FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wilson, PWF AF Wilson, PWF TI Diabetes mellitus and coronary heart disease SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Review DE diabetes; coronary heart disease ID ACUTE MYOCARDIAL-INFARCTION; IMPAIRED GLUCOSE-TOLERANCE; LEFT-VENTRICULAR DYSFUNCTION; CARDIOVASCULAR RISK-FACTORS; UNITED-STATES POPULATION; METABOLIC CONTROL; GLYCEMIC CONTROL; VASCULAR COMPLICATIONS; INSULIN-RESISTANCE; PLATELET-FUNCTION AB The prevalence of diabetes mellitus rises with age in men and women in the United States and in westernized regions, and the risk of vascular disease is typically increased twofold in diabetic men and threefold in diabetic women. Population-based data concerning the prevalence of diabetes mellitus and its impact on coronary heart disease (CHD) are reviewed. The vascular disease endpoints considered include death, angina pectoris, myocardial infarction (MI), cardiac failure, cardiac arrhythmias, and the experience of diabetics who have undergone angioplasty and revascularization. The impact of coronary risk factors in diabetics is considered for glycemic control, arterial pressure, microalbuminuria, and lipids. Recent guidelines and recommendations concerning lipids, glucose, and blood pressure for diabetics are discussed. This is a US government work. There are no restrictions on its use. C1 NHLBI, Framingham Heart Study, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Wilson, PWF (reprint author), 5 Thurber St, Framingham, MA 01701 USA. EM peter@fram.nhlbi.nih.gov NR 116 TC 71 Z9 74 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 1998 VL 32 IS 5 SU 3 BP S89 EP S100 DI 10.1053/ajkd.1998.v32.pm9820468 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 136GB UT WOS:000076849200007 PM 9820468 ER PT J AU Wilson, PWF Culleton, BF AF Wilson, PWF Culleton, BF TI Epidemiology of cardiovascular disease in the United States SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE coronary heart disease; cardiac failure; risk factors ID CORONARY HEART-DISEASE; PRIMARY-PREVENTION TRIAL; INDEPENDENT RISK FACTOR; VITAMIN-E CONSUMPTION; ALL-CAUSE MORTALITY; 10-YEAR FOLLOW-UP; MYOCARDIAL-INFARCTION; PHYSICAL-ACTIVITY; ARTERY DISEASE; BLOOD-PRESSURE AB A brief review of cardiovascular disease incidence and risk factors for coronary heart disease and cardiac failure Is presented. The emphasis is placed on evidence from Targe scale prospective studies, and the pertinent US guidelines and recommendations for care are provided. Key risk factors are considered, including lipids, blood pressure, smoking, and diabetes mellitus. Additional information is also given concerning the role of vitamins, homocysteine metabolism, and left ventricular hypertrophy. This review focuses on commonly accepted risk factors that are of particular interest to health professionals. This is a US government work. There are no restrictions on its use. C1 NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. RP Wilson, PWF (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01701 USA. EM peter@fram.nhlbi.nih.gov FU NHLBI NIH HHS [N01-HV-92922, N01-HV-52971] NR 90 TC 14 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 1998 VL 32 IS 5 SU 3 BP S56 EP S65 DI 10.1053/ajkd.1998.v32.pm9820465 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 136GB UT WOS:000076849200004 PM 9820465 ER PT J AU Letovsky, SI Whitehead, SHJ Paik, CH Miller, GA Gerber, J Herskovits, EH Fulton, TK Bryan, RN AF Letovsky, SI Whitehead, SHJ Paik, CH Miller, GA Gerber, J Herskovits, EH Fulton, TK Bryan, RN TI A brain image database for structure/function analysis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article AB BACKGROUND AND PURPOSE: Lesion-deficit-based structure-function analysis has traditionally been empirical and nonquantitative. Our purpose was to establish a new brain image database (BRAID) that allows the statistical correlation of brain functional measures with anatomic lesions revealed by clinical brain images. METHODS: Data on 303 participants in the MR Feasibility Study of the Cardiovascular Health Study were tested for lesion/deficit correlations. Functional data were derived from a limited neurologic examination performed at the time of the MR examination. Image data included 3D lesion descriptions derived from the MR examinations by hand segmentation. MR images were normalized in-plane using local, linear Talairach normalization. A database was implemented to support spatial data structures and associated geometric and statistical operations. The database stored the segmented lesions, patient functional scores, and several anatomic atlases, Lesion-deficit association was sought by contingency testing (chi(2)-test) for every possible combination of each neurologic variable and each labeled atlas structure. Significant associations that confirmed accepted lesion-deficit relationships were sought. RESULTS: Two-hundred thirty-five infarctlike lesions in 117 subjects were viewed collectively after mapping into Talairach cartesian coordinates. Anatomic structures most strongly correlated with neurologic deficits tended to be situated in anatomically appropriate areas. For example, infarctlike lesions associated with visual field defects were correlated with structures in contralateral occipital structures, including the optic radiations and occipital gyri, CONCLUSION: Known lesion-deficit correlations can be established by a database using a standard coordinate system for representing spatial data and incorporating functional and structural data together with appropriate query mechanisms. Improvements and further applications of this methodology may provide a powerful technique for uncovering new structure function relationships. C1 Johns Hopkins Hosp, Dept Radiol & Radiol Sci, Div Neuroradiol, Baltimore, MD 21287 USA. RP Bryan, RN (reprint author), NIH, Ctr Clin, Bldg 10,Room 1 C-660, Bethesda, MD 20892 USA. RI Bryan, R. Nick/P-1661-2014 FU NHLBI NIH HHS [N01-HC-15103]; NIA NIH HHS [R0I AG13743-01] NR 11 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 1998 VL 19 IS 10 BP 1869 EP 1877 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 149DJ UT WOS:000077589600017 PM 9874539 ER PT J AU Athayde, N Edwin, SS Romero, R Gomez, R Maymon, E Pacora, P Menon, R AF Athayde, N Edwin, SS Romero, R Gomez, R Maymon, E Pacora, P Menon, R TI A role for matrix metalloproteinase-9 in spontaneous rupture of the fetal membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the Society-of-Perinatal-Obstetricians CY FEB 02-07, 1998 CL MIAMI, FLORIDA SP Soc Perinatal Obstetricians DE premature rupture of the membranes; matrix metalloproteinases; gelatinase B; microbial invasion of amniotic cavity; amniotic fluid; chorioamnionitis; prematurity ID PREMATURE RUPTURE; TISSUE INHIBITOR; IV COLLAGENASES; PRETERM LABOR; DEGRADATION; ORGANIZATION; GELATINASES; INFECTION AB OBJECTIVES: Preterm premature rupture of fetal membranes is responsible for 30% to 40% of preterm deliveries. Fetal membranes are composed primarily of collagen. Matrix metalloproteinases are enzymes capable of degrading extracellular matrix macromolecules, including collagens. Expression of matrix metalloproteinase-g (gelatinase B, 92 kd) and its tissue inhibitor (tissue inhibitor of metalloproteinase-l) has been localized in amnion and chorion. The objective of this study was to determine whether rupture of fetal membranes and intrauterine infection are associated with changes in the expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1. STUDY DESIGN: Two hundred one women in the following categories had amniotic fluid retrieved: (1) preterm labor and intact membranes in the presence (n = 42) or absence (n = 21) of microbial invasion of the amniotic cavity, (2) preterm premature rupture of the membranes with (n = 29) or without (n = 23) microbial invasion of the amniotic cavity, and (3) term gestation with intact membranes (n = 50) or with premature rupture of the membranes (n = 40). Women in groups 1 and 2 were matched for gestational age at amniocentesis. Microbial invasion of the amniotic cavity was defined by a positive amniotic fluid culture for micro-organisms. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-l were measured with use of sensitive and specific immunoassays that were validated for amniotic fluid. RESULTS: Spontaneous rupture of membranes at term is associated with a significant increase in the amniotic fluid concentrations of matrix metalloproteinase-g (premature rupture of membranes, no labor: median 3.9 ng/mL, range 2.7 to 11.1 ng/mL vs no premature rupture of membranes, no labor: median <0.4 ng/mL, range <0.4 to 22.4 ng/mL; P < .001). Patients with preterm premature rupture of the membranes had higher median matrix metalloproteinase-g concentrations than those with preterm labor and intact membranes who were delivered at term (7.6 ng/mL, range <0.4 to 230.81 ng/mL vs <0.4 ng/mL, range <0.4 to 1650 ng/mL; P = .06). Women with microbial invasion of the amniotic cavity had higher median matrix metalloproteinase-9 concentrations than did those without microbial invasion regardless of membrane status (preterm labor: 54.5 ng/mL, range <0.4 to 3910 ng/mL vs <0.4 ng/mL, range <0.4 to 1650 ng/mL; P < .01; preterm premature rupture of membranes: 179.8 ng/mL, range <0.4 to 611 ng/mL vs 7.6 ng/mL, range <0.4 to 230.81; P < .001). CONCLUSION: Our data support a role for matrix metalloproteinase-9 in the mechanisms responsible for membrane rupture in term and preterm gestations. C1 Womens Hlth Res & Educ Fdn, Perinatal Res Ctr, Nashville, TN USA. Wayne State Univ, Hutzel Hosp, NICHD, Perinatol Res Branch,Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, NICHD, Perinatol Res Branch,Dept Obstet & Gynecol, 4707 St Antoine Blvd, Detroit, MI 48201 USA. NR 25 TC 134 Z9 139 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 1998 VL 179 IS 5 BP 1248 EP 1253 DI 10.1016/S0002-9378(98)70141-3 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 140BK UT WOS:000077066400028 PM 9822510 ER PT J AU Levinson, RD Hooks, JJ Wang, Y Chiu, MT Kellaway, J Chan, CC AF Levinson, RD Hooks, JJ Wang, Y Chiu, MT Kellaway, J Chan, CC TI Triple viral retinitis diagnosed by polymerase chain reaction of the vitreous biopsy in a patient with Richter syndrome SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CYTOMEGALOVIRUS RETINITIS; FLUID AB PURPOSE: To report the evaluation and identification of herpes viruses associated with retinitis in a patient with Richter syndrome. METHODS: Diagnostic vitrectomy was performed on a patient with systemic leukemia and retinitis, The vitreous sample was evaluated by cytology, analysis of cytokines by ELISA, and detection of virus by polymerase chain reaction. RESULTS: The vitreous biopsy specimen showed no malignant cells but predominant CD8(+) lymphocyte infiltration with elevated interferon gamma and interleukin-6, DNA amplification and Southern blot analysis demonstrated DNA of herpes simplex, varicella-zoster, and cytomegalovirus. CONCLUSION: Retinitis associated with multiple viruses in the vitreous biopsy may mimic leukemic infiltration in the eye. (Am J Ophthalmol 1998; 126:732-733. (C) 1998 by Elsevier Science Inc. All rights reserved,). C1 Eye Associates New Mexico & SW Colorado, Albuquerque, NM 87102 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX USA. RP Levinson, RD (reprint author), Eye Associates New Mexico & SW Colorado, 806 Martin Luther King Jr Ave NE, Albuquerque, NM 87102 USA. NR 3 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 1998 VL 126 IS 5 BP 732 EP 733 DI 10.1016/S0002-9394(98)00138-X PG 2 WC Ophthalmology SC Ophthalmology GA 136BQ UT WOS:000076838300020 PM 9822244 ER PT J AU Lippa, CF Fujiwara, H Mann, DMA Giasson, B Baba, M Schmidt, ML Nee, LE O'Connell, B Pollen, DA George-Hyslop, PS Ghetti, B Nochlin, D Bird, TD Cairns, NJ Lee, VMY Iwatsubo, T Trojanowski, JQ AF Lippa, CF Fujiwara, H Mann, DMA Giasson, B Baba, M Schmidt, ML Nee, LE O'Connell, B Pollen, DA George-Hyslop, PS Ghetti, B Nochlin, D Bird, TD Cairns, NJ Lee, VMY Iwatsubo, T Trojanowski, JQ TI Lewy bodies contain altered alpha-synuclein in brains of many familiar Alzheimer's disease patients with mutations in presenilin and amyloid precursor protein genes SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BODY DISEASE; DOWNS-SYNDROME; IMMUNOCYTOCHEMISTRY; IDENTIFICATION; DEGENERATION; DIAGNOSIS; DEMENTIA AB Missense mutations in the alpha-synuclein gene cause familial Parkinson's disease (PD), and alpha-synuclein is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer's disease (AD). To determine whether alpha-synuclein is a component of LBs in familial AD (FAD) patients with known mutations in presenilin (n = 65) or amyloid precursor protein (n = 9) genes, studies were conducted with antibodies to alpha-, beta-, and gamma-synuclein. LBs were detected with alpha- but not beta- or gamma-synuclein antibodies in 22% of FAD brains, and alpha-synuclein-positive LBs were most numerous in amygdala where some LBs co-localized with tau-positive neurofibrillary tangles. As 12 (63%) of 19 FAD amygdala samples contained alpha-synuclein-positive LBs, these inclusions may be more common in FAD brains than previously reported. Furthermore, alpha-synuclein antibodies decorated LB filaments by immunoelectron microscopy, and Western blots revealed that the solubility of alpha-synuclein was reduced compared with control brains. The presence of alpha-synuclein-positive LBs was not associated with any specific FAD mutation. These studies suggest that insoluble alpha-synuclein aggregates into filaments that form LBs in many FAD patients, and we speculate that these inclusions may compromise the function and/or viability of affected neurons in the FAD brain. C1 Allegheny Univ Hlth Sci, Dept Neurol, MCP Div, Philadelphia, PA 19129 USA. Univ Tokyo, Dept Neuropathol & Neurosci, Tokyo, Japan. Univ Manchester, Dept Pathol Sci, Manchester, Lancs, England. Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NINDS, Family Studies Unit, Ctr Clin, Bethesda, MD 20892 USA. Univ Massachusetts, Med Ctr, Dept Neurol, Worcester, MA 01655 USA. Univ Toronto, Dept Med Neurol, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Indiana Univ, Med Ctr, Dept Pathol, Indianapolis, IN USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. VA Med Ctr, Dept Neurol, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. Inst Psychiat, London, England. RP Lippa, CF (reprint author), Allegheny Univ Hlth Sci, Dept Neurol, MCP Div, 3300 Henry Ave, Philadelphia, PA 19129 USA. FU NIA NIH HHS [P30 AG010124, P30 AG010133, AG09215, P50 AG005136, P01 AG009215, AG10124, U01 AG006781, AG13623] NR 33 TC 323 Z9 326 U1 1 U2 8 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1998 VL 153 IS 5 BP 1365 EP 1370 DI 10.1016/S0002-9440(10)65722-7 PG 6 WC Pathology SC Pathology GA 135ME UT WOS:000076805100007 PM 9811326 ER PT J AU Lim, MS Straus, SE Dale, JK Fleisher, TA Stetler-Stevenson, M Strober, W Sneller, MC Puck, JM Lenardo, MJ Elenitoba-Johnson, KSJ Lin, AY Raffeld, M Jaffe, ES AF Lim, MS Straus, SE Dale, JK Fleisher, TA Stetler-Stevenson, M Strober, W Sneller, MC Puck, JM Lenardo, MJ Elenitoba-Johnson, KSJ Lin, AY Raffeld, M Jaffe, ES TI Pathological findings in human autoimmune lymphoproliferative syndrome SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article DE T-cell-rich B-cell lymphoma and nodular lymphocyte; predominance Hodgkin's disease; respectively ID FAS GENE-MUTATIONS; NEGATIVE T-CELLS; PEDIATRIC-PATIENTS; MICE; APOPTOSIS; DISEASE; LYMPHOCYTES; LIGAND; IMMUNODEFICIENCY; DIFFERENTIATION AB The defects in lymphocyte apoptosis that underlie the autoimmune lymphoproliferative syndrome (ALPS) are usually attributable to inherited mutations of the CD95 (Fas) gene. In this report, we present the histopathological and immunophenotypic features seen hi the lymph nodes (n = 16), peripheral blood (n = 10), bone marrow (n = 2), spleen (n = 3), and liver (n = 2) from 10 patients with ALPS, Lymph nodes showed marked paracortical hyperplasia. Interfollicular areas were expanded and populated by T cell receptor-alpha beta CD3(+) CD4(-)CD8(-) (double-negative, DN) T cells that were negative for CD45RO. CD45RA(+) T cells were increased in all cases studied. The paracortical infiltrate was a result of both reduced apoptosis and increased proliferation, as measured by in situ detection of DNA fragmentation and staining with MIB-1, respectively. The paracortical proliferation may be extensive enough to suggest a diagnosis of malignant lymphoma. Many of the paracortical lymphocytes expressed markers associated with cytotoxicity, such as perforin, TIA-1, and CD57, CD25 was negative. in addition, most lymph nodes exhibited florid follicular hyperplasia, often with focal progressive transformation of germinal centers; in some cases, follicular involution was seen. A polyclonal plasmacytosis also was present, The spleens were markedly enlarged, more than 10 times normal size. There was expansion of both white pulp and red pulp, with increased DN T cells. DN T cells also were observed in Liver biopsies exhibiting portal triaditis, In the peripheral blood, the T cells showed increased expression of HLA-DR and CD57 but not CD25, CD45RA(+) T cells were increased in the four cases studied. Polyclonal B cell lymphocytosis with expansion of CD5(+) B cells was a characteristic finding, Taken together, the histopathological and immunophenotypic findings, particularly in lymph nodes and peripheral blood, are sufficiently distinctive to suggest a diagnosis of ALPS. Of note, two affected family members of one proband developed lymphoma (T-cell-rich B-cell lymphoma and nodular lymphocyte predominance Hodgkin's disease, respectively). C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NIAID, Warren Grant Magnuson Clin Ctr, Clin Invest Lab, Bethesda, MD 20892 USA. NIAID, Warren Grant Magnuson Clin Ctr, Immunoregulat Lab, Bethesda, MD 20892 USA. NIAID, Warren Grant Magnuson Clin Ctr, Immunol Lab, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2N 202,10 Ctr Dr,MSC-1500, Bethesda, MD 20892 USA. EM elaine.jaffe@nih.gov NR 34 TC 125 Z9 129 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1998 VL 153 IS 5 BP 1541 EP 1550 DI 10.1016/S0002-9440(10)65742-2 PG 10 WC Pathology SC Pathology GA 135ME UT WOS:000076805100027 PM 9811346 ER PT J AU Fuhrer, MJ Keith, RA AF Fuhrer, MJ Keith, RA TI Facilitating patient learning during medical rehabilitation - A research agenda SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE learning; patient education; medical rehabilitation AB Although patient learning is widely acknowledged to be an integral part of many medical rehabilitation practices, it has been the subject of little systematic research. A workshop conducted August 18 to 19, 1997, was organized by the National Center for Medical Rehabilitation Research (National Institute of Child Health and Human Development, National Institutes of Health) and several co-sponsoring organizations to formulate recommendations concerning learning-oriented rehabilitation practices. The recommendations and their supporting rationale are summarized in the topic areas of motor learning and control, cognitive learning, recovery of functioning, generalization and transfer of training, and applications for patients with strokes, traumatic brain injury, amputations, and infants and children. C1 NICHHD, Natl Ctr Med Rehabil Res, NIH, Rockville, MD 20852 USA. Casa Colina Hosp, Pomona, CA USA. RP Fuhrer, MJ (reprint author), NICHHD, Natl Ctr Med Rehabil Res, NIH, Bldg 6100,Room 2A03,6100 Execut Blvd, Rockville, MD 20852 USA. RI Winstein, Carolee/A-8375-2008 NR 3 TC 18 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD NOV-DEC PY 1998 VL 77 IS 6 BP 557 EP 561 DI 10.1097/00002060-199811000-00022 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 147RZ UT WOS:000077487100017 PM 9862546 ER PT J AU Dastych, J Taub, D Hardison, MC Metcalfe, DD AF Dastych, J Taub, D Hardison, MC Metcalfe, DD TI Tyrosine kinase-deficient W-v c-kit induces mast cell adhesion and chemotaxis SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE stem cell factor; W/W-v mice; phosphatidylinositol 3-kinase-dependent adhesion; fibronectin ID CONNECTIVE-TISSUE-TYPE; SIGNAL TRANSDUCTION; STEEL FACTOR; HISTAMINE-SECRETION; HERBIMYCIN-A; MUTANT MICE; W/WV MICE; RECEPTOR; LIGAND; MUTATIONS AB W/W-v mice are deficient in tissue mast cells, and mast cells cultured from these mice do not proliferate in response to the c-kit ligand, stem cell factor (SCF). In this paper, we report that mouse bone marrow cultured mast cells derived from W/W-v mice do adhere to fibronectin in the presence of SCF and exhibit chemotaxis to SCF, and we explore this model for the understanding of c-kit-mediated signaling pathways. Both in vitro and in vivo (in intact cells) phosphorylation experiments demonstrated a low residual level of W/W-v c-kit protein phosphorylation. SCF-induced responses in W/W-v mast cells were abolished by the tyrosine kinase inhibitor herbimycin A and by the phospatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin but were not affected by protein kinase C inhibitors. These observations are consistent with the conclusions that W-v c-kit initiates a signaling process that is PI S-kinase dependent and that mutated W-v c-kit retains the ability to initiate mast cell adhesion and migration. C1 Polish Acad Sci, Dept Biogenic Amines, PL-90950 Lodz, Poland. NCI, Clin Serv Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Dastych, J (reprint author), Polish Acad Sci, Dept Biogenic Amines, POB 225, PL-90950 Lodz, Poland. NR 43 TC 9 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 1998 VL 275 IS 5 BP C1291 EP C1299 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 137UH UT WOS:000076934400016 PM 9814978 ER PT J AU Inoue, T Nielsen, S Mandon, B Terris, J Kishore, BK Knepper, MA AF Inoue, T Nielsen, S Mandon, B Terris, J Kishore, BK Knepper, MA TI SNAP-23 in rat kidney: colocalization with aquaporin-2 in collecting duct vesicles SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE syntaxin-4; VAMP-2; synaptobrevin-2; exocytosis ID REGULATED WATER CHANNEL; SYNAPTIC VESICLES; PLASMA-MEMBRANE; PROTEIN; VASOPRESSIN; FUSION; IDENTIFICATION; SYNAPTOBREVIN; SYNTAXIN; CELLS AB Vesicle targeting proteins ("SNAREs") have been proposed to direct vasopressin-induced trafficking of aquaporin-2 water channels in kidney collecting ducts. A newly identified SNARE protein, SNAP-23, is proposed to mediate vesicle targeting to the plasma membrane in diverse tissues. The current studies were done to determine whether SNAP-23 is expressed in collecting ducts with an intracellular distribution compatible with a role in aquaporin-2 trafficking. RT-PCR demonstrated SNAP-23 mRNA in microdissected collecting ducts and other tubular segments including the proximal tubule and thick ascending limb. Immunoblotting using a polyclonal antibody raised against a COOH-terminal peptide revealed a solitary band at an apparent molecular mass of 30 kDa in renal medullary membrane fractions and inner medullary collecting duct suspensions. Differential centrifugation revealed that SNAP-23 is present in membrane fractions including the low-density fraction enriched in intracellular vesicles. Immunocytochemistry revealed SNAP-23 labeling at both the apex and the cytoplasm of collecting duct principal cells. Immunoblotting of intracellular vesicles immunoisolated using an aquaporin-2 antibody revealed the presence of both SNAP-23 and synaptobrevin-2 (VAMP-2) in aquaporin-2-bearing vesicles. We conclude that SNAP-23 is strongly expressed in collecting duct principal cells, consistent with a role in vasopressin-regulated trafficking of aquaporin-2. However, localization of SNAP-23 in both intracytoplasmic vesicles and plasma membranes suggests a function different from that originally proposed for SNAP-25 in synaptic vesicle targeting. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Univ Aarhus, Inst Anat, Dept Cell Biol, DK-8000 Aarhus, Denmark. Uniformed Serv Univ Hlth Sci, Dept Physiol, Bethesda, MD 20814 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. NR 36 TC 60 Z9 61 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 1998 VL 275 IS 5 BP F752 EP F760 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 138QT UT WOS:000076984500011 PM 9815132 ER PT J AU Kwon, TH Frokiaer, J Knepper, MA Nielsen, S AF Kwon, TH Frokiaer, J Knepper, MA Nielsen, S TI Reduced AQP1, -2, and -3 levels in kidneys of rats with CRF induced by surgical reduction in renal mass SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE aquaporins; vasopressin; polyuria ID AQUAPORIN-2 WATER CHANNEL; ISOLATED UREMIC NEPHRON; COLLECTING DUCT; ARGININE VASOPRESSIN; FUNCTIONAL PROFILE; PROXIMAL TUBULE; REMNANT KIDNEY; HEART-FAILURE; EXPRESSION; FAMILY AB Urinary concentration characteristically decreases in response to a reduction in renal mass in chronic renal failure (CRF). In the present study, we examined whether there are changes in the expression of aquaporins in rats where CRF was induced by 5/6 nephrectomy. Plasma creatinine levels were significantly elevated consistent with significant CRF: 135.7 +/- 15.1 (n = 17, CRF) vs. 33.9 +/- 1.1 mu mol/l (n = 11, sham), P < 0.05. Two weeks after 5/6 nephrectomy, the remnant kidneys were hypertrophied, and total renal mass increased to 65 +/- 3% of sham levels (P < 0.05). Urine production increased markedly from 40 +/- 2 to 111 +/- 3 mu l.min(-1).kg(-1) in CRF rats (P < 0.05), whereas urine osmolality and solute-free water reabsorption decreased significantly. Quantitative immunoblotting of total kidney membrane fractions revealed a significant decrease in total kidney AQP2 expression in CRF rats to 43 +/- 12% of sham levels (P < 0.05). A similar reduction was observed for AQP1 and AQP3. Furthermore, the increased urine output and decreased urine osmolality persisted in CRF rats despite 7 days treatment with 1-desamino-[8-D-arginine]vasopressin (DDAVP, 0.1 mu g/h SC) compared with untreated sham-operated controls. Also, there was no change in AQP2 expression (which remained at 38 +/- 3% of sham levels, P < 0.05), urine output, or urine osmolality between CRF rats with or without DDAVP treatment. Immunocytochemistry confirmed the decreased AQP2 expression in collecting duct principal cells in CRF rats, with a predominant apical labeling. In conclusion, the results demonstrated that there was a significant vasopressin-resistant downregulation of AQP2 and AQP3 as well as downregulation of AQP1 associated with the polyuria in CRF rats. C1 Univ Aarhus, Inst Anat, Dept Cell Biol, DK-8000 Aarhus C, Denmark. Aarhus Univ Hosp, Dept Clin Physiol, DK-8000 Aarhus, Denmark. Inst Expt Clin Res, DK-8000 Aarhus, Denmark. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Univ Aarhus, Inst Anat, Dept Cell Biol, DK-8000 Aarhus C, Denmark. NR 50 TC 82 Z9 85 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 1998 VL 275 IS 5 BP F724 EP F741 PG 18 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 138QT UT WOS:000076984500009 PM 9815130 ER PT J AU Leavey, SF Arend, LJ Dare, H Dressler, GR Briggs, JP Margolis, BL AF Leavey, SF Arend, LJ Dare, H Dressler, GR Briggs, JP Margolis, BL TI Expression of Grb7 growth factor receptor signaling protein in kidney development and in adult kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE receptor tyrosine kinase; gene expression; reverse transcription-polymerase chain reaction; in situ hybridization; Grb7 ID SH2 DOMAIN PROTEINS; TYROSINE KINASE; BETA-RECEPTOR; GENE; FAMILY; ONCOGENE; CLONING; INSULIN; MICE; RET AB Grb7, a signaling protein whose physiological function is unknown, binds receptor tyrosine kinases important for normal kidney development. By investigating and correlating Grb7 gene expression with that reported for Grb7-binding receptors, we provide clues to Grb7 function(s). RT-PCR and immunoblot were used to demonstrate Grb7 gene and protein expression in the mature kidney. Additional RT-PCR studies detected gene expression in all microdissected adult nephron segments examined, except glomeruli, and in the mouse metanephric kidney from embryonic day 11 (Ell) through to day 17(E17). In situ hybridization at E14 demonstrated the following cellular pattern of localization: Grb7 mRNA in metanephric epithelia of mesenchymal and ureteric bud origin; no expression in the undifferentiated mesenchyme; and little expression in podocyte-destined cells or primitive glomeruli. Grb7 mRNA was also present in the epithelia of the lung and gut at E14. Thus Grb7 may have a basic function in growth factor signaling in terminally differentiated epithelia along the nephron and in developing epithelia in the kidney, lung, and gut. It is localized in a pattern permissive for a role in Her2 and Ret receptor signaling. C1 Univ Michigan, Med Ctr, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA. Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Leavey, SF (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, Div Nephrol, 1150 W Med Ctr Dr,1560 Med Sci Bldg 2, Ann Arbor, MI 48109 USA. RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU NIDDK NIH HHS [IF32-DK-09471-01] NR 26 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 1998 VL 275 IS 5 BP F770 EP F776 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 138QT UT WOS:000076984500013 PM 9815134 ER PT J AU Miller, DS Sussman, CR Renfro, JL AF Miller, DS Sussman, CR Renfro, JL TI Protein kinase C regulation of p-glycoprotein-mediated xenobiotic secretion in renal proximal tubule SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE confocal microscopy; fluorescence microscopy; killifish; multidrug resistance transporter; phorbol ester; renal secretion; staurosporine; teleost fish; winter flounder ID MULTIDRUG-RESISTANCE GENE; TRANSEPITHELIAL TRANSPORT; DRUG TRANSPORT; ORGANIC-ANIONS; PHOSPHORYLATION; EXPRESSION; EPITHELIUM; MECHANISMS; CULTURE; TISSUES AB Fluorescence microscopy, fluorescent substrates [daunomycin and a fluorescent cyclosporin A (CSA) derivative] and digital image analysis were used to examine the role of protein kinase C (PKC) in the control of p-glycoprotein in killifish renal proximal tubules. PKC activators, phorbol ester (phorbol la-myristate 13-acetate, PMA) and dioctylglycerol, reduced luminal drug accumulation, and protein kinase inhibitors, staurosporine and l-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), increased luminal accumulation; a PMA analog that does not activate PKC was without effect. PMA effects were blocked by staurosporine. The increase in luminal fluorescence caused by staurosporine was blocked by the p-glycoprotein substrate, CSA, indicating that this component of transport was indeed mediated by p-glycoprotein. Neither PMA, dioctylglycerol, nor protein kinase inhibitors altered cellular drug accumulation. Finally, in primary cultures of flounder proximal tubule cells, PMA decreased transepithelial [(3)H]daunomycin secretion. This pharmacological approach demonstrates that in teleost renal proximal tubule, p-glycoprotein-mediated xenobiotic secretion is negatively correlated with changes in PKC activity, a finding that conflicts with results from studies using mammalian tumor cells that express p-glycoprotein. C1 NIEHS, Lab Pharmacol & Chem, NIH, Intracellular Regulat Sect, Res Triangle Pk, NC 27709 USA. Univ Connecticut, Dept Physiol & Neurobiol, Storrs, CT 06269 USA. RP Miller, DS (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, Intracellular Regulat Sect, POB 12233, Res Triangle Pk, NC 27709 USA. NR 35 TC 24 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 1998 VL 275 IS 5 BP F785 EP F795 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 138QT UT WOS:000076984500015 PM 9815136 ER PT J AU Stone, EJ McKenzie, TL Welk, GJ Booth, ML AF Stone, EJ McKenzie, TL Welk, GJ Booth, ML TI Effects of physical activity interventions in youth - Review and synthesis SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE physical fitness; youth; intervention studies; community; schools; schoolage population; African Americans; Hispanics; physical education and training; leisure activities (recreation) ID ELEMENTARY-SCHOOL-CHILDREN; CARDIOVASCULAR HEALTH CATCH; CORONARY HEART-DISEASE; ADOLESCENT TRIAL; RISK-FACTORS; OBESITY PREVENTION; ACTIVITY PROGRAM; YOUNG-CHILDREN; UNITED-STATES; PUBLIC-HEALTH AB Introduction: Physical inactivity has been identified as an important public health concern for youth. School and community settings can be important infrastructures for promoting physical activity (PA). This paper reviews studies of physical activity in school and community settings among preschool through college-aged persons to determine characteristics and effects of interventions. Studies in progress are included. Methods: Studies from 1980 to 1997 testing physical activity interventions in schools and community settings were identified by computerized search methods and reference lists of published reviews. Studies needed to have used a quantitative assessment of PA, used a comparison or control group, included participants who were preschool through college age, and be conducted in the United States or foreign school or community settings. Significance of effects was examined overall and for various types of interventions. Results: Twenty-two school-based studies were reviewed, 14 completed and 8 in progress. Three studies were in countries other than the United States. The 8 studies in progress were all in the United States. Only 7 community studies were reviewed, all in the United States. Four studies were in progress. Several community studies involved a high percentage of African-American or Hispanic youth and their families. Studies showing the best results used randomized designs, valid and reliable measurements, and more extensive interventions. Some follow-up results showed PA was sustained after interventions ended. Conclusions: The collection of school and community studies is limited for several age groups with none below third grade and only three at college age. There are few community studies. The most is known about upper-elementary-age-students, including the first multicenter randomized trial to report significant results for increasing moderate to vigorous physical activity (MVPA) in physical education (PE) and increase vigorous PA outside of school. A number of older study designs were weak and assessments less than optimal, but studies in progress are stronger. Special attention is needed for girls, middle schools, and community settings for all youth. More objective assessments are needed for measuring PA outside of school and in younger children, since they cannot provide reliable self-report. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. San Diego State Univ, Dept Exercise & Nutr Sci, San Diego, CA 92120 USA. Cooper Inst Aerob Res, Div Childhood & Adolescent Hlth, Dallas, TX 75230 USA. Univ Sydney, Dept Publ Hlth & Community Med, Natl Ctr Hlth Promot, Sydney, NSW 2006, Australia. RP Stone, EJ (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr,Room 8134,MSC 7936, Bethesda, MD 20892 USA. RI Loureiro, Nuno/I-6400-2012 OI Loureiro, Nuno/0000-0002-1166-3219 NR 108 TC 255 Z9 257 U1 5 U2 45 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 1998 VL 15 IS 4 BP 298 EP 315 DI 10.1016/S0749-3797(98)00082-8 PG 18 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 138QC UT WOS:000076982900004 PM 9838974 ER PT J AU Simons-Morton, DG Calfas, KJ Oldenburg, B Burton, NW AF Simons-Morton, DG Calfas, KJ Oldenburg, B Burton, NW TI Effects of interventions in health care settings on physical activity or cardiorespiratory fitness SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE physical fitness; exercise; cardiovascular disease; primary prevention; intervention studies; leisure activities (recreation) ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; CARDIAC REHABILITATION; CONTROLLED TRIAL; COMPREHENSIVE REHABILITATION; COUNSELING PRACTICES; EXERCISE PROGRAM; GENERAL-PRACTICE; RISK REDUCTION; HEART-DISEASE AB Introduction: This paper reviews studies of physical activity interventions in health care settings to determine effects on physical activity and/or fitness and characteristics of successful interventions. Methods: Studies testing interventions to promote physical activity in health care settings for primary prevention (patients without disease) and secondary prevention (patients with cardiovascular disease [CVD]) were identified by computerized search methods and reference lists of reviews and articles. Inclusion criteria included assignment to intervention and control groups, physical activity or cardiorespiratory fitness outcome measures, and, for the secondary prevention studies, measurement 12 or more months after randomization. The number of studies with statistically significant effects was determined overall as well as for studies testing interventions with various characteristics. Results: Twelve studies of primary prevention were identified, seven of which were randomized. Three of four randomized studies with short-term measurement (4 weeks to 3 months after randomization), and two of five randomized studies with long-term measurement (6 months after randomization) achieved significant effects on physical activity. Twenty-four randomized studies of CVD secondary prevention were identified; 13 achieved significant effects on activity and/or fitness at twelve or more months. Studies with measurement at two time points showed decaying effects over time, particularly if the intervention were discontinued. Successful interventions contained multiple contacts, behavioral approaches, supervised exercise, provision of equipment, and/or continuing intervention. Many studies had methodologic problems such as low follow-up rates. Conclusion: Interventions in health care settings can increase physical activity for both primary and secondary prevention. Long-term effects are more likely with continuing intervention and multiple intervention components such as supervised exercise, provision of equipment, and behavioral approaches. Recommendations for additional research are given. C1 NHLBI, Prevent Sci Res Grp, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. San Diego State Univ, San Diego, CA 92182 USA. Queensland Univ Technol, Red Hill, Qld, Australia. RP Simons-Morton, DG (reprint author), NHLBI, Prevent Sci Res Grp, Div Epidemiol & Clin Applicat, 2 Rockledge Ctr,Room 8138,6701 Rockledge Dr,MSC 7, Bethesda, MD 20892 USA. RI Burton, Nicola/G-3313-2010; OI Burton, Nicola/0000-0002-3221-2265; Oldenburg, Brian/0000-0002-7712-5413 NR 67 TC 97 Z9 97 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 1998 VL 15 IS 4 BP 413 EP 430 DI 10.1016/S0749-3797(98)00078-6 PG 18 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 138QC UT WOS:000076982900011 PM 9838981 ER PT J AU Heinz, A Ragan, P Jones, DW Hommer, D Williams, W Knable, MB Gorey, JG Doty, L Geyer, C Lee, KS Coppola, R Weinberger, DR Linnoila, M AF Heinz, A Ragan, P Jones, DW Hommer, D Williams, W Knable, MB Gorey, JG Doty, L Geyer, C Lee, KS Coppola, R Weinberger, DR Linnoila, M TI Reduced central serotonin transporters in alcoholism SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID HEALTHY-HUMAN SUBJECTS; I-123 BETA-CIT; IN-VIVO; DOPAMINE TRANSPORTER; SYNAPTIC DOPAMINE; MESSENGER-RNA; BINDING; ETHANOL; BRAIN; SENSITIVITY AB Objective: Dysfunction of monoamine uptake mechanisms has been implicated in the pathogenesis of alcohol dependence. The authors explored whether serotonergic dysfunction is associated with anxiety and depression, which increase the risk of relapse in alcoholics. Method: The availability of serotonin and dopamine transporters in 22 male alcoholics and 13 healthy male volunteers was measured with the use of [I-123]beta-CIT and single photon emission computed tomography, and psychopathological correlates were assessed. Results: A significant reduction (a mean of about 30%) in the availability of brainstem serotonin transporters was found in the alcoholics, which was significantly correlated with lifetime alcohol consumption and with ratings of depression and anxiety during withdrawal. Conclusions: The findings support the hypothesis of serotonergic dysfunction in alcoholism and in withdrawal-emergent depressive symptoms. C1 NIMH, St Elizabeths Hosp, Ctr Neurosci, Clin Brain Disorders Branch, Washington, DC 20032 USA. NIAAA, Div Intramural Clin Biol Res, Clin Studies Lab, Bethesda, MD 20892 USA. RP Heinz, A (reprint author), Ruhr Univ Bochum, St Josef Hosp, Dept Neurol, Gudrunstr 56, D-44791 Bochum, Germany. EM jonesjeinz@aol.com NR 51 TC 196 Z9 200 U1 1 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1998 VL 155 IS 11 BP 1544 EP 1549 PG 6 WC Psychiatry SC Psychiatry GA 135DQ UT WOS:000076786000013 PM 9812115 ER PT J AU Perlmutter, SJ Garvey, MA Castellanos, X Mittleman, BB Giedd, J Rapoport, JL Swedo, SE AF Perlmutter, SJ Garvey, MA Castellanos, X Mittleman, BB Giedd, J Rapoport, JL Swedo, SE TI A case of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID OBSESSIVE COMPULSIVE SCALE; TOURETTES-SYNDROME; SYDENHAMS CHOREA; CHILDHOOD C1 NIMH, Pediat & Dev Neuropsychiat Branch, Rockville, MD 20857 USA. NIMH, Child Psychiat Branch, Rockville, MD 20857 USA. RP Perlmutter, SJ (reprint author), 1800 Michael Faraday,Suite 206, Reston, VA 20190 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 21 TC 37 Z9 40 U1 2 U2 4 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1998 VL 155 IS 11 BP 1592 EP 1598 PG 7 WC Psychiatry SC Psychiatry GA 135DQ UT WOS:000076786000021 PM 9812123 ER PT J AU Postolache, TT Hardin, TA Myers, FS Turner, EH Yi, LY Barnett, RL Matthews, JR Rosenthal, NE AF Postolache, TT Hardin, TA Myers, FS Turner, EH Yi, LY Barnett, RL Matthews, JR Rosenthal, NE TI Greater improvement in summer than with light treatment in winter in patients with seasonal affective disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID THERAPY AB Objective: The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. Method: By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: during winter when the patients were depressed, during winter following 2 weeks of light therapy, and during the following summer. They compared the three conditions by using Friedman's analysis of variance and the Wilcoxon signed ranks test, Results: The patients' scores on the depression scale were significantly higher after 2 weeks of light therapy in winter than during the following summer. Conclusions: Light treatment for 2 weeks in winter is only partially effective when compared to summer, Further studies will be necessary to assess if summer's light or other factors are the main contributors to this difference. C1 NIMH, Sect Biol Rhythms, Clin Psychobiol Branch, Bethesda, MD 20892 USA. RP Postolache, TT (reprint author), NIMH, Sect Biol Rhythms, Clin Psychobiol Branch, Bldg 10,Rm 3S231, Bethesda, MD 20892 USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 9 TC 12 Z9 12 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1998 VL 155 IS 11 BP 1614 EP 1616 PG 3 WC Psychiatry SC Psychiatry GA 135DQ UT WOS:000076786000028 PM 9812130 ER PT J AU Harik-Khan, RI Wise, RA Fozard, JL AF Harik-Khan, RI Wise, RA Fozard, JL TI Determinants of maximal inspiratory pressure - The Baltimore Longitudinal Study of Aging SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID RESPIRATORY MUSCLE STRENGTH; NORMAL VALUES; EXPIRATORY PRESSURES; ADULTS; DECLINE; MASS; MEN AB A variety of methods for subject selection and test procedures have been used for the determination of normal values and reference equations for maximal inspiratory pressure (MIP). In the cross-sectional study described here, we made MIP measurements on 668 men and women in the Baltimore Longitudinal Study of Aging (BLSA), using a standardized electronic procedure. Results were combined with spirometric and anthropometric measurements. After subjecting them to rigorous health screening, we analyzed a well-defined, healthy subgroup of 139 men and 128 women with a wide age range (20 to 90 yr), using multiple linear regression, for the purpose of determining the effect of age, other correlates, normal values, and gender-specific reference equations for MIP. The gender effect was strong, with the average MIP values of the men being about 30% higher than those of the women (101 cm H2O and 72 cm H2O, respectively). The reference equation for men is: MIP +/- standard error of the estimate (SEE) = 126 - 1.028 x age + 0.343 x weight (kg) +/- (22.4); and for women: MIP +/- SEE = 171 - 0.694 x age + 0.861 x weight (kg) -0.743 x height (cm) +/- (18.5). These equations may be used for the assessment of inspiratory muscle strength. C1 NIA, Gerontol Res Ctr, Longitudinal Study Sect, Clin Invest Lab, Baltimore, MD 21224 USA. Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. RP Harik-Khan, RI (reprint author), NIA, Gerontol Res Ctr, Longitudinal Study Sect, Clin Invest Lab, 5600 Nathan Shock Dr,Box 6, Baltimore, MD 21224 USA. RI Fozard, James Leonard/B-3660-2009; OI Wise, Robert/0000-0002-8353-2349 NR 27 TC 84 Z9 97 U1 1 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV PY 1998 VL 158 IS 5 BP 1459 EP 1464 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 139TA UT WOS:000077044700014 PM 9817693 ER PT J AU Frokiaer, J Marples, D Knepper, MA Nielsen, S AF Frokiaer, J Marples, D Knepper, MA Nielsen, S TI Pathophysiology of aquaporin-2 in water balance disorders SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE water channels; vasopressin; nephrogenic diabetes insipidus; renal disease; water retention ID INDUCED DOWN-REGULATION; RAT-KIDNEY MEDULLA; CHANNEL EXPRESSION; COLLECTING DUCT; NEPHROTIC SYNDROME; SODIUM RETENTION; HEART-FAILURE; VASOPRESSIN; CIRRHOSIS; PATHOGENESIS AB The recent identification of aquaporin water channel proteins has provided detailed information about the molecular basis for transepithelial water transport. At least five aquaporins have been identified in the kidney; they have provided detailed molecular insight into the fundamental physiology of water balance. This article focuses primarily on the physiology and pathophysiologic significance of the vasopressin regulated water channel aquaporin-2 (AQP2) in a number of conditions where body water balance is disturbed. AQP2 is regulated by vasopressin by both short- and longterm mechanisms. Acutely, vasopressin induces exocytic insertion of AQP2 into the apical plasma membrane to increase collecting duct water reabsorption. Moreover, long-term regulation of body water balance is achieved by changes in total collecting duct levels of AQP2. Recent studies have documented that both vasopressin and vasopressin-independent regulation play important roles in this. In conditions with acquired nephrogenic diabetes insipidus (eg, lithium treatment, hypokalemia, postobstructive polyuria), AQP2 expression and targeting have been found to be markedly reduced, providing an explanation for the polyuria and the inability to concentrate urine associated with these conditions. Conversely, in conditions with water retention (eg, heart failure, pregnancy), it has been shown that AQP2 levels and plasma membrane targeting are increased. Continued analysis of aquaporins is providing detailed molecular insight into the physiology and pathophysiology of water balance disorders. C1 Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus, Denmark. Aarhus Univ Hosp, Dept Clin Physiol, DK-8000 Aarhus, Denmark. Aarhus Univ, Inst Expt Clin Res, DK-8000 Aarhus, Denmark. Univ Leeds, Dept Physiol, Leeds LS2 9JT, W Yorkshire, England. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus, Denmark. EM SN@ANA.AAU.DK NR 44 TC 19 Z9 24 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD NOV PY 1998 VL 316 IS 5 BP 291 EP 299 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 137TW UT WOS:000076933300002 PM 9822111 ER PT J AU Chu, MC Dong, XQ Zhou, X Garon, CF AF Chu, MC Dong, XQ Zhou, X Garon, CF TI A cryptic 19-kilobase plasmid associated with US isolates of Yersinia pestis: A dimer of the 9.5-kilobase plasmid SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID VIRULENCE-ASSOCIATED FACTORS; CATASTROPHE HYPOTHESIS; GENETIC-ANALYSIS; PLAGUE AB Yersinia pestis, the etiologic agent of plague, carries three prototypic plasmids with sizes of 110 kb (pFra, pTox), 70 kb (pLcr, pVW, pCad), and 9.5 kb (pPla, pPst). Studies suggest that geographic isolates of Y. pestis may be differentiated by plasmid profiles. Yersinia pestis isolated from the western United States harbor an additional plasmid, estimated to be approximately 19 kb in size. This cryptic plasmid was characterized by restriction endonuclease digestion, amplification and sequencing of the plasminogen activator gene segment, Southern blotting, and visualized by electron microscopy. Results revealed that this cryptic plasmid is a supercoiled DNA plasmid, 18.85 +/- 0.59 (mean +/- SD) kb in length, and is a dimer of the 9.5-kb plasmid. The genetic reason for the appearance of this form of the 9.5-kb plasmid in Y. pestis from Arizona, California, Colorado, New Mexico, and Texas is under study. C1 Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, Ft Collins, CO 80522 USA. Yunnan Prov Inst Epidem Dis Control & Res, Dali, Yunnan, Peoples R China. Chinese Base Control & Treatment Plague & Brucell, Baicheng, Jilin, Peoples R China. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Chu, MC (reprint author), Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, POB 2087, Ft Collins, CO 80522 USA. NR 26 TC 16 Z9 21 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 1998 VL 59 IS 5 BP 679 EP 686 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 141JL UT WOS:000077140000004 PM 9840581 ER PT J AU Sang, CN Hostetter, MP Gracely, RH Chappell, AS Schoepp, DD Lee, G Whitcup, S Caruso, R Max, MB AF Sang, CN Hostetter, MP Gracely, RH Chappell, AS Schoepp, DD Lee, G Whitcup, S Caruso, R Max, MB TI AMPA/kainate antagonist LY293558 reduces capsaicin-evoked hyperalgesia but not pain in normal skin in humans SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Neuroscience CY OCT 25-30, 1997 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci DE allodynia; glutamate; nociception; sensory testing ID EXCITATORY AMINO-ACIDS; CENTRAL SENSITIZATION; GLUTAMATE RECEPTORS; MECHANICAL HYPERALGESIA; (3S,4AR,6R,8AR)-6-<2-(1(2)H-TETRAZOLE-5-YL)ETHYL>DECAHYDROISOQUINOLINE-3 -CARBOX.; POSTHERPETIC NEURALGIA; SYNAPTIC TRANSMISSION; DIABETIC NEUROPATHY; NMDA RECEPTORS; IN-VITRO AB Background: Animal studies suggest that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-kainate (AMPA-KA) receptors are involved in pain processing. The effects of the competitive AMPA-KA antagonist LY293558 in two types of experimental pain in human volunteers, brief pain sensations in normal skin, and mechanical allodynia-piaprick hyperalgesia were studied after the Injection of intradermal capsaicin. Methods: Brief intravenous infusions of the competitive AMPA-KA antagonist LY293558 were given to 25 healthy volunteers to examine acute toxicity and analgesic effects. Fifteen volunteers then entered a double-blinded, three-period crossover study. In a Phase II study, LY293558 infusions (100% maximally tolerated dose vs. 33% maximally tolerated dose vs. placebo) began 10 min after intradermal injection of 250 mu g capsaicin in volar forearm. Spontaneous pain, areas of mechanical allodynia and pinprick. hyperalgesia, and side effects were determined every 5 min for 60 min. Results: The median maximally tolerated dose was 1.3 +/- 0.4 (range, 0.9-2.0) mg/kg. Tests of cognitive and nearological function were unchanged. Dose-limiting side effects were hazy vision in 95% of volunteers and sedation in 40%. There were no significant changes in electrical or warm-cool detection and pain thresholds or heat pain thresholds. LY293558 had Little effect on brief pain sensations in normal skin. Both high and low doses of LY293558 significantly reduced pain intensity, pain unpleasantness, and the area in which light brush evoked pain after intradermal capsaicin. There was a trend toward a dose-response effect of LY293558 on the area in which pinprick evoked pain after intradermal capsaicin, which did not reach statistical significance. Conclusions: The authors infer that AMPA-KA receptor blockade reduces the spinal neuron sensitization that mediates capsaicin-evoked pain and allodynia. The low incidence of side effects at effective doses of LY293558 suggests that this class of drugs may prove to be useful in clinical pain states. C1 NIH, Bethesda, MD 20892 USA. Lilly Res Labs, Indianapolis, IN USA. RP Sang, CN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, 55 Fruit St,Clin 3, Boston, MA 02114 USA. NR 46 TC 83 Z9 84 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 1998 VL 89 IS 5 BP 1060 EP 1067 DI 10.1097/00000542-199811000-00005 PG 8 WC Anesthesiology SC Anesthesiology GA 137AN UT WOS:000076891400004 PM 9821993 ER PT J AU Hampton, RR Shettleworth, SJ Westwood, RP AF Hampton, RR Shettleworth, SJ Westwood, RP TI Proactive interference, recency, and associative strength: Comparisons of black-capped chickadees and dark-eyed juncos SO ANIMAL LEARNING & BEHAVIOR LA English DT Article ID FOOD-STORING BIRDS; RADIAL-ARM MAZE; SPATIAL MEMORY; DORSAL STRIATUM; HIPPOCAMPUS; PERFORMANCE; SPECIALIZATION; LOCATION; AMYGDALA; LESIONS AB Black-capped chickadees (Parus atricapillus) and dark-eyed juncos (Junco hyemalis) were required to match to the last item from a series of up to three stimuli differing in both location and color. When rewarded for pecking the target stimulus during the study phase of each series, black-capped chickadees demonstrated proactive interference (PI) from stimuli presented prior to the target, whereas juncos did not. When they made an error, chickadees were more Likely than were juncos to choose a distracter from the study series rather than a novel stimulus. When reward was no longer associated with presentation of the final target sample in a series, juncos also suffered PI. These results indicate that chickadees and juncos differ in the degree to which the recency of stimuli and the associative strength of stimuli control correct matching. C1 Univ Toronto, Toronto, ON, Canada. RP Hampton, RR (reprint author), NIMH, Neuropsychol Lab, Bldg 49,Room 1B-80, Bethesda, MD 20892 USA. RI Piper, Walter/B-7908-2009 NR 32 TC 16 Z9 16 U1 0 U2 11 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0090-4996 J9 ANIM LEARN BEHAV JI Anim. Learn. Behav. PD NOV PY 1998 VL 26 IS 4 BP 475 EP 485 DI 10.3758/BF03199241 PG 11 WC Psychology, Biological; Behavioral Sciences; Psychology, Experimental; Zoology SC Psychology; Behavioral Sciences; Zoology GA 150XB UT WOS:000077690400013 ER PT J AU Bara-Jimenez, W Catalan, MJ Hallett, M Gerloff, C AF Bara-Jimenez, W Catalan, MJ Hallett, M Gerloff, C TI Abnormal somatosensory homunculus in dystonia of the hand SO ANNALS OF NEUROLOGY LA English DT Article ID DIPOLE SOURCE ANALYSIS; EVOKED POTENTIALS; FOCAL DYSTONIA; ADULT MONKEYS; CORTEX; LOCALIZATION; IMPROVEMENTS; CRAMPS AB Abnormalities of the sensory system have been proposed as causative factors for dystonia By mapping the human cortical hand somatosensory area of 6 patients with focal dystonia of the hand, we found an abnormality of the normal homuncular organization of the finger representations in the primary somatosensory cortex (S1). Although a remote antecedent event or even a developmental anomaly cannot entirely be ruled out, our findings may support the concept that abnormal plasticity is involved in the development of dystonia. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. RI Abbott, J./B-2976-2008 OI Abbott, J./0000-0001-6468-7284 NR 20 TC 232 Z9 237 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1998 VL 44 IS 5 BP 828 EP 831 DI 10.1002/ana.410440520 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 136VX UT WOS:000076880800019 PM 9818942 ER PT J AU Lin, L Gillies, SD Schlom, J Pestka, S AF Lin, L Gillies, SD Schlom, J Pestka, S TI Construction of phosphorylatable monoclonal antibody CC49 with a casein kinase II recognition site SO ANTICANCER RESEARCH LA English DT Article DE monoclonal antibody; Chimeric antibody; Casein kinase II protein kinase recognition site; casein kinase II protein kinase; protein kinase; tumor associated antigens; cancer therapy; cancer diagnosis ID SUBSTRATE-SPECIFICITY DETERMINANTS; TUMOR-ASSOCIATED ANTIGENS; COLORECTAL-CANCER; INTERFERON-ALPHA; PROTEIN-KINASE; COLON CANCER; PHASE-I; B72.3; EXPRESSION; CELLS AB A phosphorylation site for casein kinase II was introduced into chimeric monoclonal antibody CC49 (MAb-chCC49) by site-specific mutation of the coding sequence. The phosphorylation site for the casein kinase II was positioned at the carboxyl terminus of the heavy chain constant region of the MAb-chCC49. The resultant modified MAb-chCC49CKII was expressed in NS0 cells and purified. The MAb-chCC49CKII protein was phosphorylated by casein kinase II with [gamma-32P]ATP to high radiospecific activity. The P-32-labeled MAb-chCC49CKII binds to cells expressing TAG-72 antigens. The introduction of the phosphorylation sites for casein kinase II into monoclonal antibodies (MAb) provides a new reagent for the diagnosis and treatment of cancers. This demonstrates that the casein kinase II recognition site can also be used to introduce phosphorylation sites into proteins. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA. Lexigen Pharmaceut Corp, Lexington, MA 02173 USA. NCI, Bethesda, MD 20892 USA. RP Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, 675 Hoes Lane, Piscataway, NJ 08854 USA. FU NCI NIH HHS [R01 CA46465, R01 CA52363] NR 38 TC 5 Z9 5 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 EI 1791-7530 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 1998 VL 18 IS 6A BP 3971 EP 3978 PG 8 WC Oncology SC Oncology GA 157HR UT WOS:000078056000001 PM 9891433 ER PT J AU Steele, VE Wyatt, GP Kellof, GJ Elmore, E AF Steele, VE Wyatt, GP Kellof, GJ Elmore, E TI Differential growth response to exogenous calcium in normal and carcinogen-exposed primary human keratinocyte cell cultures SO ANTICANCER RESEARCH LA English DT Article DE growth response; calcium; keratinocytes; carcinogen; retinoic acid; chemoprevention ID MOUSE EPIDERMAL-CELLS; BRONCHIAL EPITHELIAL-CELLS; TERMINAL DIFFERENTIATION; PROLIFERATION; SERUM; RESISTANT AB The purpose of these studies was to examine an early carcinogen-induced change in primary human epithelial cell cultures and to attempt to reverse this change with retinoic acid. Pnmary cultures of human foreskin keratinocytes were prepared and exposed to the carcinogen propane sultone. After each passage, a portion of cells were plated into medium containing increasing amounts of calcium. In a series of experiments it became evident that carcinogen exposed cells continued to grow in the presence of added calcium. Solvent control cell growth was decreased under such conditions. This new phenotype became apparent after the third subculture, but was pronounced after the fourth subculture. The addition of retinoic acid to the culture medium at each medium change reduced this effect and the keratinocytes grew more slowly, similar to control cells, in the presence of added calcium;The results suggest that carcinogen-exposed human keratinocytes acquire a resistance to calcium-induced differentiation or growth cessation and that retinoic acid can ameliorate this process. Although the mechanism of retinoic acid's inhibition remains unclear; these studies do provide a human cell model system which can be used to screen potential chemopreventive agents and for further mechanistic research. C1 ManTech Environm Sci Inc, Cellular & Mol Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Steele, VE (reprint author), NCI, Chemoprevent Lab, DCP, Execut Plaza N,Room 201,MSC 7322, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CN55503-01] NR 17 TC 3 Z9 3 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 1998 VL 18 IS 6A BP 4067 EP 4070 PG 4 WC Oncology SC Oncology GA 157HR UT WOS:000078056000014 PM 9891446 ER PT J AU Petraitis, V Petraitiene, R Groll, AH Bell, A Callender, DP Sein, T Schaufele, RL McMillian, CL Bacher, J Walsh, TJ AF Petraitis, V Petraitiene, R Groll, AH Bell, A Callender, DP Sein, T Schaufele, RL McMillian, CL Bacher, J Walsh, TJ TI Antifungal efficacy, safety, and single-dose pharmacokinetics of LY303366, a novel echinocandin B, in experimental pulmonary aspergillosis in persistently neutropenic rabbits SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO ACTIVITY; AMPHOTERICIN-B; CILOFUNGIN; GRANULOCYTOPENIA; LY-303366; LY121019; SYNTHASE; INVITRO AB LY303366 is a novel semisynthetic derivative of echinocandin B and a potent inhibitor of fungal (1,3)-beta-D-glucan synthase. The antifungal efficacy and safety of LY303366 were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due to Aspergillus firmigatus in persistently neutropenic rabbits. Treatment study groups sere either not treated (controls) or treated with amphotericin B (AmB) at 1 mg/kg of body weight per day or with LY303366 at 1, 5, 10, and 20 mg/kg/day. In rabbits treated with LY303366, there was a significant improvement in survival and a reduction in organism-mediated pulmonary injury measured by the number of infarcts, total lung weight, and ultrafast computerized tomography scan pulmonary lesion score. Rabbits receiving prophylactic LY303366 also demonstrated significant improvement in survival and reduction in organism-mediated pulmonary injury. AmB and LY303366 had comparable therapeutic efficacies by all parameters with the exception of reduction in tissue burden of A. fumigatus, where AmB was superior to LY303366. LY303366 demonstrated a dose-dependent effect on hyphal injury with progressive truncation, swelling, and vacuolization. LY303366 administered in single doses of 1, 5, 10, and 20 mg/kg demonstrated dose-proportional increases in the maximum concentration of drug in plasma and the area under the concentration-time curve from 0 to 72 h with no changes in plasma drug clearance. The 1-mg/kg dosage maintained plasma drug levels above the MIC for 18 h, and dosages of greater than or equal to 5 mg/kg maintained plasma drug levels above the MIC for the entire 24-h dosing interval. There was no significant elevation of the concentrations of hepatic transaminases or creatinine in serum in LY303366-treated rabbits. In summary, LY303366 improved survival and decreased pulmonary injury with no apparent toxicity in the treatment and prevention of invasive pulmonary aspergillosis in persistently neutropenic rabbits. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Res Resources, Surg Branch, Vet Resources Serv, Bethesda, MD 20892 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bldg 10,Rm 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@pbmac.nci.nih.gov NR 30 TC 88 Z9 91 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 1998 VL 42 IS 11 BP 2898 EP 2905 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 133NK UT WOS:000076692500021 PM 9797223 ER PT J AU Hong, H Neamati, N Winslow, HE Christensen, JL Orr, A Pommier, Y Milne, GWA AF Hong, H Neamati, N Winslow, HE Christensen, JL Orr, A Pommier, Y Milne, GWA TI Identification of HIV-1 integrase inhibitors based on a four-point pharmacophore SO ANTIVIRAL CHEMISTRY & CHEMOTHERAPY LA English DT Article DE HIV; integrase; inhibitors; drug design; AIDS; chemotherapy; pharmacophore ID IMMUNODEFICIENCY-VIRUS TYPE-1; DRUG INFORMATION-SYSTEM; 3D DATABASE; PROTEASE INHIBITORS; DESIGN; DISCOVERY; INFECTION; COMPLEXES AB The rapid emergence of human immunodeficiency virus (HIV) strains resistant to available drugs implies that effective treatment modalities will require the use of a combination of drugs targeting different sites of the HIV life cycle. Because the virus cannot replicate without integration into a host chromosome, HIV-1 integrase (IN) is an attractive therapeutic target. Thus, an effective IN inhibitor should provide additional benefit in combination chemotherapy. A four-point pharmacophore has been identified based on the structures of quinalizarin and purpurin, which were found to be potent IN inhibitors using both a preintegration complex assay and a purified enzyme assay in vitro. Searching with this four-point pharmacophore in the 'open' part of the National Cancer Institute three-dimensional structure database produced 234 compounds containing the pharmacophore. Sixty of these compounds were tested for their inhibitory activity against IN using the purified enzyme; 19 were found to be active against IN with IC50 values of less than 100 mu M, among which 10 had IC50 values of less than 10 mu M. These inhibitors can further serve as leads, and studies are in progress to design novel inhibitors based on the results presented in this study. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Milne, GWA (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bldg 37,5B29, Bethesda, MD 20892 USA. NR 27 TC 36 Z9 36 U1 0 U2 1 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 0956-3202 J9 ANTIVIR CHEM CHEMOTH JI Antivir. Chem. Chemother. PD NOV PY 1998 VL 9 IS 6 BP 461 EP 472 PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology GA 148UH UT WOS:000077551200002 PM 9865384 ER PT J AU Pina, S Jofre, J Emerson, SU Purcell, RH Girones, R AF Pina, S Jofre, J Emerson, SU Purcell, RH Girones, R TI Characterization of a strain of infectious hepatitis E virus isolated from sewage in an area where hepatitis E is not endemic SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID PCR AMPLIFICATION; MOLECULAR-CLONING; PROTOTYPE STRAIN; POLLUTED WATERS; HEV; SEQUENCE; MONKEYS; CHINA AB Raw sewage samples from an area where hepatitis E is not endemic (Barcelona, Spain) were analyzed by reverse transcriptase-PCR followed by nested PCR. One of the 37 tested samples showed a positive result for hepatitis E virus (HEV), The detected strain was amplified by inoculation into rhesus monkeys, and the course of the infection was studied by analyzing serological and biochemical parameters and by monitoring the presence of HEV in serum and feces. Fecal suspensions from the rhesus monkeys were used as the source of viral particles for sequence analysis. Eighty percent of the genome of the isolated strain, named BCN, was sequenced and found to be phylogenetically related to Asian (Indian) strains, with a 98% nucleotide identity with an isolate from Madras, India. Since this was a single isolation we cannot conclude that HEV is regularly present in the sewage. However, the finding of viable HEV in sewage has implications for contamination of the environment and shellfish by HEV and must be considered in the diagnosis of viral hepatitis in regions of nonendemic hepatitis. C1 Univ Barcelona, Sch Biol, Dept Microbiol, E-08028 Barcelona, Spain. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Girones, R (reprint author), Univ Barcelona, Sch Biol, Dept Microbiol, Avd Diagonal 645, E-08028 Barcelona, Spain. EM Rosina@bio.ub.es RI Girones, Rosina/B-2975-2009 OI Girones, Rosina/0000-0002-1097-6395 NR 22 TC 94 Z9 98 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD NOV PY 1998 VL 64 IS 11 BP 4485 EP 4488 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 133PD UT WOS:000076694200057 PM 9797311 ER PT J AU Goldstein, SR McQueen, PG Bonner, RF AF Goldstein, SR McQueen, PG Bonner, RF TI Thermal modeling of laser capture microdissection SO APPLIED OPTICS LA English DT Article AB A first-order thermal analysis is applied to Laser Capture Microdissection (LCM), a new microscope technique for routine targeting and extraction of specific cells from tissue sections for subsequent multiplex molecular analysis. In LCM a polymer film placed in contact with the tissue is focally activated by a pulsed IR laser beam and is melted and bonded to adjacent targeted cells. A three-dimensional finite-element model is used to predict the thermal transients within the polymer, the captured tissue, and its macromolecules. The simulations allow a comparison of models for the physical process of LCM with the experimental data on the dependence of the transfer spot size on laser power. The validated physical model and the thermal simulations permit optimization of the complex LCM parameter space for a wide variety of configurations and applications. (C) 1998 Optical Society of America OCIS codes: 140.6810. 160.6840, 170.1530, 170.4730, 350.5340. C1 Natl Inst Hlth, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Goldstein, SR (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015 NR 10 TC 21 Z9 21 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0003-6935 J9 APPL OPTICS JI Appl. Optics PD NOV 1 PY 1998 VL 37 IS 31 BP 7378 EP 7391 DI 10.1364/AO.37.007378 PG 14 WC Optics SC Optics GA 134VJ UT WOS:000076764100031 PM 18301572 ER PT J AU Raghunath, M Hennies, HC Velten, F Wiebe, V Steinert, PM Reis, A Traupe, H AF Raghunath, M Hennies, HC Velten, F Wiebe, V Steinert, PM Reis, A Traupe, H TI A novel in situ method for the detection of deficient transglutaminase activity in the skin SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE transglutaminase; epidermis; lamellar ichthyosis; skin; histochemistry ID RECESSIVE LAMELLAR ICHTHYOSIS; CORNIFIED CELL-ENVELOPE; KERATINOCYTE TRANSGLUTAMINASE; CROSS-LINKING; EPIDERMAL TRANSGLUTAMINASE; PROTRANSGLUTAMINASE-E; EXPRESSION; MUTATIONS; MOUSE; GENE AB Autosomal recessive congenital ichthyoses are disorders of epidermal cornification, but are clinically and etiologically heterogeneous. Some cases, known as lamellar ichthyosis, are caused by mutations in the TGM1 gene encoding transglutaminase 1, which result in markedly diminished or lost enzyme activity and/or protein. In some cases, this enzyme is present but there is little detectable activity, and in other clinically similar cases, transglutaminase 1 levels appear to be normal. Since conventional enzyme assays and mutational analyses are tedious, we developed a novel assay for the rapid screening of transglutaminase 1 activity using covalent incorporation of biotinylated substrate peptides into skin cryostat sections. Coupled with immunohistochemical assays using transglutaminase 1 antibodies, our method allows rapid identification of those cases caused by alterations in this enzyme. C1 Univ Munster, Dept Dermatol, D-48149 Munster, Germany. Univ Hosp Rudolf Virchow, Inst Human Genet, Berlin, Germany. INRA, CEA, Lab Radiobiol Appl, Jouy En Josas, France. NIH, Skin Biol Lab, Bethesda, MD 20892 USA. RP Raghunath, M (reprint author), Univ Munster, Dept Dermatol, Von Esmarchstr 56, D-48149 Munster, Germany. EM raghuna@uni-muenster.de RI Raghunath, Michael/E-6483-2010; Reis, Andre/D-2309-2009 OI Raghunath, Michael/0000-0002-2138-6614; Reis, Andre/0000-0002-6301-6363 NR 42 TC 49 Z9 49 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD NOV PY 1998 VL 290 IS 11 BP 621 EP 627 DI 10.1007/s004030050362 PG 7 WC Dermatology SC Dermatology GA 141HM UT WOS:000077137400007 PM 9860283 ER PT J AU Goldman, D Bergen, A AF Goldman, D Bergen, A TI General and specific inheritance of substance abuse and alcoholism SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material C1 NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, 12420 Pk Lawn Dr,Room 451, Rockville, MD 20852 USA. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Bergen, Andrew/0000-0002-1237-7644 NR 8 TC 50 Z9 51 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 1998 VL 55 IS 11 BP 964 EP 965 DI 10.1001/archpsyc.55.11.964 PG 2 WC Psychiatry SC Psychiatry GA 134WA UT WOS:000076748200001 PM 9819063 ER PT J AU Lappalainen, J Long, JC Eggert, M Ozaki, N Robin, RW Brown, GL Naukkarinen, H Virkkunen, M Linnoila, M Goldman, D AF Lappalainen, J Long, JC Eggert, M Ozaki, N Robin, RW Brown, GL Naukkarinen, H Virkkunen, M Linnoila, M Goldman, D TI Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CROSS-FOSTERING ANALYSIS; VIOLENT OFFENDERS; FIRE SETTERS; DISORDERS; ADOPTION; VARIANTS; BEHAVIOR; ABUSE AB Background: In mice, quantitative trait locus studies and behavioral evaluation of animals deleted for 5-HT1B have implicated this seretonin autoreceptor in alcohol consumption and aggressive behavior. We therefore investigated whether the 5-HT1B gene (HTR1B) is linked to alcoholism with aggressive and impulsive behavior in the human, as represented by 2 psychiatric diagnoses: antisocial personality disorder and intermittent explosive disorder comorbid with alcoholism. Methods: Linkage was first tested in 640 Finnish subjects, including 166 alcoholic criminal offenders, 261 relatives, and 213 healthy controls. This was followed by a study in a large multigenerational family derived from a Southwestern American Indian tribe (n = 418) with a high rate of alcoholism. All subjects were psychiatrically interviewed, blind-rated for psychiatric diagnoses, and typed for a HTR1B G861C polymorphism and for a closely linked short-tandem repeat locus, D6S284. Linkage was evaluated in sib pairs, and by using an association approach in which pedigree randomization corrects for nonindependence of observations on related subjects. Results: In Finnish sib pairs, antisocial alcoholism showed significant evidence of linkage to HTR1B G861C (P = .04) and weak evidence with D6S284 (P = .06). By association analysis, the 183 Finnish antisocial alcoholics had a significantly higher HTR1B-86IC allele frequency than the other 457 Finns we studied (P = .005). In the Southwestern American Indian tribe, significant sib pair linkage of antisocial alcoholism to HTR1B G861C (P = .01) was again observed, and there was also significant linkage to D6S284 (P = .01). Conclusion: These results suggest that a locus predisposing to antisocial alcoholism may be linked to HTR1B at 6q13-15. C1 NIAAA, Sect Populat Genet & Linkage, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NIAAA, Clin Studies Lab, NIH, Rockville, MD 20852 USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. RP Lappalainen, J (reprint author), NIAAA, Sect Populat Genet & Linkage, Neurogenet Lab, NIH, 12501 Washington Ave, Rockville, MD 20852 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 FU NCRR NIH HHS [1 P41 RR03655] NR 36 TC 224 Z9 230 U1 5 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 1998 VL 55 IS 11 BP 989 EP 994 DI 10.1001/archpsyc.55.11.989 PG 6 WC Psychiatry SC Psychiatry GA 134WA UT WOS:000076748200005 PM 9819067 ER PT J AU O'Brien, TP Li, Q Ashraf, MF Matteson, DM Stark, WJ Chan, CC AF O'Brien, TP Li, Q Ashraf, MF Matteson, DM Stark, WJ Chan, CC TI Inflammatory response in the early stages of wound healing after excimer laser keratectomy SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID MACROPHAGES AB Objective: To evaluate the inflammatory response and its potential role in the early stages of corneal wound healing after excimer laser keratectomy. Materials and Methods: Lewis rats underwent excimer keratectomy using a 193-nm excimer laser. The central corneas were ablated in 3 depths: group A, epithelium; group B, superficial stroma; or group C, deep stroma. Eyes were harvested 1, 12, 24, and 36 hours, and 1 week after the rats were killed. Immunohistochemistry was used to test frozen sections with monoclonal antibodies of various inflammatory cellular markers. Results: Reepithelialization was observed at 12 hours in group A, and at 24 hours in groups B and C. Regenerated epithelium covered the denuded corneal surface in groups B and C after 1 week. The expression of major histocompatibility complex II antigen was detected in infiltrating cells, corneal epithelial cells, and endothelial cells 1 hour after surgery. Only a few macrophages and Langerhans cells were in the limbus at baseline, Macrophages migrated from the limbus to the corneal ablation zone and increased 2-fold after 36 hours in all 3 groups compared with baseline. Occasional lymphocytic infiltration was identified after 25 to 36 hours. Conclusion: Macrophages play an active role in the wound healing after laser keratectomy and may contribute to transient corneal haze. C1 Johns Hopkins Univ, Wilmer Eye Inst, Cornea Serv, Baltimore, MD 21287 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP O'Brien, TP (reprint author), Johns Hopkins Univ, Wilmer Eye Inst, Refractory Surg Serv, 600 N Wolfe St,Woods Bldg,Room 255, Baltimore, MD 21287 USA. NR 15 TC 66 Z9 68 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 1998 VL 116 IS 11 BP 1470 EP 1474 PG 5 WC Ophthalmology SC Ophthalmology GA 137KK UT WOS:000076913800010 PM 9823348 ER PT J AU Vajo, Z Stratakis, CA AF Vajo, Z Stratakis, CA TI Picture of the month - Klippel-Trenaunay syndrome SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article C1 NICHD, Genet Unit, Sect Pediat Endocrinol, Dev Endocrinol Branch,NIH, Bethesda, MD 20892 USA. NICHD, Unit Endocrinol, Sect Pediat Endocrinol, Dev Endocrinol Branch,NIH, Bethesda, MD 20892 USA. NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Genet Unit, Sect Pediat Endocrinol, Dev Endocrinol Branch,NIH, 10 Ctr Dr,MSC 1862,Bldg 10,Room 10N262, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD NOV PY 1998 VL 152 IS 11 BP 1149 EP 1150 PG 2 WC Pediatrics SC Pediatrics GA 134HB UT WOS:000076736500019 PM 9811297 ER PT J AU Nyska, A Herbert, RA Chan, PC Haseman, JK Hailey, JR AF Nyska, A Herbert, RA Chan, PC Haseman, JK Hailey, JR TI Theophylline-induced mesenteric periarteritis in F344/N rats SO ARCHIVES OF TOXICOLOGY LA English DT Article DE theophylline; alkaloid; pharmaceutical; bronchodilator; arteritis ID FENOLDOPAM MESYLATE; DOPAMINERGIC VASODILATOR; REGRESSION-ANALYSIS; MEDIAL NECROSIS; TOXICOLOGY; HEMORRHAGE; INFUSION; ARTERIES AB The toxicity and carcinogenic potential of theophylline (an alkaloid bronchodilator drug) was investigated in male and female F344/N rats in 16-day, 14-week, and 2-year gavage and feeding studies. In 16-day studies, rats were fed diets containing 0, 500, 1000, 2000, 4000, and 8000 ppm of theophylline or given 0, 12.5 (twice daily), 25 (once daily), 50 (once daily), 50 (twice daily), 100 (once daily), 200 (once daily), 200 (twice daily), and 400 (once daily) mg theophylline/kg body weight in corn oil by gavage. In 14-week studies, rats were fed diets containing 0, 1000, 2000, and 4000 ppm theophylline or given 0, 37.5, 75, and 150 mg/kg body weight theophylline in corn oil by gavage. In 2-year gavage studies, rats were given 0, 7.5, 25, and 75 mg/kg body weight in corn oil. In 16-day gavage studies, treatment-related periarteritis occurred in arteries of the pancreas and adjacent to the mesenteric lymph nodes of early death male and female rats given 400 mg/kg once daily. In the 14-week studies, treatment-related periarteritis occurred at similar sites and in male rats exposed to 75 and 150 mg/kg, and in all exposed female rats (gavage studies), in females exposed to 1000 ppm, and in both sexes exposed to 2000 and 4000 ppm (feeding studies). In the 2-year study, chronic periarteritis was significantly increased only in the males receiving 75 mg/kg of theophylline. The adventitia, media and intima of medium- and large-sized mesenteric arteries were involved. Similar to other vasodilator chemicals, the pathogenesis of theophylline-induced vascular lesions may be a consequence of hemodynamic changes induced in the vascular wall. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), NIEHS, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 30 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD NOV PY 1998 VL 72 IS 11 BP 731 EP 737 DI 10.1007/s002040050567 PG 7 WC Toxicology SC Toxicology GA 150FN UT WOS:000077653400008 PM 9879811 ER PT J AU Ernst, M London, ED AF Ernst, M London, ED TI More ethical challenges: Commentary on Fischman and Johanson's - Ethical and practical issues involved in behavioral pharmacology research that administers drugs of abuse to human volunteers SO BEHAVIOURAL PHARMACOLOGY LA English DT Editorial Material C1 NIDA, Brain Imaging Ctr, NIH, Baltimore, MD 21224 USA. RP Ernst, M (reprint author), NIDA, Brain Imaging Ctr, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD NOV PY 1998 VL 9 IS 7 BP 499 EP 501 DI 10.1097/00008877-199811000-00003 PG 3 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 145LA UT WOS:000077371400003 PM 10094591 ER PT J AU Preston, KL Bigelow, GE AF Preston, KL Bigelow, GE TI Opioid discrimination in humans: discriminative and subjective effects of progressively lower training dose SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE drug discrimination; fading procedure; training dose; humans; hydromorphone; opioids ID AGONIST-ANTAGONIST OPIOIDS; DRUG DISCRIMINATION; SALINE DISCRIMINATION; CAFFEINE DISCRIMINATION; HYDROMORPHONE; COCAINE; SUBSTITUTION; AMPHETAMINE; POSTADDICTS; MORPHINE AB The purpose of this study was to examine the extent of covariation of subjective and discriminative drug effects as the dose of the discriminated training drug was progressively lowered. Six adult male volunteers with histories of opioid abuse, who were not currently physically dependent, were trained to discriminate the mu-receptor agonist hydromorphone (20 mg, oral) from placebo in daily sessions. They received financial reinforcement for correct responses. The hydromorphone training dose was then progressively reduced (20, 14, 10, 7, 5, and 3.5 mg) while the discrimination reinforcement contingencies remained in effect. Measures of subjective and physiological effects were concurrently collected during each discrimination session. As the training dose decreased, discriminative performance was generally well maintained, although the percent of drug-appropriate responses to hydromorphone did decline from 98% to 75%. The magnitude of the subjective and physiological effects of hydromorphone also decreased as the training dose decreased. At the lowest training dose, there were no physiological effects and few subjective effects of hydromorphone statistically different from placebo, although discrimination behavior remained statistically significant at all doses. These data indicate covariation of subjective effects and discrimination performance and suggest that discrimination behavior may be more sensitive for differentiating among drug conditions than traditional subjective effects measures. Behav Pharmacol 1998; 9:533-543 (C) 1998 Lippincott Williams & Wilkins. C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Preston, KL (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU NIDA NIH HHS [DA-00050, DA-04089] NR 31 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD NOV PY 1998 VL 9 IS 7 BP 533 EP 543 DI 10.1097/00008877-199811000-00009 PG 11 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 145LA UT WOS:000077371400009 PM 9862079 ER PT J AU Merezhinskaya, N Kuijpers, GAJ Raviv, Y AF Merezhinskaya, N Kuijpers, GAJ Raviv, Y TI Reversible penetration of alpha-glutathione S-transferase into biological membranes revealed by photosensitized labelling in situ SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN-KINASE-C; IDENTIFICATION; ACTIVATION; CELLS; PURIFICATION; FLUORESCENCE; CAPACITANCE; TRANSPORTER; ISOZYMES; BILAYER AB Fluorescent lipid analogue 3,3'-dioctadecyloxacarbocyanine incorporated into biological membranes was used to induce photoactivation of a hydrophobic probe 5-[I-125]iodonaphthyl-azide ((125)INA) by energy transfer and to thereby confine subsequent radiolabelling of proteins to the lipid bilayer. This approach was applied in bovine chromaffin cells to discover cytosolic proteins that reversibly penetrate into membrane domains. alpha-Glutathione S-transferase (alpha-GST) was identified as the only labelled protein in bovine chromaffin-cell cytosol, indicating that it inserts reversibly into the membrane lipid bilayer. The selectivity of the labelling towards the lipid bilayer is demonstrated by showing that influenza virus haemagglutinin becomes labelled by (125)INA only after the insertion of this protein into the target membrane. The molar (125)INA:protein ratio was used as a quantitative criterion for evaluation of the penetration of proteins into the membrane lipid bilayer. This ratio was calculated for four integral membrane proteins and four soluble proteins that interact with biological membranes. The values for four integral membrane proteins (erythrocyte anion transporter, multidrug transporter gp-170, dopamine transporter and fusion-competent influenza virus haemagglutinin) were 1, 8, 2 and 2, respectively, whereas for soluble proteins (annexin VII, protein kinase C, BSA and influenza virus haemagglutinin) the values were 0.002, 0, 0.002 and 0.02, respectively. The molar ratio for alpha-GST was found to be 1, compatible with the values obtained for integral membrane proteins. C1 NIDDK, Cell Biol & Genet Lab, NIH, Bethesda, MD 20892 USA. RP Merezhinskaya, N (reprint author), Armed Forces Inst Pathol, Div Biochem, Alaska Ave & 14th St,NW, Washington, DC 20306 USA. NR 43 TC 8 Z9 8 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 1998 VL 335 BP 597 EP 604 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 138XP UT WOS:000076980300018 PM 9794800 ER PT J AU Schedin, S Pentchev, P Dallner, G AF Schedin, S Pentchev, P Dallner, G TI Reduced cholesterol accumulation and improved deficient peroxisomal functions in a murine model of Niemann-Pick type C disease upon treatment with peroxisomal proliferators SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Niemann-Pick; peroxisomes; peroxisomal proliferation; lipid metabolism; cholesterol; dolichol ID RAT-LIVER AB Niemann-Pick type C disease is an inherited disorder characterized by lysosomal accumulation of cholesterol and the mutant gene has recently been identified. The predicted gene product is a transmembrane protein showing homology to proteins involved in the regulation of cholesterol homeostasis, such as 3-hydroxy-3-methylglutaryl-coenzyme A and the sterol regulatory element binding protein cleavage-activating protein. Recent investigations have established a peroxisomal deficiency, which raised the question of whether peroxisomal proliferation could affect this cholesterol-processing error. Mutant mice with Niemann-Pick type C disease were treated with the peroxisomal inducer perfluorooctanoic acid, which increased peroxisomal beta-oxidation and catalase activity to the same level as in control mice. Not only the peroxisomal, but also the lysosomal malfunctions were corrected and the cholesterol content was decreased. Clofibrate, another peroxisomal inducer, restored both peroxisomal enzyme activities and ubiquinone content. It appears that in Niemann-Pick type C disease treatment with appropriate peroxisomal inducers restores basic cellular functions, indicating a relationship between peroxisomes and cholesterol homeostasis, and thereby may effectively interfere with the development of the disease. (C) 1998 Elsevier Science Inc. C1 Univ Stockholm, Dept Biochem, S-10691 Stockholm, Sweden. Karolinska Inst, Novum, Clin Res Ctr, S-14186 Huddinge, Sweden. NINDS, NIH, Bethesda, MD 20892 USA. RP Schedin, S (reprint author), Univ Stockholm, Dept Biochem, S-10691 Stockholm, Sweden. EM fia@biokemi.su.se NR 12 TC 11 Z9 11 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 1 PY 1998 VL 56 IS 9 BP 1195 EP 1199 DI 10.1016/S0006-2952(98)00234-2 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 132PP UT WOS:000076639000016 PM 9802331 ER PT J AU Lebowitz, J Teale, M Schuck, PW AF Lebowitz, J Teale, M Schuck, PW TI Analytical band centrifugation of proteins and protein complexes SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Colloquium on Advances in Ultracentrifuge Analysis CY MAR 26-27, 1998 CL UNIV NOTTINGHAM, NOTTINGHAM, ENGLAND HO UNIV NOTTINGHAM ID DNA; REPAIR C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Mol Genet & Biochem, Birmingham, AL 35294 USA. NIH, Bioengn & Phys Sci Program, Bethesda, MD 20892 USA. RP Lebowitz, J (reprint author), Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. OI Schuck, Peter/0000-0002-8859-6966 NR 15 TC 11 Z9 11 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 1998 VL 26 IS 4 BP 745 EP 749 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 153TL UT WOS:000077848700040 PM 10047819 ER PT J AU Huang, HW Tsoi, SCM Sun, H Li, SSL AF Huang, HW Tsoi, SCM Sun, H Li, SSL TI Identification and characterization of the SMT3 cDNA and gene encoding ubiquitin-like protein from Drosophila melanogaster SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article ID NUCLEAR-PORE COMPLEX; HUMAN HOMOLOG; CENP-C; COMPONENT; RANGAP1; MIF2 C1 NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung 80424, Taiwan. Acad Sinica, Inst Mol Biol, Taipei 11529, Taiwan. RP Li, SSL (reprint author), NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM Li@NIEHS.NIH.GOV NR 16 TC 19 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE, NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD NOV PY 1998 VL 46 IS 4 BP 775 EP 785 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 143GQ UT WOS:000077247200016 PM 9844739 ER PT J AU Bera, TK Pastan, I AF Bera, TK Pastan, I TI Comparison of recombinant immunotoxins against Le(Y) antigen expressing tumor cells: Influence of affinity, size, and stability SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY B3; PSEUDOMONAS EXOTOXIN; FV FRAGMENT; NUCLEOTIDE-SEQUENCE; ANTITUMOR-ACTIVITY; VARIABLE DOMAINS; HEAVY-CHAIN; TOXINS; PROTEINS; BINDING AB Monoclonal antibody B3 (MAb B3) reacts with many epithelial cancers. It recognizes a carbohydrate antigen (Le(v)) which is expressed in a variety of solid tumors including breast and colon. We have used the Fab portion of MAE, B3 and a portion of the constant domain of human IgG1 to make recombinant immunotoxins of different compositions. The toxin component employed is a truncated farm of Pseudomonas exotoxin (PE38). The light chain or Fd of the antibody was cloned from hybridoma RNA and fused to PE38. Immunotoxin (IT) was then expressed in Escherichia coli as a fusion protein and refolded with either the Fd or the light chain. We have also made B3(Fab) immunotoxins of different sizes ranging 85-140 kDa, by introducing different portions of the constant domain of human IgG1 at the junction of Fd and PE38 fusion site. We compared the properties of the resulting immunotoxins with existing anti-Le(y) immunotoxins side by side. All recombinant Fab-immunotoxins made in this study were cytotoxic to antigen-positive cancer cell lines. However, in contrast to the B3(scFv) immunotoxin, the B3(Fab) immunotoxins are very stable, retaining 90% of their activity after 24 h of incubation in human serum albumin at 37 degrees C. A pharmacokinetics study with these immunotoxin molecules showed a longer survival in the circulation of mice compared to the smaller Fv immunotoxins. The smaller size of the Fab immunotoxins compared to B3Lys-PE38 and the increased T-1/2 value compared to B3(scFv)-PE38 and B3(dsFv)-PE38 make these recombinant immunotoxins alternative therapeutic agents to treat Le(y) antigen positive cancers. C1 NCI, Mol Biol Lab, DBS, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, DBS, NIH, Bldg 37,Room 4E16,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 27 TC 20 Z9 20 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 1998 VL 9 IS 6 BP 736 EP 743 DI 10.1021/bc980028o PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 141KU UT WOS:000077143700013 PM 9815167 ER PT J AU Rubinow, DR Schmidt, PJ Roca, CA AF Rubinow, DR Schmidt, PJ Roca, CA TI Estrogen-serotonin interactions: Implications for affective regulation SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Neuroscience Discussion Forum on a Decade of Serotonin Research CY NOV 16-18, 1997 CL AMELIA ISLAND, FLORIDA SP Soc Biol Psychiat, Eli Lilly & Co DE estrogen; serotonin; mood; reproductive endocrinology ID MONOAMINE-OXIDASE ACTIVITY; ACUTE TRYPTOPHAN DEPLETION; MESSENGER-RNA EXPRESSION; H-3 IMIPRAMINE BINDING; RAT SEXUAL-BEHAVIOR; PREMENSTRUAL-SYNDROME; MENSTRUAL-CYCLE; D-FENFLURAMINE; FEMALE RATS; POSTMENOPAUSAL WOMEN AB A burgeoning literature documents the convergence of reproductive endocrine and central serotonergic systems in the regulation of a variety of behaviors. This review will focus on one element of this interaction, the modulation of serotonergic function by estrogen. After describing the manifold neuroregulatory effects of gonadal steroids, we summarize the effects of estrogen on central serotonin systems in animals and humans as inferred from studies demonstrating the impact of gender, estrus (or menstrual) cycle, or hormone manipulation. Finally, we summarize the putative roles of estrogen and serotonin in two reproductive-endocrine-related mood disorders: premenstrual syndrome and perimenopausal depression. Published 1998 Society of Biological Psychiatry. C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. RP Rubinow, DR (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10,Room 3N238,10 Ctr Dr MSC 1276, Bethesda, MD 20892 USA. NR 137 TC 307 Z9 315 U1 4 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 1998 VL 44 IS 9 BP 839 EP 850 DI 10.1016/S0006-3223(98)00162-0 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 133NM UT WOS:000076692700005 PM 9807639 ER PT J AU Rose, AM Mellett, BJ Valdes, R Kleinman, JE Herman, MM Li, R El-Mallakh, RS AF Rose, AM Mellett, BJ Valdes, R Kleinman, JE Herman, MM Li, R El-Mallakh, RS TI Alpha2 isoform of the Na,K-adenosine triphosphatase is reduced in temporal cortex of bipolar individuals SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; schizoaffective disorders; schizophrenia; sodium- and potassium-activated adenosine triphosphatase; alpha isoforms; temporal cortex ID INTRACELLULAR CALCIUM-CONCENTRATION; MANIC-DEPRESSIVE PSYCHOSIS; ADENOSINE-TRIPHOSPHATASE; AFFECTIVE-DISORDERS; HUMAN-LYMPHOCYTES; SODIUM-PUMP; RAT-BRAIN; LITHIUM; NA,K-ATPASE; SUBUNIT AB Background: The pathophysiology of bipolar illness has been associated with changes in transmembrane ion flux and redistribution of biologically active ions. The recent identification of multiple isoforms of Na,K-adenosine triphosphatase (ATPase) alpha and beta subunits raises the possibility of altered pump isoform expression. Methods: We determined Na,K-ATPase alpha subunit expression in postmortem temporal col tex gray matter from individuals suffering from bipolar disorder, schizoaffective disorder, schizophrenia, and matched normal controls. Quantification of isoform expression was accomplished via densitometric scanning of Western blots utilizing isoform-specific antibodies. Results: Bipolar individuals exhibited a significant reduction in the abundance of the alpha 2 isoform of Na,K-ATPase compared to normal controls. Schizophrenic and schizoaffective brains were not. significantly different from normal controls. Conclusion: These data suggest that previously observed abnormalities in regulation and distribution of ions in bipolar illness may be related to specific alpha 2 dysregulation. Published 1998 Society of Biological Psychiatry. C1 Univ Louisville, Sch Med, Dept Psychiat & Behav Sci, Mood Disorders Res Program, Louisville, KY 40292 USA. Univ Louisville, Sch Med, Dept Pathol, Louisville, KY 40292 USA. NIMH, Neurosci Ctr St Elizabeths, Clin Brain Disorders Branch, Washington, DC 20032 USA. RP El-Mallakh, RS (reprint author), Univ Louisville, Sch Med, Dept Psychiat & Behav Sci, Mood Disorders Res Program, Louisville, KY 40292 USA. FU NHLBI NIH HHS [HLR01-36172] NR 48 TC 52 Z9 52 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 1998 VL 44 IS 9 BP 892 EP 897 DI 10.1016/S0006-3223(97)00440-X PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 133NM UT WOS:000076692700010 PM 9807644 ER PT J AU Kosmidis, MH Duncan, CC Mirsky, AF AF Kosmidis, MH Duncan, CC Mirsky, AF TI Sex differences in seasonal variations in P300 SO BIOLOGICAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 4th National Conference of Psychological Research of the Hellenic-Psychological-Society CY 1993 CL THESSALONIKI, GREECE SP Hellenic Psychol Soc DE event-related brain potentials; P300; season; sex differences ID EVENT-RELATED POTENTIALS; TESTOSTERONE LEVELS; GENERATORS; TIME; FLUCTUATIONS; PROBABILITY; INFORMATION; HORMONES; RHYTHMS; GENDER AB Previous reports of seasonal variations in P300 were based on cross-sectional observations of subjects tested at different times of the year. In this study, we tested three groups of subjects in each of two seasons: winter and spring, spring and summer, and summer and winter. We found winter or spring maxima in auditory and visual P300 and visual slow wave. This pattern of results, with the amplitude of P300 being inversely related to the amount of sunlight in a season, supports the hypothesis that the allocation of processing resources Varies across the seasons. Our results also suggest a trend for an increased sensitivity of women, as compared with men, to seasonal influences on P300. Although our findings do not provide strong evidence that P300 varies systematically as a function of season, seasonal factors appear to affect cognitive processing (as indexed by P300) differentially in men and women. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIMH, Sect Clin & Expt Neuropsychol, Lab Brain & Cognit, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. RP Duncan, CC (reprint author), NIMH, Sect Clin & Expt Neuropsychol, Lab Brain & Cognit, Bldg 15K,Room 101A, Bethesda, MD 20892 USA. EM connie_duncan@nih.gov NR 49 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD NOV PY 1998 VL 49 IS 3 BP 249 EP 268 DI 10.1016/S0301-0511(98)00043-X PG 20 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 144XC UT WOS:000077340100002 PM 9858056 ER PT J AU Resnick, JL Ortiz, M Keller, JR Donovan, PJ AF Resnick, JL Ortiz, M Keller, JR Donovan, PJ TI Role of fibroblast growth factors and their receptors in mouse primordial germ cell growth SO BIOLOGY OF REPRODUCTION LA English DT Article ID LEUKEMIA INHIBITORY FACTOR; LIGAND-BINDING; SKELETAL-MUSCLE; STEM-CELLS; EXPRESSION; CULTURE; FGF-4; GENE; PROLIFERATION; GASTRULATION AB Primordial germ cells (PGCs) are the embryonic progenitors of mature germ cells. During their proliferative stage, murine PGCs may be transiently cultured on mitotically inactive feeder layers. This culture system has permitted identification of several growth factors active toward PGCs. We and others have previously identified basic fibroblast growth factor (bFGF) as a powerful mitogen in this system. Here we characterize some of the functions of bFGF in PCC culture. Our data demonstrate that fibroblast growth factor (FGF) receptors I and II are present in the developing gonad and are consistent with expression of these receptors by PGCs. Moreover, PGCs can bind radiolabeled bFGF in vitro, demonstrating that the factor can act directly on these cells. While mitotic PGCs of either sex are shown to bind radiolabeled bFGF, oogonia that are undergoing meiotic arrest exhibit reduced bFGF binding, indicating potential developmental regulation of an FGF receptor. C1 NCI, Cell Biol Dev & Differentiat Grp, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res & Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Donovan, PJ (reprint author), Thomas Jefferson Univ, BLSB Room 706, 233 S 10th St, Philadelphia, PA 19107 USA. NR 46 TC 45 Z9 50 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 1998 VL 59 IS 5 BP 1224 EP 1229 DI 10.1095/biolreprod59.5.1224 PG 6 WC Reproductive Biology SC Reproductive Biology GA 133FP UT WOS:000076676400028 PM 9780331 ER PT J AU Guan, J Zhu, XK Tachibana, Y Bastow, KF Brossi, A Hamel, E Lee, KH AF Guan, J Zhu, XK Tachibana, Y Bastow, KF Brossi, A Hamel, E Lee, KH TI Antitumor agents. Part 186: Synthesis and biological evaluation of demethylcolchiceinamide analogues as cytotoxic DNA topoisomerase II inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE colchicine; colchiceinamide; tubulin; topoisomerase; demethylation ID COLCHICINE; DERIVATIVES AB Demethylation of colchiceinamide (2) and its analogues (3-10) afforded a novel class of mammalian DNA topoisomerase II inhibitors (2a-10a) without displaying tubulin inhibitory activity. All target compounds inhibited the catalytic activity of topoisomerase II at drug concentrations at 100 mu M. An in vitro cytotoxicity assay indicated that compounds 3a and 8a were strong and tissue-selective cytotoxic agents against the MCF-7 breast cancer cell line (IC50 = 0.36 and 0.48 mu g/mL, respectively) and the CAKI-1 renal cancer cell line (IC50 = 0.72 and 0.96 mu g/mL, respectively). (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Nat Prod Lab, Chapel Hill, NC 27599 USA. NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment Diagnosis & Ctr, Dev Therapeut Program,Lab Drug Discovery Res & De, Ft Detrick, MD 21702 USA. RP Lee, KH (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Nat Prod Lab, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [CA17625] NR 16 TC 6 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD NOV PY 1998 VL 6 IS 11 BP 2127 EP 2131 DI 10.1016/S0968-0896(98)00165-5 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 147HK UT WOS:000077483100014 PM 9881102 ER PT J AU Kornyshev, AA Leikin, S AF Kornyshev, AA Leikin, S TI Symmetry laws for interaction between helical macromolecules SO BIOPHYSICAL JOURNAL LA English DT Article ID COLLAGEN TRIPLE HELICES; DNA DOUBLE HELICES; HYDRATION FORCES; MOLECULAR-STRUCTURE; WATER-STRUCTURE; B-DNA; CONDENSATION; RESOLUTION; POLYAMINES; SOLVATION AB The power of symmetry laws is applied in many scientific areas from elementary particle physics to structural biology. The structures of many biological helices, including DNA, were resolved with the use of pertinent symmetry constraints, It was not recognized, however, that similar constraints determine cardinal features of helix-helix interactions vital for many recognition and assembly reactions in living cells. We now formulate such symmetry-determined interaction laws and apply them to explain DNA "over-winding" from 10.5 base pairs per turn in solution to 10 in hydrated fibers, counterion specificity in DNA condensation, and forces observed over the last 15 Angstrom of separation between DNA, collagen, and four-stranded guanosine helices. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Forschungszentrum Julich, Res Ctr Julich, D-52425 Julich, Germany. RP Leikin, S (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bldg 12A,Rm 2041, Bethesda, MD 20892 USA. EM leikin@helix.nih.gov RI Leikin, Sergey/A-5518-2008; Kornyshev, Alexei/C-3404-2008 OI Leikin, Sergey/0000-0001-7095-0739; NR 38 TC 32 Z9 34 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1998 VL 75 IS 5 BP 2513 EP 2519 PG 7 WC Biophysics SC Biophysics GA 132PF UT WOS:000076638200042 PM 9788947 ER PT J AU Zeng, G AF Zeng, G TI Sticky-end PCR: New method for subcloning (vol 25, pg 206, 1998) SO BIOTECHNIQUES LA English DT Correction ID RESTRICTION ENZYMES; CLONING C1 NCI, NIH, Bethesda, MD 20892 USA. RP Zeng, G (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 5 TC 6 Z9 6 U1 1 U2 6 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD NOV PY 1998 VL 25 IS 5 BP 788 EP 788 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 137CE UT WOS:000076896100007 ER PT J AU Ellenberg, J Lippincott-Schwartz, J Presley, JF AF Ellenberg, J Lippincott-Schwartz, J Presley, JF TI Two-color green fluorescent protein time-lapse imaging SO BIOTECHNIQUES LA English DT Article ID LIVING CELLS; GOLGI PROTEINS; BREFELDIN-A; MICROSCOPY; MOLECULES; TRANSPORT; MUTANTS; ER AB The Aequorea victoria green fluorescent protein (GFP) is widely recognized as a powerful tool in cell biology, serving as a vital reporter for monitoring localization and dynamics of intracellular proteins and organelles over time. GFP variants with shifted spectral characteristics have been described and offer enormous potential Sor double-labeling experiments and protein-protein interaction studies. However, most GFP variant combinations are not suitable for double-label, time-lapse imaging experiments because of either extremely rapid photobleaching of blue-shifted GFP variants or crossover of their excitation and emission spectra, which must then be computer corrected. Here, we describe the successful use of two photostable spectral GFP variants, W7 and 10C, in dual-color, time-lapse imaging of fusion proteins in living cells using either wide-field or confocal microscopy. W7 and 10C were highly photostable during repetitive long-term imaging and were cleanly separated by their different excitation spectra alone with negligible crossover of fluorescence. We present time-lapse image sequences of COS-7 cells co-expressing both a marker of the Golgi complex (galactosyl transferase) fused to W7 and a marker of the nuclear envelope (lamin-B receptor) fused to 10C. To our knowledge, these image sequences provide the first simultaneous visualization of Golgi and nuclear envelope membranes in living cells. C1 NICHHD, NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Presley, JF (reprint author), NICHHD, NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RI Ellenberg, Jan/I-4688-2014 OI Ellenberg, Jan/0000-0001-5909-701X NR 23 TC 47 Z9 49 U1 0 U2 5 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD NOV PY 1998 VL 25 IS 5 BP 838 EP + PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 137CE UT WOS:000076896100015 PM 9821586 ER PT J AU Chesi, M Nardini, E Lim, RSC Smith, KD Kuehl, WM Bergsagel, PL AF Chesi, M Nardini, E Lim, RSC Smith, KD Kuehl, WM Bergsagel, PL TI The t(4;14) translocation in myeloma dysregulates both FGFR3 and a novel gene, MMSET, resulting in IgH/MMSET hybrid transcripts SO BLOOD LA English DT Article ID WOLF-HIRSCHHORN SYNDROME; MULTIPLE-MYELOMA; CHROMOSOMAL TRANSLOCATIONS; EXPRESSION; TRITHORAX; REGION; MUTATIONS; COMPLEXES; SEQUENCES; FAMILY AB Previously we reported that a karyotypically silent t(4; 14)(p16.3;q32.3) translocation is present in about 25% of multiple myeloma (MM) tumors, and causes overexpression of FGFR3, which is 50 to 100 kb telomeric to the 4p16 breakpoints. Frequent FGFR3 kinase activating mutations in MM with t(4;14) translocations substantiate an oncogenic role for FGFR3. We now report that the 4p16 breakpoints occur telomeric to and within the 5' introns of a novel gene, MMSET (Multiple Myeloma SET domain). in normal tissues, MMSET has a complex pattern of expression with a short form (647 amino acids [aa]) containing an HMG box and hath region, and an alternatively spliced long form (1365 aa) containing the HMG box and hath region plus 4 PHD fingers and a SET domain. Although t(4;14) translocation results in IgH/MMSET hybrid transcripts, overexpression of MMSET also occurs from endogenous promoters on 4p16. Given the homology to HRX/MLL1/ALL1 at 11q23 that is dysregulated by translocations in acute leukemia, we hypothesize that dysregulation of MMSET contributes to neoplastic transformation in MM with t(4;14) translocation. This is the first example of an IgH translocation that simultaneously dysregulates two genes with oncogenic potential: FGFR3 on der(14) and MMSET on der(4). (C) 1998 by The American Society of Hematology. C1 Cornell Univ, Weill Med Coll, Dept Med, Div Hematol & Oncol, New York, NY USA. NCI, Dept Genet, Med Branch, Bethesda, MD 20892 USA. RP Bergsagel, PL (reprint author), 525 E 68th St,Room C609, New York, NY 10021 USA. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NCI NIH HHS [CA74265] NR 32 TC 332 Z9 340 U1 2 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1998 VL 92 IS 9 BP 3025 EP 3034 PG 10 WC Hematology SC Hematology GA 133NG UT WOS:000076692200003 PM 9787135 ER PT J AU Kruyt, FAE Hoshino, T Liu, JM Joseph, P Jaiswal, AK Youssoufian, H AF Kruyt, FAE Hoshino, T Liu, JM Joseph, P Jaiswal, AK Youssoufian, H TI Abnormal microsomal detoxification implicated in Fanconi anemia group C by interaction of the FAC protein with NADPH cytochrome P450 reductase SO BLOOD LA English DT Article ID MITOMYCIN-C; ESCHERICHIA-COLI; NADPH-CYTOCHROME-P-450 REDUCTASE; CYTOPLASMIC LOCALIZATION; LIVER-MICROSOMES; DT-DIAPHORASE; IN-VITRO; ACTIVATION; CELLS; COMPLEMENTATION AB The FAC protein encoded by the Fanconi anemia (FA) complementation group C gene is thought to function in the cytoplasm at a step before DNA repair. Because FA cells are susceptible to mitomycin C, we considered the possibility that FAC might interact with enzymes involved in the bioreductive activation of this drug, Here we report that FAC binds to NADPH cytochrome-P450 reductase (RED), a microsomal membrane protein involved in electron transfer, in both transfected COS-1 and normal murine liver cells. FAC-RED interaction requires the amino-terminal region of FAC and the cytosolic, membrane-proximal domain of the reductase. The latter contains a known binding site for flavin mononucleotide (FMN), Addition of FMN to cytosolic lysates disrupts FAC-reductase complexes, while flavin dinucleotide, which binds to a distinct carboxy-terminal domain, fails to alter FAG-RED complexes at concentrations similar to FMN. FAC is also functionally coupled to this enzyme as its expression in COS-1 cells suppresses the ability of RED to reduce cytochrome c in the presence of NADPH, We propose that FAC plays a fundamental role in vivo by attenuating the activity of RED, thereby regulating a major detoxification pathway in mammalian cells. (C) 1998 by The American Society of Hematology. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Youssoufian, H (reprint author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza, Houston, TX 77030 USA. EM hagopy@bcm.tmc.edu FU NHLBI NIH HHS [HL52138] NR 51 TC 112 Z9 112 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1998 VL 92 IS 9 BP 3050 EP 3056 PG 7 WC Hematology SC Hematology GA 133NG UT WOS:000076692200006 PM 9787138 ER PT J AU Pinto, LA Sharpe, S Cohen, DI Shearer, GM AF Pinto, LA Sharpe, S Cohen, DI Shearer, GM TI Alloantigen-stimulated anti-HIV activity SO BLOOD LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CD8(+) T-CELLS; NONLYTIC SUPPRESSION; REPLICATION; TYPE-1; INFECTION; AIDS; INDIVIDUALS; MIP-1-ALPHA; MIP-1-BETA AB A number of studies have suggested that an immune response to human leukocyte antigen (HLA) alloantigens may contribute to protection against HIV infection. In the present study, we examined the effect of alloantigen-stimulated cell lines obtained from peripheral blood mononuclear cells (PBMC) of HIV-uninfected (HIV-) individuals and the soluble factors produced by these cell lines on HIV-1 replication. Multiple in vitro restimulation with irradiated allogeneic PBMC from HIV- donors resulted in the expansion of CD8(+) T-cell lines that inhibited HIV-1 replication when cocultured with either autologous or heterologous in vitro-infected phytohemagglutinin (PHA) blasts. Supernatants from the alloantigen-stimulated cell lines also inhibited HIV replication in both PHA blasts and a chronically infected cell line, The alloantigen-stimulated cell lines and the factors they produced inhibited both T cell-tropic (T) and macrophage-tropic (M) isolates of HIV-1, Blocking experiments using anti-chemokine antibodies suggested that this inhibition of HIV replication was not due to the beta-chemokines present in cocultures of cell lines with HIV-infected blasts, These results indicate that alloantigen-stimulation of PBMC from HIV-individuals activates CD8+ T cells that produce soluble factor(s) that inhibit HIV replication of a wide spectrum of HIV-1 isolates through a chemokine-independent mechanism. This is a US government work, There are no restrictions on its use. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Tumor Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Shearer, GM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. EM ShearerG@exchange.nih.gov NR 41 TC 37 Z9 37 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1998 VL 92 IS 9 BP 3346 EP 3354 PG 9 WC Hematology SC Hematology GA 133NG UT WOS:000076692200040 PM 9787172 ER PT J AU Sakai, A Thieblemont, C Wellmann, A Jaffe, ES Raffeld, M AF Sakai, A Thieblemont, C Wellmann, A Jaffe, ES Raffeld, M TI PTEN gene alterations in lymphoid neoplasms SO BLOOD LA English DT Article ID TUMOR-SUPPRESSOR GENE; NON-HODGKINS-LYMPHOMA; GERMLINE MUTATIONS; PROSTATE-CANCER; COWDEN-DISEASE; PHOSPHATASE; PTEN/MMAC1; FREQUENT; BREAST; CARCINOMAS AB Recently, a novel phosphatase designated PTEN/MMAC1/TEP1 and located on chromosome 10q23.3 has been implicated as a new tumor suppressor gene in human cancer. Allelic loss and mutation of this gene has been reported in epithelial derived tumors, including breast cancer and prostate cancer, and in glioblastoma multiforme. The present study was designed to evaluate the potential involvement of PTEN in the pathogenesis of lymphoid neoplasms. We analyzed 27 hematopoietic cell lines (representing a variety of lymphoid lineages), 65 primary lymphoid tumors (including 24 lymphoblastic leukemia/lymphoma [LBL], 30 large B-cell lymphoma [LBCL], 7 Burkitt's lymphoma [BL], and 4 anaplastic large cell lymphoma [ALCL]), and 25 nonmalignant lymph node controls. Gene deletion and gross rearrangement were evaluated using Southern blot analysis, and mutations were studied by polymerase chain reaction (PCR)single-strand conformation polymorphism (SSCP) (PCR-SSCP) and sequencing. Six of 27 cell lines (22.2%) and 3 of 65 primary lymphomas (4.6%) contained alterations of this gene. A large homozygous deletion spanning exons 2 through 5 was detected in one LBL cell line, and two insertions potentially resulting in premature termination, were detected in a second LBL cell line. Nonconservative nucleotide variations were found in two other cell lines (one LBCL and one BL) and in one primary case of LBCL. In addition, two other cell lines (one BL and one myeloma) and two primary lymphomas, both LBCL, contained small deletions within intron 7. These deletions mapped to a poly-T-rich tract just 5' to the intron 7/exon 8 spice site. Their significance is unclear, as they may represent polymorphisms. Overall, our results suggest that abnormalities of the PTEN gene can contribute to pathogenesis in a small percentage of malignant lymphomas. This is a US government work. There are no restrictions on its use. C1 NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. RP Raffeld, M (reprint author), NCI, Pathol Lab, Hematopathol Sect, NIH, Bldg 10,Room 2N110,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mraff@box-m.nih.gov NR 22 TC 136 Z9 140 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1998 VL 92 IS 9 BP 3410 EP 3415 PG 6 WC Hematology SC Hematology GA 133NG UT WOS:000076692200049 PM 9787181 ER PT J AU Childs, R Sanchez, C Engler, H Preuss, J Rosenfeld, S Dunbar, C van Rhee, F Plante, M Phang, S Barrett, AJ AF Childs, R Sanchez, C Engler, H Preuss, J Rosenfeld, S Dunbar, C van Rhee, F Plante, M Phang, S Barrett, AJ TI High incidence of adeno- and polyomavirus-induced hemorrhagic cystitis in bone marrow allotransplantation for hematological malignancy following T cell depletion and cyclosporine SO BONE MARROW TRANSPLANTATION LA English DT Article DE hemorrhagic cystitis; adenovirus; polyoma virus; allogeneic bone marrow transplantation ID TRANSPLANTATION; BK; CYTOMEGALOVIRUS; ASSOCIATION; ELUTRIATION; VIDARABINE; INFECTION; THERAPY; VIRUS AB Nine of 56 (20% actuarial) patients receiving a T cell-depleted, HLA-identical sibling BMT for hematological malignancy developed hemorrhagic cystitis (HC) 15-368 days post BMT. Hematuria was severe and prolonged (median duration 18 days). In eight patients (89%), a viral etiology was confirmed (four adenovirus, four polyomavirus), HC was associated with significant morbidity, with all patients requiring continuous bladder irrigation and transfusion support for blood loss and thrombocytopenia, HC occurring before day 100 was significantly associated with a reduction in longterm survival: 1/7 (14.3%) patients developing HC before day 100 became long-term survivors vs 21/49 (42.8%) without HC by day 100 (P = 0.034). In univariate analysis, HC was associated with a diagnosis of multiple myeloma (P = 0.02). There was a trend towards a higher incidence of HC in patients reactivating cytomegalovirus (CMV) compared with those remaining CMV negative (18.4 vs 5.5% respectively, P = 0.17). HC was not associated with graft-versus-host disease, or with the transplant dose of CD34(+) progenitors or CD3(+) cells, patient age or sex. Life-threatening, viral-induced HC and the unusually high incidence of adenovirus-induced HC may have been caused by immune deficiency associated with T cell depletion in this series. C1 NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Childs, R (reprint author), NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bldg 10,Rm 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 70 Z9 70 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 1998 VL 22 IS 9 BP 889 EP 893 DI 10.1038/sj.bmt.1701440 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 135BW UT WOS:000076781100008 PM 9827817 ER PT J AU Honda, M Wise, SP Weeks, RA Deiber, MP Hallett, M AF Honda, M Wise, SP Weeks, RA Deiber, MP Hallett, M TI Cortical areas with enhanced activation during object-centred spatial information processing - A PET study SO BRAIN LA English DT Article DE cerebral blood flow; object-centred coordinate; screen-centred coordinate; occipitotemporal cortex; frontoparietal network ID POSTERIOR PARIETAL CORTEX; POSITRON EMISSION TOMOGRAPHY; LATERAL INTRAPARIETAL AREA; HUMAN EXTRASTRIATE CORTEX; FUNCTIONAL-ANATOMY; VISUAL PATHWAYS; MACAQUE MONKEYS; GRASP REPRESENTATIONS; PRIMATE PREMOTOR; FRONTAL-CORTEX AB The phenomenon of object-centred unilateral neglect suggests that some neural networks process spatial information relative to reference objects. To examine object-centred information processing, we measured regional cerebral blood flow in 11 normal subjects with PET. During each PET scan, a subject viewed a sample stimulus followed by a cue on a video screen, The sample consisted of two polygons, termed 'objects', each located in a corner of the screen. A small target spot appeared in a corner of each polygon, There were two tasks: the visuomotor task and the matching-to-sample task, In the visuomotor task, the subject moved a joystick in a direction indicated by either the location of the target spot inside the object (if object-centred coordinates were operative) or the location of the object relative to the video screen (if screen-centred coordinates were operative;), In the matching-to-sample task, the subject moved the joystick to report whether the relevant spatial information (object- or screen-centred) in the cue matched the sample. In both the visuomotor and the matching-to-sample task, use of object-centred (versus screen- or viewer-centred) information caused augmented activation in the inferior occipitotemporal cortex, bilaterally, in the left superior occipital gyrus, and in both the thalamus and the brainstem, In addition, in the visuomotor task such activation occurred in the right posterior parietal cortex and in the left ventral premotor, dorsolateral prefrontal and anterior supplementary motor areas. These findings suggest the involvement of the occipitotemporal cortex and a broad frontoparietal network when, as in the visuomotor task, object-centred information guides movement, When the same data underlie declarative reports, as in the matching-to-sample task, thp occipitotemporal cortex remains engaged but frontoparietal network diminishes in importance. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Lab Syst Neurosci, NIH, Poolesville, MD USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. RI Deiber, Marie-Pierre/M-5949-2014 NR 69 TC 33 Z9 33 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 1998 VL 121 BP 2145 EP 2158 DI 10.1093/brain/121.11.2145 PN 11 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 145KY UT WOS:000077371100012 PM 9827774 ER PT J AU Honda, M Deiber, MP Ibanez, V Pascual-Leone, A Zhuang, P Hallett, M AF Honda, M Deiber, MP Ibanez, V Pascual-Leone, A Zhuang, P Hallett, M TI Dynamic cortical involvement in implicit and explicit motor sequence learning - A PET study SO BRAIN LA English DT Article DE PET; serial reaction time task; implicit learning; explicit learning; motor sequence ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; REMEMBERED REACHING SEQUENCES; FUNCTIONAL-ANATOMY; NEURONAL-ACTIVITY; PREMOTOR CORTEX; BRAILLE READERS; FRONTAL-CORTEX; SENSORY CORTEX; BASAL GANGLIA AB We examined the dynamic involvement of different brain regions in implicit and explicit motor sequence learning using PET. In a serial reaction time task, subjects pressed each of four buttons with a different finger of the right hand in response to a visually presented number. Test sessions consisted of 10 cycles of the same 10-item sequence. The effects of explicit and implicit learning were assessed separately using a different behavioural parameter for each type of learning: correct recall of the test sequence for explicit learning and improvement of reaction time before the successful recall of any component of the test sequence for implicit learning. Regional cerebral blood flow was measured repeatedly during the task, and a parametric analysis was performed to identify brain regions in which activity was significantly correlated with subjects' performances: i.e. with correct recall of the test sequence or with reaction time. Explicit learning, shown as a positive correlation with the correct recall of the sequence, was associated with increased activity in the posterior parietal cortex, precuneus and premotor cortex bilaterally, also in the supplementary motor area (SMA) predominantly in the left anterior part, left thalamus, and right dorsolateral prefrontal cortex. In contrast, the reaction time showed a different pattern of correlation during different learning phases. During the implicit learning phase, when the subjects were not aware of the sequence, improvement of the reaction time was associated with increased activity in the contralateral primary sensorimotor cortex (SM1), During the explicit learning phase, the reaction time was significantly correlated with activity in a part of the frontoparietal network, During the post-learning phase, when the subjects achieved all components of the sequence explicitly, the reaction time was correlated with the activity in the ipsilateral SM1 and posterior part of the SMA. These results show that different sets of cortical regions are dynamically involved in implicit and explicit motor sequence learning. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. RI Pascual-Leone, Alvaro/G-6566-2011; Deiber, Marie-Pierre/M-5949-2014 NR 72 TC 220 Z9 220 U1 1 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 1998 VL 121 BP 2159 EP 2173 DI 10.1093/brain/121.11.2159 PN 11 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 145KY UT WOS:000077371100013 PM 9827775 ER PT J AU Lazarova, Z Hsu, R Yee, C Yancey, KB AF Lazarova, Z Hsu, R Yee, C Yancey, KB TI Antiepiligrin cicatricial pemphigoid represents an autoimmune response to subunits present in laminin 5 (alpha 3 beta 3 gamma 2) SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID BASEMENT-MEMBRANES; SPLIT SKIN; EPILIGRIN; AUTOANTIBODIES; LIGAND; EXPRESSION; COMPONENT; CONTAINS; VARIANT; PROTEIN AB Sera from 20 patients with antiepiligrin cicatricial pemphigoid were studied to define the specific reactivity of their IgG autoantibodies. IgG from all patients bound exclusively to the dermal side of 1 mol/L NaCl split skin and immunoprecipitated laminin 5 (alpha 3 beta 3 gamma 2) from extracts of human keratinocytes (HKs), Immunoblot studies on purified laminin 5 subunits demonstrated that patient IgG bound alpha 3 alone in 16 patients. In two patients, IgG autoantibodies were directed predominantly to the gamma 2 subunit, yet showed trace reactivity to alpha 3 as well. Sera from two patients did not immunoblot any laminin 5 subunits, their IgG presumably immunoprecipitating laminin 5 via a conformational epitope. Sera from patients with alpha 3 subunit-specific IgG immunoprecipitated all subunits of laminin 5 as well as polypeptides of 190 and 200 kDa from the conditioned media of HKs. Preclearance studies and experiments utilizing affinity-purified patient IgG demonstrated that the latter signified laminin 6 (alpha 3 beta 1 gamma 1) that was bound by cross-reactive alpha 3 subunit-specific patient IgG. Sera from patients with gamma 2 subunit-specific IgG showed no reactivity to laminin 6, except for faint reactivity provided by low levels of their alpha 3 subunit-specific IgG, Taken together, these findings indicate that antiepiligrin cicatricial pemphigoid signifies an autoimmune response to subunits present in laminin 5. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Yancey, KB (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. NR 29 TC 55 Z9 56 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD NOV PY 1998 VL 139 IS 5 BP 791 EP 797 PG 7 WC Dermatology SC Dermatology GA 143BF UT WOS:000077234700005 PM 9892943 ER PT J AU Hay, DF Vespo, JE Zahn-Waxler, C AF Hay, DF Vespo, JE Zahn-Waxler, C TI Young children's quarrels with their siblings and mothers: Links with maternal depression and bipolar illness SO BRITISH JOURNAL OF DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID CONFLICT; FAMILY AB Patterns of conflict amongst a mother and two young children were recorded for 55 families in the US. The mother was well in 19 families, depressed in 20, and had bipolar illness in 16. Sibling conflict occurred least often when the mother had bipolar illness. Mother-child conflict occurred most often when the elder child was male, but depressed mothers were likely to quarrel with their elder daughters. Mothers allied with elder rather than younger children, but depressed mothers were especially likely to uphold the rights of protesters. Compensatory influence was noted across relationships, so that children whose actions were protested by mothers were less likely to object to the behaviour of their siblings. In general, when mothers were well, families experienced frequent, but mild conflict; when mothers had bipolar illness, the relationship between the mother and the elder son was especially fraught; and when mothers were depressed, conflicts were more likely to escalate and to occur between mothers and daughters. C1 Univ Cambridge, Fac Social & Polit Sci, Cambridge CB5 8BA, England. Syracuse Univ, Utica Coll, Syracuse, NY 13244 USA. NIMH, Bethesda, MD 20892 USA. RP Hay, DF (reprint author), Univ Cambridge, Fac Social & Polit Sci, 8-9 Jesus Lane, Cambridge CB5 8BA, England. RI Hay, Dale/A-1779-2010 NR 54 TC 10 Z9 10 U1 3 U2 5 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER, LEICS, ENGLAND LE1 7DR SN 0261-510X J9 BRIT J DEV PSYCHOL JI Br. J. Dev. Psychol. PD NOV PY 1998 VL 16 BP 519 EP 538 PN 4 PG 20 WC Psychology, Developmental SC Psychology GA 144ZF UT WOS:000077345300008 ER PT J AU Kameda, H Mimori, T Kaburaki, J Fujii, T Takahashi, T Akaishi, M Ikeda, Y AF Kameda, H Mimori, T Kaburaki, J Fujii, T Takahashi, T Akaishi, M Ikeda, Y TI Systemic sclerosis complicated by procainamide-induced lupus and antiphospholipid syndrome SO BRITISH JOURNAL OF RHEUMATOLOGY LA English DT Article ID DRUG-INDUCED LUPUS; ANTICARDIOLIPIN ANTIBODIES; ERYTHEMATOSUS; ANTICOAGULANT; SCLERODERMA; AMPUTATION; PREVALENCE; SERUM C1 Keio Univ, Sch Med, Dept Internal Med, Shinjuku Ku, Tokyo 160, Japan. RP Kameda, H (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Eicosanoid Biochem Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0263-7103 J9 BRIT J RHEUMATOL JI Br. J. Rheumatol. PD NOV PY 1998 VL 37 IS 11 BP 1236 EP 1239 PG 4 WC Rheumatology SC Rheumatology GA 143PC UT WOS:000077263700020 PM 9851277 ER PT J AU De Vries, G Sherman, A Zhu, HR AF De Vries, G Sherman, A Zhu, HR TI Diffusively coupled bursters: Effects of cell heterogeneity SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; CHEMICAL OSCILLATORS; NEURAL OSCILLATORS; MOUSE; ISLETS; MODEL; LANGERHANS; SYNCHRONIZATION; STABILITY; SYSTEMS AB The interaction of a pair of weakly coupled biological bursters is examined. Bursting refers to oscillations in which an observable slowly alternates between phases of relative quiescence and rapid oscillatory behavior. The motivation for this work is to understand the role of electrical coupling in promoting the synchronization of bursting electrical activity (BEA) observed in the beta-cells of the islet of Langerhans, which secrete insulin in response to glucose. By studying the coupled fast subsystem of a model of BEA, we focus on the interaction that occurs during the rapid oscillatory phase. Coupling is weak, diffusive and non-scalar. in addition, non-identical oscillators are permitted. Using perturbation methods with the assumption that the uncoupled oscillators are near a Hopf bifurcation, a reduced system of equations is obtained. A detailed bifurcation study of this reduced system reveals a variety of patterns but suggests that asymmetrically phase-locked solutions are the most typical. Finally, the results are applied to the unreduced full bursting system and used to predict the burst pattern for a pair of cells with a given coupling strength and degree of heterogeneity. (C) 1998 Society for Mathematical Biology. C1 NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA. RP De Vries, G (reprint author), NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA. EM gerda@helix.nih.gov; sherman@helix.nih.gov; zhu@jchslab.la.asu.edu NR 38 TC 48 Z9 48 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD NOV PY 1998 VL 60 IS 6 BP 1167 EP 1200 DI 10.1006/bulm.1998.0057 PG 34 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 147KL UT WOS:000077485900008 PM 20957827 ER PT J AU Shapiro, JD Rothenberg, ML Sarosy, GA Steinberg, SM Adamo, DO Reed, E Ozols, RF Kohn, EC AF Shapiro, JD Rothenberg, ML Sarosy, GA Steinberg, SM Adamo, DO Reed, E Ozols, RF Kohn, EC TI Dose intensive combination platinum and cyclophosphamide in the treatment of patients with advanced untreated epithelial ovarian cancer SO CANCER LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 17-21, 1997 CL DENVER, COLORADO SP Amer Soc Clin Oncol DE ovarian cancer; chemotherapy; dose intensive ID CHEMOTHERAPY REGIMENS; STAGE-III; PHASE-II; CISPLATIN; CARBOPLATIN; CARCINOMA; THERAPY; TRIAL; PACLITAXEL; SURVIVAL AB BACKGROUND, The authors combined cisplatin and carboplatin together with cyclophosphamide to maximize platinum dose intensity in patients with advanced epithelial ovarian cancer (AOC). METHODS, The authors treated 26 consecutive, newly diagnosed patients with International Federation of Gynecology and Obstetrics (FIGO) Stage III/IV AOC with carboplatin, 600 mg/m(2), on Day 1; cyclophosphamide, 250 mg/m(2), on Day 1; and cisplatin, 100 mg/m(2), on Day 8 every 4 weeks with or without pretreatment with amifostine (range, 740-1140 mg/m(2)). Platinum dose intensity was estimated using a 4:1 conversion for equipotent doses of cisplatin and carboplatin for expression as cisplatin dose equivalents (CDE). RESULTS. The mean administered CDE was 49.4 mg/m(2)/week, which was 79% of the planned dose. Hematologic toxicity was severe, with FIGO Grade 3-4 anemia in 81% of patients, Grade 3-4 neutropenia in 92% of patients, and Grade 4 thrombocytopenia in 90% of patients. Eleven patients (42%) were admitted to the hospital for febrile neutropenia and there was 1 toxic death. Sensory neuropathy greater than or equal to Grade 2 occurred in 10 patients (38%), ototoxicity greater than or equal to Grade 2 occurred in 18 patients (69%), and 6 patients (23%) required long term hearing aids. Elevations in serum creatinine greater than or equal to Grade 2 occurred in 7 patients (27%) and greater than or equal to Grade 2 hypomagnesemia was noted in 23 patients (88%). Other Grade 3 toxicities were nausea (42%), emesis (38%), fatigue (15%), mucositis (4%), and respiratory toxicities (4%). Twenty-two of 26 patients (85%) had a clinical response (19 with a complete response [CRI and 3 with a partial response). Pathologic CR was demonstrated in 10 of 26 patients (38%) and residual microscopic disease in 4 of 26 patients (15%) for a total pathologic response rate of 53%. The median progression free survival was 13.5 months and the median overall survival was 37.2 months at a median potential follow-up of 79.3 months. Three of 26 patients remained free of disease at 60, 71, and 103 months, respectively. CONCLUSIONS, Although dose intensive combination platinum treatment combined with cyclophosphamide in patients with AOC is active, it also is associated with substantial toxicity. Cancer 1998;83:1980-8. (C) 1998 American Cancer Society. C1 NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, Med Branch, 10 Ctr Dr,MSC 1500,Bldg 10,Room 2A33, Bethesda, MD 20892 USA. NR 41 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1998 VL 83 IS 9 BP 1980 EP 1988 DI 10.1002/(SICI)1097-0142(19981101)83:9<1980::AID-CNCR14>3.3.CO;2-F PG 9 WC Oncology SC Oncology GA 133QJ UT WOS:000076697000014 PM 9806657 ER PT J AU Takeuchi, H Ara, G Sausville, EA Teicher, B AF Takeuchi, H Ara, G Sausville, EA Teicher, B TI Jasplakinolide: interaction with radiation and hyperthermia in human prostate carcinoma and Lewis lung carcinoma SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE jasplakinolide; hyperthermia; radiation sensitization; prostate cancer ID CANCER; INVITRO; ACTIN; CELLS; CYCLOOXYGENASE; DISRUPTION; INHIBITORS; JASPAMIDE; SPONGE; GROWTH AB Purpose: Jasplakinolide is a novel natural product anticancer agent which acts by inducing over-polymerization of actin. The aim of the current study was to explore the activity of jasplakinolide with hyperthermia and radiation. Methods: The response of human PC-3 and DU-145 prostate carcinoma cells and DU-145 xenografts and the response of the Lewis lung carcinoma to jasplakinolide were studied. Results: Jasplakinolide was cytotoxic toward human prostate carcinoma cells, DU-145, PC-3 and LNCaP in culture, killing 1 log of cells with 0.8, 0.3 and 0.07 mu M of drug in 24 h, respectively. The combination of jasplakinolide and hyperthermia resulted in primarily additive cell killing by the two modalities in the three prostate carcinoma lines. In combination with radiation, jasplakinolide produced some diminution in the shoulder of the survival curve of normally oxygenated PC-3 cells and was a radiation sensitizer of hypoxic DU-145 cells and hypoxic PC-3 cells. In vivo, jasplakinolide was an active antitumor agent against the Lewis lung carcinoma and the DU-145 prostate carcinoma xenograft. Jasplakinolide was a radiation sensitizer in the Lewis lung carcinoma. Jasplakinolide was also effective against the systemic Lewis lung carcinoma, decreasing lung metastases. Lung metastases were further decreased when jasplakinolide was administered along with radiation to the subcutaneous primary tumor. In the DU-145 tumor, the effects of jasplakinolide and fractionated radiation for 1 or 2 weeks appeared to be primarily additive. Conclusion: Jasplakinolide is an interesting new anticancer agent for which further study both as an anticancer agent and in combined modality regimens is warranted. C1 Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46033 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. NCI, Div Canc Treatment, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. RP Teicher, B (reprint author), Lilly Corp Ctr, Lilly Res Labs, DC 0540, Indianapolis, IN 46033 USA. NR 22 TC 21 Z9 23 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 1998 VL 42 IS 6 BP 491 EP 496 DI 10.1007/s002800050850 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 129GF UT WOS:000076454900009 PM 9788576 ER PT J AU Hildesheim, A Schiffman, M Scott, DR Marti, D Kissner, T Sherman, ME Glass, AG Manos, MM Lorincz, AT Kurman, RJ Buckland, J Rush, BB Carrington, M AF Hildesheim, A Schiffman, M Scott, DR Marti, D Kissner, T Sherman, ME Glass, AG Manos, MM Lorincz, AT Kurman, RJ Buckland, J Rush, BB Carrington, M TI Human leukocyte antigen class I/II alleles and development of human papillomavirus-related cervical neoplasia: Results from a case-control study conducted in the United States SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; ASSOCIATION; CARCINOMA; TYPE-16; WOMEN; INFECTION; CANCER; RISK; DNA; PEPTIDES AB The host immune response to human papillomaviruses (HPVs) is believed to be an important determinant of progression of HPV-associated cervical neoplasia, Human leukocyte antigens (HLAs) are important in the presentation of foreign antigens to the immune system. Previous studies have suggested a possible association between HLA and cervical neoplasia, but the specific alleles found to be associated with disease have varied between studies. To further evaluate this issue, we conducted a nested case-control study within a 24,000-woman cohort study in the United States. A total of 711 women were selected for the study: 141 women diagnosed with high-grade squamous intraepithelial lesions (HSILs) of the cervix; 202 women diagnosed with low-grade SILs (LSILs); 166 women with no history of cervical neoplasia, but evidence of HPV-16 infection; and 202 women with no history of cervical abnormalities and who were HPV negative during follow-up as part of our cohort, Cervicovaginal lavage samples collected from participants were used for HPV testing by L1 consensus primer PCR and the Hybrid Capture tube test methods. DNA extracted from these same lavage samples were used for PCR-based HLA genotyping, Our results suggest a positive association between HLA B7 and KLA DQB1*0302 and disease. A negative association with disease was observed for HLA DRB1*1501-DQB1*0602 and DRB1*13, Associations were strongest when analyses were restricted to HPV-16-positive cases as follows. Compared with women who were cytologically normal and HPV negative, HLA B7 was associated with a 1.5-fold increased risk of HPV/LSIL [95% confidence interval (CI) = 0.95-2.5] and a 2.5-fold increased risk of HSIL (95% CI = 1.2-5.1). HLA DQB1*0302 was associated with a 1.5-fold increased risk of HPV/LSIL (95% CI = 0.94-2.4) and a 1.7-fold increased risk of HSIL (95% CI = 0.84-3.5), HLA DRB1*1501-DQB1*0602 was associated with a decreased risk of HSIL [relative risk (RR) = 0.21; 95% CI = 0.07-0.62], HLA DRB1*13 was associated with a decreased risk of HPV/LSIL (RR = 0.78; 95% CI = 0.51-1.2) and HSIL (RR = 0.63; 95% CI = 0.30-1.3), individuals who were either homozygous for DQB1*0302 or carriers of both B7 and DQB1*0302 were found to be at highest risk of disease (RR = 4.5, 95% CI = 1.5-14 for HPV/LSIL; and RR = 9.0, 95% CI = 2.4-34 for HSIL), No synergistic effect was observed for the alleles found to be associated with reduced risk of cervical neoplasia. Our findings support previous studies that have found HLA B7 and DQB1*0302 to be positively associated with cervical neoplasia and are consistent with those that have suggested that DRB1*13 is negatively associated with disease, but do not confirm previous assertions that DRB1*1501-DQB1*0602 increases the risk of cervical disease. C1 NCI, Interdisciplinary Studies Sect, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Kaiser Permanente, Portland, OR 97227 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Kaiser Permanente, Oakland, CA 94611 USA. Digene Corp, Silver Spring, MD 20904 USA. Informat Management Syst, Silver Spring, MD 20904 USA. RP Hildesheim, A (reprint author), NCI, Interdisciplinary Studies Sect, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6130 Execut Blvd,EPN 443, Bethesda, MD 20892 USA. NR 27 TC 89 Z9 96 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 1998 VL 7 IS 11 BP 1035 EP 1041 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 136UP UT WOS:000076877800011 PM 9829713 ER PT J AU Wright, P Zheng, CY Moyana, T Xiang, J AF Wright, P Zheng, CY Moyana, T Xiang, J TI Intratumoral vaccination of adenoviruses expressing fusion protein RM4/tumor necrosis factor (TNF)-alpha induces significant tumor regression SO CANCER GENE THERAPY LA English DT Article DE recombinant adenovirus; fusion protein; tumor necrosis factor ID MEDIATED GENE-TRANSFER; COLONY-STIMULATING FACTOR; CYTOTOXIC T-CELLS; IN-VIVO; FACTOR-ALPHA; PHASE-I; CYSTIC-FIBROSIS; EARLY REGION-1; BRAIN-TUMORS; MURINE AB Recombinant adenovirus (AdV) vectors are highly efficient at in vitro and in vivo gene delivery. VKCK is a murine myeloma cell line expressing the light chain of the fusion protein RM4/tumor necrosis factor (TNF)-alpha. The in vitro transfection of VKCK cells with the AdV AdV5LacZ which contains the marker gene beta-galactosidase, can reach a maximal 75% at a multiplicity of infection of 1000. Intratumoral injections of AdV5LacZ (2 x 10(9) plaque-forming units) resulted in substantial gene transfer in nearly 50% of VKCK tumors. The AdV pLpA/M4-TNF-alpha, which contains a fused gene M4-TNF-alpha that codes for the heavy chain of fusion protein RM4/TNF-alpha, was constructed. After the in vitro transfection of pLpA/M4-TNF-alpha at a multiplicity of infection of 1000, transfected VKCK cells showed significant secretion of RM4/TNF-alpha (36 ng/mL/10(6) cells) containing the functional TNF-alpha moiety in tissue culture. The secretion peaks at day 3 and is diminished at day 6 following the viral infection. These transfected VKCK cells also became more immunogenic with enhanced expression of major histocompatibility complex class I antigen. Intratumoral injections of 2 x 10(9) plaque-forming units of pLpA/M4-TNF-alpha virus with a repeated booster resulted in significant VKCK tumor regression in immune-competent mice, but not in athymic nude mice with a mean tumor weight of 0.07 g that were compared with 1.58 g and 1.70 g for tumors injected with AdV5LacZ and phosphate-buffered saline, respectively (P <.01). The tumor regression also results in protective immunity against a second challenge with parental tumor cells, which is mainly mediated by VKCK tumor-specific CD8(+) T cells. These results indicate that AdV-mediated cytokine gene therapy may be a useful approach in the clinical management of solid human tumors. C1 Univ Saskatchewan, Dept Microbiol, Saskatoon Canc Ctr, Saskatoon, SK S7N 4H4, Canada. Univ Saskatchewan, Dept Pathol, Saskatoon Canc Ctr, Saskatoon, SK S7N 4H4, Canada. NIDR, Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Xiang, J (reprint author), Univ Saskatchewan, Dept Microbiol, Saskatoon Canc Ctr, 20 Campus Dr, Saskatoon, SK S7N 4H4, Canada. NR 35 TC 19 Z9 19 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1998 VL 5 IS 6 BP 371 EP 379 PG 9 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 159JH UT WOS:000078168500006 PM 9917092 ER PT J AU Bonovich, M Radecki, C Szilak, L Vinson, C AF Bonovich, M Radecki, C Szilak, L Vinson, C TI Chemosensitivity of human ovarian cancer cells to cis-platinum can be increased with a dominant negative to Fos SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1998 VL 5 IS 6 SU S MA O57 BP S19 EP S19 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 159JM UT WOS:000078169000064 ER PT J AU Bost, F Potapova, O McKay, R Dean, N Mercola, D AF Bost, F Potapova, O McKay, R Dean, N Mercola, D TI Inhibition of Jun kinase 2 but not Jun kinase 1 blocks epidermal growth factor (EGF)-induced transformation of A549 lung carcinoma cells SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Sidney Kimmel Canc Ctr, San Diego, CA USA. NIA, NIH, Baltimore, MD 21224 USA. ISIS Pharmaceut, Carlsbad, CA 92008 USA. Univ Calif San Diego, Ctr Mol Genet, La Jolla, CA 92093 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1998 VL 5 IS 6 SU S MA PD97 BP S32 EP S32 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 159JM UT WOS:000078169000105 ER PT J AU Parkhurst, MR Fitzgerald, EB Southwood, S Sette, A Rosenberg, SA Kawakami, Y AF Parkhurst, MR Fitzgerald, EB Southwood, S Sette, A Rosenberg, SA Kawakami, Y TI Identification of a shared HLA-A*0201 restricted T-cell epitope from the melanoma antigen tyrosinase-related protein 2 (TRP2) SO CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; PEPTIDE BINDING; IN-VITRO; IMMUNODOMINANT PEPTIDE; METASTATIC MELANOMA; SYNTHETIC PEPTIDES; MULTIPLE EPITOPES; HLA-A2 MELANOMAS; PERIPHERAL-BLOOD; SELF-PEPTIDES AB Tyrosinase-related protein 2 (TRP2) is a melanosomal enzyme expressed in most mammalian melanocytes and melanomas, This protein has been identified as a melanoma antigen recognized by tumor reactive CTLs derived from tumor infiltrating Lymphocytes in the context of HLA-A31 and HLA-A33, The frequencies of these HLA-A alleles among melanoma patients in the United States is low (similar to 6% for HLA-A31 rand similar to 2% for HLA-A33) compared with that of HLA-A*0201 (similar to 46%). Therefore, to extend significantly the use of TRP2-based immunotherapies for the treatment of patients with melanoma, we searched for new HLA-A*0201-restricted epitopes from this protein by screening TRP2-derived peptides for the induction of melanoma-reactive CTL. Fifty-one peptides were selected from TRP2 based on a permissive HLA-A*0201 binding motif, and the 21 peptides with the highest experimentally determined binding affinities were used to stimulate peripheral blood lymphocytes from HLA-A*0201(+) melanoma patients in vitro. One peptide, TRP2(180-188) (SVYDFFVWL), induced CTLs from three of four patients that specifically recognized peptide-pulsed T2 cells, COS-7 cells expressing HLA-A*0201 and TRP2, and HLA-A2(+) TRP2(+) melanomas, TRP2(180-188) is identical to a previously identified TRP2 epitope recognized by murine melanoma-reactive CTLs in the context of H-2K(b). These results suggest that TRP2 may be useful for the development of murine tumor immunotherapy models and for the treatment of melanoma patients who are diverse in HLA expression. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Epimmune Inc, San Diego, CA 92121 USA. RP Parkhurst, MR (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Maria_Parkhurst@nih.gov RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 FU NIAID NIH HHS [N01-AI-45241] NR 68 TC 138 Z9 144 U1 2 U2 8 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1998 VL 58 IS 21 BP 4895 EP 4901 PG 7 WC Oncology SC Oncology GA 134XE UT WOS:000076768400026 PM 9809996 ER PT J AU Zaks, TZ Rosenberg, SA AF Zaks, TZ Rosenberg, SA TI Immunization with a peptide epitope (p369-377) from HER-2/neu leads to peptide-specific cytotoxic T lymphocytes that fail to recognize HER-2/neu+ tumors SO CANCER RESEARCH LA English DT Article ID OVARIAN-CANCER; BREAST-CANCER; IN-VITRO; HER2/NEU-DERIVED PEPTIDE; IMMUNODOMINANT PEPTIDE; MELANOMA PATIENTS; PERIPHERAL-BLOOD; CELL TOLERANCE; NEU ONCOGENE; PROTOONCOGENE AB The oncogene HER-2/neu is genetically amplified and overexpressed in a large number of human adenocarcinomas and has been implicated in the tumorigenic phenotype, Although it is a nonmutated self-protein, it is barely detectable in adult tissues, and immune responses toward it have been described in a number of patients. It is, thus, an attractive candidate antigen for the immunotherapy of cancer patients. HLA-A2(+) patients with metastatic breast, ovarian, or colorectal adenocarcinomas that overexpressed HER-2/neu were immunized with the HLA-A2-binding epitope p369-377 (p369). Patients were treated by repeated immunization with 1 mg of p369 in Freund's incomplete adjuvant every 3 weeks. Peripheral blood mononuclear cells were collected prior to immunization and following two and Four immunizations and were stimulated in vitro with peptide and assayed for peptide and tumor recognition. In three of four patients, peptide-specific CTLs were detected in post- but not preimmunization blood. These CTLs recognized peptide-pulsed target cells at peptide concentrations of greater than or equal to 1 ng/ml yet failed to react with a panel of HLA-A2(+) HER-2/neu(+) tumor lines. In addition, infecting HLA-A2(+) cells with recombinant vaccinia virus encoding HER-2/neu or up-regulating HLA-A2 with IFN-gamma in HER-2/neu(+) cells also faded to confer reactivity by p369-reactive T-cells. A T-cell response to the HLA-A2 binding epitope p369 can be easily generated by immunizing patients with peptide in Freund's incomplete adjuvant, However, the CTLs failed to react with HER-2/neu(+) tumor cells, Further studies are needed to determine whether and how HER-2 might serve as an antigen for tumor immunotherapy. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Zaks, TZ (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B-46, Bethesda, MD 20892 USA. NR 39 TC 170 Z9 173 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1998 VL 58 IS 21 BP 4902 EP 4908 PG 7 WC Oncology SC Oncology GA 134XE UT WOS:000076768400027 PM 9809997 ER PT J AU Zhang, J Yergey, A Kowalak, J Kovac, P AF Zhang, J Yergey, A Kowalak, J Kovac, P TI Studies towards neoglycoconjugates from the monosaccharide determinant of Vibrio cholerae O : 1, serotype Ogawa using the diethyl squarate reagent SO CARBOHYDRATE RESEARCH LA English DT Article DE vaccine; dialkyl squarate; immunogen; antigen; neoglycoconjugate; Vibrio cholerae ID METHYL ALPHA-GLYCOSIDE; O-SPECIFIC ANTIGEN; REPEATING UNIT; CRYSTAL-STRUCTURE; POLYSACCHARIDE; INABA; PROTEINS; TERMINUS; O/1; DISACCHARIDE AB The effect of reaction time, concentration and molar excess of hapten upon the efficiency of the conjugation of carbohydrates to proteins using the diethyl squarate reagent has been studied using chicken serum albumin (CSA) as the carrier protein and a linker-equipped D-glucose derivative as the hapten. A high degree of incorporation of the latter into CSA was achieved with high efficiency, and the use of a large excess of the ligand was not necessary. Conjugation of the immunodominant monosaccharide determinant of Vibrio cholerae O:1, serotype Ogawa, bearing the same spacer, followed a similar pattern, showing that the nature of the carbohydrate does not substantially affect the outcome of the conjugation and that a predicted degree of antigen-loading onto carrier protein is possible to achieve. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, Med Chem Lab, NIH, 8 Ctr Dr, Bethesda, MD 20892 USA. NR 24 TC 34 Z9 35 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV PY 1998 VL 313 IS 1 BP 15 EP 20 DI 10.1016/S0008-6215(98)00261-4 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 144YN UT WOS:000077343600002 PM 9861698 ER PT J AU Kiang, J Wang, LX Tang, M Szu, SC Lee, YC AF Kiang, J Wang, LX Tang, M Szu, SC Lee, YC TI Simultaneous determination of glucosamine and glucosamine 4-phosphate in Lipid A with high-performance anion-exchange chromatography (HPAEC) SO CARBOHYDRATE RESEARCH LA English DT Article DE glucosamine; glucosamine-4-phosphate; HPAEC; Lipid A; analysis ID BACTERIAL LIPOPOLYSACCHARIDES; HYDROLYTIC CONDITIONS; ENDOTOXINS AB A method for simultaneous determination of glucosamine (GlcN) and glucosamine 4-phosphate (GlcN-4-P) in Lipid A with high-performance anion-exchange chromatography (HPAEC) is described. Lipid A is hydrolyzed with 4 M HCl for 16 h at 100 degrees C, and the peaks of glucosamine and glucosamine 4-phosphate were measured. The true GlcN value can be computed from the GlcN value after correction for the incomplete hydrolysis of GlcN-4-P, or by the combined yield of GlcN and GlcN-4-P. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Lee, YC (reprint author), Johns Hopkins Univ, Dept Biol, 3400 N Charles St, Baltimore, MD 21218 USA. NR 9 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV PY 1998 VL 312 IS 1-2 BP 73 EP 76 DI 10.1016/S0008-6215(98)00226-2 PG 4 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 141EY UT WOS:000077130700008 PM 9836452 ER PT J AU Baldwin, WS Travlos, GS Risinger, JI Barrett, JC AF Baldwin, WS Travlos, GS Risinger, JI Barrett, JC TI Melatonin does not inhibit estradiol-stimulated proliferation in MCF-7 and BG-1 cells SO CARCINOGENESIS LA English DT Article ID BREAST-CANCER-CELLS; ESTROGEN; RECEPTOR; MODULATION; EXPRESSION; 5-LIPOXYGENASE; CULTURE; BLOCK; GLAND; LINE AB Melatonin, an indolic pineal hormone, is produced primarily at night in mammals and is important in controlling biological rhythms, Previous research suggested that melatonin can attenuate proliferation in the estrogen-responsive MCF-7 breast cancer cell line. We tested whether these antiproliferative effects may have physiological consequences upon two estrogen-responsive cell lines, MCF-7 (a breast cancer cell line) and BG-1 (an ovarian adenocarcinoma cell line). Melatonin (10(-9)-10(-5) M) attenuated proliferation of MCF-7 and BG-1 cells by >20% in the absence of estrogen, However, 17 beta-estradiol exposure negated the ability of melatonin to inhibit proliferation. To substantiate this finding, cells were estrogen starved followed by multiple treatments with estradiol and melatonin, Melatonin did not inhibit estradiol-stimulated proliferation under this protocol. Estradiol increased MCF-7 and BG-1 cell cycle transition from G(1) to S phase, however, melatonin did not inhibit this transition nor did it down-regulate estradiol-induced pS2 mRNA levels measured by northern blotting, further indicating that melatonin was unable to attenuate estradiol-induced proliferation and gene expression. We also examined the effects of melatonin on estradiol-induced proliferation in MCF-7 cell xenografts in athymic nude mice. Melatonin at a dose 28 times greater than 17 beta-estradiol did not inhibit estradiol-induced proliferation in vivo. Furthermore, pinealectomy did not increase proliferation. Therefore, we conclude that melatonin does not directly inhibit estradiol-induced proliferation. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM barrett@niehs.nih.gov NR 30 TC 25 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1998 VL 19 IS 11 BP 1895 EP 1900 DI 10.1093/carcin/19.11.1895 PG 6 WC Oncology SC Oncology GA 140JR UT WOS:000077084600003 PM 9854999 ER PT J AU Glaab, WE Risinger, JI Umar, A Barrett, JC Kunkel, TA Tindall, KR AF Glaab, WE Risinger, JI Umar, A Barrett, JC Kunkel, TA Tindall, KR TI Resistance to 6-thioguanine in mismatch repair-deficient human cancer cell lines correlates with an increase in induced mutations at the HPRT locus SO CARCINOGENESIS LA English DT Article ID DNA-DAMAGE TOLERANCE; MICROSATELLITE INSTABILITY; TUMOR-CELLS; MUTATOR PHENOTYPE; CHROMOSOME-ABERRATIONS; REPLICATION FIDELITY; METHYLATING AGENTS; GENOME INSTABILITY; ENDOMETRIAL CANCER; COLORECTAL-CANCER AB Although the resistance to the cytotoxic response of certain DNA damaging agents has been well characterized in cells deficient in mismatch repair, little is known about how such resistance affects mutagenesis. Using human cancer cell lines defective in mismatch repair (MMR) and complementary cell lines in which the MMR defects were corrected by chromosome transfer, we present the cytotoxic effect and the mutagenic response at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus following exposure to the chemotherapeutic agent, 6-thioguanine (6-TG). Upon exposure to 6-TG, there was a differential cytotoxic response. The MMR-deficient cells were resistant to 6-TG exposure up to 5 mu M, whereas the MMR-proficient cell lines were significantly more sensitive at the same levels of exposure. Furthermore, the mutagenic response at HPRT induced by 6-TG was substantially increased in the MMR-deficient lines relative to the MMR-proficient cell lines. These findings support the notion that cytotoxicity to 6-TG is mediated through functional MMR and that resistance to the cytotoxic effects of 6-TG is directly associated with an increase in induced mutations in MMR-defective cells. These data suggest that the use of 6-TG as a chemotherapeutic agent may result in the selection of MMR-defective cells, thereby predisposing the patient to an increased risk for developing secondary tumors. C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. RP Tindall, KR (reprint author), NIEHS, Lab Environm Carcinogenesis & Mutagenesis, POB 12233, Res Triangle Pk, NC 27709 USA. EM tindall@niehs.nih.gov NR 51 TC 51 Z9 52 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1998 VL 19 IS 11 BP 1931 EP 1937 DI 10.1093/carcin/19.11.1931 PG 7 WC Oncology SC Oncology GA 140JR UT WOS:000077084600009 PM 9855005 ER PT J AU Millikan, RC Pittman, GS Tse, CKJ Duell, E Newman, B Savitz, D Moorman, PG Boissy, RJ Bell, DA AF Millikan, RC Pittman, GS Tse, CKJ Duell, E Newman, B Savitz, D Moorman, PG Boissy, RJ Bell, DA TI Catechol-O-methyltransferase and breast cancer risk SO CARCINOGENESIS LA English DT Article ID CARCINOGENESIS; POLYMORPHISM; METABOLISM AB Recent studies suggest that a polymorphism in catechol-O-methyltransferase (COMT) is associated with increased risk of breast cancer. Methylation by COMT is the principal pathway for inactivation of catechol estrogens, which are hypothesized to participate in estrogen-induced carcinogenesis. We examined the association of COMT genotype and breast cancer risk in a population-based, case-control study of invasive breast cancer in North Carolina. The study population consisted of 654 cases and 642 controls, with approximately equal numbers of African-American and white women and women under the age of 50 and aged 50 or over. Contrary to previous reports, we did not observe an association between one or more copies of the low activity COMT allele (COMT-L) and breast cancer risk. Multivariate relative risks (RRs) were 0.8 (95% confidence interval: 0.6-1.1) for COMT-HL and 0.8 (0.6-1.1) for COMT-LL, compared with the COMT-HH genotype, RRs for COMT did not differ among African-American and white women and we did not observe strong modification of RR estimates by menopausal status, body mass index, physical activity or other covariates, Our results suggest that COMT genotype is not related to breast cancer risk. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Millikan, RC (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, CB 7400, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [P50-CA58223, R21-CA66201]; NIEHS NIH HHS [R01-ES07128] NR 37 TC 94 Z9 96 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1998 VL 19 IS 11 BP 1943 EP 1947 DI 10.1093/carcin/19.11.1943 PG 5 WC Oncology SC Oncology GA 140JR UT WOS:000077084600011 PM 9855007 ER PT J AU Zhang, LP Rothman, N Wang, YX Hayes, RB Li, GL Dosemeci, M Yin, SN Kolachana, P Titenko-Holland, N Smith, MT AF Zhang, LP Rothman, N Wang, YX Hayes, RB Li, GL Dosemeci, M Yin, SN Kolachana, P Titenko-Holland, N Smith, MT TI Increased aneusomy and long arm deletion of chromosomes 5 and 7 in the lymphocytes of Chinese workers exposed to benzene SO CARCINOGENESIS LA English DT Article ID IN-SITU HYBRIDIZATION; MALIGNANT MYELOID DISEASES; MOLECULAR DELINEATION; DNA PROBES; ABERRATIONS; LEUKEMIA; MELPHALAN; BREAKAGE; CANCER; HUMANS AB Two of the most common cytogenetic changes in therapy- and chemical-related leukemia are the loss and long (q) arm deletion of chromosomes 5 and 7, The detection of these aberrations in lymphocytes of individuals exposed to potential leukemogens may serve as useful biomarkers of increased leukemia risk. We have used a novel fluorescence in situ hybridization (FISH) procedure to determine if specific aberrations in chromosomes 1, 5 and 7 occur at an elevated rate in the blood cells of workers exposed to benzene. Forty-three healthy workers exposed to a wide range of benzene concentrations (median 31 p.p.m,, 8 h time-weighted average) and 44 unexposed controls from Shanghai were studied. Whole blood was cultured and metaphase spreads were harvested at 72 h, Benzene exposure was associated with increases in the rates of monosomy 5 and 7 but not monosomy 1 (P < 0.001, P < 0.0001 and P = 0.94, respectively) and with increases in trisomy and tetrasomy frequencies of all three chromosomes. Long arm deletion of chromosomes 5 and 7 was increased in a dose-dependent fashion (P = 0.014 and P < 0.0001) up to 3.5-fold in the exposed workers. These results demonstrate that leukemia-specific changes in chromosomes 5 and 7 can be detected by FISH in the peripheral blood of otherwise healthy benzene-exposed workers. We suggest that aberrations in chromosomes 5 and 7 may be useful biomarkers of early biological effect for benzene exposure. C1 Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Acad Prevent Med, Inst Occupat Med, Beijing 100051, Peoples R China. RP Smith, MT (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. FU NIEHS NIH HHS [P30 ES01896, R01 ES06721, P42 ES04705] NR 39 TC 79 Z9 87 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1998 VL 19 IS 11 BP 1955 EP 1961 DI 10.1093/carcin/19.11.1955 PG 7 WC Oncology SC Oncology GA 140JR UT WOS:000077084600013 PM 9855009 ER PT J AU Peters, JM Aoyama, T Cattley, RC Nobumitsu, U Hashimoto, T Gonzalez, FJ AF Peters, JM Aoyama, T Cattley, RC Nobumitsu, U Hashimoto, T Gonzalez, FJ TI Role of peroxisome proliferator-activated receptor alpha in altered cell cycle regulation in mouse liver SO CARCINOGENESIS LA English DT Article ID COENZYME-A OXIDASE; ACYL-COA OXIDASE; <4-CHLORO-6-(2,3-XYLIDINO)-2-PYRIMIDINYLTHIO>ACETIC ACID WY-14,643; GENE-EXPRESSION; RAT-LIVER; NUCLEAR ANTIGEN; DNA-SYNTHESIS; PPAR-ALPHA; C-MYC; HEPATOCELLULAR CARCINOMAS AB The mechanisms underlying peroxisome proliferator-induced hepatocarcinogenesis are unclear but are mediated by the peroxisome proliferator-activated receptor a (PPAR alpha), To determine the role of PPAR alpha in the mechanisms of hepatocarcinogenesis, the effect of Wy-14,643 on expression patterns of acyl CoA oxidase (ACO) and proteins involved in cell proliferation in the PPAR alpha-null mouse were evaluated. AGO, CDK-1, CDK-2, CDK-4, PCNA and c-myc proteins were significantly increased in wild-type mice fed Wy-14,643 for 5 weeks or 11 months, as compared with controls. This effect was not observed in Wy-14,643-treated PPARa-null mice. Expression patterns of cyclin B1, cyclin D, cyclin E and p53 were not different in any of the groups. mRNAs encoding CDK-1, CDK-4, cyclin D1 and c-myc were also increased in wild-type mice fed Wy-14,643 but not in PPARa-null mice. These results indicate that the increase in CDK-1, CDK-4 and c-myc may be caused by an increase in transcription that is mediated directly or indirectly by PPAR alpha. Thus PPAR alpha-dependent alterations in cell cycle regulatory proteins induced by peroxisome proliferators are likely to contribute to the hepatocarcinogenicity of peroxisome proliferators. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Shinshu Univ, Sch Med, Dept Biochem, Matsumoto, Nagano 390, Japan. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. RP Peters, JM (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RI Peters, Jeffrey/D-8847-2011 NR 63 TC 114 Z9 114 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1998 VL 19 IS 11 BP 1989 EP 1994 DI 10.1093/carcin/19.11.1989 PG 6 WC Oncology SC Oncology GA 140JR UT WOS:000077084600018 PM 9855014 ER PT J AU Mebazaa, A Wetzel, RC Dodd-o, JM Redmond, EM Shah, AM Maeda, K Maistre, G Lakatta, EG Robotham, JL AF Mebazaa, A Wetzel, RC Dodd-o, JM Redmond, EM Shah, AM Maeda, K Maistre, G Lakatta, EG Robotham, JL TI Potential paracrine role of the pericardium in the regulation of cardiac function SO CARDIOVASCULAR RESEARCH LA English DT Article DE atrial natriuretic factor; endothelin; mesothelium; nitric oxide; prostaglandins ID EPICARDIAL MESOTHELIAL CELLS; NITRIC-OXIDE SYNTHASE; ENDOTHELIAL-CELLS; ENDOCARDIAL ENDOTHELIUM; RAT; FLUID; PROSTACYCLIN; MYOCYTES; HEART; PROSTAGLANDINS AB Objective: Both coronary and endocardial endothelium regulate cardiac contractile function via paracrine pathways. We investigated whether pericardial fluid (PF) and pericardial mesothelial cells (PMC) could exert a similar paracrine action. Methods: Both PF and PMC were extracted from sheep pericardial space. Endothelin-1, prostaglandins and atrial natriuretic factor were measured in PF in vivo. In the other hand, PMC were grown on T-75 flasks and microcarrier beads to investigate endothelin-1, nitric oxide and prostaglandin pathways in vitro. In addition, effects of PF and PMC effluent were tested on adult rat cardiac myocyte contraction in vitro. Results: In vitro, cultured PMC expressed endothelin-1 mRNA but not the endothelial nitric oxide synthase III, and released endothelin-1 and prostaglandins. Both PF and cultured PMC superfusate induced a potent, rapidly reversible decrease in the shortening of isolated rat cardiac myocytes. This effect was not associated with changes in intracellular calcium. In vivo, prostaglandins, atrial natriuretic factor and endothelin were present in PF. A greater concentration of atrial natriuretic factor was present in PF than in serum, suggesting molecular diffusion from the myocardium to PF. Preliminary results show that the instillation of vasoactive agents into the pericardial space of dogs rapidly alter coronary and systemic vascular tone, consistent with a molecular diffusion of these substances from PF into the myocardium and circulation. Conclusions: In addition to its mechanical role, the pericardium may contribute to the integration and the regulation of cardiovascular function via a paracrine mechanism. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Pulm Anesthesiol Lab, Baltimore, MD 21287 USA. NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Univ Wales Coll Med, Dept Cardiol, Cardiff CF4 4XN, S Glam, Wales. Fac Med Pitie Salpetriere, Biochim Lab, Paris, France. Hop Lariboisiere, APHP, Dept Anesthesiol & Crit Care Med, F-75475 Paris, France. RP Mebazaa, A (reprint author), Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Pulm Anesthesiol Lab, Baltimore, MD 21287 USA. OI Shah, Ajay/0000-0002-6547-0631 FU NHLBI NIH HHS [R0-1 HL 39138-03] NR 41 TC 35 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD NOV PY 1998 VL 40 IS 2 BP 332 EP 342 DI 10.1016/S0008-6363(98)00134-5 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 135PB UT WOS:000076810500014 PM 9893727 ER PT J AU Desai, KV Flanders, KC Kondaiah, P AF Desai, KV Flanders, KC Kondaiah, P TI Expression of transforming growth factor-beta isoforms in the rat male accessory sex organs and epididymis SO CELL AND TISSUE RESEARCH LA English DT Article DE coagulating gland; epididymis; gene expression; prostate; seminal vesicle; rat (Wistar) ID TGF-BETA; PROSTATE-CANCER; FACTOR-BETA-1; LOCALIZATION; MICE; GROWTH-FACTOR-BETA-1; RECEPTORS; DEATH; CELLS; PROLIFERATION AB We studied the expression and distribution of transforming growth factor-beta (TGF-beta) isoforms in the rat male accessory sex glands and the epididymis. Our data demonstrate the expression of both TGF-beta 1 and -beta 3 isoforms in ventral prostate (VP), seminal vesicle (SV), coagulating gland (CG), and epididymis (E) by Northern blot analysis. In addition, there was differential expression of TGF-beta 3 in the three regions of epididymis, the corpus region being the highest. Immunostaining data showed intense staining for latent TGF-beta 1 in all the male accessory glands. In contrast, no staining using antibodies specific for active TGF-beta 1 was observed. No expression of TGF-beta 2 was evident either by immunohistochemistry or Northern blot analysis. The presence of mature TGF-beta 3 protein was observed in the secretory epithelium of VP, CG, and corpus E. There was no detectable staining of TGF-beta 3 in the seminal vesicle and caput and cauda regions of epididymis. These data suggest possible differential regulation of TGF-beta isoform expression in the male reproductive system and predict unique roles for individual TGF-beta isoforms in sperm maturation and maintenance. C1 Indian Inst Sci, Dept Mol Reprod Dev & Genet, Bangalore 560012, Karnataka, India. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Kondaiah, P (reprint author), Indian Inst Sci, Dept Mol Reprod Dev & Genet, Bangalore 560012, Karnataka, India. NR 37 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD NOV PY 1998 VL 294 IS 2 BP 271 EP 277 DI 10.1007/s004410051177 PG 7 WC Cell Biology SC Cell Biology GA 133YV UT WOS:000076715900008 PM 9799443 ER PT J AU Adachi, H Adams, A Hughes, FM Zhang, JD Cidlowski, JA Jetten, AM AF Adachi, H Adams, A Hughes, FM Zhang, JD Cidlowski, JA Jetten, AM TI Induction of apoptosis by the novel retinoid AHPN in human T-cell lymphoma cells involves caspase-dependent and independent pathways SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE retinoids; apoptosis; lymphoma; caspase; cell proliferation ID ACTIVATION-INDUCED APOPTOSIS; FAS-MEDIATED APOPTOSIS; ACID RECEPTOR; CYTOCHROME-C; CARCINOMA CELLS; CANCER CELLS; RAR-ALPHA; IN-VIVO; DEATH; BCL-2 AB Retinoids play an important role in the control of lymphocyte function and homeostasis in the thymus. In this study, we show that the induction of growth arrest and apoptosis ire a variety of T-cell lymphoma cell lines, including Jurkat and Molt-4 cells, is highly specific for the synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN) since all-trans retinoic acid (RA), the RAR-selective retinoid TTAB, the RXR-selective retinoid SR11217 and the retinoid SR11302 exhibiting selective anti-AP1 activity, do not induce apoptosis or cause growth arrest. These findings support the concept that the effects of AHPN on proliferation and induction of apoptosis are mediated by a novel signaling pathway. AHPN-induced apoptosis is associated with an induction of internucleosomal DNA-fragmentation, increased annexin V binding and a 30-fold stimulation of caspase-3-like activity. Overexpression of Bcl-2 in Molt-4 cells greatly inhibits the induction of apoptosis by AHPN as indicated by the inhibition of DNA-fragmentation, annexin V binding and caspase-3-like activity. However, Bcl-2 overexpression does not interfere with the ability of AHPN to cause growth arrest or accumulation of cells in the early S-phase of the cell cycle, indicating that the effects of AHPN on growth arrest can be uncoupled from the effects on apoptosis, The caspase inhibitor Z-VAD-FMK, at concentrations that totally block caspase activity, delays but does not prevent cell death and does not affect the accumulation of cells in the S-phase of the cell cycle. Our results show that induction of caspase-3-like activity plays an important role in the execution of AHPN-induced apoptosis but cells can undergo cell death in the absence of this activity suggesting that AHPN-induced cell death involves caspase-dependent and -independent mechanisms. C1 NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Endocrinol Sect, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Program Mol Med, Durham, NC 27710 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 NR 58 TC 44 Z9 44 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD NOV PY 1998 VL 5 IS 11 BP 973 EP 983 DI 10.1038/sj.cdd.4400445 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 136UQ UT WOS:000076877900007 PM 9846184 ER PT J AU Kurenova, E Champion, L Biessmann, H Mason, JM AF Kurenova, E Champion, L Biessmann, H Mason, JM TI Directional gene silencing induced by a complex subtelomeric satellite from Drosophila SO CHROMOSOMA LA English DT Article ID POSITION-EFFECT VARIEGATION; GYPSY TRANSPOSABLE ELEMENT; BROKEN CHROMOSOME ENDS; FUNCTIONAL-ANALYSIS; WHITE LOCUS; HET-A; MELANOGASTER; HETEROCHROMATIN; EXPRESSION; CHROMATIN AB The telomeric regions in Drosophila cause transcriptional silencing of integrated transgenes. A complex satellite has recently been identified in the subterminal region of the left arm of chromosome 2 that is a good candidate for the source of the observed telomeric silencing, because genetically marked transposable elements that have inserted into this subtelomeric array show repression and variegation of the reporter gene. We asked whether this satellite can also cause transcriptional repression in ectopic chromosomal positions by placing it upstream of a mini-white reporter gene in P element constructs used for germ line transformation. The transgenes are shielded from external influences at the integration site using SU(HW) binding sites at either end. It was found that the satellite represses transcription of the reporter gene in an orientation dependent and an array length dependent manner. The satellite does not, however, induce variegation under the conditions used. The repressed transgenes do not respond to typical modifiers of centromeric position effect variegation, such as Su(var)205(5) Su(var)2-1(1), Su(var)3-1(1), and Su(var)3-6(1) or to the addition of a Y chromosome. However, as with the original variegating telomeric insertion, suppression in the transgenes is relieved by Su(z)2(5), suggesting that suppression induced by the subtelomeric satellite retains aspects of telomeric silencing in ectopic positions. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. RP Mason, JM (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. FU NIAID NIH HHS [AI36248]; NIGMS NIH HHS [GM46211] NR 62 TC 31 Z9 31 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD NOV PY 1998 VL 107 IS 5 BP 311 EP 320 DI 10.1007/s004120050313 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 146TZ UT WOS:000077448600005 PM 9880764 ER PT J AU Duna, GE Cotch, MF Galperin, C Hoffman, DB Hoffman, GS AF Duna, GE Cotch, MF Galperin, C Hoffman, DB Hoffman, GS TI Wegener's granulomatosis: Role of environmental exposures SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE Wegener's granulomatosis; epidemiology; inhalants; host susceptibility ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES AB Objective The etiology of Wegener's granulomatosis (WG) remains unknown. The predominant involvement of the airways and the presence of neutrophilic alveolitis at disease onset have led us to postulate that an inhaled agent may trigger the onset of WG. This study is designed to analyze differences in self-reported environmental exposures between patients with WG and various control populations. Methods We conducted a standard interviewer-administered questionnaire case controlled survey of 101 patients with WG, 54 healthy controls, 24 patients with sarcoidosis or idiopathic pulmonary fibrosis, and 45 patients with various inflammatory rheumatologic diseases. We assessed environmental exposures for one year prior to the onset of symptoms or prior to the interview date for healthy controls. Results Seasonal differences in the onset of WG were not apparent. More than 75% of the patients in all groups noted remarkable environmental exposure to inhaled substances (fumes or particulate matter), within one year prior to disease onset for WG and other diseases or prior to the interview date for healthy controls. Differences between WG and control groups were apparent in several categories of exposure. Statistically significant differences occurred in regard to avocational exposure to fumes or particulate materials (WG > healthy controls and rheumatic disease controls), residential exposure to particulate materials from construction (WC > pulmonary disease controls) and occupational exposure to pesticides (WG > healthy, pulmonary and rheumatic disease controls). Conclusion This study confirms the absence of seasonal differences in the onset of WG. It also demonstrates high rates of self-reported environmental exposures to inhaled substances in WG and all control populations. It is possible that more significant differences in the quality, quantity and intensity of exposure to inhaled potential precipitants of WG had occurred between groups, but were not detected by our survey Alternatively, the absence of substantial differences in patients with WG and controls may reflect the more important role of host susceptibility factors. C1 Cleveland Clin Fdn, Dept Rheumat & Immunol Dis, Cleveland, OH 44195 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Hoffman, GS (reprint author), Cleveland Clin Fdn, Dept Rheumat & Immunol Dis, A50,9500 Euclid Ave, Cleveland, OH 44195 USA. OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z99 EY999999] NR 15 TC 44 Z9 47 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD NOV-DEC PY 1998 VL 16 IS 6 BP 669 EP 674 PG 6 WC Rheumatology SC Rheumatology GA 134LF UT WOS:000076743900005 PM 9844758 ER PT J AU Foss, FM Raubitscheck, A Mulshine, JL Fleisher, TA Reynolds, JC Paik, CH Neumann, RD Boland, C Perentesis, P Brown, MR Frincke, JM Lollo, CP Larson, SM Carrasquillo, JA AF Foss, FM Raubitscheck, A Mulshine, JL Fleisher, TA Reynolds, JC Paik, CH Neumann, RD Boland, C Perentesis, P Brown, MR Frincke, JM Lollo, CP Larson, SM Carrasquillo, JA TI Phase I study of the pharmacokinetics of a radioimmunoconjugate, Y-90-T101, in patients with CD5-expressing leukemia and lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID T-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; T101 MONOCLONAL-ANTIBODY; ANTI-CD20 ANTIBODY; RADIOIMMUNOTHERAPY; THERAPY; RADIOIMMUNODETECTION; ANTIGEN AB Ten patients with advanced or refractory CDS-expressing hematologic neoplasms [two with chronic lymphocytic leukemia and eight with cutaneous T-cell lymphoma (CTCL)] were treated in a Phase I study with the radioimmunoconjugate Y-90-T101, which targets CD5+ lymphocytes, Prior imaging studies using In-111-T101 demonstrated uptake in involved lymph nodes and skin in patients with CTCL, and Phase I studies with unmodified T101 demonstrated transient responses. In this study, patients were treated with 5 or 10 mCi of Y-90 chelated to T101 via isothiocyanatobenzyl diethylenetriamine pentaacetic acid, along with tracer doses of In-111-T101 for imaging. The biodistribution of the radioimmunoconjugate was determined by measuring Y-90 and In-111 blood clearance, urine excretion, and accumulation in bone marrow and in involved skin lesions. The intravascular pharmacokinetics of Y-90 were predicted by In-111-labeled T101, The greatest differences in biodistribution between "'In and 90Y were in the higher bone accumulation of 90Y and its lower urinary excretion. Imaging studies demonstrated targeting of skin lesions and involved lymph nodes in CTCL patients. The predominant toxicity was bone marrow suppression. Rapid antigenic modulation of CD5 on circulating T and B cells was observed. Recovery of T-cell populations occurred within 2-3 weeks; however, suppression of B-cell populations persisted after 5+ weeks, All CTCL patients developed human antimouse antibody after one cycle and thus were not retreated; one patient with chronic lymphocytic leukemia received a second cycle of therapy. Partial responses occurred in five patients, two with chronic lymphocytic leukemia and three with CTCL, The median response duration was 23 weeks. One CTCL patient who subsequently received electron beam irradiation to a residual lesion is disease-free after 6 years. C1 NCI, Navy Med Oncol Branch, Bethesda, MD 20889 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20889 USA. NIH, Warren G Magnuson Clin Ctr, Dept Clin Pathol, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. Hybritech Inc, San Diego, CA 92121 USA. RP Foss, FM (reprint author), Tufts Univ, New England Med Ctr, 750 Washington St,NEMC 542, Boston, MA 02111 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 21 TC 33 Z9 34 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1998 VL 4 IS 11 BP 2691 EP 2700 PG 10 WC Oncology SC Oncology GA 136UK UT WOS:000076877400014 PM 9829731 ER PT J AU Ren, QF Kao, V Grem, JL AF Ren, QF Kao, V Grem, JL TI Cytotoxicity and DNA fragmentation associated with sequential gemcitabine and 5-fluoro-2 '-deoxyuridine in HT-29 colon cancer cells SO CLINICAL CANCER RESEARCH LA English DT Article ID MOUSE FM3A CELLS; PHASE-II TRIAL; 2',2'-DIFLUORODEOXYCYTIDINE GEMCITABINE; CARCINOMA CELLS; LEUKEMIA-CELLS; STRAND BREAKS; DEATH; MECHANISM; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; FLUOROURACIL AB The combined cytotoxic effects of the antimetabolites gemcitabine (dFdCyd) and 5-fluoro-2'-deoxyuridine (FdUrd) were studied. Cytotoxicity, biochemical perturbations, and DNA damage seen with dFdCyd and FdUrd alone and in combination were evaluated in HT-29 human colon cancer cells. A 4-h exposure to dFdCyd followed by FdUrd for 24 h produced more than additive cytotoxicity and marked S-phase accumulation. Cells progressed through the cell cycle, however, after a 22-h drug-free interval. [H-3]dFdCyd was rapidly metabolized to the 5'-triphosphate and incorporated into DNA, [H-3]FdUrd was anabolized exclusively to FdUrd monophosphate, and preexposure to dFdCyd did not affect FdUrd monophosphate formation. Thymidylate synthase catalytic activity was inhibited by 48% after a 4-h exposure to 10 nM FdUrd and by 80% after exposure to the combination, Sequential 4-h exposures to 15 nM dFdCyd and 10 nM FdUrd led to greater depletion of dTTP pools (29% of control) than with either drug alone. Greater effects on nascent DNA integrity were seen with sequential dFdCyd followed by FdUrd, Although parental DNA damage was not evident immediately after exposure to 15 nM dFdCyd for 4 h followed by 10 nM FdUrd for 24 h, high molecular mass DNA fragmentation was evident 72-96 h after drug removal. Sequential dFdCyd/FdUrd was associated with prominent disturbance of the cell cycle, dTTP pool depletion, dATP/dTTP imbalance, and nascent DNA damage. Induction of double-strand parental DNA damage and cell death was delayed, consistent with postmitotic apoptosis. C1 NCI, Navy Med Branch, NMNC, Dev Therapeut Dept,Div Clin Sci, Bethesda, MD 20889 USA. RP Grem, JL (reprint author), NCI, Navy Med Branch, NMNC, Dev Therapeut Dept,Div Clin Sci, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM jgrem@helix.nih.gov NR 34 TC 63 Z9 65 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1998 VL 4 IS 11 BP 2811 EP 2818 PG 8 WC Oncology SC Oncology GA 136UK UT WOS:000076877400030 PM 9829747 ER PT J AU Akamatsu, Y Murphy, JC Nolan, KF Thomas, P Kreitman, RJ Leung, SO Junghans, RP AF Akamatsu, Y Murphy, JC Nolan, KF Thomas, P Kreitman, RJ Leung, SO Junghans, RP TI A single-chain immunotoxin against carcinoembryonic antigen that suppresses growth of colorectal carcinoma cells SO CLINICAL CANCER RESEARCH LA English DT Article ID DISULFIDE-STABILIZED FV; PSEUDOMONAS EXOTOXIN; RECOMBINANT IMMUNOTOXINS; INTERLEUKIN-2 RECEPTOR; MONOCLONAL-ANTIBODIES; COMPLETE REGRESSION; LINE MIP-101; TUMOR-CELLS; NUDE-MICE; EXPRESSION AB We have engineered an anti-carcinoembryonic antigen (CEA) single-chain immunotoxin derived from humanized anti-CEA antibody (hMN14) and a truncated Pseudomonas exotoxin (PE), PE40, The purified anti-CEA immunotoxin (hMN14(FV)-PE40) was first measured for binding affinity against a CEA-positive colorectal carcinoma cell line and compared with its parental IgG and the monovalent Fab fragment. The K-a of sFv-PE40, Fab, and IgG were 5 x 10(7), 6 x 10(7), and 3 x 10(8) M-1, respectively. There was no significant affinity loss by conversion of Fab to the single-chain Fv, but these monovalent forms were 5-6-fold reduced in affinity compared with the parental IgG, In cytotoxicity assays, the hMN14(Fv)-PE40 showed specific growth suppression of CEA-expressing colon cancer cell lines MIP-CEA (high CEA) and LS174T (moderate CEA) with IC(50)s of 12 ng/ml (0.2 nM) and 69 ng/ml (1.1 nM), These IC(50)s correlated inversely with the surface expression of CEA, such that 50% killing was equivalent for each cell type when expressed in toxin molecules bound/cell (3000-5000), The presence of soluble CEA up to 1000 ng/ml did not affect the cytotoxicity against CEA-expressing cells, with 50% suppression only at 4000 ng/ml that correlated with the binding K-d of the single-chain Fv, The stability of the hMN14(Fv)-PE40 molecule at 37 degrees C was confirmed by bioassay and by lack of aggregation. Our hMN14(Fv)-PE40 may be clinically useful for tumors with high CEA expression without affecting normal tissues with low or absent CEA, even in patients with high soluble antigen levels. C1 Harvard Univ, Inst Med,Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol,Biotherapeut Dev Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Immunomed Inc, Morris Plains, NJ 07950 USA. RP Junghans, RP (reprint author), Harvard Univ, Inst Med,Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol,Biotherapeut Dev Lab, Room 403, Boston, MA 02215 USA. NR 39 TC 12 Z9 13 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1998 VL 4 IS 11 BP 2825 EP 2832 PG 8 WC Oncology SC Oncology GA 136UK UT WOS:000076877400032 PM 9829749 ER PT J AU Schrump, DS Matthews, W Chen, GA Mixon, A Altorki, NK AF Schrump, DS Matthews, W Chen, GA Mixon, A Altorki, NK TI Flavopiridol mediates cell cycle arrest and apoptosis in esophageal cancer cells SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENES; BREAST-CARCINOMA CELLS; BARRETTS-ESOPHAGUS; KINASE INHIBITOR; LUNG-CANCER; EXPRESSION; LINES; P16(INK4); PROTEIN; ADENOCARCINOMA AB Esophageal adenocarcinoma (SKGT-2, SKGT-4, and SKGT-5) and epidermoid carcinoma (HCE-4) cells containing variable retinoblastoma (Rb), cyclin D1, p16, and p53 expression patterns were exposed to the synthetic flavone, flavopiridol. The IC(50) was approximately 100-150 nM for each of these cell lines. Exposure of esophageal carcinoma cells to 300 nM flavopiridol induced cell cycle arrest and apoptosis, resulting in a 90% inhibition of proliferation relative to that of nontreated cells after a 5-day exposure to the drug. Western blot analysis revealed diminution of cyclin D1, Rb, and p107 protein levels after flavopiridol exposure. Whereas cell cycle arrest and overall growth inhibition did not correlate in any obvious manner with the genotype of these cell lines, apoptosis seemed to be more pronounced in SKGT-2 and SKGT-4 cells that lack Rb expression. Pretreatment of esophageal cancer cells with 9-cis-retinoic acid did not substantially potentiate flavopiridol activity in these cell lines. Although the precise mechanism of flavopiridol-mediated cytotoxicity has not been fully defined, this drug is an attractive agent for molecular intervention in esophageal cancers and their precursor lesions; further evaluation of flavopiridol in this clinical context is warranted. C1 NCI, Surg Branch, NIH, Thorac Oncol Sect, Bethesda, MD 20892 USA. Cornell Univ, Coll Med, Dept Cardiothorac Surg, New York, NY 10021 USA. RP Schrump, DS (reprint author), NCI, Surg Branch, NIH, Thorac Oncol Sect, 10 Ctr Dr,Room 2B-07, Bethesda, MD 20892 USA. NR 45 TC 61 Z9 64 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1998 VL 4 IS 11 BP 2885 EP 2890 PG 6 WC Oncology SC Oncology GA 136UK UT WOS:000076877400039 PM 9829756 ER PT J AU Berg, SL Murry, DJ McCully, CL Godwin, K Balis, FM AF Berg, SL Murry, DJ McCully, CL Godwin, K Balis, FM TI Pharmacokinetics of O-6-benzylguanine and its active metabolite 8-oxo-O-6-benzylguanine in plasma and cerebrospinal fluid after intrathecal administration of O-6-benzylguanine in the nonhuman primate SO CLINICAL CANCER RESEARCH LA English DT Article ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; IN-VITRO; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA; DNA; O6-BENZYLGUANINE; SENSITIVITY; VIVO; BCNU AB O-6-Benzylguanine (O(6)BG) irreversibly inactivates the single-turnover DNA repair protein alkylguanine-alkyltransferase. Thus, O(6)BG increases tumor-cell sensitivity to alkylating agents such as carmustine, lomustine, procarbazine, and temozolomide, We investigated the pharmacokinetic behavior of O(6)BG and O-6-benzyl-8-oxoguanine (8-oxo-O(6)BG) in cerebrospinal fluid (CSF) and plasma after intraventricular administration of O(6)BG in a nonhuman primate model, In our study, three animals received a single l-mg dose of O(6)BG into the lateral ventricle. CSF from the 4(th) ventricle and plasma samples were collected after administration, and O(6)BG and 8-oxo-O(6)BG concentrations were measured by high-performance liquid chromatography, Four additional animals received 1 mg of O(6)BG via the intralumbar route weekly for 6 weeks to assess the feasibility and toxicity of this route of administration. The peak O(6)BG CSF concentration was 412 +/- 86 mu M, the t(1/2) was 0.52 +/- 0.02 h, the clearance was 0.22 +/- 0.01 ml/min, and the area under the concentration-time curve was 319 +/- 15 mu M.h in 4(th) ventricular CSF, The peak CSF concentration of 8-oxo-O(6)BG in CSF was 1.9 +/- 0.4 mu M, the t(1/2) was 0.76 +/- 0.03 h, and the area under the concentration-time curve was 5.0 +/- 1.1 mu M.h. Both O(6)BG and 8-oxo-O(6)BG were detected in the plasma 0.5-3 h after intraventricular O(6)BG administration. The plasma peak concentration of O(6)BG was 0.4 mu M at 30 min, and the concentration was <0.1 mu M by 3 h, The plasma concentration of 8-oxo-O(6)BG was 0.2 mu M at 30 min and 0.6 mu M at 3 h, The animals tolerated the single intraventricular dose and 6 weekly intralumbar doses of O(6)BG without toxicity. We concluded that intrathecal administration of O(6)BG is well tolerated in the nonhuman primate and seems to have a substantial pharmacokinetic advantage over systemic administration for meningeal tumors. C1 Texas Childrens Hosp, Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Berg, SL (reprint author), Texas Childrens Canc Ctr, MC3-3320,6621 Fannin St, Houston, TX 77030 USA. NR 21 TC 2 Z9 2 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1998 VL 4 IS 11 BP 2891 EP 2894 PG 4 WC Oncology SC Oncology GA 136UK UT WOS:000076877400040 PM 9829757 ER PT J AU Teschan, PE Beck, GJ Dwyer, JT Greene, T Klahr, S Levy, AS Mitch, WE Snetselaar, LG Steinman, TI Walser, M AF Teschan, PE Beck, GJ Dwyer, JT Greene, T Klahr, S Levy, AS Mitch, WE Snetselaar, LG Steinman, TI Walser, M TI Effect of a ketoacid-aminoacid-supplemented very low protein diet on the progression of advanced renal disease: a reanalysis of the MDRD feasibility study SO CLINICAL NEPHROLOGY LA English DT Article DE progressive renal disease; protein intake restriction; ketoacid-aminoacid; glomerular filtration rate ID LONGITUDINAL DATA; ACID SUPPLEMENT; FAILURE; RESTRICTION; INSUFFICIENCY; DIALYSIS AB Background: We reanalyzed the data of the Modification of Diet in Renal Disease (MDRD) feasibility study to ascertain the effects of ketoacid- and aminoacid-supplemented very low protein diets. Methods: Sixty-six patients with advanced renal disease (Study B, baseline glomerular filtration rate (GFR) 7.5-24 ml/min/1.73 m(2)) were randomly assigned to a low protein diet (L, 0.575 g/kg/d), or a very low protein diet (0.28 g/kg/d) supplemented either with a ketoacid-aminoacid mixture (diet K) or with a mixture of essential aminoacids (diet J). Thirty patients with moderate renal disease (Study A, baseline GFR 25-80 ml/min/1.73 m2) were randomly assigned to a usual protein diet (M, 1.2 g/kg/d), diet L, or diet K. Mean follow-up was 14 months. Results: In Study B, GFR decline differed among the three diets (p = 0.028). Pairwise comparisons showed that the mean +/- SE GFR decline in ml/min/mo in diet K [-0.250 +/- 0.072] was slower than in diet J [-0.533 +/- 0.074] (p = 0.008) despite similar achieved protein intakes. The mean GFR decline in diet L [-0.394 +/- 0.068] was intermediate between, and did not differ significantly from the rates of decline in the other two groups. In Study A, consistent with a hemodynamic effect, the mean GFR decline varied directly with the reduction in protein intake in diets M, L and K (p = 0.028) during the first four months of follow-up, but thereafter did not differ among the diet groups (p = 0.76). Conclusion: The study suggests that supplementation of a very low protein diet with the ketoacid-aminoacid mixture used in this feasibility study slowed the progression of advanced renal disease more than supplementation with an amino acid mixture. C1 Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Vanderbilt Univ, Nashville, TN 37240 USA. New England Med Ctr, Boston, MA 02111 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Iowa, Iowa City, IA 52242 USA. Beth Israel Hosp, Boston, MA 02215 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Beck, GJ (reprint author), Cleveland Clin Fdn, Dept Biostat & Epidemiol, Wb4,9500 Euclid Ave, Cleveland, OH 44195 USA. OI Dwyer, Johanna/0000-0002-0783-1769 NR 26 TC 24 Z9 32 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD NOV PY 1998 VL 50 IS 5 BP 273 EP 283 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 138PF UT WOS:000076980900002 PM 9840314 ER PT J AU Blanchet, PJ Fang, J Gillespie, M Sabounjian, LA Locke, KW Gammans, R Mouradian, MM Chase, TN AF Blanchet, PJ Fang, J Gillespie, M Sabounjian, LA Locke, KW Gammans, R Mouradian, MM Chase, TN TI Effects of the full dopamine D1 receptor agonist dihydrexidine in Parkinson's disease SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE Parkinson's disease; dihydrexidine; D1 agonist; dopamine; dyskinesia ID RADIOLIGAND BINDING; LEVODOPA; MONKEYS; D-1; CLASSIFICATION; STIMULATION; HEART AB The contribution of dopamine D1 receptor stimulation to the motor effects of dopaminergic drugs in patients with Parkinson's disease remains undetermined. The authors of this article studied the clinical efficacy, pharmacokinetics, and tolerability of the full D1 receptor agonist dihydrexidine, (+/-)-trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a] phenanthridine hydrochloride in a double-blind, placebo-controlled trial in four patients with Parkinson's disease. Single intravenous doses were carefully titrated according to a fixed schedule ranging from 2 mg to the highest tolerated dose (or a maximum of 70 mg) infused over either 15 of 120 minutes. The only patient to achieve a plasma drug concentration greater than 100 ng/ml had a brief but definite motor improvement accompanied by choreic dyskinesias similar to the response to levodopa. Dose-limiting adverse effects, including flushing, hypotension, and tachycardia, were observed in all cases, especially with rapid infusions. No nausea or emesis occurred. Pharmacokinetic studies yielded a plasma half-life <5 minutes. These preliminary data suggest that dihydrexidine has a marginal therapeutic window for providing an antiparkinsonian effect, although it remains uncertain how much of this effect is attributable to pure D1 receptor stimulation. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Interneuron Pharmaceut Inc, Lexington, MA USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Room 5C103,10 Ctr Dr MSC 1406, Bethesda, MD 20892 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 24 TC 33 Z9 34 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD NOV-DEC PY 1998 VL 21 IS 6 BP 339 EP 343 PG 5 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 144CZ UT WOS:000077297300004 PM 9844789 ER PT J AU Piscitelli, SC Forrest, A Vogel, S Chaitt, D Metcalf, J Stevens, R Baseler, M Davey, RT Kovacs, JA AF Piscitelli, SC Forrest, A Vogel, S Chaitt, D Metcalf, J Stevens, R Baseler, M Davey, RT Kovacs, JA TI Pharmacokinetic modeling of recombinant interleukin-2 in patients with human immunodeficiency virus infection SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID COLONY-STIMULATING FACTOR; PURIFIED HUMAN INTERLEUKIN-2; NATURAL-KILLER; INVIVO; DISPOSITION; MECHANISM; CHILDREN; CANCER; TRIAL; CELLS AB A novel model was developed to characterize the time-varying clearance of recombinant interleukin-2 (IL-2), Sixty-eight patients with human immunodeficiency virus infection received 83 cycles of IL-2 either by continuous infusion or by subcutaneous injection for 5 days, IL-2 concentrations after intravenous infusions peaked at 24 hours and then declined by 55% to 78% during the remainder of the infusion. Soluble IL-2 receptors increased greater than 10-fold before gradually returning to baseline. Subcutaneous administration showed a dose-dependent decrease in area under the concentration-time curve (AUC) between days 1 and 5. A model was developed in 9 patients who had IL-2 concentrations and soluble IL-2 receptors determined by ELISA, Concentrations were fitted by an indirect stimulatory pharmacodynamic model, An additional 59 patients with only IL-2 concentrations were fitted to a simplified empiric model. Both models provided an overall r(2) of 0.99 for the plot of observed versus fitted concentrations. The time-dependent increase in IL-2 clearance, likely receptor-mediated, was well described with use of an indirect-effects pharmacokinetic-pharmacodynamic model. C1 NIAID, Ctr Clin, Dept Pharm, NIH, Bethesda, MD 20892 USA. NIAID, Ctr Clin, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Sch Pharm, Amherst, NY USA. Sci Applicat Int Corp, Frederick, MD USA. RP Piscitelli, SC (reprint author), NIAID, Ctr Clin, Dept Pharm, NIH, Bldg 10,Room 1N257, Bethesda, MD 20892 USA. NR 26 TC 12 Z9 12 U1 1 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 1998 VL 64 IS 5 BP 492 EP 498 DI 10.1016/S0009-9236(98)90132-1 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 141WT UT WOS:000077167800004 PM 9834041 ER PT J AU Dionne, RA Max, MB Gordon, SM Parada, S Sang, C Gracely, RH Sethna, NF MacLean, DB AF Dionne, RA Max, MB Gordon, SM Parada, S Sang, C Gracely, RH Sethna, NF MacLean, DB TI The substance P receptor antagonist CP-99,994 reduces acute postoperative pain SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DORSAL HORN NEURONS; RAT SPINAL-CORD; TRIGEMINAL NUCLEUS CAUDALIS; PRIMARY SENSORY NEURONS; GENE-RELATED PEPTIDE; METHYL-D-ASPARTATE; INFLAMMATORY HYPERALGESIA; IMMUNOREACTIVE NEURONS; NOCICEPTIVE RESPONSES; PERSISTENT PAIN AB Background: Animal studies suggest that substance P, a peptide that preferentially activates the neurokinin-1 (NK1) receptor, is involved in pain transmission, with particular importance in pain after inflammation. Methods: The analgesic efficacy of CP-99,994, a NK1 receptor antagonist, was compared with ibuprofen and placebo in 78 subjects undergoing third molar extraction. The initial 60 subjects randomly received 1 of 3 possible treatments in a double-blind fashion before oral surgery: 750 mu g/kg CP-99,994 infused intravenously over 5 hours on a tapering regimen starting 2 hours before surgery, 600 mg oral ibuprofen 30 minutes before surgery, or placebo. In a second study, 18 subjects were randomized to the same regimens starting 30 minutes before surgery to maximize the amount of CP-99,994 circulating during pain onset. Results: In the first study, ibuprofen significantly reduced pain, as measured by visual analog scale, from 90 to 240 minutes postoperatively compared with placebo, CP-99,994 produced analgesia that was significant at 90 minutes (P < 0.01 compared with placebo), but not at subsequent time points. In the second study, ibuprofen and, to a lesser extent, CP-99,994 significantly suppressed pain in comparison to placebo at 60, 90, and 120 minutes (P < 0.05). The incidence of side effects was similar across groups, Conclusions: This replicate demonstration that a NK1 receptor blocker relieves clinical pain supports the hypothesis that substance P contributes to the generation of pain in humans. The reduction in postoperative pain at doses not producing side effects suggests that NK1 antagonists may be clinically useful. C1 NIDR, Pain & Neurosensory Mechanisms Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. Pfizer Inc, Pfizer Cent Res, Dept Expt Med, Groton, CT 06340 USA. RP Dionne, RA (reprint author), 10 Ctr Dr,Room 1N-103, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [Z01 DE 00286 NA, Z01 DE 00366 NA] NR 45 TC 59 Z9 61 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 1998 VL 64 IS 5 BP 562 EP 568 DI 10.1016/S0009-9236(98)90140-0 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 141WT UT WOS:000077167800012 PM 9834049 ER PT J AU Qualls, CW Lubet, RA Lochmiller, RL Elangbam, CS Lish, JW Nims, RW AF Qualls, CW Lubet, RA Lochmiller, RL Elangbam, CS Lish, JW Nims, RW TI Cytochrome P450 induction in feral Cricetid rodents: a review of field and laboratory investigations SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY LA English DT Review DE Cricetidae; P450 induction; Sigmodon; Reithrodontomys; Microtus; Peromyscus ID RATS SIGMODON-HISPIDUS; DRUG-METABOLIZING-ENZYMES; MONOOXYGENASE ACTIVITIES; DIETARY EXPOSURE; AROCLOR-1254; HAMSTER; LIVER; DEHYDROGENASE; ETHANOL; MOUSE AB The constitutive and inducible hepatic cytochromes P450 of various feral Cricetid rodents (family Cricetidae, comprising various New World rats and mice, hamsters, gerbils and voles), have been examined in a relatively limited number of field and laboratory investigations. These studies, reviewed herein, have employed substrates and immunochemical reagents that are diagnostic for individual P450 subfamilies of Rattus norvegicus (the common laboratory species derived from the Norway rat, a member of the family Muridae). The results have demonstrated that the feral rodents display hepatic responses to prototypic CYP1A inducers (3-methylcholanthrene, beta-naphthoflavone) similar to those displayed by R. norvegicus and Mus musculus (the common laboratory species derived from the house mouse, another member of the family Muridae). At least one study has demonstrated the induction, by ethanol, of a protein immunochemically similar to CYP2E1 in a Cricetid rodent. In Cricetid rodents, phenobarbital-type inducers cause the induction of a hepatic protein immunologically similar to that primarily induced (CYP2B) in R. norvegicus and M. musculus. The proteins induced in the Cricetid rodents, however, exhibit striking differences in substrate specificity, compared to the proteins induced in R. norvegicus. These results indicate that the previously described differences between the P450 induction responses exhibited by the commonly utilized laboratory species R. norvegicus and M. musculus (family Muridae) and the Syrian hamster and gerbil (family Cricetidae) are observed as a generality for members of the Cricetid family of rodents. (C) 1998 Elsevier Science Inc. All rights reserved. C1 Oklahoma State Univ, Dept Anat Pathol & Pharmacol, Stillwater, OK 74078 USA. NCI, Chemoprevent Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. Oklahoma State Univ, Dept Zool, Stillwater, OK 74078 USA. NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Nims, RW (reprint author), MA BioServ Inc, 9900 Blackwell Rd, Rockville, MD 20850 USA. EM rn-ims@microbio.com NR 35 TC 17 Z9 17 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0742-8413 J9 COMP BIOCHEM PHYS C JI Comp. Biochem. Physiol. C-Pharmacol. Toxicol. Endocrinol. PD NOV PY 1998 VL 121 IS 1-3 BP 55 EP 63 DI 10.1016/S0742-8413(98)10029-4 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology GA 144ZA UT WOS:000077344800005 PM 9972450 ER PT J AU Jones, CR Lubet, RA Henneman, JR Nims, RW AF Jones, CR Lubet, RA Henneman, JR Nims, RW TI Dose-response relationships for cytochrome P450 induction by phenobarbital in the cotton rat (Sigmodon hispidus) SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY LA English DT Article DE Cricetidae; P450 induction; Sigmodon hispidus; phenobarbital ID SUBSTITUTED CONGENERS; PLEIOTROPIC RESPONSE; SENSITIVE ASSAY; LIVER; INDUCERS; ENZYME; 3-METHYLCHOLANTHRENE; DEETHYLATION; HEPATOCYTES; PROTEINS AB The induction of a hepatic pleiotropic response, including increase in liver/body weight ratio, induction of hepatic CYP2B and CYP3A protein and catalytic activity, and hepatic microsomal epoxide hydration activity, was investigated in male cotton rats (Sigmodon hispidus) administered graded dietary concentrations (0-1500 ppm) of phenobarbital (PB) for 14 days. A dose-dependent induction of each endpoint was observed, although plateaus in the various dose-response curves were not obtained, and ED50 values (PB concentrations associated with half-maximal responses) for the various endpoints were not able to be calculated. A maximal 1.31-fold increase, compared to the control value, in liver/body weight ratio was observed, while microsomal epoxide hydration activity was increased as much as 3.6-fold by PB administration. Pentoxy- and benzyloxyresorufin O-dealkylation and testosterone 16 beta-hydroxylation activities (considered to be relatively selective for CYP2B in the Norway rat (Rattus norvegicus)), were induced maximally less than five-fold. Testosterone 6 beta-hydroxylation (considered to be relatively selective for CYP3A in R. norvegicus) was induced maximally less than two-fold. Maximal induction of 7-ethoxy-4-trifluorometlhyl-coumarin O-deethylation was 18-fold, compared to the control rate. Western blotting studies indicated that hepatic microsomal proteins immunoreactive with polyclonal antisera to R. norvegicus CYP2B1 or CYP3A1 were induced, in a dose-responsive manner, by PB in the cotton rats. These results indicate that the cotton rat responds to PB treatment with a coordinate pleiotropic response similar to that displayed by R. norvegicus, although the substrate specificity of the induced proteins appears to differ between the two rodent species. (C) 1998 Published by Elsevier Science Inc. C1 NIA, Neurosci Lab, Bethesda, MD 20892 USA. NCI, BCDP, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bethesda, MD 20892 USA. NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Nims, RW (reprint author), BioServ Inc, 9900 Blackwell Rd, Rockville, MD 20850 USA. EM rnims@mabioservices.com NR 30 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0742-8413 J9 COMP BIOCHEM PHYS C JI Comp. Biochem. Physiol. C-Pharmacol. Toxicol. Endocrinol. PD NOV PY 1998 VL 121 IS 1-3 BP 197 EP 203 DI 10.1016/S0742-8413(98)10040-3 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology GA 144ZA UT WOS:000077344800016 PM 9972461 ER PT J AU Tims, FM AF Tims, FM TI Cocaine addiction: Theory, research and treatment SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review C1 NIDA, Serv Res Branch, NIH, Lexington, KY 40583 USA. RP Tims, FM (reprint author), Univ S Florida, Coll Med, Dept Psychiat & Behav Med, Tampa, FL 33620 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD NOV PY 1998 VL 43 IS 11 BP 753 EP 754 PG 2 WC Psychology, Multidisciplinary SC Psychology GA 137YW UT WOS:000076945500013 ER PT J AU Slonim, AD Ognibene, FP AF Slonim, AD Ognibene, FP TI Sedation for pediatric procedures, using ketamine and midazolam, in a primarily adult intensive care unit: A retrospective evaluation SO CRITICAL CARE MEDICINE LA English DT Article DE sedation; anesthesia; ketamine; midazolam; conscious sedation; drug monitoring ID INTRAVENOUS SEDATION; SAFETY; EFFICACY; CHILDREN AB Objective: To evaluate the effectiveness and safety of pediatric procedures performed by adult critical care practitioners, using the combination of ketamine and midazolam for anesthesia and sedation. Design: A retrospective case series. Setting: The intensive care unit (ICU) of a 325-bed tertiary research hospital. Patients: Individuals from 1 to 18 yrs of age who had intravenous midazolam sedation and ketamine anesthesia administered while undergoing lumbar puncture, bone biopsy, central venous catheter placement, liver biopsy, thoracentesis, or bone marrow aspirate/biopsy. Interventions: None. Measurements and Main Results: A retrospective chart review was performed. The dosages of medications used were tabulated, and milligram per kilogram dosages were calculated. The procedures performed, their durations, and any complications of the anesthesia and sedation were noted. These complications included: oxygen desaturations <90%, vital sign alterations requiring intervention, rashes, subjective complaints of dizziness by the patient, and emergence reactions to ketamine. A total of 127 pediatric patients were admitted to the ICU sedation area for a total of 295 procedures. All patients received ketamine and midazolam intravenously in divided doses and titrated to effect. A total of nine complications were observed. These complications included oxygen desaturation <90% (n =1), vital sign alterations requiring treatment (n = 3), rash (n = 2), dizziness (n = 1), wheezing (n =1), and emergence reaction (n =1). No patient required admission to the ICU because of a complication. There were no episodes of bradycardia or other cardiopulmonary compromise. Conclusions: Pediatric anesthesia and sedation, using ketamine and midazolam, can be performed in a designated monitored setting, outside of the operating room, by experienced personnel, including nonpediatricians. This therapeutic combination allows painful procedures to be performed with less anxiety and discomfort. In experienced hands, a limited number of side effects occur. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Ognibene, FP (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr MSC 1662, Bethesda, MD 20892 USA. NR 17 TC 34 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 1998 VL 26 IS 11 BP 1900 EP 1904 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 138XV UT WOS:000076999100033 PM 9824086 ER PT J AU Danis, M AF Danis, M TI Potential hazards of changing attitudes regarding the critically ill patient - The authors reply SO CRITICAL CARE MEDICINE LA English DT Letter ID PHYSICIANS RESPONSIBILITY C1 NIH, Bethesda, MD 20892 USA. RP Danis, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 1998 VL 26 IS 11 BP 1922 EP 1922 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 138XV UT WOS:000076999100041 ER PT J AU Fuss, IJ Strober, W AF Fuss, IJ Strober, W TI Animal models of inflammatory bowel disease: insights into the immunopathogenesis of Crohn's disease and ulcerative colitis SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article ID CD4(+) T-CELLS; TUMOR-NECROSIS-FACTOR; RESIDENT INTESTINAL FLORA; HAPTEN-INDUCED MODEL; ALPHA MUTANT MICE; INTERLEUKIN-10-DEFICIENT MICE; COLONIC INFLAMMATION; IL-2-DEFICIENT MICE; TOLERANCE; RESPONSES AB Many diseases, including those characterized by inflammation of the gastrointestinal tract (Crohn's disease and ulcerative colitis), are due to an array of factors that act in concert to produce pathologic change. The immunologic factors that mediate the development of such mucosal inflammation have been at the center of intense research. Recently, a better understanding of the mechanisms involved in mucosal homeostasis and the occurrence of inflammatory bower disease (IBD) has been achieved with the advent of animal models of mucosal inflammation. This review discusses these models and the insights they provide into the pathogenesis and treatment of IBD. C1 NIAID, Mucosal Immun Sect, LCI, NIH, Bethesda, MD 20892 USA. RP Fuss, IJ (reprint author), NIAID, Mucosal Immun Sect, LCI, NIH, Bldg 10,Room 11N238, Bethesda, MD 20892 USA. NR 47 TC 7 Z9 7 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 1998 VL 14 IS 6 BP 476 EP 482 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 132RD UT WOS:000076642700010 ER PT J AU Schumacher, JM Ashcroft, N Donovan, PJ Golden, A AF Schumacher, JM Ashcroft, N Donovan, PJ Golden, A TI A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos SO DEVELOPMENT LA English DT Article DE aurora; Caenorhabditis elegans; microtubule; centrosome; PIE-1; P-granule ID C-ELEGANS; PROTEIN-KINASE; MICROTUBULE DYNAMICS; CHROMOSOME SEGREGATION; BLASTOMERE IDENTITY; CLEAVAGE SPINDLE; P-GRANULE; DROSOPHILA; ASYMMETRY; MITOSIS AB S. cerevisiae Ipl1, Drosophila Aurora, and the mammalian centrosomal protein IAK-1 define a new subfamily of serine/threonine kinases that regulate chromosome segregation and mitotic spindle dynamics. Mutations in ipl1 and aurora result in the generation of severely aneuploid cells and, in the case of aurora, monopolar spindles arising from a failure in centrosome separation. Here we show that a related, essential protein from C. elegans, AIR-1 (Aurora/Ipl1 related), is localized to mitotic centrosomes, Disruption of AIR-1 protein expression in C, elegans embryos results in severe aneuploidy and embryonic lethality. Unlike aurora mutants, this aneuploidy does not arise from a failure in centrosome separation. Bipolar spindles are formed in the absence of AIR-1, but they appear to be disorganized and are nucleated by abnormal-looking centrosomes, In addition to its requirement during mitosis, AIR-1 may regulate microtubule-based developmental processes as well. Our data suggests AIR-1 plays a role in P-granule segregation and the association of the germline factor PIE-1 with centrosomes. C1 NCI, Frederick Canc Res & Dev Ctr, Cell Biol Dev & Differentiat Grp, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Dev Signal Transduct Grp, ABL Basic Res Program, Frederick, MD 21702 USA. RP Donovan, PJ (reprint author), Thomas Jefferson Univ, Kimmel Canc Ctr, 233 S 10th St, Philadelphia, PA 19107 USA. EM pdonovan@lac:jci.tju.edu RI Schumacher, Jill/B-2932-2012 NR 58 TC 128 Z9 133 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 1998 VL 125 IS 22 BP 4391 EP 4402 PG 12 WC Developmental Biology SC Developmental Biology GA 150DZ UT WOS:000077649200005 PM 9778499 ER PT J AU Mehlmann, LM Carpenter, G Rhee, SG Jaffe, LA AF Mehlmann, LM Carpenter, G Rhee, SG Jaffe, LA TI SH2 domain-mediated activation of phospholipase C gamma is not required to initiate Ca2+ release at fertilization of mouse eggs SO DEVELOPMENTAL BIOLOGY LA English DT Article DE fertilization; mouse; calcium; phospholipase C ID GROWTH-FACTOR RECEPTOR; SEA-URCHIN EGGS; TYROSINE KINASE SUBSTRATE; SPERM-INDUCED ACTIVATION; INOSITOL-TRISPHOSPHATE; INTRACELLULAR CALCIUM; ZONA-PELLUCIDA; HAMSTER EGGS; MEIOTIC MATURATION; ACROSOMAL EXOCYTOSIS AB The initiation of Ca2+ release at fertilization of mammalian eggs requires inositol trisphosphate (Miyazaki et al., 1992, Science 257, 251-255), indicating that an enzyme of the phospholipase C family is probably activated. Because Ca2+ release at fertilization in echinoderm eggs is initiated by SH2 domain-mediated activation of phospholipase C gamma (Carroll et nl., 1997, T Cell Biol. 138, 1303-1311), we examined the possible role of PLC gamma in initiating Ca2+ release at fertilization in mouse eggs. Both PLC gamma isoforms, PLC gamma 1 and PLC gamma 2, are present in mouse eggs and sperm, and stimulation of these enzymes in the egg by way of an exogenously expressed PDGF receptor causes Ca2+ release. Recombinant SH2 domains of PLC gamma 1 and PLC gamma 2 inhibit PLC gamma 1 and PLC gamma 2 activation by the PDGF receptor, completely preventing Ca2+ release in response to PDGF when injected at an approximate to 20- to 40-fold excess over the concentrations of endogenous proteins. However, even at an approximate to 100- to 400-fold excess over endogenous protein levels, PLC gamma 1 and PLC gamma 2 3112 domains do not inhibit Ca2+ release at fertilization. These findings indicate that Ca2+ release at fertilization of mouse eggs does not require SH2 domain-mediated activation of PLC gamma. However, activation of PLC gamma in the egg by an alternative pathway, or introduction of activated PLC gamma from the sperm, may be important. (C) 1998 Academic Press. C1 Univ Connecticut, Ctr Hlth, Dept Physiol, Farmington, CT 06032 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. NHLBI, Lab Cell Signalling, NIH, Bethesda, MD 20892 USA. RP Mehlmann, LM (reprint author), Univ Connecticut, Ctr Hlth, Dept Physiol, Farmington, CT 06032 USA. FU NICHD NIH HHS [F32HD08204, R01HD14939] NR 75 TC 116 Z9 116 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 1 PY 1998 VL 203 IS 1 BP 221 EP 232 DI 10.1006/dbio.1998.9051 PG 12 WC Developmental Biology SC Developmental Biology GA 136PY UT WOS:000076869400019 PM 9806786 ER PT J AU McGibbon, NH Andrade, CK Widener, G Cintas, HL AF McGibbon, NH Andrade, CK Widener, G Cintas, HL TI Effect of an equine-movement therapy program on gait, energy expenditure, and motor function in children with spastic cerebral palsy: a pilot study SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID SPATIAL PARAMETERS; COST INDEX; WALKING AB The purpose of this study was to evaluate the effects of an 8-week program of hippotherapy on energy expenditure during walking; on the gait dimensions of stride length, velocity, and cadence; and on performance on the Gross Motor Function Measure (GMFM) in five children with spastic cerebral palsy (CP), A repeated-measures within-subjects design was used consisting of two baseline measurements taken 8 weeks apart, followed by an 8-week intervention period, then a posttest. After hippotherapy, all five children showed a significant decrease (X-r(2)=7.6, P<0.05) in energy expenditure during walking and a significant increase (X-r(2)=7.6, P<0.05) in scores on Dimension E (Walking, Running, and Jumping) of the GMFM, A trend toward increased stride length and decreased cadence was observed. This study suggests that hippotherapy may improve energy expenditure during walking and gross motor function in children with CP. C1 Therapeut Riding Tucson, Tucson, AZ USA. Samuel Merritt Coll, Oakland, CA USA. NIH, Bethesda, MD 20892 USA. RP Santa Rita Ranch, Box 647, Green Valley, AZ 85622 USA. NR 58 TC 67 Z9 75 U1 4 U2 23 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0012-1622 EI 1469-8749 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD NOV PY 1998 VL 40 IS 11 BP 754 EP 762 PG 9 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 148PR UT WOS:000077541500008 PM 9881805 ER PT J AU Nadon, NL West, M AF Nadon, NL West, M TI Myelin proteolipid protein: Function in myelin structure is distinct from its role in oligodendrocyte development SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE dysmyelination; transgenic mice; DM20; rumpshaker ID CENTRAL-NERVOUS-SYSTEM; INTRACELLULAR-TRANSPORT; SPINAL-CORD; JIMPY MOUSE; MUTATION; GENE; PLP; EXPRESSION; DM-20; MICE AB The myelin proteolipid proteins PLP and DM20 are essential for the compaction of central nervous system myelin and they play an important role in the maturation of the oligodendrocyte. The specific function of the less abundant DM20 isoform is still unknown, but rescue experiments previously indicated that both isoforms an necessary for oligodendrocyte maturation. In vitro experiments have suggested DM20 may assist in the translocation of PLP into the membrane. We tested this hypothesis in vivo, by investigating whether wild-type PLP derived from a transgene could be incorporated into the myelin membrane of Plp mutant rumpshaker mice. We previously demonstrated that expression of the PLP transgene alone in a more severe Pip mutant, jimpy mouse, did not result in PLP incorporation into the myelin. Here we report that there was significantly more PLP in white matter from rumpshaker expressing the PLP transgene than their nontransgenic rumpshaker littermates and that myelin structure was improved. The delay in oligodendrocyte development was not alleviated by expression of the PLP transgene however, supporting an essential role for DM20 in oligodendrocyte maturation. C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. RP Nadon, NL (reprint author), NIA, Biol Aging Program, 7201 Wisconsin Ave,Gateway Bldg,2C231, Bethesda, MD 20892 USA. NR 34 TC 17 Z9 17 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD NOV-DEC PY 1998 VL 20 IS 6 BP 533 EP 539 DI 10.1159/000017354 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 153GK UT WOS:000077824500005 PM 9858842 ER PT J AU Beamer, BA Yen, CJ Andersen, BE Muller, D Elahi, D Cheskin, LJ Andres, R Roth, J Shuldiner, AR AF Beamer, BA Yen, CJ Andersen, BE Muller, D Elahi, D Cheskin, LJ Andres, R Roth, J Shuldiner, AR TI Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-gamma 2 gene with obesity in two Caucasian populations SO DIABETES LA English DT Article ID PPAR-GAMMA; EXPRESSION; RECEPTORS; INSULIN C1 Univ Maryland, Sch Med, Div Diabet Obes & Nutr, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Div Gastroenterol, Baltimore, MD 21218 USA. NIA, NIH, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Shuldiner, AR (reprint author), Univ Maryland, Sch Med, Div Diabet Obes & Nutr, 725 W Lombard St,Room S-422, Baltimore, MD 21201 USA. OI YEN, CHUNG-JEN/0000-0001-5372-3657 FU NIA NIH HHS [T32-AG-00120] NR 10 TC 227 Z9 240 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 1998 VL 47 IS 11 BP 1806 EP 1808 DI 10.2337/diabetes.47.11.1806 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 131PA UT WOS:000076583400022 PM 9792554 ER PT J AU Wagenknecht, LE D'Agostino, RB Haffner, SM Savage, PJ Rewers, M AF Wagenknecht, LE D'Agostino, RB Haffner, SM Savage, PJ Rewers, M TI Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness - The insulin resistance atherosclerosis study SO DIABETES CARE LA English DT Article ID CORONARY HEART-DISEASE; INTIMA-MEDIA THICKNESS; CARDIOVASCULAR RISK-FACTORS; B-MODE ULTRASOUND; ARTERIAL-WALL; MELLITUS; SENSITIVITY; HYPERGLYCEMIA; PROGRESSION; GLYCATION AB OBJECTIVE - To assess whether people with impaired glucose tolerance (IGT) exhibit an increased risk of atherosclerosis as measured by the thickness of the carotid artery. RESEARCH DESIGN AND METHODS - We examined the relationship between glucose tolerance status and subclinical atherosclerosis in the Insulin Resistance Atherosclerosis Study (IRAS). The IRAS is an epidemiological study of 1,625 Hispanic, African-American, and white men and women, with approximately equal numbers of subjects with normal glucose tolerance (NGT), IGT, and type 2 diabetes as assessed by an oral glucose tolerance test. Half of those with diabetes were previously unaware of their condition and were defined as having new diabetes. Persons using insulin were excluded, The intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA) was measured as an index of subclinical atherosclerosis using B-mode ultrasonography, RESULTS - Adjusted for demographics and smoking, CCA-IMT increased most notably at the level of established diabetes (802, 822, 831, and 896 mu m for NGT, IGT, new diabetes, and established diabetes, respectively). Adjustment for coronary heart disease (CHD) risk factors, which tended to worsen across glucose tolerance category, further minimized the slightly graded relationship. The relationship with the ICA-IMT was steeper and again suggested that the increased wall thickness is associated with diabetes, not with IGT, The relationship between glucose tolerance category and IMT was similar in men and women, CONCLUSIONS - We observed considerably greater IMT among persons with established diabetes but no significant increase in persons with IGT. These data suggest that the increased risk of CHD observed in persons with diabetes may largely develop after the onset of overt diabetes. C1 Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med Biometr, Denver, CO 80262 USA. RP Wagenknecht, LE (reprint author), Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 FU NHLBI NIH HHS [HL-47890, HL47887, HL-47889] NR 48 TC 100 Z9 118 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1998 VL 21 IS 11 BP 1812 EP 1818 DI 10.2337/diacare.21.11.1812 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 130NR UT WOS:000076526600006 PM 9802726 ER PT J AU Resnick, HE Valsania, P Halter, JB Lin, XH AF Resnick, HE Valsania, P Halter, JB Lin, XH TI Differential effects of BMI on diabetes risk among black and white Americans SO DIABETES CARE LA English DT Article ID BODY-FAT DISTRIBUTION; UNITED-STATES POPULATION; CORONARY HEART-DISEASE; FOLLOW-UP; STROKE INCIDENCE; GLUCOSE-LEVELS; INSULIN; OBESITY; PREVALENCE; MELLITUS AB OBJECTIVE - To determine whether the associations of BMI and fat distribution with diabetes risk are modified by race. RESEARCH DESIGN AND METHODS - Data from the National Health and Nutrition Examination Survey, Epidemiologic Follow-up Study (1971-1992), were used to investigate potential interactions of BMI and fat distribution with race. Incident diabetes was defined by self-report of physician-diagnosed diabetes, hospital and nursing home discharge records, and death certificates. RESULTS - Among the 1,531 black and 9,852 white subjects who were nondiabetic at baseline, 1,139 (10.0%) developed diabetes during 20 years of follow-up. Although the cumulative risk of diabetes increased with baseline BMI in all four race-sex groups, the sex-specific odds ratios (ORs) for black:white subjects decreased with increasing BMI. In particular, for BMI of 22 kg/m(2), the OR of diabetes for black:white individuals was 1.87 and 1.76 (P < 0.01) for men and women, respectively; for BMI of 32 kg/m(2), the OR decreased to 0.99 and 1.20 (NS) for men and women, respectively. Skinfold ratio was also associated with increased diabetes risk in all race-sex groups, but did not modify the association between race and diabetes. CONCLUSIONS - These findings suggest that the effect of BMI on diabetes risk is different for black and white Americans, with a larger risk for blacks than whites at low BMI and an equivalent risk for both groups at high BMI. A lower degree of visceral adiposity among blacks at higher BMI or a greater impact of visceral adiposity among blacks at low BMI may help explain the interaction of race and BMI on diabetes risk. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Ctr Hlth Outcomes & Evaluat, Plymouth, Devon, England. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Div Geriatr Med, Ann Arbor, MI 48109 USA. Vet Adm Med Ctr, Ann Arbor, MI 48105 USA. Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. RP Resnick, HE (reprint author), NIA, Epidemiol Demog & Biometry Program, Gatway Bldg,Room 3C309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM resnickh@nih.gov FU NIA NIH HHS [AG-00114] NR 48 TC 97 Z9 97 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1998 VL 21 IS 11 BP 1828 EP 1835 DI 10.2337/diacare.21.11.1828 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 130NR UT WOS:000076526600009 PM 9802729 ER PT J AU Jovanovic, L Metzger, BE Knopp, RH Conley, MR Park, E Lee, YJ Simpson, JL Holmes, L Aarons, JH Mills, JL AF Jovanovic, L Metzger, BE Knopp, RH Conley, MR Park, E Lee, YJ Simpson, JL Holmes, L Aarons, JH Mills, JL CA NICHD-Diabetes Early Pregnancy Stu TI The diabetes in early pregnancy study - beta-Hydroxybutyrate levels in type 1 diabetic pregnancy compared with normal pregnancy SO DIABETES CARE LA English DT Article ID GLUCOSE; MALFORMATIONS; WOMEN; METABOLISM; INFANTS; MOTHERS; RATS; HYPERKETONEMIA; ORGANOGENESIS; STARVATION AB OBJECTIVE - The objective was to assess relationships between beta-hydroxybutyrate (beta-OHB) level and pregnancy outcome in human pregnancy in light of the fact that high levels of beta-OHB cause malformations and growth retardation in in vitro studies. RESEARCH DESIGN AND METHODS - We analyzed beta-OHB in prospectively collected specimens from the National Institute of Child Health and Human Development-Diabetes in Early Pregnancy Study, in gestational weeks 6-12 in diabetic (n = 204-239) and nondiabetic (n = 316-312) pregnant women. RESULTS - Levels of beta-OHB in diabetic women were 2.5-fold higher than in nondiabetic pregnant women at 6 weeks' gestation and declined to 1.6-fold above nondiabetic women by 12 weeks' gestation (P < 0.0001 at all times). beta-OHB was positively correlated with glucose levels (P < 0.0001) in diabetic mothers, probably reflecting degree of diabetic control. beta-OHB correlated inversely with glucose (P < 0.0003) (gestational week 6 only) in nondiabetic mothers, possibly reflecting caloric intake. beta-OHB tended to be lower (not higher) in diabetic and nondiabetic mothers with malformed infants or pregnancy losses, but the difference was not statistically significant. beta-OHB in diabetic mothers at 8, 10, and 12 weeks correlated inversely with birthweight (P = 0.004-0.02), even after adjusting for maternal glucose levels. beta-OHB levels were also generally lower in diabetic mothers of macrosomic infants, and week 12 ultrasound crown-rump measurements were inversely related to beta-OHB levels. CONCLUSIONS - The 1st trimester beta-OHB is significantly higher in diabetic than nondiabetic pregnant women. In both groups, beta-OHB tended to be lower, not higher, in mothers who had a malformed infant or pregnancy loss. beta-OHB was inversely related to crown-rump length and birth weight. The modest beta-OHB elevation in the 1st trimester of reasonably well-controlled diabetic pregnancy is not associated with malformations, probably because beta-OHB levels causing malformations in embryo culture models are 20- to 40-fold higher. The mechanism of the beta-OHB association with impaired fetal growth is unknown. C1 Sansum Med Res Inst, Santa Barbara, CA 93105 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Univ Washington, NW Lipid Res Clin, Seattle, WA 98195 USA. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. NICHHD, Biometry Branch, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Genet & Teratol Unit, Boston, MA 02115 USA. Univ Pittsburgh, Magee Womens Hosp, Dept Med, Pittsburgh, PA 15213 USA. RP Jovanovic, L (reprint author), Sansum Med Res Inst, 2219 Bath St, Santa Barbara, CA 93105 USA. EM lois@sansumres.com NR 30 TC 24 Z9 26 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1998 VL 21 IS 11 BP 1978 EP 1984 DI 10.2337/diacare.21.11.1978 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 130NR UT WOS:000076526600034 PM 9802754 ER PT J AU Lin, BC Morris, DW Chou, JY AF Lin, BC Morris, DW Chou, JY TI Hepatocyte nuclear factor 1 alpha is an accessory factor required for activation of glucose-6-phosphatase gene transcription by glucocorticoids SO DNA AND CELL BIOLOGY LA English DT Article ID FACTOR-BINDING PROTEIN-1; RAT-LIVER GLUCOSE-6-PHOSPHATASE; INSULIN; RECEPTOR; CELLS; EXPRESSION; SEQUENCE; PROMOTER; ENHANCER; FAMILY AB Deficiency of glucose-6-phosphatase (G6Pase), a key enzyme in glucose homeostasis, causes glycogen storage disease type la (GSD-la), also know as von Gierke disease. Expression of the G6Pase gene is regulated by multiple hormones, including glucocorticoids, The synthetic glucocorticoid dexamethasone increased G6Pase mRNA abundance and gene transcription in H4-IIE hepatoma cells. Transient transfection assays demonstrated that the G6Pase promoter was active in H4-IIE cells only in the presence of dexamethasone. The minimal G6Pase promoter was contained within nucleotides -234/+3, which has two putative glucocorticoid response elements (GREs) at nucleotides -178/-164 (site 1) and -154/-140 (site 2). Electromobility shift and transient transfection assays showed that only GRE site 1 was required for glucocorticoid-activated transcription from the G6Pase promoter. Deletion analysis demonstrated that the DNA elements absolutely essential for glucocorticoid-stimulated transcription from the G6Pase promoter were contained within nucleotides -234/-212, encompassing binding motifs for hepatocyte nuclear factors (HNFs) 1 (-226/-212) and 4 (-231/-220). Electromobility shift and cotransfection assays showed that HNF1 alpha bound to its cognate site and mediated transcription activation of the G6Pase gene by glucocorticoids. C1 NICHHD, NIH, Heritable Disorders Branch, Bethesda, MD 20892 USA. George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. RP Chou, JY (reprint author), NICHHD, NIH, Heritable Disorders Branch, Bldg 10,Room 95241, Bethesda, MD 20892 USA. RI Lin, Baochuan/A-8390-2009 OI Lin, Baochuan/0000-0002-9484-0785 NR 38 TC 33 Z9 33 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD NOV PY 1998 VL 17 IS 11 BP 967 EP 974 DI 10.1089/dna.1998.17.967 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 143XA UT WOS:000077281700006 PM 9839806 ER PT J AU van den Bree, MBM Johnson, EO Neale, MC Pickens, RW AF van den Bree, MBM Johnson, EO Neale, MC Pickens, RW TI Genetic and environmental influences on drug use and abuse/dependence in male and female twins SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE drug use; drug abuse/dependence; twins; genetic and environmental influences; gender ID SUBSTANCE-ABUSE; ALCOHOL DEPENDENCE; ADOPTION; PERSONALITY; FAMILY; TRAITS; TRANSMISSION; HERITABILITY; ADOLESCENCE; COMORBIDITY AB Twins were recruited through alcohol and drug treatment programs. With structural equation modeling, genetic and environmental estimates were obtained for use and DSM-III abuse/dependence of sedatives, opioids, cocaine, stimulants, and cannabis as well as any illicit drug. Analyses were conducted separately for males and females. Models included thresholds based on population prevalence of use or abuse/dependence and ever having been in treatment. Genetic influences were found for most measures. They were generally stronger for males than females and for clinical diagnoses of abuse/dependence compared to use. Common environmental influences played a greater role in use than abuse:dependence. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NIDA, Intramural Res Program, Addict Res Ctr, Baltimore, MD 21224 USA. Henry Ford Hlth Sci Ctr, Dept Psychiat, Detroit, MI 48202 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Psychiat, Richmond, VA 23298 USA. RP van den Bree, MBM (reprint author), NIDA, Intramural Res Program, Addict Res Ctr, POB 5180, Baltimore, MD 21224 USA. EM mvandenb@intra.nida.nih.gov RI Neale, Michael/B-1418-2008; turton, miranda/F-4682-2011 FU NIA NIH HHS [AG06886]; NIAAA NIH HHS [AA06500]; NIDA NIH HHS [DA05147] NR 56 TC 137 Z9 142 U1 1 U2 10 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD NOV 1 PY 1998 VL 52 IS 3 BP 231 EP 241 DI 10.1016/S0376-8716(98)00101-X PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 140ME UT WOS:000077090400007 PM 9839149 ER PT J AU Jacobson, KA Moro, S Kim, YC Li, AH AF Jacobson, KA Moro, S Kim, YC Li, AH TI A(3) adenosine receptors: Protective vs. damaging effects identified using novel agonists and antagonists SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT 6th International Symposium on Adenosine and Adenine Nucleotides, New Frontiers in the 3rd-Millennium CY MAY 19-24, 1998 CL FERRARA, ITALY DE purines; A(3) receptors; cell viability; dihydropyridines; pyridines; molecular modeling ID MAST-CELL LINE; I-125 4-AMINOBENZYL-5'-N-METHYLCARBOXAMIDOADENOSINE; MOLECULAR-CLONING; RABBIT HEART; RAT-BRAIN; IN-VIVO; ACTIVATION; EXPRESSION; DEGRANULATION; DERIVATIVES AB Investigation of the physiologic role of the A(3) adenosine receptor has been facilitated by the availability of selective agonists and antagonists. Selective agonists include IB-MECA and the 2-chloro derivative Cl-IB-MECA. Selective antagonists have been identified and designed with the aid of molecular modeling among various nonpurine classes of heterocycles: flavonoids, 1,4-dihydropyridine derivatives, triazoloquinazolines, isoquinolines, and a triazolonaphthyridine. The dihydropyridine 3-ethyl 5-benzyl 2-methyl-6-phenyl-4-phenylethynyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS 1191) is 1,300-fold selective for human A(3) (K-i of 31 nM) vs. A(1)/A(2A) adenosine receptors and also 28-fold A(3) selective in rat tissue (K-i of 1.42 mu M). 9-Chloro-2-(2-furyl)-5-phenylacetylamino[1,2,4]-triazolo[1,5-c]quinazoline (MRS 1220) is useful as an A(3) selective antagonist only in human tissue, with a K-i value of 0.65 nM. The pyridine derivative 5-propyl 2-ethyl-4-propyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate (MRS 1523) is a selective antagonist of both rat and human A(3) receptors, with K-i values of 113 and 19 nM, respectively. Paradoxical effects of A(3) agonists in the brain, heart and other tissues indicate that acute activation of A(3) receptors at greater than 10 mu M concentrations acts as a lethal input to cells, whereas low, nanomolar concentrations of A(3) receptor agonists protect against apoptosis or ischemic damage. Adenosine A(3) receptor agonists, antagonists, or both, may be useful in treating inflammatory conditions. Drug Dev. Res. 45:113-124, 1998. Published 1998 Wiley-Liss, Inc.dagger C1 NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 NR 63 TC 40 Z9 41 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD NOV-DEC PY 1998 VL 45 IS 3-4 BP 113 EP 124 DI 10.1002/(SICI)1098-2299(199811/12)45:3/4<113::AID-DDR5>3.0.CO;2-S PG 12 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 172PT UT WOS:000078933600005 ER PT J AU Smith, PT Armstrong, J Koshiba, M Huang, S Apasov, S Sitkovsky, M AF Smith, PT Armstrong, J Koshiba, M Huang, S Apasov, S Sitkovsky, M TI Studies of expression and possible functional role of purinergic receptors in cell-mediated immunity: Experimental approaches, controls, and caveats SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT 6th International Symposium on Adenosine and Adenine Nucleotides, New Frontiers in the 3rd-Millennium CY MAY 19-24, 1998 CL FERRARA, ITALY DE ATP; adenosine; T-lymphocytes; purinergic receptors ID TOXIC LYMPHOCYTES-T; GATED ION-CHANNEL; EXTRACELLULAR ATP; EFFECTOR FUNCTIONS; SURFACE-PROTEINS; MESSENGER-RNA; ADENOSINE; PHOSPHORYLATION; ACTIVATION; THYMOCYTES AB The expression of purinergic receptors for the physiologically abundant molecules of extracellular ATP (eATP) and e adenosine (Ado) in lymphoid cells of T-cell lineage has been demonstrated convincingly in short-term biochemical and pharmacologic assays. T-cell differentiation-related expression of P2X(7) receptors for ATP was demonstrated in murine T-cells, whereas A(2A) adenosine receptors were shown to be responsible for observed increases in cAMP during incubation of T-cells with adenosine. The possibility of a feed-back regulation mechanism of T-cell functions with eATP is suggested by patterns of expression of purinergic receptors, which may follow the immediate early response genes. The functioning of adenosine receptors was suggested to be involved in the pathogenesis of human disease, adenosine deaminase severe combined immunodeficiency. Extracellular ATP and adenosine affect T-cell differentiation and effector functions in vitro; however, convincing evidence of purinergic modulation of immune response in vivo or in long-term immunoassays in vitro is still lacking. An explanation of the effects of eATP and eAdo on T-lymphocytes' differentiation and effector functions must include considerations of (1) possible intracellular effects of ATP, adenosine, and/or their metabolites; 2) the effects of eAdo- and eATP-triggered transmembrane signaling through P1 and P2 classes of purinergic receptors, respectively; and (3) the reversible phosphorylation of extracellular domains of functionally important cell surface proteins by ATP. The use of existing agonists and antagonists of purinergic receptors and of ATP and of adenosine-hydrolyzing enzymes has some limited mechanistic implications, but it may lead to artifacts due to uncertainties between extracellular and intracellular effects of these reagents and the possible presence of contaminants in commercial preparations of enzymes. Drug Dev. Res. 45:229-244, 1998. Published 1998 Wiley-Liss, Inc.dagger C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sitkovsky, M (reprint author), NIAID, Immunol Lab, NIH, 10-11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 51 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD NOV-DEC PY 1998 VL 45 IS 3-4 BP 229 EP 244 DI 10.1002/(SICI)1098-2299(199811/12)45:3/4<229::AID-DDR21>3.0.CO;2-Z PG 16 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 172PT UT WOS:000078933600021 ER PT J AU Abbracchio, MP Ceruti, S Brambilla, R Barbieri, D Camurri, A Franceschi, C Giammarioli, AM Jacobson, KA Cattabeni, F Malorni, W AF Abbracchio, MP Ceruti, S Brambilla, R Barbieri, D Camurri, A Franceschi, C Giammarioli, AM Jacobson, KA Cattabeni, F Malorni, W TI Adenosine A(3) receptors and viability of astrocytes SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT 6th International Symposium on Adenosine and Adenine Nucleotides, New Frontiers in the 3rd-Millennium CY MAY 19-24, 1998 CL FERRARA, ITALY DE adenosine A(3) receptors; astrocytes; rat; human; cell survival ID SPECIES-DIFFERENCES; AGONISTS; DERIVATIVES; ANTAGONISTS; APOPTOSIS; N-6-BENZYLADENOSINE-5'-URONAMIDES; HL-60; CELLS AB We investigated the role of the A(3) adenosine receptor in cells of the astroglial lineage (both rat primary astrocytes and human astrocytoma ADF cells) by means of the selective A(3) agonists N-6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) and CI-IB-MECA, and by utilizing the selective AS receptor antagonist MRS1191. Exposure of ADF cells to mu M concentrations of either agonist resulted in reduction of cell number, likely due to cell death. In both rat astrocytes and human astrocytoma cells, at concentrations 2-3 orders of magnitude lower (which were not associated with cytotoxicity), these same agonists induced a marked reorganization of the cytoskeleton, with appearance of stress fibers and numerous cell protrusions. Functionally, these morphological changes were associated with cell protection, as demonstrated by a significant reduction of spontaneous apoptosis in A(3) agonist-treated cells. To confirm a role for the A(3) receptor in this effect, MRS1191 completely counteracted CI-IB-MECA-induced reduction of spontaneous apoptosis. In ADF cells, Ay agonists also induced changes in the intracellular distribution of the anti-apoptotic protein Bcl-X-L which became localized in cell protrusions. Also, this effect was specifically antagonized by MRS1191. These dual actions of A(3) agonists in vitro may have important in vivo implications. For example, a robust and acute activation of the A(3) receptor following massive adenosine release during ischemia may contribute to brain cell death; conversely, a subthreshold activation of this receptor prior to ischemia may trigger protective mechanisms (i.e., induction of stress fibers and of a Bcl-X-L-dependent reorganization of cytoskeleton) making the brain more resistant to subsequent insults ("ischemic tolerance"). Drug Dev. Res. 45:379-386, 1998. (C) 1998 Wiley-Liss, Inc. C1 Univ Milan, Inst Pharmacol Sci, I-20133 Milan, Italy. Dept Biol Sci, Sect Gen Pathol, Modena, Italy. INRCA, Dept Gerontol, Ancona, Italy. Ist Super Sanita, Dept Ultrastruct, I-00161 Rome, Italy. NIDDK, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RP Abbracchio, MP (reprint author), Univ Milan, Inst Pharmacol Sci, Via Balzaretti 9, I-20133 Milan, Italy. EM Mariapia.Abbracchio@unimi.it RI Ceruti, Stefania/A-6376-2008; Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014; Malorni, Walter/G-5874-2016 OI Ceruti, Stefania/0000-0003-1663-4211; Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388; NR 39 TC 35 Z9 35 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD NOV-DEC PY 1998 VL 45 IS 3-4 BP 379 EP 386 DI 10.1002/(SICI)1098-2299(199811/12)45:3/4<379::AID-DDR38>3.0.CO;2-Y PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 172PT UT WOS:000078933600038 ER PT J AU Lee, AE Wilcox, K Jacobson, KA Dichter, M Liang, BT AF Lee, AE Wilcox, K Jacobson, KA Dichter, M Liang, BT TI Adenosine receptor subtypes and cardioprotection SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT 6th International Symposium on Adenosine and Adenine Nucleotides, New Frontiers in the 3rd-Millennium CY MAY 19-24, 1998 CL FERRARA, ITALY DE myocardium; adenosine; receptor; purinergic; ischemia ID CHICK HEART-CELLS; PROTEIN-KINASE-C; INTRACORONARY ADENOSINE; CORONARY ANGIOPLASTY; VENTRICULAR MYOCYTES; SIMULATED ISCHEMIA; ADENYLATE-CYCLASE; CARDIAC MYOCYTES; INJURY; CONTRACTILITY AB Brief ischemia prior to a sustained period of ischemia reduces myocardial infarct size, a phenomenon known as preconditioning. A cardiac ventricular myocyte model has been developed to investigate the role and signaling mechanism of adenosine receptor subtypes in cardiac preconditioning. A 5-min exposure of cardiac myocytes to simulated ischemia, termed preconditioning ischemia, prior to a subsequent 90-min period of ischemia protected them against injury incurred during the 90-min ischemia. Preconditioning ischemia preserved ATP content, reduced percentage of cells killed, and decreased release of creatine kinase into the medium. Activation of the adenosine A(1) receptor with CCPA or the A(3) receptor with IB-MECA can replace preconditioning ischemia and mimic the protective effect of preconditioning ischemia. Blockade of the A(1) receptor with its selective antagonist DPCPX or of the A(3) receptor with the A(3) selective antagonist MRS1191 during the preconditioning ischemia resulted in only a partial attenuation of the subsequent protection. Incubation with both DPCPX and MRS1191 or with the nonselective antagonist 8-SPT during the preconditioning ischemia completely abolished the protective effect of preconditioning ischemia. The K-ATP channel opener pinacidil caused a large activation of the K-ATP channel current and was able to precondition the myocyte. The K-ATP channel antagonist glibenclamide blocked the cardioprotective effect of preconditioning ischemia when it was included during myocyte exposure to the preconditioning ischemia, indicating that K-ATP channel is a requisite effector in mediating preconditioning. A receptor-mediated stimulation of phospholipase C or phospholipase D,with consequent activation of protein kinase C and K-ATP channel, appears to be the signaling mechanism linking adenosine A(1) and A(3) receptors to the induction of preconditioning. A model of how ischemic preconditioning is triggered and mediated is proposed. Evidence is accumulating to support its validity. Drug Dev. Res. 45:394-401; 1998. (C) 1998 Wiley-Liss, Inc. C1 Univ Penn, Med Ctr, David Mahoney Inst Neurol Sci, Philadelphia, PA 19104 USA. Dept Med, Div Cardiovasc, Philadelphia, PA USA. NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Liang, BT (reprint author), Univ Penn, Med Ctr, David Mahoney Inst Neurol Sci, 3610 Hamilton Walk, Philadelphia, PA 19104 USA. EM liangb@mail.med.upenn.edu RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 42 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD NOV-DEC PY 1998 VL 45 IS 3-4 BP 394 EP 401 PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 172PT UT WOS:000078933600040 ER PT J AU Kapetanovic, IM Torchin, CD Thompson, CD Miller, TA McNeilly, PJ MacDonald, TL Kupferberg, HJ Perhach, JL Sofia, RD Strong, JM AF Kapetanovic, IM Torchin, CD Thompson, CD Miller, TA McNeilly, PJ MacDonald, TL Kupferberg, HJ Perhach, JL Sofia, RD Strong, JM TI Potentially reactive cyclic carbamate metabolite of the antiepileptic drug felbamate produced by human liver tissue in vitro SO DRUG METABOLISM AND DISPOSITION LA English DT Article; Proceedings Paper CT 8th North American International Society-for-the-Study-of-Xenobiotics Meeting CY OCT 26-30, 1997 CL HILTON HEAD ISL, SOUTH CAROLINA SP N Amer Int Soc Study Xenobiot ID IN-VITRO; RAT; IDENTIFICATION; OXIDATION AB Felbamate (FBM) is a novel antiepileptic drug that was approved in 1993 for treatment of several forms of epilepsy. After its introduction, toxic reactions (aplastic anemia and hepatotoxicity) associated with its use were reported. It is unknown whether FBM or one of its metabolites is responsible for these idiosyncratic adverse reactions. Although the metabolism of FBM has not been fully characterized, three primary metabolites of FBM have been identified, i.e. 2-hydroxy, p-hydroxy, and monocarbamate metabolites. In addition, the monocarbamate metabolite leads to a carboxylic acid, which is the major metabolite of FBM in humans. Formation of the hydroxylated products of FBM involves cytochrome P450 enzymes, but the enzymes involved in the formation and further metabolism of the monocarbamate have not yet been elucidated. Recently, mercapturate metabolites of FBM have been identified in human urine, and a metabolic scheme involving reactive aldehyde metabolite formation from the monocarbamate metabolite has been proposed. The present study confirmed the formation of the proposed metabolites using human liver tissue in vitro. The aldehyde intermediates were trapped as oxime derivatives, and the cyclic equilibrium product (proposed as a storage and transport form for the aldehydes) was monitored directly bit HPLC or CC/MS. Formation of putative toxic aldehyde intermediates and the major carboxylic acid metabolite of FBM was differentially effected with the cofactors NADP(+) and NAD(+). It is possible that the cofactors may influence the relative metabolism via activation and inactivation pathways. C1 US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Laurel, MD 20708 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22903 USA. NINDS, Epilepsy Branch, Bethesda, MD 20892 USA. RP Strong, JM (reprint author), US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, MOD-1 CDER Room 2017,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 17 TC 39 Z9 39 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD NOV PY 1998 VL 26 IS 11 BP 1089 EP 1095 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 136PV UT WOS:000076869100007 PM 9806951 ER PT J AU Mankani, MH Robey, PG AF Mankani, MH Robey, PG TI Transplantation of bone-forming cells SO ENDOCRINOLOGIST LA English DT Article ID MARROW STROMAL CELLS; FIBROBLAST GROWTH-FACTOR; EX-VIVO EXPANSION; HEMATOPOIETIC MICROENVIRONMENT; STEM-CELLS; IN-VIVO; OSTEOGENIC PRECURSORS; CFU-F; DIFFERENTIATION; CULTURES AB The transplantation of bone forming cells in eludes the transfer of discrete pieces of viable bone and of ex vivo expanded osteoprogenitor cells. These progenitor cells, derived from bone marrow stroma, have been termed bone marrow stromal cells (BMSCs), BMSCs are pluripotent cells with several distinct phenotypes including bone, cartilage, fat, and muscle. In vitro and in vivo analyses of BMSCs have been utilized to discern the influence of the donor and of growth factors on BMSC proliferation and differentiation. In vitro parameters utilized to evaluate cultured BMSCs include colony morphology, cell morphology, bone specific and bone related proteins, and enzyme expression. In vivo analyses historically have utilized diffusion chambers, implants beneath the renal capsule, and, most recently, subcutaneous implants. In anticipation of their potential clinical ap plications, BMSCs have been used to close bone defects in animals and as vehicles for gene mediated therapy. However, limited success to date in the latter effort suggests that further innovation and investigation is warranted. C1 NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Mankani, MH (reprint author), NIDR, Craniofacial & Skeletal Dis Branch, NIH, 9000 Rockville Pike,Bldg 30,Room 228, Bethesda, MD 20892 USA. EM mankani@nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 52 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD NOV-DEC PY 1998 VL 8 IS 6 BP 459 EP 467 DI 10.1097/00019616-199811000-00009 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 148BL UT WOS:000077488300009 ER PT J AU Tang, PZ Tsai-Morris, CH Dufau, ML AF Tang, PZ Tsai-Morris, CH Dufau, ML TI Regulation of 3 beta-hydroxysteroid dehydrogenase in gonadotropin-induced steroidogenic desensitization of Leydig cells SO ENDOCRINOLOGY LA English DT Article ID BETA-HYDROXYSTEROID DEHYDROGENASE; MESSENGER-RIBONUCLEIC-ACID; TISSUE-SPECIFIC EXPRESSION; ANDROGEN RECEPTOR; GENE; HORMONE; ELEMENT; RNA; CYTOCHROME-P450; P45017-ALPHA AB 3 beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerases (SP-HSD) are enzymes that catalyze the conversion of Delta(5) to Delta(4) steroids in the gonads and adrenal for the biosynthesis of sex steroid and corticoids. In gonadotropin-desensitized Leydig cells, from rats treated with high doses of human CG (hCG), testosterone production is markedly reduced, a finding that was attributed in part to reduction of CYP17 expression. In this study, we present evidence for an additional steroidogenic lesion induced by gonadotropin. Using differential display analysis of messenger RNA (mRNA) from Leydig cells of rats treated with a single desensitizing dose of hCG (2.5 pg), we found that transcripts for type I and type II SP-HSD were substantially (5- to 8-fold) down-regulated. This major reduction, confirmed by RNase protection assay, was observed at the high hCG dose (2.5 mu g), whereas minor or no change was found at lower doses (0.01 and 0.1 mu g). In contrast, 3 beta-HSD mRNA transcripts were not changed in luteinized, ovaries of pseudopregnant rats treated with 2.5 pg hCG. The down-regulation of IP-HSD mRNA in the Leydig cell resulted from changes at the transcriptional level. Western blot analysis showed 3 beta-HSD protein was significantly reduced by hCG treatment, with changes that were coincidental with the reduction of enzyme activity and temporally consistent with the reduction of 3 beta-HSD mRNA but independent of LH receptor down-regulation. The reduction of SP-HSD mRNA resulting from transcriptional inhibition of gene expression, and the consequent reduction of SP-HSD activity could contribute to the inhibition of androgen production in gonadotropin-induced steroidogenic desensitization of leydig cells. The gender-specific regulation of 3 beta-HSD by hCG reflects differential transcriptional regulation of the enzymes to accommodate physiological hormonal requirements and reproductive function. C1 NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), NIH, Bldg 49,Room 6A-36,49 Convent Rd, Bethesda, MD 20892 USA. EM dufau@helix.nih.gov NR 38 TC 31 Z9 33 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 NOV PY 1998 VL 139 IS 11 BP 4496 EP 4505 DI 10.1210/en.139.11.4496 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 131ZT UT WOS:000076605700011 PM 9794458 ER PT J AU Migliaccio, S Washburn, TF Fillo, S Rivera, H Teti, A Korach, KS Wetsel, WC AF Migliaccio, S Washburn, TF Fillo, S Rivera, H Teti, A Korach, KS Wetsel, WC TI Modulation of estrogen receptor levels in mouse uterus by protein kinase C isoenzymes SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; BREAST-CANCER-CELLS; VITAMIN-D-RECEPTOR; PROGESTERONE-RECEPTOR; PHORBOL ESTER; MOLECULAR HETEROGENEITY; MESSENGER-RNA; MCF-7 CELLS; PHOSPHORYLATION; ACTIVATION AB We have recently shown that protein kinase C (PKC) modifies estrogen receptor (ER) binding and modulates the responsiveness to estrogens in a clonal osteoblast-like cell line stably transfected with the ER. The purpose of the present study was to determine whether the interaction observed between the ER and PKC signaling in these cells occurs in additional estrogen target organs, such as the uterus. When uteri were incubated for 2 h with increasing concentrations of a kinase inhibitor (H7), ER binding was enhanced in a dose-dependent manner. Stimulation of PKC with phorbol ester reduced PKC activity levels, but increased ER binding. Interestingly, the changes in binding appeared to be due primarily to alterations in cytosolic ER levels, as binding in the nuclear fraction was minimally enhanced. When levels of ER messenger RNA were evaluated by Northern blot analysis, no differences were observed among the H7- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated and untreated groups. Western blot analysis, however, demonstrated that levels of ER cytosolic protein in the H7-, TPA-, and staurosporine-heated groups were increased relative to those in the unheated controls. When uteri were incubated with diethylstilbestrol in the presence of either H7 or TPA, no change in cytosolic ER levels was found, suggesting that only unoccupied ERs are responsive to modulation by PKC. Western blotting of the various PKC isoforms indicated that although PKC alpha, -beta(I), -beta(II), -delta, and -zeta are expressed in the uterus, only PKCa and -beta(I) are translocated from the soluble to the particulate fraction and then degraded after phorbol ester stimulation. Hence, one or both of these latter PKC isoforms may regulate cytosolic ER levels. Collectively, these data indicate that PKC may play an important role in the modulation of uterine ER levels and that PKC may exert its effect on the ER at some posttranscriptional or posttranslational step. Finally, our results show that an ER-PKC interaction occurs in a whole organ such as the uterus and that this interaction may be important in the regulation of the ER activity in a variety of estrogen-responsive tissues. C1 Univ Roma La Sapienza, Dept Histol, I-00161 Rome, Italy. Univ Roma La Sapienza, Med Embryol Inst, I-00161 Rome, Italy. NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Hormone Act Grp, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. RP Migliaccio, S (reprint author), Univ Roma La Sapienza, Histol & Med Embryol Dept, Via Antonio Scarpa 14, I-00161 Rome, Italy. EM ateti@axrma.uniroma1.it OI Migliaccio, Silvia/0000-0002-4563-6630; Korach, Kenneth/0000-0002-7765-418X; Teti, Anna Maria/0000-0002-5887-4419 NR 54 TC 15 Z9 16 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1998 VL 139 IS 11 BP 4598 EP 4606 DI 10.1210/en.139.11.4598 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 131ZT UT WOS:000076605700024 PM 9794471 ER PT J AU van Birgelen, APJM AF van Birgelen, APJM TI Hexachlorobenzene as a possible major contributor to the dioxin activity of human milk SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-of-Toxicology CY MAR 01-05, 1998 CL SEATTLE, WASHINGTON SP Soc Toxicol DE breast milk; hexachlorobenzene; TEQ; toxic equivalents ID DIBENZO-P-DIOXINS; HUMAN-BREAST-MILK; POLYCHLORINATED-BIPHENYLS; ORGANOCHLORINE PESTICIDES; INDUCED PORPHYRIA; CHLORINATED-HYDROCARBON; DIETARY-INTAKE; FEMALE RATS; PCBS; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN AB A dioxinlike compound is a compound that binds to the agyl hydrocarbon (Ah) receptor, results in dioxinlike effects, and bioaccumulates. These are the three factors for including dioxinlike chemicals in the toxic equivalency factor (TEF) concept. Risk assessment of dioxinlike compounds is based on using these TEFs. Hexachlorobenzene (HCB) has all three features and should therefore be included in this TEF concept. Relative potency values express the potency of a specific compound in comparison to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCD D), the most potent dioxinlike compound, with a relative potency value of 1. For the estimation of the total dioxin activity in an environmental biological sample, the TEF value of a compound is multiplied by the concentration in the specific matrix. This results in a certain amount of toxic equivalents (TEQs) for this compound. The summation of all TEQs in a certain mixture gives the total dioxin activity of this mixture. HCB binds to the Ah receptor about 10,000 times less than TCDD. HCB is also about 10,000 times less potent than TCDD based on in vitro cytochrome P4501A induction and porphyrin accumulation. Using a relative potency value of 0.0001, HCB could add 10-60% to the total TEQ in human milk samples in most countries. In a few countries such as Spain, Slovakia, and the Czech Republic, HCB levels in human milli expressed as TEQ could contribute up to a factor of six to the total TEQ in comparison to the contribution of polychlorinated dioxins, dibenzofurans, and biphenyls together, i.e., up to a daily intake of about 1 ng TEQ/kg for a breast-fed infant. The HCB levels in human milk in these countries are about the same as in India. Biochemical, immunological, and neurological alterations have been observed in infants fed breast milk in countries with relatively low TEQ levels in human milk. Based on the above information, it is clear that HCB should be classified as a dioxinlike compound, that more studies are needed to reduce the uncertainty in the estimation of a relative potency value for HCB, and that epidemiological studies should be undertaken in infants fed breast milk in countries with high HCB exposure levels. Furthermore, measurements of HCB levels in human and environmental samples in conjunction with other dioxinlike compounds is a prerequisite to estimate the total dioxin activity in these samples. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP van Birgelen, APJM (reprint author), NIEHS, POB 12233,MD B3-07, Res Triangle Pk, NC 27709 USA. NR 100 TC 74 Z9 75 U1 0 U2 6 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1998 VL 106 IS 11 BP 683 EP 688 DI 10.2307/3434256 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 144TM UT WOS:000077331200017 PM 9799183 ER PT J AU Colt, JS Zahm, SH Camann, DE Hartge, P AF Colt, JS Zahm, SH Camann, DE Hartge, P TI Comparison of pesticides and other compounds in carpet dust samples collected from used vacuum cleaner bags and from a high-volume surface sampler SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE carpet dust; high-volume surface sampler; pesticides; polychlorinated biphenyls; polycyclic aromatic hydrocarbons AB Epidemiologic studies of the association between residential pesticide use and cancer risk require an assessment of past pesticide exposures. Pesticide levels in carpet dust are believed to reflect long-term pesticide use. Recent epidemiologic studies have found collection of dust samples using the high-volume surface sampler (HVS3) to be expensive and cumbersome. We compared the levels of pesticides and other compounds in dust obtained from subjects' personal used vacuum cleaner bags to that collected by the HVS3 to see if this simpler method could replace the HVS3 in epidemiologic research. We visited the homes of 15 subjects, took the used bags from their vacuums, and collected carpet dust samples with the HVS3. The samples were analyzed for 42 target compounds: 26 pesticides, 10 polycyclic aromatic hydrocarbons (PAHs), and six polychlorinated biphenyl (PCB) congeners using GC/MS in selected ion monitoring mode. The two methods agreed in detecting the presence of the target compounds between 80% and 100% of the time. Neither sampling method was consistently more sensitive. The median target compound concentrations were similar, and a paired t-test showed no significant differences. For many compounds, the concentrations of compounds in the HVS3 samples were higher than those in the used bag samples at the upper end of the concentration ranges. However, the Spearman rank correlation coefficients were 0.85 or higher for most compounds, indicating that homes would be ranked similarly using both methods. Overall, there appears to be no clear difference in the quality of the pesticide, PAH, or PCB concentration data for the two dust collection methods. C1 NCI, Occupat Epidemiol Branch, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. SW Res Inst, San Antonio, TX 78228 USA. RP Colt, JS (reprint author), NCI, Occupat Epidemiol Branch, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, 6130 Execut Blvd,Room 418, Bethesda, MD 20892 USA. RI Zahm, Shelia/B-5025-2015 NR 6 TC 57 Z9 59 U1 1 U2 9 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1998 VL 106 IS 11 BP 721 EP 724 DI 10.1289/ehp.98106721 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 144TM UT WOS:000077331200021 PM 9799187 ER PT J AU Hale, RC Enos, C Gallagher, K AF Hale, RC Enos, C Gallagher, K TI Sources and distribution of polychlorinated terphenyls at a major US aeronautics research facility SO ENVIRONMENTAL MANAGEMENT LA English DT Article DE polychlorinated terphenyls; aroclor; contaminated sediments; hydraulic fluid; enzyme induction; polychlorinated biphenyls ID RESOLUTION GAS-CHROMATOGRAPHY; FUNDULUS-HETEROCLITUS; BIPHENYL CONGENERS; MASS-SPECTROMETRY; AQUATIC BIOTA; SEDIMENTS; ENVIRONMENT; EFFLUENTS; INDUCTION; RIVER AB High concentrations of an unusual, complex mixture of chlorinated compounds were discovered in sediments and oysters near a federal aeronautics facility during implementation of a pollutant screening protocol. The mixture was identified as Aroclor 5432, a polychlorinated terphenyl (PCT) formulation, produced in the US until 1972. PCTs, particularly low chlorinated mixtures, have rarely been reported in the environment, despite significant manufacture and usage. Releases were traced to two outfalls. Creek sediments downstream of one contained concentrations as high as 200,000 mu g/kg (dry weight basis); those in indigenous oysters reached 35,000 mu g/kg, indicating significant bioavailability and bioaccumulation potential. Subsequent work showed that PCTs were widely disseminated in marsh grass, crabs, and fish. PCTs, PCBs, and mercury were also detected in storm drain lines entering these outfalls. The lines received input from both storm water and research buildings. Historical hydraulic fluid leaks and in-service compressor fluids in some buildings contained PCTs and PCBs. Contaminated materials on-site were removed to minimize pollutant spread. Aroclor 5432 usage, most likely as compressor/hydraulic fluid additives, probably ended about ten years prior to its on-site detection. in terms of biological effects, intraperitoneal injection of fish with Aroclor 5432 induced cytochrome P-4501A (CYP1A) and ethoxyresorufin O-deethylase (EROD) activity to a similar degree as PCB Aroclor 1254 and to a greater extent than PCT Aroclor 5460. The presence of high concentrations of PCTs contributed to the facility being included on the National Priorities List. It subsequently became the first US federal facility to sign a Federal Facility Agreement, identifying cleanup responsibilities, prior to formal listing. C1 Coll William & Mary, Virginia Inst Marine Sci, Dept Environm Sci, Gloucester Point, VA 23062 USA. PRC Environm Management Inc, Kansas City, KS 66101 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Hale, RC (reprint author), Coll William & Mary, Virginia Inst Marine Sci, Dept Environm Sci, Gloucester Point, VA 23062 USA. NR 35 TC 2 Z9 2 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-152X J9 ENVIRON MANAGE JI Environ. Manage. PD NOV-DEC PY 1998 VL 22 IS 6 BP 937 EP 945 DI 10.1007/s002679900160 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA 118ZN UT WOS:000075871000012 ER PT J AU Troisi, R Weiss, HA Hoover, RN Potischman, N Swanson, CA Brogan, DR Coates, RJ Gammon, MD Malone, KE Daling, JR Brinton, LA AF Troisi, R Weiss, HA Hoover, RN Potischman, N Swanson, CA Brogan, DR Coates, RJ Gammon, MD Malone, KE Daling, JR Brinton, LA TI Pregnancy characteristics and maternal risk of breast cancer SO EPIDEMIOLOGY LA English DT Article DE breast cancer; pregnancy; twinning; toxemia; weight gain; gestational diabetes ID HUMAN CHORIONIC-GONADOTROPIN; MULTIPLE BIRTHS; ESTRADIOL LEVELS; CORD BLOOD; SERUM; MOTHERS; NAUSEA; WOMEN AB In a population based case control study of parous women less than 45 years of age, we evaluated the relations of various pregnancy characteristics to maternal breast cancer risk. Cases (N = 1,239) diagnosed with in situ or invasive breast cancer from 1990 to 1992 in Atlanta, GA, Seattle/Puget Sound, WA, and five counties in central New Jersey, and population controls (N = 1,166) identified by random-digit dialing, were interviewed regarding the details of their pregnancies. We used logistic regression to estimate relative risks (RR) and 95% confidence intervals (CI) and to adjust for breast cancer risk factors. Women who reported nausea or vomiting in their first pregnancy had a slightly lower risk of breast cancer (RR = 0.87; 95% CI = 0.72-1.0). We found no strong or consistent associations for maternal risk related to gestational length, pregnancy weight gain, gestational diabetes, pregnancy hypertension, or gender of the offspring, although we found some evidence for reductions in risk for toxemia (RR = 0.81; 95% CI = 0.61-1.1) and specific sex (RR for female twins us singletons = 0.48; 95% CI = 0.20-1.3) and timing characteristics of twinning. Overall, these data provide little support for the hypothesis that pregnancy hormone levels are associated with subsequent maternal risk of breast cancer in young women. C1 NCI, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, Bethesda, MD 20892 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Columbia Univ, Sch Publ Hlth, Div Epidemiol, New York, NY USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Troisi, R (reprint author), NCI, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, Execut Plaza N Room 443,6130 Execut Blvd, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 27 TC 59 Z9 59 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 1998 VL 9 IS 6 BP 641 EP 647 DI 10.1097/00001648-199811000-00014 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 130BR UT WOS:000076499800014 PM 9799175 ER PT J AU Mendola, P Moysich, KB Freudenheim, JL Shields, PG Schisterman, EF Graham, S Vena, JE Marshall, JR Ambrosone, CB AF Mendola, P Moysich, KB Freudenheim, JL Shields, PG Schisterman, EF Graham, S Vena, JE Marshall, JR Ambrosone, CB TI Risk of recurrent spontaneous abortion, cigarette smoking, and genetic polymorphisms in NAT2 and GSTM1 SO EPIDEMIOLOGY LA English DT Article DE N-acetyltransferase 2; glutathione S-transferase M1; spontaneous abortion; genetic polymorphism; gene-environment interaction; molecular epidemiology ID POSTMENOPAUSAL BREAST-CANCER; N-ACETYLTRANSFERASE; EPIDEMIOLOGY AB Maternal smoking increases the risk of spontaneous abortion. Polymorphic N-acetyltransferase (NAT2) and glutathione S-transferase (GSTM1) affect metabolism of some mutagens found in tobacco smoke. Genotypes and smoking were studied in women with at least two spontaneous abortions (N = 32) and those with at least two livebirths (N = 179). Smoking slightly increased risk (odds ratio = 1.3; 95% confidence interval = 0.6-2.9), but NAT2 and GSTM1 did not. NAT2 or GSTM1 polymorphisms did not appreciably modify smoking-related risk. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Ambrosone, CB (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, HFT-100,3900 NCTR Rd, Jefferson, AR 72079 USA. RI Shields, Peter/I-1644-2012; OI Mendola, Pauline/0000-0001-5330-2844; Schisterman, Enrique/0000-0003-3757-641X FU NCI NIH HHS [CA-01633, CA-11535, CA-62995] NR 17 TC 10 Z9 10 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 1998 VL 9 IS 6 BP 666 EP 668 DI 10.1097/00001648-199811000-00018 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 130BR UT WOS:000076499800018 PM 9799179 ER PT J AU Duc, HH Hefter, H Stremmel, W Castaneda-Guillot, C Hernandez, AH Cox, DW Auburger, G AF Duc, HH Hefter, H Stremmel, W Castaneda-Guillot, C Hernandez, AH Cox, DW Auburger, G TI His1069Gln and six novel Wilson disease mutations: analysis of relevance for early diagnosis and phenotype SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE Wilson disease; mutation analysis; haplotypes; single strand conformation polymorphism (SSCP) ID COPPER TRANSPORTING ATPASE; MOTOR IMPAIRMENT; GENE; HAPLOTYPE; ATP7B AB In the present study we examined 33 German and 10 Cuban unrelated Wilson disease (WND) index patients and their relatives, The common His1069Gln mutation accounted for 42% of all WND chromosomes in the German series and the haplotype C was found to be highly predictive for this mutation. Six WND gene mutations have not been described previously and involved a splice site at intron 18 (3903 + del1G), a termination codon in the copper-binding region of exon 2 (Cys271X), and missense mutations in transmembrane region 2 (Gly710Ala), in transmembrane region 3 (Tyr741Cys), in the DKTGT motif (Thr1031Ile) and in the ATP loop region (Gly1176Arg), In 15 German WND index patients and three sibs both WND mutations could be determined and a genotype-phenotype correlation was attempted. Patients homozygous for the His1069Gln mutation showed almost the complete range of clinical presentations, and thus in our study this mutation is not associated with a late, neurological presentation. C1 Univ Hosp, Dept Neurol, Dusseldorf, Germany. Univ Heidelberg, Dept Gastroenterol, Heidelberg, Germany. Inst Nacl Gastroenterol, Dept Pediat Gastroenterol, Havana, Cuba. Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. Univ Alberta, Dept Med Genet, Edmonton, AB, Canada. RP Auburger, G (reprint author), NIH, NHGR, Room 2A35,Bldg 49, Bethesda, MD 20892 USA. NR 23 TC 24 Z9 24 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD NOV-DEC PY 1998 VL 6 IS 6 BP 616 EP 623 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 155TN UT WOS:000077962600014 PM 9887381 ER PT J AU Constantin, G Brocke, S Izikson, A Laudanna, C Butcher, EC AF Constantin, G Brocke, S Izikson, A Laudanna, C Butcher, EC TI Tyrphostin AG490, a tyrosine kinase inhibitor, blocks actively induced experimental autoimmune encephalomyelitis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE tyrosine kinase; encephalomyelitis; adhesion; lymphocyte ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; INTERFERON-GAMMA; SIGNAL-TRANSDUCTION; DRUG DEVELOPMENT; SJL/J MOUSE; CYTOKINES; INTEGRINS; ADHESION; IL-10; CELLS AB Migration of lymphocytes from blood into the brain is a critical event in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Previous observations made in our laboratory showed that protein tyrosine kinase inhibitors were able to block lymphocyte adhesion to brain endothelium and prevent the entry of encephalitogenic T cell lines into the brain of SJL/J mice. Here we show that systemic administration of the protein tyrosine kinase inhibitor, tyrphostin AG490, blocks the development of actively induced EAE in a dose-dependent manner. Administration of 1 mg of drug daily significantly decreased the severity of the disease, while 3 mg of AG 490 daily totally blocked the disease in 62 % of treated animals, and in those that developed the disease, paralysis was delayed and clinical score was significantly reduced. Blood leukocytes isolated from mice treated with tyrphostin AG490 were less adhesive on VCAM-1 and fibronectin, when compared with control animals. AG490 treatment had no effect on the proliferation by antigen-stimulated peripheral lymph nodes cells. Interestingly, cells obtained from draining lymph nodes in AG490-treated animals and stimulated with antigen secreted two times more IFN-gamma and four times more IL-10, when compared with control animals, whereas no difference was observed in TNF-alpha production. Our results suggest that tyrphostin AG490 may have therapeutic potential by blocking tyrosine kinase activities involved in key mechanisms leading to demyelinating diseases of the central nervous system. C1 Univ Verona, Ist Patol Gen, I-37134 Verona, Italy. Stanford Univ, Sch Med, Dept Pathol, Lab Immunol & Vasc Biol, Palo Alto, CA 94304 USA. Stanford Univ, Sch Med, Ctr Digest Dis, Palo Alto, CA 94304 USA. Vet Adm Med Ctr, Foothill Res Ctr, Ctr Mol Biol Med, Palo Alto, CA 94304 USA. NINDS, Neurol Dis Sect, NIH, Bethesda, MD 20892 USA. RP Constantin, G (reprint author), Univ Verona, Ist Patol Gen, Str Grazie, I-37134 Verona, Italy. EM constant@borgoroma.univr.it NR 33 TC 35 Z9 39 U1 1 U2 4 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 1998 VL 28 IS 11 BP 3523 EP 3529 DI 10.1002/(SICI)1521-4141(199811)28:11<3523::AID-IMMU3523>3.0.CO;2-X PG 7 WC Immunology SC Immunology GA 138RD UT WOS:000076985600013 PM 9842895 ER PT J AU Johanson, CE Preston, K AF Johanson, CE Preston, K TI The influence of an instruction on the stimulus effects of drugs in humans SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID AGONIST-ANTAGONIST OPIOIDS; D-AMPHETAMINE; DISCRIMINATION; EXPECTANCY; PAIN AB Participants discriminated between tripelennamine and placebo in experiments differing in instructional set. In 1 experiment (SED), participants were told that 1 of the 2 drugs was more sedative-like, and during the other (STIM), 1 was more stimulant-like. During generalization tests, participants received diazepam or d-amphetamine. Percent correct was the same in both experiments. Tripelennamine increased sedative and decreased stimulant effects. Amphetamine and diazepam produced typical subjective effects. Some subjective effects differed across experiments with more sedative and less stimulant effects during SED than STIM. In SED and STIM, capsules were labeled 80% of the time as a sedative and stimulant, respectively. Thus, instructions designed to give expectations had no effect on discrimination and only a few changes in subjective effects. When asked to name the drug that they believed they received, labels reflected instructional set. C1 Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI 48207 USA. NIDA, Intramural Res Program, Lexington, KY USA. RP Johanson, CE (reprint author), Wayne State Univ, Dept Psychiat & Behav Neurosci, 2761 E Jefferson, Detroit, MI 48207 USA. EM cjohans@med.wayne.edu RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 23 TC 3 Z9 3 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD NOV PY 1998 VL 6 IS 4 BP 427 EP 432 DI 10.1037//1064-1297.6.4.427 PG 6 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 146JP UT WOS:000077425800010 PM 9861557 ER PT J AU Steiner, H Gerfen, CR AF Steiner, H Gerfen, CR TI Role of dynorphin and enkephalin in the regulation of striatal output pathways and behavior SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the European-Brain-and-Behaviour-Society CY SEP 15-18, 1997 CL TUTZING, GERMANY SP European Brain & Behaviour Soc DE basal ganglia; dopamine; dynorphin; enkephalin; opioid; striatum; substantia nigra ID KAPPA-OPIOID RECEPTOR; MESSENGER-RNA EXPRESSION; IMMEDIATE-EARLY GENE; IN-SITU HYBRIDIZATION; D1 DOPAMINE-RECEPTOR; RAT NUCLEUS-ACCUMBENS; C-FOS EXPRESSION; ULTRASTRUCTURAL IMMUNOCYTOCHEMICAL LOCALIZATION; TRANSCRIPTION FACTOR GENES; FREELY MOVING RATS AB Projection neurons in the striatum give rise to two output systems, the "direct" and "indirect" pathways, which antagonistically regulate basal ganglia output. While all striatal projection neurons utilize GABA as their principal neurotransmitter, they express different opioid peptide co-transmitters and also different dopamine receptor subtypes. Neurons of the direct pathway express the peptide dynorphin and the D1 dopamine receptor, whereas indirect pathway neurons express the peptide enkephalin and the D2 receptor. In the present review, we summarize our findings on the function of dynorphin and enkephalin in these striatal output pathways. In these studies, we used D1- or D2-receptor-mediated induction of immediate-early genes as a cellular response in direct or indirect projection neurons, respectively, to investigate the role of these opioid peptides. Our results suggest that the specific function of dynorphin and enkephalin is to dampen excessive activation of these neurons by dopamine and other neurotransmitters. Levels of these opioid peptides are elevated by repeated, excessive activation of these pathways, which appears to be an adaptive or compensatory response. Behavioral consequences of increased opioid peptide function in striatal output pathways may include behavioral sensitization (dynorphin) and recovery of motor function (enkephalin). C1 Univ Tennessee, Coll Med, Dept Anat & Neurobiol, Memphis, TN 38163 USA. NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Steiner, H (reprint author), Univ Tennessee, Coll Med, Dept Anat & Neurobiol, 855 Monroe Ave, Memphis, TN 38163 USA. EM hsteiner@nb.utmem.edu; gerfen@helix.nih.gov FU NINDS NIH HHS [NS26473] NR 156 TC 246 Z9 247 U1 1 U2 15 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD NOV PY 1998 VL 123 IS 1-2 BP 60 EP 76 DI 10.1007/s002210050545 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 137MV UT WOS:000076919300009 PM 9835393 ER PT J AU Ingram, DK Ikari, H Umegaki, H Chernak, JM Roth, GS AF Ingram, DK Ikari, H Umegaki, H Chernak, JM Roth, GS TI Application of gene therapy to treat age-related loss of dopamine D-2 receptor SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT 4th International Symposium on the Neurobiology and Neuroendocrinology of Aging CY JUL 26-31, 1998 CL BREGENZ, AUSTRIA SP SO Ill Univ, Sch Med, RW Johnson Pharmaceut Res Inst, Junifur Fdn, Orentreich Fdn Advancement Sci, Searle Pharmaceut, SO Ill Univ, Grad Sch DE Parkinson's disease; Huntington's disease; motor performance; striatum; adenovirus; apomorphine ID ADENOVIRUS-MEDIATED TRANSFER; PARKINSONS-DISEASE; TURNING BEHAVIOR; CYSTIC-FIBROSIS; RAT STRIATUM; INVIVO; BRAIN; VECTORS; EXPRESSION; SENESCENCE AB We have investigated the feasibility of using gene therapy to attenuate the age-related decline in striatal dopamine D-2 receptors (D2R) associated with reduced motor control. To this end, we have constructed an adenoviral vector containing the cDNA for the rat D2R. When injected into HeLa and HS24 cells in vitro, the vector induced an abundant message for D2R, as demonstrated by Northern analysis, and produced a membrane-bound protein capable of binding a D2R ligand, [H-3]spiperone. When injected into rat striatum in vivo, the vector produced a marked increase in D2R near the site of injection, as evidenced by increased [H-3]spiperone binding as well as by another more specific ligand, [I-125]iodosulpride. The D2R produced in the striatum were functional, as evidenced by rotational behavior induced by a subcutaneous injection of the dopamine agonist, apomorphine. However, we did not observe any significant improvement in motor performance during preliminary experiments in which aged rats received bilateral striatal injections of the vector. In young rats, vector-induced expression of D2R in striatum was increased markedly three to five days after infection, but then declined to baseline levels by day 21. Loss of expression in aged rats proceeded at a somewhat lower rate. Because of the loss of expression and lack of significant performance enhancement in aged rats following vector injection into the striatum, we are now pursuing other strategies. These include functional assessment of the current vector in D2R null mutant mice as well as construction of new vectors that may yield more long-ten expression. Published by Elsevier Science Inc. C1 NIA, Mol Physiol & Genet Sect, Lab Cellular & Mol Biol, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. Nagoya Univ, Sch Med, Dept Geriatr, Nagoya, Aichi 466, Japan. Lion Pharmaceut, Bard Life Sci Ctr, Baltimore, MD 21202 USA. RP Ingram, DK (reprint author), NIA, Mol Physiol & Genet Sect, Lab Cellular & Mol Biol, Gerontol Res Ctr,NIH, 5600 Nathan Shock Lane, Baltimore, MD 21224 USA. NR 30 TC 18 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD NOV-DEC PY 1998 VL 33 IS 7-8 BP 793 EP 804 DI 10.1016/S0531-5565(98)00043-6 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 150EH UT WOS:000077650200013 PM 9951623 ER PT J AU McCann, SM Licinio, J Wong, ML Yu, WH Karanth, S Rettorri, V AF McCann, SM Licinio, J Wong, ML Yu, WH Karanth, S Rettorri, V TI The nitric oxide hypothesis of aging SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT 4th International Symposium on the Neurobiology and Neuroendocrinology of Aging CY JUL 26-31, 1998 CL BREGENZ, AUSTRIA SP SO Ill Univ, Sch Med, RW Johnson Pharmaceut Res Inst, Junifur Fdn, Orentreich Fdn Advancement Sci, Searle Pharmaceut, SO Ill Univ, Grad Sch DE nitric oxide synthase; cyclic GMP; cyclooxygenase; bacterial lipopolysaccharide; cytokines; hypothalamus; brain; pituitary gland; pineal gland; degenerative diseases; inflammation; infection; stress ID HORMONE-RELEASING HORMONE; RELAXING FACTOR; MESSENGER-RNA; SYNTHASE; BRAIN; RAT; HYPOTHALAMUS; NOREPINEPHRINE; ACTIVATION; RECEPTORS AB Nitric oxide (NO), generated by endothelial (e) NO synthase (NOS) and neuronal (n) NOS, plays a ubiquitous role in the body in controlling the function of almost every, if not every, organ system. Bacterial and viral products, such as bacterial lipopolysaccharide (LPS), induce inducible (i) NOS synthesis that produces massive amounts of NO toxic to the invading viruses and bacteria, but also host cells by inactivation of enzymes leading to cell death. The actions of all forms of NOS are mediated not only by the free radical oxidant properties of this soluble gas, but also by its activation of guanylate cyclase (GC), leading to the production of cyclic guanosine monophosphate (cGMP) that mediates many of its physiological actions. In addition, NO activates cyclooxygenase and lipoxygenase, leading to the production of physiologically relevant quantities of prostaglandin E-2 (PGE(2)) and leukotrienes. In the case of iNOS, the massive release of NO, PGE(2), and leukotrienes produces toxic effects. Systemic injection of LPS causes induction of interleukin (IL)-1 beta mRNA followed by IL-beta synthesis that induces iNOS mRNA with a latency of two and four hours, respectively, in the anterior pituitary and pineal glands, meninges, and choroid plexus, regions outside the blood-brain barrier, and shortly thereafter, in hypothalamic regions, such as the temperature-regulating centers, paraventricular nucleus containing releasing and inhibiting hormone neurons, and the arcuate nucleus, a region containing these neurons and axons bound for the median eminence. We are currently determining if LPS similarly activates cytokine and iNOS production in the cardiovascular system and the gonads. Our hypothesis is that recurrent infections over the life span play a significant role in producing aging changes in all systems outside the blood-brain barrier via release of toxic quantities of NO. NO may be a major factor in the development of coronary heart disease (CHD). Considerable evidence has accrued indicating a role for infections in the induction of CHD and, indeed, patients treated with a tetracycline derivative had 10 times less complications of CHD than their controls. Stress, inflammation, and infection have all been shown to cause induction of iNOS in rats, and it is likely that this triad of events is very important in progression of coronary arteriosclerosis leading to coronary occlusion. Aging of the anterior pituitary and pineal with resultant decreased secretion of pituitary hormones and the pineal hormone, melatonin, respectively, may be caused by NO. The induction of iNOS in the temperature-regulating centers by infections may cause the decreased febrile response in the aged by loss of thermosensitive neurons. iNOS induction in the paraventricular nucleus may cause the decreased nocturnal secretion of growth hormone (GH) and prolactin that occurs with age, and its induction in the arcuate nucleus may destroy luteinizing hormone-releasing hormone (LHRH) neurons, thereby leading to decreased release of gonadotropins. Recurrent infections may play a role in aging of other parts of the brain, because there are increased numbers of astrocytes expressing IL-1 beta throughout the brain in aged patients. IL-l and products of NO activity accumulate around the plaques of Alzheimer's, and may play a role in the progression of the disease. Early onset Parkinsonism following flu encephalitis during World War I was possibly due to induction of iNOS in cells adjacent to substantia nigra dopaminergic neurons leading to death of these cells, which, coupled with ordinary aging fall out, led to Parkinsonism. The central nervous system (CNS) pathology in AIDS patients bears striking resemblance to aging changes, and may also be largely caused by the action of iNOS. Antioxidants, such as melatonin, vitamin C, and vitamin E, probably play an important acute and chronic role in reducing or eliminating the oxidant damage produced by NO. (C) 1998 Elsevier Science Inc. C1 Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. CONICET, CEFYBO, Consejo Nacl Invest Cient & Tecn, Ctr Estud Farmacol, RA-1414 Buenos Aires, DF, Argentina. RP McCann, SM (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 FU NIDDK NIH HHS [DK43900]; NIMH NIH HHS [MH51853] NR 37 TC 113 Z9 120 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD NOV-DEC PY 1998 VL 33 IS 7-8 BP 813 EP 826 DI 10.1016/S0531-5565(98)00050-3 PG 14 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 150EH UT WOS:000077650200015 PM 9951625 ER PT J AU Vawter, MP Hemperly, JJ Hyde, TM Bachus, SE VanderPutten, DM Howard, AL Cannon-Spoor, HE McCoy, MT Webster, MJ Kleinman, JE Freed, WJ AF Vawter, MP Hemperly, JJ Hyde, TM Bachus, SE VanderPutten, DM Howard, AL Cannon-Spoor, HE McCoy, MT Webster, MJ Kleinman, JE Freed, WJ TI VASE-containing N-CAM isoforms are increased in the hippocampus in bipolar disorder but not schizophrenia SO EXPERIMENTAL NEUROLOGY LA English DT Article DE schizophrenia; bipolar disorder; hippocampus; prefrontal cortex; neural cell adhesion molecule; variable alternative spliced exon; isoelectric focusing; immunohistochemistry; Western immunoblot; in situ hybridization histochemistry ID CELL-ADHESION MOLECULE; NEURITE OUTGROWTH; NCAM; EXPRESSION; EXON; CSF; L1; PERSPECTIVE; NEURONS; GROWTH AB The neural cell adhesion molecule (N-CAM) is a cell recognition molecule that is involved in cellular migration, synaptic plasticity, and CNS development. In schizophrenia, a 105- to 115-kDa N-CAM protein is increased in CSF and in the hippocampus and prefrontal cortex. The variable alternatively spliced exon (VASE) of N-CAM is developmentally regulated and can be spliced into any of the major 120-, 140-, and 180-kDa N-CAM isoforms. We determined that the variable alternative spliced exon of N-CAM (VASE) also is increased in bipolar disorder by quantitative Western immunoblot. VASE immunoreactive proteins (triplet bands around 140 kDa and a single band around 145 kDa) were identified in soluble and membrane brain extracts and quantified in the hippocampus. Soluble VASE 140 kDa was increased in the hippocampus of patients with bipolar disorder as compared to controls, patients with schizophrenia, and suicide cases. Membrane-extracted VASE 140 and 145 kDa were unchanged in the same groups. Multiple 145-kDa VASE-immunoreactive proteins that also reacted to are NCAM antibody were separated by isoelectric focusing and electrophoresis followed by western immunoblotting; however, the VASE 140-kDa proteins were only weakly N-CAM immunoreactive. By immunohistochemistry, VASE colocalized with GFAP-positive astrocytes in the hippocampus. VASE immunostaining was also observed in the cytoplasm of CA4 pyramidal neurons that were positive for phosphorylated high molecular weight neurofilament and synaptophysin terminals. Thus no differences in VASE were found in patients with schizophrenia, but there was a marked increase of VASE immunoreactive proteins in bipolar disorder. It is possible that abnormal regulation of N-CAM proteins results in differing patterns of abnormal expression in neuropsychiatric disorders. C1 NIDA, Sect Plast & Dev, Addict Res Ctr, Washington, DC 20024 USA. NIDA, Mol Neuropsychiat Sect, Addict Res Ctr, Washington, DC 20024 USA. Becton Dickinson & Co, Res Ctr, Neurobiol Sect, Res Triangle Pk, NC 27709 USA. NIMH, Lab Geriatr Psychiat, Bethesda, MD 20892 USA. St Elizabeth Hosp, NIMH, Ctr Neurosci, Clin Brain Disorders Branch, Washington, DC 20032 USA. St Elizabeth Hosp, NIMH, Ctr Neurosci, Stanley Consortium Fdn, Washington, DC 20032 USA. RP Vawter, MP (reprint author), NIDA, Sect Plast & Dev, Addict Res Ctr, Washington, DC 20024 USA. NR 29 TC 37 Z9 37 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 1998 VL 154 IS 1 BP 1 EP 11 DI 10.1006/exnr.1998.6889 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 144TX UT WOS:000077332100001 PM 9875262 ER PT J AU El Hachimi, KH Chaunu, MP Brown, P Foncin, JF AF El Hachimi, KH Chaunu, MP Brown, P Foncin, JF TI Modifications of oligodendroglial cells in spongiform encephalopathies SO EXPERIMENTAL NEUROLOGY LA English DT Article DE prions; immunohistochemistry; ultrastructure; Creutzfeld-Jakob disease; white matter ID CREUTZFELDT-JAKOB-DISEASE; PRION PROTEIN; ULTRASTRUCTURAL PATHOLOGY; WHITE MATTER; SCRAPIE; MICE; DEGENERATION; INFECTION; PLAQUE; PRP AB Although gray matter lesions involving neurones and astrocytes are prominent in human transmissible spongiform encephalopathies (TSE), white matter lesions have also been occasionally observed. Secondary (Wallerian) degeneration and direct myelin damage have been invoked, but the physiopathology of white matter involvement is still debated. We performed an immunohistochemistry study with anti-PrP antibodies of autopsy material of four patients with Creutzfeldt-Jakob disease (CJD), together with transmission electron microscopy (TEM) studies of conventionally processed biopsy specimens of the same patients. Light microscopy immunolabeling was observed as arrays adjacent to myelinic fibers and as a clumps adjacent to oligodendroglial nuclei; both cerebrum and cerebellum were involved. At the ultrastructural level, two types of intracellular inclusions were seen in the white matter. They were associated with dense lysosomes in oligodendroglial perikarya and in their processes. The inclusions were made of finely fibrillar, paracrystalline, amorphous, or densely osmophilic material. Thus, our findings may suggest that white matter involvement in spongiform encephalopathy is due to direct modifications of oligodendroglial cells associated with abnormal metabolism of PrP. (C) 1998 Academic Press. C1 Hop La Pitie Salpetriere, Ecole Prat Hautes Etud, F-75651 Paris 13, France. Hop La Pitie Salpetriere, INSERM, U106, F-75651 Paris, France. CHU Reims, Serv Neurol, F-51100 Reims, France. NINCDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. RP El Hachimi, KH (reprint author), Hop La Pitie Salpetriere, Ecole Prat Hautes Etud, Bat Pediat,47 Bd Hop, F-75651 Paris 13, France. NR 27 TC 12 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 1998 VL 154 IS 1 BP 23 EP 30 DI 10.1006/exnr.1998.6894 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 144TX UT WOS:000077332100003 PM 9875264 ER PT J AU Weiss, SRB Eidsath, A Li, XL Heynen, T Post, RM AF Weiss, SRB Eidsath, A Li, XL Heynen, T Post, RM TI Quenching revisited: Low level direct current inhibits amygdala-kindled seizures SO EXPERIMENTAL NEUROLOGY LA English DT Article DE epilepsy; kindling; amygdala; quenching; seizure threshold; afterdischarge threshold; rats; direct current ID STIMULATION; DEPRESSION; MECHANISMS AB We have reported that low frequency stimulation (1 Hz for 15 min), applied after kindling stimulation of the amygdala, inhibited the development and expression of amygdala-kindled seizures, an effect we termed quenching. Subsequently we discovered that this effect could only be achieved when certain stimulators were used that also emitted a low-level direct current (DC). The studies reported here indicate that DC, applied once daily for 15 min at intensities of 5-15 mu A, produced an intensity-related attenuation of kindling development and an increase in the afterdischarge threshold. This effect persisted in some animals for at least 1 month after discontinuation of the DC. In fully kindled animals, a robust increase in seizure threshold and persistent seizure inhibition were also observed using 10 mu A of DC administered for 14 days. These results clarify and extend our original findings of a quenching effect; however, the mechanisms by which low level DC induces quenching require further elucidation. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NIH, Biomed Engn & Instrumentat Program, Bethesda, MD 20892 USA. RP Weiss, SRB (reprint author), NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NR 15 TC 58 Z9 63 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 1998 VL 154 IS 1 BP 185 EP 192 DI 10.1006/exnr.1998.6932 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 144TX UT WOS:000077332100018 PM 9875279 ER PT J AU de la Cruz, F Shifrin, H Elias, S Bianchi, DW Jackson, L Evans, MI Simpson, JL Holzgreve, W Klinger, K AF de la Cruz, F Shifrin, H Elias, S Bianchi, DW Jackson, L Evans, MI Simpson, JL Holzgreve, W Klinger, K TI Low false-positive rate of aneuploidy detection using fetal cells isolated from maternal blood SO FETAL DIAGNOSIS AND THERAPY LA English DT Letter C1 NICHHD, Bethesda, MD 20892 USA. RP Elias, S (reprint author), Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA. NR 2 TC 25 Z9 25 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-3837 J9 FETAL DIAGN THER JI Fetal Diagn. Ther. PD NOV-DEC PY 1998 VL 13 IS 6 BP 380 EP 380 DI 10.1159/000020874 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 165WW UT WOS:000078545700012 PM 10075448 ER PT J AU Dar, DE Zinder, O AF Dar, DE Zinder, O TI Catecholamine secretion from bovine adrenal chromaffin cells induced by the dextrorotatory isomer of anatoxin-a SO GENERAL PHARMACOLOGY LA English DT Article DE (+)anatoxin alpha; nicotine; acetylcholine; oxotremorine-M; catecholamines; chromaffin cells ID NICOTINIC ACETYLCHOLINE-RECEPTOR; POTENT AGONIST; PATCH-CLAMP; BINDING AB 1. The nicotinic agonist (+)anatoxin-a was studied in acute preparations of adrenal chromaffin cells and was compared with other known stimulants in this system. 2. (+)Anatoxin-a was found to be a potent stimulant of catecholamine secretion with EC50 = 545.7 nM, which was 5.8 times as strong as nicotine (EC50 = 3,165 nM). (+)-Anatoxin-a action was time dependent and saturable. 3. The pharmacological characteristics of (+)anatoxin a were tested by using nicotinic and muscarinic antagonists (mecamylamine and atropine, respectively). Mecamylamine (1 mu M) and atropine (100 mu M) inhibited the secretion induced by (+)anatoxin-a (1 mu M), as well as that induced by nicotine (10 mu M), acetylcholine (10 mu M and 100 mu M) and oxotremorine-M (100 mu M) 4. The calcium requirement for (+)anatoxin a action was tested in comparison with the aforementioned stimulants, Addition of the calcium antagonist verapamil (10 mu M) or the calcium chelator EGTA (3 mM) reduced all stimulants' action. 5. These results show that the (+)enantiomer of anatoxin-a is both dose and time dependent. Its action is mediated through the classical operation of the nicotinic acetylcholine receptor, by using calcium influx. (C) 1998 Elsevier Science Inc. C1 Rambam Med Ctr, Dept Clin Biochem, IL-31096 Haifa, Israel. Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel. RP Dar, DE (reprint author), NIDA, Div Intramural Res, Mol Neurobiol Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 22 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-3623 J9 GEN PHARMACOL JI Gen. Pharmacol. PD NOV PY 1998 VL 31 IS 5 BP 737 EP 740 DI 10.1016/S0306-3623(98)00113-X PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 131UE UT WOS:000076593000013 PM 9809471 ER PT J AU Chester, N Kuo, F Kozak, C O'Hara, CD Leder, P AF Chester, N Kuo, F Kozak, C O'Hara, CD Leder, P TI Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom's syndrome gene SO GENES & DEVELOPMENT LA English DT Article DE Bloom's syndrome; knockout mouse; genome instability; sister chromatid exchange; micronuclei; apoptosis ID WERNERS-SYNDROME GENES; SYNDROME FIBROBLASTS; GENOME STABILITY; DNA HELICASE; HOMOLOG; MOUSE; MUTATION; GROWTH; SGS1; RECOMBINATION AB Bloom's syndrome is a human autosomal genetic disorder characterized at the cellular level by genome instability and increased sister chomatid exchanges (SCEs). Clinical features of the disease include proportional dwarfism and a predisposition to develop a wide variety of malignancies. The human BLM gene has been cloned recently and encodes a DNA helicase. Mouse embryos homozygous for a targeted mutation in the murine Bloom's syndrome gene (Blm) are developmentally delayed and die by embryonic day 13.5. The fact that the interrupted gene is the homolog of the human BLM gene was confirmed by its homologous sequence, its chromosomal location, and by demonstrating high numbers of SCEs in cultured murine Blm(-/-) fibroblasts. The proportional dwarfism seen in the human is consistent with the small size and developmental delay (12-24 hr) seen during mid-gestation in murine Blm(-/-) embryos. Interestingly, the growth retardation in mutant embryos can be accounted for by a wave of increased apoptosis in the epiblast restricted to early post-implantation embryogenesis. Mutant embryos do not survive past day 13.5, and at this time exhibit severe anemia. Red blood cells and their precursors from Blm(-/-) embryos are heterogeneous in appearance and have increased numbers of macrocytes and micronuclei. Both the apoptotic wave and the appearance of micronuclei in red blood cells are likely cellular consequences of damaged DNA caused by effects an replicating or segregating chromosomes. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Leder, P (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. EM Leder@Rascal.med.harvard.edu NR 49 TC 140 Z9 141 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 1 PY 1998 VL 12 IS 21 BP 3382 EP 3393 DI 10.1101/gad.12.21.3382 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 139BE UT WOS:000077006900009 PM 9808625 ER PT J AU Collins, FS AF Collins, FS TI Genetics: not just in there somewhere, but at the very center of medicine SO GENETICS IN MEDICINE LA English DT Editorial Material C1 Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RP Collins, FS (reprint author), Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NR 0 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV-DEC PY 1998 VL 1 IS 1 BP 3 EP 3 DI 10.1097/00125817-199811000-00003 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 238HF UT WOS:000082704300003 ER PT J AU Pilz, DT Macha, ME Precht, KS Smith, ACM Dobyns, WB Ledbetter, DH AF Pilz, DT Macha, ME Precht, KS Smith, ACM Dobyns, WB Ledbetter, DH TI Fluorescence in situ hybridization analysis with LIS1 specific probes reveals a high deletion mutation rate in isolated lissencephaly sequence SO GENETICS IN MEDICINE LA English DT Article DE lissencephaly; LIS1 gene; FISH ID MILLER-DIEKER SYNDROME; SUBCORTICAL LAMINAR HETEROTOPIA; NEURONAL MIGRATION; CHROMOSOME 17P13.3; PRENATAL-DIAGNOSIS; HUMAN BRAIN; GENE; MALFORMATIONS; MICRODELETIONS; ENCODES AB Purpose: Recent revision of the lissencephaly critical region on chromosome 17p13.3 and confirmation of LIS1 as the causative gene for classical lissencephaly has allowed the development and application of fluorescence in situ hybridization (FISH) probes corresponding directly to this gene. Method: We have analyzed patients with isolated lissencephaly sequence (ILS) by FISH with probes at D17S379, an anonymous locus distal to LIS1, and with LIS1 specific probes. Results: In 110 patients with ILS, a deletion at D17S379 was detected in 23.6%. Of those patients without a deletion, 32 were available for further study with LIS1 probes. Deletions were found in eight additional individuals. Conclusion: The overall deletion mutation rate detectable by FlSH with LIS1 probes is approximate to 40%. This rate is significantly higher than the deletion rate observed at D17S379. This indicates that FISH studies using probes specific to LIS1 should be undertaken as the initial diagnostic assay for the evaluation of patients with ILS, and the high frequency of deletions raises the possibility of "hotspots" for chromosome breakage in this region. C1 Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. RP Ledbetter, DH (reprint author), Univ Chicago, Dept Human Genet, 924 E 57th St, Chicago, IL 60637 USA. OI Dobyns, William/0000-0002-7681-2844 NR 25 TC 35 Z9 35 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV-DEC PY 1998 VL 1 IS 1 BP 29 EP 33 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 238HF UT WOS:000082704300007 PM 11261426 ER PT J AU Pruitt, KD AF Pruitt, KD TI WebWise: Web sites of the Human Genome Project SO GENOME RESEARCH LA English DT Article C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Pruitt, KD (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD NOV PY 1998 VL 8 IS 11 BP 1109 EP 1111 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 147QF UT WOS:000077577000002 PM 9847075 ER PT J AU Centola, M Chen, XG Sood, R Deng, ZM Aksentijevich, I Blake, T Ricke, DO Chen, X Wood, G Zaks, N Richards, N Krizman, D Mansfield, E Apostolou, S Liu, JM Shafran, N Vedula, A Hamon, M Cercek, A Kahan, T Gumucio, D Callen, DF Richards, RI Moyzis, RK Doggett, NA Collins, FS Liu, PP Fischel-Ghodsian, N Kastner, DL AF Centola, M Chen, XG Sood, R Deng, ZM Aksentijevich, I Blake, T Ricke, DO Chen, X Wood, G Zaks, N Richards, N Krizman, D Mansfield, E Apostolou, S Liu, JM Shafran, N Vedula, A Hamon, M Cercek, A Kahan, T Gumucio, D Callen, DF Richards, RI Moyzis, RK Doggett, NA Collins, FS Liu, PP Fischel-Ghodsian, N Kastner, DL TI Construction of an similar to 700-kb transcript map around the familial Mediterranean fever locus on human chromosome 16p13.3 SO GENOME RESEARCH LA English DT Article ID ZINC-FINGER PROTEIN; TRANSFER-RNA GENES; POLYMERASE CHAIN-REACTION; POSITIONAL CLONING; HUMAN GENOME; HUMAN DNA; MOLECULAR ANALYSIS; CANDIDATE REGION; CODING REGIONS; MOUSE HOMOLOG AB We used a combination of cDNA selection, exon amplification, and computational prediction from genomic sequence to isolate transcribed sequences from genomic DNA surrounding the familial Mediterranean fever (FMF) locus. Eighty-seven kb of genomic DNA around D16S3370, a marker showing a high degree of linkage disequilibrium with FMF, was sequenced to completion, and the sequence annotated. A transcript map reflecting the minimal number of genes encoded within the similar to 700 kb of genomic DNA surrounding the FMF locus was assembled. This map consists of 27 genes with discreet messages detectable on Northerns, in addition to three olfactory-receptor genes, a cluster of 18 tRNA genes, and two putative transcriptional units that have typical intron-exon splice junctions yet do not detect messages on Northerns. Four of the transcripts are identical to genes described previously, seven have been independently identified by the French FMF Consortium, and the others are novel. Six related zinc-finger genes, a cluster of tRNAs, and three olfactory receptors account for the majority of transcribed sequences isolated from a 315-kb FMF central region (between D16S468/D16S3070 and cosmid 377A12). Interspersed among them are several genes that may be important in inflammation. This transcript map not only has permitted the identification of the FMF gene (MEFV), but also has provided us an opportunity to probe the structural and functional features of this region of chromosome 16. C1 NIAMSD, Athrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA. Cedars Sinai Med Ctr, Dept Med Genet, Los Angeles, CA 90048 USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. Univ Calif Los Alamos Natl Lab, Ctr Human Genome Studies, Los Alamos, NM 87545 USA. Univ Michigan, Dept Anat & Cell Biol, Ann Arbor, MI 48109 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Adelaide Womens & Childrens Hosp, Dept Cytogenet & Mol Genet, Adelaide, SA 5006, Australia. Univ Adelaide, Dept Genet, Adelaide, SA 5000, Australia. RP Kastner, DL (reprint author), NIAMSD, Athrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. EM kastnerd@arb.niams.nih.gov RI Liu, Paul/A-7976-2012; Callen, David/G-1975-2012; Hamon, Melanie/B-3501-2013; OI Liu, Paul/0000-0002-6779-025X; Callen, David/0000-0002-6189-9991 FU NIAMS NIH HHS [NIH-P60-AR20527] NR 97 TC 8 Z9 10 U1 1 U2 6 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD NOV PY 1998 VL 8 IS 11 BP 1172 EP 1191 PG 20 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 147QF UT WOS:000077577000007 PM 9847080 ER PT J AU Cerritelli, SM Crouch, RJ AF Cerritelli, SM Crouch, RJ TI Cloning, expression, and mapping of ribonucleases H of human and mouse related to bacterial RNase HI SO GENOMICS LA English DT Article ID DOUBLE-STRANDED-RNA; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; REVERSE-TRANSCRIPTASE; DOMAIN; GENES; BINDING; LOCALIZATION; TRANSLATION; SEQUENCE AB We identified two human sequences and one mouse sequence in the database of expressed sequence tags that are highly homologous to the N-terminal sequence of eukaryotic RNases H1. The cDNAs for human RNASEH1 and mouse Rnaseh1 were obtained, their nucleotide sequences determined, and the proteins expressed in Escherichia coli and partially purified. Both proteins have RNase H activity in vitro and they bind to dsRNA and RNA-DNA hybrids through the N-terminal conserved motif present in eukaryotic RNases H1. The RNASEH1 gene is expressed in all human tissues at similar levels, indicating that RNase H1 may be a housekeeping protein. The human RNASEH1 and mouse Rnaseh1 cDNAs were used to isolate BAC genomic clones that were used as probes for fluorescence in situ hybridization. The human gene was localized to chromosome 17p11.2 and the mouse gene to a nonsyntenic region on chromosome 12A3. The chromosomal location and possible disease association of the human RNASEH1 gene are discussed. (C) 1998 Academic Press. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Crouch, RJ (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM robert_crouch@nih.gov NR 36 TC 39 Z9 41 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD NOV 1 PY 1998 VL 53 IS 3 BP 300 EP 307 DI 10.1006/geno.1998.5497 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 137WC UT WOS:000076938900007 PM 9799596 ER PT J AU Chidambaram, A Gerrard, B Hanson, M Dean, M AF Chidambaram, A Gerrard, B Hanson, M Dean, M TI Chromosomal localization of the human and murine orthologues of the Drosophila smoothened gene SO GENOMICS LA English DT Article ID HEDGEHOG; EXPRESSION; RECEPTOR; ENCODES C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. RP Dean, M (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 5 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 1 PY 1998 VL 53 IS 3 BP 416 EP 417 DI 10.1006/geno.1998.5531 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 137WC UT WOS:000076938900026 PM 9799615 ER PT J AU Kim, HJ Noben-Trauth, K Morell, RJ AF Kim, HJ Noben-Trauth, K Morell, RJ TI Tectorin-beta (Tectb) maps to mouse chromosome 19 SO GENOMICS LA English DT Article C1 Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, Rockville, MD 20850 USA. RP Morell, RJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, 5 Res Court, Rockville, MD 20850 USA. OI Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [ZO1 DC00039-01] NR 6 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 1 PY 1998 VL 53 IS 3 BP 419 EP 420 DI 10.1006/geno.1998.5543 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 137WC UT WOS:000076938900028 PM 9799617 ER PT J AU Joyce, S Woods, A De Silva, A Embers, M Boesteanu, A Brutkiewicz, R Yewdell, J Bennink, J Cotter, R AF Joyce, S Woods, A De Silva, A Embers, M Boesteanu, A Brutkiewicz, R Yewdell, J Bennink, J Cotter, R TI The role of cellular glycolipids in CD1 structure and function SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 Penn State Univ, Coll Med, Hershey, PA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Indiana Univ, Indianapolis, IN 46204 USA. NIAID, NIH, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 1998 VL 8 IS 11 MA 26 BP 1111 EP 1111 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130CC UT WOS:000076505300033 ER PT J AU Quarles, RH Tanner, SL Bartoszewicz, ZP AF Quarles, RH Tanner, SL Bartoszewicz, ZP TI Oligosaccharides of glycoproteins in the formation and maintenance of myelinated axons SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NINDS, Myelin & Brain Dev Sect, Cellular & Mol Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 1998 VL 8 IS 11 MA 33 BP 1113 EP 1113 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130CC UT WOS:000076505300040 ER PT J AU Qasba, PK Boeggeman, E Ramakrishnan, B Hirata, J Iyer, L AF Qasba, PK Boeggeman, E Ramakrishnan, B Hirata, J Iyer, L TI Structural Investigations of the stem region of Bovine beta 1,4-galatosyltransferase SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NCI, Struct Gycobiol Sect, Lab Expt & Computat Biol, Div Biol Sci, Bethesda, MD 20892 USA. NCI, Frederick Canc Res Facil, SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 1998 VL 8 IS 11 MA 120 BP 1136 EP 1136 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130CC UT WOS:000076505300127 ER PT J AU Ramakrishnan, B Qasba, PK AF Ramakrishnan, B Qasba, PK TI Structural investigation on bovine beta 1,4-galactosyltransferase: The presence and role of an flexible C-terminal SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NCI, Struct Glycobiol Sect, Lab Expt & Computat Biol, Div Biol Sci, Bethesda, MD 20892 USA. NCI, Frederick Canc Res Facil, SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 1998 VL 8 IS 11 MA 123 BP 1136 EP 1136 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130CC UT WOS:000076505300130 ER PT J AU Boeggeman, E Qasba, PK AF Boeggeman, E Qasba, PK TI Use of site directed mutagenesis to identify the beta-1,4-galactosyltransferase binding sites for metal ions and UDP-Galactose. SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NCI, Struct Glycobiol Sect, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. SAIC, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 1998 VL 8 IS 11 MA 141 BP 1141 EP 1141 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130CC UT WOS:000076505300148 ER PT J AU Iyer, LK Qasba, PK AF Iyer, LK Qasba, PK TI Molecular modeling of platypus alpha-lactalbumin and its complex with sugar and its application to engineer a sugar binding domain in rat alpha-lactalbumin SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Struct Glycobiol Sect, Lab Expt & Computat Biol, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 1998 VL 8 IS 11 MA 161 BP 1147 EP 1147 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 130CC UT WOS:000076505300168 ER PT J AU Grady, C AF Grady, C TI Science in the service of healing SO HASTINGS CENTER REPORT LA English DT Article C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 18 TC 20 Z9 20 U1 0 U2 0 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD NOV-DEC PY 1998 VL 28 IS 6 BP 34 EP 38 DI 10.2307/3528267 PG 5 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 153YQ UT WOS:000077861600021 PM 9868609 ER PT J AU Everhart, J AF Everhart, J TI Diet and gallstones SO HEPATOLOGY LA English DT Letter C1 NIDDKD, Epidemiol & Clin Trials Branch, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. RP Everhart, J (reprint author), NIDDKD, Epidemiol & Clin Trials Branch, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. NR 2 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 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 1998 VL 28 IS 5 BP 1438 EP 1438 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 133RG UT WOS:000076699100042 PM 9841231 ER PT J AU Chen, L Nelson, DM Zheng, ZL Morgan, RA AF Chen, L Nelson, DM Zheng, ZL Morgan, RA TI Ex vivo fibroblast transduction in rabbits results in long-term (> 600 days) factor IX expression in a small percentage of animals SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; CLOTTING FACTOR-IX; HERITABLE HYPERLIPIDEMIC RABBIT; MODIFIED SKIN FIBROBLASTS; HEMOPHILIA-B; ADENOASSOCIATED VIRUS; PERSISTENT EXPRESSION; RETROVIRAL VECTORS; INVIVO EXPRESSION; MICE AB Delivery of human factor IX to the circulation was analyzed in rabbits by ex vivo fibroblast transduction followed by subcutaneous implantation. Kinetic studies of human factor IX in rabbits demonstrated a half-life of approximately 16 hr and a volume distribution of 22%, where intraperitoneal and subcutaneous bioavailability was three- to sevenfold lower than by intravenous administration. Ex vivo retroviral transduction of autologous fibroblasts was performed on 15 animals. After subcutaneous injection of fibroblast-collagen mixtures, the expression of human factor IX in rabbit plasma was followed by ELISA, Of 15 rabbits injected, expression of human factor IX was detected in 2 animals, and expression was long term (>600 days), One animal had stable levels of human factor IX, at 20 ng/ml, while the second animal had lower and gradually decreasing levels of human factor IX, There were no gross differences in pathology at the injection sites, when comparing animals with human factor IX in plasma and those without. Immunological studies demonstrated antibody formation in response to injection mixture components (including human factor IX), but again there was no correlation with immune response and long-term factor IX production in animals. Tissues at the implantation sites were positive for factor IX DNA by PCR analysis, regardless of whether there was detectable plasma factor IX or not. Small numbers of PCR-positive cells were detected in the internal organs of the long term-expressing rabbits while similar tissues were negative in nonexpressing animals. C1 Natl Human Genome Res Inst, Gene Transfer Technol Sect, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), Natl Human Genome Res Inst, Gene Transfer Technol Sect, Clin Gene Therapy Branch, NIH, Bldg 10,Room 10C103, Bethesda, MD 20892 USA. NR 31 TC 18 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 1 PY 1998 VL 9 IS 16 BP 2341 EP 2351 DI 10.1089/hum.1998.9.16-2341 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 135NC UT WOS:000076807600005 PM 9829533 ER PT J AU Touraine, RL Vahanian, N Ramsey, WJ Blaese, RM AF Touraine, RL Vahanian, N Ramsey, WJ Blaese, RM TI Enhancement of the herpes simplex virus thymidine kinase ganciclovir bystander effect and its antitumor efficacy in vivo by pharmacologic manipulation of gap junctions SO HUMAN GENE THERAPY LA English DT Article ID INTERCELLULAR COMMUNICATION; GENE-THERAPY; NEOPLASTIC TRANSFORMATION; MEMBRANE-PERMEABILITY; RETROVIRAL VECTORS; IN-VITRO; CELLS; EXPRESSION; PROTEIN; CONNEXIN43 AB Apigenin, a flavinoid, and lovastatin, an HMG-CoA reductase inhibitor, upregulated gap junction (GJ) function and dye transfer in tumors expressing GJ and were inactive in the GJ-negative tumor line N2a. N2a cells transfected with the connexin 43 gene showed restored cell-to-cell dye transfer, which could then be improved nearly fourfold by addition of apigenin, To test the drugs in HSV thymidine kinase/ganciclovir (HSV-tk/GCV) tumor killing, mixtures of 90% wild-type (WT) with 10% HSV-tk gene-modified MCA38 adenocarcinoma cells were exposed in vitro to GCV +/- apigenin or lovastatin. A significant bystander effect (BSE) was seen following GCV treatment alone, while neither apigenin or lovastatin alone had any effect on the recovery of viable tumor colonies. However, GCV-treated cultures also exposed to apigenin or lovastatin showed an increased BSE and reduced tumor cell recovery. Thirty percent of mice bearing tumors from the same mixture of 90% WT and 10% HSV-tk MCA38 cells treated with GCV alone became tumor free. Tumor-bearing mice given only two or three injections of lovastatin or apigenin during GCV treatment had a doubling of the antitumor response rate, with 60-70% of the mice achieving complete remission. These results support the hypothesis that the transfer of phosphorylated GCV from HSV-tk gene-expressing cells to neighboring WT tumor cells is a major component of the BSE and that pharmacological manipulation of GJ function with lovastatin or apigenin can result in striking improvement in the antitumor response in mice with tumors modified to contain as few as 10% HSV-tk cells. C1 Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Touraine, RL (reprint author), Hop Necker Enfants Malad, Ctr Genet Humaine, U393, Tour Lavoisier,2eme Etage,149 Rue Sevres, F-75743 Paris 15, France. NR 36 TC 76 Z9 82 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 1 PY 1998 VL 9 IS 16 BP 2385 EP 2391 DI 10.1089/hum.1998.9.16-2385 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 135NC UT WOS:000076807600009 PM 9829537 ER PT J AU Nelson, DM Wahlfors, JJ Chen, L Onodera, M Morgan, RA AF Nelson, DM Wahlfors, JJ Chen, L Onodera, M Morgan, RA TI Characterization of diverse viral vector preparations, using a simple and rapid whole-virion dot-blot method SO HUMAN GENE THERAPY LA English DT Article ID EXPRESSION VECTORS; GENE-THERAPY; CLONES AB A number of different viruses have been adapted as gene transfer vectors, including retroviruses, adenoviruses, adenoassociated viruses (AAVs), herpes simplex virus, SV40 viruses, and alphaviruses (both Semliki Forest and Sindbis viruses), One of the major rate-limiting and time-consuming steps in the characterization of these vectors is the process of determining the viral vector titers, In addition, there is no "universal" method that can be used to rapidly estimate the titer and the utility of viral vector preparations. We demonstrate here that supernatant from diverse classes of viral victors, with either RNA or DNA genomes, can be rapidly evaluated by a simple virus dot-blot hybridization without prior extraction of nucleic acids. This system can provide a reliable screen for physical titer of viral vector supernatants in 1 day. C1 Natl Human Genome Res Inst, Gene Transfer Technol Sect, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), Natl Human Genome Res Inst, Gene Transfer Technol Sect, Clin Gene Therapy Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10C103, Bethesda, MD 20892 USA. NR 13 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 1 PY 1998 VL 9 IS 16 BP 2401 EP 2405 DI 10.1089/hum.1998.9.16-2401 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 135NC UT WOS:000076807600011 PM 9829539 ER PT J AU Meng, X Lu, XJ Li, ZZ Green, ED Massa, H Trask, BJ Morris, CA Keating, MT AF Meng, X Lu, XJ Li, ZZ Green, ED Massa, H Trask, BJ Morris, CA Keating, MT TI Complete physical map of the common deletion region in Williams syndrome and identification and characterization of three novel genes SO HUMAN GENETICS LA English DT Article ID SUPRAVALVULAR AORTIC-STENOSIS; ELASTIN GENE; CHROMOSOME 17P13.3; 7Q11.23; HOMOLOGY; PROTEIN; HEMIZYGOSITY; FAMILY; KB AB Williams syndrome (WS) is a contiguous gene deletion disorder caused by haploinsufficiency of genes at 7q11.23. We have shown that hemizygosity of elastin is responsible for one feature of WS, supravalvular aortic stenosis (SVAS). We have also implicated LIM-kinase I hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS-However, the common WS deletion region has not been completely characterized, and genes for additional features of WS, including mental retardation, infantile hypercalcemia, and unique personality profile, are yet to be discovered. Here, we present a physical map encompassing 1.5 Mb DNA that is commonly deleted in individuals with WS. Fluorescence in situ hybridization analysis of 200 WS individuals shows that WS individuals have the consistent deletion interval. In addition, we identify three novel genes from the common deletion region: WS-beta TRP, WS-beta HLH, and BCL7B. WS-beta TRP has four putative beta-transducin (WD40) repeats, and WS-bHLH is a novel basic helix-loop-helix leucine zipper (bHLHZip) gene. BCL7B belongs to a novel family of highly conserved genes. We describe the expression profile and genomic structure for each of these genes. Hemizygous deletion of one or more of these genes may contribute to developmental defects in WS. C1 Univ Utah, Howard Hughes Med Inst, Dept Human Genet, Salt Lake City, UT 84112 USA. Univ Utah, Div Cardiol, Salt Lake City, UT 84112 USA. Univ Utah, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Mol Biotechnol, Seattle, WA 98195 USA. Univ Nevada, Sch Med, Dept Pediat, Div Genet, Las Vegas, NV 89102 USA. RP Keating, MT (reprint author), Univ Utah, Howard Hughes Med Inst, Dept Human Genet, Salt Lake City, UT 84112 USA. EM mark@howard.genetics.utah.edu FU NCRR NIH HHS [M01-RR0064]; NICHD NIH HHS [R01HD29957]; NINDS NIH HHS [R01NS35102-01] NR 35 TC 82 Z9 87 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 1998 VL 103 IS 5 BP 590 EP 599 DI 10.1007/s004390050874 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 145BH UT WOS:000077350700009 PM 9860302 ER PT J AU Haddad, BR Schrock, E Meck, J Cowan, J Young, H Ferguson-Smith, MA du Manoir, S Ried, T AF Haddad, BR Schrock, E Meck, J Cowan, J Young, H Ferguson-Smith, MA du Manoir, S Ried, T TI Identification of de novo chromosomal markers and derivatives by spectral karyotyping SO HUMAN GENETICS LA English DT Article ID STRUCTURALLY ABNORMAL CHROMOSOMES; IN-SITU HYBRIDIZATION; PRENATAL DIAGNOSES; FOLLOW-UP; FLUORESCENCE; CYTOGENETICS; REARRANGEMENTS; SERIES; FISH; AGE AB Despite major advances in molecular cytogenetics during the past decade and the important diagnostic role that fluorescence in situ hybridization (FISH) plays in the characterization of chromosomal abnormalities, the usefulness of this technique remains limited by the number of spectrally distinguishable fluorochromes or fluorochrome combinations. Overcoming this major limitation would allow one to use FISH to screen the whole human genome for Introduction chromosomal aberrations which, until recently, was possible only through conventional karyotyping. A recently described molecular cytogenetics technology, 24-color FISH using spectral karyotyping (SKY), permits the simultaneous visualization of all human chromosomes in 24 different colors. Most chromosomal aberrations detected during cytogenetic evaluation can be resolved using routine cytogenetic techniques alone or in combination with single- or dual-color FISH. However, some cases remain unresolved, in particular de novo supernumerary marker chromosomes and de novo unbalanced structural rearrangements. These findings cause particular diagnostic and counseling concerns when detected during prenatal diagnosis. The purpose of this report is to demonstrate the application of SKY in the characterization of these de novo structural chromosomal abnormalities. Eight cases are described in this report. SKY has considerable diagnostic applications in prenatal diagnosis because of its reliability and speed. The identification of the chromosomal origin of markers and unbalanced translocations provides the patient, physician, and genetic counselor with better predictive information on the phenotype of the carrier. C1 Georgetown Univ, Inst Mol & Human Genet, Med Ctr, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. RP Haddad, BR (reprint author), Georgetown Univ, Inst Mol & Human Genet, Med Ctr, M-4000,3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 25 TC 54 Z9 55 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 1998 VL 103 IS 5 BP 619 EP 625 DI 10.1007/s004390050878 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 145BH UT WOS:000077350700013 PM 9860306 ER PT J AU Ko, MSH Threat, TA Wang, XQ Horton, JH Cui, YS Wang, XH Pryor, E Paris, J Wells-Smith, J Kitchen, JR Rowe, LB Eppig, J Satoh, T Brant, L Fujiwara, H Yotsumoto, S Nakashima, H AF Ko, MSH Threat, TA Wang, XQ Horton, JH Cui, YS Wang, XH Pryor, E Paris, J Wells-Smith, J Kitchen, JR Rowe, LB Eppig, J Satoh, T Brant, L Fujiwara, H Yotsumoto, S Nakashima, H TI Genome-wide mapping of unselected transcripts from extraembryonic tissue of 7.5-day mouse embryos reveals enrichment in the t-complex and under-representation on the X chromosome SO HUMAN MOLECULAR GENETICS LA English DT Article ID EXPRESSED SEQUENCE TAGS; GENE; MAMMALS; LOCUS; PCR; MAP; IDENTIFICATION; MUTATIONS; EVOLUTION; DATABASE AB Mammalian embryos can only survive if they attach to the uterus (implantation) and establish proper maternal-fetal interactions. To understand this complex implantation pathway, we have initiated genomic analysis with a systematic study of the cohort of genes expressed in extraembryonic cells that are derived from the conceptus and play a major role in this process. A total of 2103 cDNAs from the extraembryonic portion of 7.5-day post-conception mouse embryos yielded 3186 expressed sequence tags, similar to 40% of which were novel to the sequence databases. Furthermore, when 155 of the cDNA clones with no homology to previously detected genes were genetically mapped, apparent clustering of these expressed genes was detected in subregions of chromosomes 2, 7, 9 and 17, with 6.5% of the observed genes localized in the t-complex region of chromosome 17, which represents only -1.5% of the mouse genome. In contrast, X-linked genes were under-represented. Semi-quantitative RT-PCR analyses of the mapped genes demonstrated that one third of the genes were expressed solely in extraembryonic tissue and an additional one third of the genes were expressed predominantly in the extraembryonic tissues, The over-representation of extraembryonic-expressed genes in dosage-sensitive autosomal imprinted regions and under-representation on the dosage-compensated X chromosome may reflect a need for tight quantitative control of expression during development. C1 Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Dept Internal Med, Detroit, MI 48202 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Tokyo Womens Med Coll, Dept Hyg & Publ Hlth, Tokyo 160, Japan. NIA, Res Resources Branch, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), Wayne State Univ, Sch Med, Ctr Mol Med & Genet, 5047 Gullen Mall, Detroit, MI 48202 USA. EM msko@cmb.biosci.wayne.edu RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU NHGRI NIH HHS [HG00941]; NICHD NIH HHS [HD32243] NR 53 TC 71 Z9 71 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1998 VL 7 IS 12 BP 1967 EP 1978 DI 10.1093/hmg/7.12.1967 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 137WD UT WOS:000076939100017 PM 9811942 ER PT J AU Roth, MJ Wang, GQ Lewin, KJ Ning, L Dawsey, SM Wesley, MN Giffen, C Xie, YQ Maher, MM Taylor, PR AF Roth, MJ Wang, GQ Lewin, KJ Ning, L Dawsey, SM Wesley, MN Giffen, C Xie, YQ Maher, MM Taylor, PR TI Histopathologic changes seen in esophagectomy specimens from the high-risk region of Linxian, China: Potential clues to an etiologic exposure? SO HUMAN PATHOLOGY LA English DT Article DE esophagus; cancer; China; etiology; anthracosis; arteriosclerosis; coal; polycyclic aromatic hydrocarbons ID INDOOR AIR-POLLUTION; LUNG-CANCER; XUAN-WEI; AROMATIC-HYDROCARBONS; COAL AB Esophageal cancer is one of the most fatal cancers worldwide and is characterized by great variation in rates among different populations. Linxian, a county in Henan Province, located in north-central China, has one of the highest rates of esophageal squamous cell carcinoma in the world. Most squamous cell carcinomas in low-risk populations are attributable to alcohol and tobacco consumption, but the causative agents in high-risk populations are less clear. The prevention and treatment of esophageal cancer in high-risk regions, such as Linxian, are limited by our inability to identify these agent(s). During a preliminary histological review the authors noticed characteristic findings in the arteries, nerves, and lymph nodes of esophagectomy specimens from Linxian and wondered whether these findings might offer clues to the cause of squamous cell carcinoma (eg, polycyclic aromatic hydrocarbon exposure) in the Linxian population. The purpose of this study was to report these previously undescribed histopathologic changes and to compare their presence and severity with those found in esophageal squamous cell carcinomas and adenocarcinomas from a lower-risk population in the United States. Forty esophagectomies were reviewed, including 13 squamous cell carcinomas from Linxian and 21 squamous cell carcinomas and six adenocarcinomas from the United States. The presence and severity of arteriosclerosis and myxoid degeneration of nerves and the presence of anthracosis in periesophageal lymph nodes were recorded. The prevalence and severity of these findings in the three groups of esophagectomies were compared. The esophageal squamous cell carcinomas from Linxian, China, had a higher prevalence of arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes than the squamous cell carcinomas from the United States (Wilcoxon test, P<.04 for all comparisons). There were also significant differences in the prevalence of arteriosclerotic vessels and anthracotic lymph nodes between the esophageal squamous cell carcinomas from Linxian and the adenocarcinomas from the United States. Arteriosclerosis and the myxoid degeneration were significantly more severe in the esophageal squamous cell carcinomas from Linxian than in the esophageal squamous cell carcinomas or adenocarcinomas from the United States (Mantel trend test, P <.006 for all comparisons). Arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes can be seen in association with esophageal squamous cell carcinomas from the high-risk region of Linxian, China. These changes appear to be more prevalent and severe than those seen in association with esophageal squamous cell carcinomas or adenocarcinomas from a low-risk population in the United States. These characteristic changes may be causatively significant and may represent histological evidence of high-level environmental exposure to polycyclic aromatic hydrocarbons. Copyright (C) 1998 by W.B. Saunders Company. C1 NCI, Canc Prevent Studies Branch, NIH, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Roth, MJ (reprint author), NCI, Canc Prevent Studies Branch, NIH, Suite 321,6006 Execut Blvd MSC 7058, Bethesda, MD 20892 USA. NR 27 TC 28 Z9 29 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 1998 VL 29 IS 11 BP 1294 EP 1298 DI 10.1016/S0046-8177(98)90260-X PG 5 WC Pathology SC Pathology GA 137EZ UT WOS:000076903000019 PM 9824110 ER PT J AU O'Donnell, CJ Kannel, WB AF O'Donnell, CJ Kannel, WB TI Is there a racial predisposition to hypertension? SO HYPERTENSION LA English DT Editorial Material DE hypertension, essential; race; genetics ID PRESSURE C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston Med Ctr, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Kannel, WB (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. EM esta@fram.nhlbi.nih.gov NR 11 TC 5 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 1998 VL 32 IS 5 BP 817 EP 819 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 141RB UT WOS:000077156300002 PM 9822437 ER PT J AU Oriji, GK Keiser, HR AF Oriji, GK Keiser, HR TI Role of nitric oxide in cyclosporine A-induced hypertension SO HYPERTENSION LA English DT Article DE cyclosporine; arginine; endothelin; acetylcholine; nitrates; rats; aortic rings ID SMOOTH-MUSCLE CELLS; TREATED RATS; VASCULAR RELAXATION; ENDOTHELIAL-CELLS; CORONARY-ARTERIES; L-ARGININE; RESPONSES; TRANSPLANTATION; DYSFUNCTION; TOXICITY AB Cyclosporine A (CsA) is an immunosuppressive agent that also causes hypertension. The effect of CsA on vascular responses was determined in Sprague-Dawley rats and isolated rat aortic rings. Male rats weighing 250 to 300 g were given either CsA (25 mg . kg(-1) . d(-1)) in olive oil or vehicle by intraperitoneal injection for 7 days. CsA administration produced a 42% increase (P<0.001) in mean arterial pressure (MAP) that reached a plateau after 3 days. Conversely, the levels of both nitrate/nitrite, metabolites of nitric oxide (NO), and cGMP, which mediates NO action, decreased by 50% (P<0.001) and 35% (P<0.001), respectively, in the urine. Thoracic aortic rings from rats treated with CsA and precontracted with endothelin (10(-9) mol/L) showed a 35% increase (P<0.001) in tension, whereas endothelium-dependent relaxation induced by acetylcholine (ACh, 10(-9) mol/L) was inhibited 65% (P<0.001) compared with that in untreated rats. This response was similar to that of endothelium-denuded aortic rings from untreated rats in which ACh-induced relaxation was completely abolished (P<0.001), but relaxation induced by S-nitroso-N-acetylpenicillamine (SNAP, 10(-8) mol/L) was unaffected (P<0.001). ACh-induced formation of both nitrate/nitrite and cGMP by both denuded and CsA-treated aortic rings was inhibited 95% (P<0.001) and 65% (P<0.001), respectively, compared with intact aortic rings, The effects of CsA were reversed both in vivo and in vitro by pretreatment with L-arginine (10 mg . kg(-1) . d(-1) IP), the precursor of NO. There were no changes in MAP and tension in rats treated with L-arginine alone. In summary, CsA inhibits endothelial NO activity, with resulting increases in MAP and tension, and this inhibition can be overcome by parenteral administration of L-arginine. C1 NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. RP Oriji, GK (reprint author), NHLBI, Hypertens Endocrine Branch, NIH, 10 Ctr Dr,MSC 1754,Bldg 10,Room 8C103, Bethesda, MD 20892 USA. NR 36 TC 62 Z9 67 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 1998 VL 32 IS 5 BP 849 EP 855 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 141RB UT WOS:000077156300008 PM 9822443 ER PT J AU Shearer, GM AF Shearer, GM TI HIV-induced immunopathogenesis SO IMMUNITY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACQUIRED IMMUNE-DEFICIENCY; T-CELLS; SEROPOSITIVE INDIVIDUALS; INFECTED INDIVIDUALS; CLASS-II; EXPRESSION; PATHOGENESIS; APOPTOSIS; AIDS C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Shearer, GM (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM Gene_Shearer@nih.gov NR 60 TC 90 Z9 91 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 1998 VL 9 IS 5 BP 587 EP 593 DI 10.1016/S1074-7613(00)80656-1 PG 7 WC Immunology SC Immunology GA 144DK UT WOS:000077298300001 PM 9846480 ER PT J AU Finco, TS Kadlecek, T Zhang, WG Samelson, LE Weiss, A AF Finco, TS Kadlecek, T Zhang, WG Samelson, LE Weiss, A TI LAT is required for TCR-mediated activation of PLC gamma 1 and the Ras pathway SO IMMUNITY LA English DT Article ID CELL ANTIGEN RECEPTOR; C-CBL PROTOONCOGENE; SIGNAL-TRANSDUCTION; T-CELLS; TYROSINE PHOSPHORYLATION; ZETA-CHAIN; PHOSPHOLIPASE C-GAMMA-1; GENE-EXPRESSION; PROTEIN; GRB2 AB In this study, we present the further characterization of a mutant Jurkat T cell line, J.CaM2, that is defective in TCR-mediated signal transduction. Although initial TOP-mediated signaling events such as the inducible tyrosine phosphorylation of the TCR-E, chain and ZAP-70 are intact in J.CaM2, subsequent events, including increases in intracellular calcium, Pas activation, and IL-2 gene expression are defective. Subsequent analysis of J.CaM2 demonstrated a severe deficiency in pp36/LAT expression, a recently cloned adaptor protein implicated in TCR signaling. Importantly, reexpression of LAT in J.CaM2 restored all aspects of TCR signaling. These results demonstrate a necessary and exclusive role for LAT in T cell activation. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. NICHHD, Sect Lymphocyte Signaling, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Weiss, A (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM aweiss@itsa.ucsf.edu OI Kadlecek, Theresa/0000-0002-1020-8169 NR 51 TC 396 Z9 399 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 1998 VL 9 IS 5 BP 617 EP 626 DI 10.1016/S1074-7613(00)80659-7 PG 10 WC Immunology SC Immunology GA 144DK UT WOS:000077298300004 PM 9846483 ER PT J AU Bonfoco, E Stuart, PM Brunner, T Lin, T Griffith, TS Gao, Y Nakajima, H Henkart, PA Ferguson, TA Green, DR AF Bonfoco, E Stuart, PM Brunner, T Lin, T Griffith, TS Gao, Y Nakajima, H Henkart, PA Ferguson, TA Green, DR TI Inducible nonlymphoid expression of Fas ligand is responsible for superantigen-induced peripheral deletion of T cells SO IMMUNITY LA English DT Article ID STAPHYLOCOCCAL-ENTEROTOXIN-B; RECEPTOR TRANSGENIC MICE; APOPTOSIS IN-VIVO; CYCLOSPORINE-A; CD95 LIGAND; LYMPHOPROLIFERATIVE SYNDROME; IMMUNE PRIVILEGE; CLONAL DELETION; LYMPHOCYTES; ACTIVATION AB Fas (CD95) and Fas ligand (FasL) play major roles in staphylococcal enterotoxin B (SEB)-induced peripheral deletion of V beta 8(+) T cells. We found that peripheral deletion was defective in radiation chimeras with nonfunctional tissue FasL, regardless of the FasL status of the bone marrow-derived cells. SEE induced a dramatic upregulation of FasL expression and function in nonlymphoid cells of liver and small intestine. This effect was resistant to inhibition by cyclosporin A, which also failed to inhibit peripheral deletion. In SCID animals nonlymphoid tissues did not express Fast in response to SEB unless transplanted lymphocytes were present. Thus, some immune responses induce Fast in nonlymphoid tissues, which in turn kills activated lymphocytes, leading to peripheral T cell deletion. C1 La Jolla Inst Allergy & Immunol, Div Cellular Immunol, San Diego, CA 92121 USA. Washington Univ, Dept Ophthalmol, St Louis, MO 63110 USA. Univ Bern, Inst Pathol, CH-3010 Bern, Switzerland. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Green, DR (reprint author), La Jolla Inst Allergy & Immunol, Div Cellular Immunol, San Diego, CA 92121 USA. EM dgreen5240@aol.com FU NEI NIH HHS [EY06765]; NIGMS NIH HHS [GM52735] NR 47 TC 127 Z9 130 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 1998 VL 9 IS 5 BP 711 EP 720 DI 10.1016/S1074-7613(00)80668-8 PG 10 WC Immunology SC Immunology GA 144DK UT WOS:000077298300013 PM 9846492 ER PT J AU Singer, DS Howcroft, TK Weissman, J Brown, J Kirshner, S Mozes, E Kohn, LD AF Singer, DS Howcroft, TK Weissman, J Brown, J Kirshner, S Mozes, E Kohn, LD TI Regulation of MHC class I gene expression: A case study SO IMMUNOLOGIST LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; HISTOCOMPATIBILITY COMPLEX GENE; TRANSCRIPTION FACTOR; THYROID-CELLS; MICE; ELEMENTS; METHIMAZOLE; MODULATION; INITIATION; INTERFERON AB MHC class I gene transcription is tightly regulated, Here, Dinah S, Singer and colleagues describe the complex mechanisms involved and propose that overexpression may lead to autoimmune disease,while underexpression may lead to unchecked viral infections. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B-17, Bethesda, MD 20892 USA. EM Dinah.Singer@nih.gov NR 40 TC 0 Z9 0 U1 0 U2 0 PU HOGREFE & HUBER PUBLISHERS PI KIRKLAND PA PO BOX 2487, KIRKLAND, WA 98083-2487 USA SN 1192-5612 J9 IMMUNOLOGIST JI Immunologist PD NOV-DEC PY 1998 VL 6 IS 6 BP 214 EP 219 PG 6 WC Immunology SC Immunology GA 158PB UT WOS:000078123000002 ER PT J AU Martin, R Ruddle, NH Reingold, S Hafler, DA AF Martin, R Ruddle, NH Reingold, S Hafler, DA TI T helper cell differentiation in multiple sclerosis and autoimmunity SO IMMUNOLOGY TODAY LA English DT Article AB Researchers from the fields of basic immunology and autoimmune disease, largely but not exclusively focused on multiple sclerosis, came together at a recent workshop* to develop a better understanding of T helper cell responses in autoimmune disease. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth & Immunobiol, New Haven, CT 06520 USA. Natl Multiple Sclerosis Soc, New York, NY 10017 USA. Harvard Univ, Brigham & Womens Hosp, Ctr Neurol Dis, Inst Med, Boston, MA 02115 USA. RP Martin, R (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr Dr MSC 1400, Bethesda, MD 20892 USA. NR 0 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD NOV PY 1998 VL 19 IS 11 BP 495 EP 498 DI 10.1016/S0167-5699(98)01345-0 PG 4 WC Immunology SC Immunology GA 136MC UT WOS:000076862000003 PM 9818541 ER PT J AU Grossman, Z Feinberg, M Kuznetsov, V Dimitrov, D Paul, W AF Grossman, Z Feinberg, M Kuznetsov, V Dimitrov, D Paul, W TI HIV infection: how effective is drug combination treatment? SO IMMUNOLOGY TODAY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; DYNAMICS IN-VIVO; POPULATION-DYNAMICS; T-CELLS; REPLICATION; RESERVOIR; INHIBITOR; PROTEASE; KINETICS AB The rate of decline of plasma HIV RNA in patients treated with anti-retroviral drugs has been postulated to reflect the half-lives of previously HIV-infected cells. Here, Zvi Grossman and colleagues argue that the observed decline is explained by the kinetics of ongoing infection cycles. Residual cell-to-cell infection that becomes increasingly difficult to block could stabilize cellular provirus reservoirs. C1 NIH, OFF AIDS Res, Bethesda, MD 20892 USA. NIH, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. RP Grossman, Z (reprint author), NIH, OFF AIDS Res, Bethesda, MD 20892 USA. EM wepaul@nih.gov RI Grossman, Zvi/A-9643-2008 NR 22 TC 46 Z9 46 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD NOV PY 1998 VL 19 IS 11 BP 528 EP 532 DI 10.1016/S0167-5699(98)01353-X PG 5 WC Immunology SC Immunology GA 136MC UT WOS:000076862000011 PM 9818549 ER PT J AU Harris, SR Thorgeirsson, UP AF Harris, SR Thorgeirsson, UP TI Tumor angiogenesis: Biology and therapeutic prospects SO IN VIVO LA English DT Review DE tumor angiogenesis; antiangiogenesis therapy; endothelial cells; biomarkers ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; SQUAMOUS-CELL CARCINOMA; HUMAN BREAST-CARCINOMA; PROSTATE-CANCER; SOLID TUMORS; PHASE-I; THYMIDINE PHOSPHORYLASE; 13-CIS-RETINOIC ACID; ANGIOSTATIC ACTIVITY AB Angiogenesis is is now recognized as a critical process in tumor progression and is required for solid tumors to grow beyond a few millimeters in size. The transition from a non-angiogenic to an angiogenic phenotype and subsequent tumor vascularization is not well understood but is likely to involve angiogenic stimulators and inhibitors. Regulation of vascular growth also involves complex interactions of extracellular matrix molecules, proteolytic enzymes and cell adhesion molecules. Each step in the angiogenic process represents a potential target for therapeutic anticancer strategies. Antiangiogenic compounds have proven very successful as cancer treatments in murine animal models and demonstrated utility in treating humans cancers in clinical trials. These agents exhibit reduced toxicity and a decreased likelihood for the development of drug resistance compared to conventional chemotherapies. This review summarizes current knowledge of tumor angiogenesis and the factors involved, and, in addition, presents an overview of current and future antiangiogenic therapies. C1 NCI, Div Basic Sci, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, UP (reprint author), NCI, Div Basic Sci, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37,Room 2D02, Bethesda, MD 20892 USA. EM Thorgeiu@dc37a.nci.nih.gov NR 111 TC 41 Z9 41 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD NOV-DEC PY 1998 VL 12 IS 6 BP 563 EP 570 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 153HB UT WOS:000077826300001 PM 9891218 ER PT J AU Kullberg, MC Ward, JM Gorelick, PL Caspar, P Hieny, S Cheever, A Jankovic, D Sher, A AF Kullberg, MC Ward, JM Gorelick, PL Caspar, P Hieny, S Cheever, A Jankovic, D Sher, A TI Helicobacter hepaticus triggers colitis in specific-pathogen-free interleukin-10 (IL-10)-deficient mice through an IL-12- and gamma interferon-dependent mechanism SO INFECTION AND IMMUNITY LA English DT Article ID CD4(+) T-CELLS; INFLAMMATORY BOWEL-DISEASE; CHRONIC INTESTINAL INFLAMMATION; CHRONIC ACTIVE HEPATITIS; MONOCLONAL-ANTIBODIES; BACTERIAL-INFECTION; ULCERATIVE-COLITIS; MUTANT MICE; SCID MICE; CYTOKINE AB Mice rendered deficient in interleukin-10 (IL-10) by gene targeting (IL-10(-/-) mice) develop chronic enterocolitis resembling human inflammatory bowel disease (IBD) when maintained in conventional animal facilities. However, they display a minimal and delayed intestinal inflammatory response when reared under specific-pathogen-free (SPF) conditions, suggesting the involvement of a microbial component in pathogenesis. We show here that experimental infection with a single bacterial agent, Helicobacter hepaticus, induces chronic colitis in SPF-reared IL-10(-/-) mice and that the disease is accompanied by a type 1 cytokine response (gamma interferon [IFN-gamma], tumor necrosis factor alpha, and nitric oxide) detected by restimulation of spleen and mesenteric lymph node cells with a soluble H. hepaticus antigen (Ag) preparation. In contrast, wild-type (WT) animals infected with the same bacteria did not develop disease and produced IL-10 as the dominant cytokine in response to Helicobacter Ag. Strong H. hepaticus-reactive antibody responses as measured by Ag-specific total immunoglobulin G (IgG), IgG1, IgG2a, IgG2b, IgG3, and IgA were observed in both WT and IL-10(-/-) mice. In vivo neutralization of IFN-gamma or IL-12 resulted in a significant reduction of intestinal inflammation in H. hepaticus-infected IL-10(-/-) mice, suggesting an important role for these cytokines in the development of colitis in the model. Taken together, these microbial reconstitution experiments formally establish that a defined bacterial agent can serve as the immunological target in the development of large bowel inflammation in IL-10(-/-) mice and argue that in nonimmunocompromised hosts IL-10 stimulated in response to intestinal flora is important in preventing IBD. C1 NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Anim Sci Branch,Off Lab Anim Resources, Div Basic Sci, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Anim Hlth Diagnost Lab, Lab Anim Sci Program,Sci Applicat Corp, Frederick, MD 21702 USA. Biomed Res Inst, Rockville, MD 20852 USA. RP Kullberg, MC (reprint author), NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bldg 4,Room 126,Ctr Dr MSC 0425, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 41 TC 275 Z9 281 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1998 VL 66 IS 11 BP 5157 EP 5166 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 132HT UT WOS:000076624800015 PM 9784517 ER PT J AU Eissa, NT AF Eissa, NT TI Nitric oxide in acute lung injury SO INTENSIVE CARE MEDICINE LA English DT Article C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Eissa, NT (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, 10 Ctr Dr,MSC-1590,BLDG 10 RM 6D03, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD NOV PY 1998 VL 24 IS 11 BP 1226 EP 1227 DI 10.1007/s001340050749 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 144XU UT WOS:000077341700018 PM 9876988 ER PT J AU Rao, VSR Lam, K Qasba, PK AF Rao, VSR Lam, K Qasba, PK TI Architecture of the sugar binding sites in carbohydrate binding proteins - a computer modeling study SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE molecular modeling; legume lectins; binding specificity ID ERYTHRINA-CORALLODENDRON LECTIN; RAY CRYSTAL-STRUCTURE; SACCHARIDE-BINDING; COMBINING SITE; PEA LECTIN; SPECIFICITY; RECOGNITION; AGGLUTININ; RESOLUTION; COMPLEXES AB Different sugars, Gal, GalNAc and Man were docked at the monosaccharide binding sites of Erythrina corallodenron (EcorL), peanut lectin (PNA), Lathyrus ochrus (LOLI), and pea lectin (PSL). To study the lectin-carbohydrate interactions, in the complexes, the hydroxymethyl group in Man and Gal favors, gg and gt conformations respectively, and is the dominant recognition determination. The monosaccharide binding site in lectins that are specific to Gal/GalNAc is wider due to the additional amino acid residues in loop D as compared to that in lectins specific to Man/Glc, and affects the hydrogen bonds of the sugar involving residues from loop D, but not its orientation in the binding site. The invariant amino acid residues Asp from loop A, and Asn and an aromatic residue (Phe or Tyr) in loop C provides the basic architecture to recognize the common features in C4 epimers. The invariant Gly in loop B together with one or two residues in the variable region of loop D/A holds the sugar tightly at both ends. Loss of any one of these hydrogen bonds leads to weak interaction. While the subtle variations in the sequence and conformation of peptide fragment that resulted due to the size and location of gaps present in amino acid sequence in the neighborhood of the sugar binding site of loop D/A seems to discriminate the binding of sugars which differ at C4 atom (galacto and gluco configurations). The variations at loop B are important in discriminating Gal and GalNAc binding. The present study thus provides a structural basis for the observed specificities of legume lectins which uses the same four invariant residues for binding. These studies also bring out the information that is important for the design/engineering of proteins with the desired carbohydrate specificity. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Struct Glycobiol Sect, Lab Expt & Computat Biol, FCRDC, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, Struct Glycobiol Sect, Lab Expt & Computat Biol, FCRDC, Bldg 469,Room 221, Frederick, MD 21702 USA. EM qasba@helix.nih.gov NR 20 TC 21 Z9 24 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0141-8130 J9 INT J BIOL MACROMOL JI Int. J. Biol. Macromol. PD NOV PY 1998 VL 23 IS 4 BP 295 EP 307 DI 10.1016/S0141-8130(98)00056-7 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 138LT UT WOS:000076973900007 PM 9849627 ER PT J AU Mishima, N Tomarev, S AF Mishima, N Tomarev, S TI Chicken Eyes absent 2 gene: isolation and expression pattern during development SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE eye; evolution; Eya2; neural crest; limb ID BRANCHIOOTORENAL BOR SYNDROME; EYELESS GENE; DROSOPHILA; PAX-6; HOMOLOGS; ENCODES; REGION; FAMILY; PROX-1; EYA1 AB In all vertebrates studied (human, mouse, chicken), there are at least three genes related to Drosophila eyes absent (eya) gene. The chicken Eyes absent 2 (Eya2) cDNA was isolated from 14 day embryonic chicken lenses, and a complete open reading frame encoding a 59 kDa protein was elucidated. The chicken Eya2 protein is moderately conserved and 78-82% identical to the mouse and human Eya2, The Eya2 gene demonstrated a dynamic expression pattern in different tissues of diverse embryological origin. Expression of Eya2 was first detected at Hamburger and Hamilton stage 9 in the foregut. At later stages of development, Eya2 mRNA was detected in neural crest derivatives (dorsal root ganglia, branchial arches and cranial nerve ganglia), In the cranial placodes, expression of Eya2 was first detected in the nasal pit at stage 13, In the eye, expression of Eya2 was first convincingly detected in neural retina at stage 24 (day 4). The highest level of Eya2 mRNA in the lens was detected around day 9. Eya2 is also expressed in the cornea and iris. Therefore, chicken Eya2 as well as mouse Eya2 is expressed relatively early in the nasal (but not in the lens) placode and may mediate induction of the nasal placode. Expression of Eya2 in the wing and limb buds is consistent with its proposed role in the patterning of limb connective tissues. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tomarev, S (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bldg 6,Room 2A04,6 Ctr Dr,MSC 2730, Bethesda, MD 20892 USA. NR 25 TC 45 Z9 45 U1 0 U2 0 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD NOV PY 1998 VL 42 IS 8 BP 1109 EP 1115 PG 7 WC Developmental Biology SC Developmental Biology GA 142BR UT WOS:000077180500005 PM 9879708 ER PT J AU Mariano, JM Montuenga, LM Prentice, MA Cuttitta, F Jakowlew, SB AF Mariano, JM Montuenga, LM Prentice, MA Cuttitta, F Jakowlew, SB TI Concurrent and distinct transcription and translation of transforming growth factor-beta type I and type II receptors in rodent embryogenesis SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE growth factor receptor; expression; development; organogenesis; mouse embryo ID MOUSE EMBRYO; DIFFERENTIAL EXPRESSION; MESSENGER-RNAS; TGF BETA-1; LOCALIZATION; TGF-BETA-1; PATTERNS; COMPLEX; REQUIRES; PROTEINS AB The transforming growth factor-betas (TGF-beta s) are multifunctional regulatory polypeptides that play a crucial role in many cell processes and function through a set of cell surface protein receptors that includes TGF-beta type I (RI) and type II (RII). The present study reports a comprehensive comparison of the patterns of expression of TGF-beta RI and RII proteins and mRNAs in the developing mouse embryo using immunohistochemical and in situ hybridization analyses. Although widespread expression of both TGF-beta receptors was detected throughout the embryonic development period so that many similarities occur in localization of the TGF-beta receptors, TGF-beta RI was expressed in a well-defined, non-uniform pattern that was different in many respects from that of TGF-beta RII. Whereas higher levels of TGF-beta RI compared to TGF-beta RII were detected in some tissues of the embryo at the beginning of organogenesis, the level of TGF-beta RII increased more dramatically than that of TGF-beta RI during late organogenesis; this was especially true in many neural structures where TGF-beta RI and RII were comparable by day 16. The lung, kidney and intestine, in which epithelial-mesenchymal interactions occur, showed a complex pattern of TGF-beta RI and RII expression. Additionally, northern blot hybridization and reverse transcription-polymerase chain reaction (RT-PCR) amplification showed non-uniform expression of the transcripts for TGF-beta RI and RII in embryonic and adult mouse and rat tissues. These data show that regulation of TGF-beta 1 RI and RII occurs concurrently, but distinctly, in a spatial and temporal manner in rodent embryogenesis which may allow control of signal transduction of TGF-beta during development. C1 NCI, Med Branch, Dept Cell & Canc Biol, Rockville, MD 20850 USA. Univ Navarra, Sch Med, Dept Histol & Pathol, E-31080 Pamplona, Spain. RP Jakowlew, SB (reprint author), NCI, Med Branch, Dept Cell & Canc Biol, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM jakowlews@bprb.nci.nih.gov NR 34 TC 29 Z9 30 U1 0 U2 0 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD NOV PY 1998 VL 42 IS 8 BP 1125 EP 1136 PG 12 WC Developmental Biology SC Developmental Biology GA 142BR UT WOS:000077180500007 PM 9879710 ER PT J AU Lasser, RA Dukoff, R Levy, J Levin, R Lehtimaki, T Seubert, P Sunderland, T AF Lasser, RA Dukoff, R Levy, J Levin, R Lehtimaki, T Seubert, P Sunderland, T TI Apolipoprotein E epsilon 4 allele in association with global cognitive performance and CSF markers in Alzheimer's disease SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE apolipoprotein E; Alzheimer's disease; tau; cognition; CSF ID CEREBROSPINAL-FLUID TAU; AMYLOID-BETA-PEPTIDE; E GENOTYPE; FOLLOW-UP; PROTEIN; DEMENTIA; SEVERITY; BINDING; POLYMORPHISM; SOMATOSTATIN AB To better define the influence of apolipoprotein E (ApoE) epsilon 4 genotype on the cognitive and biochemical features of Alzheimer's disease (AD), cross-sectional analysis of global cognitive measures and cerebrospinal fluid studies gathered on AD subjects at a tertiary care facility between 1986 and 1997 was carried out. The 112 AD patients examined included 62 women and 50 men with a mean (SD) age of 64.2 (9.2) years. Patient demographics, illness onset age and duration, education level and global cognitive measures were recorded systematically. Genetic analysis for ApoE allele type and biochemical characterization of CSF, including total tau concentration, was performed. Descriptive statistics of demographics, cognitive and CSF measures were performed by chi-square, ANOVA and Tukey's tests. Overrepresentation of the epsilon 4 allele was found, with 45.5% of AD patients heterozygous and 20.5% homozygous for ApoE epsilon 4. Overall, ApoE epsilon 4 status had no effect on mean onset age of AD (F = 1.56; p = 0.214), but an earlier mean onset age of AD (F = 4.10; p = 0.02) was seen in the late-onset subjects. No differences were found with regard to ApoE epsilon 4 status and measures of disease, duration of illness or global cognitive performance. Although CSF tau was elevated in our sample (575.4 +/- 290.3 pg/ml), ApoE epsilon 4 status did not influence total CSF tau or neurotransmitter metabolite levels. ApoE epsilon 4 genotype had no impact on a variety of illness severity, cognitive and CSF examinations in the largest cross-sectional analysis of AD subjects yet reported. (C) 1998 US Government. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland. Athena Neurosci, San Francisco, CA USA. RP Lasser, RA (reprint author), Novartis Pharmaceut Corp, 59 Route 10, E Hanover, NJ 07936 USA. NR 65 TC 12 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD NOV PY 1998 VL 13 IS 11 BP 767 EP 774 DI 10.1002/(SICI)1099-1166(1998110)13:11<767::AID-GPS866>3.0.CO;2-F PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 140JL UT WOS:000077084100004 PM 9850873 ER PT J AU Maxwell, GL Risinger, JI Shaw, H Alvarez, A Barrett, JC Futreal, PA Berchuck, A AF Maxwell, GL Risinger, JI Shaw, H Alvarez, A Barrett, JC Futreal, PA Berchuck, A TI Mutations in the PTEN tumor suppressor gene in cervical carcinomas SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE cervical cancer; PTEN; tumor suppressor gene ID ENDOMETRIAL CARCINOMA; PROSTATE-CANCER; PTEN/MMAC1; FREQUENT; BREAST AB To elucidate further the molecular pathogenesis of cervical cancer we sought to determine whether mutations in the PTEN tumor suppressor gene are a feature of these cancers. Genomic DNA was extracted from 67 primary cervical cancers and 9 immortalized cervical cancer cell lines. Using the polymerase chain reaction, the nine exons and intronic splice sites of the PTEN gene were amplified using 11 primer pairs. Single strand conformation polymorphism analysis was used to screen for mutations in the PTEN gene and variant bands were subjected to DNA sequencing. The primary cancers were also tested for the presence of HPV DNA. Mutations in the PTEN gene were not detected in any of the immortalized cell lines, but sequence alterations were noted in 4/67 (6%) primary cervical cancers. Three mutations resulted in frameshifts that predict truncated protein products, including two cases in which we found an identical 4-base-pair deletion in codons 318-319. In addition, a one-base-pair insertion in codon 320 was seen in another case. Finally, a missense mutation (G143 A) was observed immediately adjacent to the catalytic site of the phosphatase domain in exon 5. In two cases with PTEN mutations in which corresponding normal DNA was available, loss of the wild type allele was demonstrated. There was no apparent relationship between the presence of a PTEN mutation and pathologic features or the presence of human papillomavirus DNA. Although mutations in the PTEN gene are found in only a small fraction of cervical cancers, alterations of this tumor suppressor gene may play a role in the development of some of these cancers. C1 Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Berchuck, A (reprint author), Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Box 3079, Durham, NC 27710 USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV-DEC PY 1998 VL 8 IS 6 BP 489 EP 493 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 152MY UT WOS:000077782400008 ER PT J AU Li, QD Tsang, B Ding, L Wei, JH AF Li, QD Tsang, B Ding, L Wei, JH TI Infection with the human immunodeficiency virus type 2: Epidemiology and transmission (Review) SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE HIV-2; AIDS; prevalence; epidemiology; transmission ID HIV-2 INFECTION; COTE-DIVOIRE; WEST-AFRICA; SEX WORKERS; ABIDJAN; AIDS; RETROVIRUS; ORGANIZATION; PREVALENCE; CHIMPANZEE AB Human immunodeficiency virus type 2 (HIV-2) is known to be one of the agents that causes acquired immunodeficiency syndrome (AIDS). It has been present in West Africa since the 1960s and is currently epidemic there. Compared with human immunodeficiency virus type 1 (HIV-1), HIV-2 is genomically different. Furthermore, it is less prevalent worldwide than HIV-1. In West Africa, seropositive rates of HIV-2 are higher in urban versus rural communities, however, there are no gender differences. Sexual contact and vertical transmission are known modes of infectivity, though HIV-2 is less contagious than HIV-1. C1 NCI, Med Branch, Dev Therapeut Dept, Div Clin Sci,NIH, Bethesda, MD 20892 USA. NIDDKD, Biochem Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Womens & Childrens Hosp, Dept Obstet & Gynecol, Liuzhou 545001, Guangxi, Peoples R China. RP Li, QD (reprint author), 7806 Havenside Terrace, Rockville, MD 20855 USA. NR 41 TC 0 Z9 1 U1 0 U2 3 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD NOV PY 1998 VL 2 IS 5 BP 573 EP 576 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 138JA UT WOS:000076967700008 PM 9858654 ER PT J AU Weyer, C Linkeschowa, R Heise, T Giesen, HT Spraul, M AF Weyer, C Linkeschowa, R Heise, T Giesen, HT Spraul, M TI Implications of the traditional and the new ACSM Physical Activity Recommendations on weight reduction in dietary treated obese subjects SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE physical activity; weight reduction; ACSM; recommendations; obesity ID EXERCISE INTERVENTION; ENERGY-EXPENDITURE; OVERWEIGHT WOMEN; BODY-COMPOSITION; ADULTS; HEALTH; METAANALYSIS; RELIABILITY; PREVENTION; VALIDITY AB OBJECTIVE: To assess the acceptance of the traditional American College of Sports Medicine (ACSM) exercise recommendation (20-60 min of vigorous exercise at least three times per week) and of the new, broader Centers for Disease Control (CDC)/ACSM physical activity recommendation (30 min of moderate intensity activities on most days of the week) in an obese population and to elucidate the implications of meeting these recommendations on weight reduction during dietary treatment. DESIGN: Prospective dietary intervention study of 1000 kcal diet daily. SUBJECTS: 109 obese subjects (age: 45.6 +/- 13.1 y, body mass index (BMI): 38.1 +/- 6.0 kg/m(2), (Female/Male: 81/19%) MEASUREMENTS: The time spent in moderate (3-6 MET, metabolic equivalents) and vigorous (6-10 MET) physical activities was assessed by use of the Stanford-7-Day-Physical-Activity-Recall-Questionnaire, with subsequent allocation of the subjects to one of three physical activity groups: meeting the traditional recommendation (TR), the new recommendation (NR) or neither of both (SED, sedentary subjects). Physical activity level, physical activity energy expenditure, total energy expenditure (based upon the questionnaire) and resting metabolic rate (by standard equation) were estimated at baseline. Body weight was determined at baseline and after a mean of 16.3 weeks of dietary treatment. RESULTS: The new, broader recommendation was met by twice as many of the obese subjects (34%) as was the traditional recommendation (17%). Weight reduction at follow up (- 8.2 +/- 6.5 kg, 16.3 +/- 4.3 weeks, mean +/- s.d.) was positively correlated with the physical activity level at baseline (r = 0.49, P < 0.001). Meeting either the traditional or the new recommendation was associated with greater weight loss [-11.9 +/- 8.5 kg (TR) and -10.1 +/- 6.4 kg (NR), respectively, not statistically significant (NS)] as compared to being sedentary [ - 6.5 +/- 5.2 kg (SED), P < 0.05 vs both NR and TR]. CONCLUSIONS: Not only participation in vigorous exercise, but also regular engagement in moderate intensity physical activities, as recently recommended by the CDC/ACSM, predicts greater weight reduction during dietary treatment, compared to being sedentary. The new, broader physical activity recommendation appears to be more readily accepted by obese subjects than the former ACSM recommendation on exercise training. C1 Univ Dusseldorf, Dept Metab Dis & Nutr, WHO Collaborating Ctr Diabet Treatment & Prevent, D-4000 Dusseldorf, Germany. RP Weyer, C (reprint author), NIDDKD, Clin Diabet & Nutr Sect, 4212 N 16Th St,Rm 5-41, Phoenix, AZ 85016 USA. NR 44 TC 18 Z9 20 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD NOV PY 1998 VL 22 IS 11 BP 1071 EP 1078 DI 10.1038/sj.ijo.0800728 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 132HY UT WOS:000076625300006 PM 9822944 ER PT J AU Li, QD Ding, L Yu, JJ Mu, CJ Tsang, B Bostick-Bruton, F Reed, E AF Li, QD Ding, L Yu, JJ Mu, CJ Tsang, B Bostick-Bruton, F Reed, E TI Cisplatin and phorbol ester independently induce ERCC-1 protein in human ovarian carcinoma cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE cisplatin; ovarian cancer; ERCC-1; phorbol ester; nucleotide excision repair ID DNA ADDUCT FORMATION; PIGMENTOSUM GROUP-F; EXCISION-REPAIR; CANCER CELLS; XPF-ERCC1 COMPLEX; MESSENGER-RNAS; RESISTANCE; LINES; CYTOTOXICITY; GLUTATHIONE AB Nucleotide excision repair (NER) is the DNA repair pathway by which cisplatin-induced damage is removed from DNA in human cells. ERCC-1 is one of the essential proteins in NER, and is essential for life. Enhanced ERCC-1 expression has been associated with clinical and cellular resistance to cisplatin. We therefore carried out this study to investigate the effect of cisplatin on ERCC-1 protein expression in A2780/ CP70 human ovarian cancer cells. Western blot analysis showed that ERCC-1 protein levels were increased to more than 3 times control after a 1 h cisplatin exposure to A2780/ CP70 cells in culture. This increase was time- and concentration-dependent. The effect of cisplatin was maximal at 40 mM and peaked 24-48 h after exposure to the drug. These results extend our previous observations that ERCC-1 mRNA expression is induced by cisplatin in this system. TPA, a known AP-1 activator and tumor-promoting phorbol ester, also induced ERCC-1 protein to the same extent as cisplatin, but did not synergize with cisplatin in this regard. These findings suggest that ERCC-1 gene up-regulation in these cells can result through a DNA damage-response pathway, or through the induction of AP-I activity, independent of the occurrence of DNA damage. C1 NCI, Med Ovarian Canc Sect, Dev Therapeut Dept,Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. NIDDKD, Biochem Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Ovarian Canc Sect, Dev Therapeut Dept,Med Branch, Div Clin Sci,NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 45 TC 32 Z9 32 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 1998 VL 13 IS 5 BP 987 EP 992 PG 6 WC Oncology SC Oncology GA 135MW UT WOS:000076806800015 PM 9772291 ER PT J AU Burger, AM Fiebig, HH Kuettel, MR Lautenberger, JA Kung, HF Rhim, JS AF Burger, AM Fiebig, HH Kuettel, MR Lautenberger, JA Kung, HF Rhim, JS TI Effect of oncogene expression on telomerase activation and telomere length in human endothelial, fibroblast and prostate epithelial cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE telomerase activity; telomeres; E6; E7; v-Ki-ras; HUVEC; fibroblasts; benign prostate hyperplasia prostate epithelial cells; tumorigenicity ID V-KI-RAS; NEOPLASTIC TRANSFORMATION; CANCER; IMMORTALIZATION; TRANSFECTION; PLASMID AB Although strong evidence is mounting that telomerase reactivation and the thereof resulting stabilization of telomeres is a major mechanism for human cells to overcome replicative senescence, a causal relationship linking telomerase activation conclusively to tumorigenesis remains to be established. Thus, the possibility exists that telomerase activation is passively co-selected as tumors develop. To elucidate the function of telomerase during tumorigenesis, we followed telomerase reactivation during immortalization of human primary cell types with in vitro transforming agents and determined the tumorigenic potential of these cells at various stages of transformation. The effects of SV40, v-Ki-ms, HPV-18 and HPV-16 E6/E7 oncoproteins on telomerase expression was examined in primary and immortalized human prostate epithelial (HPE), human prostate fibroblast (HPF), and umbilical vein endothelial cells (HUVEC). All of five SV40-transformed HPE and HPF lines were telomerase positive and had shorter telomeres than primary cells. The two HPV-18 immortalized HPE cell lines also expressed telomerase activity. In contrast, EG or E7 alone could not produce immortalized HUVEC and did not reactivate telomerase. Life-span, however, was extended. The E6/E7 immortalized HUVEC had telomerase activity and short but stable telomeres. HPE, HPF or HUVEC cells which had been transformed by one oncoprotein alone were not tumorigenic although they had overcome cellular senescence and reactivated telomerase. However, if these cells were transformed by a second agent, either infection with v-Ki-ras or X-ray treatment, they were able to form tumors in nude mice. This suggests that tumorigenesis is a multistep process and that telomerase activation alone is not sufficient for malignant transformation in human cells. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Frederick, MD 21702 USA. Univ Freiburg, Tumor Biol Ctr, D-79106 Freiburg, Germany. Georgetown Univ, Sch Med, Vincent T Lombardi Canc Res Ctr, Dept Radiat Med, Washington, DC USA. RP Rhim, JS (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Frederick, MD 21702 USA. NR 25 TC 23 Z9 24 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 1998 VL 13 IS 5 BP 1043 EP 1048 PG 6 WC Oncology SC Oncology GA 135MW UT WOS:000076806800022 PM 9772298 ER PT J AU Hijazi, MM Young, PE Dougherty, MK Bressette, DS Cao, TT Pierce, JH Wong, LM Alimandi, M King, CR AF Hijazi, MM Young, PE Dougherty, MK Bressette, DS Cao, TT Pierce, JH Wong, LM Alimandi, M King, CR TI NRG-3 in human breast cancers: Activation of multiple erbB family proteins SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE breast cancer; erbB genes ID EPIDERMAL GROWTH-FACTOR; NEU DIFFERENTIATION FACTOR; FACTOR RECEPTOR; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; FACTOR-ALPHA; CELL-LINE; IN-VIVO; NEUREGULIN; HEREGULIN AB Ligands of the EGF/Heregulin family control the growth of epithelial cells by binding to receptors of the erbB family. By searching a large database of cDNA sequences at Human Genome Sciences Inc. we have identified a new encoded protein sequence containing all the conserved elements of the EGF/Heregulin family. The same sequence has recently been independently identified as NRG-3. The EGF-like domain of NRG-3 was generated as a recombinant protein in E. coli and used to test the specificity of receptor binding. In human breast cancer cells and in 32D cells transfected by erbB family members, NRG-3 activated multiple erbB family members. These include EGF receptor (erbB1) and erbB4 when expressed individually and erbB2 and erbB3 when expressed together. Recombinant NRG-3 altered the growth of human breast cancer cells growing in vitro. NRG-3 was expressed in cell lines derived from breast cancer. These results indicate that NRG-3 is a potential regulator of normal and malignant breast epithelial cells in vivo. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Human Genome Sci Inc, Dept Mol Biol, Rockville, MD USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP King, CR (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Room 508,Res Bldg,3970 Reservoir Rd, Washington, DC 20007 USA. NR 37 TC 20 Z9 20 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 1998 VL 13 IS 5 BP 1061 EP 1067 PG 7 WC Oncology SC Oncology GA 135MW UT WOS:000076806800024 PM 9772300 ER PT J AU Mitchell, JB DeGraff, W Kim, S Cook, JA Gamson, J Christodoulou, D Feelisch, M Wink, DA AF Mitchell, JB DeGraff, W Kim, S Cook, JA Gamson, J Christodoulou, D Feelisch, M Wink, DA TI Redox generation of nitric oxide to radiosensitize hypoxic cells SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 10TH International Conference on Chemical Modifiers of Cancer Treatment CY JAN 28-31, 1998 CL CLEARWATER, FLORIDA DE nitric oxide; nitroxyl; radiation; hypoxia; sensitizer ID SUPEROXIDE-DISMUTASE; SYNTHASE; TEMPOL; CANCER AB Purpose: Previous studies have shown that nitric oxide (NO) delivered from NO donor agents sensitizes hypoxic cells to ionizing radiation. In the present study, nitroxyl (NO-), a potential precursor to endogenous NO production, was evaluated for hypoxic cell radiosensitization, either alone or in combination with electron acceptor agents. Methods and Materials: Radiation survival curves of Chinese hamster V79 lung fibroblasts under aerobic and hypoxic conditions were assessed by clonogenic assay. Hypoxia induction was achieved by metabolism-mediated oxygen depletion in dense cell suspensions, Cells were treated with NO- produced from the nitroxyl donor Angeli's salt (AS, Na2N2O3, sodium trioxodinitrate), in the absence or presence of electron acceptor agents, ferricyanide, or tempol, NO concentrations resulting from the combination of AS and ferricyanide or tempol were measured under hypoxic conditions using an NO-sensitive electrode. Results: Treatment of V79 cells under hypoxic conditions with AS alone did not result in radiosensitization; however, the combination of AS with ferricyanide or tempol resulted in significant hypoxic radiosensitization with SERs of 2.5 and 2.1, respectively. Neither AS alone nor AS incombination with ferricyanide or tempol influenced aerobic radiosensitivity, The presence of NO generated under hypoxic conditions from the combination of AS with ferricyanide or tempol was confirmed using an NO-sensitive electrode. Conclusion: Combining NO- generated from AS with electron accepters results in NO generation and substantial hypoxic cell radiosensitization. NO- derived from donor agents or endogenously produced in tumors, combined with electron accepters, may provide an important strategy for radiosensitizing hypoxic cells and warrants in vivo evaluation. (C) 1998 Elsevier Science Inc. C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. Natl Canc Inst, FRDC, Comparat Carcinogenesis Lab, Frederick, MD USA. Wolfson Inst, London, England. RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. RI Feelisch, Martin/C-3042-2008 OI Feelisch, Martin/0000-0003-2320-1158 NR 16 TC 23 Z9 26 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 1998 VL 42 IS 4 BP 795 EP 798 DI 10.1016/S0360-3016(98)00327-7 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 142GC UT WOS:000077191000021 PM 9845098 ER PT J AU Hahn, SM DeLuca, AM Coffin, D Krishna, CM Mitchell, JB AF Hahn, SM DeLuca, AM Coffin, D Krishna, CM Mitchell, JB TI In vivo radioprotection and effects on blood pressure of the stable free radical nitroxides SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 10TH International Conference on Chemical Modifiers of Cancer Treatment CY JAN 28-31, 1998 CL CLEARWATER, FLORIDA DE nitroxide; radioprotection; hypotension; murine; free radicals ID TEMPOL; DAMAGE AB Purpose: The purpose of this study was to screen several water soluble nitroxides for in vivo radioprotection, to evaluate their pharmacology, and to measure the effect of nitroxides on systemic blood pressure as a means of exploring the mechanism of in vivo radioprotection, Methods and Materials: A number of water soluble nitroxides were screened for in vivo radioprotection in C3H mice at a single radiation dose. Selected nitroxides were administered by the intraperitoneal route 10 minutes prior to a whole body radiation dose of 9 Gy, Electron paramagnetic resonance spectroscopy (EPR) was used to measure whole blood levels of nitroxides. The nitroxides were evaluated for effects on systemic blood pressure in C3H mice. Results: All of the nitroxides studied demonstrated radioprotection compared to saline-treated controls. The 6-membered piperidine ring nitroxides including Tempol were reduced to the inactive hydroxylamine rapidly over 10-20 minutes. The 5-membered ring nitroxides were reduced more slowly over time. The 5-membered ring 3-carbamoyl-PROXYL did not produce a substantial decrease in systemic blood pressure after intraperitoneal administration compared to the other nitroxides studied. 3-carbamoyl-PROXYL was further evaluated over a range of whole body radiation doses and was found to provide radioprotection, Conclusion: All of the nitroxides studied provided radioprotection, In vivo radioprotection for all of the compounds except 3-carbamoyl-PROXYL may be at least partially explained by the induction of hypotension and bone marrow hypoxia, 3-carbamoyl-PROXYL provided in vivo radioprotection similar in magnitude to Tempol and had little effect on blood pressure compared to the other nitroxides, Other mechanisms for radioprotection, including scavenging of free radicals are likely. 3-carbamoyl-PROXYL should be evaluated further as a systemic radioprotector, (C) 1998 Elsevier Science Inc. C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Bldg 10,Room B3-B69,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 9 TC 43 Z9 45 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 1998 VL 42 IS 4 BP 839 EP 842 DI 10.1016/S0360-3016(98)00317-4 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 142GC UT WOS:000077191000030 PM 9845107 ER PT J AU Okunieff, P Wang, X Rubin, P Finkelstein, JN Constine, LS Ding, I AF Okunieff, P Wang, X Rubin, P Finkelstein, JN Constine, LS Ding, I TI Radiation-induced changes in bone perfusion and angiogenesis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 10TH International Conference on Chemical Modifiers of Cancer Treatment CY JAN 28-31, 1998 CL CLEARWATER, FLORIDA DE aFGF; bFGF; IFN; IGF; LDF; TGF beta; TNF ID FIBROBLAST GROWTH-FACTOR; FACTOR-BETA; BLOOD-FLOW; TUMOR BED; CELLS; FIBROSIS; OXYGEN; PROLIFERATION; IRRADIATION; MODULATION AB Purpose: To determine whether blood flow of bone is altered by limb irradiation and whether bFGF, an angiogenic cytokine, might alleviate any flow or growth abnormality resulting from 30 Gy single fraction irradiation. Methods and Materials: C3H mice received whole right hind limb radiation at doses of 0 to 30 Gy. Additional groups received 30 Gy, and then beginning 1 or 5 weeks later received intravenous bFGF at a dose of 6 mu g/mouse, twice a week for 4 weeks. Serial X-ray films were taken to measure the tibias. At 33 weeks, laser Doppler how (LDF) measurements were made of both limbs. Cytokine measurements were made using ELISA and RNase protection. Results: Bone growth was reduced following radiation in a dose dependent manner, bFGF improved bone growth after radiation even when begun 5 weeks after radiation, however, we detected no significant improvement in LDF of the irradiated bone or periosteum. Muscle tissue surrounding bone of the irradiated leg showed no increase in isoforms of TGF beta, TNF, or IFN. There was also no difference in the circulating plasma TGF beta 1 in irradiated mice. In contrast, LDF increased significantly as a function of radiation dose in the nonirradiated tibia. Systemic delivery of bFGF appears to further enhance the increase in flow seen in the nonirradiated limb. Conclusion: Radiation induces a chronic antiangiogenic effect contributing to reduced limb growth. At 33 weeks the antiangiogenesis was not associated with local soft tissue elevations of TNF, IFN, or TGF beta. Radiation toxicity to bone is alleviated by bFGF therapy suggesting that powerful locally-acting antiangiogenic mechanisms are involved. We postulate that the increased LDF of the contralateral tibia is due to circulating angiogenesis factors that are elevated to compensate for the radiation-induced antiangiogenesis. (C) 1998 Elsevier Science Inc. C1 Univ Rochester, Dept Radiat Oncol, Strong Mem Hosp, Rochester, NY 14642 USA. Univ Rochester, Dept Pediat, Strong Mem Hosp, Rochester, NY 14642 USA. NCI, Radiat Oncol Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Okunieff, P (reprint author), Univ Rochester, Dept Radiat Oncol, Strong Mem Hosp, 601 Elmwood Ave,Box 647, Rochester, NY 14642 USA. FU NCI NIH HHS [2-P01-CA11051-2582] NR 20 TC 20 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 1998 VL 42 IS 4 BP 885 EP 889 DI 10.1016/S0360-3016(98)00339-3 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 142GC UT WOS:000077191000038 PM 9845115 ER PT J AU Kantorow, M Kays, T Horwitz, J Huang, QL Sun, J Piatigorsky, J Carper, D AF Kantorow, M Kays, T Horwitz, J Huang, QL Sun, J Piatigorsky, J Carper, D TI Differential display detects altered gene expression between cataractous and normal human lenses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID METALLOTHIONEIN-IIA GENE; OXIDATIVE STRESS; MESSENGER-RNA; EPITHELIAL-CELLS; OKADAIC ACID; PROTEIN; PHOSPHATASE; IRRADIATION; GLUTATHIONE; INDUCTION AB PURPOSE. TO identify and analyze differentially genes expressed between lens epithelia dissected from age-related cataractous and noncataractous human lenses. METHODS. RNAs from 50 pooled cataractous and 25 pooled noncataractous epithelia were compared by reverse transcription-polymerase chain reaction differential display (RT-PCR-DD). Two differentially displayed bands were chosen for further study. These were reamplified, cloned, and sequenced. Expression of these genes was further evaluated in pooled and individual epithelia by RT-PCR with gene-specific primers. RESULTS. Significant differences in gene expression were detected between the cataractous and the noncataractous epithelia. Three mRNAs displayed higher levels and 12 mRNAs displayed lower levels of expression in the cataractous samples compared with that in the noncataractous samples. Of the mRNAs expressed at higher levels, one was identified as metallothionein IIa (METII). Of the mRNAs with decreased expression, one was identified as protein phosphatase 2A regulatory subunit (P2A-RS). Overexpression of METII and underexpression of P2A-RS were confirmed in pooled and individual epithelia. CONCLUSIONS. These results provide evidence that age-related cataract is associated with alterations in the expression of multiple epithelial genes including METII and P2A-RS. METII is a detoxification protein induced by oxidative stress, and P2A-RS is a mitotic suppressor involved in cell-cycle control. These results implicate these proteins and their associated functions in the maintenance of lens transparency. C1 Jules Stein Eye Inst, Los Angeles, CA 90095 USA. NEI, Bethesda, MD 20892 USA. RP Kantorow, M (reprint author), Jules Stein Eye Inst, 100 Stein Plaza,Room B160, Los Angeles, CA 90095 USA. NR 48 TC 35 Z9 40 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 1998 VL 39 IS 12 BP 2344 EP 2354 PG 11 WC Ophthalmology SC Ophthalmology GA 132HW UT WOS:000076625100018 PM 9804143 ER PT J AU Bulte, JWM Wu, CC Brechbiel, MW Brooks, RA Vymazal, J Holla, M Frank, JA AF Bulte, JWM Wu, CC Brechbiel, MW Brooks, RA Vymazal, J Holla, M Frank, JA TI Dysprosium-DOTA-PAMAM dendrimers as macromolecular T2 contrast agents - Preparation and relaxometry SO INVESTIGATIVE RADIOLOGY LA English DT Article DE dysprosium; dendrimers; macromolecular contrast media; relaxometry; Curie spin relaxation ID NUCLEAR-RELAXATION; CEREBRAL-ISCHEMIA; GD3+ COMPLEXES; PERFUSION; WATER; NMRD; SPECTROSCOPY; MECHANISM; LIGANDS; TUMORS AB RATIONALE AND OBJECTIVES. The authors have investigated dysprosium [Dy]-DOTA-PAMAM, generation 5 (G=5) dendrimers as a possible new class of macromolecular T2 contrast agents. The use of DOTA provides a metal complex with greater stability than can be achieved using DTPA as ligand, an important factor in the design of blood pool agents with long half-lives. METHODS. Generation 5 ammonia-core PAMAM dendrimers were linked to the bifunctional ligand p-SCN-Bz-DOTA, After determination of the number of conjugated DOTA molecules by H-1 nuclear magnetic resonance, Dy3+ was titrated at a 90% molar ratio. For comparison, single ionic chelates of Dy-DTPA and Dy-DOTA also were prepared. Using a variable field relaxometer, T1 and T2 relaxation times mere measured at 13 different held strengths from 0.05 to 1.5 T and temperatures of 3, 10, 20 and 37 degrees C. RESULTS. The synthesis resulted in a preparation with 76 DOTA and 68 Dy3+ ions per dendrimer molecule, The T1 relaxivity values for Dy-DTPA, Dy-DOTA, and the Dy-DOTA-based dendrimer all were independent of field strength, with values between 0.12 and 0.20 mM(-1)sec(-1). At lower fields (0.05-0.1 T), 1/T2 was identical to 1/T1, At higher fields, however, 1/T2 increased quadratically with field strength, with a strong dependence on temperature, The field-dependent component of 1/T2 was up to three times higher for the Dy-DOTA-based dendrimer compared with the single chelate molecules, with coefficients of 0.37 to 0.03 sec(-1)/Tesla(2) for T = 3 to 37 degrees C. CONCLUSIONS. The results are interpreted with the "inner sphere" theory of susceptibility effects (Curie spin relaxation). The large temperature dependence suggests that the dominant mechanism of relaxation is the contact interaction effect, with the proton residence time as the primary time constant, This largely unexplored relaxation mechanism has the potential to create a new class of T2-selective contrast agents. C1 NIH, Lab Diagnost Radiol Res, CC, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. RP Bulte, JWM (reprint author), NIH, Lab Diagnost Radiol Res, CC, Bldg 10,Room B1N256,10 Ctr Dr,MSC 1074, Bethesda, MD 20892 USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 34 TC 34 Z9 34 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD NOV PY 1998 VL 33 IS 11 BP 841 EP 845 DI 10.1097/00004424-199811000-00008 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 136PP UT WOS:000076868600008 PM 9818319 ER PT J AU Nottelmann, ED Jensen, PS AF Nottelmann, ED Jensen, PS TI Current issues in childhood bipolarity SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Editorial Material ID COMORBIDITY; ADOLESCENTS; DISORDER; CHILDREN C1 NIMH, Rockville, MD 20857 USA. RP Nottelmann, ED (reprint author), NIMH, 5600 Fishers Land,Room 18C-17, Rockville, MD 20857 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 12 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV PY 1998 VL 51 IS 2 BP 77 EP 80 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 173CZ UT WOS:000078964800002 PM 10743840 ER PT J AU Knize, MG Sinha, R Brown, ED Salmon, CP Levander, OA Felton, JS Rothman, N AF Knize, MG Sinha, R Brown, ED Salmon, CP Levander, OA Felton, JS Rothman, N TI Heterocyclic amine content in restaurant-cooked hamburgers, steaks, ribs, and chicken SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE heterocyclic amines; PhIP; MeIQx; DiMeIQx; cooking mutagens ID AROMATIC-AMINES; MEAT-PRODUCTS; PAN RESIDUES; FOOD-PRODUCTS; FISH; MUTAGENICITY; CARCINOGENS AB As part of a comprehensive survey of the heterocyclic amine content of foods, beef hamburgers, steaks, and pork ribs were purchased from restaurants, with cooking doneness specified. Samples were pooled by meat type, doneness, and cooking method and analyzed for heterocyclic amine content using HPLC. Results show detectable levels of heterocyclic amines in all samples, ranging from 0.5 ng/g PhIP from a pooled sample of ribs to 20 ng/g total of MeIQx and PhIP from a sample pooled of well-done charbroiled hamburgers. Grilled chicken samples from fast-food restaurant sandwiches or rotisserie-cooked chicken contained MeIQx and PhIP at combined levels of <2 ng/g. Compared to fast-food meat products from this and previous studies, restaurant products are similar to 10-fold higher in heterocyclic amine content. The amounts of heterocyclic amines measured in these restaurant foods show that samples prepared for laboratory studies are representative of commonly consumed restaurant samples. C1 Univ Calif Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94551 USA. NCI, Environm Epidemiol Branch, NIH, Rockville, MD 20892 USA. USDA ARS, BHNRC, Nutrient Requirements & Funct Lab, Beltsville, MD 20705 USA. RP Knize, MG (reprint author), Univ Calif Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, POB 808,L-452, Livermore, CA 94551 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 19 TC 65 Z9 65 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD NOV PY 1998 VL 46 IS 11 BP 4648 EP 4651 DI 10.1021/jf980639a PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 140CH UT WOS:000077068800034 ER PT J AU Preston, KL Goldberger, BA Cone, EJ AF Preston, KL Goldberger, BA Cone, EJ TI Occurrence of cocaine in urine of substance-abuse treatment patients SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID CLINICAL-TRIALS; HUMANS; BENZOYLECGONINE; PHARMACOKINETICS; DISPOSITION; METABOLITES; ELIMINATION; INTRANASAL; URINALYSIS; KINETICS C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. RP Preston, KL (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 30 TC 11 Z9 12 U1 2 U2 3 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD NOV-DEC PY 1998 VL 22 IS 7 BP 580 EP 586 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 141XX UT WOS:000077170500005 PM 9847008 ER PT J AU Tilly, K Lubke, L Rosa, P AF Tilly, K Lubke, L Rosa, P TI Characterization of circular plasmid dimers in Borrelia burgdorferi SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE AGENT; LINEAR-PLASMID; OSPC GENE; CHROMOSOME; SPIROCHETE; SEQUENCE; GROWTH; DNA; MAP AB We have inactivated the ospC, oppAIV, and guaB genes on the 26-kb circular plasmid of Borrelia burgdorferi (cp26) by allelic exchange. On several occasions following such transformations, the cp26 of transformants had an aberrant mobility through agarose gels. Characterization of these cp26 molecules showed that the plasmid had dimerized. These dimers were quite stable during either selective or nonselective passage. Subsequent transformations with dimer DNA supported the hypothesis that in B. burgdorferi, transforming cp26 DNA most likely does not displace the resident homologous plasmid but rather must recombine in order to donate sequences that it carries. These serendipitous findings provide a mechanism for obtaining heterozygous complemented control strains when mutant phenotypes are characterized. C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Microscopy Branch, Hamilton, MT 59840 USA. RP Tilly, K (reprint author), NIAID, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 35 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 1998 VL 180 IS 21 BP 5676 EP 5681 PG 6 WC Microbiology SC Microbiology GA 134TG UT WOS:000076758900023 PM 9791118 ER PT J AU Graumann, PL Losick, R Strunnikov, AV AF Graumann, PL Losick, R Strunnikov, AV TI Subcellular localization of Bacillus subtilis SMC, a protein involved in chromosome condensation and segregation SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; CELL-DIVISION; SACCHAROMYCES-CEREVISIAE; BIPOLAR LOCALIZATION; FTSZ; FAMILY; PARTITION; NUCLEAR; HOMOLOG; DNA AB We have investigated the subcellular localization of the SMC protein in the gram-positive bacterium Bacillus subtilis. Recent work has shown that SMC is required for chromosome condensation and faithful chromosome segregation during the B. subtilis cell cycle. Using antibodies against SMC and fluorescence microscopy, we have shown that SMC is associated with the chromosome but is also present in discrete foci near the poles of the cell. DNase treatment of permeabilized cells disrupted the association of SMC with the chromosome but not with the polar foci. The use of a truncated sme gene demonstrated that the C-terminal domain of the protein is required for chromosomal binding but not for the formation of polar foci. Regular arrays of SMC-containing foci were still present between nucleoids along the length of aseptate filaments generated by depleting cells of the cell division protein FtsZ, indicating that the formation of polar foci does not require the formation of septal structures. In slowly growing cells, which have only one or two chromosomes, SMC foci were principally observed early in the cell cycle, prior to or coincident with chromosome segregation. Cell cycle-dependent release of stored SMC from polar foci may mediate segregation by condensation of chromosomes. C1 Harvard Univ, Biol Labs, Cambridge, MA 02138 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Harvard Univ, Biol Labs, 16 Divin Ave, Cambridge, MA 02138 USA. EM graumann@fas.harvard.edu OI Strunnikov, Alexander/0000-0002-9058-2256 FU NIGMS NIH HHS [R37 GM018568, R01 GM018568, GM18568] NR 44 TC 63 Z9 64 U1 0 U2 1 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 NOV PY 1998 VL 180 IS 21 BP 5749 EP 5755 PG 7 WC Microbiology SC Microbiology GA 134TG UT WOS:000076758900033 PM 9791128 ER PT J AU Chen, HD Chen, CL Huang, SW Kung, HF Chen, HC AF Chen, HD Chen, CL Huang, SW Kung, HF Chen, HC TI Characterization of latex allergenic components by capillary zone electrophoresis and N-terminal sequence analysis SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE latex; capillary zone electrophoresis; sequence; hevein ID RUBBER ELONGATION-FACTOR; HEVEA-BRASILIENSIS; CONTACT URTICARIA; MAJOR ALLERGEN; IDENTIFICATION; PROTEINS; PROHEVEIN; GLOVES AB In a previous study, protein components purified from latex gloves that elicited allergenic reactions were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and yielded apparent molecular weights of 14, 22, 30, 34, 46, and 58 kD, These allergenic components were isolated for further characterization by capillary zone electrophoresis and N-terminal amino acid sequence analysis. These components all migrated at approximately 25 and 35 min on capillary zone electrophoresis, Diode array spectral analysis detected indistinguishable characteristics between these two protein peaks, In addition, complex formation of these components with patients' immunoglobulin was demonstrated by capillary zone electrophoresis. Analysis of components separated by SDS-PAGE on a polyvinylidene difluoride membrane showed that the first 13 residues were identical to the sequence of hevein, Based on the criteria of charge-to-mass ratio and N-terminal amino acid sequence, our results suggest that these components of latex proteins are similar in the primary structure. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Div Basic Sci, Frederick, MD 21701 USA. Natl Chung Hsing Univ, Dept Vet Med, Taichung 40227, Taiwan. Univ Florida, Coll Vet Med, Dept Large Anim Clin Sci, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Chen, HD (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Div Basic Sci, Bldg 567,Rm 152, Frederick, MD 21701 USA. EM hchen@mail.ncifcrf.gov NR 24 TC 3 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD NOV-DEC PY 1998 VL 5 IS 6 BP 421 EP 427 DI 10.1159/000025356 PG 7 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 147AH UT WOS:000077465700003 PM 9845845 ER PT J AU Alexander, DL Ganem, LG Fernandez-Salguero, P Gonzalez, F Jefcoate, CR AF Alexander, DL Ganem, LG Fernandez-Salguero, P Gonzalez, F Jefcoate, CR TI Aryl-hydrocarbon receptor is an inhibitory regulator of lipid synthesis and of commitment to adipogenesis SO JOURNAL OF CELL SCIENCE LA English DT Article DE CYP1B1; adipogenesis; aryl-hydrocarbon receptor (AhR) ID 3T3-L1 PREADIPOCYTE DIFFERENTIATION; TERMINAL ADIPOCYTE DIFFERENTIATION; PROLIFERATOR-ACTIVATED RECEPTORS; PEROXISOME PROLIFERATOR; AH RECEPTOR; PPAR-GAMMA; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; CYTOCHROME P4501B1; HUMAN FIBROBLASTS AB The aryl-hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates the biological effects of 23,7,8-tetrachlorodibenzo-p-dioxin (TCDD), In mouse embryo fibroblasts, TCDD activates expression of multiple genes, including CYP1B1, the predominant cytochrome P450 expressed in these cells. Here, we analyze constitutive functions of the AhR in primary mouse embryo fibroblasts (MEFs) and spontaneously immortalized MEF cell lines derived from wild-type (WT) C57BL/6 mice and also from congenic mice with a targeted disruption of the AhR gene (AhR(-/-)). After multiple passages, primary MEFs exhibit spontaneous differentiation, growth cessation and senescence. Eventually, colonies of immortalized MEFs arise to provide clonal lines. The senescent phase occurs much earlier for AhR(-/-) MEFs, while immortalization is substantially delayed. Comparison of AhR(-/-) and WT MEFs also indicates that constitutive AhR activity is required for basal expression of CYP1B1 and suppresses lipogenesis in subconfluent cultures. Primary WT and AhR(-/-) MEFs and the corresponding lines undergo adipogenesis when treated at confluence with the appropriate hormonal inducers. Addition of TCDD before or concurrent with hormonal induction suppressed PPAR gamma mRNA and adipogenesis, as measured by lipid accumulation, glycerol phosphate dehydrogenase activity and stearoyl CoA desaturase type 1 mRNA expression. This effect of TCDD treatment was absent in AhR(-/-) MEFs, establishing the role of AhR in hormone-induced adipogenesis, Such hormonal activation of confluent MEFs and preadipocytes results in a limited proliferative expansion followed by irreversible growth arrest, TCDD-treated MEFs undergo the mitotic expansion but fail to exit the cell cycle. In AhR(-/-) MEFs, there is no such effect of TCDD, These findings implicate the AhR as a constitutive inhibitor of triglyceride synthesis, and as an early regulator of adipocyte differentiation. AhR interference with cell-cycle arrest in differentiation may be linked to the increased rate of senescence. C1 Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. Univ Wisconsin, Ctr Environm Toxicol, Madison, WI 53706 USA. NCI, Bethesda, MD 20892 USA. RP Jefcoate, CR (reprint author), Univ Wisconsin, Dept Pharmacol, 1300 Univ Ave, Madison, WI 53706 USA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 FU NCI NIH HHS [CA16265] NR 58 TC 123 Z9 127 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV PY 1998 VL 111 BP 3311 EP 3322 PN 22 PG 12 WC Cell Biology SC Cell Biology GA 148UZ UT WOS:000077552900006 PM 9788873 ER PT J AU Feng, LX Precht, P Balakir, R Horton, WE AF Feng, LX Precht, P Balakir, R Horton, WE TI Evidence of a direct role for Bcl-2 in the regulation of articular chondrocyte apoptosis under the conditions of serum withdrawal and retinoic acid treatment SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE cartilage; aging; osteoarthritis; programmed cell death; cell culture; human ID HYPERTROPHIC CHONDROCYTES; GROWTH-PLATE; CELL-DEATH; MATURATION; EXPRESSION; CARTILAGE; RECEPTORS; PATHWAY AB The regulation of chondrocyte apoptosis in articular cartilage may underlay age-associated changes in cartilage and the development of osteoarthritis. Here we demonstrate the importance of Bcl-2 in regulating articular chondrocyte apoptosis in response to both serum withdrawal and retinoic acid treatment. Both stimuli induced apoptosis of primary human articular chondrocytes and a rat chondrocyte cell line as evidenced by the formation of DNA ladders. Apoptosis was accompanied by decreased expression of aggrecan, a chondrocyte specific matrix protein. The expression of Bcl-2 was downregulated by both agents based on Northern and Western analysis, while the level of Bar expression remained unchanged compared to control cells. The importance of Bcl-2 in regulating chondrocyte apoptosis was confirmed by creating cell lines overexpressing sense and antisense Bcl-2 mRNA. Multiple cell lines expressing antisense Bcl-2 displayed increased apoptosis even in the presence of 10% serum as compared to wild-type cells. in contrast, chondrocytes overexpressing Bcl-2 were resistant to apoptosis induced by both serum withdrawal and retinoic acid treatment. Finally, the expression of Bcl-3 did not block the decreased aggrecan expression in IRC cells treated with retinoic acid. We conclude that Bcl-2 plays an important role in the maintenance of articular chondrocyte survival and that retinoic acid inhibits aggrecan expression independent of the apoptotic process. J. Cell. Biochem. 71 :302-309, 1998. (C) 1998 Wiley-Liss, Inc.dagger C1 NIA, Biol Chem Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Horton, WE (reprint author), NIA, Biol Chem Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 26 TC 39 Z9 42 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD NOV 1 PY 1998 VL 71 IS 2 BP 302 EP 309 DI 10.1002/(SICI)1097-4644(19981101)71:2<302::AID-JCB14>3.3.CO;2-P PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 125UD UT WOS:000076254700014 PM 9779827 ER PT J AU O'Connell, AC Lillibridge, CD Zheng, CY Baum, BJ O'Connell, BC Ambudkar, IS AF O'Connell, AC Lillibridge, CD Zheng, CY Baum, BJ O'Connell, BC Ambudkar, IS TI gamma-irradiation-induced cell cycle arrest and cell death in a human submandibular gland cell line: Effect of E2F1 expression SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HUMAN SALIVARY-GLAND; INTRACELLULAR CALCIUM; PROTEIN-SYNTHESIS; RADIATION; APOPTOSIS; GROWTH; RADIOTHERAPY; ACTIVATION; SECRETION; OVERCOMES AB This study examined the effect of gamma-irradiation (5 and 10 Gy) on the human submandibular cell line (HSG). Radiation treatment (5 Gy and 10 Gy) induced a dose-dependent decrease in cell proliferation, with a G(2)/M arrest of the cell cycle, and an increase in cell death (cells with <2n DNA increased from 7% in control cells to 34% and 40% in 5 and 10 Gy irradiated cells, respectively). [Ca2+](i) measurements demonstrated that the status of internal Ca2+ stores, and muscarinic receptor-mediated Ca2+ mobilization, in irradiated cells was comparable to that in non-irradiated cells. These data suggest that ii irradiated HSG cells maintain normal physiology and 2) internal Ca2+ store depletion does not account for the decreased cell proliferation. To manipulate the radiation-induced cell cycle arrest, we examined the effect of the transcription factor E2F1, which has been shown to induce cell cycle progression in HSG cells (Lillibridge and O'Connell, 1997, J. Cell. Physiol., 172:343-350). The ability of irradiated HSC cells to express and appropriately route proteins was demonstrated by using adenovirus-mediated expression of beta-galactosidase, alpha 1-antitrypsin, and aquaporin-1. Infection of HSC cells with an adenoviral vector encoding E2F1, Either 12 h before or immediately following irradiation, but not post-irradiation, induced maintenance of cells in the S phase of the cell cycle, reduced the number of cells arrested at G(2)/M, and decreased the rare of appearance of cells with <2n DNA. While the mechanism of irradiation-induced cell death has not yet been confirmed, these data suggest that expression of the E2F1 gene product in HSC cells can be a useful strategy to manipulate cell cycle events and reduce the initial loss of cells due to radiation. I. Cell. Physiol. 177:264-273, 1998. (C) 1998 Wiley-Liss, Inc.dagger. C1 NIDR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP O'Connell, AC (reprint author), NIDR, Gene Therapy & Therapeut Branch, NIH, Bldg 10,10 Ctr Dr,MSC 1190, Bethesda, MD 20892 USA. OI O'Connell, Anne C/0000-0002-1495-3983; O'Connell, Brian/0000-0003-4529-7664 NR 32 TC 18 Z9 20 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 1998 VL 177 IS 2 BP 264 EP 273 DI 10.1002/(SICI)1097-4652(199811)177:2<264::AID-JCP8>3.0.CO;2-L PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 126EC UT WOS:000076279100008 PM 9766523 ER PT J AU Endres, CJ Carson, RE AF Endres, CJ Carson, RE TI Assessment of dynamic neurotransmitter changes with bolus or infusion delivery of neuroreceptor ligands SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; INDUCED DOPAMINE RELEASE; C-11 RACLOPRIDE BINDING; ENDOGENOUS DOPAMINE; NONHUMAN-PRIMATES; KINETIC-ANALYSIS; PET; RECEPTOR; MICRODIALYSIS; SPECT AB To describe the effect of endogenous dopamine an [C-11]raclopride binding, we previously extended the conventional receptor ligand model to include dynamic changes in neurotransmitter concentration. Here, we apply the extended model in simulations of neurotransmitter competition studies using either bolus or bolus-plus-infusion (B/I) tracer delivery. The purpose of this study was (1) to develop an interpretation of the measured change in tracer binding in terms of underlying neurotransmitter changes, and (2) to determine tracer characteristics that maximize sensitivity to neurotransmitter release. A wide range of kinetic parameters was tested based on existing reversible positron emission tomography tracers. In simulations of bolus studies, the percent reduction in distribution volume (Delta V) caused by a neurotransmitter pulse was calculated. For B/I simulations, equilibrium was assumed, and the maximum percent reduction in tissue concentration (Delta C) after neurotransmitter release was calculated. Both Delta V and Delta C were strongly correlated with the integral of the neurotransmitter pulse. The values of Delta V and Delta C were highly dependent on the kinetic properties of the tracer in tissue, and Delta V could be characterized in terms of the tissue free tracer concentration. The value of Delta V was typically maximized for binding potentials of similar to 3 to 10, with Delta C being maximized at binding potentials of similar to 1 to 2. Both measures increased with faster tissue-to-blood clearance of tracer and lower nonspecific binding. These simulations provide a guideline for interpreting the results of neurotransmitter release studies and for selecting radiotracers and experimental design. C1 NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Carson, RE (reprint author), NIH, PET Dept, Ctr Clin, Bldg 10,Room 1C-401,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 27 TC 60 Z9 60 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 1998 VL 18 IS 11 BP 1196 EP 1210 PG 15 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 134VP UT WOS:000076764600006 PM 9809509 ER PT J AU Turkheimer, F Sokoloff, L Bertoldo, A Lucignani, G Reivich, M Jaggi, JL Schmidt, K AF Turkheimer, F Sokoloff, L Bertoldo, A Lucignani, G Reivich, M Jaggi, JL Schmidt, K TI Estimation of component and parameter distributions in spectral analysis SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE kinetic modeling; tracer kinetics ID CEREBRAL GLUCOSE-UTILIZATION; PET; TOMOGRAPHY; LECTURE AB A method is presented for estimating the distributions of the components and parameters determined with spectral analysis when it is applied to a single data set. The method uses bootstrap resampling to simulate the effect of noise on the computed spectrum and to correct for possible bias in the estimates. A number of bootstrap procedures are reviewed, and one is selected for application to the kinetic analysis of positron emission tomography dynamic studies. The technique is shown to require minimal assumptions about noise in the measurements, and its small sample properties are established through Monte-Carlo simulations. The advantages and limitations of spectral analysis with bootstrap resampling for deriving inferences for tracer kinetic modeling are illustrated through sample analyses of time-activity curves for [(18)F]fluorodeoxyglucose and [(15)O]-labeled water. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. Univ Milan, Ist Sci H San Raffaele, CNR, INB, Milan, Italy. Univ Penn, Cerebrovasc Res Ctr, Philadelphia, PA 19104 USA. Univ Padua, Dept Elect & Informat, I-35100 Padua, Italy. RP Schmidt, K (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,Room 1A-07,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Lucignani, Giovanni/C-6773-2008; Turkheimer, Federico/B-9485-2012; OI Turkheimer, Federico/0000-0002-3766-3815; Bertoldo, Alessandra/0000-0002-6262-6354 FU Medical Research Council [MC_U120085814] NR 27 TC 27 Z9 27 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 1998 VL 18 IS 11 BP 1211 EP 1222 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 134VP UT WOS:000076764600007 PM 9809510 ER PT J AU Moro, S Li, AH Jacobson, KA AF Moro, S Li, AH Jacobson, KA TI Molecular modeling studies of human A(3) adenosine antagonists: Structural homology and receptor docking SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID PROTEIN-COUPLED RECEPTORS; LIGAND RECOGNITION; DRUG DESIGN; MAST-CELLS; RAT-BRAIN; DERIVATIVES; BINDING; STIMULATION; SELECTIVITY; INHIBITION AB Molecular modeling studies were conducted on various chemically diverse classes of human Ag adenosine receptor antagonists (hA3ANTs), such as adenines, xanthines, triazoloquinazolines, flavonoids,thiazolopyridines, 6-phenyl-1,4-dihydropyridines, and 6-phenylpyridines. Using a combination of ab initio quantum mechanical calculations, electrostatic potential map comparison, and the steric and electrostatic alignment (SEAL) method, a general pharmacophore map for hA3ANTs has been derived. Based on the proposed pharmacophore map, we hypothesize that the receptor binding properties of different A(3) antagonist derivatives are due to recognition at a common region inside the receptor binding site and, consequently, a common electrostatic potential profile. A model of the human Ag receptor, docked with the triazoloquinazoline reference ligand CGS 15953 (9-chloro-2-(2-furyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine), was built and analyzed to help interpret these results. All other antagonist structures were docked inside the receptor according to the results obtained through the steric and electrostatic alignment (SEAL) approach using the structure of CGS 15953 as a template. The receptor model was derived from primary sequence comparison, secondary structure predictions, and three-dimensional homology building, using rhodopsin as a template. An energetically refined 3D structure of the ligand-receptor complex was obtained using our recently introduced cross-docking procedure (J. Med. Chem. 1998, 41, 1456-1466), which simulates the ligand-induced reorganization of the native receptor structure. C1 NIDDK, LBC, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, LBC, Mol Recognit Sect, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 NR 54 TC 48 Z9 50 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD NOV-DEC PY 1998 VL 38 IS 6 BP 1239 EP 1248 DI 10.1021/ci980080e PG 10 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 142EE UT WOS:000077186300037 PM 9845970 ER PT J AU Snitker, S Tataranni, PA Ravussin, E AF Snitker, S Tataranni, PA Ravussin, E TI Respiratory quotient is inversely associated with muscle sympathetic nerve activity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 24-HOUR ENERGY-EXPENDITURE; BODY-WEIGHT GAIN; LEPTIN; OBESE; STIMULATION; METABOLISM; HUMANS; MEN AB The relative amounts of the macronutrients oxidized by an individual are reflected in the respiratory quotient (RQ), which varies inversely with lipid oxidation. A high RQ, indicating a relatively low lipid oxidation, and a low activity of the sympathetic nervous system have both been identified as risk factors for body weight gain. The stimulatory effect of norepinephrine on lipid oxidation suggests that low lipid oxidation may contribute to the relationship between low sympathetic nervous activity and body weight gain. The purpose of the present study was to determine whether low basal muscle sympathetic nerve activity (MSNA), a direct measure of sympathetic nervous outflow, is independently associated with low lipid oxidation. Intraneural recordings of basal MSNA were performed in 39 healthy, nondiabetic males, 19 Caucasians (mean +/-SD, 33 +/- 9 yr,91 +/- 23 kg, and 28 +/- 11% body fat) and 20 Pima Indians (30 +/- 5 yr, 94 +/- 25 kg, and 35 +/- 8% fat) immediately after measurement of 24-h RQ in a respiratory chamber. Basal MSNA, energy balance, and age were independent determinants of 24-h RQ, together explaining 45% of its variability. Accordingly, 24-h RQ adjusted for energy balance and age was inversely related to MSNA (r = -0.41; P = 0.01). Race, percent body fat, and fasting plasma insulin were not independent determinants of 24-h RQ. Although MSNA explained only a limited part of the variability in 24-h RQ, the results support the hypothesis that an effect on lipid oxidation contributes to the demonstrated relationship between low activity of the sympathetic nervous system and body weight gain. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Snitker, S (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St,Room 541, Phoenix, AZ 85016 USA. EM ssnitker@phx.niddk.nih.gov NR 16 TC 44 Z9 45 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1998 VL 83 IS 11 BP 3977 EP 3979 DI 10.1210/jc.83.11.3977 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 137VY UT WOS:000076938500036 PM 9814478 ER PT J AU Snitker, S Hellmer, J Boschmann, M Odeleye, OE Monroe, MB Young, JB Ravussin, E AF Snitker, S Hellmer, J Boschmann, M Odeleye, OE Monroe, MB Young, JB Ravussin, E TI In situ lipolytic responses to isoproterenol and physiological stressors are similar in obese Pima Indians and Caucasians SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SUBCUTANEOUS ADIPOSE-TISSUE; MICRODIALYSIS ETHANOL TECHNIQUE; BETA-ADRENERGIC STIMULATION; SKELETAL-MUSCLE METABOLISM; FAT-CELLS; BLOOD-FLOW; CATECHOLAMINE RESISTANCE; ENERGY-EXPENDITURE; LIPOLYSIS; OXIDATION AB Evidence suggests that impaired lipolysis may contribute to fat accumulation. To test whether the lipolytic response to adrenergic stimulation is lower in Pima Indians, a population prone to obesity and type 2 diabetes mellitus, than in Caucasians, 48 healthy, nondiabetic subjects were studied: 27 Pima Indians (12 males and 15 females, 30 +/- 7 yr, 85 +/- 18 kg, 36 +/- 10% body fat; mean If: so) and 21 Caucasians (11 males and 10 females, 34 +/- 7 yr, 105 +/- 26 kg, 39 +/- 11% body fat). Lipolysis in the abdominal sc adipose tissue was assessed in situ by glycerol concentration in microdialysis samples at baseline and during local infusion of the nonselective beta-adrenergic agonist isoproterenol (10(-6) mol/L), mental stress, and submaximal exercise. The baseline dialysate glycerol concentrations were similar in Pima Indians and Caucasians. Lipolytic response (relative increment in dialysate glycerol concentration, percentage above the baseline) was similar in Pima Indians and Caucasians in response to local isoproterenol infusion (77 +/- 36% and 76 +/- 40%) and exercise (38 +/- 38% and 41 +/- 41%). During mental stress, the dialysate concentration did not change significantly from baseline in either group. Changes in local blood flow, determined by ethanol dilution, did not differ between the hive groups. In conclusion, the high propensity for obesity in Pima Indians does not seem to be due to an impaired lipolytic response to stimuli. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Rockefeller Univ, Human Behav & Metab Lab, New York, NY 10021 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. RP Snitker, S (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St,Room 5-41, Phoenix, AZ 85016 USA. EM ssnitker@phx.niddk.nih.gov NR 38 TC 2 Z9 2 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1998 VL 83 IS 11 BP 4054 EP 4058 DI 10.1210/jc.83.11.4054 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 137VY UT WOS:000076938500049 PM 9814491 ER PT J AU Licinio, J Negrao, AB Mantzoros, C Kaklamani, V Wong, ML Bongiorno, PB Negro, PP Mulla, A Veldhuis, JD Cearnal, L Flier, JS Gold, PW AF Licinio, J Negrao, AB Mantzoros, C Kaklamani, V Wong, ML Bongiorno, PB Negro, PP Mulla, A Veldhuis, JD Cearnal, L Flier, JS Gold, PW TI Sex differences in circulating human leptin pulse amplitude: Clinical implications SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS INDEX; PLASMA LEPTIN; SERUM LEPTIN; LUTEINIZING-HORMONE; MOUSE HYPOTHALAMUS; ENERGY-EXPENDITURE; GENE-EXPRESSION; NORMAL-CHILDREN; FAT-METABOLISM; DIURNAL RHYTHM AB Leptin, a product of fat cells, provides a signal of nutritional status to the central nervous system. Leptin concentrations have ultradian and diurnal fluctuations. We conducted this study to assess sex differences in the levels of organization of frequently sampled leptin concentrations in healthy, normal weight women and men. Leptin levels were sampled every 7 min for 24 h in 14 healthy, normal weight individuals (6 women and 8 men). The 14 leptin time series containing a total of 2898 leptin measurements were assessed by 1) algorithms that characterize statistically significant pulsatility, 2) Spectral (Fourier) analysis, 3) analysis of time intervals and variability, and 4) approximate entropy. We found that frequently sampled plasma leptin concentrations have a 24-h profile that is numerically more than twice as high in women as in men, and leptin pulse amplitude is likewise more than twice as high in women. However, healthy men and women have nearly identical concentration-independent and frequency-related 24-h and ultradian patterns. Leptin concentrations have nonrandom fluctuations over 24 h, independent of their absolute value and underlying 24-h periodicity, that are similar in men and women. Ultradian periodicities detected by Fourier time series have similar values in men and women. The strongest distinction between the sexes in the level of organization of leptin concentration is not at the level of pulse organization or oscillation frequency, but, rather, in the mass or amount of leptin released (or removed) per unit time, indicating that women might be more resistant to the effects of leptin than men. Because leptin is clinically relevant to the regulation of body weight, future studies should examine whether the relative leptin resistance exhibited by women might contribute to their increased susceptibility to disorders whose pathophysiology involves dysregulation of food intake and body weight. C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Med, Div Endocrinol,Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Virginia, Hlth Sci Ctr, Dept Internal Med, Natl Sci Fdn,Ctr Biol Timing, Charlottesville, VA 22908 USA. RP Licinio, J (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, Bldg 10-2D46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. EM licinio@nih.gov RI Wong, Ma-Li/D-7903-2011; Negrao, Andre Brooking/C-9526-2014; OI Negrao, Andre Brooking/0000-0002-8133-6723; Mulla, Abeda/0000-0002-0364-7972; Licinio, Julio/0000-0001-6905-5884 FU PHS HHS [1R01-147991] NR 59 TC 123 Z9 125 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1998 VL 83 IS 11 BP 4140 EP 4147 DI 10.1210/jc.83.11.4140 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 137VY UT WOS:000076938500062 PM 9814504 ER PT J AU Alizadeh, A Eisen, M Botstein, D Brown, PO Staudt, LM AF Alizadeh, A Eisen, M Botstein, D Brown, PO Staudt, LM TI Probing lymphocyte biology by genomic-scale gene expression analysis SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE microarray; gene expression; genome; lymphocyte activation; cytokines ID ANTIGEN RECEPTOR; DNA MICROARRAY; B-LYMPHOCYTES; HYBRIDIZATION; ARRAYS; OLIGONUCLEOTIDES; SEQUENCES; PATTERNS; PROTEIN; CANCER AB The identity and abundance of mRNA species within a cell dictate, to a large extent, the biological potential of that cell. Although posttranscriptional mechanisms modify protein expression in critical ways, cellular differentiation requires key changes in gene transcription, as evidenced by the potent phenotypes that result from disruption of transcription factor genes in mice. It is now possible to assess the mRNA profile of a cell globally using recently developed genomics techniques. This review focuses on the potential of cDNA microarrays to define gene expression in lymphoid cells, a field which is in its infancy. Examples of cellular activation genes and cytokine inducible genes discovered using this technology are presented but these represent only a taste of the fruit that this new technology will ultimately bear. Gene expression profiles should provide essential new insights into lymphocyte differentiation and activation, the pathogenesis of immune disorders, and the molecular abnormalities in lymphoid malignancies. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA. RP Brown, PO (reprint author), NCI, Metab Branch, NIH, Bldg 10,Room 4N114,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Eisen, Michael/0000-0002-7528-738X; Alizadeh, Arash Ash/0000-0002-5153-5625 NR 31 TC 89 Z9 92 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 1998 VL 18 IS 6 BP 373 EP 379 DI 10.1023/A:1023293621057 PG 7 WC Immunology SC Immunology GA 146NZ UT WOS:000077438400001 PM 9857281 ER PT J AU Patel, V Senderowicz, AM Pinto, D Igishi, T Raffeld, M Quintanilla-Martinez, L Ensley, JF Sausville, EA Gutkind, JS AF Patel, V Senderowicz, AM Pinto, D Igishi, T Raffeld, M Quintanilla-Martinez, L Ensley, JF Sausville, EA Gutkind, JS TI Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE antineoplastic agents; cell cycle; cell death; oral xenografts; oral cancer ID ORAL-CANCER; FLAVONE; PHOSPHORYLATION; OVEREXPRESSION; IRRADIATION; EXPRESSION; L86-8275; ARREST AB Flavopiridol (HMR 1275) has been identified recently as a novel antineoplastic agent in the primary screen conducted by the Developmental Therapeutics Program, National Cancer Institute, Flavopiridol inhibits most cyclin-dependent kinases (cdks) and displays unique anticancer properties. Here, we investigated whether this compound was effective against head and neck squamous cell carcinomas (HNSCC). Exposure of HNSCC cells to flavopiridol diminished cdc2 and cdk2 activity and potently inhibited cell proliferation (IC50 43-83 nM), which was concomitant with the appearance of cells with a sub-G(1) DNA content. Moreover, DNA fragmentation and TUNEL (terminal deoxynucleotidyl transferase-mediated nick end labeling) reaction confirmed that flavopiridol induces apoptosis in all cell lines, even on certain HNSCC cells that are insensitive to apoptosis to DNA-damaging agents (gamma-irradiation and bleomycin). A tumorigenic HNSCC cell line was used to assess the effect of flavopiridol in vivo. Treatment (5 mg/kg per day, intraperitoneally) for 5 d led to the appearance of apoptotic cells in the tumor xenografts and caused a 60-70% reduction in tumor size, which was sustained over a period of 10 wk, Flavopiridol treatment also resulted in a remarkable reduction of cyclin D1 expression in HNSCC cells and turner xenografts, Our data indicate that flavopiridol exerts antitumor activity in HNSCC, and thus it can be considered a suitable candidate drug for testing in the treatment of refractory carcinomas of the head and neck. C1 NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diagnosis, Dev Therapeut Program, Bethesda, MD 20892 USA. Wayne State Univ, Div Hematol Oncol, Detroit, MI 48201 USA. RP Gutkind, JS (reprint author), NIDR, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. EM gutkind@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Pinto, Decio/B-6041-2011 OI Pinto, Decio/0000-0001-6198-5155 NR 40 TC 190 Z9 198 U1 2 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV 1 PY 1998 VL 102 IS 9 BP 1674 EP 1681 DI 10.1172/JCI3661 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 137BW UT WOS:000076895100005 PM 9802881 ER PT J AU Murphy, WJ Welniak, LA Taub, DD Wiltrout, RH Taylor, PA Vallera, DA Kopf, M Young, H Longo, DL Blazar, BR AF Murphy, WJ Welniak, LA Taub, DD Wiltrout, RH Taylor, PA Vallera, DA Kopf, M Young, H Longo, DL Blazar, BR TI Differential effects of the absence of interferon-gamma and IL-4 in acute graft-versus-host disease after allogeneic bone marrow transplantation in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE graft-versus-host disease; bone marrow transplant; IFN; IL-4; cytokine knockout ID T-CELLS; TH1/TH2 PARADIGM; IFN-GAMMA; INTERLEUKIN-10; PROTECTION; INDUCTION; CYTOKINES AB Graft-versus-host disease (GVHD), in which immunocompetent donor cells attack the host, remains a major cause of morbidity after allogeneic bone marrow transplantation (BMT), To understand the role of cytokines in the pathobiology of GVHD, we used cytokine knockout (KO) mice as a source of donor T cells. Two different MHC-disparate strain combinations were examined: BALB/c (H2(d)) donors into lethally irradiated CS7BL/6 (H2(b)) recipients or C57BL/6 (H2(b)) donors into B10.BR (H2(k)) recipients. Donor cells were hom mice in which either the interferon-gamma (IFN-gamma) or the IL-4 gene was selectively disrupted to understand the role of these cytokines in acute GVHD. In both strain combinations the same pattern was noted with regard to GVHD onset and morbidity. All mice exhibited the classic signs of acute GVHD: weight loss with skin, gut, and liver pathology resulting in morbidity and mortality. Surprisingly, donor cells obtained from mice lacking IFN-gamma gave rise to accelerated morbidity from GVHD when compared with cells from wild-type control donors. Similar results were obtained using normal donors when neutralizing antibodies to TFN-gamma were administered immediately after the BMT. These results suggest that IFN-gamma plays a role in protection from acute GVHD, In marked contrast, cells obtained from IL-4 KO mice resulted in protection from GVHD compared with control donors. Splenocytes from IFN KO mice stimulated with a mitogen proliferated to a significantly greater extent and produced more IL-2 compared with splenocytes obtained from IL-4 KO or control mice. Additionally, there was increased IL-2 production in the spleens of mice undergoing GVHD using IFN-gamma KO donors. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Div Basic Sci, Frederick, MD 21702 USA. Basel Inst Immunol, CH-4005 Basel, Switzerland. NIA, NIH, Baltimore, MD 21224 USA. Univ Minnesota, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Therapeut Radiol, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. RP Murphy, WJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Bldg 567,Room 210, Frederick, MD 21702 USA. EM murphyw@mail.nciferf.gov FU NCI NIH HHS [N01-CO-5600]; NHLBI NIH HHS [R01 HL56067]; NIAID NIH HHS [R01 AI34495-05] NR 32 TC 166 Z9 170 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV 1 PY 1998 VL 102 IS 9 BP 1742 EP 1748 DI 10.1172/JCI3906 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 137BW UT WOS:000076895100012 PM 9802888 ER PT J AU Madico, G Quinn, TC Rompalo, A McKee, KT Gaydos, CA AF Madico, G Quinn, TC Rompalo, A McKee, KT Gaydos, CA TI Diagnosis of Trichomonas vaginalis infection by PCR using vaginal swab samples SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; SEXUALLY-TRANSMITTED DISEASES; CHLAMYDIA-TRACHOMATIS; PREGNANT-WOMEN; RISK-FACTORS; WET-MOUNT; SPECIMENS; PREVALENCE; VAGINITIS; CULTURE AB Trichomonas vaginalis infection is the most prevalent nonviral sexually transmitted disease (STD) in the world. A PCR test using vaginal swab samples for the detection of T. vaginalis was developed to add T, vaginalis infection to the growing list of STDs that can be detected by DNA amplification techniques. A primer set, BTUB 9/2, was designed to target a well-conserved region in the beta-tubulin genes of T, vaginalis, All strains (15 of 15) of T. vaginalis tested were successfully detected by PCR giving a single predicted product of 112 bp in gel electrophoresis. No such targeted product was amplified with DNA from Trichomonas tenax, Trichomonas gallinae, Chlamydia trachomatis, Neisseria gonorrhoeae, Giardia lamblia, Chilomastix sulcatus, Dientamoeba fragilis, and Entamoeba histolytica. An optimal analytical sensitivity of one T. vaginalis organism per PCR was achieved. Culture, performed with the Inpouch TV culture system, was examined daily with a light microscope to identify T. vaginalis, Twenty-three of 350 (6.6%) vaginal swab samples from women attending an army medical clinic were culture positive for T. vaginalis, Of these culture positive specimens, PCR detected 22 of 23 (96%) with primer set BTUB 9/2, and wet preparation detected only 12 of 23 (52%). Seventeen specimens were BTUB 9/2-PCR positive and culture negative. Ten of these discordant specimens were determined to be as true positive by PCR using primer sets TVA 5-1/6 and/or AP65 A/B, which target different regions in the T. vaginalis genome, and seven were determined to be false positive. The sensitivity of BTUB 9/2-PCR was 97% and the specificity was 98%, The sensitivities of culture and wet preparation were 70 and 36%, respectively. The diagnosis of T. vaginalis infection by PCR is a sensitive and specific method that could be incorporated into a joint strategy for the screening of multiple STDs by using molecular amplification methods. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Div Infect Dis, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. Univ Peruana Cayetano Heredia, Lima, Peru. NIAID, NIH, Bethesda, MD 20892 USA. Womack Army Med Ctr, Ft Bragg, NC USA. RP Gaydos, CA (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Div Infect Dis, 1154 Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM cgaydos@welchlink.welch.jhu.edu RI Gaydos, Charlotte/E-9937-2010; Quinn, Thomas/A-2494-2010 NR 28 TC 126 Z9 143 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 1998 VL 36 IS 11 BP 3205 EP 3210 PG 6 WC Microbiology SC Microbiology GA 129YG UT WOS:000076491200018 PM 9774566 ER PT J AU Peyton, CL Schiffman, M Lorincz, AT Hunt, WC Mielzynska, I Bratti, C Eaton, S Hildesheim, A Morera, LA Rodriguez, AC Herrero, R Sherman, ME Wheeler, CM AF Peyton, CL Schiffman, M Lorincz, AT Hunt, WC Mielzynska, I Bratti, C Eaton, S Hildesheim, A Morera, LA Rodriguez, AC Herrero, R Sherman, ME Wheeler, CM TI Comparison of PCR- and hybrid capture-based human papillomavirus detection systems using multiple cervical specimen collection strategies SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; DNA DETECTION; INFECTION; WOMEN; CANCER; SMEARS; IDENTIFICATION; RISK AB This study compared the performances of three human papillomavirus (HPV) detection tests with specimens collected by three alternative procedures. The HPV tests included the Hybrid Capture Tube test (HCT), the microplate-based Hybrid Capture II test (HC II), and the MY0Q-MY11 L1 consensus primer PCR-based assay. Initial cervical specimens were collected from study subjects with a broom device, and after Papanicolaou smears were made, residual specimens were placed into PreservCyt (PC), a liquid cytology medium. A second specimen was collected from each subject and placed into Digene Specimen Transport Medium (STM). The device for collection of the second specimen alternated with consecutive subjects between a conical cytology brush and a Dacron swab, At the 1.0-pg/ml cutoff, the results of the HC II agreed well with those of the PCR. Specifically, when PCR data were restricted to the types found by the HC II (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), there was greater than 90% agreement between the HC II and PCR results with both STM and PC. At a lower cutoff (0.2 pg/ml), HC II-positive results increased further, especially when the test was applied to the PC specimens. However, false-positive HC II results were more often observed at the 0.2-pg/ml cutoff. HC II yielded the highest HPV positivity with specimens placed into PC, followed by specimens collected with a conical brash and placed into STM and, last, by those collected with a Dacron swab and placed into STM. Our results demonstrate the utility of both the STM and PC specimen collection methods and show good agreement between the HC II and PCR. C1 Univ New Mexico, Sch Med, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. Digene Corp, Silver Spring, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Caja Costarricense Seguro Social, San Jose, Costa Rica. RP Wheeler, CM (reprint author), Univ New Mexico, Sch Med, Dept Mol Genet & Microbiol, 915 Camino Salud NE, Albuquerque, NM 87131 USA. FU NCI NIH HHS [RFP-NCI-CA-CN-55044-07] NR 35 TC 144 Z9 153 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 1998 VL 36 IS 11 BP 3248 EP 3254 PG 7 WC Microbiology SC Microbiology GA 129YG UT WOS:000076491200026 PM 9774574 ER PT J AU Gerloff, C Uenishi, N Hallett, M AF Gerloff, C Uenishi, N Hallett, M TI Cortical activation during fast repetitive finger movements in humans: Dipole sources of steady-state movement-related cortical potentials SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE sensorimotor cortex; premotor cortex; motor control; dipole analysis; Bereitschaftspotential; EEG ID SUPPLEMENTARY MOTOR AREA; POSITRON EMISSION TOMOGRAPHY; PARKINSONS-DISEASE; NEURONAL-ACTIVITY; PREMOTOR CORTEX; SEQUENTIAL MOVEMENTS; VOLUNTARY MOVEMENTS; CEREBRAL-CORTEX; MONKEY; GENERATION AB Fast repetitive finger movements are associated with characteristic EEG patterns described in humans as steady-state movement-related cortical potentials (ssMRCPs). The objective of the present study was to determine the electrical generators of ssMRCPs (movement rate, 2 Hz) by dipole modelling. The generators for the initial ssMRCP phase (peak similar to 60 msec before EMG onset) were located in the central region bilaterally, with largely radial orientation, consistent with activation of the crown of the precentral gyrus. The generator of the next phase (peak similar to 10 msec after EMG onset) was located in the contralateral central region with tangential posterior orientation, consistent with activation of the anterior wall of the central sulcus. The postmovement phase (peak similar to 95 msec after EMG onset) was explained by another source in the contralateral central region with tangential anterior orientation, consistent with activation of the posterior wall of the central sulcus. This pattern probably corresponds to a sequence of activation of the bilateral dorsal premotor cortex, contralateral primary motor, and primary somatosensory cortex that takes place within similar to 200 msec around EMG onset. Steady-slate movement-related cortical potentials in combination with dipole modelling provide a novel, noninvasive approach to assessing changes of human cortical premotor, motor, and somatosensory activation in the millisecond range. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Gerloff, C (reprint author), Univ Tubingen, Dept Neurol, Cort Physiol Res Grp, Sch Med, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. NR 44 TC 34 Z9 34 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD NOV PY 1998 VL 15 IS 6 BP 502 EP 513 DI 10.1097/00004691-199811000-00009 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 176TU UT WOS:000079168500009 PM 9881923 ER PT J AU Friedman, HS Kokkinakis, DM Pluda, J Friedman, AH Cokgor, I Haglund, MM Ashley, DM Rich, J Dolan, ME Pegg, AE Moschel, RC McLendon, RE Kerby, T Herndon, JE Bigner, DD Schold, SC AF Friedman, HS Kokkinakis, DM Pluda, J Friedman, AH Cokgor, I Haglund, MM Ashley, DM Rich, J Dolan, ME Pegg, AE Moschel, RC McLendon, RE Kerby, T Herndon, JE Bigner, DD Schold, SC TI Phase I trial of O-6-benzylguanine for patients undergoing surgery for malignant glioma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY; HUMAN-TUMOR-CELLS; ALKYLATING-AGENTS; CYTO-TOXICITY; BRAIN-TUMORS; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; HELA-CELLS; DNA; SENSITIVITY; XENOGRAFTS AB Purpose: The major mechanism of resistance to alkylnitrosourea therapy is the DNA repair protein O-6-alkylguanine-DNA alkyltransferase (AGT), which removes chlorethylation or methylation damage from the O-6-position of guanine. O-6-benzylguanine (O-6-BG) is an AGT substrate that inhibits AGT by suicide inactivation. We conducted a phase I trial to define the presurgical dose required for depletion of tumor AGT activity in patients with malignant glioma. Material and Methods: patients were to be treated 18 hours before craniotomy with intravenous doses that ranged between 40 and 100 mg/m(2) given over 1 hour. Resected tumor was snap-frozen in liquid nitrogen and AGT activity analyzed by high-pressure liquid chromatography (HPLC). Up to 13 patients were treated at a specific dose of O-6-BG, with a target end point of greater than or equal to 11 of 13 patients with undetectable tumor AGT levels (< 10 fmol/mg protein). Results: Thirty patients with malignant gliomas were enrolled; with 11 of 11 patients treated at 100 mg/m(2) O-6-BG demonstrating tumor AGT levels less than 10 fmol/mg protein. No toxicity was noted in any patient treated. Conclusion: These results indicate that 100 mg/m(2) of O-6-BG can maintain tumor AGT levels less than 10 fmol/mg protein for at least 18 hours after treatment, a time interval in which bis(2-chloroethyl)nitrosourea (BCNU)-induced chloroethyl adducts are fully converted into interstrand cross-links. A 100-mg/m(2) dose of O-6-BG will be used in combination with BCNU in another phase I trial designed to determine the maximal-tolerated dose of BCNU. (C) 1998 by American Society of Clinical Oncology. C1 Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75235 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Penn State Univ, Milton S Hershey Med Ctr, Sch Med, Dept Cellular & Mol Physiol & Pharmacol, Hershey, PA 17033 USA. NCI, Frederick Canc Res & Dev Ctr, Chem Carcinogenesis Lab, Adv Biosci Labs, Frederick, MD USA. NCI, Invest Drug Branch, NIH, Bethesda, MD 20892 USA. RP Friedman, HS (reprint author), Duke Univ, Med Ctr, Dept Pediat, DUMC 3624, Durham, NC 27710 USA. FU NCI NIH HHS [CA57725]; NINDS NIH HHS [NS20023, NS30245] NR 41 TC 170 Z9 175 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1998 VL 16 IS 11 BP 3570 EP 3575 PG 6 WC Oncology SC Oncology GA 134KK UT WOS:000076742000015 PM 9817277 ER PT J AU Longo, DL AF Longo, DL TI Interferon toxicity worse in retrospect; Impact on Q-TWiST? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID MULTIPLE-MYELOMA; CHEMOTHERAPY; ALFA C1 NIA, Baltimore, MD 21224 USA. RP Longo, DL (reprint author), NIA, Baltimore, MD 21224 USA. NR 8 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1998 VL 16 IS 11 BP 3716 EP 3716 PG 1 WC Oncology SC Oncology GA 134KK UT WOS:000076742000036 PM 9817297 ER PT J AU Zee, B James, K Pater, J AF Zee, B James, K Pater, J TI Can the Q-TWiST method provide information on patients' preferences without collecting preference data from the patients? In reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 NCI, Clin Trials Grp, Kingston, ON, Canada. RP Zee, B (reprint author), NCI, Clin Trials Grp, Kingston, ON, Canada. NR 4 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1998 VL 16 IS 11 BP 3718 EP 3718 PG 1 WC Oncology SC Oncology GA 134KK UT WOS:000076742000038 ER PT J AU Ludlow, CL Cikoja, DB AF Ludlow, CL Cikoja, DB TI Is there a self-monitoring speech perception system? SO JOURNAL OF COMMUNICATION DISORDERS LA English DT Article ID AUDITORY-FEEDBACK; VOICE PITCH; RESPONSES; PERTURBATIONS; LIP C1 Natl Inst Deafness & Other Commun Disorders, Voice & Speech Sect, NIH, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), Natl Inst Deafness & Other Commun Disorders, Voice & Speech Sect, NIH, Bldg 10 Room 5D38, Bethesda, MD 20892 USA. EM ludlowc@nidcd.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 NR 21 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0021-9924 J9 J COMMUN DISORD JI J. Commun. Disord. PD NOV-DEC PY 1998 VL 31 IS 6 BP 505 EP 510 DI 10.1016/S0021-9924(98)00022-7 PG 6 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 139ZK UT WOS:000077061000006 PM 9836139 ER PT J AU Kultz, D Burg, M AF Kultz, D Burg, M TI Evolution of osmotic stress signaling via map kinase cascades SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Review DE MAP kinase; osmotic stress; signal transduction; homeostasis; programmed cell death; molecular evolution ID ACTIVATED PROTEIN-KINASE; N-TERMINAL KINASE; TRANSDUCTION PATHWAY; MAMMALIAN-CELLS; CHLORIDE CELLS; YEAST; TRANSCRIPTION; GENES; REGULATOR; TARGET AB Cells respond to changes in osmotic pressure with compensatory molecular adaptations that allow them to reestablish homeostasis of osmotically disturbed aspects of cell structure and function, In addition, some cell types respond to osmotic stress by changing their phenotype or, if their tolerance threshold is exceeded, by initiating programmed cell death, To understand how cells achieve these different types of adaptive response to osmotic stress, it is necessary to identify the key elements of osmosensory signal transduction and to analyze the complex networks that process osmotic stimuli imposed upon cells by their environment. This review highlights mitogen-activated protein kinase (MAPK) cascades as important intracellular signal-transduction pathways activated in response to changes in osmolality, A unifying theme of osmotic stress signaling via MAPKs seems to be regulation of the cell cycle as part of the cellular stress response. This very important physiological capacity may have been conserved throughout evolution as a major function of MAPKs from many different subfamilies. The evidence for this conjecture is discussed, and our current knowledge about osmotic stress signaling pathways in yeast, animals and plants is briefly reviewed. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Kultz, D (reprint author), Univ Florida, Whitney Lab, 9505 Ocean Shore Blvd, St Augustine, FL 32086 USA. EM dkkw@whitney.ufl.edu NR 37 TC 114 Z9 119 U1 1 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD NOV PY 1998 VL 201 IS 22 BP 3015 EP 3021 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 148QH UT WOS:000077543000001 PM 9787121 ER PT J AU Lebowitz, BD AF Lebowitz, BD TI Priorities for agenda building: Mental health and primary care SO JOURNAL OF FAMILY PRACTICE LA English DT Editorial Material C1 NIMH, Rockville, MD 20857 USA. RP Lebowitz, BD (reprint author), NIMH, 5600 Fishers Lane,Room 10-75, Rockville, MD 20857 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD NOV PY 1998 VL 47 IS 5 BP 341 EP 341 PG 1 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 141DF UT WOS:000077126800002 PM 9834767 ER PT J AU Blank, PS Cho, MS Vogel, SS Kaplan, D Kang, A Malley, J Zimmerberg, J AF Blank, PS Cho, MS Vogel, SS Kaplan, D Kang, A Malley, J Zimmerberg, J TI Submaximal responses in calcium-triggered exocytosis are explained by differences in the calcium sensitivity of individual secretory vesicles SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE cytoplasmic vesicles; fertilization; membrane fusion; sea urchins; secretion ID SEA-URCHIN EGGS; SQUID GIANT SYNAPSE; ADRENAL-MEDULLARY CELLS; TRANSMITTER RELEASE; CORTICAL GRANULES; RAPID-FLOW; FUSION; MICROSCOPY; MODEL; DEPENDENCE AB A graded response to calcium is the defining feature of calcium-regulated exocytosis. That is, there exist calcium concentrations that elicit submaximal exocytotic responses in which only a fraction of the available population of secretory vesicles fuse. The role of calcium-dependent inactivation in defining the calcium sensitivity of sea urchin egg secretory vesicle exocytosis in vitro was examined. The cessation of fusion in the continued presence of calcium was not due to calcium-dependent inactivation. Rather, the calcium sensitivity of individual vesicles within a population of exocytotic vesicles is heterogeneous. Any specific calcium concentration above threshold triggered subpopulations of vesicles to fuse and the size of the subpopulations was dependent upon the magnitude of the calcium stimulus. The existence of multiple, stable subpopulations of vesicles is consistent with a fusion process that requires the action of an even greater number of calcium ions than the numbers suggested by models based on the assumption of a homogeneous vesicle population. C1 NICHD, LCMB, NIH, Bethesda, MD 20892 USA. NIH, Computat Biol & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Blank, PS (reprint author), NICHD, LCMB, NIH, Bldg 10,Rm 10D14,10 Ctr Dr MSC 1855, Bethesda, MD 20892 USA. EM psblank@helix.nih.gov RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 NR 34 TC 40 Z9 41 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD NOV PY 1998 VL 112 IS 5 BP 559 EP 567 DI 10.1085/jgp.112.5.559 PG 9 WC Physiology SC Physiology GA 136KL UT WOS:000076857900005 PM 9806965 ER PT J AU Blank, PS Vogel, SS Cho, MS Kaplan, D Bhuva, D Malley, J Zimmerberg, J AF Blank, PS Vogel, SS Cho, MS Kaplan, D Bhuva, D Malley, J Zimmerberg, J TI The calcium sensitivity of individual secretory vesicles is invariant with the rate of calcium delivery SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE cytoplasmic vesicles; fertilization; membrane fusion; sea urchins; secretion ID RECEPTOR MODIFICATION; ADAPTATION; EXOCYTOSIS; MECHANISM AB Differences in the calcium sensitivity of individual secretory vesicles can explain a defining feature of calcium-regulated exocytosis, a graded response to calcium The role of the time dependence of calcium delivery in defining the observed differences in the calcium sensitivity of sea urchin egg secretory vesicles in vitro was examined. The calcium sensitivity of individual secretory vesicles (i.e., the distribution of calcium thresholds) is invariant over a range of calcium delivery rates from faster than micromolar per millisecond to slower than micromolar per second. Any specific calcium concentration above tl:threshold triggers subpopulations of vesicles to fuse, and the size of these subpopulations is independent of the time course required to reach that calcium concentration. All evidence supports the hypothesis that the magnitude of the free calcium is the single controlling variable that determines the fraction of vesicles that fuse, and that this fraction is established before the application of calcium. Submaximal responses to calcium cannot be attributed to alterations in the calcium sensitivity of individual secretory vesicles arising from the temporal properties of the calcium delivery. Models that attempt to explain the cessation of fusion using changes in the distribution of calcium thresholds arising from the rate of calcium delivery and/or adaptation are not applicable to this system, and thus cannot be general. C1 NICHD, LCMB, NIH, Bethesda, MD 20892 USA. NIH, Computat Biol & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Blank, PS (reprint author), NICHD, LCMB, NIH, Bldg 10,Rm 10D14,10 Ctr Dr MSC 1855, Bethesda, MD 20892 USA. RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 NR 9 TC 12 Z9 12 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD NOV PY 1998 VL 112 IS 5 BP 569 EP 576 DI 10.1085/jgp.112.5.569 PG 8 WC Physiology SC Physiology GA 136KL UT WOS:000076857900006 PM 9806966 ER PT J AU Davis, RE Mysore, V Browning, JC Hsieh, JC Lu, QAT Katsikis, PD AF Davis, RE Mysore, V Browning, JC Hsieh, JC Lu, QAT Katsikis, PD TI In situ staining for poly(ADP-ribose) polymerase activity using an NAD analogue SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE poly(ADP-ribose) polymerase; ADP-ribosyl transferase; EC 2.4.2.30; ethenoadenine; ethenoadenosine; 1,N6-etheno-NAD ID PLASMA-MEMBRANE; MONOCLONAL-ANTIBODIES; ADP-RIBOSYLATION; VINYL-CHLORIDE; DNA-DAMAGE; IN-VIVO; CELLS; PROTEINS; FLUORESCENCE; MACROPHAGES AB Poly(ADP-ribose) polymerase (PARP) is a highly abundant nuclear enzyme which metabolizes NAD, in response to DNA strand breakage, to produce chains of poly(ADP-ribose) attached to nuclear proteins. PARP activation has been implicated in ischemia/reperfusion injury, but its biological significance is not fully understood. We have modified an existing in situ method for detection of PARP activity by using an NAD analogue in which adenine is modified by an "etheno" (vinyl) bridge. Etheno-NAD serves as a PARP substrate in an initial enzymatic reaction; a specific antibody to ethenoadenosine is then used in an immunohistochemical reaction to detect the production of modified poly(ADP-ribose). The method produces strong and specific labeling of nuclei in which PARP has been activated, i.e., those in which DNA strand breaks have been produced, and the results can be analyzed by microscopy, flow cytometry, or colorimetry. The method is applicable to cultured cells in several formats and to frozen tissue sections. The particular characteristics of the new method may assist in future in situ studies of PARP activation. C1 Stanford Univ, Med Ctr, Dept Pathol, Palo Alto, CA 94304 USA. Stanford Univ, Med Ctr, Dept Genet, Palo Alto, CA 94304 USA. RP Davis, RE (reprint author), NCI, Metab Branch, NIH, Bldg 10,Rm 5A02,10 Ctr Dr,MSC 1374, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 42509] NR 60 TC 10 Z9 11 U1 1 U2 2 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD NOV PY 1998 VL 46 IS 11 BP 1279 EP 1289 PG 11 WC Cell Biology SC Cell Biology GA 130KF UT WOS:000076518700008 PM 9774627 ER PT J AU Wang, JM Deng, XY Gong, WH Su, SB AF Wang, JM Deng, XY Gong, WH Su, SB TI Chemokines and their role in tumor growth and metastasis SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Review DE leukocyte; chemokines; growth and metastasis of tumors ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTERFERON-INDUCIBLE PROTEIN-10; NECROSIS-FACTOR-ALPHA; HUMAN-MELANOMA CELLS; PLATELET FACTOR-IV; IN-VIVO; STIMULATORY ACTIVITY; ANTITUMOR IMMUNITY; MURINE MELANOMA; GENE-TRANSFER AB Chemokines are a superfamily of pro-inflammatory polypeptide cytokines that selectively attract and activate different cell types. Many patho-physiological conditions require the participation of chemokines, including inflammation, infection, tissue injury, allergy, cardiovascular diseases, as well as malignant tumors. Chemokines activate cells through their binding to shared or unique cell surface receptors which belong to the seven-transmembrane, G-protein-coupled Rhodopsin superfamily. The role of chemokines in malignant tumors is complex: while some chemokines may enhance innate or specific host immunity against tumor implantation, others may favor tumor growth and metastasis by promoting tumor cell proliferation, migration or neovascularization in tumor tissue. In this review, the authors summarize some of the recent advances in chemokine research and emphasis is made on the effect of chemokines in tumor growth and metastasis. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Bldg 560,Room 31-40, Frederick, MD 21702 USA. NR 101 TC 237 Z9 259 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD NOV 1 PY 1998 VL 220 IS 1-2 BP 1 EP 17 DI 10.1016/S0022-1759(98)00128-8 PG 17 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 140UX UT WOS:000077107700001 PM 9839921 ER PT J AU Hutchcroft, JE Slavik, JM Lin, HM Watanabe, T Bierer, BE AF Hutchcroft, JE Slavik, JM Lin, HM Watanabe, T Bierer, BE TI Uncoupling activation-dependent HS1 phosphorylation from nuclear factor of activated T cells transcriptional activation in Jurkat T cells: Differential signaling through CD3 and the costimulatory receptors CD2 and CD28 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; LYMPHOCYTE SURFACE-RECEPTOR; ANTIGEN-RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; INTERLEUKIN-2 PRODUCTION; HEMATOPOIETIC LINEAGE; MEDIATED APOPTOSIS; MAJOR SUBSTRATE; CROSS-LINKING; SH3 DOMAIN AB CD3, CD2, and CD28 are functionally distinct receptors on T lymphocytes, Engagement of any of these receptors induces the rapid tyrosine phosphorylation of a shared group of intracellular signaling proteins, including Vav, Cbl, p85 phosphoinositide 3-kinase, and the Src family kinases Lck and Fyn, Ligation of CD3 also induces the tyrosine phosphorylation of HS1, a 75-kDa hematopoietic cell-specific intracellular signaling protein of unknown function, We have examined changes in HS1 phosphorylation after differential stimulation of CD3, CD2, and CD28 to elucidate its role in T cells and to further delineate the signaling pathways recruited by these receptors, Unlike ligation of CD3, stimulation with anti-CD28 mAb or CHO cells expressing the CD28 ligands CD80 or CD86 did not lead to tyrosine phosphorylation of HS1 in Jurkat T cells, Additionally, no tyrosine phosphorylation of HS1 was induced by mitogenic pairs of anti-CD2 mAbs capable of activating the transcription factor NFAT (nuclear factor of activated T cells), Costimulation through CD28 and/or CD2 did not modulate the CD3-dependent phosphorylation of HS1, Ln vivo studies indicated that CD3-induced HS1 phosphorylation was dependent upon both the Src family tyrosine kinase Lck and the tyrosine phosphatase CD45, did not require MEK1 kinase activity, and was regulated by protein kinase C activation, Thus, although CD3., CD28, and CD2 activate many of the same signaling molecules, they differed in their capacity to induce the tyrosine phosphorylation of HS1. Furthermore, activation-dependent tyrosine phosphorylation of HS1 was not required for NEAT transcriptional activation. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Kyushu Univ, Dept Mol Immunol, Fukuoka 812, Japan. Harvard Univ, Sch Med, Dept Pediat & Med, Boston, MA 02115 USA. RP Bierer, BE (reprint author), NHLBI, Bldg 10,Room 5D49,10 Ctr Dr, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI35297, AI28554] NR 59 TC 19 Z9 19 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1998 VL 161 IS 9 BP 4506 EP 4512 PG 7 WC Immunology SC Immunology GA 131NA UT WOS:000076581100010 PM 9794375 ER PT J AU Gurunathan, S Irvine, KR Wu, CY Cohen, JI Thomas, E Prussin, C Restifo, NP Seder, RA AF Gurunathan, S Irvine, KR Wu, CY Cohen, JI Thomas, E Prussin, C Restifo, NP Seder, RA TI CD40 ligand/trimer DNA enhances both humoral and cellular immune responses and induces protective immunity to infectious and tumor challenge SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PLASMID DNA; IN-VIVO; LEISHMANIA-MAJOR; INTERFERON-GAMMA; IL-12 PRODUCTION; DENDRITIC CELLS; T-LYMPHOCYTES; B-CELLS; INTERLEUKIN-12; IMMUNIZATION AB CD40/CD40 ligand interactions have a central role in the induction of both humoral and cellular immunity. In this study, we examined whether a plasmid expressing CD40 ligand/trimer (CD40LT) could enhance immune responses in vivo. BALB/c mice were injected with plasmid expressing beta-galactosidase DNA with or without CD40LT DNA or IL-12 DNA, and immune responses were assessed. Mice vaccinated with beta-gal DNA plus CD40LT DNA or IL-12 DNA had a striking increase in Ag-specific production of IFN-gamma, cytolytic T cell activity, and IgG2a Ab, The mechanism by which CD40LT DNA enhanced these responses was further assessed by treating vaccinated mice with anti-IL-12 mAb or CTLA-4 Ig (CTLA4Ig), Production of IFN-gamma and CTL activity was abrogated by these treatments, suggesting that CD40LT DNA was mediating its effects on IFN-gamma and CTL activity through induction of IL-12 and enhancement of B7 expression, respectively. Physiologic relevance for the ability of CD40LT DNA to enhance immune responses by the aforementioned pathways was shown in two in vivo models. First, with regard to CTL activity, mice vaccinated with CD40LT DNA did not develop metastatic tumor following challenge with lethal dose of tumor. Moreover, in a mouse model requiring IL-12-dependent production of IFN-gamma, mice vaccinated with soluble Leishmania Ag and CD40LT DNA were able to control infection with Leishmania major. These data suggest that CD40LT DNA could be a useful vaccine adjuvant for diseases requiring cellular and/or humoral immunity. C1 NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Immunex Res & Dev Corp, Seattle, WA 98101 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11C215, Bethesda, MD 20892 USA. EM rseder@nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580; Prussin, Calman/0000-0002-3917-3326 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 54 TC 120 Z9 124 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1998 VL 161 IS 9 BP 4563 EP 4571 PG 9 WC Immunology SC Immunology GA 131NA UT WOS:000076581100018 PM 9794383 ER PT J AU Leggatt, GR Hosmalin, A Pendleton, CD Kumar, A Hoffman, S Berzofsky, JA AF Leggatt, GR Hosmalin, A Pendleton, CD Kumar, A Hoffman, S Berzofsky, JA TI The importance of pairwise interactions between peptide residues in the delineation of TCR specificity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTE; CELL RECEPTOR ANTAGONISTS; CLASS-I H-2K(B); VACCINE CONSTRUCTS; NEUTRALIZING ANTIBODY; MOLECULAR ANALYSIS; PARTIAL AGONISTS; VIRAL PEPTIDES; BINDING; ANTIGEN AB A minimal, nonamer epitope (TEMEKEGKI) from the reverse transcriptase protein of HIV-1, restricted by R-2K(k), was identified and the function of individual residues determined. Besides classical anchor residues at positions 2 and 9, methionine at position 3 was identified as an important MWC anchor and improved binding of a different (malarial) nonamer epitope to H-2K(k), albeit while also abolishing CTL recognition. Lysine at position 5 was replaceable by alanine for CTL raised against mild-type peptide but abolished recognition for CTL raised against the variant 5ALA peptide, indicating a unidirectional cross-reactivity, Interestingly, one CTL line raised against the 5ALA substituted peptide was permissive for a double substitution at positions 5 and 6, in which lysine was permissive at position 5 only if the adjacent glutamic acid was replaced by alanine, Extensive analysis revealed three distinct patterns of responses with peptides doubly substituted in this region: recognition of both single substitutions but not the double substitution, recognition of only one single substitution but also the double substitution, or recognition of both single substitutions and the double substitution. A second complementary substitution can therefore restore function lost through a first substitution. Thus, no residue acts independently of its neighbors, and pairs of substitutions may give results not predictable from the effects of each taken singly. This finding may have bearing on viral infections (such as HIV), in which the accumulation of two mutations in the epitope may lead to the reengagement of memory CTL previously silenced by the initial mutation. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. USN, Med Res Inst, Malaria Program, Bethesda, MD 20889 USA. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bldg 10,Room 6B-12, Bethesda, MD 20892 USA. RI Leggatt, Graham/G-1924-2010; OI Leggatt, Graham/0000-0002-4078-5653 NR 46 TC 21 Z9 22 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1998 VL 161 IS 9 BP 4728 EP 4735 PG 8 WC Immunology SC Immunology GA 131NA UT WOS:000076581100038 PM 9794403 ER PT J AU Pelletier, C Varin-Blank, N Rivera, J Iannascoli, B Marchand, F David, B Weyer, A Blank, U AF Pelletier, C Varin-Blank, N Rivera, J Iannascoli, B Marchand, F David, B Weyer, A Blank, U TI Fc epsilon RI-mediated induction of TNF-alpha gene expression in the RBL-2H3 mast cell line: Regulation by a novel NF-kappa B-like nuclear binding complex SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACTIVATED T-CELLS; TRANSCRIPTIONAL REGULATION; MESSENGER-RNA; INTACT-CELLS; PROTEIN; MACROPHAGES; RECEPTOR; PROMOTER; ELEMENT AB Using rat basophilic leukemia (RBL-2H3) cells as a model, we investigated how aggregation of the high affinity receptor for IgE (Fc epsilon RI) regulates TNF-alpha gene expression. Antigenic stimulation of RBL-2H3 cells led to an increase in newly synthesized TNF-alpha mRNA that was dependent on continuous receptor aggregation and did nut require de novo protein synthesis, Kinetic analysis showed that maximal levels were achieved at 60 min and waned by 180 min of stimulation. Concomitant with the transcriptional activation of the TNF-alpha gene, the rapid appearance and disappearance of a previously uncharacterized nuclear NF-kappa B DNA binding activity, comprised of two distinct protein complexes, were observed. These protein complexes bound to NF-kappa B sites within the TNF-alpha gene and contained novel proteins (three species of M-r between 90,000-110,000) distinct from the classical proteins in NF-kappa B complexes. The induced NF-kappa B binding activity required continuous receptor stimulation and induced NF-kappa B-dependent reporter gene expression, Consistent with a role for the novel NF-kappa B nuclear binding activity in TNF-alpha gene expression, deletion of several 5' KB elements in the TNF-alpha promoter abolished all measurable Fc epsilon RI-dependent induction of a reporter construct. Pharmacologic agents that inhibited the NF-kappa B binding activity also inhibited TNF-alpha mRNA expression, Our results demonstrate Chat a novel NF-kappa B-like nuclear binding activity plays an important role in regulation of the rapid and transient transcriptional activation of the TNF-alpha gene via Fc epsilon RI. C1 Inst Pasteur, Unite Immunoallergie, F-75724 Paris 15, France. Hop Cochin, U363 INSERM, Inst Cochin Genet Mol, F-75674 Paris, France. NIAMSD, Sect Chem Immunol, NIH, Bethesda, MD 20892 USA. RP Blank, U (reprint author), Inst Pasteur, Unite Immunoallergie, 25-28 Rue Dr Roux, F-75724 Paris 15, France. NR 51 TC 48 Z9 48 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1998 VL 161 IS 9 BP 4768 EP 4776 PG 9 WC Immunology SC Immunology GA 131NA UT WOS:000076581100043 PM 9794408 ER PT J AU Kitani, A Nakashima, N Izumihara, T Inagaki, M Baoui, X Yu, S Matsuda, T Matsuyama, T AF Kitani, A Nakashima, N Izumihara, T Inagaki, M Baoui, X Yu, S Matsuda, T Matsuyama, T TI Soluble VCAM-1 induces chemotaxis of Jurkat and synovial fluid T cells bearing high affinity very late antigen-4 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; SYSTEMIC LUPUS-ERYTHEMATOSUS; GTP-BINDING-PROTEIN; RHEUMATOID-ARTHRITIS; VIMENTIN PHOSPHORYLATION; TYROSINE PHOSPHORYLATION; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; KINASE-II; EXPRESSION AB It has been shown that cells with high affinity very late Ag (VLA)-integrins have up-regulated expression of a beta(1)-subunit epitope, which is detected by 15/7 mAb, In this study, we demonstrate that soluble VCAM-1 (sVCAM-1) exhibits chemotactic activity of T cells with high affinity VLA-4 against VCAM-1, such as Jurkat T cells and IL-2-dependent T cells. Moreover, we found that T cells in the synovial fluid show high basal migration in the absence of sVCAM-1, compared with peripheral blood T cells in patients with rheumatoid arthritis. Among T cells in the synovial fluid, CD45RO(+) memory T cells, in response to sVCAM-1, showed a much higher than basal migratory response when compared with CD45RA(+) naive cells, while no significant difference was observed between CD4(+) and CD8(+) T cells, The chemotactic activity of sVCAM-1 is inhibited in the presence of anti-VCAM-1 and anti-VLA-4, which interfered with the binding between VCAM-1 and VLA-I. Inhibition studies using various kinase inhibitors (C3 exoenzyme, KN62, and H7) show that Rho, Ca2+/calmodulin-dependent kinase II, and protein kinase C are involved in signal transduction in sVCAM-1-induced chemotaxis, respectively, whereas tyrosine kinase seems to play a lesser role, since genistein showed only partial inhibition of T cell chemotaxis, Western blot analysis using an anti-phospho-serine mAb (MO82) reveals that Ser(82) in the vimentin is phosphorylated specifically by Ca2+/calmodulin-dependent kinase II through sVCAM-1 activation in the IL-2 dependent T cells. Collectively, by inducing migration and recruitment of T cells through several kinase activations, sVCAM-1 contributes to the development of the inflammation of synovial lesion. C1 Kagoshima Univ, Sch Med, Dept Immunol & Med Zool, Kagoshima 890, Japan. Kagoshima Univ, Sch Med, Dept Hyg, Kagoshima 890, Japan. Kagoshima Red Cross Hosp, Ctr Rheumat Dis, Kagoshima, Japan. Aichi Canc Ctr, Res Inst, Biochem Lab, Nagoya, Aichi 464, Japan. RP Kitani, A (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bldg 10,11N238, Bethesda, MD 20892 USA. NR 48 TC 48 Z9 49 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1998 VL 161 IS 9 BP 4931 EP 4938 PG 8 WC Immunology SC Immunology GA 131NA UT WOS:000076581100063 PM 9794428 ER PT J AU Hinnebusch, BJ Fischer, ER Schwan, TG AF Hinnebusch, BJ Fischer, ER Schwan, TG TI Evaluation of the role of the Yersinia pestis plasminogen activator and other plasmid-encoded factors in temperature-dependent blockage of the flea SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 1997 CL ORLANDO, FLORIDA SP Amer Soc Trop Med & Hyg ID PLAGUE BACILLUS; CAPSULAR ANTIGEN; GENETIC-ANALYSIS; SIPHONAPTERA; VIRULENCE; HEMIN; CERATOPHYLLIDAE; TRANSMISSION; PHENOTYPE; PULICIDAE AB Yersinia pestis, the plague bacillus, has a plasminogen activator (pla) gene on the 9.5-kb plasmid pPIa that is hypothesized to play a role in producing the foregut blockage in the flea vector that precedes transmission. In this study, however, Y. pestis that lacked pPla, the 70-kb virulence plasmid, or both plasmids, proved able to block Xenopsylla cheopis fleas normally. Blockage rates decreased with increasing environmental temperature for fleas infected with either wild type or pPla(-) Y. pestis. Thus, procoagulant ability of the Y. pestis pla gene product does not mediate blockage, nor does its ability to induce fibrinolysis at >28 degrees C account for failure to block at elevated temperatures. A I: pestis strain that lacked all or part of the third plasmid of 110 kb, however, failed to colonize the flea midgut normally, indicating that one or more genes on the large plasmid may be required for vectorborne transmission. C1 NIAID, Lab Microbial Struct & Funct & Microscopy Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Hinnebusch, BJ (reprint author), NIAID, Lab Microbial Struct & Funct & Microscopy Branch, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 62 TC 89 Z9 93 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1998 VL 178 IS 5 BP 1406 EP 1415 DI 10.1086/314456 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 138TQ UT WOS:000076989500022 PM 9780262 ER PT J AU Marques, AR Lau, DTY McKenzie, R Straus, SE Hoofnagle, JH AF Marques, AR Lau, DTY McKenzie, R Straus, SE Hoofnagle, JH TI Combination therapy with famciclovir and interferon-alpha for the treatment of chronic hepatitis B SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 37th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 28-OCT 03, 1997 CL TORONTO, CANADA ID TERM FOLLOW-UP; VIRUS-REPLICATION; PENCICLOVIR; INFECTION; ALFA AB Interferon-alpha (IFN-alpha) treatment results in long-term remissions in only 25%-40% of patients with chronic hepatitis B virus (HBV) infection. Famciclovir, the oral-prodrug of penciclovir, inhibits HBV DNA replication. Five adults with chronic HBV infection in whom previous IFN-alpha therapy had failed were treated in a pilot study of overlapping IFN-alpha and famciclovir therapy totaling 20 weeks. HBV DNA levels decreased by 0.9 log units during the initial 4-week period of famciclovir alone, followed by a further decrease of 1.8 logs during the middle 12-week period of combination therapy. HBV DNA rose by 0.9 log during the final 4-week period of IFN-cr alone. Two patients cleared HBV DNA, and their liver disease improved by clinical and histologic criteria. The combination of famciclovir and IFN-a appeared to be at least additive in suppressing HBV DNA, Efficacy trials of combination therapy with famciclovir and IFN-a are warranted. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Marques, AR (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. EM amarques@atlas.niaid.nih.gov NR 15 TC 25 Z9 26 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1998 VL 178 IS 5 BP 1483 EP 1487 DI 10.1086/314430 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 138TQ UT WOS:000076989500031 PM 9780271 ER PT J AU Kimura, H Straus, SE Williams, RK AF Kimura, H Straus, SE Williams, RK TI Baculovirus expression, purification, and properties of varicella-zoster virus gE, gI, and the complex they form SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 3rd International Conference of the Varicella-Zoster Virus CY MAR 09-11, 1997 CL PALM BEACH GARDENS, FLORIDA SP VZV Res Fdn ID HIGH-LEVEL EXPRESSION; INSECT CELLS; RECEPTOR AB Varicella-zoster virus (VZV) expresses six known glycoproteins. High level expression of recombinant soluble forms of the VZV glycoproteins E and I (gE and gI) was achieved in the baculovirus system. gE and gI associate in VZV-infected cells to form an intermolecular complex. To purify large amounts of these glycoproteins, gE was produced with a C-terminal six-histidine (HIS-6) tag sequence, and gI was produced both with and without the HIS-6 sequence. The individual glycoproteins or the gE/gI complex were purified in their native forms by use of affinity chromatography, Recombinant soluble VZV gE and gI provided important tools in the biochemical analysis and may contribute further to the functional and immunologic studies of these VZV envelope components. C1 NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Williams, RK (reprint author), NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11N228,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Kimura, Hiroshi/I-2246-2012 NR 11 TC 2 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1998 VL 178 SU 1 BP S13 EP S15 DI 10.1086/514256 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 139MY UT WOS:000077034100004 PM 9852966 ER PT J AU Vestal, DJ Buss, JE McKercher, SR Jenkins, NA Copeland, NG Kelner, GS Asundi, VK Maki, RA AF Vestal, DJ Buss, JE McKercher, SR Jenkins, NA Copeland, NG Kelner, GS Asundi, VK Maki, RA TI Murine GBP-2: A new IFN-gamma-induced member of the GBP family of GTPases isolated from macrophages SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID GUANYLATE-BINDING-PROTEIN; SIGNAL TRANSDUCTION PATHWAYS; GDP DISSOCIATION INHIBITOR; INTERFERON-GAMMA; ALPHA-INTERFERON; MEMBRANE ASSOCIATION; MAMMALIAN-CELLS; GENE; INDUCTION; ACTIVATION AB We have cloned a new member of the interferon (IFN)-induced guanylate-binding protein (GBP) family of GTPases, murine GBP-2 (mGBP-2), from bone marrow-derived macrophages, mGBP-2 is located on murine chromosome 3, where it is linked to mGBP-1, With the identification of mGBP-2 there are now two human and two murine GBPs, Like other GBPs, mGBP-2 RNA and protein are induced by IFN-gamma, In addition, mGBP-2 shares with the other GBPs important structural features that distinguish this family from other GTPases, First, mGBP-2 contains only two of the three consensus sequences for nucleotide binding found within the classic GTP binding regions of other GTPases, A second amino acid motif found in mGBP-2 is a potential C-terminal site for isoprenoid modification, called a CaaX sequence. mGBP-2 is prenylated, as detected by [H-3]mevalonate incorporation, when expressed in COS cells and preferentially incorporates the C-20 isoprenoid geranylgeraniol, Surprisingly, despite having a functional CaaX sequence, mGBP-2 is primarily cytosolic, GBP proteins are very abundant in IFN-exposed cells, but little is known about their function. mGBP-2 is expressed by IFN-gamma-treated cells from C57Bl/6 mice, whereas mGBP-1 is not. Thus, the identification of mGBP-2 makes possible the study of GBP function in the absence of a second family member. C1 Cleveland Clin Fdn, Dept Biol Mol, Cleveland, OH 44195 USA. Burnham Inst, La Jolla, CA 92037 USA. Iowa State Univ, Dept Biochem & Biophys, Ames, IA 50011 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. Neurocrine Biosci Inc, La Jolla, CA 92037 USA. Geisinger Med Clin, Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA. RP Vestal, DJ (reprint author), Cleveland Clin Fdn, Dept Biol Mol, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NIAID NIH HHS [AI20194] NR 58 TC 31 Z9 32 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD NOV PY 1998 VL 18 IS 11 BP 977 EP 985 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 145HT UT WOS:000077365600009 PM 9858320 ER PT J AU Lee, YS Yuspa, SH Dlugosz, AA AF Lee, YS Yuspa, SH Dlugosz, AA TI Differentiation of cultured human epidermal keratinocytes at high cell densities is mediated by endogenous activation of the protein kinase C signaling pathway SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE bryostatin; filaggrin; involucrin; keratins; loricrin; SPR-1 ID TRANSFORMED HUMAN KERATINOCYTES; INTRACELLULAR FREE CALCIUM; MOUSE KERATINOCYTES; GENE-EXPRESSION; HUMAN-SKIN; EXTRACELLULAR CALCIUM; MURINE KERATINOCYTES; INDUCTION; INVITRO; MARKERS AB Normal human epidermal keratinocytes (NHEK) grown in serum-free medium on a plastic substrate spontaneously differentiate at high cell densities in vitro, Because protein kinase C (PKC) regulates murine keratinocyte differentiation triggered by a variety of stimuli, we examined the role of this signaling pathway in density-dependent activation of NHEK differentiation. Relative to subconfluent cultures, confluent NHEK expressed markedly higher levels of multiple differentiation markers assayed by immunoblotting, including keratin 1, loricrin, filaggrin, involucrin, TG(K), and SPR-1. Expression of several of these markers continued to increase for several days after cells reached confluency, The total level of several PKC isoforms was not substantially altered in NHEK harvested at different cell densities, based on immunoblotting; however, subcellular fractionation revealed that PKC alpha underwent a redistribution to the particulate fraction in confluent and postconfluent NHEK cultures, suggesting that this isozyme was activated under these conditions and may be involved in triggering the terminal differentiation program. Supporting this concept, inhibition of PKC function using bryostatin 1 or GF 109203X blocked the induction of keratinocyte differentiation markers at high cell densities. These data suggest that endogenous activation of PKC is responsible for cell density-mediated stimulation of NHEK differentiation, establishing a critical role for this pathway in regulating human as well as murine keratinocyte differentiation. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37,Rm 3B25,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 41 TC 76 Z9 77 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1998 VL 111 IS 5 BP 762 EP 766 DI 10.1046/j.1523-1747.1998.00365.x PG 5 WC Dermatology SC Dermatology GA 132KA UT WOS:000076627800009 PM 9804335 ER PT J AU Cohen, SS Weinstein, MD Herndier, BG Anhalt, GJ Blauvelt, A AF Cohen, SS Weinstein, MD Herndier, BG Anhalt, GJ Blauvelt, A TI No evidence of human herpesvirus 8 infection in patients with paraneoplastic pemphigus, pemphigus vulgaris, or pemphigus foliaceus SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE in situ hybridization; Kaposi's sarcoma; polymerase chain reaction; serology ID SARCOMA-ASSOCIATED HERPESVIRUS; MULTICENTRIC CASTLEMANS-DISEASE; KAPOSIS-SARCOMA; DNA-SEQUENCES; MULTIPLE-MYELOMA; IMMUNOSUPPRESSED PATIENTS; VASCULAR-LESIONS; SKIN CANCERS; HUMAN-HERPESVIRUS-8; HHV8 AB Paraneoplastic pemphigus has been associated with both malignancies and multicentric Castleman's disease; the latter is a rare angiolymphoproliferative disorder that has also been linked with human herpesvirus 8 (HHV8) infection. Other diseases definitively associated with HHV8 include Kaposi's sarcoma and primary effusion lymphoma. In a search for additional HHV8-associated diseases, patients with paraneoplastic pemphigus, as well as patients with pemphigus vulgaris and pemphigus foliaceus, were studied. Using an immunofluorescence assay able to specifically detect antibodies directed against lytically induced HHV8 antigens, HHV8 antibodies were not detected in sera from 24 patients with paraneoplastic pemphigus (including 10 with concomitant Castleman's disease) nor from 19 patients with pemphigus vulgaris. Sera from patients with Kaposi's sarcoma and from healthy U.S. blood donors were positive (25 of 26) and negative (none of 20), respectively. In addition, HHV8 DNA was not found in frozen lesional skin of five patients with pemphigus vulgaris and five patients with pemphigus foliaceus by nested polymerase chain reaction (lower limit of detection = 10 copies viral DNA per mu g total cellular DNA), Finally, tissue sections of lesional skin from 10 patients with pemphigus vulgaris were negative for HHV8 by in situ hybridization, using probes able to detect both latently and lyrically expressed HHV8 genes in Kaposi's sarcoma tissue. In summary, no evidence of HHV8 infection was found in all types of pemphigus using a variety of methods. These findings do not support a general role for HHV8 in skin diseases associated with immunosuppression. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Dermatol, Baltimore, MD 21218 USA. RP Blauvelt, A (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. NR 41 TC 23 Z9 23 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1998 VL 111 IS 5 BP 781 EP 783 DI 10.1046/j.1523-1747.1998.00384.x PG 3 WC Dermatology SC Dermatology GA 132KA UT WOS:000076627800012 PM 9804338 ER PT J AU Khan, SG Levy, HL Legerski, R Quackenbush, E Reardon, JT Emmert, S Sancar, A Li, L Schneider, TD Cleaver, JE Kraemer, KH AF Khan, SG Levy, HL Legerski, R Quackenbush, E Reardon, JT Emmert, S Sancar, A Li, L Schneider, TD Cleaver, JE Kraemer, KH TI Xeroderma pigmentosum group C splice mutation associated with autism and hypoglycinemia SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE alternative splicing; amino acid metabolism; DNA repair; skin cancer ID REPAIR EXCISION NUCLEASE; DNA-REPAIR; SKIN-CANCER; CELLS; EXPRESSION; GENE; TRANSCRIPTION; PURIFICATION; PROTEIN; REMOVES AB A 4 y old boy of Korean ancestry had xeroderma pigmentosum (XP) with sun sensitivity, multiple cutaneous neoplasms, and inability to speak. Neurologic examination revealed hyperactivity and autistic features without typical XP neurologic abnormalities, Cultured skin fibroblasts (XP22BE) showed decreased post-UV survival, reduced post-UV plasmid host cell reactivation and defective DNA repair (16% of normal unscheduled DNA synthesis in intact cells and undetectable excision repair in a cell free extract). In vitro and in vivo complementation assigned XP22BE to XP group C (XPC) and a markedly reduced level of XPC mRNA was found, Two XPC cDNA hands were identified. One band had a deletion of 161 bases comprising the entire exon 9, which resulted in premature termination of the mutant XPC mRNA. The larger band also had the same deletion of exon 9 but, in addition, had an insertion of 155 bases in its place (exon 9a), resulting in an in-frame XPC mRNA, Genomic DNA analysis revealed a T-->G mutation at the splice. donor site of XPC exon 9, which markedly reduced its information content. The 155 base pair XPC exon 9a insertion was located in intron 9 and was flanked by strong splice donor and acceptor sequences. Analysis of the patient's blood showed persistently low levels of glycine (68 mu M; NL, 125-318 mu M). Normal glycine levels mere maintained with oral glycine supplements and his hyperactivity diminished. These data provide evidence of an association of an XPC splice site mutation with autistic neurologic features and hypoglycinemia. C1 NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. Childrens Hosp, Genet Serv, Boston, MA 02115 USA. MD Anderson Hosp & Tumor Inst, Houston, TX USA. Ctr Blood Res, Boston, MA 02115 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA. NCI, Lab Expt & Computat Biol, Frederick, MD 21701 USA. Univ Calif San Francisco, Dept Radiobiol, San Francisco, CA 94143 USA. RP Kraemer, KH (reprint author), NCI, Mol Carcinogenesis Lab, Bldg 37,Room 3E24, Bethesda, MD 20892 USA. OI Schneider, Thomas/0000-0002-9841-1531 FU Intramural NIH HHS [Z01 BC004517-31]; NCI NIH HHS [CA52461]; NIGMS NIH HHS [GM3283] NR 39 TC 47 Z9 48 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1998 VL 111 IS 5 BP 791 EP 796 DI 10.1046/j.1523-1747.1998.00391.x PG 6 WC Dermatology SC Dermatology GA 132KA UT WOS:000076627800014 PM 9804340 ER PT J AU Gruschus, JM Ferretti, JA AF Gruschus, JM Ferretti, JA TI N-15-edited three-dimensional NOESY-HMQC with water flipback: Enhancement of weak labile H-1 resonances of protein side chains contacting DNA SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE water flipback; WATERGATE; homeodomain; protein/DNA complex; NOESY-HMQC; radiation damping ID SPECTROSCOPY; HOMEODOMAIN; NMR; BINDING AB Two pulse sequences are described that employ a modified water flipback technique to enhance the signal intensity of weak side chain resonances at the protein-DNA interface of the vnd/NK-2 homeodomain/DNA complex in an N-15-edited three-dimensional NOESY-HMQC spectrum. The pulse sequences presented employ water flipback pulses at the beginning of the NOESY mixing time, optimizing the direct NOE transfer of magnetization from the water to the protein by maximizing the z-component of the water magnetization, In one of the pulse sequences, radiation damping during the the indirect H-1 and N-15 evolution times is suppressed. A modified version of the WATERGATE water suppression technique is employed during the HMQC portion of the experiment. The signal enhancement is demonstrated for the resonances of the side chain amide of Asn51, an invariant homeodomain residue whose contact with the DNA is critical for binding. An ancillary advantage of the experiment is the ability to observe NOE transfer of magnetization from water. The information present in the water resonance plane of the three-dimensional spectrum is illustrated in a comparison with the corresponding HMQC spectrum of the protein/DNA complex. (C) 1998 Academic Press. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Gruschus, JM (reprint author), NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 10 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 1998 VL 135 IS 1 BP 87 EP 92 DI 10.1006/jmre.1998.1532 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 137FF UT WOS:000076903600014 PM 9799680 ER PT J AU Antzutkin, ON Lee, YK Levitt, MH AF Antzutkin, ON Lee, YK Levitt, MH TI C-13 and N-15 chemical shift anisotropy of ampicillin and penicillin-V studied by 2D-PASS and CP/MAS NMR SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE antibiotics; C-13 and N-15 solid state NMR; CP/MAS; CSA; 2D-PASS ID ANGLE-SPINNING NMR; NUCLEAR-MAGNETIC-RESONANCE; SIDE-BAND SEPARATION; TENSOR PRINCIPAL VALUES; CP-MAS NMR; MAGIC-ANGLE; POWDERED SOLIDS; SPECTRA; SPECTROSCOPY; RESOLUTION AB The principal values of the chemical shift tensors of all C-13 and N-15 sites in two antibiotics, ampicillin and penicillin-V, were determined by 2-dimensional phase adjusted spinning sideband (2D-PASS) and conventional CP/MAS experiments. The C-13 and N-15 chemical shift anisotropies (CSA), and their confidence limits, were evaluated using a Mathematica program. The CSA values suggest a revised assignment of the a-methyl C-13 sites in the case of ampicillin. We speculate on a relationship between the chemical shift principal values of many of the C-13 and N-15 sites and the beta-lactam ring conformation. (C) 1998 Academic Press. C1 Lulea Univ Technol, Div Inorgan Chem, S-97187 Lulea, Sweden. Univ Stockholm, Div Phys Chem, S-10691 Stockholm, Sweden. RP Antzutkin, ON (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. RI Levitt, Malcolm/B-3746-2010 OI Levitt, Malcolm/0000-0001-9878-1180 NR 51 TC 81 Z9 84 U1 3 U2 20 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 1998 VL 135 IS 1 BP 144 EP 155 DI 10.1006/jmre.1998.1576 PG 12 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 137FF UT WOS:000076903600022 PM 9799688 ER PT J AU Dzekunov, SM Spring, KR AF Dzekunov, SM Spring, KR TI Maintenance of acidic lateral intercellular spaces by endogenous fixed buffers in MDCK cell epithelium SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE pH; glycocalyx; strontium; microclimate; fluorescence microscopy ID DIVALENT-CATIONS; PROTON MOVEMENT; MOBILE BUFFERS; PH; PERMEABILITY; MEMBRANES AB The lateral intercellular spaces (LIS) of MDCK cell epithelia grown on permeable supports are about 0.4 pH units acidic to the bathing solutions, presumably because of buffering by the fixed negative charges on the surface of the lateral cell membranes. To test the hypothesis that fixed buffers are responsible for the acidity, a theoretical and experimental approach was developed for the determination of the concentration and pK of the fixed buffer constituted by the glycocalyx. The pH of the solution in the LIS was measured by ratiometric fluorescence microscopy while the buffer concentration or composition of the bathing solutions was altered. In addition, the divalent cation Sr2+ was added to the perfusion solutions to displace protons from the fixed buffer sites for the determination of the fixed buffer properties. We conclude that the LIS contain 3.7 mM of pK 6.2 fixed buffer and that this buffer is responsible for the acidic microenvironment in the LIS. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Spring, KR (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Room 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. NR 13 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD NOV 1 PY 1998 VL 166 IS 1 BP 9 EP 14 DI 10.1007/s002329900443 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 132PE UT WOS:000076638100002 PM 9784582 ER PT J AU Weiss, GH Kiefer, JE AF Weiss, GH Kiefer, JE TI A numerical study of the statistics of penetration depth of photons re-emitted from irradiated media SO JOURNAL OF MODERN OPTICS LA English DT Article ID DIFFUSION; MIGRATION; TISSUE; TIME AB An important question in the utilization of optical methods to estimate optical parameters non-invasively in human tissue is that of describing properties of the trajectories of laser-injected photons. It is relatively easy to calculate an expression for the average depth experienced by these photons starting from either a random-walk or a diffusion model. It is much harder to characterize more detailed descriptive parameters. Here we make use of a novel variation of the method of exact enumeration to provide essentially numerically exact results for the random-walk model of a continuous-wave experiment. C1 NIH, Bethesda, MD 20892 USA. RP Weiss, GH (reprint author), NIH, Bethesda, MD 20892 USA. NR 12 TC 3 Z9 3 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0950-0340 J9 J MOD OPTIC JI J. Mod. Opt. PD NOV PY 1998 VL 45 IS 11 BP 2327 EP 2337 PG 11 WC Optics SC Optics GA 138FM UT WOS:000076960700010 ER PT J AU Lundberg, MS Curto, KA Bilato, C Monticone, RE Crow, MT AF Lundberg, MS Curto, KA Bilato, C Monticone, RE Crow, MT TI Regulation of vascular smooth muscle migration by mitogen-activated protein kinase and calcium/calmodulin-dependent protein kinase II signaling pathways SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE vascular smooth muscle cells; cell migration; MAPK; calcium/calmodulin-dependent protein kinase II; platelet-derived growth factor; integrins ID FIBROBLAST GROWTH-FACTOR; CELL-MIGRATION; DIRECTED MIGRATION; PHOSPHORYLATION; INTEGRIN; ALPHA(V)BETA(3); PROLIFERATION; INHIBITION; ANTIBODY; INSULIN AB Platelet-derived growth factor BE (PDGF BE) activation of the mitogen-activated protein kinases (MAPK), ERK1 and ERK2, has been shown to be necessary for mitogen-stimulated proliferation, but its role in regulating cell migration and its relationship to other chemotactic signaling events, such as CamKII activation, has not been defined. Using a modified Boyden chamber apparatus, we tested the effects of a selective inhibitor of the upstream activator of ERK1/2, MEK1, on PDGF-stimulated rat aortic vascular smooth muscle cells (VSMCs) alone and in combination with KN62, a selective inhibitor of CamKII. The MEK1 inhibitor, PD98059, caused a dose-dependent reduction in ERK2 activity that paralleled a decrease in migration up to 60%, This inhibition of migration was, similar to that seen with KN62 and the combined effects of both inhibitors were non-additive. Although KN62 did not affect ERK2 activity in response to PDGF, PD98059 markedly inhibited PDGF-stimulated CamKII activity, suggesting that activation of CamKII by PDGF was dependent on ERK activity and that the effects of ERK inhibition on migration may be mediated through its ability to inhibit CamKII activity. To directly test this, VSMCs were infected with a recombinant adenovirus expressing constitutively activated CamKII. Infection reversed the inhibitory effects of KN62 on migration, but had no effect on the inhibition of migration seen with PD98059. These results suggest that while MAPK may act upstream of CamKII to control its activation in response to PDGF, it also regulates migration independently of CamKII activation. (C) 1998 Academic Press. C1 NIA, Vasc Biol Unit, Cardiovasc Sci Lab, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Crow, MT (reprint author), NIA, Vasc Biol Unit, Cardiovasc Sci Lab, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 41 TC 40 Z9 42 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD NOV PY 1998 VL 30 IS 11 BP 2377 EP 2389 DI 10.1006/jmcc.1998.0795 PG 13 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 145JH UT WOS:000077367100021 PM 9925373 ER PT J AU Eizirik, E Bonatto, SL Johnson, WE Crawshaw, PG Vie, JC Brousset, DM O'Brien, SJ Salzano, FM AF Eizirik, E Bonatto, SL Johnson, WE Crawshaw, PG Vie, JC Brousset, DM O'Brien, SJ Salzano, FM TI Phylogeographic patterns and evolution of the mitochondrial DNA control region in two neotropical cats (Mammalia, Felidae) SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE Leopardus pardalis; Leopardus wiedii; mitochondrial DNA control region phylogeography; felid evolution ID PHYLOGENETIC ANALYSES; MOLECULAR PHYLOGENY; CYTOCHROME-B; GENE FLOW; SEQUENCES; CONSERVATION; DIFFERENTIATION; SYSTEMATICS; CONFIDENCE; ORIGINS AB The ocelot (Leopardus pardalis) and margay (L. wiedii) are sister-species of Neotropical cats which evolved from a lineage that migrated into South America during the formation of the Panamanian land bridge 3-5 million years ago. Patterns of population genetic divergence of each species were studied by phylogenetic analyses of mitochondrial DNA (mtDNA) control region sequences in individuals sampled across the distribution of these taxa. Abundant genetic diversity and remarkably concordant phylogeographic partitions for both species were observed, identifying parallel geographic regions which likely reflect historical faunal barriers. Inferred aspects of phylogeography, population genetic structure, and demographic history were used to formulate conservation recommendations for these species. In addition, observed patterns of sequence variation provided insight into the molecular evolution of the mtDNA control region in closely related felids. C1 Univ Fed Rio Grande do Sul, Inst Biociencias, Dept Genet, BR-90049 Porto Alegre, RS, Brazil. NCI, Lab Genom Divers, FCRDC, Frederick, MD 21702 USA. IBAMA, Ctr Nacl Predadores, Rio De Janeiro, Brazil. Univ Nacl Autonoma Mexico, Fac Med Vet & Zootecn, Mexico City, DF, Mexico. Univ Fed Rio Grande do Sul, Inst Biociencias, Dept Genet, BR-90049 Porto Alegre, RS, Brazil. RP Eizirik, E (reprint author), NCI, Lab Genom Divers, FCRDC, Bldg 560,Room 11-26, Frederick, MD 21702 USA. EM eizirike@mail.ncifcrf.gov RI Eizirik, Eduardo/K-8034-2012; Salzano, Francisco/L-7916-2015; Johnson, Warren/D-4149-2016; Bonatto, Sandro/A-1240-2010 OI Eizirik, Eduardo/0000-0002-9658-0999; Johnson, Warren/0000-0002-5954-186X; Bonatto, Sandro/0000-0002-0064-467X NR 68 TC 53 Z9 57 U1 0 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 EI 1432-1432 J9 J MOL EVOL JI J. Mol. Evol. PD NOV PY 1998 VL 47 IS 5 BP 613 EP 624 DI 10.1007/PL00006418 PG 12 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 134JN UT WOS:000076739900013 PM 9797412 ER PT J AU Rall, JE AF Rall, JE TI Where are the genes specifying mental illness? SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Editorial Material ID GENOTYPE C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Rall, JE (reprint author), NIDDKD, NIH, Bldg 10 Rm 6C201, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 1998 VL 186 IS 11 BP 722 EP 723 DI 10.1097/00005053-199811000-00010 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 136UJ UT WOS:000076877300010 PM 9824176 ER PT J AU MacLean, PD AF MacLean, PD TI The temporal lobe and limbic system SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NIMH, Washington, DC 20032 USA. RP MacLean, PD (reprint author), NIMH, Washington, DC 20032 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 1998 VL 186 IS 11 BP 728 EP 730 DI 10.1097/00005053-199811000-00015 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 136UJ UT WOS:000076877300015 ER PT J AU Espey, MG Kustova, Y Sei, Y Basile, AS AF Espey, MG Kustova, Y Sei, Y Basile, AS TI Extracellular glutamate levels are chronically elevated in the brains of LP-BM5-infected mice: A mechanism of retrovirus-induced encephalopathy SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE glutamate; transporter; striatum; glutamine synthetase; microdialysis; cerebrospinal fluid; mouse; retrovirus; AIDS dementia complex ID PLATELET-ACTIVATING-FACTOR; CENTRAL NERVOUS-SYSTEM; NITRIC-OXIDE; INDUCED IMMUNODEFICIENCY; ARACHIDONIC-ACID; QUINOLINIC ACID; AMINO-ACIDS; TAURINE CHLORAMINE; SUPEROXIDE ANION; LEUKEMIA-VIRUS AB Mice infected with the LP-BM5 leukemia retrovirus mixture develop a progressive immunodeficiency with associated behavioral, histological, and neurochemical alterations consistent with glutamatergic hyperactivation, To gain insight into the contribution of excitatory amino acids to the neurodegeneration observed in these mice, their concentrations were measured in the CSF and striatal microdialysates. Glutamate concentrations were significantly elevated in CSF but not plasma as early as 4 weeks postinoculation. Steady-state glutamate levels in striatal microdialysates were increased threefold and could be reduced 40% by application of L-alpha-aminoadipate, an inhibitor of microglial glutamate transport. Stimulation of infected mice with KCl/L-trans-2,4-pyrrolidine dicarboxylate further increased glutamate levels 170-270% above those evoked in control mice. Tetrodotoxin suppressed the depolarization-evoked increase in glutamate by 88% in control mice, but it had only negligible effects in 40% of infected mice. Analysis of glutamate transport and catabolism suggests that abnormal astrocytic function does not contribute to the increase in basal extracellular glutamate levels. These findings are the first direct evidence that infection with an immunodeficiency-inducing retrovirus leads to a chronic elevation of extracellular free glutamate levels in the brain, which contributes to the neurodegenerative and cognitive deficits observed in these mice. C1 NIDDK, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anesthesiol, Bethesda, MD 20814 USA. RP Espey, MG (reprint author), NIDDK, Neurosci Lab, NIH, Bldg 8,Room 1A15,MSC 0826, Bethesda, MD 20892 USA. NR 53 TC 49 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1998 VL 71 IS 5 BP 2079 EP 2087 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 131KW UT WOS:000076576100031 PM 9798933 ER PT J AU Sihag, RK AF Sihag, RK TI Brain beta-spectrin phosphorylation: Phosphate analysis and identification of threonine-347 as a heparin-sensitive protein kinase phosphorylation site SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE beta-spectrin; phosphorylation; heparin-sensitive protein kinase; neuronal cytoskeleton ID ERYTHROCYTE SPECTRIN; MEMBRANE SKELETON; SYNAPTIC VESICLES; PLASMA-MEMBRANE; BINDING DOMAIN; SUBUNIT; CELLS; FODRIN; ACTIN; SPECTRIN(240/235E) AB Phosphorylation of brain spectrin was studied by a combination of in vivo and in vitro approaches. Chemical analysis of phosphate groups on electrophoretically purified mouse brain beta-spectrin yielded a stoichiometry of 3.2 +/- 0.18 mot of PO4/mol of beta-spectrin. The spectrin isolated by chromatographic methods from mouse brain, pig brain, and human erythrocytes yielded 4.1, 5.6, and 3.2 mol of PO4/mol of spectrin heterodimer, respectively. The P-32 labeling of spectrin in retinal ganglion cell neurons or NE 2a/d1 neuroblastoma cells with [P-32]orthophosphate showed phosphorylation of only beta-spectrin in vivo. Two-dimensional phosphopeptide map analyses showed that most of the in vivo sites on beta-spectrin were phosphorylated by either a heparin-sensitive endogenous cytoskeleton-associated protein kinase or protein kinase A. Phosphoamino acid analysis of in vivo and in vitro phosphorylated beta-spectrin showed that [P-32]phosphate groups were incorporated into both serine (>90%) and threonine residues. In vitro, phosphate groups were incorporated into threonine residues by the heparin-sensitive endogenous protein kinase. The amino acid sequence VQQQLQAFNTY of an alpha-chymotryptic P-32-labeled peptide phosphorylated by the heparin-sensitive cytoskeleton-associated endogenous protein kinase corresponded to amino acid residues 338-348 on the pi repeat of beta-spectrin, (beta SPIIa) gene. These data suggest that phosphorylation of Thr(347), which is localized on the presumptive synapsin I binding domain of beta-spectrin(G), may play a role in synaptic function by regulating the binding of spectrin to synaptic vesicles. C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Belmont, MA 02178 USA. RP NINDS, Neurobiol Lab, NIH, Bldg 36,Room 2A-21,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 37 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1998 VL 71 IS 5 BP 2220 EP 2228 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 131KW UT WOS:000076576100048 PM 9798950 ER PT J AU House, SB Thomas, A Kusano, K Gainer, H AF House, SB Thomas, A Kusano, K Gainer, H TI Stationary organotypic cultures of oxytocin and vasopressin magnocellular neurones from rat and mouse hypothalamus SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE slice-explants; neurophysin; magnocellular neurones; neurohypophysis; c-fos; veratridine; depolarization ID SLICE-EXPLANT CULTURES; DORSAL-ROOT GANGLIA; C-FOS EXPRESSION; SUPRAOPTIC NEURONS; LONG-TERM; SUPRACHIASMATIC NUCLEUS; ARGININE-VASOPRESSIN; GENE-EXPRESSION; JUN EXPRESSION; NERVOUS-TISSUE AB Rat and mouse hypothalami from postnatal animals containing highly differentiated neurones survive very well in long-term (>15 days in vitro, DIV) stationary organotypic cultures. Magnocellular oxytocin (OT) and vasopressin (VP) neurones are present in identifiable paraventricular (PVN), supraoptic (SON) and accessory (ACC) nuclei in these cultures. After 15 DIV in standard medium immunocytochemistry revealed 427 +/- 63 OT cells and 217 +/- 27 VP cells per cultured rat hypothalamus, and 380 +/- 72 OT cells and 622 +/- 91 VP cells per cultured mouse hypothalamus. Following a 7-day adaptation period in standard culture medium containing serum, the rat slice-explants survived very well after subsequent transfer to defined, serum- free media (SFM) for an additional 8 days. The number of OT cells surviving in SFM was 612 +/- 147 OT cells per cultured rat hypothalamus. Only 0.5% of the magnocellular OT and VP neurones in the cultures appeared to express both peptides, Experiments on c-fos gene expression in these cultures showed that while only 12% of the magnocellular OT and VP neurones contained barely detectable Fos protein in their nuclei under control conditions, potassium depolarization of these cultures for 3 h produced intense c-fos expression in 87-91% of these cells. Thus, magnocellular neurones in these cultures are sufficiently stable and responsive to permit long-term physiological and gene expression studies to be done under defined media conditions. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,4D-20, Bethesda, MD 20892 USA. NR 65 TC 54 Z9 54 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD NOV PY 1998 VL 10 IS 11 BP 849 EP 861 PG 13 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 137TX UT WOS:000076933400005 PM 9831261 ER PT J AU Polymeropoulos, MH AF Polymeropoulos, MH TI Autosomal dominant Parkinson's disease SO JOURNAL OF NEUROLOGY LA English DT Article; Proceedings Paper CT 6th Symposium on the Treatment of Parkinson's Disease CY NOV 08, 1997 CL TOKYO, JAPAN ID ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; GENE; BRAIN AB Multiple factors have been hypothesized over the years to be contributory and or causative for Parkinson's disease (PD). Hereditary factors, although originally discounted, have recently emerged in the focus of PD research. The study of a large Italian family with PD using a genome scan approach led to the mapping of a PD susceptibility gene to the 4q21-q23 genomic region, where the gene for alpha-synuclein was previously mapped. Mutation analysis of the alpha-synuclein in four unrelated families with PD revealed a missense mutation segregating with the illness. alpha-Synuclein is an abundant presynaptic protein of the human brain of unknown function. It is conceivable that the mutation identified in the PD families may result in self-aggregation and or decreased degradation of the protein, leading to the development of intracytoplasmic inclusion bodies and eventually to neuronal cell death. Moreover, the discovery of a mutation in the synuclein gene may offer us new insights into the understanding of the pathways that lead to neuronal degeneration. C1 Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. RP Polymeropoulos, MH (reprint author), Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bldg 49,Room 4A66, Bethesda, MD 20892 USA. NR 19 TC 5 Z9 5 U1 0 U2 1 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD NOV PY 1998 VL 245 SU 3 BP P1 EP P3 DI 10.1007/PL00007740 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 129AL UT WOS:000076440900001 PM 9808333 ER PT J AU Litvan, I Cummings, JL Mega, M AF Litvan, I Cummings, JL Mega, M TI Neuropsychiatric features of corticobasal degeneration SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE corticobasal degeneration; progressive supranuclear palsy; neurobehaviour ID PROGRESSIVE SUPRANUCLEAR PALSY; BASAL GANGLIONIC DEGENERATION; ADVANCED PARKINSONS-DISEASE; NURSING-HOME PLACEMENT; PSYCHIATRIC-SYMPTOMS; ALZHEIMERS-DISEASE; PICKS-DISEASE; FRONTAL-LOBE; DEPRESSION; HYPOMETABOLISM AB Objective-To characterise the neuropsychiatric symptoms of patients with corticobasal degeneration (CBD). Methods-The neuropsychiatric inventory (NPI), a tool with established validity and reliability, was administered to 15 patients with CBD (mean (SEM), age 67.9 (2) years); 34 patients with progressive supranuclear palsy (PSP) (66.6 (1.2) years); and 25 controls (70 (0.8) years), matched for age and education. Both patient groups had similar duration of symptoms and mini mental state examination scores. Semantic fluency and motor impairment were also assessed. Results-Patients with CBD exhibited depression (73%), apathy (40%), irritability (20%), and agitation (20%) but less often had anxiety, disinhibition, delusions, or aberrant motor behaviour (for example, pacing). The depression and irritability of patients with CBD were more frequent and severe than those of patients with PSP. Conversely, patients with PSP exhibited significantly more apathy than patients with CBD. The presence of high depression and irritability and low apathy scale scores correctly differentiated the patients with CBD 88% of the time. The irritability of patients with CBD was significantly associated with disinhibition (r = 0.85) and apathy (r = 0.72). In CBD, apathy was associated with disinhibition (r = 0.67); disinhibition was associated with aberrant motor behaviour (r = 0.68) and apathy (r = 0.67); and aberrant motor behaviour with delusions (r = 1.0). On the other hand, depression was not associated with any other behaviour, suggesting that it has a different pathophysiological mechanism. Symptom duration was associated with total motor scores (r = 0.69). However, total motor score was not associated with any behaviour or cognitive scores. Conclusions-The findings indicate that frontosubcortical pathways mediating cognition, emotion, and motor function in CBD are not affected in parallel. Patients with CBD and PSP have overlapping neuropsychiatric manifestations, but they express distinctive symptom profiles. Evaluating the behavioural abnormalities of parkinsonian patients may help clarify the role of the basal ganglia in behaviour. C1 NINDS, Neuropharmacol Unit, Def & Vet Head Injury Program, Jackson Fdn,NIH, Bethesda, MD 20892 USA. NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Litvan, I (reprint author), NINDS, Neuropharmacol Unit, Def & Vet Head Injury Program, Jackson Fdn,NIH, Fed Bldg,Room 714, Bethesda, MD 20892 USA. OI Litvan, Irene/0000-0002-3485-3445 FU NIA NIH HHS [AG 01023] NR 40 TC 81 Z9 83 U1 1 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD NOV PY 1998 VL 65 IS 5 BP 717 EP 721 DI 10.1136/jnnp.65.5.717 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 133VC UT WOS:000076706400019 PM 9810944 ER PT J AU Lenz, FA Suarez, JI Metman, LV Reich, SG Karp, BI Hallett, M Rowland, LH Dougherty, PM AF Lenz, FA Suarez, JI Metman, LV Reich, SG Karp, BI Hallett, M Rowland, LH Dougherty, PM TI Pallidal activity during dystonia: somatosensory reorganisation and changes with severity SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE globus pallidus; Parkinson's disease; apomorphine; dystonia; plasticity ID BASAL GANGLIA; NEURONAL-ACTIVITY; HEMIBALLISMUS; PALLIDOTOMY; DISORDERS; MOVEMENT AB A woman with progressive, medically intractable right upper Limb dystonia underwent a pallidotomy with only transient improvement. During the procedure her dystonia became more severe as she repeatedly made a fist to command in order to provoke dystonia transiently (movement provoked dystonia). Comparisons within cells in the internal segment of the globus pallidus (Gpi) disclosed that the firing rate was the same at rest, with making a fist, and during movement provoked dystonia. However, the firing rate compared between cells decreased significantly throughout the procedure as the patient made a fist repeatedly. During the second half of the procedure the firing rate of cells in the Gpi was similar to that in hemiballismus. The proportion of cells in the GPi which responded to sensory stimulation was significantly higher in dystonia (53%) than in hemiballismus (13%). These results suggest that pallidal activity can correlate inversely with the severity of dystonia, perhaps due to activity dependent changes in neuronal function resulting from repeated voluntary movement. C1 Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Lenz, FA (reprint author), Johns Hopkins Hosp, Dept Neurosurg, Meyer Bldg 7-113,600 N Wolfe St, Baltimore, MD 21287 USA. OI Dougherty, Patrick/0000-0002-2177-2734 FU NINDS NIH HHS [P01 NS32386] NR 21 TC 111 Z9 112 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD NOV PY 1998 VL 65 IS 5 BP 767 EP 770 DI 10.1136/jnnp.65.5.767 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 133VC UT WOS:000076706400029 PM 9810954 ER PT J AU Wrathall, JR Li, W Hudson, LD AF Wrathall, JR Li, W Hudson, LD TI Myelin gene expression after experimental contusive spinal cord injury SO JOURNAL OF NEUROSCIENCE LA English DT Article DE myelin; spinal cord injury; mRNA; proteolipid protein; myelin basic protein; protein zero; myelin transcription factor 1; in situ hybridization; Western analysis; immunocytochemistry ID TRANSCRIPTION FACTOR-1 MYT1; DNA-BINDING PROTEIN; ZINC-FINGER; BASIC-PROTEIN; RAT-BRAIN; OLIGODENDROCYTES; APOPTOSIS; AXONS; CAT; REMYELINATION AB After incomplete traumatic spinal cord injury (SCI), the spared tissue exhibits abnormal myelination that is associated with reduced or blocked axonal conductance. To examine the molecular basis of the abnormal myelination, we used a standardized rat model of incomplete SCI and compared normal uninjured tissue with that after contusion injury. We evaluated expression of mRNA for myelin proteins using in situ hybridization with oligonucleotide probes to proteolipid protein (PLP), the major protein in central myelin; myelin basic protein (MBP), a major component of central myelin and a minor component of peripheral myelin; and protein zero (PO), the major structural protein of peripheral myelin, as well as myelin transcription factor 1 (MYT1). We found reduced expression of PLP and MBP chronically after SCI in the dorsal, lateral, and ventral white matter both rostral and caudal to the injury epicenter. Detailed studies of PLP at 2 months after injury indicated that the density of expressing cells was normal but mRNA per cell was reduced. In addition, PO, normally restricted to the peripheral nervous system, was expressed both at the epicenter and in lesioned areas at least 4 mm rostral and caudal to it. Thus, after SCI, abnormal myelination of residual axons may be caused, at least in part, by changes in the transcriptional regulation of genes for myelin proteins and by altered distribution of myelin-producing cells. In addition, the expression of MYT1 mRNA and protein seemed to be upregulated after SCI in a pattern suggesting the presence of undifferentiated progenitor cells in the chronically injured cord. C1 Georgetown Univ, Dept Cell Biol, Div Neurobiol, Washington, DC 20007 USA. NINDS, Lab Dev Neurogenet, Bethesda, MD 20892 USA. RP Wrathall, JR (reprint author), Georgetown Univ, Dept Cell Biol, Div Neurobiol, 3900 Reservoir Rd, Washington, DC 20007 USA. FU NINDS NIH HHS [NS35647, NS28130] NR 46 TC 85 Z9 86 U1 0 U2 5 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 NOV 1 PY 1998 VL 18 IS 21 BP 8780 EP 8793 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 132ED UT WOS:000076616600023 PM 9786985 ER PT J AU Baumann, MH Ayestas, MA Rothman, RB AF Baumann, MH Ayestas, MA Rothman, RB TI Functional consequences of central serotonin depletion produced by repeated fenfluramine administration in SO JOURNAL OF NEUROSCIENCE LA English DT Article DE fenfluramine; serotonin depletion; neuroendocrine; corticosterone; prolactin; behavior; neurotoxicity; serotonin function; rat ID BRAIN-SEROTONIN; RAT-BRAIN; 5-HYDROXYTRYPTAMINE RELEASE; EXTRACELLULAR SEROTONIN; PARA-CHLOROAMPHETAMINE; BEHAVIORAL EVIDENCE; NERVE-TERMINALS; INVIVO DIALYSIS; TIME-COURSE; IN-VIVO AB Repeated administration of D,L-fenfluramine (FEN) is known to cause prolonged depletion of forebrain serotonin (5-HT) in animals. Ironically, few studies have evaluated functional consequences of such FEN-induced 5-HT loss. In the present work, we examined neuroendocrine and behavioral responses evoked by acute FEN injection in rats that had previously received a 4 d FEN-dosing regimen known to deplete forebrain 5-HT (D,L-FEN, 20 mg/kg, s.c., b.i.d.). Rats were fitted with indwelling jugular catheters before the study to allow for repeated intravenous challenge injections and stress-free blood sampling. At 1 and 2 weeks after the 4 d dosing regimen, acute FEN (1.5 or 3.0 mg/kg, i.v.) produced dose-related elevations in plasma corticosterone and prolactin; these hormonal responses were markedly attenuated in FEN-pretreated rats. Behavioral effects of acute FEN, namely flat body posture and forepaw treading, were also blunted in FEN-pretreated rats. Interestingly, rats exposed to repealed FEN did not display overt abnormalities in hormonal or behavioral parameters under basal (i.e., unprovoked) conditions, despite dramatic decreases in postmortem tissue levels of 5-HT in numerous brain areas. Our results suggest that FEN-induced 5-HT depletion is accompanied by multiple impairments in 5-HT function. Although the clinical relevance of our data are debatable, the findings clearly show the utility of the FEN challenge test for uncovering in vivo functional deficits that might otherwise go undetected. FEN should remain an important pharmacological tool for determining the role of 5-HT neurons in mediating diverse physiological and behavioral processes. C1 NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Baumann, MH (reprint author), NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mbaumann@intra.nida.nih.gov NR 53 TC 40 Z9 39 U1 0 U2 0 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 NOV 1 PY 1998 VL 18 IS 21 BP 9069 EP 9077 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 132ED UT WOS:000076616600048 PM 9787010 ER PT J AU Oldfield, EH Doppman, JL AF Oldfield, EH Doppman, JL TI Petrosal versus cavernous sinus sampling SO JOURNAL OF NEUROSURGERY LA English DT Letter ID CORTICOTROPIN-RELEASING HORMONE; CUSHINGS-SYNDROME; DIFFERENTIAL-DIAGNOSIS; ADENOMAS C1 NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 12 TC 12 Z9 13 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 1998 VL 89 IS 5 BP 890 EP 892 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 168TE UT WOS:000078708100029 PM 9817432 ER PT J AU Clarke, SD Kim, SK AF Clarke, SD Kim, SK TI Molecular methodologies in nutrition research SO JOURNAL OF NUTRITION LA English DT Article ID EXPRESSION; RECEPTOR; GENE C1 NIH, Nutr Study Sect, Nutr & Metabol Sci Initial Review Grp, Ctr Sci Review, Bethesda, MD 20892 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. RP Kim, SK (reprint author), NIH, Nutr Study Sect, Nutr & Metabol Sci Initial Review Grp, Ctr Sci Review, 6701 Rockledge Dr, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 1998 VL 128 IS 11 BP 2036 EP 2037 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 136WA UT WOS:000076881100031 PM 9808662 ER PT J AU Cocco, P Dosemeci, M Heineman, EF AF Cocco, P Dosemeci, M Heineman, EF TI Brain cancer and occupational exposure to lead SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID SMELTER WORKERS; MORTALITY; DEATH; TUMORS; RISK; BIAS AB A recent report in the literature suggested a link between occupational exposure to lend and brain cancer. To explore the hypothesis, we applied a job-exposure matrix for lead to the occupation and industry codes given on the death certificate of 27,060 brain cancer cases and 108,240 controls who died of non-malignant diseases in 24 US states in 1984-1992, Brain cancer risk increased by probability of exposure to lend among Caucasian men and women with high-level exposure, with a significant twofold excess among Caucasian men with high probability and high level of exposure to lend (odds ratio = 2.1; 95 % confidence interval, 1.1-4.0), Risks were also elevated in the low- and medium-probability cells for African-American men with high-level exposure to lead. Trend by intensity level was statistically significant among African-American men (all probabilities combined), Although exposure assessment was based solely on the occupation and industry reported on the death certificate, these results add to other epidemiologic and experimental findings in lending some support to the hypothesis of an association between occupational exposure to lead and brain cancer risk. Analytic studies are warranted to further test this hypothesis. C1 NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. Univ Cagliari, Inst Occupat Med, Cagliari, Italy. RP Dosemeci, M (reprint author), NCI, Occupat Epidemiol Branch, 6130 Execut Blvd,EPN Room 418, Bethesda, MD 20892 USA. NR 26 TC 33 Z9 36 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD NOV PY 1998 VL 40 IS 11 BP 937 EP 942 DI 10.1097/00043764-199811000-00001 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 140AD UT WOS:000077062600001 PM 9830598 ER PT J AU Nicholas, JS Lackland, DT Dosemeci, M Mohr, LC Dunbar, JB Grosche, B Hoel, DG AF Nicholas, JS Lackland, DT Dosemeci, M Mohr, LC Dunbar, JB Grosche, B Hoel, DG TI Mortality among US commercial pilots and navigators SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID AIRLINE CABIN ATTENDANTS; RENAL-CELL CANCER; BREAST-CANCER; OCCUPATIONAL EXPOSURE; REPRODUCTIVE FACTORS; RISK; EPIDEMIOLOGY; ASSOCIATION; COHORT; TISSUE AB The airline industry may be an occupational setting with specific health risks. Two environmental agents to which flight crews are known to be exposed are cosmic radiation and magnetic fields generated by the aircraft's electrical system. Other factors to be considered are circadian disruption and conditions specific to air travel, such as noise, vibration, mild hypoxia, reduced at most have pressure, low humidity, and air quality. This study investigated mortality among US commercial pilots and navigators, using proportional mortality ratios for cancer and noncancer end points. Proportional cancer mortality ratios and mortality odds ratios were also calculated for comparison to the proportional mortality ratios for cancer causes of death, Results indicated that US pilots and navigators have experienced significantly increased mortality due to cancer of the kidney and renal pelvis, motor neuron disease, and external causes. In addition, increased mortality due to prostate cancer, brain cancer, colon cancer, and cancer of the lip, buccal cavity, and pharynx was suggested. Mortality was significantly decreased for II causes. To determine if these health outcomes are related to occupational exposures, it will be necessary to quantify each exposure separately, to study the potential synergy of effects, and to couple this information with disease data on an individual basis. C1 Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Med Univ S Carolina, Environm Hazards Assessment Program, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. NCI, Bethesda, MD 20892 USA. BFS Fed Off Radiat Protect, Oberschleissheim, Germany. RP Nicholas, JS (reprint author), Med Univ S Carolina, Dept Biometry & Epidemiol, 550 MUSC Complex,Suite 1148, Charleston, SC 29425 USA. NR 31 TC 54 Z9 55 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD NOV PY 1998 VL 40 IS 11 BP 980 EP 985 DI 10.1097/00043764-199811000-00008 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 140AD UT WOS:000077062600008 PM 9830605 ER PT J AU Longui, CA Amhold, IJP Mendonca, BB D'Osvaldo, AF Bloise, W AF Longui, CA Amhold, IJP Mendonca, BB D'Osvaldo, AF Bloise, W TI Serum inhibin levels before and after gonadotropin stimulation in cryptorchid boys under age 4 years SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE inhibin; cryptorchidism; gonadotropins; testis; biopsy ID IMMUNOREACTIVE INHIBIN; NORMAL MEN; HYPOGONADOTROPIC HYPOGONADISM; HORMONE; LIFE; FSH; TESTIS AB We evaluated eleven cryptorchid boys under four years of age to determine the usefulness of serum inhibin as a marker of seminiferous tubule dysfunction, Serum testosterone, inhibin, LH and FSH concentrations were measured by RIA before and after 6 weeks of human chorionic gonadotropin plus human menopausal gonadotropin therapy, and bilateral testicular biopsies were performed at orchiopexy, Hormonal results from the cryptorchid group were compared to those from an age-matched control group. Basal LH and testosterone levels were similar in the two groups. Cryptorchid boys had lower basal inhibin and higher FSH levels than controls. After gonadotropin treatment the inhibin/FSH ratio was lower in cryptorchid than control children, suggesting the presence of seminiferous tubule damage (p = 0.002), Normal numbers of spermatogonia were seen in 6/9 scrotal and in 1/13 cryptorchid testes. The peak of inhibin was positively correlated to the number of spermatogonia (r = 0.68; p = 0.02). We conclude that basal and stimulated inhibin concentrations, as well as basal and stimulated inhibin/FSH ratio, provide additional information on seminiferous tubule function in cryptorchid boys and can be useful to evaluate Sertoli cell function in these patients. C1 Irmandade Santa Casa Misericordia Sao Paulo, Pediat Endocrinol Unit, Sao Paulo, Brazil. Univ Sao Paulo, Hosp Clin, Div Endocrinol, BR-05508 Sao Paulo, Brazil. Assoc Apoio Crianca Defeituosa, Sao Paulo, Brazil. RP Longui, CA (reprint author), NICHD, NIH, Bld 10,Room 10N242, Bethesda, MD 20892 USA. RI Mendonca, Berenice/C-2827-2012; ARNHOLD, IVO/D-2672-2012 NR 22 TC 14 Z9 15 U1 2 U2 3 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD NOV-DEC PY 1998 VL 11 IS 6 BP 687 EP 692 PG 6 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 129WL UT WOS:000076487000002 PM 9829221 ER PT J AU Funkhouser, AW Katzman, PJ Sickel, JZ Lambert, JS AF Funkhouser, AW Katzman, PJ Sickel, JZ Lambert, JS TI CD30-positive anaplastic large cell lymphoma (ALCL) of T-cell lineage in a 14-month-old infant with perinatally acquired HIV-1 infection SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE malignancy; HIV-1 infection; CD30-positive; lymphoma; T-cell lymphoma ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 INFECTION; CHILDREN; MALIGNANCIES; PATIENT; AIDS AB Purpose: CD30-positive anaplastic large cell lymphoma (ALCL) has been described in adults with HIV-1 infection but is extremely rare in HIV-1-infected infants and children. Patient and Methods: A 14-month-old girl with congenitally acquired HIV-1 infection presented with fever and a tender, erythematous, cystic mass on the right labium majorum. The mass was biopsied. Histologic examination and immunohistochemistry were performed. Results: Histologic examination showed Touton-like giant cells resembling histiocytes and focally abundant neutrophils obscuring the lymphoid infiltrate. Immunocytochemistry revealed a CD30-positive ALCL of T-cell lineage. Conclusion: Although non-Hodgkin's lymphoma is known to be associated with HIV-1 infection in children, large cell lymphomas of T-cell lineage are extremely rare in this population. Early diagnosis should be aggressively pursued in an HIV-1-infected child who presents with a fever and cutaneous mass. C1 Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. NIAID, Infect Dis Lab, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. Univ Rochester, Strong Mem Hosp, Rochester, NY 14627 USA. Dept Pathol, Rochester, NY USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. RP Funkhouser, AW (reprint author), Univ Chicago, Dept Pediat, MC 6054,Room C638B,5841 S Maryland Ave, Chicago, IL 60637 USA. NR 18 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD NOV-DEC PY 1998 VL 20 IS 6 BP 556 EP 559 DI 10.1097/00043426-199811000-00011 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 147WV UT WOS:000077521100009 PM 9856678 ER PT J AU Infante, AJ Britton, HA DeNapoli, T Middelton, LA Lenardo, MJ Jackson, CE Wang, J Fleisher, T Straus, SE Puck, JM AF Infante, AJ Britton, HA DeNapoli, T Middelton, LA Lenardo, MJ Jackson, CE Wang, J Fleisher, T Straus, SE Puck, JM TI The clinical spectrum in a large kindred with autoimmune lymphoproliferative syndrome caused by a Fas mutation that impairs lymphocyte apoptosis SO JOURNAL OF PEDIATRICS LA English DT Article ID GENE-MUTATIONS AB Autoimmune lymphoproliferative syndrome (ALPS) is characterized by chronic, histologically benign splenomegaly and generalized lymphadenopathy, hypergammaglobulinemia, and autoantibody formation. ALPS has been attributed to defective programmed cell death of lymphocytes, most often arising as a result of mutations in the gene encoding the lymphocyte apoptosis receptor Fas/APO-I/CD95. We identified a novel mutation in the intracellular apoptosis signaling domain of Fas in 11 members of a family, individual members of which have been monitored for up to 25 years, with 1 or more features of ALPS. This study of a large number of family members carrying the same Fas defect demonstrates that ALPS is inherited in an autosomal dominant fashion but with a high degree of variability in clinical expression. Although 1 affected individual died of postsplenectomy sepsis and 1 has been treated for lymphoma, the Fas mutation in this family has been compatible with a healthy adulthood, as clinical features of ALPS have receded with increasing age. C1 Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78284 USA. Santa Rosa Childrens Hosp, Dept Pathol, San Antonio, TX USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, Bethesda, MD USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. NIAID, Immunol Lab, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Infante, AJ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pediat, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 21 TC 79 Z9 83 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 1998 VL 133 IS 5 BP 629 EP 633 DI 10.1016/S0022-3476(98)70102-7 PG 5 WC Pediatrics SC Pediatrics GA 137MZ UT WOS:000076919800009 PM 9821419 ER PT J AU Hemmer, B Pinilla, C Appel, J Pascal, J Houghten, R Martin, R AF Hemmer, B Pinilla, C Appel, J Pascal, J Houghten, R Martin, R TI The use of soluble synthetic peptide combinatorial libraries to determine antigen recognition of T cells SO JOURNAL OF PEPTIDE RESEARCH LA English DT Article DE T cells; synthetic peptide combinatorial libraries; antigen recognition; epitope mapping; T-cell receptor; positional scanning ID MYELIN BASIC-PROTEIN; INFLUENZA-VIRUS PEPTIDE; VIRAL PEPTIDES; MHC PROTEIN; LIGANDS; RECEPTOR; COMPLEX; IDENTIFICATION; EPITOPES; BINDING AB T cells identify by their T-cell receptor (TCR) short peptides in the context of major histocompatiblity complex (MHC) molecules. The interaction of the trimolecular complex composed of the TCR and MHC bound peptide was extensively studied using substitution analogs of the original peptide ligands to define those residues important for T-cell recognition in the peptide chain. This approach has led to the observation that T-cell recognition is highly flexible and that many different peptides can be recognized by an individual TCR. Others and we have recently introduced synthetic peptide combinatorial libraries (SCL) to investigate T-cell recognition. Here we review the SCL-based approaches and describe our current techniques for mapping TCR motifs for CD4+ T cells. The implications of our findings for the understanding of T-cell recognition, as well as for future applications to study T-cell responses in infectious diseases, autoimmune disorders and cancer are discussed. C1 NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Marburg, Dept Neurol, D-35039 Marburg, Germany. Torrey Pines Inst Mol Studies, San Diego, CA USA. Multiple Peptide Syst, San Diego, CA USA. RP Martin, R (reprint author), NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr DR MSC 1400, Bethesda, MD 20892 USA. NR 42 TC 23 Z9 23 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD NOV PY 1998 VL 52 IS 5 BP 338 EP 345 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 147UC UT WOS:000077515000004 PM 9894839 ER PT J AU Kokate, TG Yamaguchi, SI Pannell, LK Rajamani, U Carroll, DM Grossman, AB Rogawski, MA AF Kokate, TG Yamaguchi, SI Pannell, LK Rajamani, U Carroll, DM Grossman, AB Rogawski, MA TI Lack of anticonvulsant tolerance to the neuroactive steroid pregnanolone in mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID AMINOBUTYRIC ACID(A) RECEPTOR; PROGESTERONE METABOLITE 5-ALPHA-PREGNAN-3-ALPHA-OL-20-ONE; MAMMALIAN CORTICAL-NEURONS; DIFFERENT SEIZURE MODELS; GABA-A RECEPTOR; WITHDRAWAL CHARACTERISTICS; PHYSICAL-DEPENDENCE; BENZODIAZEPINE; COMPLEX; NEUROSTEROIDS AB GABA-potentiating neuroactive steroids such as pregnanolone have potent protective effects in the pentylenetetrazol seizure test. We sought to determine if tolerance develops to the anticonvulsant activity of pregnanolone with chronic administration. Mice were treated with two daily injections of a 2 x ED50 dose of pregnanolone (25 mg/kg, i.p.) for 7 days. On the day after the chronic treatment protocol, the dose-response relationship for protection in the pentylenetetrazol seizure test was obtained. The ED50 value after the chronic treatment protocol was not significantly different from that in naive mice (12 mg/kg), indicating that tolerance does not develop to the anticonvulsant activity of pregnanolone. In subsequent experiments, we extended the chronic treatment protocol to 14 days with three daily injections of pregnanolone (25 mg/kg, i.p.). Again, no tolerance was observed (ED50, 13 mg/kg). The anticonvulsant activity of pregnanolone was well correlated with plasma levels in both the naive and chronically (14 day) treated mice. The estimated plasma concentrations of pregnanolone representing threshold (10%) protection (125-150 ng/ml) and 50% protection (575-700 ng/ml) were similar in naive and chronically treated animals. In both chronically treated and naive animals, plasma levels of pregnanolone declined rapidly (t(1/2), 16-19 min) and there was a corresponding reduction in the anticonvulsant activity. Our results with pregnanolone suggest that tolerance does not develop to the anticonvulsant activity of neuroactive steroids as it does with other GABA potentiating drugs such as benzodiazepines, supporting the potential clinical utility of neuroactive steroids in chronic seizure therapy. C1 NINDS, NIH, Epilepsy Res Branch, Neuronal Excitabil Sect, Bethesda, MD 20892 USA. NIDDKD, Analyt Chem Lab, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, NIH, Epilepsy Res Branch, Neuronal Excitabil Sect, Bldg 10,Room 5N-250,10 Ctr Dr MSC 1408, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 32 TC 48 Z9 51 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 1998 VL 287 IS 2 BP 553 EP 558 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 138FZ UT WOS:000076962200015 PM 9808680 ER PT J AU Song, LS Sham, JSK Stern, MD Lakatta, EG Cheng, HP AF Song, LS Sham, JSK Stern, MD Lakatta, EG Cheng, HP TI Direct measurement of SR release flux by tracking 'Ca2+ spikes' in rat cardiac myocytes SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID SKELETAL-MUSCLE FIBERS; CALCIUM-RELEASE; HEART-CELLS; VENTRICULAR MYOCYTES; SARCOPLASMIC-RETICULUM; SPATIAL NONUNIFORMITIES; RYANODINE RECEPTORS; INTRACELLULAR CA2+; LOCAL-CONTROL; CONTRACTION AB 1. Ca2+ release flux across the sarcoplasmic reticulum (SR) during cardiac excitation-contraction coupling was investigated using a novel fluorescence method. Under whole-cell voltage-clamp conditions, rat ventricular myocytes were dialysed with a high concentration of EGTA (4.0 mM, 150 nM free Ca2+), to minimize the residence time of released Ca2+ in the cytoplasm, and a low-affinity, fast Ca2+ indicator, Oregon Green 488 BAPTA-5N (OG-5N; 1.0 mM, K-d approximate to 31 mu M), to optimize the detection of localized high [Ca2+] in release site microdomains. Confocal microscopy was employed to resolve intracellular [Ca2+] at high spatial and temporal resolution. 2. Analytical and numerical analyses indicated that, under conditions of high EGTA concentration, the free [Ca2+] change is the sum of two terms: one major term proportional to the SR release flux/Ca2+ influx, and the other reflecting the running integral of the released Ca2+. 3. Indeed, the OG-5N transients in EGTA-containing cells consisted of a prominent spike followed by a small pedestal. The OG-5N spike closely resembled the first derivative (d[Ca2+]/dt) of the conventional Ca2+ transient (with no EGTA), and mimicked the model-derived SR Ca2+ release function reported previously. In SR Ca2+-depleted cells, the OG-5N transient also closely followed the waveform of L-type Ca2+ current (I-Ca). Using I-Ca as a known source of Ca2+ influx, SR flux can be calibrated in vivo by a linear extrapolation of the I-Ca-elicited OG-5N signal. 4 The OG-5N image signal was localized to discrete release sites at the Z-line level of sarcomeres, indicating that the local OG-5N spike arises from 'Ca2+ spikes' at transverse (T) tubule-SR junctions (due to the imbalance between calcium ions entering the cytosol and the buffer molecules). 5. Both peak SR release flux and total amount of released Ca2+ exhibited a bell-shaped voltage dependence. The temporal pattern of SR release also varied with membrane voltage: Ca2+ release was most synchronized and produced maximal peak release flux (4.2 mM s(-1)) at 0 mV; in contrast, maximal total release occurred at -20 mV(71 versus 61 mu M at 0 mV), but the localized release signals were partially asynchronous. Since the maximal conventional [Ca2+] transient and contraction were elicited at 0 mV, it appears that not only the amount of Ca2+ released, but also the synchronization among release sites affects the whole-cell Ca2+ transient and the Ca2+-myofilament interaction. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA. RP Cheng, HP (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Song, Long-Sheng/D-5899-2012 FU NHLBI NIH HHS [HL-52652] NR 48 TC 128 Z9 133 U1 0 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 1 PY 1998 VL 512 IS 3 BP 677 EP 691 DI 10.1111/j.1469-7793.1998.677bd.x PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 142XJ UT WOS:000077225500006 PM 9769413 ER PT J AU Plisov, SU Poirot, ME Modarress, KJ Cavanaugh, AH Edwards, DP Simons, SS AF Plisov, SU Poirot, ME Modarress, KJ Cavanaugh, AH Edwards, DP Simons, SS TI Different populations of progesterone receptor-steroid complexes in binding to specific DNA sequences: Effects of salts on kinetics and specificity SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID HUMAN GLUCOCORTICOID RECEPTOR; LONG TERMINAL REPEAT; CALF THYMUS DNA; ESTROGEN-RECEPTOR; RESPONSE ELEMENT; FK506-BINDING IMMUNOPHILIN; DEOXYRIBONUCLEIC-ACID; TRANSCRIPTION FACTORS; HORMONE RECEPTORS; TARGET DNA AB We previously reported evidence for two subpopulations of several classes of steroid receptors that could be distinguished by their requirement of a low molecular weight factor (M-r=700-3000 Da) for binding to nonspecific, calf thymus DNA-cellulose [Cavanaugh, A. H. and Simons Jr., S. S., Journal of Steroid Biochemistry and Molecular Biology, 48, 433-446 (1994)]. This factor appeared to be enriched in (NH4)(2)SO4 precipitates of nuclear extracts. Using human progesterone receptors (PRs) and biologically active DNA sequences in a modified avidin/biotin-coupled DNA (ABCD) binding assay, we now report a factor-mediated increase in PR binding to specific DNA sites that was indistinguishable from that seen with nonspecific sites. The main advantages of this modified assay are that both kinetic and equilibrium binding of receptor-steroid complexes to DNA can be directly monitored in solution. The ability of either Sephadex G-50 chromatography or sodium arsenite to prevent that binding which is increased by added factor supported the existence of PR subpopulations that are independent of the acceptor DNA sequence. The factor was found, surprisingly, to be low concentrations (greater than or equal to 5 mM) of (NH4)(2)SO4, which anomalously is partially excluded from Sephadex G-10 columns, and can be mimicked by some salts but not sodium arsenite. Kinetic analyses demonstrated that the mechanism of action of salt was to accelerate the rate of binding of PR. Salt also had a much greater effect on the nonspecific binding of PR, such that the ratio of specific to nonspecific DNA binding was greatest at elevated salt concentrations (similar to 75 mM) that afforded submaximal levels of PR binding to specific DNA sites. Further analysis of the DNA-bound receptors revealed that the smaller, A-form of PR is preferentially bound to specific DNA sequences both in the presence and in the absence of various salt concentrations. Thus, the differences in DNA binding of PR +/- salt do not correlate with the preferential binding of A or B isoform. The unequal behavior of PR subpopulations and/or isoforms for binding to specific DNA sequences offers added mechanisms for selective transcriptional regulation of genes in intact cells. Published by Elsevier Science Ltd. All rights reserved. C1 NIDDK, Steroid Hormones Sect, LMCB, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. RP Simons, SS (reprint author), NIDDK, Steroid Hormones Sect, LMCB, NIH, Bethesda, MD 20892 USA. RI Poirot, Marc/K-3551-2012 OI Poirot, Marc/0000-0002-5711-6624 FU NCI NIH HHS [CA46938] NR 62 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD NOV PY 1998 VL 67 IS 3 BP 251 EP 266 DI 10.1016/S0960-0760(98)00118-6 PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 147BT UT WOS:000077468600008 PM 9879984 ER PT J AU Nedvidkova, J Haluzik, M Pacak, K Schreiber, V Starka, L AF Nedvidkova, J Haluzik, M Pacak, K Schreiber, V Starka, L TI Estrogenic effect of estradiol-sulfamate on the male rat anterior pituitary SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID ESTRONE-3-O-SULFAMATE; SULFATASE; INCREASE AB Estrogen sulfamates (ES) are used for a new treatment strategy to avoid liver-hormone and hormone-liver interactions. ES represent new synthetic steroids having an increased systemic and reduced hepatic estrogenicity when given orally [1, 2]. In the present study effects of ES and estradiol-benzoate (EB) on adenohypophyseal (AP) and serum concentrations of prolactin (PRL), luteinizing hormone (LH), and pituitary contents of cAMP and cGMP in the male rat are demonstrated. The weight gain of experimental animals treated by ES, EB or both hormones simultaneously was significantly lower compared to controls. EB but not ES significantly increased the weight of the AP. The amounts of PRL in the AP and serum were significantly increased after EB administration. ES significantly increased only AP content of PRL. EB administered simultaneously with ES exhibited an additive effect on the AP plasma concentrations of PRL. The EB or ES significantly decreased AP and serum concentrations of LH. ES given simultaneously with EB further decreased AP and serum concentrations of LH. After administration of either ES or EB, AP contents of cAMP and cGMP were significantly increased. An additive effect of these estrogens on the cGMP content was found. ES given simultaneously with EB further increased cGMP content in the AP but partially inhibited the effect of EB on the AP cAMP content. The present results demonstrate that the effects of ES on the AP content of PRL, LH, cAMP, and cGMP differ from the effects of EB. Whether this is due to lower levels of estradiol after the administration of ES secondary to its different absorption when compared to EB is unknown. Thus, our data support the concept that the ES has a lesser estrogenic effect on the AP function. (C) 1998 Published by Elsevier Science Ltd. All rights reserved. C1 Inst Endocrinol, Prague, Czech Republic. Charles Univ, Fac Med 1, Dept Med 3, Prague, Czech Republic. NICHD, Dev Endocrinol Branch, Bethesda, MD USA. NINDS, Clin Neurosci Branch, Bethesda, MD 20892 USA. RP Nedvidkova, J (reprint author), Inst Endocrinol, Prague, Czech Republic. NR 14 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD NOV PY 1998 VL 67 IS 4 BP 359 EP 362 DI 10.1016/S0960-0760(98)00129-0 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 151LT UT WOS:000077722100010 PM 9883994 ER PT J AU Beuron, F Maurizi, MR Belnap, DM Kocsis, E Booy, FP Kessel, M Steven, AC AF Beuron, F Maurizi, MR Belnap, DM Kocsis, E Booy, FP Kessel, M Steven, AC TI At sixes and sevens: Characterization of the symmetry mismatch of the ClpAP chaperone-assisted protease SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE energy-dependent proteolysis; Clp protease; symmetry; electron microscopy; three-dimensional image reconstruction ID ESCHERICHIA-COLI HOMOLOG; ATP-DEPENDENT PROTEASE; ELECTRON-MICROGRAPHS; ACTIVATED ATPASE; PROTEOLYSIS; MICROSCOPY; RESOLUTION; COMPONENT; COMPLEX; MODEL AB ClpAP, a typical energy-dependent protease, consists of a proteolytic component (ClpP) and a chaperone-like ATPase (ClpA). ClpP is composed of two apposed heptameric rings, whereas in the presence of ATP or ATP gamma S, ClpA is a single hexameric ring. Formation of ClpAP complexes involves a symmetry mismatch as sixfold ClpA stacks axially on one or both faces of sevenfold ClpP. We have analyzed these structures by cryo-electron microscopy. Our three-dimensional reconstruction of CIpA at 29-Angstrom resolution shows the monomer to be composed of two domains of similar size that, in the hexamer, form two tiers enclosing a large cavity. Cylindrical reconstruction of ClpAP reveals three compartments: the digestion chamber inside ClpP; a compartment between ClpP and ClpA; and the cavity inside ClpA. They are connected axially via narrow apertures, implying that substrate proteins should be unfolded to allow translocation into the digestion chamber. The cavity inside ClpA is structurally comparable to the "Anfinsen cage" of other chaperones and may play a role in the unfolding of substrates, A geometrical description of the symmetry mismatch was obtained by using our model of ClpA and the crystal structure of ClpP (Wang et al., 1997, Cell 91, 447-456) to identify the particular side views presented by both molecules in individual complexes. The interaction is characterized by a key pair of subunits, one of each protein. A small turn (8.6 degrees = 2 pi/42; equivalent to a 4-Angstrom shift) would transfer the key interaction to another pair of subunits. We propose that nucleotide hydrolysis results in rotation, facilitating the processive digestion of substrate proteins. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bldg 6,Room B2-34,Ctr Dr,MSC 2717, Bethesda, MD 20892 USA. EM Alasdair_Steven@nih.gov NR 50 TC 105 Z9 106 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD NOV PY 1998 VL 123 IS 3 BP 248 EP 259 DI 10.1006/jsbi.1998.4039 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 157XU UT WOS:000078087600007 PM 9878579 ER PT J CA Project Match Res Grp TI Matching alcoholism treatments to client heterogeneity: Treatment main effects and matching effects on drinking during treatment SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID SUBSTANCE-ABUSE AB Objective:This article examines client drinking and related psychosocial functioning during the course of alcoholism treatment. It focuses on (1) the main effects of the three Project MATCH treatments, (2) the prognostic value of client attributes employed in the matching hypotheses, and (3) the attribute by treatment interaction effects. Method: Clients recruited from outpatient settings (n = 952) or from aftercare settings (n = 774) were randomized to one of the following treatments: Motivational Enhancement Therapy (MET), Cognitive Behavioral Therapy (CBT) and Twelve-Step Facilitation (TSF). Alcohol consumption and psychosocial functioning during treatment were assessed at the end of the 12-week treatment phase. Results: During the treatment phase, small but statistically significant differences among treatments were found only in the outpatient arm on measures of alcohol consumption and alcohol-related negative consequences. Forty-one percent (41%) of CBT and TSF clients were abstinent or drank moderately without alcohol-related consequences, compared with 28% of MET clients. Tests of 10 a priori primary client-treatment matching hypotheses failed to find any interaction effects that had an impact on drinking throughout the treatment phase. Conclusions: In the outpatient setting there appears to be a temporary advantage to assigning individuals to CBT or TSF rather than MET. When there is a need to quickly reduce heavy drinking and alcohol-related consequences, it appears that CBT or TSF should be the treatment of choice. C1 NIAAA, Sci Commun Branch, Bethesda, MD 20892 USA. RP NIAAA, Sci Commun Branch, Willco Bldg,Suite 409,6000 Execut Blvd, Bethesda, MD 20892 USA. RI Cooney, Ned/C-5176-2014; OI Cooney, Ned/0000-0001-6698-8312; Carroll, Kathleen/0000-0003-3263-3374; Litt, Mark/0000-0002-8319-6090 NR 26 TC 0 Z9 0 U1 2 U2 4 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD NOV PY 1998 VL 59 IS 6 BP 631 EP 639 PG 9 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 131MV UT WOS:000076580600002 ER PT J AU Kumra, S AF Kumra, S TI Multidimensionally Impaired Disorder - Dr. Kumra replies SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter ID DEVELOPMENTAL DISORDER; SCHIZOPHRENIA; CHILDHOOD C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Kumra, S (reprint author), NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 1998 VL 37 IS 11 BP 1125 EP 1126 DI 10.1097/00004583-199811000-00002 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 132KN UT WOS:000076629100002 ER PT J AU Tiet, QQ Bird, HR Davies, M Hoven, C Cohen, P Jensen, PS Goodman, S AF Tiet, QQ Bird, HR Davies, M Hoven, C Cohen, P Jensen, PS Goodman, S TI Adverse life events and resilience SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE resilience; adverse life events; psychopathology; adjustment; risk factor; protective factor; resource factor; epidemiology ID ANOREXIA-NERVOSA; HIGH-RISK; CHILDREN; CHILDHOOD; FAMILY; STRESS; PSYCHOPATHOLOGY; ADOLESCENCE; COMPETENCE; DEPRESSION AB Objective: Adverse life events are well-documented risk factors of psychopathology and psychological dysfunction in children and adolescents. Youth with good adjustment despite high levels of adverse life events are considered resilient. This study identifies factors that characterize resilience. Method: Household probability samples of youth aged 9 through 17 years at four sites were used. Main and interaction effects of 11 factors were examined to assess their impact on youth adjustment. Results: Children at risk because of higher levels of adverse life events exhibited a greater degree of resilience when they had a higher IQ, better family functioning, closer parental monitoring, more adults in the household, and higher educational aspiration. The interaction between maternal psychopathology and adversity was significant, and the interaction between IQ and adversity approached significance. Conclusion: Resilient youth received more guidance and supervision by their parents and lived in higher-functioning families. Other adults in the family probably complemented the parents in providing guidance and support to the youth and in enhancing youth adjustment. Higher educational aspirations might have provided high-risk youth with a sense of direction and hope. Although IQ had no impact in youth at low risk, youth at high risk who had a higher IQ might have coped better. C1 Columbia Univ, New York State Psychiat Inst, Dept Child & Adolescent Psychiat, New York, NY 10032 USA. Emory Univ, Atlanta, GA 30322 USA. NIMH, Rockville, MD 20857 USA. RP Tiet, QQ (reprint author), Columbia Univ, New York State Psychiat Inst, Dept Child & Adolescent Psychiat, Unit 43,722 168th St, New York, NY 10032 USA. OI Hoven, Christina/0000-0003-1274-2936; Jensen, Peter/0000-0003-2387-0650 FU NIMH NIH HHS [UO1 MH46717, UO1 MH46718, UO1 MH46725] NR 42 TC 114 Z9 117 U1 5 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 1998 VL 37 IS 11 BP 1191 EP 1200 DI 10.1097/00004583-199811000-00020 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 132KN UT WOS:000076629100019 PM 9808931 ER PT J AU Cardillo, C Kilcoyne, CM Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Cannon, RO Panza, JA TI Impairment of the nitric oxide-mediated vasodilator response to mental stress in hypertensive but not in hypercholesterolemic patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ENDOTHELIUM-DEPENDENT VASODILATION; FOREARM RESISTANCE VESSELS; SYMPATHOADRENAL RESPONSES; SIGNAL-TRANSDUCTION; VASCULAR RELAXATION; FLOW; CELLS; INHIBITION; PATHWAY; HUMANS AB Objectives. This study investigated whether mental stress-induced vasodilation mediated by endothelium-derived nitric oxide (NO) is defective in conditions with endothelial dysfunction, such as hypertension and hypercholesterolemia. Background. Vascular release of NO modulates the vasodilator response to mental stress in healthy subjects. Previous studies have shown that hypertensive and hypercholesterolemic patients have impaired endothelium-dependent vasodilation to pharmacologic agents due to decreased NO activity, However, whether this abnormality also operates in response to physiologic stimuli such as mental stress has not been defined. Methods. Forearm blood flow responses (plethysmography) to mental stress were compared in 12 normal subjects, 12 hypertensive patients and 10 hypercholesterolemic patients before and during NO synthesis inhibition with N-G-monomethyl-L arginine (4 mu mol/min). Vascular responses to acetylcholine (7.5, 15 and 30 mu g/min), an endothelium-dependent vasodilator, and sodium ni troprusside (0.8, 1.6 and 3.2 mu g/min), an exogenous NO donor, were also assessed in each group. Results. During saline the vasodilator response to mental stress was significantly blunted in hypertensive (37 +/- 11%; p = 0.01) but not in hypercholesterolemic (85 +/- 21%; p = 0.78) patients compared with controls (93 +/- 15%), N-G-Monomethyl-L-arginine administration significantly blunted mental stress-induced vaso dilation in healthy subjects (p = 0.004 vs. saline) and hypercholesterolemic patients (p = 0.03 vs. saline), but not in hypertensive patients (p = 0.69 vs. saline). The vasodilator effect of the highest dose of acetylcholine was similarly blunted in hypertensive (215 +/- 44%; p = 0.02) and hypercholesterolemic (172 +/- 71%; p = 0.02) patients compared with controls (364 +/- 34), whereas the vasorelaxing response to sodium nitroprusside was similar in the three groups. Conclusions. Hypertensive but not hypercholesterolemic patients have impaired NO-dependent vasodilation during mental stress. These findings may be accounted for by different mechanisms underlying endothelial dysfunction in these two conditions and might explain an increased susceptibility of hypertensive patients to vascular damage over repeated exposure to stressful situations. (C) 1998 by the American College of Cardiology. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Panza, JA (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B-15,10 Ctr Dr, Bethesda, MD 20892 USA. NR 39 TC 34 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 1 PY 1998 VL 32 IS 5 BP 1207 EP 1213 DI 10.1016/S0735-1097(98)00391-X PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 134TN UT WOS:000076759600007 PM 9809927 ER PT J AU Haider, AW Larson, MG Benjamin, EJ Levy, D AF Haider, AW Larson, MG Benjamin, EJ Levy, D TI Increased left ventricular mass and hypertrophy are associated with increased risk for sudden death SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; CHRONIC HYPERTENSION; CARDIAC DEATH; ECHOCARDIOGRAPHIC DETERMINATION; PROGNOSTIC IMPLICATIONS; MYOCARDIAL-INFARCTION; ANATOMIC VALIDATION; HEART-DISEASE; ARRHYTHMIAS; DOGS AB Objectives. This study examined the relations of echocardiographically graphically determined left ventricular (LV) mass and hypertrophy to the risk of sudden death. Background. Echocardiographic LV hypertrophy is associated with increased risk for all-cause mortality and cardiovascular disease morbidity and mortality. However, little is known about the association of echocardiographic LV hypertrophy with sudden death. Methods. We examined the relations of LV mass and hypertrophy to the incidence of sudden death in 3,661 subjects enrolled in the Framingham Heart Study who were greater than or equal to 40 years of age. The baseline examination was performed from 1979 to 1983 and LV hypertrophy was defined as LV mass (adjusted for height) > 143 g/m in men and > 102 g/m in women. During up to 14 years of follow-up there were 60 sudden deaths. Cox models examined the relations of LV mass and LV hypertrophy to sudden death risk after adjusting for known risk factors. Results. The prevalence of LV hypertrophy was 21.5%. The risk factor-adjusted hazard ratio (HR) for sudden death was 1.45 (95% confidence interval [CI] 1.10 to 1.92, p = 0.008) for each 50-g/m increment in LV mass. For LV hypertrophy, the risk factor-adjusted IIR for sudden death was 2.16 (95% CI 1.22 to 3.81, p = 0.008), After excluding the first I years of follow-up, both increased LV mass and LV hypertrophy conferred long-term risk of sudden death (HR 1.53, 95% CI 1.01 to 2.28, p = 0.047 and IIR 3.28, 95% CI 1.58 to 6.83, p = 0.002, respectively). Conclusions. Increased LV mass and hypertrophy are associated with increased risk for sudden death after accounting for known risk factors. (C) 1998 by the American College of Cardiology. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. Boston Med Ctr, Div Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Clin Epidemiol, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. EM dan@fram.nhlbi.nih.gov OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-38038] NR 53 TC 399 Z9 417 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 1 PY 1998 VL 32 IS 5 BP 1454 EP 1459 DI 10.1016/S0735-1097(98)00407-0 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 134TN UT WOS:000076759600042 PM 9809962 ER PT J AU Slavkin, HC AF Slavkin, HC TI Diseases and disorders that open a seam between the face and the self SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material ID CHROMOSOME-TRANSLOCATION; MOBIUS-SYNDROME C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), Natl Inst Dent & Craniofacial Res, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 1998 VL 129 IS 11 BP 1608 EP 1611 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 137DC UT WOS:000076898700021 PM 9818581 ER PT J AU McDermott, MM Liu, K Guralnik, JM Mehta, S Criqui, MH Martin, GJ Greenland, P AF McDermott, MM Liu, K Guralnik, JM Mehta, S Criqui, MH Martin, GJ Greenland, P TI The ankle brachial index independently predicts walking velocity and walking endurance in peripheral arterial disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 4th International Conference on Prevention Cardiology CY JUN 29-JUL 03, 1997 CL MONTREAL, CANADA ID CARDIOVASCULAR HEALTH; PARKINSONS-DISEASE; 6-MINUTE WALK; DISABILITY; PERFORMANCE; POPULATION; MORTALITY AB OBJECTIVES: Maintaining function among older men and women is an important public health goal as the population lives longer with chronic disease. We report the relationships between lower extremity peripheral arterial disease (PAD), PAD severity, and PAD-related symptoms with walking velocity and endurance among men and women aged 55 and older. DESIGN: Across-sectional design. SETTING: An academic medical center. PARTICIPANTS: Participants with PAD were men and women aged 55 and older identified from a blood flow laboratory or a general medicine practice (n = 158). Randomly selected controls without PAD were identified from the general medicine practice (n = 70). MEASUREMENTS: PAD was diagnosed and quantified using the ankle brachial index (ABI). Subjects were categorized according to whether they had severe PAD (ABI < 0.40), mild to moderate PAD (ABI 0.40 to < 0.90), or no PAD (ABI 0.90 to < 1.50). Walking endurance was assessed with the 6-minute walk. Usual walking velocity and maximal walking velocity were assessed with "usual" and "maximal" paced 4-meter walks, respectively. RESULTS: Average distances achieved in the 6-minute walk were 1569 +/- 390 feet for subjects with ABT 0.90-1.50, 1192 +/- 368 feet for subjects with ABI 0.40 to < 0.90, and 942 +/- 334 feet for subjects with ABI < 0.40 (trend P value < .001). Walking velocities for both the usual and maximal paced 4-meter walks were slowest among subjects with ABI < 0.40 and fastest among subjects with ABI 0.90 to < 1.50. Subjects with PAD who had pain at rest had slower walking velocity and poorer walking endurance than other subjects with PAD. In multiple linear regression analyses that included subjects with PAD only, ABI level was an independent predictor of 6-minute walk performance (regression coefficient = 159 ft/0.40 ABI units, P = .011), usual paced 4-meter walk (regression coefficient = .095 meters/sec/0.40 ABI units, P = .031), and maximal paced 4-meter walk (regression coefficient = .120 meters/sec/0.40 ABI units, P = .050) adjusting for age, sex, race, leg symptoms, and comorbid diseases known to affect functioning. Pain at rest was associated independently with the maximally paced 4-meter walk (-0.201 meters/sec, P = .024), but not with the other walks. CONCLUSION: ABI level has a measurable and independent association with walking endurance and both usual and maximal walking velocity. These data suggest that PAD may impair lower extremity function by diminishing function of both Type I ("slow twitch") and Type II ("fast twitch") muscle fibers. Because walking velocity has important prognostic implications for functioning, these data also suggest that ABI may be used to identify patients at increased risk of mobility loss. C1 Northwestern Univ, Sch Med, Div Gen Internal Med, Dept Med, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. RP McDermott, MM (reprint author), Northwestern Univ, Sch Med, Div Gen Internal Med, Dept Med, 303 E Ohio St,Suite 300, Chicago, IL 60611 USA. FU NCRR NIH HHS [RR-00048] NR 28 TC 62 Z9 63 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 1998 VL 46 IS 11 BP 1355 EP 1362 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 135CZ UT WOS:000076784000004 PM 9809756 ER PT J AU Kayser-Jones, J Schell, ES Porter, C Barbaccia, JC Steinbach, C Bird, WF Redford, M Pengilly, K AF Kayser-Jones, J Schell, ES Porter, C Barbaccia, JC Steinbach, C Bird, WF Redford, M Pengilly, K TI A prospective study of the use of liquid oral dietary supplements in nursing homes SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID NUTRITIONAL-STATUS; ALZHEIMERS-DISEASE; ELDERLY PATIENTS; OLDER PERSONS; WEIGHT-LOSS; MALNUTRITION; UNDERNUTRITION; CONSEQUENCES; RESIDENTS; CARE AB OBJECTIVE: To investigate the use of liquid oral dietary supplements among nursing home residents who were eating poorly and losing weight. DESIGN: A prospective, descriptive, anthropological study. SETTING: Two proprietary nursing homes with 105 and 138 beds. PARTICIPANTS: Purposive sampling was used to select 40 residents from among the 100 residents who were not eating well. Dietary data were collected on this sub-sample of 40 residents. MEASUREMENTS: Participant observation, in-depth interviews, event analysis, bedside dysphagia screenings, oral health ex-aminations, body weight, body mass index (BMI), and chart review were used to collect data. Dietary data were collected over a 3-day period, and data were gathered on how supplements were ordered, served, and consumed. RESULTS: Supplements had been ordered for 29 of the subsample of 40 residents. Only nine of 29 residents were served the correct number and type of supplements as ordered by their physicians, and only two residents consumed the full amount of supplement as ordered. The overall mean percentage of supplement consumed compared with that ordered was 55.1%. Although supplements were ordered primarily to prevent weight loss and to facilitate weight gain, nearly half (n = 14) of the residents continued to lose weight. Supplements were ordered without investigating the underlying factors contributing to weight loss, such as inadequate staffing and lack of supervision at mealtime, undiagnosed dysphagia, and poor oral health. Without evaluation of these factors, it is unknown which residents might benefit from oral supplements. CONCLUSION: Findings indicate that supplements were used nonspecifically as an intervention for weight loss in nursing home residents without regard to dose, diagnosis and management of underlying problem(s), amount of supplement consumed, and outcome. Further research is needed to establish when supplements should be ordered, how to ensure that they will be taken, and whether they are effective. C1 Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. Univ Calif San Francisco, Med Anthropol Program, San Francisco, CA 94143 USA. Univ Calif San Francisco, Nutr Serv, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Restorat Dent & Publ Hlth & Hyg, San Francisco, CA 94143 USA. NIDR, NIH, San Francisco, CA USA. Univ Calif San Francisco, Dept Rehabil Serv, San Francisco, CA 94143 USA. RP Kayser-Jones, J (reprint author), Univ Calif San Francisco, Dept Physiol Nursing, Box 0610, San Francisco, CA 94143 USA. FU NIA NIH HHS [AG10131-03]; NIMHD NIH HHS [2262-MD338998-1] NR 41 TC 68 Z9 70 U1 5 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 1998 VL 46 IS 11 BP 1378 EP 1386 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 135CZ UT WOS:000076784000007 PM 9809759 ER PT J AU Wood, FB Cid, VH Siegel, ER AF Wood, FB Cid, VH Siegel, ER TI Evaluating Internet end-to-end performance: Overview of test methodology and results SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article AB Objective: An evaluation of Internet end-to-end performance was conducted for the purpose of better understanding the overall performance of Internet pathways typical of those used to access information in National Library of Medicine (NLM) databases and, by extension, other Internet-based biomedical information resources. Design: The evaluation used a three-level test strategy: 1) user testing to collect empirical data on Internet performance as perceived by users when accessing NLM Web-based databases, 2) technical testing to analyze the Internet paths between the NLM and the user's desktop computer terminal, and 3) technical testing between the NLM and the World Wide Web ("Web") server computer at the user's institution to help characterize the relative performance of Internet pathways. Measurements: Time to download the front pages of NLM Web sites and conduct standardized searches of NLM databases, data transmission capacity between NLM and remote locations (known as the bulk transfer capacity [BTC]), "ping" round-trip time as an indication of the latency of the network pathways, and the network routing of the data transmissions (number and sequencing of hops). Results: Based on 347 user tests spread over 16 locations, the median time per location to download the main NLM home page ranged from 2 to 59 seconds, and 1 to 24 seconds for the other NLM Web sites tested. The median time to conduct standardized searches and get search results ranged from 2 to 14 seconds for PubMed and 4 to 18 seconds for Internet Grateful Med. The overall problem rate was about 1 percent; that is, on the average, users experienced a problem once every 100 test measurements. The user terminal tests at five locations and Web host tests at 13 locations provided profiles of ETC, RTT, and network routing for both dial-up and fixed Internet connections. Conclusion: The evaluation framework provided a profile of typical Internet performance and insights into network performance and time-of-day/day-of-week variability. This profile should serve as a frame of reference to help identify and diagnose connectivity problems and should contribute to the evolving concept of Internet quality of service. C1 Natl Lib Med, Off Hlth Informat Programs Dev, Bethesda, MD 20894 USA. RP Wood, FB (reprint author), Natl Lib Med, Off Hlth Informat Programs Dev, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 17 TC 13 Z9 13 U1 0 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 1998 VL 5 IS 6 BP 528 EP 545 PG 18 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 138PP UT WOS:000076981700005 PM 9824800 ER PT J AU DeGnore, JP Qin, J AF DeGnore, JP Qin, J TI Fragmentation of phosphopeptides in an ion trap mass spectrometer SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID HEAVY-CHAIN KINASE; PHOSPHORYLATION SITES; SELECTIVE DETECTION; CATALYTIC DOMAIN; COMPLEX-MIXTURES; IDENTIFICATION; PEPTIDES; CHROMATOGRAPHY; PROTEIN AB A systematic study of the fragmentation pattern of phosphopeptides in an electrospray (ESI) ion trap mass spectrometer is presented. We show that phosphotyrosine- and phosphothreonine-containing peptides show complicated fragmentation patterns. These phosphopeptides were observed to lose the phosphate moiety in the form of H3PO4 and/or HPO3, but were also detected with no loss of the phosphate group. The tendency to lose the phosphate moiety depends strongly on the charge state. Thus, the highest observed charge state tends to retain the phosphate moiety with extensive fragmentation along the peptide backbone. We also show that phosphoserine-containing peptides have relatively simple fragmentation patterns of losing H3PO4. This loss is independent of the charge state. We suggest strategies for the accurate identification of phosphorylation sites using the ion trap mass spectrometer. (J Am Soc Mass Spectrom 1998, 9, 1175-1188) (C) 1998 American Society for Mass Spectrometry. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Qin, J (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10,Rm 7N307,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 207 Z9 215 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD NOV PY 1998 VL 9 IS 11 BP 1175 EP 1188 DI 10.1016/S1044-0305(98)00088-9 PG 14 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 129XR UT WOS:000076489800008 PM 9794085 ER PT J AU Ishii, M Jones, M Shiota, T Yamada, I Sinclair, B Heinrich, RS Yoganathan, AP Sahn, DJ AF Ishii, M Jones, M Shiota, T Yamada, I Sinclair, B Heinrich, RS Yoganathan, AP Sahn, DJ TI Temporal variability of vena contracta and jet areas with color Doppler in aortic regurgitation: A chronic animal model study SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID FLOW MAPPING PREDICTS; MITRAL REGURGITATION; ORIFICE AREA; SEVERITY; ECHOCARDIOGRAPHY; INSUFFICIENCY; QUANTITATION; INVITRO; VOLUME; SYSTEM AB Objective. The purpose of our study was to determine the temporal variability of regurgitant color Doppler jet areas and the width of the color Doppler imaged vena contracta for evaluating the severity of aortic regurgitation. Methods. Twenty-nine hemodynamically different states were obtained pharmacologically in 8 sheep 20 weeks after surgery to produce aortic regurgitation. Aortic regurgitation was quantified by peak and mean regurgitant flow rates, regurgitant stroke volumes, and regurgitant fractions determined using pulmonary and aortic electromagnetic flow probes and meters balanced against each other. The regurgitant jet areas and the widths of color Doppler imaged. vena contracta were measured at 4 different times during diastole to determine the temporal variability of this parameter Results. Wizen measured at 4 different temporal points ill diastole, a significant change was observed in the size of the color Doppler imaged regurgitant jet (percent of difference: from 31.1% to 904%; 233% +/- 245%). Simple Linear regression analysis between each color jet area at 4 different periods in diastole and how meter-based severity of the aortic regurgitation showed only weak correlation (0.23 < r < 0.49). In contrast, for most conditions only a slight change was observed in the width of the color Doppler Imaged vena contracta during the diastolic regurgitant period (percent of difference, vena contracts: from 2.4% to 12.9%, 5.8% +/- 3.2%). In addition, for each period the width of the color Doppler imaged vena contracta at the 4 different time periods In diastole correlated quite strongly with volumetric measures of the severity of aortic regurgitation (0.81 < r < 0.90) and with the instantaneous flow rate for the corresponding period (0.85 < r < 0.87). Conclusions. Color Doppler imaged vena contracta may provide a simple, practical, and accurate method for quantifying aortic regurgitation, even when using a single frame color Doppler how mapping image. C1 Oregon Hlth Sci Univ, Clin Care Ctr Congenital Heart Dis, Portland, OR 97201 USA. Georgia Inst Technol, Atlanta, GA 30332 USA. NHLBI, Bethesda, MD 20892 USA. RP Sahn, DJ (reprint author), Oregon Hlth Sci Univ, Clin Care Ctr Congenital Heart Dis, 3181 SW Sam Jackson Pk Rd,UHN 60, Portland, OR 97201 USA. FU NHLBI NIH HHS [HL43287] NR 30 TC 6 Z9 6 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD NOV PY 1998 VL 11 IS 11 BP 1064 EP 1071 DI 10.1016/S0894-7317(98)70158-0 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 139PV UT WOS:000077038900010 PM 9812100 ER PT J AU Lenz, O Striker, LJ Jacot, TA Elliot, SJ Killen, PD Striker, GE AF Lenz, O Striker, LJ Jacot, TA Elliot, SJ Killen, PD Striker, GE TI Glomerular endothelial cells synthesize collagens but little gelatinase A and B SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GROWTH-FACTOR-BETA; MESANGIAL CELLS; EXTRACELLULAR-MATRIX; EPITHELIAL-CELLS; IV COLLAGEN; TRANSFORMING GROWTH-FACTOR-BETA-1; MESSENGER-RNA; VI COLLAGEN; CULTURE; GLOMERULOSCLEROSIS AB Mesangial sclerosis is a major feature of progressive renal disease. The mesangium contains mesangial cells and is bounded by the peripheral glomerular basement membrane and endothelial cells. Mesangial cells synthesize and degrade extracellular matrix. Whereas both mesangial and endothelial cells synthesize extracellular matrix components, the degradative pathway, well studied in the former, has not been investigated in endothelial cells. This study examines lines of all three glomerular cell types derived from female B6SJLF1/J mice, as well as mRNA levels for collagens alpha 1 (I), alpha 1 (IV), alpha 3 (IV), alpha 5 (IV), and alpha 1 (VI), laminin, tenascin, matrix metallo-proteinase-2 (MMP-2), and MMP-9. Type I and IV collagen synthesis was confirmed by enzyme-linked immunosorbent assay. MMP-2 and MMP-9 enzyme activity was measured by zymography. It was found that glomerular endothelial cells are a significant source of collagens, laminin, and tenascin. However, they express only low levels of MMP-2 and no detectable MMP-9. Stimulation with exogenous transforming growth factor-pr leads to a significant increase in collagen I, tissue inhibitors of metalloproteinase-l, and MMP-9 in conditioned media. These data suggest that glomerular endothelial cells may play an active role in extracellular matrix remodeling in glomerular disease. C1 NIDDKD, Renal Cell Biol Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. IVAX Res Inst, Miami, FL USA. RP Striker, GE (reprint author), Univ Miami, Sch Med, Dept Med, Div Nephrol,Renal Cell Biol Lab, POB 016960 R126, Miami, FL 33101 USA. RI Lenz, Oliver/M-4672-2016 OI Lenz, Oliver/0000-0003-2997-3976 NR 27 TC 34 Z9 35 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 1998 VL 9 IS 11 BP 2040 EP 2047 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 130YD UT WOS:000076547400008 PM 9808089 ER PT J AU Pass, HI Donington, JS Wu, P Rizzo, P Nishimura, M Kennedy, R Carbone, M AF Pass, HI Donington, JS Wu, P Rizzo, P Nishimura, M Kennedy, R Carbone, M TI Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 03-06, 1998 CL BOSTON, MASSACHUSETTS SP Amer Assoc Thorac Surg ID SIMIAN-VIRUS-40 AB Background: A cohort (20%) of patients with mesothelioma will not have an exposure to asbestos. Recently, a DNA tumor virus (simian virus 40) has been shown to cause hamster mesotheliomas; we previously described simian virus 40-like DNA amino terminus sequences in 29 of 48 mesotheliomas. We analyzed an additional 42 mesotheliomas to determine (1) whether our initial observations were durable and (2) the extent to which the simian virus 40 genome is present in mesotheliomas.,Methods: Genomic DNA was extracted from snap frozen mesothelioma tumor samples and from the simian virus 40-induced hamster mesothelioma tumor H9A, Polymerase chain reaction primers were used to amplify various simian virus 40 large T-antigen regions including a 105-base pair amino terminus fragment, a 281-base pair carboxyl terminus fragment, and a 310-base pair fragment of the enhancer promoter region. Endonuclease digestions and Southern blotting were used to verify the expected product, Results: Thirty of the 42 (71%) samples amplified T-antigen amino sequences, and specificity was verified by Southern hybridization. Sixteen of 42 samples (38%) amplified the appropriate size fragment for the carboxyl terminus, and digestion with BsaB1 matched that of H9A. Twenty-two of 42 samples (52%) amplified simian virus 40 regulatory sequences and Fok1 digestion matched that of the hamster control tumor. Sequence analysis (4 patients) revealed 100% homology with the regulatory region of simian virus 40 strain 776, Conclusions: These data suggest an association between the simian virus 40 virus and human mesothelioma that could be exploited for diagnostic/therapeutic options including early detection and potential vaccination strategies. C1 Karmanos Canc Inst Aerodigest Program, Detroit, MI USA. Natl Canc Inst, Thorac Oncol Sect, NIH, Bethesda, MD USA. Loyola Univ, Ctr Canc, Maywood, IL USA. Univ Oklahoma, Dept Microbiol, Oklahoma City, OK USA. RP Pass, HI (reprint author), Harper Grace Hosp, 3990 John R,Suite 2102, Detroit, MI 48201 USA. NR 14 TC 32 Z9 33 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 1998 VL 116 IS 5 BP 854 EP 858 DI 10.1016/S0022-5223(98)00438-3 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 133NU UT WOS:000076693300033 PM 9806392 ER PT J AU Demeter, LM D'Aquila, R Weislow, O Lorenzo, E Erice, A Fitzgibbon, J Shafer, R Richman, D Howard, TM Zhao, YQ Fisher, E Huang, D Mayers, D Sylvester, S Arens, M Sannerud, K Rasheed, S Johnson, V Kuritzkes, D Reichelderfer, P Japour, A AF Demeter, LM D'Aquila, R Weislow, O Lorenzo, E Erice, A Fitzgibbon, J Shafer, R Richman, D Howard, TM Zhao, YQ Fisher, E Huang, D Mayers, D Sylvester, S Arens, M Sannerud, K Rasheed, S Johnson, V Kuritzkes, D Reichelderfer, P Japour, A CA ACTG Sequencing Working Grp TI Interlaboratory concordance of DNA sequence analysis to detect reverse transcriptase mutations in HIV-1 proviral DNA SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV-1; sequence analysis; drug resistance ID HUMAN-IMMUNODEFICIENCY-VIRUS; COMBINATION THERAPY; TYPE-1 VARIANTS; RESISTANCE; ZIDOVUDINE; POLYMERASE; L-697,661; INHIBITOR; DISEASE; PCR AB Thirteen laboratories evaluated the reproducibility of sequencing methods to detect drug resistance mutations in HIV-1 reverse transcriptase (RT). Blinded, cultured peripheral blood mononuclear cell pellets were distributed to each laboratory. Each laboratory used its preferred method for sequencing proviral DNA. Differences in protocols included: DNA purification: number of PCR amplifications; PCR product purification; sequence/location of PCR/sequencing primers; sequencing template; sequencing reaction label; sequencing polymerase; and use of manual versus automated methods to resolve sequencing reaction products. Five unknowns were evaluated. Thirteen laboratories submitted 39 043 nucleotide assignments spanning codons 10-256 of HIV-I RT. A consensus nucleotide assignment (defined as agreement among greater than or equal to 75% of laboratories) could be made in over 99% of nucleotide positions, and was more frequent in the three laboratory isolates. The overall rate of discrepant nucleotide assignments was 0.29%. A consensus nucleotide assignment could not be made at RT codon 41 in the clinical isolate tested. Clonal analysis revealed that this was due to the presence of a mixture of wild-type and mutant genotypes. These observations suggest that sequencing methodologies currently in use in ACTG laboratories to sequence HIV-I RT yield highly concordant results for laboratory strains; however, more discrepancies among laboratories may occur when clinical isolates are tested. (C) 1998 Elsevier Science B.V. C1 Univ Rochester, Infect Dis Unit, Sch Med & Dent, Rochester, NY 14642 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. SRA Technol, Rockville, MD USA. Univ Miami, Miami, FL 33152 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ So Calif, Los Angeles, CA USA. Northwestern Univ, Chicago, IL 60611 USA. Rush Presbyterian St Lukes Hosp, Chicago, IL USA. Walter Reed Army Inst Res, Rockville, MD USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Alabama, Birmingham, AL USA. Univ Colorado, Denver, CO 80202 USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Hosp, Boston, MA USA. RP Demeter, LM (reprint author), Univ Rochester, Infect Dis Unit, Sch Med & Dent, 601 Elmwood Ave,Box 689, Rochester, NY 14642 USA. FU NIAID NIH HHS [AI-27659, 5UO1-AI-27658, AI-29193] NR 17 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD NOV PY 1998 VL 75 IS 1 BP 93 EP 104 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 132MT UT WOS:000076634400010 PM 9820578 ER PT J AU Mulloy, JC Kislyakova, T Cereseto, A Casareto, L LoMonico, A Fullen, J Lorenzi, MV Cara, A Nicot, C Giam, CZ Franchini, G AF Mulloy, JC Kislyakova, T Cereseto, A Casareto, L LoMonico, A Fullen, J Lorenzi, MV Cara, A Nicot, C Giam, CZ Franchini, G TI Human T-cell lymphotropic/leukemia virus type 1 Tax abrogates p53-induced cell cycle arrest and apoptosis through its CREB/ATF functional domain SO JOURNAL OF VIROLOGY LA English DT Article ID P53 TUMOR-SUPPRESSOR; WILD-TYPE P53; HUMAN PAPILLOMAVIRUS TYPE-16; HTLV-I TAX1; LEUKEMIA-VIRUS; TRANSFORMED-CELLS; P53-INDEPENDENT MECHANISMS; CONSTITUTIVE ACTIVATION; INDUCE APOPTOSIS; HUMAN RETROVIRUS AB Human T-cell lymphotropic/leukemia virus type 1 (HTLV-1) transforms human T cells in vitro, and Tax, a patent transactivator of viral and cellular genes, plays a key role in cell immortalization, Tax activity is mediated by interaction with cellular transcription factors including members of the CREB/ATF family, the NF-kappa B/c-Rel family, serum response factor, and the coactivators CREB binding protein-p300. Although p53 is usually not mutated in HTLV-1-infected T cells, its half-life is increased and its function is impaired, Here we report that transient coexpression of p53 and Tax results in the suppression of p53 transcriptional activity. Expression of Tax abrogates p53-induced G(1) arrest in the Calu-6 cell line and prevents the apoptosis induced by overexpressing p53 in the HeLa/Tat cell line. The Tax mutants M22 and G148V, which selectively activate the CREB/ATF pathway, exert these same biological effects on p53 function. In contrast, the NF-kappa B-active Tax mutant M47 has no effect on p53 activity in any of these systems. Consistent with the negative effect of Tax on p53, no activity on a p53-responsive promoter was observed upon transfection of HTLV-1-infected T-cell lines. The p53 protein is expressed at high levels in the nucleus, and nuclear extracts of HTLV-1-infected T cells bind constitutively to a DNA oligonucleotide containing the p53 response element, indicating that Tax does not interfere with p53 binding to DNA, Tax is able to suppress the transactivation function of p53 in three different cell lines, and this suppression required Tax-mediated activation of the CREB/ATF, but not the NF-kappa B/c-Rel, pathway, Tax and the active Tax mutants were able to abrogate the G(1) arrest and apoptosis induced by p53, and this effect does not correlate with an altered localization of nuclear p53 or with the disruption of p53-DNA complexes. The suppression of p53 activity by Tax could be important in T-cell immortalization induced by HTLV-1. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP Mulloy, JC (reprint author), NCI, Basic Res Lab, 37 Convent Dr,Bldg 37,Room 6A11, Bethesda, MD 20892 USA. EM jmulloy@helix.nih.gov RI Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 63 TC 135 Z9 137 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1998 VL 72 IS 11 BP 8852 EP 8860 PG 9 WC Virology SC Virology GA 127WN UT WOS:000076373700049 PM 9765430 ER PT J AU Mochizuki, H Schwartz, JP Tanaka, K Brady, RO Reiser, J AF Mochizuki, H Schwartz, JP Tanaka, K Brady, RO Reiser, J TI High-titer human immunodeficiency virus type 1-based vector systems for gene delivery into nondividing cells SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRAL VECTOR; HUMAN-LYMPHOCYTES; MURINE RETROVIRUSES; NUCLEOTIDE-SEQUENCE; LENTIVIRAL VECTOR; AIDS VIRUS; IN-VIVO; HIV; EXPRESSION; GLYCOPROTEIN AB Previously we designed novel pseudotyped high-titer replication defective human immunodeficiency virus type 1 (HIV-1) vectors to deliver genes into nondividing cells (J. Reiser, G. Harmison, S. Kluepfel-Stahl, R. O. Brady, S. Karlsson, and M. Schubert, Proc. Natl. Acad. Sci. USA 93:15266-15271, 1996). Since then we have made several improvements with respect to the safety, flexibility, and efficiency of the vector system. A three-plasmid expression system is used to generate pseudotyped HIV-1 particles by transient transfection of human embryonic kidney 293T cells with a defective packaging construct, a plasmid coding for a heterologous envelope (Env) protein, and a vector construct harboring a reporter gene such as neo, ShlacZ (encoding a phleomycin resistance/beta-galactosidase fusion protein), HSA (encoding mouse heat-stable antigen), or EGFP (encoding enhanced green fluorescent protein). The packaging constructs lack functional Vif, Vpr, and Vpu proteins and/or a large portion of the Env coding region as well as the 5' and 3' long terminal repeats, the Nef function, and the presumed packaging signal. Using G418 selection, we routinely obtained vector particles pseudotyped with the vesicular stomatitis virus G glycoprotein (VSV-G) with titers of up to 8 x 10(7) CFU/mu g of p24, provided that a functional Tat coding region was present in the vector. Vector constructs lacking a functional Tat protein yielded titers of around 4 x 10(6) to 8 x 10(6) CFU/mu g of p24. Packaging constructs with a mutation within the integrase (IN) core domain profoundly affected colony formation and expression of the reporter genes, indicating that a functional IN protein is required for efficient transduction. We explored the abilities of other Env proteins to allow formation of pseudotyped HIV-1 particles, The rabies virus and Mokola virus G proteins yielded high-titer infectious pseudotypes, while the human foamy virus Env protein did not. Using the improved vector system, we successfully transduced contact-inhibited primary human skin fibroblasts and postmitotic rat cerebellar neurons and cardiac myocytes, a process not affected by the lack of the accessory proteins. C1 NINDS, Mol & Med Genet Sect, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Mol Genet Sect, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Reiser, J (reprint author), NINDS, Mol & Med Genet Sect, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3d04,10 Ctr Dr,MSC 1260, Bethesda, MD 20892 USA. NR 65 TC 213 Z9 221 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1998 VL 72 IS 11 BP 8873 EP 8883 PG 11 WC Virology SC Virology GA 127WN UT WOS:000076373700051 PM 9765432 ER PT J AU Bowzard, JB Bennett, RP Krisina, NK Ernst, SM Rein, A Wills, JW AF Bowzard, JB Bennett, RP Krisina, NK Ernst, SM Rein, A Wills, JW TI Importance of basic residues in the nucleocapsid sequence for retrovirus Gag assembly and complementation rescue SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; PARTICLE FORMATION; MATRIX PROTEIN; VIRAL-RNA; IN-VITRO; BINDING; MYRISTYLATION; LOCALIZATION AB The Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus (HIV) contain small interaction (I) domains within their nucleocapsid (NC) sequences. These overlap the zinc finger motifs and function to provide the proper density to viral particles, There are two zinc fingers and at least two I domains within these Gag proteins. To more thoroughly characterize the important sequence features and properties of I domains, we analyzed Gag proteins that contain one or no zinc finger motifs, Chimeric proteins containing the amino-terminal half of RSV Gag and various portions of the carboxy terminus of murine leukemia virus (MLV) (containing one zinc finger) Gag had only one I domain, whereas similar chimeras with human foamy virus (HFV) (containing no zinc fingers) Gag had at least two. Mutational analysis of the MLV NC sequence and inspection of I domain sequences within the zinc-fingerless C terminus of HFV Gag suggested that clusters of basic residues, but not the zinc finger motif residues themselves, are required for the formation of particles of proper density. In support of this, a simple string of strongly basic residues was found to be able to substitute for the RSV I domains. We also explored the possibility that differences in I domains (e.g., their number) account for differences in the ability of Gag proteins to be rescued into particles when they are unable to bind to membranes. Preciously published experiments have shown that such membrane-binding mutants of RSV and HIV (two I domains) can be rescued but that those of MLV (one I domain) cannot. Complementation rescue experiments with RSV-MLV chimeras now map this difference to the NC sequence of MLV. Importantly, the same RSV-MLV chimeras could be rescued by complementation when the block to budding was after, rather than before, transport to the membrane. These results suggest that MLV Gag molecules begin to interact at a much later time after synthesis than those of RSV and HIV. C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Wills, JW (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Microbiol & Immunol, 500 Univ Dr,POB 850, Hershey, PA 17033 USA. EM jwills@psu.edu FU NCI NIH HHS [CA60395, T32 CA060395, R01 CA047482, CA47482, R37 CA047482] NR 40 TC 91 Z9 91 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1998 VL 72 IS 11 BP 9034 EP 9044 PG 11 WC Virology SC Virology GA 127WN UT WOS:000076373700067 PM 9765448 ER PT J AU Power, C McArthur, JC Nath, A Wehrly, K Mayne, M Nishio, J Langelier, T Johnson, RT Chesebro, B AF Power, C McArthur, JC Nath, A Wehrly, K Mayne, M Nishio, J Langelier, T Johnson, RT Chesebro, B TI Neuronal death induced by brain-derived human immunodeficiency virus type 1 envelope genes differs between demented and nondemented AIDS patients SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MURINE LEUKEMIA-VIRUS; MONONUCLEAR PHAGOCYTES; MACROPHAGE TROPISM; CELL TROPISM; DISEASE PROGRESSION; VIRAL DETERMINANTS; MICROGLIAL CELLS; TRANSGENIC MICE; PROTEIN GP120 AB Human immunodeficiency virus type 1 (HIV-1) infection of the brain results in viral replication primarily in macrophages and microglia. Despite frequent detection of viral genome and proteins in the brains of AIDS patients with and without HIV dementia, only 20% of AIDS patients become demented. To investigate the role of viral envelope gene variation in the occurrence of dementia, we examined regions of variability in the viral envelope gene isolated from brains of AIDS patients. Brain-derived HIV-1 V1-V2 envelope sequences from seven demented and six nondemented AIDS patients displayed significant sequence differences bt tween clinical groups, and by phylogenetic analysis, sequences from the demented group showed clustering. Infectious recombinant viruses containing brain derived V3 sequences from both clinical groups were macrophagetropic, and viruses containing brain-derived V1, V2, and V3 sequences from both clinical groups spread efficiently in macrophages. In an indirect in vitro neurotoxicity assay using supernatant fluid from HIV-1-infected macrophages, recombinant viruses from demented patients induced greater neuronal death than viruses from nondemented patients. Thus, the HIV-1 envelope diversity observed in these patient groups appeared to influence the release of neurotoxic molecules from macrophages and might account in part for the variability in occurrence of dementia in AIDS patients. C1 Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0W3, Canada. Univ Manitoba, Dept Internal Med, Winnipeg, MB R3E 0W3, Canada. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21287 USA. Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Power, C (reprint author), Univ Calgary, Dept Clin Neurosci, 107-3330 Hosp Dr, Calgary, AB T2N 4N1, Canada. EM power@ucalgary.ca RI Power, Christopher/C-7181-2013; OI Power, Christopher/0000-0002-5131-9711 FU NCRR NIH HHS [M01 RR000722]; NIAID NIH HHS [AI35042, U01 AI035042]; NINDS NIH HHS [NS26643] NR 71 TC 134 Z9 140 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1998 VL 72 IS 11 BP 9045 EP 9053 PG 9 WC Virology SC Virology GA 127WN UT WOS:000076373700068 PM 9765449 ER PT J AU Joag, SV Liu, ZQ Stephens, EB Smith, MS Kumar, A Li, Z Wang, CY Sheffer, D Jia, FL Foresman, L Adany, I Lifson, J McClure, HM Narayan, O AF Joag, SV Liu, ZQ Stephens, EB Smith, MS Kumar, A Li, Z Wang, CY Sheffer, D Jia, FL Foresman, L Adany, I Lifson, J McClure, HM Narayan, O TI Oral immunization of macaques with attenuated vaccine virus induces protection against vaginally transmitted AIDS SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; PIG-TAILED MACAQUES; CD4(+) T-CELLS; PERIPHERAL-BLOOD; RHESUS MACAQUES; VIRAL LOAD; INFECTION; HIV-1; SIVMAC AB The chimeric simian-human immunodeficiency virus SHIVKU-1, bearing the envelope of human immunodeficiency virus type 1 (HIV-1), causes fulminant infection with subtotal loss of CD4(+) T cells followed by development of AIDS in intravaginally inoculated macaques and thus provides a highly relevant model of sexually transmitted disease caused by HIV-1 in human beings. Previous studies using this SHIV model had shown that the vpu and nef genes were important in pathogenesis of the infection, and so we deleted portions of these genes to create two vaccines, Delta vpu Delta nefSHIV-4 (vaccine 1) and Delta vpuSHIV(PPc), (vaccine 2). Six adult macaques were immunized subcutaneously with vaccine I, and six were immunized orally with vaccine 2. Both viruses caused infection in all inoculated animals, but whereas vaccine 1 virus caused only a nonproductive type of infection, vaccine 2 virus replicated productively but transiently for a 6- to 10-week period. Both groups were challenged 6 to 7 months later with pathogenic SHIVKU-1 by the intravaginal route. All four unvaccinated controls developed low CD4(+) T-cell counts (<200/mu l) and AIDS. The 12 vaccinated animals all became infected with SHIVKU-1, and two in group 1 developed a persistent productive infection followed by development of AIDS in one. The other 10 have maintained almost complete control over virus replication even though spliced viral RNA was detected in lymph nodes. This suppression of virus replication correlated,vith robust antiviral cell-mediated immune responses. This is the first demonstration of protection against virulent SHIV administered by the intravaginal route. This study supports the concept that sexually transmitted HIV disease can be prevented by parenteral or oral immunization. C1 Univ Kansas, Med Ctr, Marion Merrell Dow Lab Viral Pathogenesis, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66160 USA. NCI, Frederick, MD 21702 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. RP Narayan, O (reprint author), Univ Kansas, Med Ctr, Marion Merrell Dow Lab Viral Pathogenesis, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. FU NCRR NIH HHS [R01 RR006753, RR-06753]; NIAID NIH HHS [AI-38492, AI-40372] NR 32 TC 64 Z9 64 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1998 VL 72 IS 11 BP 9069 EP 9078 PG 10 WC Virology SC Virology GA 127WN UT WOS:000076373700071 PM 9765452 ER PT J AU Steele, SJS Levin, HL AF Steele, SJS Levin, HL TI A map of interactions between the proteins of a retrotransposon SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RNASE-H-DOMAIN; REVERSE-TRANSCRIPTASE; ESCHERICHIA-COLI; HIV-1 INTEGRASE; DNA-BINDING; PREINTEGRATION COMPLEXES; RETROVIRAL INTEGRASE; 2-HYBRID SYSTEM; FUSION PROTEINS AB The yeast two-hybrid system and in vitro binding assays were used to characterize 53 potential interactions between the proteins of Tf1, an LTR-retrotransposon found in Schizosaccharomyces pombc. The Tf1 integrase (IN) protein was found to interact strongly with itself and not with other control proteins. In addition, the IN core domain interacted strongly with itself and full-length IN. Interestingly, the two-hybrid analysis detected an interaction between the RNase H domain of reverse transcriptase and IN. The biological implications of these interactions are discussed. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. RP Levin, HL (reprint author), NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. EM Henry_Levin@nih.gov NR 36 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1998 VL 72 IS 11 BP 9318 EP 9322 PG 5 WC Virology SC Virology GA 127WN UT WOS:000076373700101 PM 9765482 ER PT J AU Sylwester, AW Grivel, JC Fitzgerald, W Rossio, JL Lifson, JD Margolis, LB AF Sylwester, AW Grivel, JC Fitzgerald, W Rossio, JL Lifson, JD Margolis, LB TI CD4(+) T-lymphocyte depletion in human lymphoid tissue ex vivo is not induced by noninfectious human immunodeficiency virus type 1 virions SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-INFECTION; CELL-DEATH; APOPTOSIS; PATHOGENESIS; PROTEIN; AIDS; HISTOCULTURES; RETROVIRUSES; ENVELOPE; ANTIGEN AB We tested infectious human immunodeficiency virus type 1 (HIV-I), noninfectious but conformationally authentic inactivated whole HIV-I virions, and purified gp120 for the ability to induce depletion of CD4(+) T cells in human lymphoid tissues ex vivo, Infectious CXCR4-tropic HIV-1, but not matched inactivated virions or gp120, mediated CD4(+) T-cell depletion, consistent with mechanisms requiring productive infection. C1 SAIC Frederick, AIDS Vaccine Program, Lab Retroviral Pathogenesis, Frederick, MD 21702 USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Margolis, LB (reprint author), SAIC Frederick, AIDS Vaccine Program, Lab Retroviral Pathogenesis, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 31 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1998 VL 72 IS 11 BP 9345 EP 9347 PG 3 WC Virology SC Virology GA 127WN UT WOS:000076373700105 PM 9765486 ER PT J AU Super, HJ Brooks, D Hasenkrug, K Chesebro, B AF Super, HJ Brooks, D Hasenkrug, K Chesebro, B TI Requirement for CD4(+) T cells in the Friend murine retrovirus neutralizing antibody response: Evidence for functional T cells in genetic low-recovery mice SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-INDUCED LEUKEMIA; IMMUNE-RESPONSE; INFECTION; COMPLEX; H-2; IMMUNOSUPPRESSION; IDENTIFICATION; RESPONSIVENESS; IMMUNOTHERAPY; IMMUNIZATION AB Recovery from infection with the Friend murine leukemia retrovirus complex (FV) requires T-helper cells and cytotoxic T cells as well as neutralizing antibodies. Several host genes, including genes of the major histocompatibility complete (H-2) and an H-2-unlinked gene, Rfv-3, influence these FV-specific immune responses. (B10.A x A/Wy)F-1 mice, which have the H-2(a/a) Rfv-3(r/s) genotype, fail to mount a detectable FV-specific T-cell proliferative response but nevertheless produce FV-specific neutralizing immunoglobulin M (IgM) antibodies and can eliminate FV viremia. Thus, this IgM response, primarily influenced by the Rfv-3 gene, mag be T-cell independent. To test this idea, mice were depleted of either CD4(+) or CD8(+) T-cell populations in vivo and were monitored for the effect on the neutralizing antibody response following FV infection. Surprisingly, miff in which CD4(+) cells were depleted showed undetectable FV-neutralizing antibody responses and high viremia levels compared to nondepleted or CD8-depleted animals. In addition to knocking out the FV antibody response, CD4(+) T-cell depletion reduced survival time significantly, further indicating the importance of CD4(+) T cells. These studies revealed the first evidence for a functional T-cell response following FV infection in these low-recovery mice and showed that CD4(+) T-helper cells are required for the Rfv-3-controlled FV antibody response. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Chesebro, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 29 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1998 VL 72 IS 11 BP 9400 EP 9403 PG 4 WC Virology SC Virology GA 127WN UT WOS:000076373700116 PM 9765497 ER PT J AU Amaducci, L Maggi, S Langlois, J Minicuci, N Baldereschi, M Di Carlo, A Grigoletto, F AF Amaducci, L Maggi, S Langlois, J Minicuci, N Baldereschi, M Di Carlo, A Grigoletto, F CA Italian Longitudinal Study Aging Grp TI Education and the risk of physical disability and mortality among men and women aged 65 to 84: The Italian longitudinal study on aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID CARDIOVASCULAR-DISEASE; SOCIOECONOMIC-STATUS; INCOME; LEVEL AB Background Most studies report that people with higher education enjoy better health and longer life. Although it is well known that most risk factors are more common among individuals with a lower level of education, the underlying mechanism of this association is not fully understood. The objective of this study was to assess the association between education, disability, and mortality. Methods. We analyzed data on 1,817 men and 1,643 women, aged 65-84 years, to assess the association of educational level with physical disability and mortality adjusting for age, sex, smoking habit, occupation, and major chronic conditions. Results. The association between educational level and disability was characterized by a dose-response effect, with the relative odds significantly decreased by about 30%, 60%, and 79% in those with 4 or 5, 6 to 8, and more than 8 years of education, compared to those with 3 or less years of education. Death rates were lower among persons with 4 or more years of education compared to those with less education. However, after adjusting for disability status, education was no longer associated with mortality (RR = 0.97, CI = 0.65-1.43). Conclusions. The strong association of low education with disability found in this study may explain the inverse association with mortality reported in previous studies. Disability, indeed, seems to be the mediator between education and mortality and might be due to the higher severity level of diseases, leading to death, in the lower educated group. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD USA. RP Amaducci, L (reprint author), Univ Padua, Ist Igiene, Via Loredan 18, I-35131 Padua, Italy. RI MINICUCI, NADIA/D-5237-2016 OI MINICUCI, NADIA/0000-0002-0970-6531 NR 29 TC 30 Z9 30 U1 9 U2 9 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 1998 VL 53 IS 6 BP M484 EP M490 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 139BU UT WOS:000077008300023 PM 9823754 ER PT J AU Yang, J McCrae, RR Costa, PT AF Yang, J McCrae, RR Costa, PT TI Adult age differences in personality traits in the United States and the People's Republic of China SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article; Proceedings Paper CT Conference on Temperament and Personality Development Across the Lifespan CY OCT, 1997 CL CARBONDALE, ILLINOIS ID 5-FACTOR MODEL; QUESTIONNAIRE; WOMEN AB Life experiences for corresponding age cohorts ill the United States (US) and the People's Republic of China (PRC) have been dramatically different. If cohort effects account for cross-sectional age differences in mean levels of personality traits, different patterns of age differences should be seen in samples from the US and the PRC. The present study examined scores on scales from the California psychological Inventory (CPI; Cough, 1987) in US (N = 348, age = 19-92 years) and PRC (N = 2,093, age = 18-67 years) samples. Very similar patterns of age correlations were seen. To compare results to other cross-cultural studies, CPI scales were interpreted in terms of the Fire-Factor Model (FFM) of personality; an FFM Age-Relatedness Index based on American data accurately predicted CPI age correlations not only in the US but also in the PRC sample. Results are consistent,vith the hypothesis that there are universal intrinsic maturational changes in personality. C1 NIA, Personal Stress & Coping Sect, Intramural Res Program, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP McCrae, RR (reprint author), NIA, Personal Stress & Coping Sect, Intramural Res Program, Gerontol Res Ctr,NIH, Box 3,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 35 TC 12 Z9 12 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD NOV PY 1998 VL 53 IS 6 BP P375 EP P383 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 138UG UT WOS:000076991100006 PM 9826970 ER PT J AU Schaefer, L Hausser, H Altenburger, M Ugorcakova, J August, C Fisher, LW Schaefer, RM Kresse, H AF Schaefer, L Hausser, H Altenburger, M Ugorcakova, J August, C Fisher, LW Schaefer, RM Kresse, H TI Decorin, biglycan and their endocytosis receptor in rat renal cortex SO KIDNEY INTERNATIONAL LA English DT Article DE small proteoglycan endocytosis receptor; glomerulosclerosis; interstitial fibrosis ID GROWTH-FACTOR-BETA; DERMATAN SULFATE PROTEOGLYCAN; POLYCYSTIC KIDNEY-DISEASE; VASCULAR SMOOTH-MUSCLE; HAN-SPRD RAT; TGF-BETA; EXPERIMENTAL GLOMERULONEPHRITIS; EXTRACELLULAR-MATRIX; CORE PROTEIN; GENE-THERAPY AB Background. Among the small proteoglycans, biglycan and decorin have been proposed to be potent modulators of TGF-beta-mediated inflammatory kidney diseases. They were considered to become induced during glomerulonephritis and to subsequently inactivate the cytokine. Methods. Decorin and biglycan as well as their endocytosis receptor were investigated in normal rat renal cortex, in anti-Thy-1 glomerulonephritis, in polycystic kidneys, in the remnant kidney following 5/6-nephrectomy, and in kidneys from the Milan normotensive strain by immunohistochemistry and in situ hybridization. Northern blots were used for the detection of mRNA expression for decorin and biglycan in isolated glomeruli. Functional aspects of the endocytosis of decorin and biglycan were studied in cultured mesangial cells. Results. In the normal adult rat kidney decorin was expressed preferentially by Bowman's capsule and by interstitial connective tissue cells, but only in trace amounts by mesangial cells. In contrast, biglycan was found in tubular epithelial cells, in association with glomerular capillaries, podocytes and occasionally in the mesangium. In the tubulointerstitium of diseased kidneys (polycystic kidneys, 5/6-nephrectomy, kidneys from the Milan normotensive strain) there was a general up-regulation of decorin expression, while biglycan was localized only in distinct foci of fibrotic lesions. Glomerulosclerosis (5/6-nephrectomy, Milan normotensive strain) was associated with an increased staining for both decorin and biglycan within glomeruli. However, even in the anti-Thy-1 model of an acute mesangioproliferative glomerulonephritis where the greatest accumulation of decorin was found there was only a slight enhancement of decorin mRNA in isolated glomeruli. Decorin and biglycan become degraded upon receptor-mediated endocytosis. Immunohistochemical investigations indicated that the pattern of expression of the receptor protein correlated well with the immunolocalization of both decorin and biglycan. In vitro experiments with cultured mesangial cells provided direct evidence for the expression of the receptor and for the cell's capability to endocytose decorin as well as biglycan. Conclusions. Decorin and biglycan are characterized by a distinct expression pattern in the normal rat kidney, whereas the presence of their endocytosis receptor protein correlates with the expression of both proteoglycans. Decorin is almost completely absent in the normal mesangium. Both proteoglycans become up-regulated in various models of renal disease. The mesangial accumulation of decorin in the anti-Thy-1 glomerulonephritis that is observed in spite of the only slightly enhanced mRNA expression could result from decreased decorin turnover and/or increased mesangial retention. C1 Univ Munster, Dept Internal Med, D-4400 Munster, Germany. Univ Munster, Dept Phys Chem & Pathobiochem, D-4400 Munster, Germany. Univ Munster, Dept Pathol, D-4400 Munster, Germany. NIDR, Cranofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Schaefer, L (reprint author), Med Poliklin, Albert Schweitzer Str 33, D-48129 Munster, Germany. EM SchaefL@uni-muenster.de OI Ugorcakova, Jana/0000-0003-4019-9221 NR 44 TC 49 Z9 52 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 1998 VL 54 IS 5 BP 1529 EP 1541 DI 10.1046/j.1523-1755.1998.00149.x PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 131DB UT WOS:000076559500013 PM 9844129 ER PT J AU Schmoelzl, S Benn, SJ Laithwaite, JE Greenwood, SJ Marshall, WS Munday, NA FitzGerald, DJ LaMarre, J AF Schmoelzl, S Benn, SJ Laithwaite, JE Greenwood, SJ Marshall, WS Munday, NA FitzGerald, DJ LaMarre, J TI Expression of hepatocyte low-density lipoprotein receptor-related protein is post-transcriptionally regulated by extracellular matrix SO LABORATORY INVESTIGATION LA English DT Article ID CELL-SURFACE PROTEOGLYCANS; ACTIVATOR INHIBITOR TYPE-1; MESSENGER-RNA STABILITY; ADULT-RAT HEPATOCYTES; ALPHA-2-MACROGLOBULIN RECEPTOR; PLASMINOGEN-ACTIVATOR; PSEUDOMONAS EXOTOXIN; PRIMARY CULTURES; LIVER-REGENERATION; PLASMA-CLEARANCE AB The low-density lipoprotein receptor-related protein (LRP) is a multifunctional member of the low-density lipoprotein receptor family that has been implicated in a variety of physiologic and pathologic processes. However, little is known about LRP regulation at the molecular level, and the factors that might mediate LRP have not yet been characterized. This is particularly true of hepatocytes, an important site of LRP expression. Hepatocyte gene expression is known to be dependent on extracellular matrix composition, although the effect of extracellular matrix on lipoprotein receptor expression has not yet been investigated. Also, the mechanisms by which the extracellular matrix affects hepatocyte gene expression are not well understood. In this study, we show that hepatocyte LRP expression decreases rapidly at the mRNA, protein, and functional levels on collagen type I, but remains high on an Engelbreth-Holm-Swarm sarcoma matrix-preparation, Matrigel. LRP function was assessed with ligand binding studies and a novel cytotoxicity assay, using Pseudomonas exotoxin A. Investigation of the mechanism of LRP down-regulation revealed a two-fold longer LRP mRNA half-life in hepatocytes cultured on Matrigel relative to collagen. Taken together, these studies reveal that LRP expression in primary hepatocytes is dependent on the extracellular matrix, and that matrix-dependent differences in hepatocyte LRP mRNA expression are primarily due to changes in mRNA stability, indicating for the first time that the expression of LRP is subject to post-transcriptional regulation. C1 Univ Guelph, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP LaMarre, J (reprint author), Univ Guelph, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada. RI Schmoelzl, Sabine/E-4169-2012 OI Schmoelzl, Sabine/0000-0002-6646-8760 NR 51 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD NOV PY 1998 VL 78 IS 11 BP 1405 EP 1413 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 142EX UT WOS:000077187900007 PM 9840615 ER PT J AU Veelken, H Licht, T Lais, A Kohler, G Mertelsmann, R Schaefer, HE Lubbert, M AF Veelken, H Licht, T Lais, A Kohler, G Mertelsmann, R Schaefer, HE Lubbert, M TI Drug resistance of secondary acute myeloid leukemia with megakaryoblastic features and p190 BCR-ABL rearrangement SO LEUKEMIA RESEARCH LA English DT Article DE acute myeloid leukemia; Philadelphia chromosome; p-glycoprotein; autologous bone marrow transplantation; alkylating agents; megakaryoblast ID DIFFERENT DIAGNOSTIC METHODS; MDR1 GENE-EXPRESSION; MULTIDRUG-RESISTANCE; PHILADELPHIA-CHROMOSOME; CLINICAL-SIGNIFICANCE; P-GLYCOPROTEIN; CELLS; CHEMOTHERAPY; INDUCTION; LYMPHOMA AB A 46-year-old female presented with acute myeloid leukemia during complete remission of multiple myeloma after extensive treatment with alkylating agents. Leukemic blasts expressed CD34, platelet esterase and gp IIIa. RT-PCR analyses of peripheral blood cells detected a p190 type BCR-ABL rearrangement and high levels of MDR1. The patient expired during neutropenia shortly after induction chemotherapy. Autopsy revealed persistent blasts in the bone marrow, spleen and liver. 'Secondary' acute myeloid leukemia with megakaryoblastic features and p190-type BCR-ABL rearrangement has not previously been reported. The possibility that the combination of a BCR-ABL rearrangement with overexpression of MDR1 may have contributed to the treatment-refractory course is discussed. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Freiburg, Med Ctr, Dept Internal Med Hematol Oncol 1, D-79106 Freiburg, Germany. Univ Freiburg, Med Ctr, Dept Pathol, D-79106 Freiburg, Germany. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Lubbert, M (reprint author), Univ Freiburg, Med Ctr, Dept Internal Med Hematol Oncol 1, Hugstetter Str 55, D-79106 Freiburg, Germany. EM luebbert@mm1l.ukl.uni-freiburg.de OI Veelken, Hendrik/0000-0002-9108-3125 NR 28 TC 3 Z9 3 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD NOV PY 1998 VL 22 IS 11 BP 1021 EP 1027 DI 10.1016/S0145-2126(98)00089-7 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 124AE UT WOS:000076157500008 PM 9783805 ER PT J AU Wojnowski, L Berna, R Park, CM Handel, MA Hollander, WF Zimmer, A AF Wojnowski, L Berna, R Park, CM Handel, MA Hollander, WF Zimmer, A TI Reduced activity of BRAF protein kinase in hop and hop(hpy) mouse mutants SO MAMMALIAN GENOME LA English DT Article ID EXPRESSION C1 NIMH, Genet Lab, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. Iowa State Univ, Dept Genet, Ames, IA 50014 USA. RP Zimmer, A (reprint author), NIMH, Genet Lab, Bethesda, MD 20892 USA. RI Bernal, Ricardo/B-2124-2010; Zimmer, Andreas/B-8357-2009 NR 14 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD NOV PY 1998 VL 9 IS 11 BP 905 EP 906 DI 10.1007/s003359900893 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 132QZ UT WOS:000076642200011 PM 9799843 ER PT J AU Potter, K Butler, JJ Adams, C Fishbein, KW McFarland, EW Horton, WE Spencer, RGS AF Potter, K Butler, JJ Adams, C Fishbein, KW McFarland, EW Horton, WE Spencer, RGS TI Cartilage formation in a hollow fiber bioreactor studied by proton magnetic resonance microscopy SO MATRIX BIOLOGY LA English DT Article DE bioreactor; cartilage formation; chondrocytes; nuclear magnetic resonance ID RELAXATION; DIFFUSION; NMR; CHONDROCYTES; CONTRAST; COLLAGEN; CELLS; ACID; KNEE AB The ideal in vitro system for investigating the regulation of cartilage formation and maintenance would allow for three-dimensional tissue growth, a wide range of biochemical interventions, and non-destructive evaluation. We have developed a hollow fiber bioreactor (HFBR) system which meets these criteria. After injection with embryonic chick sternal chondrocytes, neocartilage is elaborated around the hollow fibers, reaching a thickness of up to a millimeter after four weeks of growth. This process was monitored over time with nuclear magnetic resonance (NMR) microimaging and correlative biochemical and histologic analyses. Tissue volume and cellularity increased greatly during development. This was accompanied by changes in magnetic resonance properties consistent with increased macromolecular content. Further, tissue heterogeneity, observed as regional variations in cell size in histologic sections, was also observed in quantitative NMR images. C1 NIA, Nucl Magnet Resonance Unit, NIH, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Cartilage Biol Unit, NIH, Baltimore, MD 21224 USA. Univ Calif Santa Barbara, Dept Chem Engn, Santa Barbara, CA USA. RP Spencer, RGS (reprint author), NIA, Nucl Magnet Resonance Unit, NIH, Intramural Res Program, GRC 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI McFarland, Eric/G-1763-2014; OI Adams, Christopher/0000-0003-2100-4417; Fishbein, Kenneth/0000-0002-6353-4603 NR 29 TC 43 Z9 45 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD NOV PY 1998 VL 17 IS 7 BP 513 EP 523 DI 10.1016/S0945-053X(98)90099-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 150TK UT WOS:000077681200008 PM 9881603 ER PT J AU Bhatia-Dey, N Taira, M Conti, MA Nooruddin, H Adelstein, RS AF Bhatia-Dey, N Taira, M Conti, MA Nooruddin, H Adelstein, RS TI Differential expression of non-muscle myosin heavy chain genes during Xenopus embryogenesis SO MECHANISMS OF DEVELOPMENT LA English DT Article DE non-muscle myosin; non-sarcomeric myosin; whole mount in situ hybridization; differential expression; Xenopus; non-muscle myosin heavy chain-A; non-muscle myosin heavy chain-B; animal caps; activin A ID EMBRYOS AB Class II non-muscle myosins are implicated in diverse biological processes such as cytokinesis, cellularization, cell shape changes and gastrulation. Two distinct non-muscle myosin heavy chain genes have been reported in all vertebrates: non-muscle myosin heavy chain-A (NMHC-A) and -B (NMHC-B), We report here the isolation of the Xenopus homolog of NMHC-A and present a comparative analysis of the developmental and spatial expression patterns of NMHC-A and the previously isolated NMHC-B to address the role of NMHCs in Xenopus development. A 7.5 kb NMHC-A mRNA is present, maternally in unfertilized eggs and throughout embryogenesis, as well as in all adult tissues examined. An additional 8.3 kb zygotic transcript for NMHC-A is also detected, but only during embryonic stages. Whole mount in situ hybridization with tailbud stage embryos shows that NMHC-A mRNA is predominantly expressed in the epidermis, whereas NMHC-B mRNA is expressed in the somites, brain, eyes and branchial arches, Interestingly, the expression of NMHC-B in developing somites is gradually restricted to the center of each somite as differentiation proceeds. DAPI nuclear staining demonstrated that NMHC-B mRNA is colocalized with the nuclei or perinuclear area. In animal cap experiments, treatment with activin A or ectopic expression of Xbra and an activated form of Xlim1 markedly up-regulates NMHC-B as well as muscle actin mRNAs and slightly down-regulates NMHC-A mRNA, consistent with NMHC-B expression in the semitic muscle and NMHC-A expression in the epidermis. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Adelstein, RS (reprint author), NIH, Bldg 10,Room 8N202,10 Ctr Dr MSC, Bethesda, MD 20892 USA. OI Adelstein, Robert/0000-0002-8683-2144 NR 6 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD NOV PY 1998 VL 78 IS 1-2 BP 33 EP 36 DI 10.1016/S0925-4773(98)00136-1 PG 4 WC Developmental Biology SC Developmental Biology GA 151ML UT WOS:000077724000003 PM 9858676 ER PT J AU Kim, SH Park, HC Yeo, SY Hong, SK Choi, JW Kim, CH Weinstein, BM Huh, TL AF Kim, SH Park, HC Yeo, SY Hong, SK Choi, JW Kim, CH Weinstein, BM Huh, TL TI Characterization of two frizzled8 homologues expressed in the embryonic shield and prechordal plate of zebrafish embryos SO MECHANISMS OF DEVELOPMENT LA English DT Article DE zebrafish; Frizzled (fz); wnt; shield; hypoblast; axial mesoderm; polster; prechordal plate; neurectoderm; goosecoid (gsc); pronephric duct; pax2; one-eyed pinhead (oep) ID GOOSECOID EXPRESSION; NO TAIL; GENE; PROTEIN; FAMILY; INDUCTION; WINGLESS; PRODUCT; PATHWAY; MEMBER AB We have isolated and characterized two complete cDNA clones, Zfz8a and Zfz8b, which encode zebrafish Frizzled (Fz) homologues. The predicted protein sequences, spanning 579 and 576 amino acid residues for ZFz8a and ZFz8b, respectively, were highly homologous (78%) to each other and contained an extracellular cysteine-rich domain and seven transmembrane domains that are well conserved in Fz receptor protein members. In comparison with other Fz family members, ZFz8a and ZFz8b showed the highest homology with mouse Fz8 (MFz8), sharing 84 and 76% amino acid identity, respectively. The presence of Zfz8a and Zfz8b transcripts was detected by in situ hybridization in zebrafish embryos from the 512 cell stage, and their appearance in the future dorsal region could be observed before embryos reached the 30% epiboly stage. Ar shield stage, Zfz8a transcripts were expressed in both epiblast and shield whereas expression of Zfz8b was only detected in the embryonic shield. During gastrula stages, both Zfz8a and Zfz8b transcripts were found in anterior dorsal regions of the involuting mesendoderm (future prechordal plate). By the 2- to 3-somite stage, expression of both Zfz8a and Zfz8b was restricted to the prechordal plate and prospective anterior neurectoderm, although expression of the Zfz8a gene was no longer present in the most anterior portion of the prechordal plate, the polster. In one-eyed pinhead mutant embryos, which lack prechordal plate, both Zfz8a and Zfz8b transcripts were reduced, confirming the prechordal plate specificity of Zfz8a and Zfz8b gene expression. These results provide an additional evidence supporting the role of Wnt signaling in organizer-mediated axial patterning. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Kyungpook Natl Univ, Dept Genet Engn, Taegu 702701, South Korea. Taegu Univ, Dept Nat Resources, Kyonbuk 712714, South Korea. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Huh, TL (reprint author), Kyungpook Natl Univ, Dept Genet Engn, Taegu 702701, South Korea. NR 24 TC 25 Z9 26 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD NOV PY 1998 VL 78 IS 1-2 BP 193 EP 198 DI 10.1016/S0925-4773(98)00137-3 PG 6 WC Developmental Biology SC Developmental Biology GA 151ML UT WOS:000077724000022 PM 9858730 ER PT J AU Esen, N Bahceci, E AF Esen, N Bahceci, E TI Investigation of the cell mediated immune deficiency in rats with protein energy malnutrition SO MEDICAL SCIENCE RESEARCH LA English DT Article DE protein energy malnutrition; cell mediated immunity; immune deficiency ID MONOCLONAL-ANTIBODIES; CALORIE MALNUTRITION; LYMPHOCYTES; NUTRITION; SUBPOPULATIONS; ACTIVATION; INFECTION; INDUCER; GROWTH; HOST AB Previous studies indicated that lymphoid tissues, especially the thymus, became atrophied and the proportion of sheep-erythrocyte-rosette-forming cells declined in individuals with protein energy malnutrition (PEM). Nevertheless, the mechanism of immune deficiency in malnutrition remains unclear. We hypothesized that the low proportion of rosette forming cells and dysfunction of lymphocytes may be caused by CD2 receptors that work improperly. 20 Wistar-albino rats received a diet containing 5.5% protein for 3 weeks. A control group was fed a normal diet containing 24% protein. By the end of 3 weeks there was a 18% weight loss, and serum total protein had decreased significantly, in the protein deficient group. Lymphocyte sub-populations including CD3+, CD19+, CD4+, CD8+ and CD2+ cells were investigated by immunofluorescence. Immunoglobulin G (IgG), IgM and IgA levels were measured by radial-immunodiffusion plaques. The proportion of CD3+ cells did not change while those of CD19+ and CD8+ cells increased significantly, with significant declines in CD4+ and CD2+, in peripheral blood. There was a moderate correlation (r = 0.52) between the declines in IgG and IgM levels, and that in the CD4+ cell proportion as well as the CD4/CD8 proportions. We believe that PEM causes a decrease in the number and/or function of lymphocyte subpopulations. As a result cell activation and antibody production are impaired. Med Sci Res 26:763-766 (C) 1998 Lippincott Williams & Wilkins. C1 Kocaeli Univ, Sch Med, Dept Physiol, TR-41900 Derince, Kocaeli, Turkey. NIH, Bethesda, MD 20892 USA. RP Esen, N (reprint author), Kocaeli Univ, Sch Med, Dept Physiol, TR-41900 Derince, Kocaeli, Turkey. EM nesen@superonline.com NR 30 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-8951 J9 MED SCI RES JI Med. Sci. Res. PD NOV PY 1998 VL 26 IS 11 BP 763 EP 766 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 146VW UT WOS:000077453700012 ER PT J AU Misra, R AF Misra, R TI Modern drug development from traditional medicinal plants using radioligand receptor-binding assays SO MEDICINAL RESEARCH REVIEWS LA English DT Article DE traditional medicinal plants; Ayurvedic medicines; psychotherapeutic compounds; antiaging; memory-enhancing; immunopotentiaters; radioligand receptor binding assay (RRA); Terminalia bellerica ID CHEBULAGIC ACID; PHARMACOLOGY AB Traditional medicinal plants in various countries, particularly in India have been used for centuries for various ailments; however, there has been little scientific effort to validate these anecdotal uses mentioned in the literature. A number of these traditionally used plant extracts and various "Ayurvedic medicines" that are highly valued in Ayurveda, the traditional system of medicine in India for antiaging, memory-enhancing, nerve tonic, anxiolytic, anti-inflammatory and immunopotentiation, have been screened using National Institutes of Mental Health (NIMH) Synthetic Screening Program for scientific validation and the development of new leads of psychotherapeutic compounds using Radioligand Receptor Binding Assays (RRA). Crude methanolic extracts of plants are screened using approximately 40 different in vitro RRA (primarily from rat brain homogenates) and 6 enzyme assays including acetylcholine esterase, choline acetyltransferase, and monoamine oxidase (MAO), A and B. The total crude extracts of many of these plants showed potent selectivity to various receptors, especially gamma-Amino Butyric Acid (GABA(A)), N-Methyl-D-Aspartic Acid (NMDA), and MAO receptors, which are presumed to be involved in mental disorders. The focus was on plants showing the highest displacement of GABA, cholecystokinin (CCK), NMDA, MAO, and benzodiazopines. Bioassay guided fractionation of the most active extracts resulted in pure compounds which retained the original activity of the crude extract validating the folkloric use. A bioactivity-guided fractionation of Terminalia bellerica fruit extract led to the isolation of several pure compounds which retained the original activity of the crude extract for CCK and GABA receptors, with the exception of compound B3EA-6, which exhibited high affinity for Neurokinin receptor (Substance K similar to NK-1). The absolute structure of B3EA-6 has been established by x-ray crystallography. (C) 1998 John Wiley & Sons, Inc. C1 Xechem Inc, Res Labs, New Brunswick, NJ 08901 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Misra, R (reprint author), Xechem Inc, Res Labs, 100 Jersey Ave,Bldg B,Suite 310, New Brunswick, NJ 08901 USA. NR 36 TC 12 Z9 13 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0198-6325 EI 1098-1128 J9 MED RES REV JI Med. Res. Rev. PD NOV PY 1998 VL 18 IS 6 BP 383 EP 402 DI 10.1002/(SICI)1098-1128(199811)18:6<383::AID-MED3>3.0.CO;2-A PG 20 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 135DF UT WOS:000076784800003 PM 9828039 ER PT J AU Longui, CA Vottero, A Harris, AG Chrousos, GP AF Longui, CA Vottero, A Harris, AG Chrousos, GP TI Plasma cortisol responses after intramuscular corticotropin 1-24 in healthy men SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID DEPRESSED-PATIENTS; STIMULATION TEST AB Intravenous infusion of corticotropin 1-24 (ACTH 1-24) followed by a plasma cortisol measurement after 60 minutes of less than 20 mu g/dL indicates clinically important glucocorticoid deficiency. In this study, we evaluated the morning plasma cortisol response to an intramuscular (IM) injection of ACTH 1-24 (250 mu g) in 64 healthy men. Plasma cortisol increased significantly 30 and 60 minutes after IM ACTH 1-24 (P < .0001). In most subjects, a maximal response was obtained at 60 minutes. The cortisol response correlated positively with the morning basal cortisol concentration. The lowest cortisol peak and the lowest increment observed after IM ACTH 1-24 were, respectively, 12.6 and 3.5 mu g/dL after 30 minutes and 16.3 and 5.3 mu g/dL after 60 minutes. We conclude that a plasma cortisol level less than 16.0 mu g/dL 60 minutes after IM ACTH 1-24 can be used as an index of glucocorticoid deficiency. Copyright (C) 1998 by W.B. Saunders Company. C1 NICHHD, Pediat Endocrinol Sect, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Schering Plough, Kenilworth, NJ USA. RP Longui, CA (reprint author), NICHHD, Pediat Endocrinol Sect, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. OI Harris, Alan/0000-0002-6618-2092 NR 16 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 1998 VL 47 IS 11 BP 1419 EP 1422 DI 10.1016/S0026-0495(98)90316-X PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 138WQ UT WOS:000076996700022 PM 9826224 ER PT J AU Maric, D Maric, I Barker, JL AF Maric, D Maric, I Barker, JL TI Buoyant density gradient fractionation and flow cytometric analysis of embryonic rat cortical neurons and progenitor cells SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article DE development; neocortex; Percoll; flow cytometry; oxonol; Fluo-3 ID SPINAL-CORD; SEPARATION; PROLIFERATION; CHANNELS; PERCOLL; CULTURE; GABA; DIFFERENTIATION; CENTRIFUGATION; TELENCEPHALON AB We have used the property of natural cell buoyant density to selectively fractionate embryonic rat neocortical cells into 20 subpopulations ranging in phenotype from proliferatively active progenitors to terminally postmitotic neurons. Immunocytochemical and cell cycle analysis of the cellular fractions with flow cytometry revealed an inverse relationship between cell buoyant density and neuronal differentiation. The most-buoyant fractions contained predominantly terminally postmitotic, tubulin beta III-positive, tetanus toxin-positive, and nestin-negative differentiating neurons, while immature, bromodeoxyuridine-positive and nestin-positive proliferating cells were more prevalent in less buoyant fractions. Double loading of isolated cells with voltage- and Ca2+-sensitive fluorescent indicator dyes followed by simultaneous recordings of membrane potential and cytoplasmic [Ca2+] ([Ca2+](c)]) using flow cytometry revealed that >50% of the least buoyant cells produced functional responses to veratridine, a Na+ channel agonist, and muscimol, a GABA, receptor agonist, but <10% responded to kainic acid, an agonist of a subset of glutamate receptors. As cells became more buoyant the percentage of cells that depolarized and produced a rise in [Ca2+](c) to each ligand increased, particularly in response to kainic acid. Short-term culture of select fractions revealed a marked enrichment for cells with morphologies and epitopes characteristic of neuronal and progenitor cell subpopulations. The results show that embryonic cortical cells exhibit a range of naturally occurring buoyant densities that can be used to expeditiously fractionate cortical cells according to their pre- or postmitotic status, thus providing ready access for cellular and molecular studies of proliferation and differentiation. (C) 1998 Academic Press. C1 NINCDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Maric, D (reprint author), NINCDS, Neurophysiol Lab, NIH, Bldg 36,Room 2C02,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dragan@codon.nih.gov NR 38 TC 23 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD NOV PY 1998 VL 16 IS 3 BP 247 EP + DI 10.1006/meth.1998.0682 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 165JP UT WOS:000078517900003 PM 10071064 ER PT J AU McCray, AT AF McCray, AT TI The nature of lexical knowledge SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE lexical knowledge; natural language processing; medical terminologies ID CONTROLLED MEDICAL TERMINOLOGY; REPRESENTATION AB This paper considers the nature of lexical knowledge and its role in language and information processing. The lexicon is the central component of language and plays a pivotal role in current linguistic theory [3, 4] and, increasingly, in natural language processing systems [5-7]. The lexicon embodies information about the lexical items of the language and serves as the foundation for morphologic, syntactic, and semantic processing. The differences as well as commonalities among dictionaries, thesauri, and lexicons are discussed, and distinctions between words, lexical items, and terms are drawn. Next, the scope and content of the SPECIALIST lexicon are presented, followed by a discussion of certain writing conventions that can be troublesome for text processing applications. One approach to handling orthographic and other lexical variation is discussed in a section that reports on the design and implementation of the SPECIALIST lexical programs. The paper concludes with a discussion of controlled terminologies for the medical domain. Throughout the discussion, examples are drawn from the SPECIALIST lexicon and from the other UMLS knowledge sources [8, 9]. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP McCray, AT (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM mccray@nlm.nih.gov NR 35 TC 19 Z9 19 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PD NOV PY 1998 VL 37 IS 4-5 BP 353 EP 360 PG 8 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 150QM UT WOS:000077676800007 PM 9865033 ER PT J AU Bidgood, WD AF Bidgood, WD TI The SNOMED DICOM Microglossary: Controlled terminology resource for data interchange in biomedical imaging SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE medical terminology; healthcare telecommunications; healthcare standards; specialty terminology ID STANDARD; EXTENSION AB This paper describes an authoritative, non-proprietary information resource that provides an efficient mechanism for embedding specialized clinical knowledge into the design of healthcare telecommunications systems. The resource marries two types of data interchange standards, a message/electronic-document standard and a terminology standard. In technical terms, it is part protocol and part database. Industry, academia, professional specialty societies, and the federal government participated in its development. The development of multi-specialty content has broadly engaged biomedical domain experts to an unprecedented degree in voluntary, non-proprietary message/document-standards development. The resource is the SNOMED DICOM Microglossary (SDM) [1], a message-terminology (or document-content) mapping resource. The message/electronic-document standard is DICOM (Digital Imaging and Communications in Medicine) [2], The terminology standard is SNOMED, (Systematized Nomenclature of Human and Veterinary Medicine) [3]. The SDM specifies the mapping of multi-specialty imaging terminology from SNOMED to DICOM data elements, DICOM provides semantic constraints and a framework for discourse that are lacking in SNOMED. Thus the message standard and the computer-based terminology both depend upon and complete each other. The combination is synergistic. By substitution of different templates of specialty terminology from the SDM, a generic message template, such as the DICOM Visible Light (Color Diagnostic) Image or the DICOM Structured Reporting specification can be reconfigured for diverse applications. Professional societies, with technical assistance from the College of American Pathologists, contribute and maintain their portions of the terminology, and can use SDM templates and term lists in clinical practice guidelines for the structure and content of computer-based patient records. C1 Duke Univ, Med Ctr, Ctr Outcomes Measurement, Durham, NC USA. NIH, Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20892 USA. RP Bidgood, WD (reprint author), 5 Osborne Pl, Durham, NC 27705 USA. NR 19 TC 16 Z9 18 U1 0 U2 5 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PD NOV PY 1998 VL 37 IS 4-5 BP 404 EP 414 PG 11 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 150QM UT WOS:000077676800012 PM 9865038 ER PT J AU Migone, TS Rodig, S Cacalano, NA Berg, M Schreiber, RD Leonard, WJ AF Migone, TS Rodig, S Cacalano, NA Berg, M Schreiber, RD Leonard, WJ TI Functional cooperation of the interleukin-2 receptor beta chain and Jak1 in phosphatidylinositol 3-kinase recruitment and phosphorylation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID T-CELL LINE; IL-2 RECEPTOR; PROTEIN-TYROSINE; SIGNAL-TRANSDUCTION; GAMMA CHAIN; ACTIVATION; KINASE; ASSOCIATION; BINDING; ADAPTER AB Phosphatidylinositol 3-kinase (PI 3-K) plays an important role in signaling via a wide range of receptors such as those for antigen, growth factors, and a number of cytokines, including interleukin-2 (IL-2). PI 3-K has been implicated in both IL-2-induced proliferation and prevention of apoptosis. A number of potential mechanisms for the recruitment of PI 3-K to the IL-2 receptor have been proposed. We now have found that tyrosine residues in the IL-2 receptor beta chain (IL-2R beta) are unexpectedly not required for the recruitment of the p85 component of PI 3-K. Instead, we find that Jak1, which associates with membrane proximal regions of the IL-2R beta cytoplasmic domain, is essential for efficient IL-2R beta-p85 interaction, although some IL-2R beta-p85 association can be seen in the absence of Jak1. We also found that Jak1 interacts with p85 in the absence of IL-2R beta and that IL-2R beta and Jak1 cooperate for the efficient recruitment and tyrosine phosphorylation of p85. This is the first report of a PI 3-K-Jak1 interaction, and it implicates Jak1 in an essential IL-2 signaling pathway distinct from the activation of STAT proteins. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Ctr Immunol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. DNAX Res Inst Mol & Cellular Biol Inc, Palo Alto, CA 94304 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7N252, Bethesda, MD 20892 USA. RI Schreiber, Robert/A-1276-2013 OI Schreiber, Robert/0000-0001-6311-0432 NR 39 TC 36 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1998 VL 18 IS 11 BP 6416 EP 6422 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 130GY UT WOS:000076512900024 PM 9774657 ER PT J AU Gwynn, B Lueders, K Sands, MS Birkenmeier, EH AF Gwynn, B Lueders, K Sands, MS Birkenmeier, EH TI Intracisternal A-particle element transposition into the murine beta-glucuronidase gene correlates with loss of enzyme activity: a new model for beta-glucuronidase deficiency in the C3H mouse SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MUCOPOLYSACCHARIDOSIS TYPE-VII; HERMANSKY-PUDLAK-SYNDROME; PALE EAR EP; HEMATOPOIETIC-CELLS; LEUKEMIA-CELLS; IAP INSERTION; MESSENGER-RNA; EXPRESSION; MUTATIONS; MICE AB The severity of human mucopolysaccharidosis type VII (MPS VII), or Sly syndrome, depends on the relative activity of the enzyme beta-glucuronidase. Loss of beta-glucuronidase activity can cause hydrops fetalis, with in utero or postnatal death of the patient. In this report, we show that beta-glucuronidase activity is not detectable by a standard fluorometric assay in C3H/HeOuJ (C3H) mice homozygous for a new mutation, gus(mps2J). These gus(mps2J)/gus(mps2J) mice are born and survive much longer than the previously characterized beta-glucuronidase-null B6.C-H-2(bm1)/ByBir-gus(mps) (gus(mps)/gus(mps)) mice. Northern blot analysis of liver from gus(mps2J)/gus(mps2J) mice demonstrates a 750-bp reduction in size of beta-glucuronidase mRNA, A 5.4-kb insertion in the Gus-s(h) nucleotide sequence from these mice was localized by Southern blot analysis to intron 8, The ends of the inserted sequences were cloned by inverse PCR and revealed an intracisternal A-particle (LAP) element inserted near the 3' end of the intron, The sequence of the long terminal repeat (LTR) regions of the IAP most closely matches that of a composite LTR found in transposed IAPs previously identified in the C3H strain, The inserted IAP may contribute to diminished beta-glucuronidase activity either by interfering,vith transcription or by destabilizing the message. The resulting phenotype is much less severe than that previously described in the gus(mps)/gus(mps) mouse and provides an opportunity to study MPS VII on a genetic background that clearly modulates disease severity. C1 Jackson Lab, Bar Harbor, ME 04609 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Gwynn, B (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. FU NIDDK NIH HHS [DK49525, DK53920, R01 DK041082, R01 DK049525, R01 DK41082] NR 43 TC 31 Z9 31 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1998 VL 18 IS 11 BP 6474 EP 6481 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 130GY UT WOS:000076512900030 PM 9774663 ER PT J AU Sabatino, DE Cline, AP Gallagher, PG Garrett, LJ Stamatoyannopoulos, G Forget, BG Bodine, DM AF Sabatino, DE Cline, AP Gallagher, PG Garrett, LJ Stamatoyannopoulos, G Forget, BG Bodine, DM TI Substitution of the human beta-spectrin promoter for the human (A)gamma-globin promoter prevents silencing of a linked human beta-globin gene in transgenic mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID YEAST ARTIFICIAL CHROMOSOME; LOCUS-CONTROL REGION; HUMAN GAMMA-GLOBIN; DOMINANT CONTROL REGION; SICKLE-CELL DISEASE; DEVELOPMENTAL REGULATION; ACTIVATION REGION; TARGETED DELETION; FETAL HEMOGLOBIN; EPSILON-GLOBIN AB During development, changes occur in both the sites of erythropoiesis and the globin genes expressed at each developmental stage. Previous work has shown that high-level expression of human beta-like globin genes in transgenic mice requires the presence of the locus control region (LCR), Models of hemoglobin switching propose that the LCR and/or stage-specific elements interact with globin gene sequences to activate specific genes in erythroid cells. To test these models, we generated transgenic mice which contain the human (A)gamma-globin gene linked to a 576-bp fragment containing the human beta-spectrin promoter. In these mice, the beta-spectrin (A)gamma-globin (beta sp/(A)gamma) transgene was expressed at high levels in erythroid cells throughout development. Transgenic mice containing a 40-kb cosmid construct with the micro LCR, beta sp/(A)gamma-, psi beta-, delta-, and beta-globin genes showed no developmental switching and expressed both human gamma- and beta-globin mRNAs in erythroid cells throughout development. Mice containing control cosmids with the (A)gamma-globin gene promoter showed developmental switching and expressed (A)gamma-globin mRNA in yolk sac and fetal liver erythroid cells and beta-globin mRNA in fetal liver and adult erythroid cells. Our results suggest that replacement of the gamma-globin promoter with the beta-spectrin promoter allows the expression of the beta-globin gene. We conclude that the gamma-globin promoter is necessary and sufficient to suppress the expression of the beta-globin gene in yolk sac erythroid cells. C1 NIH, Natl Human Genome Res Inst, Genet & Mol Biol Branch, Hematopoiesis Sect, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT USA. Univ Washington, Seattle, WA 98195 USA. RP Bodine, DM (reprint author), NIH, Natl Human Genome Res Inst, Genet & Mol Biol Branch, Hematopoiesis Sect, Bldg 49,Room 3A14 MSC 444, Bethesda, MD 20892 USA. NR 59 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1998 VL 18 IS 11 BP 6634 EP 6640 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 130GY UT WOS:000076512900045 PM 9774678 ER PT J AU Hoff, EF Levin, HL Boeke, JD AF Hoff, EF Levin, HL Boeke, JD TI Schizosaccharomyces pombe retrotransposon Tf2 mobilizes primarily through homologous cDNA recombination SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PRIMED REVERSE TRANSCRIPTION; RNA-POLYMERASE-III; LINKER INSERTION MUTAGENESIS; YEAST TRANSPOSON TY1; FISSION YEAST; SACCHAROMYCES-CEREVISIAE; INTEGRATIVE TRANSFORMATION; ELEMENTS; MECHANISM; GENE AB The Tf2 retrotransposon, found in the fission yeast Schizosaccharomyces pombe, is nearly identical to its sister element, Tf1, in its reverse transcriptase-RNase H and integrase domains but is very divergent in the gag domain, the protease, the 5' untranslated region, and the U3 domain of the long terminal repeats. It has now been demonstrated that a neo-marked copy of Tf2 overexpressed from a heterologous promoter can mobilize into the S. pombe genome and produce true transposition events. However, the Tf2-neo mobilization frequency is 10- to 20-fold lower than that of Tf1-neo, and 70% of the Ta-neo events are homologous recombination events generated independently of a functional Tf2 integrase. Thus, the Tf2 element is primarily dependent on homologous recombination with preexisting copies of Ta for its propagation. Finally, production of Tf2-neo proteins and cDNA was also analyzed; surprisingly, Tf2 was found to produce its reverse transcriptase as a single species in which it is fused to protease, unlike all other retroviruses and retrotransposons. C1 Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. RP Boeke, JD (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Hunterian Bldg,Rm 617,725 N Wolfe St, Baltimore, MD 21205 USA. NR 61 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1998 VL 18 IS 11 BP 6839 EP 6852 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 130GY UT WOS:000076512900064 PM 9774697 ER PT J AU Lin, JH Levin, HL AF Lin, JH Levin, HL TI Reverse transcription of a self-primed retrotransposon requires an RNA structure similar to the U5-IR stem-loop of retroviruses SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FISSION YEAST; MECHANISM; TF1; INITIATION; CONSTRUCTION; INTEGRATION; MUTATIONS; PROTEINS; COMPLEX AB An inverted repeat (IR) within the U5 region of the Rous sarcoma virus (RSV) mRNA forms a structure composed of a 7-bp stem and a 5-nucleotide (nt) loop. This U5-IR structure has been shown to be required for the initiation of reverse transcription. The mRNA of Tf1, long terminal repeat-containing retrotransposon from fission yeast (Schizosaccharomyces pombe) contains nucleotides,vith the potential to form a U5-IR stem-loop that is strikingly similar to that of RSV, The putative US-IR stem-loop of Tf1 consists of a 7-bp stem and a 25-nt loop, Results from mutagenesis studies indicate that the US-IR stem-loop in the mRNA of TM does form and that it is required for Tf1 transposition. Although the loop is required for transposition, we were surprised that the specific sequence of the nucleotides within the loop was unimportant for function. Additional investigation indicates that the loss of transposition activity due to a reduction in the loop size to 6 nt could be rescued by increasing the GC content of the stem. This result indicates that the large loop in the Tf1 mRNA relative to that of the RSV allows the formation of the relatively weak US-IR stem. The levels of Tf1 proteins expressed and the amounts of Tf1 RNA packaged into the virus-like particles were not affected by mutations in the US-IR structure. However, all of the mutations in the US-IR structure that caused defects in transposition produced low amounts of reverse transcripts. A unique feature in the initiation of Tf1 reverse transcription is that, instead of a tRNA, the first 11 nt of the Tf1 mRNA serve as the minus-strand primer, Analysis of the 5' end of TM mRNA revealed that the mutations in the U5-IR stem-loop that resulted in defects in reverse transcription caused a reduction in the cleavage activity required to generate the Tf1 primer, Our results indicate that the U5-IR stems of Tf1 and RSV are conserved in size, position, and function. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. RP NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. EM Henry_Levin@nih.gov NR 29 TC 19 Z9 20 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1998 VL 18 IS 11 BP 6859 EP 6869 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 130GY UT WOS:000076512900066 PM 9774699 ER PT J AU Bergen, AW Pratt, M Mehlman, PT Goldman, D AF Bergen, AW Pratt, M Mehlman, PT Goldman, D TI Evolution of RPS4Y SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE RPS4Y; RPS4X; hominidae; relative rates; phylogenetic reconstruction ID HUMAN SEX-CHROMOSOMES; MOUSE-X-CHROMOSOME; Y-CHROMOSOME; PSEUDOAUTOSOMAL BOUNDARY; RIBOSOMAL PROTEIN-S4; NUCLEOTIDE SUBSTITUTION; SEQUENCE ORGANIZATION; MOLECULAR EVOLUTION; TURNER SYNDROME; DNA-SEQUENCES AB Sequence variation within RPS4Y, a ribosomal protein gene located in the nonpseudoautosomal region of the Y chromosome, was used to elucidate the origin of this gene in primates. Complete coding and additional flanking sequences (949 bp) of the RPS4Y locus were determined in four nonhuman primate species. Phylogenetic reconstruction of RPS4 sequence evolution supports the monophyly of mammalian RPS4 and RPS4Y. Molecular evolutionary rate estimation reveals significantly elevated rates of DNA and protein evolution in RPS4Y compared with its X-chromosome homologs. These rates enable us to estimate the timing of the transposition of RPS4X to the Y chromosome (95% confidence interval, 32 MYA-74 MYA), and this estimate was verified by Southern hybridization analysis of prosimian and simian genomic DNA. These data support a transposition event of ancestral primate RPS4X to the Y chromosome prior to the divergence of Prosimii. C1 NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. NCI, Genet Epidemiol Branch, Div Canc Genet & Epidemiol, Rockville, MD USA. Labs Virginia Inc, Yemassee, SC USA. RP Bergen, AW (reprint author), 12420 Parklawn Dr,Pk 5 Bldg,Room 451, Rockville, MD 20852 USA. EM awb@dicbr.niaaa.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Bergen, Andrew/0000-0002-1237-7644 NR 47 TC 8 Z9 12 U1 0 U2 0 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 USA SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD NOV PY 1998 VL 15 IS 11 BP 1412 EP 1419 PG 8 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 136ZF UT WOS:000076888400005 PM 12572605 ER PT J AU Klausner, RD AF Klausner, RD TI Cancer genetics: Identifying mutations that count in a disease of genomic instability. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1 BP 1A EP 1A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700002 ER PT J AU Brown, PO Botstein, D Alizadeh, A Derisi, J Diehn, M Eisen, M Iyer, V Perou, C Pollack, J Ross, D Spellman, P Staudt, L AF Brown, PO Botstein, D Alizadeh, A Derisi, J Diehn, M Eisen, M Iyer, V Perou, C Pollack, J Ross, D Spellman, P Staudt, L TI DNA microarrays as "microscopes" for watching a genome in action SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. NCI, Bethesda, MD 20892 USA. OI Alizadeh, Arash Ash/0000-0002-5153-5625 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 7 BP 2A EP 2A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700010 ER PT J AU Wang, F Harvey, EV Hammer, JA Sellers, JR AF Wang, F Harvey, EV Hammer, JA Sellers, JR TI Expression and characterization of a myosin V-HMM like fragment SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 107 BP 19A EP 19A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700107 ER PT J AU Haddad, EK Wu, X Henkart, PA Hammer, JA AF Haddad, EK Wu, X Henkart, PA Hammer, JA TI Myosin Va is not required for efficient target cell killing by natural killer (NK) cells, cytotoxic T lymphocytes (CTL), and lymphokine-activated killer (LAK) cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, LCB, Bethesda, MD 20892 USA. NCI, EIB, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 113 BP 20A EP 20A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700113 ER PT J AU Wu, X Bowers, B Rao, K Wei, Q Hammer, JA AF Wu, X Bowers, B Rao, K Wei, Q Hammer, JA TI Visualization of melanosome dynamics within wild type and dilute melanocytes reveals a paradigm for myosin V function in vivo. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 LCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 114 BP 20A EP 20A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700116 ER PT J AU Buxton, DB Adelstein, RS AF Buxton, DB Adelstein, RS TI Partial purification of a mammalian DLGL kinase homolog SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 133 BP 23A EP 23A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700134 ER PT J AU Horowits, R Luo, G AF Horowits, R Luo, G TI Molecular interactions for N-RAP, a nebulin-related protein of striated muscle SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 144 BP 25A EP 25A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700145 ER PT J AU Galbraith, JA AF Galbraith, JA TI Substrate tension directs neurite outgrowth SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Duke Univ, Dept Mech Engn & Mat Sci, Durham, NC 27708 USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 183 BP 32A EP 32A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700183 ER PT J AU Kachar, B Belyantseva, I Frolenkov, G Riordan, G AF Kachar, B Belyantseva, I Frolenkov, G Riordan, G TI Molecular organization of the mechanism of outer hair cell electromotility. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 197 BP 35A EP 35A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700198 ER PT J AU Elmendorf, HG Nash, TE AF Elmendorf, HG Nash, TE TI The role of ankyrin repeats in cytoskeleton-associated proteins of Giardia lamblia SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 209 BP 37A EP 37A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700212 ER PT J AU Katz, BZ Zamir, E Bershadsky, A Kam, Z Yamada, KM Geiger, B AF Katz, BZ Zamir, E Bershadsky, A Kam, Z Yamada, KM Geiger, B TI Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 210 BP 37A EP 37A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700210 ER PT J AU Parry, DAD Marekov, LN Steinert, PM AF Parry, DAD Marekov, LN Steinert, PM TI Molecular parameters of type IV alpha-internexin and type IV-type III alpha-internexin-vimentin copolymer intermediate filaments. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 252 BP 44A EP 44A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700252 ER PT J AU Steinert, PM Jang, SJ Wu, K Marekov, LN Parry, DAD Prahlad, V Chou, YH Goldman, RD AF Steinert, PM Jang, SJ Wu, K Marekov, LN Parry, DAD Prahlad, V Chou, YH Goldman, RD TI Isolation of type VI nestin from BHK-21 cells: Co-assembly in vitro with type III vimentin and type IV alpha-internexin to form heterodimer coiled-coil molecules and intermediate filaments. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. Northwestern Univ, Sch Med, CMS Biol, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 251 BP 44A EP 44A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700254 ER PT J AU Wu, K Jang, SI Idler, W Marekov, LN Parry, DAD Yang, JM Steinert, PM AF Wu, K Jang, SI Idler, W Marekov, LN Parry, DAD Yang, JM Steinert, PM TI Conserved ionic pairs essential for the stabilization of coiled-coil molecules of intermediate filaments. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. Samsung Med Ctr, Dept Dermatol, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 250 BP 44A EP 44A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700251 ER PT J AU Cabral, WA Marini, JC AF Cabral, WA Marini, JC TI Osteoblasts from three OI probands permit greater intracellular survival and secretion of mutant collagen than do fibroblasts. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, HDB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 336 BP 58A EP 58A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700335 ER PT J AU Forlino, A Cabral, WA Marini, JC AF Forlino, A Cabral, WA Marini, JC TI Mutant collagen synthesis, matrix incorporation and retention by cultured fibroblasts and osteoblasts from two OI type IV probands. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, Connect Tissue Disorders Sect, NIH, Bethesda, MD USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 337 BP 58A EP 58A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700338 ER PT J AU Ikonomi, P Rivera, C Schechter, AN Noguchi, CT AF Ikonomi, P Rivera, C Schechter, AN Noguchi, CT TI GATA-1/GATA-2 levels affect globin gene expression and can alter hematopoietic cell phenotype. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Biol Chem Lab, Bethesda, MD USA. Natl Inst Hlth, Warren Grant Magnuson Clin Ctr, Dept Clin Pathol, Hematol Serv, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 421 BP 73A EP 73A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700423 ER PT J AU Jamik, M DeViragh, PA Bundman, D Roop, DR Steven, AC AF Jamik, M DeViragh, PA Bundman, D Roop, DR Steven, AC TI Loricrin-less cell envelopes: A back-up system in loricrin knockout mice. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, LSBR, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Dermat Cell Biol, Houston, TX 77030 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 423 BP 73A EP 73A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700424 ER PT J AU Smith, RD Li, J Noguchi, CT Schechter, AN AF Smith, RD Li, J Noguchi, CT Schechter, AN TI Butyric acid increases absolute gamma-globin mRNA levels in primary human adult erythroid cultures. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 420 BP 73A EP 73A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700420 ER PT J AU Yu, XB Liu, C Liu, ZY Noguchi, CT AF Yu, XB Liu, C Liu, ZY Noguchi, CT TI Activity of the erythropoietin receptor promoter in hematopoietic and neutral tissue of transgenic mice. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 422 BP 73A EP 73A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700421 ER PT J AU Jang, SI Rossi, A Ceci, R Steinert, PM AF Jang, SI Rossi, A Ceci, R Steinert, PM TI SP1 and SP3 are involved in the regulation of human loricrin gene transcription SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Univ Rome Tor Vergata, Dept Expt Med, Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 424 BP 74A EP 74A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700425 ER PT J AU Park, GT Morasso, MI AF Park, GT Morasso, MI TI Transcriptional regulation of distal-less 3 (Dlx3) homeobox gene SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 425 BP 74A EP 74A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700428 ER PT J AU Ko, KWS McLeod, RS Avramoglu, RK Nimpl, J FitzGerald, DJ Vukmirica, J Yao, Z AF Ko, KWS McLeod, RS Avramoglu, RK Nimpl, J FitzGerald, DJ Vukmirica, J Yao, Z TI Mutation at the furin cleavage site of LRP impairs exit from the ER but does not affect endocytosis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Ottawa, Inst Heart, Ottawa, ON K1Y 4W7, Canada. Univ Vienna, A-1030 Vienna, Austria. Bioctr, A-1030 Vienna, Austria. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 453 BP 78A EP 78A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700454 ER PT J AU Jin, AJ Edidin, M Nossa, R Gershfeld, NL AF Jin, AJ Edidin, M Nossa, R Gershfeld, NL TI A unique state of membrane lipids at physiological growth temperatures. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, LPB, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. NICHD, LIMB, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 459 BP 80A EP 80A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700460 ER PT J AU Kachar, B Azzam, NA Azzam, RN Hallenbeck, JM AF Kachar, B Azzam, NA Azzam, RN Hallenbeck, JM TI Temperature-induced formation of gel-phase lipid domains in the endoplasmic reticulum membranes of the hibernating squirrel. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIDCD, Sect Struct Cell Biol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 465 BP 81A EP 81A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700466 ER PT J AU Suchy, SF Nussbaum, RL AF Suchy, SF Nussbaum, RL TI Subcellular localization of the Lowe syndrome protein (ocrl1) by differential centrifugation: comparison of its distribution to Golgi-associated proteins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHGRI, GDRB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 582 BP 101A EP 101A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700583 ER PT J AU Beck, JC Bender, PK Cristofalo, V Johnson, RT AF Beck, JC Bender, PK Cristofalo, V Johnson, RT TI Unique resource for cellular aging research. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIA, Coriell Inst Med Res, Camden, NJ 08103 USA. Allegheny Univ Hlth Sci, Ctr Gerontol Res, Philadelphia, PA 19129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 611 BP 106A EP 106A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700612 ER PT J AU Rogakou, EP Nieves-Niera, W Boon, C Pommier, Y Bonner, WM AF Rogakou, EP Nieves-Niera, W Boon, C Pommier, Y Bonner, WM TI Histone H2AX serine-139 phosphorylation is induced by the introduction of the initial breaks into DNA as a result of the apoptotic endonuclease SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 629 BP 109A EP 109A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700632 ER PT J AU Varnai, P Balla, T AF Varnai, P Balla, T TI Visualization of phosphoinositides that bind pleckstrin homology domains SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, ERRB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 691 BP 120A EP 120A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700692 ER PT J AU Presley, JF Miller, C Zaal, K Ellenberg, J Lippincott-Schwartz, J AF Presley, JF Miller, C Zaal, K Ellenberg, J Lippincott-Schwartz, J TI In vivo dynamics of COP I. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 746 BP 129A EP 129A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700748 ER PT J AU Donaldson, JG Radhakrishna, H Brown, FD Al-Awar, OS AF Donaldson, JG Radhakrishna, H Brown, FD Al-Awar, OS TI Regulation of plasma membrane traffic and cortical actin structures by the ARF6 GTPase. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 760 BP 131A EP 131A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700761 ER PT J AU Pu, RT Kalab, P Damjanovski, S Azuma, Y Shi, YB Steinmann, KE Dasso, M AF Pu, RT Kalab, P Damjanovski, S Azuma, Y Shi, YB Steinmann, KE Dasso, M TI Dependence of the S phase checkpoint upon the Ran GTPase. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RI Damjanovski, Sashko/N-8728-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 768 BP 133A EP 133A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700771 ER PT J AU Zimmerberg, J AF Zimmerberg, J TI Phospholipid bilayer fusion, calcium-dependent exocytosis in vitro, and viral envelope glycoprotein mediated cell cell fusion. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 775 BP 134A EP 134A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700777 ER PT J AU Uren, D Tullio, AN Hwang, H Kawamoto, S Takeda, K Yu, ZX Ferrans, VJ Xu, S Frank, J Tresser, N Preston, YA Adelstein, RS AF Uren, D Tullio, AN Hwang, H Kawamoto, S Takeda, K Yu, ZX Ferrans, VJ Xu, S Frank, J Tresser, N Preston, YA Adelstein, RS TI Gene dosage affects the cardiac and brain phenotype in nonmuscle myosin II-B depleted mice. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 828 BP 143A EP 143A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700830 ER PT J AU Wei, Q Adelstein, RS AF Wei, Q Adelstein, RS TI Using doxycycline controlled expression of nonmuscle myosin heavy chain II-A to study HeLa cell morphology. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, LMC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 829 BP 143A EP 143A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700829 ER PT J AU Ward, RD Sackett, DL AF Ward, RD Sackett, DL TI Tubulin-GDP polymerizes into microtubules in the presence of the natural osmolyte trimethylamine-N-oxide (TMAO). SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Drug Discovery Res & Dev, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 865 BP 149A EP 149A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700866 ER PT J AU Bai, R Verdier-Pinard, P Luduena, RF Banerjee, A Sausville, E Hamel, E AF Bai, R Verdier-Pinard, P Luduena, RF Banerjee, A Sausville, E Hamel, E TI Tubulin content and beta-tubulin isotype distribution of cell lines used in the NCI in vitro drug screen. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 877 BP 151A EP 151A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700878 ER PT J AU Durso, NA Sackett, DL Gamble, WO Cardellina, JH Hamel, E AF Durso, NA Sackett, DL Gamble, WO Cardellina, JH Hamel, E TI Tubulin interactions with the antimitotic tripeptide hemiasterlin, an anticancer candidate SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 880 BP 152A EP 152A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700880 ER PT J AU Verdier-Pinard, P Bai, R Hamel, E AF Verdier-Pinard, P Bai, R Hamel, E TI Retention of dolastatin 10 by cellular tubulin: basis for the higher potency of peptide-like antimitotic agents. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, LDDRD, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 879 BP 152A EP 152A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700882 ER PT J AU Loomis, P Steinert, P Goldman, R AF Loomis, P Steinert, P Goldman, R TI The role of neuronal intermediate filaments (NIF) in neurite outgrowth and maintenance SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Northwestern Univ, Sch Med, Dept Cell & Mol Biol, Chicago, IL USA. NIH, Skin Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 926 BP 160A EP 160A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700928 ER PT J AU Yoon, M Yoon, K Moir, RD Steinert, PM Goldman, RD AF Yoon, M Yoon, K Moir, RD Steinert, PM Goldman, RD TI Motile properties of keratin and vimentin intermediate filament (IF) networks within the same cell. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Northwestern Univ, Sch Med, Dept Cell & Mol Biol, Evanston, IL 60208 USA. NIH, Skin Biol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 961 BP 166A EP 166A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700963 ER PT J AU Packard, BZ Komoriya, A Brown, MJ Yamada, KM AF Packard, BZ Komoriya, A Brown, MJ Yamada, KM TI Detection of the proteolytic activity of cathepsin D in living cells for evaluation of its physiolgoic role(s). SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. OncoImmunin Inc, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 966 BP 167A EP 167A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700968 ER PT J AU Ponce, ML Nomizu, M Yamada, Y Kleinman, HK Malinda, KM AF Ponce, ML Nomizu, M Yamada, Y Kleinman, HK Malinda, KM TI Identification of angiogenic laminin beta 1 sequences using a systematic screening of overlapping peptides SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR, CDBRB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 963 BP 167A EP 167A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906700964 ER PT J AU Damjanovski, S Shi, YB AF Damjanovski, S Shi, YB TI MMP distribution in early xenopus embryos: Effects of ectopic TR expression SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RI Damjanovski, Sashko/N-8728-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1015 BP 176A EP 176A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701016 ER PT J AU Balasundaram, D Benedik, M Levin, HL AF Balasundaram, D Benedik, M Levin, HL TI The retrotransposon Tf1 possesses a specific pathway of nuclear import SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. Univ Houston, Houston, TX 77204 USA. RI Benedik, Michael/H-2478-2011 OI Benedik, Michael/0000-0002-7435-0092 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1079 BP 187A EP 187A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701080 ER PT J AU Kim, HK Kawamoto, S AF Kim, HK Kawamoto, S TI TFEC, TFE3 and USF2 interact with a cis-regulatory element of the nonmuscle myosin heavy chain (MHC)-A gene. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, LMC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1117 BP 193A EP 193A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701117 ER PT J AU Kim, YH Choi, CY Lee, SJ Conti, MA Jeon, BH Kim, Y AF Kim, YH Choi, CY Lee, SJ Conti, MA Jeon, BH Kim, Y TI Hipks: A novel family of nuclear protein kinases that act as co-repressors for homeodomain transcription factors. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1116 BP 193A EP 193A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701119 ER PT J AU Hinshaw, JE Sweitzer, SM Peffley, N AF Hinshaw, JE Sweitzer, SM Peffley, N TI Dynamin helical tubes constrict and vesiculate upon GTP addition SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1130 BP 195A EP 195A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701130 ER PT J AU Coorssen, JR Blank, PS Tahara, M Zimmerberg, J AF Coorssen, JR Blank, PS Tahara, M Zimmerberg, J TI The final steps of exocytosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, LCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1164 BP 201A EP 201A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701166 ER PT J AU Vogel, KM Cabaniols, JP Roche, PA AF Vogel, KM Cabaniols, JP Roche, PA TI Kinetics of t-SNARE assembly in vivo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1165 BP 201A EP 201A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701164 ER PT J AU Phair, RD Hirschberg, K Lippincott-Schwartz, J AF Phair, RD Hirschberg, K Lippincott-Schwartz, J TI Kinetic modeling and quantification of secretory traffic: Role of post-Golgi carriers (PGCs) SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 BioInformat Serv, Rockville, MD 20854 USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1189 BP 205A EP 205A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701190 ER PT J AU Marmorstein, AD Csaky, KG Rodriguez-Boulan, E AF Marmorstein, AD Csaky, KG Rodriguez-Boulan, E TI Saturation of, and competition within an N-glycan independent apical secretory pathway. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Cornell Univ, Coll Med, Margaret M Dyson Vis Res Inst, New York, NY 10021 USA. NEI, Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1208 BP 209A EP 209A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701209 ER PT J AU Anderson, HA Roche, PA AF Anderson, HA Roche, PA TI Phosphorylation regulates the delivery of MHC class II-invariant chain complexes to antigen processing compartments. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1232 BP 213A EP 213A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701235 ER PT J AU Dell'Angelica, EC Shotelersuk, V Gahl, WA Bonifacino, JS AF Dell'Angelica, EC Shotelersuk, V Gahl, WA Bonifacino, JS TI Mutations in the beta 3A subunit of the AP-3 adaptor complex in patients with Hermansky-Pudlak syndrome (HPS). SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1233 BP 213A EP 213A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701233 ER PT J AU Valdez, AC Cabaniols, JP Brown, MJ Roche, PA AF Valdez, AC Cabaniols, JP Brown, MJ Roche, PA TI Syntaxin 11 associates with SNAP-23 in the trans-Golgi network and late endosomes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1231 BP 213A EP 213A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701232 ER PT J AU Hunyady, L Gaborik, Z Zhang, M Catt, KJ AF Hunyady, L Gaborik, Z Zhang, M Catt, KJ TI Chimeric AT(1)-AT(2) angiotensin receptors demonstrate divergent structural requirements of G protein coupling and receptor internalization. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Semmelweis Univ Med, Dept Physiol, H-1085 Budapest, Hungary. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1252 BP 216A EP 216A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701251 ER PT J AU Ralston, E Lu, Z Ploug, T AF Ralston, E Lu, Z Ploug, T TI The Golgi complex (GC) cisternae of skeletal muscle are localized at the ER exit sites. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, LN, NIH, Bethesda, MD 20892 USA. Copenhagen Muscle Res Ctr, Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1284 BP 222A EP 222A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701284 ER PT J AU Dehejia, AM Mezey, E Brownstein, MJ Polymeropoulos, MH AF Dehejia, AM Mezey, E Brownstein, MJ Polymeropoulos, MH TI Expression of alpha-synuclein in neurodegenerative diseases and model cellular systems SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINCDS, Bethesda, MD USA. NIMH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1298 BP 224A EP 224A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701299 ER PT J AU Tullio, AN Tresser, N Hara, Y Chan, CC Adelstein, RS AF Tullio, AN Tresser, N Hara, Y Chan, CC Adelstein, RS TI Structural abnormalities in the brain following ablation of the gene encoding nonmuscle myosin II-B heavy chain. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1306 BP 226A EP 226A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701308 ER PT J AU Uhm, CS Lowe, B Daniels, MP AF Uhm, CS Lowe, B Daniels, MP TI Agrin and neuregulin induce formation of microvilli and ruffles on cultured rat myotubes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Biochim Genet Lab, Bethesda, MD 20892 USA. Korea Univ, Coll Med, Dept Anat, Seoul 136701, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1311 BP 227A EP 227A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701317 ER PT J AU Ishaq, M Fan, M Natarajan, V AF Ishaq, M Fan, M Natarajan, V TI Accumulation of functionally inhibitory RXR alpha during activation-induced apoptosis of human T lymphocytes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1375 BP 237A EP 237A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701373 ER PT J AU Rajapandi, T Greene, LE Eisenberg, E AF Rajapandi, T Greene, LE Eisenberg, E TI p60 is not required for formation of the active Hsp90-glucocorticoid receptor complex. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1374 BP 237A EP 237A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701375 ER PT J AU Zhang, ZP Teng, C AF Zhang, ZP Teng, C TI Human estrogen receptor-related orphan receptor, hERR alpha1: Binds ERE, interacts with estrogen receptor, and has transactivating activity. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS, LRDT, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1373 BP 237A EP 237A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701372 ER PT J AU Choi, YH Lee, SM Lee, J Poston, J Lee, SJ Ha, MJ Kang, WK Nguyen, PM Wang, XF Kima, SJ Trepel, JB AF Choi, YH Lee, SM Lee, J Poston, J Lee, SJ Ha, MJ Kang, WK Nguyen, PM Wang, XF Kima, SJ Trepel, JB TI Transcriptional induction of p21WAF1/CIP1 by cyclic AMP SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, DCS, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, DBS, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1388 BP 239A EP 239A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701388 ER PT J AU Racz, A Barsony, J AF Racz, A Barsony, J TI Flexibility of the C-terminus plays a role in vitamin D receptor translocation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, Dept Biochem & Cell Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1386 BP 239A EP 239A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701387 ER PT J AU Tang, XM Beesley, J Grinspan, J Seth, P Kamholz, J Cambi, F AF Tang, XM Beesley, J Grinspan, J Seth, P Kamholz, J Cambi, F TI Cell cycle arrest induced by p27 is not sufficient to promote oligodendrocyte differentiation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NIH, Bethesda, MD 20892 USA. Wayne State Univ, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1391 BP 240A EP 240A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701390 ER PT J AU Tamura, M Gu, J Yamada, KM AF Tamura, M Gu, J Yamada, KM TI Tumor suppressor PTEN inhibition of cell invasion, migration, and growth: Involvement of focal adhesion kinase SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1429 BP 246A EP 246A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701427 ER PT J AU Xu, X Weaver, Z Li, C Gotay, J Ried, T Deng, CX AF Xu, X Weaver, Z Li, C Gotay, J Ried, T Deng, CX TI Centrosome abnormality genetic instability and apoptosis in mice with a targeted deletion of exon 11 of the BRCA1 tumor suppressor gene SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, LBM, Bethesda, MD 20892 USA. NHGRI, GTB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1438 BP 248A EP 248A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701440 ER PT J AU Nguyen, P Ha, M Lee, S Kang, W Kim, S Kaye, F Kaye, M Custer, S Sackett, D Nishioka, D Trepel, J AF Nguyen, P Ha, M Lee, S Kang, W Kim, S Kaye, F Kaye, M Custer, S Sackett, D Nishioka, D Trepel, J TI Association of the retinoblastoma protein with the interphase microtubule cytoskeleton SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1443 BP 249A EP 249A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701448 ER PT J AU Carabeo, RA Hackstadt, T AF Carabeo, RA Hackstadt, T TI ATP-dependent and ATP-independent mechanisms of entry by Chlamydia trachomatis in hela cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1470 BP 254A EP 254A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701476 ER PT J AU Ghedin, E Debrabant, A Dwyer, D AF Ghedin, E Debrabant, A Dwyer, D TI Trafficking and targeting studies of a unique surface enzyme in the parasitic protozoan Leishmania donovani using green fluorescent protein chimeras SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, LPD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1479 BP 255A EP 255A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701480 ER PT J AU Tiwari, S Weissman, AM AF Tiwari, S Weissman, AM TI Identification and characterization of two mammalian ubiquitin conjugating enzymes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Lab Immune Cell Biol, DHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1508 BP 260A EP 260A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701509 ER PT J AU Sihag, RK Smith, C Winters, CA Reese, TS Cheng, JH AF Sihag, RK Smith, C Winters, CA Reese, TS Cheng, JH TI Localization of spectrin in hippocampal neurons with domain- and isoform-specific antibodies: A confocal laser imaging and immunoelectron microscopy study. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1531 BP 264A EP 264A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701532 ER PT J AU Felsenfeld, DP Schwartzberg, PL Venegas, A Sheetz, MP AF Felsenfeld, DP Schwartzberg, PL Venegas, A Sheetz, MP TI Regulation of vitronectin receptor cytoskeleton linkages by the tyrosine kinase SRC. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. NHGRI, GDRB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1677 BP 289A EP 289A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701680 ER PT J AU Chandrasekaran, L Roberts, DD AF Chandrasekaran, L Roberts, DD TI Mutation of anti-angiogenic sequences in the type I repeats of thrombospondin-1 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1732 BP 298A EP 298A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701730 ER PT J AU Danen, EHJ Yamada, KM AF Danen, EHJ Yamada, KM TI Integrin/matrix specificity in anchorage-dependent growth SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR, CDBRB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1754 BP 302A EP 302A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701754 ER PT J AU Malinda, KM Nomizu, M Yamada, Y Kleinman, HK Ponce, ML AF Malinda, KM Nomizu, M Yamada, Y Kleinman, HK Ponce, ML TI Laminin alpha 1 chain peptides promote endothelial cell adhesion, tube formation and aortic sprouting SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR, CDBRB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1765 BP 304A EP 304A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701765 ER PT J AU Rankin, TL Talbot, P Lee, E Dean, J AF Rankin, TL Talbot, P Lee, E Dean, J TI Abnormal zona pellucida and decreased fertility in mice lacking ZP1 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1802 BP 311A EP 311A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701804 ER PT J AU Qi, CF Heath, LT Coleman, A Ohta, Y Torrey, TA Hartley, JW Chattopadhyay, SK Morse, HC AF Qi, CF Heath, LT Coleman, A Ohta, Y Torrey, TA Hartley, JW Chattopadhyay, SK Morse, HC TI Altered genomic organization of Bcl6 in murine large cell lymphomas. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Immunopathol Lab, Bethesda, MD 20892 USA. NIH, Genet Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1829 BP 315A EP 315A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701826 ER PT J AU Bonner, WM Boon, EP Rogakou, EP AF Bonner, WM Boon, EP Rogakou, EP TI Antibody to histone H2AX phosphorylated on serine 139 detects structures formed immediately after introduction of DNA double-stranded breaks SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1858 BP 320A EP 320A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701858 ER PT J AU Love, DC Prince, JM Lubas, WB Sweitzer, TD Wu, W Hanover, JA AF Love, DC Prince, JM Lubas, WB Sweitzer, TD Wu, W Hanover, JA TI Nuclear transport is inhibited by overexpression of O-linked N-acetylglucosaminyltransferase SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, LCBB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1870 BP 322A EP 322A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701870 ER PT J AU Al-Hasani, H Kunamneni, RK Hinck, CS Cushman, SW AF Al-Hasani, H Kunamneni, RK Hinck, CS Cushman, SW TI The c-terminus of the glucose transporter GLUT4 lacks targeting signals but modulates endocytosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1897 BP 327A EP 327A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701897 ER PT J AU Dhanvantari, S Loh, YP AF Dhanvantari, S Loh, YP TI Missorting of mutant proinsulin to the constitutive secretory pathway in familial hyperproinsulinemia. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. RI Dhanvantari, Savita/B-5362-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1909 BP 329A EP 329A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701909 ER PT J AU Shen, FS Loh, YP AF Shen, FS Loh, YP TI Identification of a putative sorting signal motif for targeting proinsulin to the regulated secretory pathway SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, LDN, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1908 BP 329A EP 329A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701914 ER PT J AU Chernomordik, LV Leikina, E Frolov, V Zimmerberg, J AF Chernomordik, LV Leikina, E Frolov, V Zimmerberg, J TI Intermediates in influenza hemagglutinin-mediated fusion SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, LCMB, NIH, Bethesda, MD USA. AN Frumkin Electrochem Inst, Moscow, Russia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1919 BP 330A EP 330A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701915 ER PT J AU Greener, T Pacold, M Eisenberg, E Greene, LE AF Greener, T Pacold, M Eisenberg, E Greene, LE TI The 20 kDa C-terminal fragment of the DnaJ homolog, auxilin, supports uncoating by Hsc70 but not clathrin polymerization. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1976 BP 340A EP 340A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701976 ER PT J AU Zhao, X Greener, T Al-Hasani, H Cushman, SW Eisenberg, E Greene, LE AF Zhao, X Greener, T Al-Hasani, H Cushman, SW Eisenberg, E Greene, LE TI Expression of the clathrin assembly proteins auxilin and AP(180) in various cells in culture inhibits endocytosis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1975 BP 340A EP 340A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701977 ER PT J AU Barr, VA Taylor, SI AF Barr, VA Taylor, SI TI Differential trafficking of different isoforms of the human leptin receptor SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, Diabet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 1995 BP 343A EP 343A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906701996 ER PT J AU Leung, SM Zeyda, T Thatcher, B AF Leung, SM Zeyda, T Thatcher, B TI A new and rapid method for phenotype screening using SELDI Proteinchip (TM) arrays demonstrated on serum from knockout and wildtype mice. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Ciphergen Biosyst Inc, Palo Alto, CA USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2040 BP 351A EP 351A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702041 ER PT J AU Glazner, GW Boland, A Brenneman, DE Gozes, I Mattson, MP AF Glazner, GW Boland, A Brenneman, DE Gozes, I Mattson, MP TI ADNF-9 protects neurons against oxidative stress-induced death by activation of the transcription factor NF-kappa B. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Neurobiol & Anat, Lexington, KY 40536 USA. NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2049 BP 353A EP 353A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702049 ER PT J AU Lins, U Farina, M Kurc, M Kachar, B AF Lins, U Farina, M Kurc, M Kachar, B TI Structural analysis of the otoconial matrix of the frog and guinea pig vestibular sensory organs. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. Fed Univ Rio De Janeiro, Rio De Janeiro, Brazil. RI Farina, Marcos/I-3744-2014; Lins, Ulysses/N-7282-2015 OI Lins, Ulysses/0000-0002-1786-1144 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2053 BP 354A EP 354A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702054 ER PT J AU Kim, JS Nguyen, PM Choi, YH Hwang, SG Thareja, N Resau, J Behan, K Parr, A Allegra, C Kimn, SJ Trepel, JB AF Kim, JS Nguyen, PM Choi, YH Hwang, SG Thareja, N Resau, J Behan, K Parr, A Allegra, C Kimn, SJ Trepel, JB TI Nuclear localization of thymidylate synthase: The retinoblastoma protein is a thymidylate synthase binding protein SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2064 BP 356A EP 356A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702065 ER PT J AU Konczalik, P Moss, J AF Konczalik, P Moss, J TI Identification of critical, conserved residues in mammalian and bacterial ADP-ribosylarginine hydrolases SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2066 BP 356A EP 356A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702066 ER PT J AU Murga, C Laguinge, L Cuadrado, A Gutkind, JS AF Murga, C Laguinge, L Cuadrado, A Gutkind, JS TI Activation of Akt/PKB by G protein-coupled receptors leads to anti-apoptotic effects: A role for alpha and beta gamma subunits of heterotrimeric G proteins acting through PI3K gamma SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; Murga, Cristina/E-1965-2014 OI Murga, Cristina/0000-0002-8964-4077 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2102 BP 362A EP 362A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702100 ER PT J AU Al Awar, OS Radhakrishna, H Donaldson, JG AF Al Awar, OS Radhakrishna, H Donaldson, JG TI Identification of amino acid residues critical for ARF6 localization and function SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2113 BP 364A EP 364A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702113 ER PT J AU Ghiani, CA Eisen, AM Yuan, X McBain, CJ Gallo, V AF Ghiani, CA Eisen, AM Yuan, X McBain, CJ Gallo, V TI Activation of neurotransmitter receptors regulates cell cycle progression and differentiation of oligodendrocyte progenitors. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2142 BP 369A EP 369A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702145 ER PT J AU Ohta, Y Qi, CF McCarthy, TC Chattopadhyay, SK Morse, HC AF Ohta, Y Qi, CF McCarthy, TC Chattopadhyay, SK Morse, HC TI A 55 kDa protein related to PKR is expressed in spleen cells from mice with retrovirus-induced immunodeficiency, maids SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Immunopathol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2169 BP 373A EP 373A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702168 ER PT J AU Iwata, T Jimenez, J Sato, S Carper, D AF Iwata, T Jimenez, J Sato, S Carper, D TI Requirement of osmotic response element for the induction of aldose reductase by inflammatory cytokine tumor necrosis factor-alpha SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20205 USA. NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2172 BP 374A EP 374A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702174 ER PT J AU Dyer, KD Rosenberg, HF AF Dyer, KD Rosenberg, HF TI Promoter analysis and transcriptional regulation of the Charcot-Leyden crystal protein gene. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Host Def Lab, Bethesda, MD 20892 USA. Georgetown Univ, Dept Physiol & Biophys, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2191 BP 377A EP 377A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702188 ER PT J AU Jamur, MC Grodzki, ACG Mello, LFC Moreno, AN Siraganian, RP Oliver, C AF Jamur, MC Grodzki, ACG Mello, LFC Moreno, AN Siraganian, RP Oliver, C TI Depletion of mast cells from the peritoneal cavity results in an increase in undifferentiated mast cells in the bone marrow and the appearance of mast cells in the circulation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UFPR, Curitiba, Parana, Brazil. NIH, Bethesda, MD 20892 USA. FMRP, Ribeirao Preto, SP, Brazil. RI Jamur, Maria Celia/L-5520-2016 OI Jamur, Maria Celia/0000-0001-7065-8543 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2196 BP 378A EP 378A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702196 ER PT J AU Wolfe, AP AF Wolfe, AP TI Chromatin control of transcription SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Mol Embryol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2208 BP 380A EP 380A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702207 ER PT J AU Copeland, WC AF Copeland, WC TI Maintenance of the mitochondrial genome by the human DNA polymerase gamma. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2234 BP 385A EP 385A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702235 ER PT J AU Kunkel, TA AF Kunkel, TA TI DNA replication fidelity and mismatch repair. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2233 BP 385A EP 385A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702238 ER PT J AU Tsutsui, T Tamura, Y Kumakura, S Sekiguchi, M Barrett, JC AF Tsutsui, T Tamura, Y Kumakura, S Sekiguchi, M Barrett, JC TI A possible involvement of genetic instability in telomere maintenance in immortal human fibroblasts. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Nippon Dent Univ, Dept Pharmacol, Tokyo 102, Japan. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2235 BP 385A EP 385A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702237 ER PT J AU Manubay, CM Wei, Q Bao, Y Mossing, MC Adelstein, RS Fishkind, DJ AF Manubay, CM Wei, Q Bao, Y Mossing, MC Adelstein, RS Fishkind, DJ TI Probing nonmuscle myosin II assembly properties in vivo using LMM-GFP fusion proteins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Mississippi, Dept Chem, University, MS 38677 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2322 BP 400A EP 400A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702319 ER PT J AU Romenskaia, IG Wei, Q Manubay, CM Adelstein, RS Fishkin, DJ AF Romenskaia, IG Wei, Q Manubay, CM Adelstein, RS Fishkin, DJ TI Nonmuscle myosin IIB GFP: An in vivo probe for cell motility and cytokinesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Notre Dame, Notre Dame, IN 46556 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2323 BP 400A EP 400A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702322 ER PT J AU Winkler, U Tang, Y Torrey, TA Morse, HC AF Winkler, U Tang, Y Torrey, TA Morse, HC TI Subcellular distribution of the cellular kinesin motor like protein KIF-4 and its association with HIV Pr55(gag). SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2349 BP 405A EP 405A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702352 ER PT J AU Orlandi, PA Fishman, PH AF Orlandi, PA Fishman, PH TI Cholera toxin-mediated ADP-ribosylation of Gs alpha and activation of adenylyl cyclase occurs at the plasma membrane of CaCo-2 cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 CFSAN, Div Virulence Assessment, FDA, Washington, DC 20204 USA. NINDS, LMCN, Membrane Biochem Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2361 BP 407A EP 407A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702363 ER PT J AU Banerjee, A Kasmala, LT Luduena, RF Hamel, E Sun, L Lee, KH AF Banerjee, A Kasmala, LT Luduena, RF Hamel, E Sun, L Lee, KH TI Interaction of novel thiocolchicine analogs with bovine brain tubulin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. NCI, NIH, Frederick, MD USA. Univ N Carolina, Nat Prod Lab, Chapel Hill, NC 27599 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2374 BP 409A EP 409A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702371 ER PT J AU Wysocki, AB Kusakabe, AO Chang, S Zhu, J Tuan, TL AF Wysocki, AB Kusakabe, AO Chang, S Zhu, J Tuan, TL TI Temporal expression of matrix metalloproteinase-9 and urokinase plasminogen activator in human chronic wound fluids. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Natl Inst Nursing Res, NIH, Bethesda, MD 20892 USA. Childrens Hosp Los Angeles, Dept Surg, Div Surg Res, Los Angeles, CA 90027 USA. Univ So Calif, Sch Med, Los Angeles, CA 90027 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2437 BP 420A EP 420A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702435 ER PT J AU Eliceiri, BP Andrews, C Schwartzerg, PL Cheresh, DA AF Eliceiri, BP Andrews, C Schwartzerg, PL Cheresh, DA TI Requirement for Src activity during VEGF but not bFGF-induced angiogenesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Vasc Biol, La Jolla, CA USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2444 BP 422A EP 422A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702450 ER PT J AU Hoegy, SE Stetler-Stevenson, WG AF Hoegy, SE Stetler-Stevenson, WG TI Characteristics of TIMP-2 cell surface binding proteins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2475 BP 427A EP 427A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702478 ER PT J AU Engbring, JA Hoffman, P Kleinman, HK AF Engbring, JA Hoffman, P Kleinman, HK TI Characterization of a heparan sulfate-containing receptor on B16-F10 melanoma cells for the metastasis promoting laminin alpha 1 chain peptide LQVQLSIRT SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR, COBRB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2482 BP 428A EP 428A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702482 ER PT J AU Bennett, TA Burt, HL Stetler-Stevenson, WG AF Bennett, TA Burt, HL Stetler-Stevenson, WG TI Disruption of cell adhesion to ECM proteins by a C-terminal MMP-2 fragment (PEX) and TIMP-2. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2496 BP 430A EP 430A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702495 ER PT J AU Kobayashi, S Yoshida, K Longenecker, G Satomura, K Levsky, JM Semba, I Sreenath, T Wistow, GJ Shum, L Slavkin, HC Kulkarni, AB AF Kobayashi, S Yoshida, K Longenecker, G Satomura, K Levsky, JM Semba, I Sreenath, T Wistow, GJ Shum, L Slavkin, HC Kulkarni, AB TI Macrophage migration inhibitory factor (MIF) and cell differentiation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR, Funct Genom Unit, NIH, Bethesda, MD 20892 USA. NIDR, Gene Targeting Facil, NIH, Bethesda, MD 20892 USA. NIDR, CSDB, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2536 BP 437A EP 437A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702535 ER PT J AU Weinstein, M Yang, X Li, CL Xu, XL Gotay, J Deng, CX AF Weinstein, M Yang, X Li, CL Xu, XL Gotay, J Deng, CX TI Failure of EGG cylinder elongation and mesoderm induction in embryos lacking the tumor suppressor SMAD2 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2542 BP 438A EP 438A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702541 ER PT J AU Misteli, T Spector, DL AF Misteli, T Spector, DL TI The spatial coordination of transcription and pre-mRNA splicing in vivo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2577 BP 444A EP 444A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702576 ER PT J AU Tvarusko, W Bentele, M Satzler, K Spector, DL Eils, R Misteli, T AF Tvarusko, W Bentele, M Satzler, K Spector, DL Eils, R Misteli, T TI A computational approach to quantitative analysis of functional processes in living cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Heidelberg, Biocomp Grp, D-69120 Heidelberg, Germany. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2576 BP 444A EP 444A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702573 ER PT J AU Bryan, JT Morasso, MI AF Bryan, JT Morasso, MI TI Dlx3 protein interactions and localization in differentiated epidermal cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2603 BP 449A EP 449A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702606 ER PT J AU Beuron, F Kessel, M Belnap, D Wickner, S Maurizi, M Steven, A AF Beuron, F Kessel, M Belnap, D Wickner, S Maurizi, M Steven, A TI Interactions of the CLP-AP energy-dependent protease: Symmetry mismatch and dynamic transitions upon substrate binding SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, LCB, NIH, Bethesda, MD 20892 USA. NCI, LMB, NIH, Bethesda, MD 20892 USA. NIAMS, LSBR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2630 BP 454A EP 454A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702636 ER PT J AU Novoradovskaya, N Lee, JH Brantly, M AF Novoradovskaya, N Lee, JH Brantly, M TI Secretion of a misfolded form of alpha-1-antitrypsin is regulated by post-translational processing. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2666 BP 460A EP 460A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702666 ER PT J AU FitzGerald, DJ McKee, ML AF FitzGerald, DJ McKee, ML TI Post-endocytic processing of Pseudomonas exotoxin A SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, DBS, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2696 BP 465A EP 465A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702699 ER PT J AU Vitale, N Moss, J Vaughan, M AF Vitale, N Moss, J Vaughan, M TI Identification of signal elements involved in targeting of ARD1 to Golgi and lysosomes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2735 BP 472A EP 472A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702741 ER PT J AU Lindner, G Menrad, A Gherardi, E Merlino, G Welker, P Handjiski, B Roloff, B Paus, R AF Lindner, G Menrad, A Gherardi, E Merlino, G Welker, P Handjiski, B Roloff, B Paus, R TI Involvement of hepatocyte growth factor scatter factor (HGF/SF) and m-Met receptor signaling in hair follicle morphogenesis and cycling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Humboldt Univ, Dept Dermatol, D-1086 Berlin, Germany. Univ Cambridge, Dept Clin Oncol, Cambridge CB2 1TN, England. Natl Canc Inst, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2771 BP 478A EP 478A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702773 ER PT J AU Zohar, O Blech-Hermoni, Y Tandon, A Yoshioka, T Alkon, D AF Zohar, O Blech-Hermoni, Y Tandon, A Yoshioka, T Alkon, D TI Localized heat production in intracellular compartments of human fibroblasts. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, LAS, NIH, Bethesda, MD 20892 USA. Waseda Univ, Dept Mol Neurobiol, Tokorozawa, Saitama, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2801 BP 483A EP 483A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702803 ER PT J AU Yang, X Letterio, JJ Chen, L Hayman, R Gu, H Roberts, AB Deng, CX AF Yang, X Letterio, JJ Chen, L Hayman, R Gu, H Roberts, AB Deng, CX TI Targeted disruption of murine SMAD3 results in impaired mucosa immunity and diminished T cell responsiveness to TGF-beta SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2815 BP 485A EP 485A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702814 ER PT J AU Gong, C Koochekpour, S Wang, P Jeffers, M Klausner, RD Woude, GFV Gnarral, JR AF Gong, C Koochekpour, S Wang, P Jeffers, M Klausner, RD Woude, GFV Gnarral, JR TI The VHL tumor suppressor controls invasion and branching morphogenesis stimulated by hepatocyte growth factor in renal carcinoma cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Louisiana State Univ, Med Ctr, Dept Biochem, New Orleans, LA 70112 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2836 BP 489A EP 489A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702839 ER PT J AU Zhang, SL Ramsay, ES Mock, BA AF Zhang, SL Ramsay, ES Mock, BA TI Cell cycle regulation in plasma cells by allelic variants of the Cdkn2a locus, a candidate gene for Pctr1. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2835 BP 489A EP 489A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702841 ER PT J AU Karaman-Jurukovska, N Jang, SI AF Karaman-Jurukovska, N Jang, SI TI Improved transient transfection of normal human epidermal keratinocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 SUNY Stony Brook, Dept Oral Biol & Pathol, Living Skin Bank, Stony Brook, NY 11794 USA. NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2880 BP 497A EP 497A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702886 ER PT J AU Kim, SY Lee, CH Marekov, LN Park, MH Steiner, PM AF Kim, SY Lee, CH Marekov, LN Park, MH Steiner, PM TI Small proline-rich protein (SPR) is a major component of cornified human opal keratinocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2897 BP 499A EP 499A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702893 ER PT J AU Lee, CH Kim, SY Steinert, PM Park, MH AF Lee, CH Kim, SY Steinert, PM Park, MH TI Transglutaminases in human oral carcinoma SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2898 BP 500A EP 500A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702903 ER PT J AU Navarro, E Nguyen, P Francesconi, A Kasai, M Peters, J Trepel, J Walsh, T AF Navarro, E Nguyen, P Francesconi, A Kasai, M Peters, J Trepel, J Walsh, T TI Candida albicans induces epithelial cell apoptosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Pediat Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2908 BP 501A EP 501A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702904 ER PT J AU Scidmore-Carlson, MA Shaw, EI Dooley, CA Fischer, ER Hackstadt, T AF Scidmore-Carlson, MA Shaw, EI Dooley, CA Fischer, ER Hackstadt, T TI Identification of three novel Chlamydia trachomatis inclusion membrane proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2906 BP 501A EP 501A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702905 ER PT J AU Debrabant, A Ghedin, E Dwyer, DM AF Debrabant, A Ghedin, E Dwyer, DM TI Functional domains of the Leishmania donovani 3 '-nucleotidase/nuclease. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2910 BP 502A EP 502A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702913 ER PT J AU Shakarian, A Dwyer, D AF Shakarian, A Dwyer, D TI Differential targeting of developmentally expressed proteins in the primitive eukaryote Leishmania SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, LPD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2909 BP 502A EP 502A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702912 ER PT J AU Shaw, EI Scidmore-Carlson, MA Hackstadt, T AF Shaw, EI Scidmore-Carlson, MA Hackstadt, T TI Temporal trancript expression from Chlamydial trachomatis inclusion memrane protein genes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 SU S MA 2911 BP 502A EP 502A PG 1 WC Cell Biology SC Cell Biology GA 137GQ UT WOS:000076906702911 ER PT J AU Tilghman, S Astin, HS Brinkley, W Chilton, MD Cummings, MP Ehrenberg, RG Fox, MF Glenn, K Green, PJ Hans, S Kelman, A LaPidus, J Levin, B McIntosh, JR Riecken, H Stephen, PE AF Tilghman, S Astin, HS Brinkley, W Chilton, MD Cummings, MP Ehrenberg, RG Fox, MF Glenn, K Green, PJ Hans, S Kelman, A LaPidus, J Levin, B McIntosh, JR Riecken, H Stephen, PE TI Trends in the early careers of life scientists - Preface and executive summary SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article C1 Princeton Univ, Princeton, NJ 08544 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Baylor Coll Med, Houston, TX 77030 USA. Ciba Geigy Biotechnol, Res Triangle Pk, NC USA. Marine Biol Lab, Woods Hole, MA 02543 USA. Cornell Univ, Ithaca, NY USA. Georgia Inst Technol, Atlanta, GA 30332 USA. GD Searle & Co, St Louis, MO USA. Michigan State Univ, E Lansing, MI 48824 USA. Pew Charitable Trusts, Philadelphia, PA USA. N Carolina State Univ, Raleigh, NC 27695 USA. Council Grad Sch, Washington, DC USA. Emory Univ, Atlanta, GA 30322 USA. Univ Colorado, Boulder, CO 80309 USA. Univ Penn, Philadelphia, PA 19104 USA. Georgia State Univ, Atlanta, GA 30303 USA. Washington Univ, St Louis, MO USA. Assoc Amer Med Coll, Washington, DC USA. Natl Sci Fdn, Arlington, VA 22230 USA. NIH, Bethesda, MD 20892 USA. Vanderbilt Inst Publ Policy Studies, Nashville, TN USA. Federat Amer Soc Expt Biol, Bethesda, MD USA. Council Grad Sch, Washington, DC USA. Amer Soc Cell Biol, Bethesda, MD USA. RP Tilghman, S (reprint author), Princeton Univ, Princeton, NJ 08544 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1998 VL 9 IS 11 BP 3007 EP 3015 PG 9 WC Cell Biology SC Cell Biology GA 136ZK UT WOS:000076888800002 ER PT J AU Berton, TR Conti, CJ Mitchell, DL Aldaz, CM Lubet, RA Fischer, SM AF Berton, TR Conti, CJ Mitchell, DL Aldaz, CM Lubet, RA Fischer, SM TI The effect of vitamin E acetate on ultraviolet-induced mouse skin carcinogenesis SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 11th International Conference on Carcinogenesis and Risk Assessment CY DEC 03-06, 1997 CL AUSTIN, TEXAS DE vitamin E acetate; ultraviolet light; DNA damage; proliferation; telomerase activity ID HAIRLESS MICE; ALPHA-TOCOPHEROL; TUMOR PROMOTION; MURINE SKIN; EPIDERMAL PROLIFERATION; TELOMERASE ACTIVITY; PYRIMIDINE DIMERS; DNA PHOTODAMAGE; UVB IRRADIATION; THYMINE DIMERS AB Despite the benefits of sunscreens, ultraviolet (UV) exposure can still lead to skin cancer. In this study we investigated the effect of topical application of the antioxidant vitamin E acetate (VEA) on the inhibition of UV-induced carcinogenesis. Hairless SKH-1 mice received 5.2 mg of VEA 30 min before (VEA/UV) or after (UV/VEA) a single minimal erythemic dose of UV light. Vehicle-control animals received acetone 30 min before UV exposure (Ace/UV). After 24 h, cyclobutane dimer repair was twofold and 1.5-fold greater in the UV/VEA and VEA/UV groups, respectively Expression of p53 protein in the UV/VEA group was maximum at 12 h after UV exposure, whereas in the Ace/UV- and VEA/UV-treated mice, maximum p53 immunostaining was statistically higher at 15 h (P = 0.03). DNA synthesis as determined by 5-bromo-2'-deoxyuridine incorporation was twofold higher after 15 h in all groups but was not statistically different among treatment groups. Protein revels of cyclin D1 and p21 were increased in both VEA groups by 6 h. In addition, VEA treatments delayed tumor formation and yield for the first 20 wk, although this difference was lost by 30 wk. The telomerase activity of carcinomas from the UV/VEA-treated mice was statistically lower than that of the Ace/UV-treated mice (P = 0.05). This study showed that although VEA may mitigate some of the initial events associated with UV irradiation such as DNA damage and p53 expression, it has limited potential in preventing UV-induced proliferation and tumor formation. (C) 1998 Wiley-Liss, Inc. C1 Univ Texas, Md Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX 78957 USA. Univ Texas, Div Nutr Sci, Austin, TX 78712 USA. NCI, Div Canc Prevent & Control, NIH, Bethesda, MD 20892 USA. RP Fischer, SM (reprint author), Univ Texas, Md Anderson Canc Ctr, Div Sci Pk Res, POB 389, Smithville, TX 78957 USA. FU NCI NIH HHS [CA57730, CN-65029-72]; NIEHS NIH HHS [ES 07784] NR 63 TC 66 Z9 68 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 1998 VL 23 IS 3 BP 175 EP 184 DI 10.1002/(SICI)1098-2744(199811)23:3<175::AID-MC6>3.0.CO;2-B PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 140YQ UT WOS:000077116200006 PM 9833778 ER PT J AU Bruning, JC Michael, MD Winnay, JN Hayashi, T Horsch, D Accili, D Goodyear, LJ Kahn, CR AF Bruning, JC Michael, MD Winnay, JN Hayashi, T Horsch, D Accili, D Goodyear, LJ Kahn, CR TI A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance SO MOLECULAR CELL LA English DT Article ID DEPENDENT DIABETES-MELLITUS; SKELETAL-MUSCLE; TRANSGENIC MICE; TARGETED DISRUPTION; RESISTANCE; GENE; KINASE; GLUT4; EXPRESSION; TRANSPORT AB Skeletal muscle insulin resistance is among the earliest detectable defects in humans with type 2 diabetes mellitus. To determine the contribution of muscle insulin resistance to the metabolic phenotype of diabetes, we used the Cre-IoxP system to disrupt the insulin receptor gene in mouse skeletal muscle. The muscle-specific insulin receptor knockout mice exhibit a muscle-specific >95% reduction in receptor content and early signaling events. These mice display elevated fat mass, serum triglycerides, and free fatty acids, but blood glucose, serum insulin, and glucose tolerance are normal. Thus, insulin resistance in muscle contributes to the altered fat metabolism associated with type 2 diabetes, but tissues other than muscle appear to be more involved in insulin-regulated glucose disposal than previously recognized. C1 Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. FU NIDDK NIH HHS [2P30DK36836, DK 31036] NR 35 TC 672 Z9 687 U1 3 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD NOV PY 1998 VL 2 IS 5 BP 559 EP 569 DI 10.1016/S1097-2765(00)80155-0 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 142MG UT WOS:000077203800004 PM 9844629 ER PT J AU Natarajan, K Jackson, BM Rhee, E Hinnebusch, AG AF Natarajan, K Jackson, BM Rhee, E Hinnebusch, AG TI YTAF(II)61 has a general role in RNA polymerase II transcription and is required by Gcn4p to recruit the SAGA coactivator complex SO MOLECULAR CELL LA English DT Article ID TATA-BINDING PROTEIN; AMINO-ACID CONTROL; SACCHAROMYCES-CEREVISIAE; ACTIVATION DOMAINS; IN-VIVO; HISTONE OCTAMER; TFIID COMPLEX; YEAST; PROMOTER; ADA2 AB We obtained a recessive insertion mutation in the gene encoding yeast TBP-associated factor yTAF(II)61/68 that impairs Gcn4p-independent and Gcn4p-activated HIS3 transcription. This mutation also reduces transcription of seven other class II genes, thus indicating a broad role for this yTAF(II) in RNA polymerase II transcription. The Gcn4p activation domain interacts with multiple components of the SAGA complex in cell extracts, including the yTAF(II) proteins associated with SAGA, but not with two yTAF(II)s restricted to TFIID. The taf61-1 mutation impairs binding of Gcn4p to SAGA/yTAF(II) subunits but not to components of holoenzyme mediator. Our results provide strong evidence that recruitment of SAGA, in addition to holoenzyme, is crucial for activation by Gcn4p in vivo and that yTAF(II)61 plays a key role in this process. C1 NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov NR 69 TC 63 Z9 64 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD NOV PY 1998 VL 2 IS 5 BP 683 EP 692 DI 10.1016/S1097-2765(00)80166-5 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 142MG UT WOS:000077203800015 PM 9844640 ER PT J AU Wu, SM Hallermeier, KM Laue, L Brain, C Berry, AC Grant, DB Griffin, JE Wilson, JD Cutler, GB Chan, WY AF Wu, SM Hallermeier, KM Laue, L Brain, C Berry, AC Grant, DB Griffin, JE Wilson, JD Cutler, GB Chan, WY TI Inactivation of the luteinizing hormone/chorionic gonadotropin receptor by an insertional mutation in Leydig cell hypoplasia SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HORMONE-RECEPTOR; MALE PSEUDOHERMAPHRODITISM; CHORIOGONADOTROPIN RECEPTOR; CHORIONIC-GONADOTROPIN; OVARIAN RESISTANCE; HUMAN-DISEASE; GENE; EXPRESSION; DUPLICATION; MECHANISMS AB We previously identified a nonsense mutation (Cys545Stop) in the paternal human LH/CG receptor (hLHR) allele in a family with two 46,XY children afflicted with Leydig cell hypoplasia. This mutation abolished the signal transduction capability of the affected hLHR. We have now examined all coding exons and the transcript of both alleles of the hLHR gene of the affected children. A 33-bp in-frame insertion was found in the maternal hLHR allele. This insertion occurred between nucleotide 54 and 55 and might be the result of a partial gene duplication. Genomic DNA-PCR showed that this defective maternal hLHR allele was inherited by the two affected children. However, examination of the inheritance of the 935-A/G polymorphism of the hLHR by genomic- and RT-PCR indicated that the maternal hLHR allele was not expressed in cultured fibroblasts of the patients. The effect of the in-frame insertion on the biological activity of the hLHR was examined by expressing the mutated hLHR construct, generated by site-directed mutagenesis, in HEK 293 cells. The expression of the mRNA for the mutant hLHR in HEK 293 cells was not affected. Response of cells expressing the mutated hLHR to hCG stimulation was impaired as demonstrated by reduced intracellular cAMP biosynthesis. This change in signal transduction was the result of a profound reduction in hormone binding at the cell surface due to altered expression and processing of the mutated receptor. We conclude that Leydig cell hypoplasia in this family is the result of compound heterozygous loss-of-function mutations of the hLHR gene. C1 Georgetown Univ, Childrens Med Ctr, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ, Dept Biol, Washington, DC 20007 USA. Georgetown Univ, Dept Cell Biol, Washington, DC 20007 USA. Hosp Sick Children, London WC1N 3JH, England. Guys Hosp, London WC1N 3JH, England. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Chan, WY (reprint author), Georgetown Univ, Childrens Med Ctr, Dept Pediat, 3800 Reservoir Rd NW, Washington, DC 20007 USA. EM wchan02@gumedlib.dml.georgetown.edu FU NICHD NIH HHS [HD-31553] NR 41 TC 41 Z9 42 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1998 VL 12 IS 11 BP 1651 EP 1660 DI 10.1210/me.12.11.1651 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 133GR UT WOS:000076679300001 PM 9817592 ER PT J AU Shohat, M Lotan, R Magal, N Danon, Y Ogur, G Tokguz, G Schlezinger, M Schwabe, A Halpern, G Fischel-Ghodsian, N Kastner, D Shohat, T Rotter, JI AF Shohat, M Lotan, R Magal, N Danon, Y Ogur, G Tokguz, G Schlezinger, M Schwabe, A Halpern, G Fischel-Ghodsian, N Kastner, D Shohat, T Rotter, JI TI Amyloidosis in familial Mediterranean fever is associated with a specific ancestral haplotype in the MEFV locus SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE familial Mediterranean fever; amyloidosis; specific haplotype ID GENE; ARMENIANS; LINKAGE AB Familial Mediterranean fever (FMF) is a recessive disease characterized by recurrent attacks of inflammation of serosal membranes, and the gene responsible, MEFV, has been recently identified. Amyloidosis is considered to be the most severe complication. Since colchicine is effective in preventing FMF amyloidosis and since this process can develop even prior to the FMF symptoms, lifelong colchicine treatment is recommended for all FMF patients. Identification of the factor which determines amyloidosis will allow treatment to be directed only to those at risk. In order to investigate the association between amyloidosis and MEFV haplotypes, we studied 56 families from three ethnic groups. We compared the haplotypes of FMF patients with and without amyloidosis in each ethnic group separately and identified 14 different MEFV core haplotypes. A significant association (P < 0.004) was found between amyloidosis and a specific core haplotype, 153bp:104bp at markers D16S3370 and D16S2617, respectively. Amyloidosis was present in 20 out of 70 homozygotes for this haplotype and in 6 out of 35 compound heterozygotes for this and other core haplotypes. None of the patients who did not carry this allele had amyloidosis. There was no association between the various haplotypes and severity of the FMF symptoms, age of onset, or age at commencement of colchicine. Further investigation of the MEFV haplotypes in additional patients is recommended as such an association may save many mildly affected or asymptomatic patients with non-amyloidotic genotypes from receiving unnecessary lifelong colchicine treatment. (C) 1998 Academic Press. C1 Rabin Med Ctr, Dept Med Genet, IL-49100 Petah Tiqwa, Israel. Rabin Med Ctr, FMRC, IL-49100 Petah Tiqwa, Israel. Tel Aviv Univ, Sackler Sch Med, IL-49100 Petah Tiqwa, Israel. Barzilai Med Ctr, Immunol Unit, Ashkelon, Israel. Ankara Univ, Fac Med, Dept Immunol, Ankara, Turkey. Ankara Univ, Fac Med, Gata Med Ctr, Ankara, Turkey. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Cedars Sinai Med Ctr, Birth Defects Ctr, Los Angeles, CA 90048 USA. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. RP Shohat, M (reprint author), Rabin Med Ctr, Dept Med Genet, Beilinson Campus, IL-49100 Petah Tiqwa, Israel. EM mshohat@ccsg.tau.ac.il NR 26 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD NOV PY 1998 VL 65 IS 3 BP 197 EP 202 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 151MA UT WOS:000077722800003 PM 9851884 ER PT J AU Gahl, WA AF Gahl, WA TI Untitled - Reply SO MOLECULAR GENETICS AND METABOLISM LA English DT Letter C1 NICHD, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NICHD, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD NOV PY 1998 VL 65 IS 3 BP 254 EP 254 DI 10.1006/mgme.1998.2768 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 151MA UT WOS:000077722800012 ER PT J AU Kaijzel, EL van Krugten, MV Brinkman, BMN Huizinga, TWJ van der Straaten, T Hazes, JMW Ziegler-Heitbrock, HWL Nedospasov, SA Breedveld, FC Verweij, CL AF Kaijzel, EL van Krugten, MV Brinkman, BMN Huizinga, TWJ van der Straaten, T Hazes, JMW Ziegler-Heitbrock, HWL Nedospasov, SA Breedveld, FC Verweij, CL TI Functional analysis of a human tumor necrosis factor alpha (TNF-alpha) promoter polymorphism related to joint damage in rheumatoid arthritis SO MOLECULAR MEDICINE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; SYSTEMIC LUPUS-ERYTHEMATOSUS; GENE-REGULATION; CELL-LINE; MONOCLONAL-ANTIBODY; REGION; SUSCEPTIBILITY; ASSOCIATION; LIPOPOLYSACCHARIDE; MICE AB Background: Functional heterogeneity in the tumor necrosis factor alpha (TNF-alpha) gene may be responsible for the TNF-alpha response in infectious and autoimmune diseases. Recently, the TNF-238 promoter polymorphism was observed as being associated with a more destructive disease in rheumatoid arthritis (RA). To determine the relation between TNF-238 and disease progression, the extent of joint destruction in a cohort of 101 RA patients followed for 12 years was analyzed. Furthermore, we have attempted to link this polymorphism to TNF-alpha gene transcription in monocytes and lymphocytes in vitro. Patients, Materials, and Methods: The extent of joint destruction determined on X-rays of hands and feet assessed after 0, 3, 6, and 12 years was compared with TNF-238 genotypes. Functional consequences of TNF-alpha gene polymorphisms using reporter gene constructs were analyzed in cells of the monocyte and lymphocyte lineage by means of transient transfection systems. Results: The rate of joint damage in -238GA patients was lower than that in the -238GG patients, independent of HLA-DR4. Damage after 12 years was 76 +/- 30 for the -238GA versus 126 +/- 13 for the -238GG patients as determined by the van der Heijde's modification of Sharp's method. Furthermore, TNF-238A was found to be in linkage disequilibrium with an additional polymorphism at position -376. Functional assays revealed no significant differences in the level of inducible reporter gene expression between the TNF-238/-376 promoter constructs in the cell types tested. Conclusion: In a prospective study, we show that the TNF-238GG genotype contributes to progression of joint destruction in RA, independent of: the presence of HLA-DR4. However, in vitro transfection assays indicate that TNF-238A by itself or in combination with TNF-376A is not likely to be of direct functional relevance for transcriptional activation. Therefore, these polymorphisms may serve as markers for additional polymorphisms in the TNF/LT locus or neighboring genes that may influence disease severity. C1 Leiden Univ, Ctr Med, Dept Rheumatol, Leiden, Netherlands. Univ Munich, Inst Immunol, D-8000 Munich, Germany. VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. Belozersky Inst Phys Chem Biol, Moscow 117984, Russia. SAIC Frederick, Intramural Res Support Program, NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Kaijzel, EL (reprint author), Leiden Univ, Ctr Med, Dept Rheumatol, Leiden, Netherlands. RI Brinkman, Brigitta/C-1100-2009; Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 FU NCI NIH HHS [N01-CO-56000] NR 45 TC 80 Z9 83 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD NOV PY 1998 VL 4 IS 11 BP 724 EP 733 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 150GG UT WOS:000077655400005 PM 9932110 ER PT J AU Dasgupta, S Fernandez, L Kameyama, L Inada, T Nakamura, Y Pappas, A Court, DL AF Dasgupta, S Fernandez, L Kameyama, L Inada, T Nakamura, Y Pappas, A Court, DL TI Genetic uncoupling of the dsRNA-binding and RNA cleavage activities of the Escherichia coli endoribonuclease RNase III - the effect of dsRNA binding on gene expression (vol 28, pg 629, 1998) SO MOLECULAR MICROBIOLOGY LA English DT Correction C1 NCI, FCRDC, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. Univ Tokyo, Inst Med Sci, IMSUT, Dept Tumor Biol,Minato Ku, Tokyo 108, Japan. RP Dasgupta, S (reprint author), NCI, FCRDC, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, POB B, Frederick, MD 21702 USA. NR 1 TC 1 Z9 1 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 1998 VL 30 IS 3 BP 679 EP 679 PG 1 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 137BF UT WOS:000076893000023 ER PT J AU Guo, BP Brown, EL Dorward, DW Rosenberg, LC Hook, M AF Guo, BP Brown, EL Dorward, DW Rosenberg, LC Hook, M TI Decorin-binding adhesins from Borrelia burgdorferi SO MOLECULAR MICROBIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; PROTEOGLYCAN DECORIN; EUKARYOTIC CELLS; DS-PGII; LOCALIZATION; ADHERENCE; SEQUENCE; PROTEINS; CARTILAGE; COLLAGEN AB Lyme disease is a tick-transmitted infection caused by the spirochete Borrelia burgdorferi. Ticks deposit B. burgdorferi into the dermis of the host, where they eventually become associated with collagen fibres. We demonstrated previously that B. burgdorferi is unable to bind collagen, but can bind the collagen-associated proteoglycan decorin and expresses decorin-binding proteins (Dbps). We have now cloned and sequenced two genes encoding the proteins, DbpA and DbpB, which have a similar structure, as revealed by circular dichroism (CD) spectroscopy of recombinant proteins. Competition experiments revealed a difference in binding specificity between DbpA and DbpB. Western blot analysis of proteinase K-treated intact B. burgdorferi and transmission electron microscopy studies using antibodies raised against recombinant Dbps demonstrated that these proteins are surface exposed. DbpA effectively inhibits the attachment of B. burgdorferi to a decorin substrate, whereas DbpB had a marginal effect, suggesting a difference in substrate specificity between the two Dbps. Polystyrene beads coated with DbpA adhered to a decorin-containing extracellular matrix produced by cultured skin fibroblasts, whereas beads coated with OspC did not. Taken together, these data suggest that Dbps are adhesins of the MSCRAMM (microbial surface component-recognizing adhesive matrix molecule) family, which mediate B. burgdorferi attachment to the extracellular matrix of the host. C1 Texas A&M Univ, Albert B Alkek Inst Biosci & Technol, Ctr Extracellular Matrix Biol, Houston, TX 77030 USA. Texas A&M Univ, Dept Biochem & Biophys, Houston, TX 77030 USA. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Montefiore Med Ctr, Orthoped Res Labs, Bronx, NY 10467 USA. RP Hook, M (reprint author), Texas A&M Univ, Albert B Alkek Inst Biosci & Technol, Ctr Extracellular Matrix Biol, 2121 W Holcombe Blvd,Suite 603, Houston, TX 77030 USA. FU NIAMS NIH HHS [AR 44415] NR 43 TC 169 Z9 175 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 1998 VL 30 IS 4 BP 711 EP 723 DI 10.1046/j.1365-2958.1998.01103.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 147LV UT WOS:000077570000004 PM 10094620 ER PT J AU Alvarez, M Robey, R Sandor, V Nishiyama, K Matsumoto, Y Paull, K Bates, S Fojo, T AF Alvarez, M Robey, R Sandor, V Nishiyama, K Matsumoto, Y Paull, K Bates, S Fojo, T TI Using the national cancer institute anticancer drug screen to assess the effect of mrp expression on drug sensitivity profiles SO MOLECULAR PHARMACOLOGY LA English DT Article ID RESISTANCE-ASSOCIATED PROTEIN; HUMAN BREAST-CARCINOMA; ATP-DEPENDENT EFFLUX; TUMOR-CELL-LINES; MEMBRANE-VESICLES; TOPOISOMERASE-II; P-GLYCOPROTEIN; GLUTATHIONE; TRANSPORT; GENE AB The MRP gene contributes to one form of multidrug resistance. To identify drugs interacting with MRP, we measured MRP mRNA expression by quantitative PCR in 60 cell lines of the National Cancer Institute Anticancer Drug Screen. Expression was detected in all cell lines (highest in lung carcinomas and central nervous system tumors) with a range of 14-fold. A mean graph of MRP mRNA levels was constructed to determine Pearson correlation coefficients (PCCs) with mean graphs of >40,000 compounds using the COMPARE analysis. Only 20 compounds had PCCs of greater than or equal to 0.500. The PCCs for VP-16, doxorubicin, and vincristine were 0.008, 0.13, and 0.257, respectively. Initially, 36 compounds with PCCs of greater than or equal to 0.428 were analyzed using two MRP-overexpressing cell lines; low levels of cross-resistance was demonstrated for 23 compounds (1.3-9.4-fold). Twenty-four compounds also were available for further studies. Using a fluorescence activated cell sorter assay to measure competition of calcein efflux from MRP-overexpressing cells, 10 compounds were found to increase calcein retention by greater than or equal to 2-fold. Ten compounds also were able to reduce ATP-dependent [(3)H]LTC(4) transport into vesicles from MRP-overexpressing cells. These results contrast with previous studies with MDR-1 in which high correlations were found and confirmed for a large number of compounds. Although other assays may be more revealing, in these unselected cell lines, MRP mRNA expression was a poor predictor of drug sensitivity. This raises the possibility that other factors, including conjugating enzymes, glutathione levels, or other transporters, confound the MRP effect. C1 Catholic Univ Chile, Dept Hematol Oncol, Santiago, Chile. NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Informat Technol Branch, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. RP Alvarez, M (reprint author), Catholic Univ Chile, Dept Hematol Oncol, Lira 44, Santiago, Chile. NR 37 TC 49 Z9 49 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1998 VL 54 IS 5 BP 802 EP 814 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 142RB UT WOS:000077213200007 PM 9804615 ER PT J AU Hacia, JG Brody, LC Collins, FS AF Hacia, JG Brody, LC Collins, FS TI Applications of DNA chips for genomic analysis SO MOLECULAR PSYCHIATRY LA English DT Article DE genetics; hybridization; microarray; mutation detection; single nucleotide polymorphisms; RNA expression ID DENSITY OLIGONUCLEOTIDE ARRAYS; GENE-EXPRESSION PATTERNS; LIGHT-DIRECTED SYNTHESIS; MUTATION DETECTION; HYBRIDIZATION; MICROARRAY; SEQUENCE; DISEASE; CANCER; DIAGNOSTICS AB A major frontier in medical genetics is the definition of the molecular basis of multifactorial diseases. This is especially relevant in the field of clinical psychiatry where the majority of common disorders display complex inheritance patterns, and are further influenced by environmental interactions. New technologies are needed to help address the pressing needs for discovering and deciphering the nature of such disease-associated genes. One such technology which has emerged within the past 3 years involves hybridization-based nucleic acid array (DNA chip) analysis. This technology has the potential to have a lasting impact on diverse genomic-based applications such as large-scale gene mapping studies, mutational analysