA OConnor, RW Adkins, B Gargas, ML Andersen, ME AF Thomas, RS Yang, RSH Morgan, DG Moorman, MP Kermani, HRS Sloane, RA OConnor, RW Adkins, B Gargas, ML Andersen, ME TI PBPK modeling Monte Carlo simulation of methylene chloride kinetic changes in mice in relation to age and acute, subchronic, and chronic inhalation exposure SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE bootstrap resampling; glutathione S-transferase; methylene chloride; Monte Carlo simulation; physiologically based pharmacokinetic modeling; risk assessment ID FEMALE B6C3F1 MICE; GLUTATHIONE-S-TRANSFERASE; PHARMACOKINETIC MODELS; PARTITION-COEFFICIENTS; DRUG-METABOLISM; INDUCED LUNG; GAS UPTAKE; LIVER; CONSTANTS; TISSUES AB During a 2-year chronic inhalation study on methylene chloride (2000 or 0 ppm: 6 hr/day, 5 days/week), gas-uptake pharmacokinetic studies and tissue partition coefficient determinations were conducted on female B6C3F(1) mice after 1 day, 1 month, 1 year, and 2 years of exposure. Using physiologically based pharmacokinetic (PBPK) modeling coupled with Monte Carlo simulation and bootstrap resampling for data analyses, a significant induction in the mixed function oxidase (MFO) rate constant (V-max) was observed at the 1-day and 1-month exposure points when compared to concurrent control mice, while decreases in glutathione S-transferase (GST) rate constant (K-fc) were observed in the 1-day and 1-month exposed mice. Within exposure groups, the apparent V-max maintained significant increases in the 1-month and 2-year control groups. Although the same initial increase exists in the exposed group, the 2-year V-max is significantly smaller than the 1-month group (p < 0.001). Within-group differences in median K-fc values show a significant decrease in both I-month and 2-year groups among control and exposed mice (p < 0.001). Although no changes in methylene chloride solubility as a result of prior exposure were observed in blood, muscle, liver, or lung, a marginal decrease in the far:air partition coefficient was found in the exposed mice at p = 0.053. Age related solubility differences were found in muscle:air, liver:air, lung:air, and fat:air partition coefficients at p < 0.001, while the solubility of methylene chloride in blood was not affected by age (p = 0.461). As a result of this study, we conclude that age and prior exposure to methylene chloride can produce notable changes in disposition and metabolism and may represent important factors in the interpretation of toxicologic data and its application to risk assessment. C1 GLAXO INC,RES TRIANGLE PK,NC 27709. NIEHS,RES TRIANGLE PK,NC 27709. MANTECH ENVIRONM TECHNOL INC,RES TRIANGLE PK,NC 27709. MCLAREN HART CHEMRISK,CLEVELAND,OH 44122. ICF KAISER,KS CRUMP DIV,MORRISVILLE,NC 27560. RP Thomas, RS (reprint author), COLORADO STATE UNIV,CTR ENVIRONM TOXICOL & TECHNOL,DEPT ENVIRONM HLTH,FT COLLINS,CO 80523, USA. OI Andersen, Melvin/0000-0002-3894-4811; Thomas, Russell/0000-0002-2340-0301 FU NIEHS NIH HHS [P42 ES05949] NR 43 TC 15 Z9 15 U1 0 U2 5 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 1996 VL 104 IS 8 BP 858 EP 865 DI 10.2307/3432940 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA VE696 UT WOS:A1996VE69600022 PM 8875160 ER PT J AU Jacobs, TL Warmerdam, JM Medina, MA Piver, WT AF Jacobs, TL Warmerdam, JM Medina, MA Piver, WT TI Second moment method for evaluating human health risks from groundwater contaminated by trichloroethylene SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE contaminant transport; groundwater flow; health risk; second moment method; stochastic modeling; trichloroethylene AB Pollutants in groundwater aquifers may constitute a significant human health risk A large variation in response may result among human populations experiencing the same level and duration of exposure to pollutants. Variability in response, as a result of exposure to a carcinogenic contaminant such as trichloroethylene (TCE), can be represented by a distribution function of safe doses. Spatial variability in aquifer characteristics and contaminant transport parameters requires the use of stochastic transport models to quantify variability in exposure concentrations. A second moment method is used to evaluate the probability of exceeding safe dose levels for a contaminated aquifer. The name of this method stems from the fact that the formulation is based on the first and second moments of the random variables. With this method, the probability is a function of the variability of contaminant concentration (which incorporates variability in hydrogeologic parameters such as hydraulic conductivity) and the variability in response in the human population. In this manner, the severity of the heath risk posed by a contaminated aquifer and the evaluation of appropriate strategies and technologies for aquifer remediation are a function of contaminant concentrations and human heath risks. The applicability and limitations of this method are demonstrated with data on groundwater contaminated by TCE at Hill Air force Base, Utah. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Jacobs, TL (reprint author), DUKE UNIV,DEPT CIVIL & ENVIRONM ENGN,BOX 90287,DURHAM,NC 27708, USA. NR 20 TC 5 Z9 5 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 1996 VL 104 IS 8 BP 866 EP 870 DI 10.2307/3432941 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA VE696 UT WOS:A1996VE69600023 PM 8875161 ER PT J AU Theodore, WH Balish, M Leiderman, D Bromfield, E Sato, S AF Theodore, WH Balish, M Leiderman, D Bromfield, E Sato, S TI Effect of seizures on cerebral blood flow measured with O-15-H2O and positron emission tomography SO EPILEPSIA LA English DT Article DE positron emission tomography; seizures; cerebral blood flow; O-15-H2O ID COMPLEX PARTIAL SEIZURES; TEMPORAL-LOBE EPILEPSY; COMPUTED-TOMOGRAPHY; INTRAVENOUS (H2O)-O-15; GLUCOSE-METABOLISM; FOCAL SEIZURES; PATTERNS; LOCALIZATION; SPECT; ONSET AB To study quantitative alterations in regional cerebral blood flow (rCBF) accompanying seizures, and to assess the utility of ictal activation PET scanning as a noninvasive clinical tool for localization of epileptogenic foci, we used pentylenetetrazole (PTZ) to induce seizures during O-15-water positron emission tomography (PET) CBF measurement in 15 patients with uncontrolled complex partial seizures (CPS) who had been referred for surgical evaluation. Continuous EEG monitoring was performed during the PET scans. After baseline scans were obtained, each patient was injected with 150-300 mg PTZ. Two patients had generalized tonic-clonic seizures (GTCs). CBF increases were asymmetrical. Two patients (in 1 the seizure occurred spontaneously, without PTZ injection) who had CPS had bitemporal 70-80% increases in CBF. Thalamic CBF increased during both CPS and GTCS. Five patients had an increase in focal EEG interictal abnormality, accompanied by focal flow decreases in 3. PTZ injection not accompanied by clinical seizures did not increase CBF. Partial seizures may be associated with bilateral increases in CBF, and subcortical gray regions are involved in ictal activation. C1 NINCDS,EEG LAB,NIH,BETHESDA,MD 20892. NIH,CTR CLIN,POSITRON EMISS TOMOG DEPT,BETHESDA,MD 20892. RP Theodore, WH (reprint author), NINCDS,EPILEPSY RES BRANCH,NIH,ROOM 5C-205,BLDG 10,BETHESDA,MD 20892, USA. NR 34 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 1996 VL 37 IS 8 BP 796 EP 802 DI 10.1111/j.1528-1157.1996.tb00654.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA VD308 UT WOS:A1996VD30800016 PM 8764821 ER PT J AU Zhang, JQ Luo, G Herrera, AH Paterson, B Horowits, R AF Zhang, JQ Luo, G Herrera, AH Paterson, B Horowits, R TI cDNA cloning of mouse nebulin - Evidence that the nebulin-coding sequence is highly conserved among vertebrates SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE nebulin; cDNA; muscle ID MOLECULAR-WEIGHT PROTEINS; SKELETAL-MUSCLE SARCOMERE; IMMUNOELECTRON MICROSCOPY; MONOCLONAL-ANTIBODIES; ACTIN-FILAMENTS; THIN-FILAMENTS; Z-LINE; TITIN; CONNECTIN; FRAGMENTS AB Nebulin is a family of giant myofibrillar proteins with molecular masses ranging over 700-900 kDa, Using a human nebulin cDNA probe, we isolated three nebulin cDNA clones from a mouse skeletal muscle cDNA library. These three clones, labeled 8c, 7a and 4b, carry inserts of 2.0, 3.0 and 3.5 kb, respectively. In Northern blots, each insert detected the same approximate to 25 kb message from Skeletal muscle as the human nebulin probe. while detecting no messages from cardiac muscle. Sequence data in combination with reverse-transcriptase PCR indicates that clones 7a and 8c overlap to form 4076 bp contiguous sequence. Alignment with the published full-length human nebulin sequence indicates that clone 4b overlaps with clone 7a over 1596 bp. However, after the first 798-bp overlap, the sequence of these two mouse nebulin clones diverge, suggesting that they derive from distinct transcripts encoding isoforms of mouse nebulin. The mouse nebulin clones encode a series of approximate to 245-residue super repeats, each of which can be subdivided into seven approximate to 35-residue, weakly repeating modules centered around a conserved tyrosine residue, consistent with the human nebulin sequence. The mouse nebulin clones align along the central third of the full-length human sequence, corresponding to super repeats 8-16 of the 22 super repeats found in human nebulin. The translated sequence is greater than 90% identical to the human sequence, with the exception of a 200-amino-acid region at the C-terminus of clone 4b, which is less than 60% identical. In genomic Southern blots, a mouse nebulin probe detected a homologous sequence in a wide variety of vertebrate species under stringent conditions. However, no significant hybridization was observed to genomic DNA from invertebrates and microorganisms, even under very low stringency. The sequence and Southern-blot data suggest that the nebulin sequence is highly conserved among vertebrate species. C1 NIAMSD, NIH, BETHESDA, MD 20892 USA. NCI, NIH, BETHESDA, MD 20892 USA. NR 29 TC 14 Z9 14 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD AUG 1 PY 1996 VL 239 IS 3 BP 835 EP 841 DI 10.1111/j.1432-1033.1996.0835u.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB017 UT WOS:A1996VB01700038 PM 8774733 ER PT J AU Heegaard, NHH Heegaard, PMH Roepstorff, P Robey, FA AF Heegaard, NHH Heegaard, PMH Roepstorff, P Robey, FA TI Ligand-binding sites in human serum amyloid P component SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE amyloid P component; heparin; Alzheimers capillary electrophoresis; peptide ID C-REACTIVE PROTEIN; AFFINITY CAPILLARY ELECTROPHORESIS; MELANOMA CELL-ADHESION; ALZHEIMERS-DISEASE; HEPARIN-BINDING; SULFATED GLYCOSAMINOGLYCANS; COMMON CONSTITUENT; HUMAN-TISSUE; I REPEATS; PEPTIDES AB Amyloid P component (AP) is a naturally occurring glycoprotein that is found in serum and basement membranes, AP is also a component of all types of amyloid, including that found in individuals who suffer from Alzheimer's disease and Down's syndrome. Because AP has been found to bind strongly and specifically to certain glycosaminoglycans that are components of amyloid deposits, AP may play an important role in the maintenance of amyloid. In the present work, we isolated and identified two proteolytic fragments of AP that are responsible for its heparin-binding activity. Neither fragment corresponds to published heparin-binding sequences. The structural requirements for activity of the peptides (amino acid residues 27-38 and 192-203 of AP) were examined by means of solid-phase inhibition assays with synthetic peptides, AP-(192-203)-peptide inhibits the Ca2+-dependent binding of AP to heparin with an IC50 of 25 mu M, while the IC50 of AP-(27-38)-peptide and AP-(33-38)-peptide are 10 mu M and 2 mu M, respectively, The understanding of the structure and function of active AP peptides will be useful for development of amyloid-targeted diagnostics and therapeutics. C1 DANISH VET LAB,DEPT BIOCHEM & IMMUNOL,COPENHAGEN,DENMARK. ODENSE UNIV,DEPT MOL BIOL,DK-5230 ODENSE,DENMARK. NIDR,NIH,PEPTIDE & IMMUNOCHEM UNIT,BETHESDA,MD 20892. RP Heegaard, NHH (reprint author), STATENS SERUM INST,DEPT AUTOIMMUNOL,BLDG 81,ROOM 528,ARTILLERIVEJ 5,DK-2300 COPENHAGEN S,DENMARK. NR 53 TC 19 Z9 20 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD AUG 1 PY 1996 VL 239 IS 3 BP 850 EP 856 DI 10.1111/j.1432-1033.1996.0850u.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB017 UT WOS:A1996VB01700040 PM 8774735 ER PT J AU Dawson, NA Lush, RM Steinberg, SM Tompkins, AC Headlee, DJ Figg, WD AF Dawson, NA Lush, RM Steinberg, SM Tompkins, AC Headlee, DJ Figg, WD TI Suramin-induced neutropenia SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE prostatic neoplasms; suramin; neutropenia; granulocyte colony-stimulating factor; toxicity ID PROSTATE-CANCER AB This paper presents a retrospective review of 6 cases of severe neutropenia attributed to suramin, the response to granulocyte-colony stimulating factor (G-CSF) and the possible mechanism. Plasma suramin concentrations, G-CSF, platelet-derived growth factor-AB (PDGF-AB) and fibroblast growth factor basic (FGF basic) levels were measured and correlated with neutropenic course. The time course of neutropenia was unpredictable and occurred both during and following discontinuation of suramin. Neutropenia rapidly resolved with G-CSF. Neither the measured growth factor levels nor plasma suramin concentrations correlated with neutropenia. We conclude that neutropenia secondary to suramin is unpredictable and responds to G-CSF administration permitting further suramin therapy. The mechanism remains unknown. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,CLIN ONCOL PROGRAM,DIV CANC TREATMENT,BETHESDA,MD 20892. RP Dawson, NA (reprint author), WALTER REED ARMY MED CTR,HEMATOL ONCOL SERV,WASHINGTON,DC 20307, USA. RI Figg Sr, William/M-2411-2016 NR 12 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD AUG PY 1996 VL 32A IS 9 BP 1534 EP 1539 DI 10.1016/0959-8049(96)00139-6 PG 6 WC Oncology SC Oncology GA VF742 UT WOS:A1996VF74200026 PM 8911114 ER PT J AU Ehrhardt, RO Harriman, GR Inman, JK Lycke, N Gray, B Strober, W AF Ehrhardt, RO Harriman, GR Inman, JK Lycke, N Gray, B Strober, W TI Differential activation requirements of isotypes, switched B cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE B cell differentiation; surface immunoglobulin; mucosal immunity; isotype switch ID ANTI-IG ANTIBODIES; LYMPHOCYTES-B; MEDIATED STIMULATION; GERMINAL CENTER; SELF-TOLERANCE; CROSS-LINKING; LYMPH-NODE; TNP-FICOLL; IMMUNOGLOBULIN; RESPONSES AB In the present studies, we compared the activation requirements of sIgM(+)/sIgD(+) B cells with those of isotype-switched sIgM(-)/sIgA(+) B cells. We found that whereas sIgM(+) B cells respond to T cell-independent (TI) and T cell-dependent (TD) Ag with no significant bias toward one stimulus, sIgA(+) B cells were deficient in their ability to respond to antigen receptor cross-linking but responded remarkably well to TD stimuli. Thus, dextran-conjugated anti-IgA antibody (anti-IgA-dextran), arti-kappa-dextran, or various immobilized anti-IgA antibodies (Ab) induced only low-level IgA B cell proliferation and no IgA secretion in the presence of various lymphokines; in marked contrast, sIgA(+) B cells responded to cognate and noncognate T cell stimulation as well as to stimulation by CD40 ligand-bearing fibroblasts by secreting large amounts of IgA (up to 240000 ng/ml per 10(5) cells). This pattern of sIgA(+) B cell responsiveness was noted with both germinal center peanut agglutinin(hi) (PNA(hi)) and non-germinal center PNA(lo) B cells. In confirmation of these results, whole Peyer's patch or lamina propria cell populations containing less than 15% sIgA(+) B cells stimulated with a noncognate T cell stimulus or T cell membranes secreted mainly IgA (68%-94% of the total Ig secreted) and relatively little IgM. The strict T cell dependence of IgA B cell activation and differentiation provides important insights into immune responses of mucosal tissues and must be considered in the development of vaccines, particularly those designed to stimulate mucosal tissues containing large numbers of isotype-switched B cells. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP Ehrhardt, RO (reprint author), NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,NIH,BETHESDA,MD 20892, USA. NR 41 TC 14 Z9 14 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 1996 VL 26 IS 8 BP 1926 EP 1934 DI 10.1002/eji.1830260838 PG 9 WC Immunology SC Immunology GA VB309 UT WOS:A1996VB30900037 PM 8765041 ER PT J AU Calvo, CF Yoshimura, T Gelman, M Mallat, M AF Calvo, CF Yoshimura, T Gelman, M Mallat, M TI Production of monocyte chemotactic protein-1 by rat brain macrophages SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE microglia; chemotactic migration; inflammatory cytokines; brain injury ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; BLOOD MONONUCLEAR LEUKOCYTES; COLONY-STIMULATING FACTOR; AMINO-ACID ANALYSIS; COMPETENCE GENE-JE; CHEMOATTRACTANT PROTEIN-1; MOLECULAR-CLONING; GROWTH-FACTOR; CDNA CLONING AB In the present study, we show that cultured rat brain macrophages release a soluble factor that stimulates the migration of bone marrow-derived macrophages, as determined by an in vitro chemotaxis assay. A checkerboard analysis indicated that most of this effect resulted from a polarized migration of the cells (chemotactic phenomenon), rather than in an increase in cell motility (chemokinesis). This activity was significantly decreased by an immune serum directed against the rat monocyte chemoattractant protein-1 (chemokine MCP-1). Northern blot analysis demonstrated expression of the MCP-1 gene in cultured brain macrophages, but its absence in unstimulated bone marrow-derived macrophages. Up-regulation of MCP-1 expression was observed when lipopolysaccharide was added to cultured brain macrophages, a peak occurring after a 6 h period of stimulation. Also, inflammatory cytokines such as interleukin (II)-1 beta, colony stimulating factor-1, tumour necrosis factor-alpha and IL-6 individually increased the basal level of MCP-1 mRNA. Subsequently, we demonstrated the in vivo production of MCP-1 in the adult rat brain following injury induced by a local injection of kainic acid. MCP-1 synthesis was localized in both astrocytes and brain macrophages. These results suggest that the activation of resting microglial cells into brain macrophages and their subsequent secretion of chemokines could contribute to the mechanism(s), leading to the infiltration of the CNS by blood-derived monocytes, as observed in several pathologies. C1 NCI,IMMUNOPATHOL SECT,IMMUNOBIOL LAB,FREDERICK,MD. RP Calvo, CF (reprint author), COLL FRANCE,INSERM,CHAIRE NEUROPHARMACOL,U114,F-75231 PARIS 05,FRANCE. NR 52 TC 68 Z9 68 U1 0 U2 2 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 AUG PY 1996 VL 8 IS 8 BP 1725 EP 1734 DI 10.1111/j.1460-9568.1996.tb01316.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA VF851 UT WOS:A1996VF85100016 PM 8921263 ER PT J AU Kinet, JP Jouvin, MH Paolini, R Numerof, R Scharenberg, A AF Kinet, JP Jouvin, MH Paolini, R Numerof, R Scharenberg, A TI IgE receptor (Fc epsilon RI) and signal transduction SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article; Proceedings Paper CT Symposium on Immunoregulation of Asthma II CY JUN 23-24, 1994 CL AMSTERDAM, NETHERLANDS SP Glaxo Wellcome, Holland DE immunoglobulin E receptor; signal transduction ID PROTEIN-TYROSINE KINASE; EPIDERMAL LANGERHANS CELLS; IMMUNOGLOBULIN-E-RECEPTOR; HIGH-AFFINITY RECEPTOR; T-CELL; ANTIGEN RECEPTOR; CYTOPLASMIC TAIL; GAMMA-CHAIN; ZETA-CHAIN; ACTIVATION AB This review suggests a model in which both beta- and gamma-chains synergize in the initiation of Fc epsilon RI signal transduction function. Receptor aggregation by antigens induces activation of lyn, which is already bound to the Fc epsilon RI beta-chain under resting conditions. Whilst activated, lyn would phosphorylate the tyrosine residues in the Fc epsilon RI gamma-chain, This phosphorylation would be responsible for the recruitment of syk (probably via its SH2 domains) as well as other signalling molecules, Syk kinase would then be activated by the engagement of its SH2 domains and/or its phosphorylation Syk could then interact with and activate (through phosphorylation) downstream effector molecules. RP Kinet, JP (reprint author), NIAID,MOL ALLERGY & IMMUNOL SECT,NIH,TWINBROOK 2 BLDG,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 31 TC 3 Z9 3 U1 0 U2 1 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 AUG PY 1996 VL 9 SU 22 BP S116 EP S118 PG 3 WC Respiratory System SC Respiratory System GA VE782 UT WOS:A1996VE78200012 ER PT J AU Celli, G Darwiche, N De Luca, LM AF Celli, G Darwiche, N De Luca, LM TI Estrogen induces retinoid receptor expression in mouse cervical epithelia SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; KERATIN GENE-EXPRESSION; GROWTH-FACTOR RECEPTOR; RAR-RXR HETERODIMERS; THYROID-HORMONE; X-RECEPTOR; NUCLEAR RECEPTORS; PROGESTERONE RECEPTORS; RESPONSE ELEMENTS; TRANSCRIPTION AB Steroid hormones and retinoids are powerful regulators of normal epithelial differentiation and function in the mouse female reproductive tract, where their actions are mediated by nuclear receptors. The expression pattern, heterodimeric interactions, and availability of Ligand of these transcription factors are thought to contribute to the biological response. Estrogen (E(2)) induces proliferation and squamous differentiation of the cervical and vaginal epithelium during the mouse estrous cycle, while progesterone and retinoids maintain the simple columnar epithelium of the endocervix and uterine horns. We wanted to investigate whether retinoid receptors are responsive to estrogen status during cervical epithelial differentiation induced by a single dose of estrogen in ovariectomized adult mice. Northern blot analysis demonstrated a prolonged induction of RXR alpha and RAR gamma gene expression by E(2) in the mouse cervix and vagina. When the induction of RXR alpha and RAR gamma was compared to genes known to be responsive to E(2), including estrogen receptor (ER) and c-fos, RXR alpha was induced within 0.5 h of hormone treatment, while RAR gamma induction was evident by 4 h. The induction of these retinoid receptors suggests that they may be implicated in epithelial growth and differentiation in response to E(2). Moreover, potential heterodimeric interactions among these receptors indicate that normal, cyclical epithelial differentiation results from the interplay of these molecules. Using in situ hybridization analysis, RXR alpha transcripts were localized preferentially in the basal cells, while ER mRNA was expressed throughout the epithelium of the ectocervix and vagina. Furthermore, FR transcripts were highly expressed in the stratified squamous foci induced by mild vitamin A depletion in the columnar epithelium of the endocervix and uterine horns. Therefore, the induction of RXR alpha and RAR gamma by E(2) and their expression pattern in relation to ER suggest that they are needed to coordinate specific genetic programs that result in cervical epithelial growth and differentiation. (C) 1996 Academic Press, Inc. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, NIH, BETHESDA, MD 20892 USA. OI Darwiche, Nadine/0000-0002-1862-5426 NR 66 TC 18 Z9 20 U1 0 U2 2 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 AUG 1 PY 1996 VL 226 IS 2 BP 273 EP 282 DI 10.1006/excr.1996.0228 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA VA835 UT WOS:A1996VA83500005 PM 8806431 ER PT J AU Shimizu, T Pommier, Y AF Shimizu, T Pommier, Y TI DNA fragmentation induced by protease activation in p53-null human leukemia HL60 cells undergoing apoptosis following treatment with the topoisomerase I inhibitor camptothecin: Cell-free system studies SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; DEATH GENE CED-3; GRANULE SERINE PROTEASES; HL-60 CELLS; IL-1-BETA-CONVERTING ENZYME; POLY(ADP-RIBOSE) POLYMERASE; INTERNUCLEOSOMAL FRAGMENTATION; DIFFERENTIAL INDUCTION; CAENORHABDITIS-ELEGANS; MAMMALIAN HOMOLOG AB We studied the role of proteases in apoptosis using a cell-free system prepared from a human leukemia cell line. HL60 cells are p53 null and extremely sensitive to a variety of apoptotic stimuli including DNA damage induced by the topoisomerase I inhibitor, camptothecin. We measured DNA fragmentation induced in isolated nuclei by cytosolic extracts using a filter elution assay. Cytosol from camptothecin-treated HL60 cells induced internucleosomal DNA fragmentation in nuclei from untreated cells. This fragmentation was suppressed by serine protease inhibitors. Serine proteases (trypsin, endoproteinase Glu-C, chymotrypsin A, and proteinase K) and papain by themselves induced DNA fragmentation in naive nuclei. This effect was enhanced in the presence of cytosol from untreated cells. Cysteine protease inhibitors (E-64, leupeptin, Ac-YVAD-CHO [ICE inhibitor]) did not affect camptothecin-induced DNA fragmentation. The apopain/Yama inhibitor, Ac-DEVD-CHO, and the proteasome inhibitor, MG-132, were also inactive both in the cell-free system and in whole cells. Interleukin-1 beta converting enzyme (ICE) or human immunodeficiency virus protease failed to induce DNA fragmentation in naive nuclei. Together, these results suggest that DNA damage activates serine protease(s) which in turn activate(s) nuclear endonuclease(s) during apoptosis in HL60 cells. (C) 1996 Academic Press, Inc. C1 NCI,LAB MOLEC PHARMACOL,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 65 TC 51 Z9 51 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 1 PY 1996 VL 226 IS 2 BP 292 EP 301 DI 10.1006/excr.1996.0230 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA VA835 UT WOS:A1996VA83500007 PM 8806433 ER PT J AU Han, W Gallahan, D Moore, MAS AF Han, W Gallahan, D Moore, MAS TI Overexpression of INT3 in mouse hematopoietic cells influences the myelopoieses. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 31 EP 31 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200031 ER PT J AU Gooya, JM Kelvin, D Lyman, S Ruscetti, FW Oppenheim, J Keller, JR AF Gooya, JM Kelvin, D Lyman, S Ruscetti, FW Oppenheim, J Keller, JR TI Interleukin-8 directly synergizes with steel factor to promote the growth of lineage-negative c-kit-positive progenitors. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,LLB,LMI,SAIC FREDERICK,IRSP,FREDERICK,MD. IMMUNEX CORP,SEATTLE,WA. ROBARTS RES INST,LONDON,ON N6A 5C1,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 78 EP 78 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200078 ER PT J AU Keller, JR Ortiz, M Lyman, S Ruscetti, F Jacobsen, SEW AF Keller, JR Ortiz, M Lyman, S Ruscetti, F Jacobsen, SEW TI Comparison of the cytokine survival requirements of purified hematopoietic stem/progenitor cell populations. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCI,LLB,SAIC FREDERICK,IRSP,FREDERICK,MD 21701. IMMUNEX CORP,SEATTLE,WA. HIPPLE CANC RES CTR,DAYTON,OH. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 79 EP 79 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200079 ER PT J AU Lohrey, N Keller, J Ortiz, M Gooya, J Ruscetti, F Spence, S AF Lohrey, N Keller, J Ortiz, M Gooya, J Ruscetti, F Spence, S TI Determination of heterogeneity of cytokine receptor RNA expression in increasingly purified populations of hematopoietic cells. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCI,LLB,DBS,FCDRC,FREDERICK,MD 21702. NCI,SAIC FREDERICK,IRSP,FCDRC,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 155 EP 155 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200155 ER PT J AU Do, BHQ Girard, LJ Orlic, D Bodine, DM AF Do, BHQ Girard, LJ Orlic, D Bodine, DM TI Gibbon Ape Leukemia virus receptor mRNA levels can be increased in HL60 cells by PMA induction and correlate with Gibbon Ape Leukemia virus transduction efficiency SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NIH,HEMATOPOIESIS SECT,LGT,NCHGR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 175 EP 175 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200175 ER PT J AU Orlic, D Girard, LJ Dunbar, CE Jordan, CT Bodine, DM AF Orlic, D Girard, LJ Dunbar, CE Jordan, CT Bodine, DM TI Induction of mRNA encoding retrovirus receptors in hematopoietic progenitor cells by in vitro exposure to cytokines. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 SOMATIX THERAPY CORP,ALAMEDA,CA. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 176 EP 176 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200176 ER PT J AU Hanazono, Y Dunbar, CE Emmons, RVB AF Hanazono, Y Dunbar, CE Emmons, RVB TI Retroviral producer cell lines containing green fluorescent protein S65T vector sequences are unstable: Evidence for toxicity in mammalian cells SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 192 EP 192 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200191 ER PT J AU Spence, S Schwarzenberger, P McCauslin, C Gooya, J Ruscetti, F Keller, J AF Spence, S Schwarzenberger, P McCauslin, C Gooya, J Ruscetti, F Keller, J TI Stable, targeted gene transfer to human hematopoietic progenitor cell lines by molecular conjugate vectors containing recombinant adenovirus. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCI,IRSP,SAIC,FCRDC,FREDERICK,MD 21701. NCI,LLB,DBS,FCRDC,FREDERICK,MD 21701. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 197 EP 197 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200196 ER PT J AU Rozemuller, H Rombouts, WJC Touw, JP Terpstra, W Prins, A FitzGerald, DJP Kreitman, RJ Pastan, I Hagenbeek, A Martens, ACM AF Rozemuller, H Rombouts, WJC Touw, JP Terpstra, W Prins, A FitzGerald, DJP Kreitman, RJ Pastan, I Hagenbeek, A Martens, ACM TI Specific elimination of acute myelocytic leukemia cells by targeting with HuGM-CSF toxin fusion proteins. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 ERASMUS UNIV ROTTERDAM,INST HEMATOL 1,ROTTERDAM,NETHERLANDS. DR DANIEL DEN HOED CANC CTR,NL-3008 AE ROTTERDAM,NETHERLANDS. NCI,LMB,DCBDC,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 370 EP 370 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200369 ER PT J AU Schwartz, GN Liao, F Szabo, JM Farber, JM Gress, RE AF Schwartz, GN Liao, F Szabo, JM Farber, JM Gress, RE TI Mig chemokine suppressed insulin like growth factor II (IGF-II) dependent stimulatory effects on CD34+ cells in liquid cultures with IL-3 and IGF-II. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 400 EP 400 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200399 ER PT J AU Smith, S Johnston, J Jahn, T Puck, J OShea, J Weinberg, K Taylor, N AF Smith, S Johnston, J Jahn, T Puck, J OShea, J Weinberg, K Taylor, N TI Stimulation of signal transduction pathways in lymphocytes from patients with X-SCID:activation through the IL-4/IL-13 receptor but not the IL-2 receptor. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 CHILDRENS HOSP LOS ANGELES,DIV IMMUNOL RES,LOS ANGELES,CA 90027. NIAMS,BETHESDA,MD. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD. RI Taylor, Naomi/H-4016-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 411 EP 411 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200410 ER PT J AU Mou, S DeBerry, C Ruscetti, F Linnekin, D AF Mou, S DeBerry, C Ruscetti, F Linnekin, D TI Stem cell factor activates the Src family member Lyn both rapidly and during mitosis. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCI,FCRDC,SAIC INV,BCDP,FREDERICK,MD. NCI,LAB LEUKOCYTE BIOL,DBS,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 470 EP 470 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200469 ER PT J AU Linnekin, D DeBerry, C AF Linnekin, D DeBerry, C TI STAT1 associates with c-kit and is activated in response to stem cell factor SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,DBS,LAB LEUKOCYTE BIOL,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 471 EP 471 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200470 ER PT J AU Wroblewski, JM Lay, LT VanZant, G Phillips, G Seth, P Curiel, D Meeker, TC AF Wroblewski, JM Lay, LT VanZant, G Phillips, G Seth, P Curiel, D Meeker, TC TI In vitro assays of recombinant adenovirus purging of tumor cells from hematopoietic stem cells. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV KENTUCKY,MARKEY CANC CTR,LEXINGTON,KY 40506. NCI,MED BRANCH,NIH,BETHESDA,MD 20892. UNIV ALABAMA,GENE THERAPY PROGRAM,BIRMINGHAM,AL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1996 VL 24 IS 9 BP 610 EP 610 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200609 ER PT J AU Gonzalez, FJ Lee, YH AF Gonzalez, FJ Lee, YH TI Cytochromes P450 .6. Constitutive expression of hepatic cytochrome P450 genes SO FASEB JOURNAL LA English DT Review DE transcription; HNF-1 alpha; C/EBP beta; STAT; cPLA(2) ID TRANSCRIPTION FACTOR GABP; GROWTH-HORMONE; AH-RECEPTOR; BINDING PROTEIN; RAT HEPATOCYTES; PROPOSED ROLE; CYP2E1 GENE; MOUSE-LIVER; PROMOTER; DNA AB One of the more challenging areas for study of the regulation of P450s is understanding the constitutive regulation of hepatic P450s. In this article, Gonzalez and Lee provide insight into how unique tissue-enriched transcription factors regulate expression of many of the hepatic P450s that are not under direct control of the ''xenobiotic'' receptors described by others. These constitutively expressed P450s are principally responsible for eliminating various hydrophobic xenobiotics such as drugs and other man-made chemicals from the body by oxidation reactions that are necessary to make them more water soluble. in addition, these tissue-enriched transcription factors probably dictate the developmental and probably sex-specific expression of P450s in the liver. Many of the tissue-enriched transcription factors are most likely under the control of second message pathways, increasing the potential diversity of regulation of the unique hepatic P450s discussed. C1 NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 49 TC 104 Z9 106 U1 0 U2 4 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 AUG PY 1996 VL 10 IS 10 BP 1112 EP 1117 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA VD429 UT WOS:A1996VD42900002 PM 8751713 ER PT J AU Roberts, DD AF Roberts, DD TI Regulation of tumor growth and metastasis by thrombospondin-1 SO FASEB JOURNAL LA English DT Review DE tumorigenesis; angiogenesis; cell-matrix interactions ID HUMAN SQUAMOUS CARCINOMA; HUMAN BREAST-CARCINOMA; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; FACTOR-BETA; MELANOMA-CELLS; ADHESION MOLECULES; EPITHELIAL-CELLS; IN-VIVO; ANGIOGENESIS AB Thrombospondin-1 (TSP1) is an extracellular matrix glycoprotein that influences cell adhesion, motility, and growth, Based on its effects on tumor and endothelial cell behavior, this member of the thrombospondin gene family has attracted interest as a potential regulator of tumor growth and metastasis, Initial studies have confirmed that increased TSP1 expression suppresses growth or metastasis of some tumors in vivo and inhibits angiogenesis. These activities are cell. type specific, however, since overexpression of TSP1 in some tumors causes increased tumor progression. One basis for these apparently conflicting observations may be the complexity of the protein, TSP1 interacts specifically with several cell-surface receptors, heparan sulfate proteoglycans, growth factors, and other matrix components. These multiple binding specificities, combined with the ability of TSP1 to activate latent transforming growth factor beta and inhibit several proteases, suggest; that exposure to TSP1 may initiate several intracellular signals, The integration of these signals may allow varied responses to TSP1, Furthermore, these signals may be received by the tumor cells, endothelial cells responsible for neovascularization, stromal cells, or cells of the host immune system, TSP1 influences specific behaviors of each cell type. Relating these phenomena to the molecular interactions of TSP1 observed in vitro may lead to novel therapeutic strategies for controlling cancer progression and metastasis. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 69 TC 217 Z9 227 U1 0 U2 4 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 AUG PY 1996 VL 10 IS 10 BP 1183 EP 1191 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA VD429 UT WOS:A1996VD42900009 PM 8751720 ER PT J AU Chu, TM Nocera, M Flanders, KC Kawinski, E AF Chu, TM Nocera, M Flanders, KC Kawinski, E TI Localization of seminal plasma transforming growth factor-beta(1) on human spermatozoa: An immunocytochemical study SO FERTILITY AND STERILITY LA English DT Article DE transforming growth factor-beta(1); spermatozoon; immunocytochemistry; confocal microscope AB Objective: To localize immunocytochemically transforming growth factor beta(1) (TGF-beta(1)) in human spermatozoa. Design: Incubation of spermatozoa with anti-TGF-beta(1) antiserum at various pH. Setting: Human volunteers in an academic research institute. Patients: Young healthy fertile men. Interventions: Semen specimens were collected. Results: At neutral pH and at physiological pH of seminal plasma, TGF-beta(1) immunostaining was detected predominantly at the postacrosomal region of the head, at the neck, and at the middle piece of the tail. Transforming growth factor-beta(1) also was found occasionally at the axial filament complex of the connecting piece and the ring. The acrosomal cap section of the head, the principal piece, or the end piece of the tail were immunocytochemically negative for TGF-beta(1). The TGF-beta(1) immunostaining pattern at acidic pH was similar to that at neutral pH and at physiological pH of seminal plasma, but a greater intensity of immunostaining was found at acidic pH than that at neutral pH. Conclusion: These results suggest that an in vivo activation of seminal plasma latent TGF-beta(1) may take place in the acidic environment of vagina, which results in a greater amount of activated TGF-beta(1) and, in turn, with an enhanced ''coating'' of TGF-beta(1) to spermatozoa. C1 NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. RP Chu, TM (reprint author), NEW YORK STATE DEPT HLTH,ROSWELL PK CANC INST,DEPT DIAGNOST IMMUNOL RES & BIOCHEM,BUFFALO,NY 14263, USA. NR 6 TC 30 Z9 31 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD AUG PY 1996 VL 66 IS 2 BP 327 EP 330 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA UY310 UT WOS:A1996UY31000025 PM 8690124 ER PT J AU Chen, F Zhou, J Ritter, JK Bondy, CA Owens, IS AF Chen, F Zhou, J Ritter, JK Bondy, CA Owens, IS TI Lobular distribution of human liver phenol and bilirubin uridine 5'-diphosphate glucuronosyltransferase messenger RNAs SO GASTROENTEROLOGY LA English DT Article ID OLTIPRAZ-INDUCED AMELIORATION; UDP-GLUCURONOSYLTRANSFERASE; ACETAMINOPHEN HEPATOTOXICITY; DRUG-METABOLISM; RAT; CELLS; GLUCURONIDATION; HETEROGENEITY; GLUTATHIONE; CONJUGATION AB Background & Aims: Heterogeneity in uridine 5'-diphosphate (UDP) glucuronosyltransferase expression across the human hepatic acinus may be important in the manifestation of certain zone-specific chemical hepatotoxicities. Previous immunohistochemical studies suggested that a phenol transferase induced by polycyclic aromatic hydrocarbons may be differentially expressed in centrilobular hepatocytes of rats. The aim of this study was to assess the distribution of the phenol and bilirubin transferases in human liver at the RNA level. Methods: In situ RNA hybridization was used with two human liver samples and specific probes for the phenol transferase RNA, HLUG P1, and the bilirubin transferase RNAs, HUG-Br1 and HUG-Br2. Results: The highest density signals were observed for the bilirubin transferase RNAs, both appearing to be evenly expressed in hepatocytes across the liver lobule. Slightly higher density of HUG-Brl message was observed in some centrilobular hepatocytes surrounding larger central vein structures. HLUG P1 RNA was expressed at low levels (approximate to fivefold greater than background signal) and was evenly distributed. Conclusions: The data suggest that a species difference exists in the distribution of the human and rat phenol transferase. No evidence was found for significant zonation in the pattern of expression of either the phenol or bilirubin transferase genes in human liver. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,RICHMOND,VA 23298. NICHHD,NATL INST HLTH,HUMAN GENET BRANCH,BETHESDA,MD 20892. NICHHD,NATL INST HLTH,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 21 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 1996 VL 111 IS 2 BP 472 EP 480 DI 10.1053/gast.1996.v111.pm8690214 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UZ864 UT WOS:A1996UZ86400023 PM 8690214 ER PT J AU Girard, L Hanna, Z Beaulieu, N Hoemann, CD Simard, C Kozak, CA Jolicoeur, P AF Girard, L Hanna, Z Beaulieu, N Hoemann, CD Simard, C Kozak, CA Jolicoeur, P TI Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTV(D)/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis SO GENES & DEVELOPMENT LA English DT Article DE Notch1; c-myc; transgenic mice; retrovirus; MuLV ID FELINE LEUKEMIA-VIRUS; T-CELL LYMPHOMAS; DROSOPHILA-NOTCH; INTEGRATION SITE; MOUSE NOTCH; V-ABL; VIRAL INTEGRATION; MAMMALIAN NOTCH; MESSENGER-RNA; HUMAN HOMOLOG AB The MMTV(D)/myc transgenic mice spontaneously develop oligoclonal CD4(+) CD8(+) T-cell tumors. Wt used provirus insertional mutagenesis in these mice to identify putative collaborators of c-myc. We found that Notch1 was mutated in a high proportion (52%) of these tumors. Proviruses were inserted upstream of the exon coding for the transmembrane domain and in both transcriptional orientations. These mutations led to high expression of truncated Notch1 RNAs and proteins (86-110 kD). In addition, many Notch1-rearranged tumors showed elevated levels of full-length Notch1 transcripts, whereas nearly all showed increased levels of full-length (330-kD) or close to full-length (280-kD) Notch1 proteins. The 5' end of the truncated RNAs were determined for some tumors by use of RT-PCR and 5' RACE techniques. Depending on the orientation of the proviruses, viral LTR or cryptic promoters appeared to be utilized, and coding potential began in most cases in the transmembrane domain. Pulse-chase experiments revealed that the 330-kD Notch1 proteins were processed into 110- and 280-kD cleavage products. These results suggest that Notch1 can be a frequent collaborator of c-myc for oncogenesis. furthermore, our data indicate that Notch1 alleles mutated by provirus insertion can lead to increased expression of truncated and full-length (330/280-kD) Notch1 proteins, both being produced in a cleaved and uncleaved form. C1 CLIN RES INST MONTREAL,MOL BIOL LAB,MONTREAL,PQ H2W 1R7,CANADA. UNIV MONTREAL,DEPT MED,MONTREAL,PQ H3J 2J7,CANADA. UNIV MONTREAL,DEPT MICROBIOL & IMMUNOL,MONTREAL,PQ H3J 2J7,CANADA. NIAID,NIH,BETHESDA,MD 20892. MCGILL UNIV,DEPT EXPT MED,MONTREAL,PQ H3G 1A4,CANADA. OI Hoemann, Caroline/0000-0003-3750-7879 NR 69 TC 182 Z9 185 U1 1 U2 3 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 AUG 1 PY 1996 VL 10 IS 15 BP 1930 EP 1944 DI 10.1101/gad.10.15.1930 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA VB850 UT WOS:A1996VB85000008 PM 8756350 ER PT J AU Hu, KH Liu, E Dean, K Gingras, M DeGraff, W Trun, NJ AF Hu, KH Liu, E Dean, K Gingras, M DeGraff, W Trun, NJ TI Overproduction of three genes leads to camphor resistance and chromosome condensation in Escherichia coli SO GENETICS LA English DT Article ID SHOCK PROTEIN; BINDING-PROTEINS; DNA-BINDING; CLONING VEHICLES; ALTERED PLOIDY; FAMILY; SEQUENCE; MUKB; MUTANTS; PARTITION AB We isolated and characterized three genes, crcA, cspE and crcB, which when present in high copy confer camphor resistance on a cell and suppress mutations in the chromosomal partition gene mukB. Both phenotypes require the same genes. Unlike chromosomal camphor resistant mutants, high copy number crcA, cspE and crcB do not result in an increase in the ploidy of the cells. The cspE gene has been previously identified as a cold shock-like protein with homologues in all organisms tested. We also demonstrate that camphor causes the nucleoids to decondense in vivo and when the three genes are present in high copy, the chromosomes do not decondense. Our results implicate camphor and mukB mutations as interfering with chromosome condensation and high copy crcA, cspE and crcB as promoting or protecting chromosome folding. C1 NCI,MOL BIOL LAB,BETHESDA,MD 20892. NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NR 58 TC 72 Z9 78 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD AUG PY 1996 VL 143 IS 4 BP 1521 EP 1532 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA VA244 UT WOS:A1996VA24400003 PM 8844142 ER PT J AU Tran, HT Gordenin, DA Resnick, MA AF Tran, HT Gordenin, DA Resnick, MA TI The prevention of repeat-associated deletions in Saccharomyces cerevisiae by mismatch repair depends on size and origin of deletions SO GENETICS LA English DT Article ID TRANSPOSON TN5 EXCISION; METHYL-DIRECTED REPAIR; DNA-REPLICATION ERRORS; HUMAN GENETIC-DISEASE; SIMPLE REPETITIVE DNA; ESCHERICHIA-COLI; MICROSATELLITE INSTABILITY; HETERODUPLEX DNA; SPONTANEOUS MUTATION; POLYMERASE-DELTA AB We have investigated the effects of mismatch repair on 1- to 61-bp deletions in the yeast Saccharomyces cerevisiae. The deletions are likely to involve unpaired loop intermediates resulting from DNA polymerase slippage. The mutator effects of mutations in the DNA polymerase delta (POL3) gene and the recombinational repair RAD52 gene were studied in combination with mismatch repair defects. The pol-3t mutation increased up to 1000-fold the rate of extended (7-61 bp) but not of I-bp deletions. In a rad52 null mutant only the I-bp deletions were increased (12-fold). The mismatch repair mutations pms1, msh2 and msh3 did not affect 31- and 61-bp deletions in the pol3-t but increased the rates of 7- and l-bp deletions. We propose that loops less than or equal to seven bases generated during replication are subject to mismatch repair by the PMS1, MSH2, MSH3 system and that it cannot act on loops greater than or equal to 31 bases. In contrast to the pol3-t, the enhancement of l-bp deletions in a rad52 mutant is not altered by a pms1 mutation. Thus, mismatch repair appears to be specific to errors of DNA synthesis generated during semiconservative replication. C1 NIEHS,MOL GENET LAB,RES TRIANGLE PK,NC 27709. ST PETERSBURG STATE UNIV,DEPT GENET,ST PETERSBURG 199034,RUSSIA. OI Gordenin, Dmitry/0000-0002-8399-1836 NR 58 TC 50 Z9 50 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD AUG PY 1996 VL 143 IS 4 BP 1579 EP 1587 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA VA244 UT WOS:A1996VA24400008 PM 8844147 ER PT J AU Chong, SS Tanigami, A Roschke, AV Ledbetter, DH AF Chong, SS Tanigami, A Roschke, AV Ledbetter, DH TI 14-3-3 epsilon has no homology to LIS1 and lies telomeric to it on chromosome 17p13.3 outside the Miller-Dieker syndrome chromosome region SO GENOME RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; SIGNAL-TRANSDUCTION; BAND 17P13.3; 14-3-3-PROTEINS; DISTINCT; P53; MEDULLOBLASTOMA; INVOLVEMENT; PHOSPHATASE; EXPRESSION AB Previously, we isolated several cDNA clones of the LIS1 gene implicated in Miller-Dieker syndrome. Analysis of the 5' end of one of the clones (8-1), which was originally thought to represent the 5' end of LIS1, indicates a striking similarity to mouse 14-3-3 epsilon. We have isolated a full-length cDNA of human 14-3-3 epsilon, for which sequence analysis reveals a strong nucleotide conservation with mouse 14-3-3 epsilon in both translated and untranslated regions (UTRs). Additionally, the predicted peptides of human, sheep, rat, and mouse 14-3-3 epsilon are identical. Using a 205-bp fragment common to LIS1 (8-1) and 14-3-3 epsilon as probe on adult and fetal multiple-tissue Northern blots, a similar to 2-kb transcript is detected, identical to the pattern observed with a full-length 14-3-3 epsilon cDNA probe. LIS1-specific transcripts of similar to 7.5 and similar to 5 kb are not detected by the 0.2-kb probe, indicating that the similarity between the 5' sequence of LIS1 (8-1) and the 3' UTR of 14-3-3 epsilon is not the result of shared homology between the two genes. Instead, clone 8-1 is a chimera of 14-3-3 epsilon and LIS1 partial cDNAs, and therefore its 5' sequence does not represent the LIS1 5' end. Interestingly, we have mapped the 14-3-3 epsilon gene to the same chromosomal sub-band as LIS1 (17p13.3). However, 14-3-3 epsilon lies telomeric to LIS1 and outside the Miller-Dieker syndrome chromosome region but in a region frequently deleted in several types of cancer, and is a reasonable candidate tumor suppressor gene. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. RI Chong, Samuel/D-8098-2015 NR 29 TC 21 Z9 23 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD AUG PY 1996 VL 6 IS 8 BP 735 EP 741 DI 10.1101/gr.6.8.735 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VB879 UT WOS:A1996VB87900009 PM 8858348 ER PT J AU Ning, Y Roschke, A Christian, SL Lesser, J Sutcliffe, JS Ledbetter, DH AF Ning, Y Roschke, A Christian, SL Lesser, J Sutcliffe, JS Ledbetter, DH TI Identification of a novel paternally expressed transcript adjacent to snRPN in the Prader-Willi syndrome critical region SO GENOME RESEARCH LA English DT Article ID MOLECULAR DIAGNOSIS; DNA METHYLATION; GENE; ANGELMAN; DEFINE AB Small nuclear ribonucleoprotein-associated polypeptide N (snRPN) and an anonymous transcript, PAR-5, are two of the paternally expressed transcripts mapped to the Prader-Willi syndrome critical region. Using, long-range PCR, we have isolated the genomic interval between snRPN and PAR-5, identified a novel transcript in this region, and termed it PAR-SN. Northern analysis demonstrates that PAR-SN is expressed in brain, skeletal muscle, and heart. Like snRPN and PAR-5, PAR-SN is expressed exclusively from the paternal homolog in cultured lymphoblasts. Sequence analysis of the transcript revealed no significant open reading frame but did include a polymorphic dinucleotide repeat (CA)(17). C1 NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT HUMAN MOL GENET,HOUSTON,TX 77030. RI Sutcliffe, James/C-1348-2012 OI Sutcliffe, James/0000-0001-5200-6007 NR 18 TC 22 Z9 22 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD AUG PY 1996 VL 6 IS 8 BP 742 EP 746 DI 10.1101/gr.6.8.742 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VB879 UT WOS:A1996VB87900010 PM 8858349 ER PT J AU Zinovieva, RD Duncan, MK Johnson, TR Torres, R Polymeropoulos, MH Tomarev, SI AF Zinovieva, RD Duncan, MK Johnson, TR Torres, R Polymeropoulos, MH Tomarev, SI TI Structure and chromosomal localization of the human homeobox gene Prox 1 SO GENOMICS LA English DT Article ID ASYMMETRIC SEGREGATION; PROSPERO GENE; DROSOPHILA; EYE; PROTEIN; EVOLUTION; ANIRIDIA; CLONING; CELLS AB The genomic organization and nucleotide sequence of the human homeobox gene Prox 1 as well as its chromosomal localization have been determined. This gene spans more than 40 kb, consists of at least 5 exons, and encodes an 83-kDa protein. It shows 89% identity with the chicken sequence at the nucleotide level in the coding region, while the human and chicken proteins are 94% identical. Among the embryonic tissues analyzed (lens, brain, lung, liver, and kidney), the human Prox 1 gene is most actively expressed in the developing lens, similar to the expression pattern of the chicken Prox 1 gene. The Prox 1 gene was mapped to human chromosome 1q32.2-q32.3. (C) 1996 Academic Press, Inc. C1 NEI,MOL & DEV BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NATL INST HLTH,NCHGR,BETHESDA,MD 20892. NR 26 TC 69 Z9 74 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 0888-7543 J9 GENOMICS JI Genomics PD AUG 1 PY 1996 VL 35 IS 3 BP 517 EP 522 DI 10.1006/geno.1996.0392 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VB758 UT WOS:A1996VB75800014 PM 8812486 ER PT J AU Clendenning, JB Humbert, R Green, ED Wood, C Traver, D Furlong, CE AF Clendenning, JB Humbert, R Green, ED Wood, C Traver, D Furlong, CE TI Structural organization of the human PON1 gene SO GENOMICS LA English DT Article ID HUMAN SERUM PARAOXONASE; CYSTIC-FIBROSIS; CHLORPYRIFOS; ARYLESTERASE; POLYMORPHISM; TOXICITY; MARKER AB Serum paraoxonase/arylesterase (PON) is an ''A'' esterase found in the HDL(2) fraction of mammalian sera closely associated with apolipoproteins Al and J. This enzyme hydrolyzes the active metabolites (oxons) of several organophosphate (OF) insecticides as well as the P-F bond of the nerve agents soman and sarin. PON also destroys biologically active, multioxygenated phospholipids. Two factors result in large individual variations in PON serum levels, a substrate-dependent activity polymorphism and large individual differences in PON protein levels that are stable over time. Animal model studies indicate that PON activity levels are likely to play a major role in determining sensitivity to OPs. The arg(192) PON isoform appears to be a risk factor in coronary artery disease, We report here the characterization of a 28-kb contig encompassing 300 bp of 5' sequence, the entire coding region, and 2 kb of 3'-flanking sequence of the PON gene. The structural portion of the paraoxonase protein is encoded by nine exons that form the primary transcript through the use of typical splice donor and acceptor sites. DNA sequences of the regions surrounding all the coding exons have been determined, A polymorphic CA repeat is located in intron 4. (C) 1996 Academic Press, Inc. C1 WASHINGTON UNIV,DEPT MED,DIV MED GENET 357720,SEATTLE,WA 98195. WASHINGTON UNIV,DEPT GENET,SEATTLE,WA 98195. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20982. NR 19 TC 41 Z9 44 U1 1 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD AUG 1 PY 1996 VL 35 IS 3 BP 586 EP 589 DI 10.1006/geno.1996.0401 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VB758 UT WOS:A1996VB75800023 PM 8812495 ER PT J AU NobenTrauth, K Copeland, NG Gilbert, DJ Jenkins, NA Sonoda, G Testa, JR Klempnauer, KH AF NobenTrauth, K Copeland, NG Gilbert, DJ Jenkins, NA Sonoda, G Testa, JR Klempnauer, KH TI Mybl2 (Bmyb) maps to mouse chromosome 2 and human chromosome 20q13.1 SO GENOMICS LA English DT Article ID FLUORESCENCE INSITU HYBRIDIZATION; B-MYB; REGULATED EXPRESSION; DNA-SEQUENCES; C-MYB; A-MYB; PROLIFERATION; TRANSCRIPTION; GENE; ACTIVATION AB Mybl2 encodes a transcription factor that is thought to play an important role in cell cycle progression, Here we report the chromosomal localization of Mybl2 in mouse and human. Using mouse Mybl2 cDNA clones as probes, we assigned Mybl2 in an interspecific backcross panel to distal Chromosome 2. Using human cDNA probes in combination with FISH analysis, we localized MYBL2 to chromosome 20q13.1, a region that is commonly deleted in myeloid disorders. Both chromosomal regions are highly homologous, and the map positions, therefore, confirm each other. However, our findings are in contrast to a previous report by Barletta et at. (Cancer Res. 51: 3821-3824, 1991) that placed the MYBL2 gene on human chromosome Xq13. (C) 1996 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FOX CHASE CANC CTR,DEPT MED ONCOL,PHILADELPHIA,PA 19111. MAX PLANCK INST IMMUNBIOL,SPEMANN LABS,D-79108 FREIBURG,GERMANY. RP NobenTrauth, K (reprint author), JACKSON LAB,600 MAIN ST,BAR HARBOR,ME 04609, USA. FU NCI NIH HHS [CA-45745, CA-06927] NR 22 TC 15 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 0888-7543 J9 GENOMICS JI Genomics PD AUG 1 PY 1996 VL 35 IS 3 BP 610 EP 612 DI 10.1006/geno.1996.0408 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VB758 UT WOS:A1996VB75800030 PM 8812502 ER PT J AU Yoshikawa, T Brkanac, Z Dupont, BR Xing, GQ Leach, RJ DeteraWadleigh, SD AF Yoshikawa, T Brkanac, Z Dupont, BR Xing, GQ Leach, RJ DeteraWadleigh, SD TI Assignment of the human nuclear hormone receptor, NUC1 (PPARD), to chromosome 6p21.1-p21.2 SO GENOMICS LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTORS; PEROXISOME PROLIFERATOR; IDENTIFICATION; SUPERFAMILY; LOCUS C1 UNIV TEXAS,CTR HLTH SCI,SAN ANTONIO,TX 78284. RP Yoshikawa, T (reprint author), NIMH,CLIN NEUROGENET BRANCH,UNIT GENE MAPPING & EXPRESS,BETHESDA,MD 20892, USA. OI Xing, Guoqiang/0000-0002-4706-3063 FU NHGRI NIH HHS [P01HG00470] NR 13 TC 27 Z9 34 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 AUG 1 PY 1996 VL 35 IS 3 BP 637 EP 638 DI 10.1006/geno.1996.0417 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VB758 UT WOS:A1996VB75800039 PM 8812511 ER PT J AU Kincade, JE Rabiner, DJ Bernard, SL Woomert, A Konrad, TR DeFriese, GH Ory, MG AF Kincade, JE Rabiner, DJ Bernard, SL Woomert, A Konrad, TR DeFriese, GH Ory, MG TI Older adults as a community resource: Results from the national survey of self-care and aging SO GERONTOLOGIST LA English DT Article DE elderly productive activity; national survey; volunteering; helping others; informal care ID SOCIAL SUPPORT; SIBLINGS AB Using data collected from the first wave of a longitudinal data set collected in the late fall and winter of 1990-1991, the National Survey of Self-Care and Aging (NSSCA), we examined the extent and type of assistance older people provided to others. Age, gender, and perceived hearth status were the most consistent predictors of the four types of assistance: personal care, child care, volunteer work, and listening/offering advice and support. Help with instrumental activities of daily living either alone or in combination with other activities of daily living was the most common type of personal care provided. C1 UNIV N CAROLINA,CURRICULUM PUBL HLTH NURSING,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT HLTH POLICY & ADM,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT SOCIAL MED,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC 27599. NIA,SOCIAL SCI RES AGING BEHAV & SOCIAL RES PROGRAM,NIH,BETHESDA,MD 20892. RP Kincade, JE (reprint author), UNIV N CAROLINA,CECIL G SHEPS CTR HLTH SERV BRANCH,SUITE 210,725 AIRPORT RD,CB 7590,CHAPEL HILL,NC 27599, USA. OI Konrad, Thomas R/0000-0002-5269-0440 FU NIA NIH HHS [AG-07929-02] NR 26 TC 24 Z9 24 U1 1 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 1996 VL 36 IS 4 BP 474 EP 482 PG 9 WC Gerontology SC Geriatrics & Gerontology GA WB159 UT WOS:A1996WB15900007 PM 8771975 ER PT J AU Kohn, EC Sarosy, GA Davis, P Christian, M Link, CE Ognibene, FP Sindelar, WF Jacob, J Steinberg, SM Premkumar, A Reed, E AF Kohn, EC Sarosy, GA Davis, P Christian, M Link, CE Ognibene, FP Sindelar, WF Jacob, J Steinberg, SM Premkumar, A Reed, E TI A phase I/II study of dose-intense paclitaxel with cisplatin and cyclophosphamide as initial therapy of poor-prognosis advanced-stage epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Gynecologic-Oncologists CY FEB 10-14, 1996 CL NEW ORLEANS, LA SP Soc Gynecol Oncologists ID COLONY-STIMULATING FACTOR; GYNECOLOGIC-ONCOLOGY-GROUP; TERM FOLLOW-UP; RANDOMIZED TRIAL; COMBINATION CHEMOTHERAPY; TAXOL; CARCINOMA; LONG; CARBOPLATIN; PLATINUM AB Epithelial ovarian cancer patients with bulky residual tumor have a poor response to therapy and limited survival. We investigated the addition of dose-intense paclitaxel to cisplatin and cyclo-phosphamide for patients with FIGO III/IV epithelial ovarian cancer. Paclitaxel dose was intensified from 135 to 250 mg/m(2) and administered in combination with cisplatin at greater than or equal to 75 mg/m(2) and cyclophosphamide at 750 mg/m(2). Thirty-one of 36 patients (86%) and 25 (70%) had greater than or equal to 2 and greater than or equal to 3 cm residual disease after surgery, respectively, One-third had stage IV disease, and 80% had grade 3 tumors, The maximally tolerated doses (MTD) were paclitaxel at 250 mg/m(2), cisplatin at 75 mg/m(2), and cyclophosphamide at 750 mg/m(2) on a 21-day cycle with G-CSF, 10 mu g/kg/day. Administered dose intensity at the MTD was greater than or equal to 86%. Reversible grade 3 peripheral neuropathy occurred in 28% of patients and fever during neutropenia in 2/352 cycles (0.5%). The pathologic response rate is 36% with an additional 25% having minimal microscopic disease, Median progression-free and overall survivals for patients receiving paclitaxel at 250 mg/m(2) at a median potential follow-up of 22 months have not been reached for the cohort nor for the greater than or equal to 3-cm subgroup. This regimen should he evaluated in a prospective, randomized clinical trial. (C) 1996 Academic Press, Inc. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIH,DEPT RADIOL,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. RP Kohn, EC (reprint author), NCI,MED OVARIAN CANC SECT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892, USA. NR 56 TC 28 Z9 28 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG PY 1996 VL 62 IS 2 BP 181 EP 191 DI 10.1006/gyno.1996.0213 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA VD603 UT WOS:A1996VD60300010 PM 8751547 ER PT J AU SimonsMorton, BG Crump, AD AF SimonsMorton, BG Crump, AD TI Empowerment: The process and the outcome SO HEALTH EDUCATION QUARTERLY LA English DT Article ID HEALTH-EDUCATION RP SimonsMorton, BG (reprint author), NICHHD,PREVENT RES BRANCH,DIV EPIDEMIOL STAT & PREVENT RES,6100 EXECUT BLVD,ROOM 7B05,BETHESDA,MD 20852, USA. OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 4 TC 5 Z9 5 U1 0 U2 0 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0195-8402 J9 HEALTH EDUC QUART JI Health Educ. Q. PD AUG PY 1996 VL 23 IS 3 BP 290 EP 292 DI 10.1177/109019819602300302 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UZ840 UT WOS:A1996UZ84000004 ER PT J AU Lam, JS Reeves, ME Cowherd, R Rosenberg, SA Hwu, P AF Lam, JS Reeves, ME Cowherd, R Rosenberg, SA Hwu, P TI Improved gene transfer into human lymphocytes using retroviruses with the gibbon ape leukemia virus envelope SO HUMAN GENE THERAPY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; PERIPHERAL-BLOOD LYMPHOCYTES; MURINE RETROVIRUSES; RIBONUCLEIC-ACID; CELL-LINES; IL-2 GENE; RECEPTOR; VECTORS; THERAPY; IMMUNOTHERAPY AB Gene-modified lymphocytes have a potential role in the therapy of cancer, infectious diseases, and genetic disorders of the immune system. Current gene therapy protocols involving gene transfer into lymphocytes utilize retroviruses with amphotropic envelope proteins. However, transduction efficiencies in lymphocytes using these viruses are relatively low. A potential strategy to improve gene transfer efficiency is the utilization of alternative retroviral envelopes that target unique receptors on the cell surface. One such alternative retroviral envelope, the gibbon ape leukemia virus (GALV) envelope, targets a distinct surface receptor (GLVR-1) that is 60% homologous but not cross-reactive to the amphotropic receptor (GLVR-2/RAM-1), Understanding the relationship between receptor expression and transduction efficiency is important for designing new strategies to improve gene transfer. Therefore, me compared GLVR-1 and GLVR-2 mRNA levels in lymphocytes and found that GLVR-1 was expressed 8- to 19-fold higher than GLVR-2. We then analyzed whether this enhanced expression of GLVR-1 correlated with increased infectivity of lymphocytes by retroviral vectors that utilize the GALV envelope compared to those that use the amphotropic envelope. We evaluated retroviral vectors packaged with either PA317 or PG13, which express the amphotropic and GALV envelopes, respectively. Lymphocyte transduction with PG13-packaged vectors was 4- to 18-fold higher than that with PA317-packaged vectors. These findings suggest that receptor expression level is an important factor in retroviral-target interactions and that gene transfer into human T lymphocytes should be performed with retroviruses that use the GALV envelope as opposed to retroviruses that use the amphotropic envelope. C1 NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NR 41 TC 59 Z9 61 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG 1 PY 1996 VL 7 IS 12 BP 1415 EP 1422 DI 10.1089/hum.1996.7.12-1415 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD321 UT WOS:A1996WD32100003 PM 8844200 ER PT J AU Mazzanti, CM Bergen, A Enoch, MA Michelini, S Goldman, D AF Mazzanti, CM Bergen, A Enoch, MA Michelini, S Goldman, D TI Identification of a Ser857-Asn857 substitution in DRK1 (KCNB1), population frequencies and lack of association to the low voltage alpha EEG trait SO HUMAN GENETICS LA English DT Article ID POTASSIUM CHANNEL; ELECTROENCEPHALOGRAM; CLONING; GENE AB A nonconservative amino acid substitution (Ser857Asn) in the human delayed-rectifier potassium channel DRK1 (KCNB1 locus), a candidate gene for the low voltage alpha electroencephalogram (EEG) trait locus (LVEEG1) at 20q13.2, and its frequency in ethnic population samples are described. The frequency of Asn857 in seven different ethnic population samples, totalling more than 1600 individuals, ranged from zero to greater than 3%. However, no association was found between Asn857 and the low voltage alpha EEG trait (LVA) in a population of 105 subjects assessed for the EEG, 24 of whom actually had LVA. C1 NIAAA,NIH,NEUROGENET LAB,ROCKVILLE,MD 20852. UNIV PISA,INST PSYCHIAT,I-56100 PISA,ITALY. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Bergen, Andrew/0000-0002-1237-7644 NR 18 TC 2 Z9 2 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 AUG PY 1996 VL 98 IS 2 BP 134 EP 137 DI 10.1007/s004390050175 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA UX049 UT WOS:A1996UX04900003 PM 8698327 ER PT J AU DeMarco, L Stratakis, CA Boson, WL Jakbovitz, O Carson, E Andrade, LM Amaral, VF Rocha, JL Choursos, GP Nordenskjold, M Friedman, E AF DeMarco, L Stratakis, CA Boson, WL Jakbovitz, O Carson, E Andrade, LM Amaral, VF Rocha, JL Choursos, GP Nordenskjold, M Friedman, E TI Sporadic cardiac myxomas and tumors from patients with Carney complex are not associated with activating mutations of the Gs alpha gene SO HUMAN GENETICS LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; PITUITARY-TUMORS; ENDOCRINE OVERACTIVITY; SPOTTY PIGMENTATION; G-PROTEIN; DNA; AMPLIFICATION; ONCOGENES AB Cardiac myxomas an rare tumors that may be encountered sporadically or in the context of the Carney complex. The molecular basis for the development of cardiac myxomas and Carney complex tumors is unclear. Pathological myocardial function and myocardial hypertrophy have been associated with alterations in the heterotrimeric GTP-binding proteins, The postulated protooncogenic character of the gene encoding the alpha subunit of the stimulatory GTP-binding protein Gs alpha (gsp) in pituitary and thyroid tumors, the finding of identical somatic gsp mutations in the myocardium of patients with McCune-Albright syndrome, and the associated endocrine anomalies of the Carney complex prompted us to investigate gate the occurrence of activating missense mutations in the Gs alpha gene in 10 sporadically occurring atrial myxomas and in 8 tumors from 7 patients with Carney complex. No gsp mutations could be demonstrated by using the polymerase chain reaction and denaturing gradient gel electrophoresis complemented by direct DNA sequencing. Thus, activating Gs alpha mutations neither are associated with the development of atrial myxomas, nor can be demonstrated in other tumors from patients with Carney complex. The significance of these mutations in the myocardium of asymptomatic patients with McCune-Albright syndrome remains to be determined. C1 CHAIM SHEBA MED CTR,INST HEMATOL,DNA ONCOGENET UNIT,IL-52621 TEL HASHOMER,ISRAEL. CHAIM SHEBA MED CTR,INST GENET,IL-52621 TEL HASHOMER,ISRAEL. UNIV FED MINAS GERAIS,DEPT PHARMACOL,BR-31270010 BELO HORIZONT,MG,BRAZIL. NICHHD,BETHESDA,MD 20892. KAROLINSKA HOSP,DEPT MOLEC MED,CLIN GENET UNIT,S-17176 STOCKHOLM,SWEDEN. UNIV FED MINAS GERAIS,HOSP CLIN,DEPT PATHOL,BR-31270010 BELO HORIZONT,MG,BRAZIL. RI De Marco, Luiz /H-6275-2012 NR 27 TC 29 Z9 29 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 AUG PY 1996 VL 98 IS 2 BP 185 EP 188 DI 10.1007/s004390050187 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA UX049 UT WOS:A1996UX04900015 PM 8698339 ER PT J AU Lee, L Loftus, D Appella, E Margulies, DH Mage, M AF Lee, L Loftus, D Appella, E Margulies, DH Mage, M TI A recombinant single-chain HLA-A2.1 molecule, with a cis active beta-2-microglobulin domain, is biologically active in peptide binding and antigen presentation SO HUMAN IMMUNOLOGY LA English DT Article ID HISTOCOMPATIBILITY COMPLEX MOLECULE; CYTOTOXIC T-CELLS; MONOCLONAL-ANTIBODIES; ESCHERICHIA-COLI; EXPRESSION; SURFACE; PROTEIN; IDENTIFICATION; LYMPHOCYTES; DEFINITION AB We have constructed a recombinant single-chain human HLA-A2.1 molecule (from A*0201) with a covalently attached beta(2)m. This molecule (MSC beta A2.1) can be detected on the surface of transfected beta(2)m(-) human cells by conformational antibodies W6/32 and BB7.2 and by anti-human beta(2)m mAb BM-63. The covalent beta(2)m, now a domain of the MSC beta A2.1 molecule, does not rescue endogenous Class I surface expression. Instead, it works in cis to achieve correct folding of the single-chain molecule. Immunoprecipitation shows that MSC beta A2.1 is a 60-kDa molecule with no dissociable beta(2)m The half-life of the MSC beta A2.1 molecule on transfected cell surfaces was as long as that of two-chain HLA-A2.1 molecules. The MSC beta A2.1 molecule was active in presentation of HTLV-I Tax 11-19 peptide and an endogenous peptide to specific CTL, MSC beta A2.1 molecules and wild-type HLA-A2.1 molecules on live cells can bind the HBV core peptide 18-27 with comparable affinities. These results show that MSC beta A2.1 molecules retain the functional ability to present both pulsed and endogenous antigens co the appropriate T cells, and thus may be useful components of antiviral vaccines. C1 NCI,BIOCHEM LAB,DIV BASIC SCI,BETHESDA,MD 20892. NCI,CELL BIOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 34 TC 7 Z9 7 U1 0 U2 2 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 AUG PY 1996 VL 49 IS 1 BP 28 EP 37 DI 10.1016/0198-8859(96)00056-0 PG 10 WC Immunology SC Immunology GA UY715 UT WOS:A1996UY71500004 PM 8839773 ER PT J AU Yamauchi, T Nishimaki, H Furusaka, A Tanaka, T Hayashi, S Tamemoto, H Taylar, S Tobe, K Kadowaki, T Nishiyama, M AF Yamauchi, T Nishimaki, H Furusaka, A Tanaka, T Hayashi, S Tamemoto, H Taylar, S Tobe, K Kadowaki, T Nishiyama, M TI Anti-IRS-1 monoclonal antibody, 6G5, cross-reacts to IRS-2 SO HYBRIDOMA LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; LIVER-REGENERATION; EXPRESSION; GENE; MICE; PROTEIN AB We previously reported the production of anti-IRS-l monoclonal antibodies against human IRS-1 C-terminal portion, One of anti IRS-1 monoclonal antibodies, 6G5, was found to immunologically cross-react with IRS-2, which has been reported recently. The data presented here provide information arising from the use of the anti-IRS-1 MAb, 6G5; this MAb was found to be a useful reagent in studying the functional role of IRSs in the insulin-signaling system. C1 JIKEI UNIV,SCH MED,DEPT BIOCHEM 2,MINATO KU,TOKYO,JAPAN. JIKEI UNIV,SCH MED,DAISAN HOSP,DEPT INTERNAL MED,TOKYO,JAPAN. UNIV TOKYO,FAC MED,DEPT INTERNAL MED 3,TOKYO 113,JAPAN. NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. NR 11 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD AUG PY 1996 VL 15 IS 4 BP 307 EP 309 DI 10.1089/hyb.1996.15.307 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA VG641 UT WOS:A1996VG64100008 PM 8880219 ER PT J AU Howard, BV Lee, ET Yeh, JL Go, O Fabsitz, RR Devereux, RB Welty, TK AF Howard, BV Lee, ET Yeh, JL Go, O Fabsitz, RR Devereux, RB Welty, TK TI Hypertension in adult American Indians - The strong heart study SO HYPERTENSION LA English DT Article DE Indians, North American; cardiovascular diseases; diabetes mellitus; ethnic groups ID CARDIOVASCULAR RISK-FACTORS; CORONARY-ARTERY DISEASE; BLOOD-PRESSURE; INSULIN-RESISTANCE; RACIAL-DIFFERENCES; MEXICAN-AMERICANS; ALASKA NATIVES; PIMA-INDIANS; PREVALENCE; HYPERINSULINEMIA AB Hypertension is a primary risk factor for cardiovascular disease in the United States. Although cardiovascular disease is the leading cause of death among American Indians, the prevalence of hypertension, its awareness and control, and its association with other cardiovascular disease risk factors and physiological variables have not been well studied in this population. The Strong Heart Study is a longitudinal study of cardiovascular disease and its risk factors in American Indians. Participants (2703 women and 1846 men) were members of 13 tribes in central Arizona, southwestern Oklahoma, and regions of South and North Dakota, At least 1500 individuals between 45 and 74 years of age participated from each center in a baseline clinical examination conducted between July 1989 and January 1992. The examination consisted of a personal interview and physical examination that included an oral glucose tolerance test and three consecutive blood pressure measurements. This study reports data from the baseline examination on the prevalence of hypertension and correlates of blood pressure. Results indicated that despite the high frequency of diabetes and obesity, prevalence rates of hypertension in Arizona and Oklahoma were similar to those in the US population in the Third National Health and Nutrition Examination Survey (NHANES III), and rates among South/North Dakota participants were significantly lower (P < .0001). Blood pressure was higher in individuals with diabetes (P < .0001) and was significantly correlated with age (P < .0001) and albuminuria (P < .0001) but only weakly related to obesity. There was no independent relation between blood pressure and insulin. Blood pressure seems to be less affected by obesity and hyperinsulinemia in American Indians compared with other populations. Nevertheless, hypertension should be aggressively treated and controlled in American Indians because it is a known precursor to morbidity and mortality associated with diabetes and cardiovascular disease. C1 UNIV OKLAHOMA,HLTH SCI CTR,CTR EPIDEMIOL RES,OKLAHOMA CITY,OK. NHLBI,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. ABERDEEN AREA INDIAN HLTH SERV,RAPID CITY,SD. RP Howard, BV (reprint author), MEDLANT RES INST,108 IRVING ST NW,WASHINGTON,DC 20010, USA. FU NHLBI NIH HHS [U01-HL-41642, U01-HL-41652, UL01-HL-41654] NR 53 TC 65 Z9 67 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 AUG PY 1996 VL 28 IS 2 BP 256 EP 264 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VA626 UT WOS:A1996VA62600017 PM 8707391 ER PT J AU Agah, R Gandjbakhche, AH Motamedi, M Nossal, R Bonner, RF AF Agah, R Gandjbakhche, AH Motamedi, M Nossal, R Bonner, RF TI Dynamics of temperature dependent optical properties of tissue: Dependence on thermally induced alteration SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article ID LASER IRRADIATION; DISTRIBUTIONS; REFLECTANCE; MYOCARDIUM; DAMAGE AB Thermal damage in heated bovine myocardial tissue is assessed from measured changes in total reflection and transmission of light, Mathematical expressions, based on random walk analysis of light propagation within tissue slabs, are used to relate the diffuse reflection and transmittance to the absorption coefficient, mu(a), and effective scattering coefficient, mu(s)' for samples of myocardial tissue which were subjected to rapid step changes in temperature, Time-dependent changes in mu(s)' indicate two processes, one with a fast and temperature-dependent rate the other with a slow and apparently temperature-independent rate. For final temperatures above 56.8 degrees C and for the first 500 s after the temperature change, the optical parameters are well fit by exponential forms that exhibit temperature-dependent time constants as predicted by Arrhenius reaction rate theory of thermal damage, The scattering changes are associated with an apparent activation energy, Delta E, of 162 kJ/mole and a frequency constant, A, of 3 x 10(23) s(-1). This method provides a means for estimating optical coefficients which are needed to assess laser tissue dosimetry. C1 NIH,DIV COMP RES,PHYS SCI LAB,BETHESDA,MD 20892. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV TEXAS,MED BRANCH,LASER & SPECT PROGRAM,GALVESTON,TX 77555. NIH,NATL CTR RES RESOURCES,BIOMED INSTRUMENTAT & ENGN PROGRAM,BETHESDA,MD 20892. RI Bonner, Robert/C-6783-2015 NR 21 TC 51 Z9 52 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD AUG PY 1996 VL 43 IS 8 BP 839 EP 846 DI 10.1109/10.508546 PG 8 WC Engineering, Biomedical SC Engineering GA VA588 UT WOS:A1996VA58800008 PM 9216156 ER PT J AU Silver, RF Crystal, RG Moller, DR AF Silver, RF Crystal, RG Moller, DR TI Limited heterogeneity of biased T-cell receptor V beta gene usage in lung but not blood T cells in active pulmonary sarcoidosis SO IMMUNOLOGY LA English DT Article ID HEAT-SHOCK PROTEIN; ANTIGEN RECEPTOR; INTERLEUKIN-2 RECEPTOR; MYCOBACTERIUM-LEPRAE; RHEUMATOID-ARTHRITIS; DISEASE-ACTIVITY; VARIABLE REGION; IMMUNE-RESPONSE; LYMPHOCYTES-T; EXPRESSION AB Sarcoidosis is a multisystem disorder characterized by non-caseating granulomas and the accumulation of CD4(+) T cells in involved tissues such as the lung. To evaluate the diversity of the CD4(+) T-cell repertoire in this disorder, a detailed clonal analysis was performed in five individuals with active sarcoidosis who demonstrated preferential accumulation of T cells expressing the T-cell receptor variable gene family V beta 8 in either the lung or blood. In three individuals, analysis of unselected samples of nucleotide sequences derived from V beta 8(+) lung T cells demonstrated degrees of clonality ranging from 11% to 46%, indicating the expansion of limited numbers of V beta 8(+) T-cell clones in the lung. Analysis of the corresponding deduced amino acid sequences demonstrated common VDJ junctional amino acid residues in the dominant V beta 8(+) T-cell clones derived from two oligoclonal V beta 8(+) lung T-cell populations, consistent with an antigen-specific T-cell response. In contrast, analysis of V beta 8(+) CD4(+) T cells from the blood of an individual with a marked bias for peripheral blood V beta 8(+) T cells demonstrated no evidence of oligoclonality, suggesting that the stimulus for circulating biased V beta-specific T cells in sarcoidosis may derive from a different, perhaps superantigenic, origin. Clinical improvement in the disease either in response to treatment with corticosteroids or as a result of spontaneous resolution was associated with a decrease in the proportion of V beta 8-specific T cells in the biased lung and/or blood T-cell compartments. Together, these observations are consistent with a role for this T-cell subset in the clinical manifestations of active granulomatous disease. C1 JOHNS HOPKINS UNIV,SCH MED,DIV PULM & CRIT CARE MED,BALTIMORE,MD 21205. NHLBI,PULM BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL-45115] NR 42 TC 26 Z9 27 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD AUG PY 1996 VL 88 IS 4 BP 516 EP 523 DI 10.1046/j.1365-2567.1996.d01-683.x PG 8 WC Immunology SC Immunology GA VB623 UT WOS:A1996VB62300007 PM 8881751 ER PT J AU Candotti, F Blaese, RM AF Candotti, F Blaese, RM TI The use of gene therapy for immunodeficiency disease SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Review ID CHRONIC GRANULOMATOUS-DISEASE; BONE-MARROW TRANSPLANTATION; ADENOSINE-DEAMINASE DEFICIENCY; PURINE-NUCLEOSIDE PHOSPHORYLASE; WISKOTT-ALDRICH SYNDROME; RECEPTOR-GAMMA-CHAIN; LEUKOCYTE ADHESION DEFICIENCY; X-LINKED AGAMMAGLOBULINEMIA; CLASS-II DEFICIENCY; HEMATOPOIETIC STEM-CELLS AB Gene therapy has been thought of as the ultimate form of treatment for inherited diseases. The concept of correcting the fundamental genetic errors leading to human diseases is certainly more appealing than attempts to treat the infectious, metabolic, and other undesirable consequences of defective gene function. In the last decade, gene therapy has moved from that speculation to early clinical applications with clinical gene transfer protocols applied to a variety of disorders including inherited genetic defects, malignancies, and infectious diseases. Inborn errors of immunity have played a key role in the development of these early gene therapy strategies and have paved the way to a broader application of this novel branch of medicine. In this article, we summarize the molecular aspects of clinical gene transfer and review recent results and future prospects of gene therapy applications for immunodeficiency diseases. RP Candotti, F (reprint author), NIH, NCHGR,CLIN GENE THERAPY BRANCH,BLDG 10,ROOM 10C103, 10 CTR DR, MSC 1582, BETHESDA, MD 20892 USA. NR 274 TC 4 Z9 4 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 EI 1557-8607 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD AUG PY 1996 VL 16 IS 3 BP 683 EP + DI 10.1016/S0889-8561(05)70266-6 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA VC478 UT WOS:A1996VC47800010 ER PT J AU Carroll, JA Dorward, DW Gherardini, FC AF Carroll, JA Dorward, DW Gherardini, FC TI Identification of a transferrin-binding protein from Borrelia burgdorferi SO INFECTION AND IMMUNITY LA English DT Article ID NEISSERIA-MENINGITIDIS; LYME-DISEASE; HEMOPHILUS-INFLUENZAE; IRON; INFECTION; RECEPTOR; CLONING; MEMBRANE; SHIGELLA; BACTERIA AB Bacterial pathogens have evolved various strategies to acquire iron from the iron-restricted environment found in mammalian hosts. Borrelia burgdorferi should be no different with regard to its requirement for ferric iron, and previous studies have suggested that transferrin (Tf) may be a source of iron in vivo. By probing blots with Tf conjugated to horseradish peroxidase, we have identified an outer membrane protein (28 kDa) from B. burgdorferi B31 that bound holo-Tf but not apo-Tf. The 28-kDa protein bound human, rat, or mouse Tf and was produced only by low-passage (less than passage 5), virulent isolates of strain B31. In addition, the Tf-binding protein (Tbp) from strain B31 retained the ability to bind Tf after treatment with 2% sodium dodecyl sulfate-1% beta-mercaptoethanol and heating to 100 degrees C for 5 min. These properties are remarkably similar to those of the Tbp of Staphylococcus aureus and Tbp2 from Neisseria meningitidis, B. burgdorferi Sh-2-82 produced an outer membrane protein different in size, i.e., 26 kDa, but with properties similar to those of to the protein from strain B31, suggesting variation in B. burgdorferi Tbps. The exact role of the 28-kDa protein in iron acquisition by B. burgdorferi remains to be determined. C1 UNIV GEORGIA,DEPT MICROBIOL,ATHENS,GA 30602. NIH,ROCKY MT LABS,HAMILTON,MT 59840. FU NIAID NIH HHS [AI33501] NR 39 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1996 VL 64 IS 8 BP 2911 EP 2916 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY893 UT WOS:A1996UY89300005 PM 8757812 ER PT J AU Yan, SH Negre, E Cashel, JA Guo, NH Lyman, CA Walsh, TJ Roberts, DD AF Yan, SH Negre, E Cashel, JA Guo, NH Lyman, CA Walsh, TJ Roberts, DD TI Specific induction of fibronectin binding activity by hemoglobin in Candida albicans grown in defined media SO INFECTION AND IMMUNITY LA English DT Article ID EXTRACELLULAR-MATRIX; RECEPTOR; IRON; INFECTION; ADHERENCE; ADHESIN; HOST; PH AB Fibronectin (FN) is a major component of host estracellular matrix that may play an important role in the initiation and dissemination of Candida albicans infections. Expression of FN binding requires growth of C. albicans blastoconidia in complex medium, and the regulation of FN receptor expression is poorly understood. We now demonstrate that hemoglobin is a potent and specific inducer of FN receptor expression and describe a defined medium supplemented with hemoglobin that greatly and stably enhances the binding activity of C. albicans for soluble FN. Enhancement of FN binding by hemoglobin in strain 44807 was concentration dependent and was maximal at 0.1% hemoglobin with 20- to 80-fold enhancement. The hemoglobin-induced FN binding to C. albicans was saturable, with a K-d of 2.7 x 10(-8) M. Enhancement required growth of C. albicans in hemoglobin-containing medium, since simply exposing blastoconidia to hemoglobin in a nongrowing status did not enhance binding. Induction was reversible following removal of hemoglobin from the growth medium and not associated with germination. Inorganic or protein-bound iron was not sufficient for the induction, since other iron-containing proteins or inorganic iron salts were inactive. Growth in the simple medium yeast nitrogen base supplemented with hemoglobin increased cell adhesion to immobilized FN and to cultured monolayers of bovine corneal endothelial cells. These data suggest that hemoglobin may be an important regulator of FN binding activity in C. albicans and thus may play a role in its pathogenesis. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 36 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1996 VL 64 IS 8 BP 2930 EP 2935 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY893 UT WOS:A1996UY89300008 PM 8757815 ER PT J AU deVries, FP vanderEnde, A vanPutten, JPM Dankert, J AF deVries, FP vanderEnde, A vanPutten, JPM Dankert, J TI Invasion of primary nasopharyngeal epithelial cells by Neisseria meningitidis is controlled by phase variation of multiple surface antigens SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; ENDOTHELIAL-CELLS; MONOCLONAL-ANTIBODIES; SEROGROUP-A; EXPRESSION; GONORRHOEAE; LIPOOLIGOSACCHARIDE; CARRIERS; PILI; OPA AB We have investigated bacterial factors required for the entry of Neisseria meningitidis serogroup B into muscosal cells using a novel in vitro infection model of primary cultures of human nasopharyngeal epithelium. An invasive meningococcal phenotype was obtained after several cycles of selection for intracellular bacteria with gentamicin. Invasive bacteria differed from those in the initial inoculum in that they lacked a capsule and pili, exhibited a nonsialylated low-molecular-weight type of lipopolysaccharide (LPS), and produced a new 28-kDa opacity outer membrane protein. LPS revertants of the selected meningococci expressed a nonsialylated L3,(7,9) type of LPS and were also invasive, while after LPS sialylation bacterial entry was inhibited. Variants lacking the 28-kDa opacity protein were poorly invasive. Coexpression of the outer membrane protein Opc and the 28-kDa opacity protein strongly inhibited microbial invasion into the primary cultured nasopharyngeal cells. Conversely, meningococcal internalization by cells of various epithelial cell lines was correlated with the expression of Opc rather than 28-kDa opacity protein. Our data indicate that a concurrent phase switching of multiple phase-variable bacterial surface components may be a prerequisite for meningococcal invasion into nasopharyngeal epithelium and that meningococcal class 5 proteins (Opa and Opc) may promote tissue tropism. C1 UNIV AMSTERDAM,RIVM,DEPT MED MICROBIOL,REFERENCE LAB BACTERIAL MENINGITIS,AMSTERDAM,NETHERLANDS. MAX PLANCK INST BIOL,INFEKT BIOL ABT,D-7400 TUBINGEN,GERMANY. NIAID,ROCKY MT LABS,HAMILTON,MT 59840. RI van der Ende, Arie/A-4346-2012; OI van Putten, Jos/0000-0002-4126-8172 NR 38 TC 84 Z9 85 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1996 VL 64 IS 8 BP 2998 EP 3006 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY893 UT WOS:A1996UY89300019 PM 8757826 ER PT J AU Bobo, L Novak, N Mkocha, H Vitale, S West, S Quinn, TC AF Bobo, L Novak, N Mkocha, H Vitale, S West, S Quinn, TC TI Evidence for a predominant proinflammatory conjunctival cytokine response in individuals with trachoma SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR NECROSIS FACTOR; LYMPHOCYTE MATURATION FACTOR; CELL STIMULATORY FACTOR; MONOCLONAL-ANTIBODY; ENZYME-IMMUNOASSAY; INTERFERON-GAMMA; GENE-EXPRESSION; INFECTION; GROWTH; HOMOLOGY AB Immune responses to Chlamydia trachomatis infection in trachoma do not protect against reinfection or the development of scarring and blindness, Tn addition, the immunoregulatory contribution of cytokines to the development of conjunctival histopathology or protection is undefined. In this study, conjunctival cytokine mRNA transcripts were compared among subgroups of chlamydia infection status and ocular disease presentations of 50 individuals from an area where trachoma is endemic, There was a significant association of elevated interleukin (IL)-1 beta, transforming growth factor beta 1, and tumor necrosis factor alpha transcripts with infection, follicular inflammation, and scarring, Both gamma interferon (IFN-gamma) and IL-2 transcripts were significantly associated with infection; slightly elevated IL-2 levels were found in inflammatory disease, High IFN-gamma transcript levels were present with follicles and inflammatory disease and to a lesser extent with inflammatory scarring, The role of IFN-gamma in protection from infection or disease was not apparent from this study, since transcripts were frequently present in both chlamydial infection and disease, IL-12 (p40) transcripts were elevated in adults and children in association with follicular inflammation but not with scarring, IL-4, IL-5, and IL-10 transcripts were not detected in any samples, In conclusion, C. trachomatis infection stimulates local cytokines which favor a strong cell-mediated and proinflammatory response in both the early and later manifestations of trachoma. In addition, cytokine transcript levels that were associated with disease but no infection were characteristically lower overall than when chlamydia was present. C1 JOHNS HOPKINS UNIV,DIV INFECT DIS,SCH MED,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,DANA CTR INVEST OPHTHALMOL,BALTIMORE,MD 21287. CENT EYE HLTH FDN,KONGWA TRACHOMA PROJECT,DODOMA,TANZANIA. NIAID,BETHESDA,MD 20892. FU NEI NIH HHS [EY01765] NR 54 TC 41 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1996 VL 64 IS 8 BP 3273 EP 3279 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY893 UT WOS:A1996UY89300057 PM 8757864 ER PT J AU Rajan, TV Porte, P Yates, JA Keefer, L Shultz, LD AF Rajan, TV Porte, P Yates, JA Keefer, L Shultz, LD TI Role of nitric oxide in host defense against an extracellular, metazoan parasite, Brugia malayi SO INFECTION AND IMMUNITY LA English DT Article ID MODEL; MICE AB The mechanisms by which mammalian hosts eliminate microparasites such as bacteria and viruses are well established, In viral infections, these mechanisms include the interferons, neutralizing and opsonizing antibodies, and cytotoxic T lymphocytes. In bacterial infections, polymorphonuclear leukocytes and macrophages, often facilitated by opsonizing antibodies, ingest the infectious agent and mediate host defense, In addition, complement, in the presence of specific antibodies directed against surface antigens, can lyse certain bacterial pathogens, In contrast, our understanding of the host defenses against metazoan, extracellular parasites is less well grounded, We obtained data by two different approaches to document the role of nitric oxide (NO) as a mediator of host defense against a human nematode parasite, First, treatment of immunocompetent, nonpermissive mice with an inhibitor of NO synthase abrogated resistance to Brugia malayi, one of the causative agents of human lymphatic filariasis, Second, treatment of permissive, immunodeficient mice with a compound that releases NO conferred resistance to infection, These data reinforce studies by James and her coworkers (I. P. Oswald, T. A. Wynn, A. Sher, and S. L. James, Comp. Biochem. Physiol. Pharmacol. Toxicol. Endocrinol. 108:11-18, 1994) on the role of NO in defense against trematode parasites and of Kanazawa et al. (T, Kanazawa, H. Asahi, H. Hata; K. Machida, N. Kagei, and M. J. Stadecker, Parasite Immunol. 15:619-623, 1993) on cestode parasites. C1 OAKLAND UNIV,DEPT BIOL,ROCHESTER,MI 48063. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. JACKSON LAB,BAR HARBOR,ME 04609. RP Rajan, TV (reprint author), UNIV CONNECTICUT,CTR HLTH,DEPT PATHOL,FARMINGTON,CT 06032, USA. NR 17 TC 79 Z9 82 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1996 VL 64 IS 8 BP 3351 EP 3353 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY893 UT WOS:A1996UY89300067 PM 8757874 ER PT J AU Gill, MJ McQuillen, DP vanPutten, JPM Wetzler, LM Bramley, J Crooke, H Parsons, NJ Cole, JA Smith, H AF Gill, MJ McQuillen, DP vanPutten, JPM Wetzler, LM Bramley, J Crooke, H Parsons, NJ Cole, JA Smith, H TI Functional characterization of a sialyltransferase-deficient mutant of Neisseria gonorrhoeae SO INFECTION AND IMMUNITY LA English DT Article ID SERUM RESISTANCE; OUTER-MEMBRANE; LIPOOLIGOSACCHARIDE; SIALYLATION; LIPOPOLYSACCHARIDE; ANTIBODIES; COMPONENTS AB Previous studies indicate that sialylation of lipopolysaccharide (LPS) by host CMP-N-acetylneuraminic acid (CMP-NANA) catalyzed by bacterial sialyltransferase rendered gonococci resistant to killing bg phagocytes, to entry into epithelial cell lines, to killing by immune serum and complement, and to absorption of complement component C3. These results have been confirmed by comparing a sialyltransferase-deficient mutant (strain JB1) with its parent (strain F62) in appropriate tests, In contrast to F62, JB1 was very susceptible to killing by human polymorphonuclear phagocytes in opsonophagocytosis tests and incubation with CMP-NANA did not decrease the level of killing. The inherent resistance of F62 in these tests was probably due to LPS sialylation by CMP NANA and lactate present in the phagocytes. A JB1 variant expressing the invasion-associated Opa protein was as able Po enter Chang human conjunctiva epithelial cells as an Opa-positive variant of F62, suggesting that the sialyltransferase is not required for Opa-mediated entry. After incubation with CMP-NANA, the number of F62 variant gonococci entering cells but not that of JB1 variant gonococci was drastically reduced, Both JB1 and F62 were killed by incubation with rabbit antibody to gonococcal major outer. membrane protein, protein I, and human complement, but only F62 was rendered resistant to the killing by incubation with CMP-NANA. Finally, both JB1 and F62 absorbed similar amounts of complement component C3 and the binding was decreased by incubation with CMP-NANA only for the wild type, F62. C1 UNIV BIRMINGHAM, SCH MED, BIRMINGHAM B15 2TT, W MIDLANDS, ENGLAND. UNIV BIRMINGHAM, SCH BIOCHEM, BIRMINGHAM B15 2TT, W MIDLANDS, ENGLAND. UNIV BIRMINGHAM, DEPT INFECT, BIRMINGHAM B15 2TT, W MIDLANDS, ENGLAND. BOSTON CITY HOSP, MAXWELL FINLAND LAB INFECT DIS, BOSTON, MA 02118 USA. NIAID, MICROBIAL STRUCT & FUNCT LAB, ROCKY MT LABS, HAMILTON, MT 59840 USA. RI Crooke, Helen/D-6710-2011; OI van Putten, Jos/0000-0002-4126-8172 FU PHS HHS [K11 A101061]; Wellcome Trust NR 23 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1996 VL 64 IS 8 BP 3374 EP 3378 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY893 UT WOS:A1996UY89300071 PM 8757878 ER PT J AU Lin, B Averett, WF Novak, J Chatham, WW Hollingshead, SK Coligan, JE Egan, ML Pritchard, DG AF Lin, B Averett, WF Novak, J Chatham, WW Hollingshead, SK Coligan, JE Egan, ML Pritchard, DG TI Characterization of PepB, a group B streptococcal oligopeptidase SO INFECTION AND IMMUNITY LA English DT Article ID LACTOCOCCUS-LACTIS; HYALURONATE LYASE; COLLAGENASE AB Group B streptococci were recently reported to possess a cell-associated collagenase. Although the enzyme hydrolyzed the synthetic collagen-like substrate N-(3-[2-furyl] acryloyl)-Leu-Gly-Pro-Ala, we found that neither the highly purified enzyme nor crude group B streptococcal cell lysate solubilized a film of reconstituted rat tail collagen, an activity regarded as obligatory for a true collagenase. We cloned and sequenced the gene for the enzyme (pepB). The deduced amino acid sequence showed 66.4% identity to the PepF oligopeptidase from Lactococcus lactis, a member of the M3 or thimet family of zinc metallopeptidases. The group B streptococcal enzyme also showed oligopeptidase activity and degraded a variety of small bioactive peptides, including bradykinin, neurotensin, and peptide fragments of substance P and adrenocorticotropin. C1 UNIV ALABAMA,SCH MED,JOINT DEPT,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,SCH DENT,DEPT ORAL BIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DIV CLIN IMMUNOL & RHEUMATOL,BIRMINGHAM,AL 35294. DEPT VET AFFAIRS MED CTR,BIRMINGHAM,AL 35233. NIAID,MOLEC STRUCT LAB,ROCKVILLE,MD 20852. FU NIAID NIH HHS [AI-30634, P30-AI-27767]; NICHD NIH HHS [HD-17812] NR 19 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1996 VL 64 IS 8 BP 3401 EP 3406 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY893 UT WOS:A1996UY89300076 PM 8757883 ER PT J AU Yi, ES Bedoya, A Lee, H Chin, E Saunders, W Kim, SJ Danielpour, D Remick, DG Yin, SM Ulich, TR AF Yi, ES Bedoya, A Lee, H Chin, E Saunders, W Kim, SJ Danielpour, D Remick, DG Yin, SM Ulich, TR TI Radiation-induced lung injury in vivo: Expression of transforming growth factor-beta precedes fibrosis SO INFLAMMATION LA English DT Article ID INDUCED PULMONARY FIBROSIS; MESSENGER-RNA EXPRESSION; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; BLEOMYCIN; PNEUMONITIS; CYTOKINE; COLLAGEN AB Cytokine release from irradiated cells has been postulated to start soon after irradiation preceding detectable clinical and pathological manifestation of lung injury. The expression of transforming growth factor beta (TGF beta), a fibrogenic and radiation-inducible cytokine, was studied from 1-16 weeks after the 15 and 30 Gray (Gy) of thoracic irradiation to rats. Thoracic irradiation caused an increase in TGF beta protein in bronchoalveolar lavage (BAL) fluid peaking at 3-6 weeks as compared to sham-irradiated control rats. Steady state TGF beta mRNA expression as shown by whole lung northern blot assay paralleled the TGF beta protein expression in BAL fluid. The peak of TGF beta protein increase in BAL fluid between 3 and 6 weeks coincided with the initial influx of inflammatory cells in BAL fluid, but preceded histologically discernable pulmonary fibrosis that was not apparent until 8-10 weeks after irradiation. In conclusion, TGF beta and mRNA and protein upregulation preceded the radiation-induced pulmonary fibrosis, suggesting a pathogenetic role in the development of radiation fibrosis. C1 UNIV CALIF SAN DIEGO, SCH MED, DEPT RADIAT ONCOL, SAN DIEGO, CA 92103 USA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. UNIV MICHIGAN, SCH MED, DEPT PATHOL, ANN ARBOR, MI USA. RP Yi, ES (reprint author), UNIV CALIF SAN DIEGO, SCH MED, DEPT PATHOL, SAN DIEGO, CA 92103 USA. NR 29 TC 50 Z9 54 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-3997 J9 INFLAMMATION JI Inflammation PD AUG PY 1996 VL 20 IS 4 BP 339 EP 352 DI 10.1007/BF01486737 PG 14 WC Cell Biology; Immunology SC Cell Biology; Immunology GA VE257 UT WOS:A1996VE25700001 PM 8872498 ER PT J AU Geetha, V AF Geetha, V TI Distortions in protein helices SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE alpha-helix; 3(10)-helix; irregularities; helical axis; distortions ID ALPHA-HELICES; ENERGETIC APPROACH; ATOMIC RESOLUTION; AMINO-ACIDS; PACKING; PREFERENCES; FEATURES; BINDING AB alpha-helices are the most common secondary structures in observed proteins. However, they are not always found in ideal helical conformation and they often exhibit structural distortions. Quantification of these irregularities become essential in understanding the packing of helices and therefore, their role in the functional characteristics of the protein. The backbone torsions phi, psi are of limited utility in this endeavor, because distorted helices often maintain the backbone geometry. The local compensatory effects are responsible for the preservation of the entire hydrogen bond network of the helical stretch. Earlier descriptions of helical linearity and curvature rest mostly on approximation, thus motivating the search for a better method for understanding and quantifying helical irregularities. We developed a method which involves the rotation and superposition of identical repeating units of the protein by the quaternion method. The set of parameters derived from the rotation-superposition algorithm helps in identifying the bends and kinks which are not necessarily induced by unusual amino acids like proline. The quantification of irregularities of observed helices might lead to a better understanding of their packing interactions. RP Geetha, V (reprint author), NIH,DIV COMP RES & TECHNOL,ANALYT BIOSTAT SECT,STRUCT BIOL LAB,BLDG 12A,ROOM 2041,BETHESDA,MD 20892, USA. NR 23 TC 5 Z9 5 U1 3 U2 5 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0141-8130 J9 INT J BIOL MACROMOL JI Int. J. Biol. Macromol. PD AUG PY 1996 VL 19 IS 2 BP 81 EP 89 DI 10.1016/0141-8130(96)01106-3 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA VA536 UT WOS:A1996VA53600001 PM 8842770 ER PT J AU Stewart, PA Stewart, WF Heineman, EF Dosemeci, M Linet, M Inskip, PD AF Stewart, PA Stewart, WF Heineman, EF Dosemeci, M Linet, M Inskip, PD TI A novel approach to data collection in a case-control study of cancer and occupational exposures SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; exposure assessment; questionnaires; job histories; occupational risk ID HISTORIES; INFORMATION; RESPONDENTS; RISK AB Background. In community and hospital-based case-control studies, the occupational data collected in interviews are usually limited to responses to general questions asked of all study subjects. A procedure is described in which more detailed information can be collected in an efficient, standardized and systematic way. Methods. A generic work history is initially collected from all subjects using a computer-assisted interview. The work history includes job title, type of business, job activities, materials and chemicals, and tools and equipment used. After responses are entered into the computer by the interviewer, the computer searches a synonym file to identify possible job-specific modules relevant to the reported job. The modules are detailed questionnaires that address specific jobs administered after obtaining the generic work history. The modules are used to ask questions about the work environment; sources of exposure; factors affecting the movement of the agent from the source to the subject, such as local exhaust ventilation; and individual and job characteristics. After the interview is completed, the work history and responses to the modules are sent electronically to an industrial hygienist who reviews the information using a custom-designed software package. Where ambiguities or contradictions occur in information reported by the respondent, or for jobs for which no module had been developed, the industrial hygienist generates up to 10 additional questions per job. These questions are sent back to the interviewer for administration of a short, second interview. Conclusions. These procedures, which are being successfully implemented in an on-going case-control study of brain tumours, should improve disease risk estimates over those derived from more traditional approaches to exposure assessment. C1 JOHNS HOPKINS UNIV,DEPT EPIDEMIOL,BALTIMORE,MD. RP Stewart, PA (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD 20892, USA. NR 18 TC 57 Z9 57 U1 2 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 1996 VL 25 IS 4 BP 744 EP 752 DI 10.1093/ije/25.4.744 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VH220 UT WOS:A1996VH22000007 PM 8921451 ER PT J AU Farrow, A Farrow, SC Little, R Golding, J AF Farrow, A Farrow, SC Little, R Golding, J TI The repeatability of self-reported exposure after miscarriage SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE exposure; self-report; repeatability; miscarriage; bias; questionnaire ID RETROSPECTIVE ASSESSMENT; OCCUPATIONAL EXPOSURE; PREGNANCY OUTCOMES; WATER-CONSUMPTION; ASBESTOS EXPOSURE; LUNG-CANCER; BIAS; QUESTIONNAIRE; REPRODUCIBILITY; CALIFORNIA AB Background. The Avon Longitudinal Study of Pregnancy and Childhood is a prospective study of women who ware resident in Avon and who were expected to deliver a baby between April 1991 and December 1992. Methods. The study provided an opportunity to test the repeatability of responses from 220 women who experienced a miscarriage and who reported exposure to occupational substances and common household products and appliances in two questionnaires. The first questionnaire was completed in the early part of the pregnancy and the second after the miscarriage. Women were asked to score their frequency of exposure on a five-point scale from 'daily' to 'never'. Their responses were analysed to assess the degree of agreement between replies to identical questions in the two questionnaires using the kappa statistic. A new frequency variable was created which compared the replies for the two questionnaires; this was analysed for all exposures by cross-tabulation with possible explanatory variables (age of mother, social class, history of miscarriage and the time lag between questionnaires). Results. In general there was good agreement in the reported exposures to 48 substances and products. The results showed a small and consistent pattern of reporting exposures less frequently in the second questionnaire, i.e. after miscarriage. This was not explained by the analysis of possible confounding variables. Given the literature, the authors had expected to find a shift in the opposite direction. Conclusion. The study reinforces the need to be cautious when using the results from single surveys of retrospective self-reported exposure. C1 MIDDLESEX UNIV,HLTH RES CTR,LONDON N17 8HR,ENGLAND. NIEHS,RES TRIANGLE PK,NC 27709. RP Farrow, A (reprint author), UNIV BRISTOL,INST CHILD HLTH,24 TYNDALL AVE,BRISTOL,AVON,ENGLAND. FU Wellcome Trust NR 30 TC 17 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 1996 VL 25 IS 4 BP 797 EP 806 DI 10.1093/ije/25.4.797 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VH220 UT WOS:A1996VH22000015 PM 8921459 ER PT J AU Xu, RH Kalechman, Y Albeck, M Kung, HF Sredni, B AF Xu, RH Kalechman, Y Albeck, M Kung, HF Sredni, B TI Inhibition of B16 melanoma metastasis by the immunomodulator AS101 SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE melanoma; metastasis; immunomodulator; natural killer cell; retinoblastoma; mouse; AS101 ID NATURAL-KILLER-CELLS; HIGH-DOSE INTERLEUKIN-2; TUMOR-CELL; ADVANCED CANCER; MICE; INVIVO; IMMUNOTHERAPY; LYMPHOCYTES; COMBINATION; INTERFERON AB The immunomodulator ammonium trichloro (dioxyethylene-O-O')tellurate (AS101) has previously been found to induce secretion of various cytokines in mouse and human, which include interleukin-l, interleukin-2, colony-stimulating factor, interferon-gamma, tumor necrosis factor, etc. It also protects mice from lethal and sublethal effects of chemotherapy and irradiation. The present studies were designed to evaluate its effect on pulmonary metastasis following intravenous (i.v.) injection of mouse B16 melanoma cells on day 0 of the experiment. AS101, given 10 mu g/mouse intraperitoneally in 7 daily injections starting the day before B16 cell infusion (day -1) led to a significant inhibition by 60%. When B16 cells were pretreated with AS101 for 24 h before injection, the lung metastases were further reduced by subsequent AS101 treatment of the tumor-loaded mice. In mice that had been depleted of natural killer (NK) cells using anti-asialo-GM1 antisera, AS101 was deprived of its stimulatory effect on the NK activity. The inhibition by AS101 on the B16 lung metastasis was also profoundly reduced by the antisera. Moreover, in vitro treatment of B16 cells with AS101 resulted in suppression of the cell growth in a semisolid culture. This was accompanied by an inhibition of the DNA synthesis and a dephosphorylation/activation of the retinoblastoma susceptibility protein (RE), a tumor suppressor gene product, in the B16 cells. Taken together, these data suggest that AS101 possesses an anti-metastatic activity, which probably involves two mechanisms: the stimulation of the host NK cell activity and the inhibition of the tumor cell proliferation. C1 BAR ILAN UNIV,DEPT LIFE SCI,CANC AIDS & IMMUNOL RES CTR,IL-52900 RAMAT GAN,ISRAEL. RP Xu, RH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702, USA. RI Xu, Ren-He/M-3125-2016 NR 40 TC 5 Z9 5 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD AUG PY 1996 VL 9 IS 2 BP 319 EP 325 PG 7 WC Oncology SC Oncology GA UX987 UT WOS:A1996UX98700020 PM 21541518 ER PT J AU Dominguez, I Boei, JJWA Balajee, AS Natarajan, AT AF Dominguez, I Boei, JJWA Balajee, AS Natarajan, AT TI Analysis of radiation-induced chromosome aberrations in Chinese hamster cells by FISH using chromosome-specific DNA libraries SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID IN-SITU HYBRIDIZATION; HUMAN PERIPHERAL LYMPHOCYTES; INSITU HYBRIDIZATION; CYTOGENETIC ANALYSIS; GOIANIA BRAZIL; X-IRRADIATION; TRANSLOCATIONS; REARRANGEMENTS; CONSTRUCTION; VALIDATION AB The frequencies of chromosome aberrations induced by different doses of X-rays were determined in both splenocytes and primary lung fibroblasts of Chinese hamster by bi-colour FISH using a combination of four chromosome-specific DNA libraries. The results indicate that the X-rays induced more translocations than dicentrics in Chinese hamster cells, in which the karyotype is comprised of both metacentric and acrocentric chromosomes. These results are similar to those reported in human lymphocytes, in which the karyotype contains many metacentric chromosomes. On the contrary, in mouse, which is characterized by acrocentric chromosomes only, the frequencies of translocations and dicentrics are induced in nearly equal proportions by X-rays. The ratio of translocations to dicentrics obtained in Chinese hamster cells was approximately 1.4-1.5, which supports the importance of the karyotypic features of a species in the relative induction of translocations to dicentrics. An analysis was also made on the yield of translocations and dicentrics involving individual chromosomes and the results indicate a non-random involvement of these chromosomes in the formation of aberrations. C1 LEIDEN UNIV,DEPT RADIAT GENET & CHEM MUTAGENESIS,NL-2300 RA LEIDEN,NETHERLANDS. UNIV SEVILLA,DEPT CELL BIOL,FAC BIOL,SEVILLE,SPAIN. NIA,MOL GENET LAB,NIH,BALTIMORE,MD 21224. INTERUNIV INST RADIOPATHOL & RADIAT PROTECT,JA COHEN INST,LEIDEN,NETHERLANDS. OI Dominguez Garcia, Inmaculada/0000-0002-5629-0604 NR 35 TC 33 Z9 35 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD AUG PY 1996 VL 70 IS 2 BP 199 EP 208 DI 10.1080/095530096145193 PG 10 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA VF329 UT WOS:A1996VF32900009 PM 8794849 ER PT J AU Cooper, PJ AF Cooper, PJ TI Untitled - Reply SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Letter ID ONCHOCERCA-VOLVULUS; RESPONSIVENESS; INDIVIDUALS; ANTIGEN RP Cooper, PJ (reprint author), NIH,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 1996 VL 37 IS 9 BP 1717 EP 1719 PG 3 WC Ophthalmology SC Ophthalmology GA VA337 UT WOS:A1996VA33700002 ER PT J AU Schooley, RT Campbell, TB Kuritzkes, DR Blaschke, T Stein, DS Rosandich, ME Phair, J Pottage, JC Messari, F Collier, A Kahn, J Ray, G Curtis, S Bakhtiari, M Kessler, H Coombs, R Corey, L Volberding, P Calandra, G Massari, F AF Schooley, RT Campbell, TB Kuritzkes, DR Blaschke, T Stein, DS Rosandich, ME Phair, J Pottage, JC Messari, F Collier, A Kahn, J Ray, G Curtis, S Bakhtiari, M Kessler, H Coombs, R Corey, L Volberding, P Calandra, G Massari, F TI Phase 1 study of combination therapy with L-697,661 and zidovudine SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE combination therapy; pharmacokinetic interactions; zidovudine; L-697,661; human immunodeficiency virus-1 ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE INHIBITORS; PLACEBO-CONTROLLED TRIAL; HIGH-LEVEL RESISTANCE; ANTIVIRAL ACTIVITY; HIV-1 REPLICATION; DOUBLE-BLIND; P24 ANTIGEN; AZT; EFFICACY AB We performed a pilot study that examined the clinical and pharmacokinetic interactions between zidovudine (ZDV) and a pyridinone derivative, L-697-661. The results indicate that the drugs were well tolerated, with no important pharmacokinetic interactions, when administered concomitantly for as long as 8 weeks. Although the number of study participants was small, we noted rapid emergence of resistance to L-697,661 among ZDV-naive study subjects who were administered L-697,661 as monotherapy but did not observe isolates of human immunodeficiency virus type 1 (HIV-I) resistant to L-697,661 among those who were administered concomitant ZDV. These results suggest a potential interaction between development of resistance to L-697,661 and ZDV. Although the clinical development of L-697,661 has been halted, our results support the need for further studies to test whether specific interactions among antiretroviral agents administered in combination and the molecular target can delay the emergence of isolates that exhibit resistance to all drugs in the regimen. C1 VET AFFAIRS MED CTR,DENVER,CO. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV WASHINGTON,SEATTLE,WA 98195. STANFORD UNIV,PALO ALTO,CA 94304. NIAID,DIV AIDS,NIH,BETHESDA,MD 20892. MERCK SHARP & DOHME RES LABS,BLUE BELL,PA. RP Schooley, RT (reprint author), UNIV COLORADO,HLTH SCI CTR,DIV INFECT DIS,4200 E 9TH AVE,B-168,DENVER,CO 80262, USA. NR 34 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD AUG 1 PY 1996 VL 12 IS 4 BP 363 EP 370 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY965 UT WOS:A1996UY96500006 PM 8673545 ER PT J AU Lee, TH Sakahara, N Fiebig, E Busch, MP OBrien, TR Herman, SA AF Lee, TH Sakahara, N Fiebig, E Busch, MP OBrien, TR Herman, SA TI Correlation of HIV-1 RNA levels in plasma and heterosexual transmission of HIV-1 from infected transfusion recipients SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Letter ID HUMAN-IMMUNODEFICIENCY-VIRUS; PARTNERS; TYPE-1; RISK; MEN C1 NCI,VIRAL EPIDEMIOL SECT,ROCKVILLE,MD. ROCHE MOL SYST,DIAGNOST DEV,SOMERVILLE,NY. RP Lee, TH (reprint author), IRWIN MEM BLOOD CTR,SAN FRANCISCO,CA, USA. NR 24 TC 56 Z9 56 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD AUG 1 PY 1996 VL 12 IS 4 BP 427 EP 428 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY965 UT WOS:A1996UY96500015 PM 8673554 ER PT J AU Brock, DB Foley, DJ Salive, ME AF Brock, DB Foley, DJ Salive, ME TI Hospital and nursing home use in the last three months of life SO JOURNAL OF AGING AND HEALTH LA English DT Article; Proceedings Paper CT 1992 American-Statistical-Association Annual Meeting CY 1992 CL BOSTON, MA SP Amer Stat Assoc ID OLDER PERSONS; QUALITY; POPULATION; DEATH AB We describe decedents' days of care and changes in residence due to episodes of hospital and institutional care in the last 90 days of life. Data are from the National Institute on Aging's Survey of the Last Days of Life (SLDOL) with informants' responses for a sample of 1,227 decedents age 65 years and older from Fairfield County, Connecticut, Overall, three-fourths of the decedents made only one transition to or from a health care facility in the last 3 months of life and another 10% made two or three transitions. Hospital days decreased slightly with age, but nursing home days increased dramatically. physical disability, lack of social contacts, incontinence, and a diagnosis of dementia were significantly associated with a long, terminal, institutional stay, Future cost savings are likely to be achieved more through the reduction of nursing home care in the last months of life than in a reduction of hospital care. RP Brock, DB (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,RM 3C-309 BETHESDA GATEWAY BLDG,7201 WISCONSIN AV,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-2-2137] NR 26 TC 15 Z9 15 U1 1 U2 3 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD AUG PY 1996 VL 8 IS 3 BP 307 EP 319 DI 10.1177/089826439600800301 PG 13 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA VB974 UT WOS:A1996VB97400001 PM 10165977 ER PT J AU Shalit, M Sekhsaria, S Li, F Mauhorter, S Mahanti, S Malech, HL AF Shalit, M Sekhsaria, S Li, F Mauhorter, S Mahanti, S Malech, HL TI Early commitment to the eosinophil lineage by cultured human peripheral blood CD34(+) cells: Messenger RNA analysis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE eosinophils; peripheral blood CD34(+) cells; mRNA; growth factors ID COLONY-STIMULATING FACTOR; RESPIRATORY BURST; INTERFERON-GAMMA; MAST-CELLS; PROGENITOR CELLS; GROWTH-FACTORS; DIFFERENTIATION; EXPRESSION; PROTEIN; IL-3 AB Early hematopoietic progenitors expressing the CD34(+) phenotype can be harvested from the peripheral blood of normal individuals. We have optimized the liquid culture of human CD34(+) peripheral blood progenitors (PBPs) to achieve differentiation into a population of cells consisting almost entirely of eosinophil progenitors and maturing eosinophils. Growth of CD34(+) PBPs for 28 days in the presence of the combination of IL-3, granulocyte-macrophage colony-stimulating factor, and IL-5 resulted in an almost 250-fold increase in cell number, yielding a population that contained 83% maturing eosinophils. The residual population consisted of basophils and mast cells (3% by acidic toluidine blue staining, 15.2% by flow cytometric assay for binding to high-affinity IgE receptor) and immature cells. This provides an opportunity to examine the kinetics of the acquisition of specialized mature eosinophil characteristics during eosinophil differentiation. Several host-defense and bioactive proteins are found almost exclusively in eosinophil granules. In addition, stimulated eosinophils, like neutrophils, produce copious amounts of toxic oxygen radicals. We used our culture system and the sensitive technique of reverse-transcriptase polymerase chain reaction to analyze the kinetics of production of messenger RNA transcripts encoding several eosinophil proteins, including five eosinophil granule proteins and four subunit peptides of the superoxide-generating reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in small numbers of differentiating eosinophils from peripheral blood CD34(+) cells. Freshly isolated CD34(+) PBPs contained transcripts for the ubiquitously present housekeeping protein phosphoglucokinase but contained no eosinophil granule protein transcripts and barely detectable amounts of some oxidase protein transcripts. On day 3 of culture, no cells recognizable by histochemical staining as eosinophils could be detected, but transcripts for all five eosinophil period. Similar kinetics were seen for all but one of the NADPH oxidase protein transcripts. However, transcripts for the p67(phox) NADPH oxidase protein were not detected until day 7, and functional oxidase activity did not appear until day 12. From that point, oxidase activity increased to the eosinophil lineage occurs very early, by day 3, but that further events in differentiation must take place before the appearance of histologically staining eosinophil granules and acquisition of functional oxidase capacity. C1 NIAID,HOST DEF LAB,NATL INST HLTH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 24 TC 21 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 1996 VL 98 IS 2 BP 344 EP 354 DI 10.1016/S0091-6749(96)70159-8 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA VC995 UT WOS:A1996VC99500014 PM 8757212 ER PT J AU Byrne, EA Fleg, JL Vaitkevicius, PV Wright, J Porges, SW AF Byrne, EA Fleg, JL Vaitkevicius, PV Wright, J Porges, SW TI Role of aerobic capacity and body mass index in the age-associated decline in heart rate variability SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE aging; fitness; body mass index; autonomic nervous system ID RESPIRATORY SINUS ARRHYTHMIA; VAGAL-STIMULATION; SHORT-TERM; SEDENTARY; HUMANS; RISK AB The extent to which age-associated changes in aerobic capacity and body composition modulate the age-associated decline in heart rate variability (HRV) is unknown. We therefore measured HRV, peak O-2 consumption (VO2peak) during treadmill testing, and relative weight (body mass index; BMI) in 164 healthy normotensive adults (75 men, age 20-87 yr) from the Baltimore Longitudinal Study on Aging. Two components of HRV, respiratory sinus arrhythmia (RSA; 0.12-0.30 Hz) and 0.10-Hz variability (0.06-0.10 Hz), were extracted from S-min electrocardiogram recordings in the supine, seated, and standing postures. RSA, 0.10-Hz variability, and VO2peak varied inversely with age; BMI was unrelated to age. Age contributed 15.5-21.1% independent variance to RSA and 13.2-17.3% independent variance to 0.10-Hz HRV. VO2peak did not contribute significantly to RSA or 0.10-Rz HRV beyond the effect of age in any posture. There were no consistent independent contributions of BMI to HRV. Thus, in this population-based sample, age-associated changes in aerobic capacity and relative body weight do not provide the primary explanation for the decline in HRV observed with advancing age. C1 UNIV MARYLAND,COLLEGE PK,MD 20742. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. FU NICHD NIH HHS [HD-22628] NR 31 TC 52 Z9 53 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD AUG PY 1996 VL 81 IS 2 BP 743 EP 750 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA VD228 UT WOS:A1996VD22800030 PM 8872642 ER PT J AU Fan, JL Patibandla, SA Kimura, S Rao, TN Desai, RK Seetharamaiah, GS Kurosky, A Prabhakar, BS AF Fan, JL Patibandla, SA Kimura, S Rao, TN Desai, RK Seetharamaiah, GS Kurosky, A Prabhakar, BS TI Purification and characterization of a recombinant human thyroid peroxidase expressed in insect cells SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE TPO; autoimmunity; purification; HPLC; expression ID COMPLEMENTARY DEOXYRIBONUCLEIC-ACID; BACULOVIRUS; DISEASE; ANTIBODIES; AUTOANTIBODIES; AUTOANTIGEN; RECEPTOR; THYROPEROXIDASE; IDENTIFICATION; MEMBRANES AB Thyroid peroxidase (TPO) is an essential enzyme for thyroid hormone biosynthesis and is an autoantigen against which antibodies are found in a number of autoimmune thyroid disorders. Large quantities of pure TPO are essential for understanding its structure and role in normal thyroid function and thyroid diseases. In this study, we describe the production of human TPO (hTPO) using a baculovirus expression vector in insect cells. TPO was sequentially extracted from insect cells using various buffers and the protein was purified to homogeneity on a C4 reversed-phase semipreparative column using high-performance Liquid chromatography. The purified protein was identified as hTPO by enzyme-linked immunosorbant assay, Western blot, and amino acid sequence analyses. Carbohydrate analysis of the recombinant hTPO showed that the protein is glycosylated and mannose is the major oligosaccharide. We have extended the carbohydrate analysis by establishing the occurrence of N-acetyl galactosamine which suggested that the recombinant hTPO might contain O-glycosyl moieties. Purified hTPO reacted specifically with sera from patients with Hashimoto's thyroiditis. Crude as well as purified hTPO did not show any enzymatic activity when produced in Sf9 insect cells grown in serum free medium. In contrast, hTPO produced in the presence of 10% fetal bovine serum containing 1 mu g/ml of haematin was enzymatically active. However the enzymatic activity of the recombinant hTPO was lower than that often found with hTPO purified from thyroid tissue. Availability of purified hTPO in relatively large quantities should allow further structural and immunological studies. (C) 1996 Academic Press Limited C1 UNIV TEXAS,MED BRANCH,DEPT MICROBIOL & IMMUNOL,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET,GALVESTON,TX 77555. UNIV MASSACHUSETTS,MED CTR,DEPT INTERNAL MED,DIV ENDOCRINOL,WORCESTER,MA 01655. NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. NIDDK,CELLULAR ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. FU NINDS NIH HHS [NS 29261] NR 31 TC 14 Z9 14 U1 1 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD AUG PY 1996 VL 9 IS 4 BP 529 EP 536 DI 10.1006/jaut.1996.0071 PG 8 WC Immunology SC Immunology GA VC545 UT WOS:A1996VC54500011 PM 8864829 ER PT J AU Ying, YA Crane, DD Barry, CE AF Ying, YA Crane, DD Barry, CE TI Stationary phase-associated protein expression in Mycobacterium tuberculosis: Function of the mycobacterial alpha-crystallin homolog SO JOURNAL OF BACTERIOLOGY LA English DT Article ID HEAT-SHOCK PROTEIN; CYCLOPROPANATED MYCOLIC ACIDS; ESCHERICHIA-COLI; CHAPERONE; IDENTIFICATION; BIOSYNTHESIS; RESISTANCE; RESPONSES; ANTIGEN; FAMILY AB The majority of active tuberculosis cases arise as a result of reactivation of latent organisms which are quiescent within the host, The ability of mycobacteria to survive extended periods without active replication is a complex process whose details await elucidation. We used two-dimensional gel electrophoresis to examine both steady-state protein composition and time-dependent protein synthetic profiles in aging cultures of virulent Mycobacterium tuberculosis. At least seven proteins were maximally synthesized 1 to 2 weeks following the end of log-phase growth, One of these proteins accumulated to become a predominant stationary-phase protein, N-terminal amino acid sequencing and immunoreactivity identified this protein as the 16-kDa alpha-crystallin-like small heat shock protein, The gene for this protein was shown to be limited to the slowly growing M. tuberculosis complex of organisms as assessed by Southern blotting, Overexpression of this protein in wild-type M. tuberculosis resulted in a slower decline in viability following the end of log-phase growth. Accumulation of this protein was observed in log-phase cultures following a shift to oxygen-limiting conditions but not by other external stimuli, The protein was purified to homogeneity from overexpressing M. smegmatis in two steps and shown to have a significant ability to suppress the thermal denaturation of alcohol dehydrogenase. Collectively, these results suggest that the mycobacterial alpha-crystallin protein may play a role in enhancing long term protein stability and therefore long-term survival of M. tuberculosis. C1 NIAID, ROCKY MT LABS, TB RES UNIT, INTRACELLULAR PARASITES LAB, HAMILTON, MT 59840 USA. RI Barry, III, Clifton/H-3839-2012 NR 41 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 1996 VL 178 IS 15 BP 4484 EP 4492 PG 9 WC Microbiology SC Microbiology GA UZ047 UT WOS:A1996UZ04700016 ER PT J AU Heinzen, RA Hackstadt, T AF Heinzen, RA Hackstadt, T TI A developmental stage-specific histone H1 homolog of Coxiella burnetii SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PROTEIN-BLOTTING PROCEDURE; CHLAMYDIA-TRACHOMATIS; PSEUDOMONAS-AERUGINOSA; H1-LIKE PROTEIN; REGULATED GENE; DNA; SEQUENCE AB Two DNA-binding proteins have been detected in Coxiella burnettii by Southwestern (DNA-protein) blotting, One of these, termed Hq1, is enriched in the small cell variant stage of the developmental cycle and displays compositional and primary amino acid sequence similarities to eukaryotic histone H1. C. burnetii appears to be another example of an intracellular parasite with morphologically distinct developmental forms whose nucleoid structure may be controlled by histone H1 homologs. C1 NIAID,HOST PARASITE INTERACT SECT,INTRACELLULAR PARASITES LAB,ROCKY MT LABS,HAMILTON,MT 59840. NR 23 TC 24 Z9 25 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 AUG PY 1996 VL 178 IS 16 BP 5049 EP 5052 PG 4 WC Microbiology SC Microbiology GA VB706 UT WOS:A1996VB70600043 PM 8759877 ER PT J AU Hilbert, SL Sword, LC Batchelder, KF Barrick, MK Ferrans, VJ AF Hilbert, SL Sword, LC Batchelder, KF Barrick, MK Ferrans, VJ TI Simultaneous assessment of bioprosthetic heart valve biomechanical properties and collagen crimp length SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID 15-YEAR EXPERIENCE; CARDIAC VALVES; STRESS; LEAFLETS; FAILURE AB A new morphologic method is described for the simultaneous quantitation of porcine aortic valve collagen crimp length and the assessment of biomechanical properties. This method utilizes the simultaneous real-time video recording of collagen crimp morphology and acquisition of crimp length data through the combination of polarized light microscopy and morphometry. We felt that the development of this method was warranted, due to the fundamental role played by collagen in porcine aortic valve performance. The development of this method involved the design and fabrication of a uniaxial microtensile stage, suitable for mounting on a standard microscope stage. The validation of our test method was accomplished by a comparison of untreated and glutaraldehyde-treated porcine aortic valve leaflet tissue, because the biomechanical and morphologic characteristics of the native and fixed aortic valve have been extensively studied. The method described in this communication enables the collection of morphologic and biomechanical data from a single tissue specimen, eliminating the need for independent studies of multiple specimens. Furthermore, this method obviates the need for making assumptions, which may be difficult to verify, concerning the homogeneity of different test specimens with respect to their morphology and corresponding mechanical response to different experimental conditions. (C) 1996 John Wiley & Sons, Inc. C1 JOHNS HOPKINS UNIV,GWC WHITING SCH ENGN,BALTIMORE,MD. NHLBI,PATHOL SECT,NIH,BETHESDA,MD 20892. RP Hilbert, SL (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,ROCKVILLE,MD 20852, USA. NR 21 TC 17 Z9 18 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD AUG PY 1996 VL 31 IS 4 BP 503 EP 509 DI 10.1002/(SICI)1097-4636(199608)31:4<503::AID-JBM10>3.0.CO;2-H PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA UY924 UT WOS:A1996UY92400010 PM 8836847 ER PT J AU Riminucci, M Fisher, LW Satomura, K Bianco, P Robey, PG AF Riminucci, M Fisher, LW Satomura, K Bianco, P Robey, PG TI Gs alpha mutations and bone cell misfunction in McCune-Albright Syndrome (MAS): An RT-PCR in situ hybridization approach SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. UNIV ROMA LA SAPIENZA,ROME,ITALY. UNIV AQUILA,LAQUILA,ITALY. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP 20 EP 20 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500020 ER PT J AU Gardella, TJ Jensen, GS Luck, M Usdin, TB Juppner, H AF Gardella, TJ Jensen, GS Luck, M Usdin, TB Juppner, H TI Converting parathyroid hormone-related peptide (PTHrP) into a potent PTH-2 receptor agonist SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP 77 EP 77 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500077 ER PT J AU Behar, V Pines, M Nakamoto, C Greenberg, Z Bisello, A Stueckle, S Bessalle, R Usdin, TB Rosenblatt, M Suva, LJ Chorev, M AF Behar, V Pines, M Nakamoto, C Greenberg, Z Bisello, A Stueckle, S Bessalle, R Usdin, TB Rosenblatt, M Suva, LJ Chorev, M TI Distinct ligand specificity of two parathyroid hormone receptor subtypes. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 BETH ISRAEL HOSP,DIV BONE & MINERAL METAB,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. 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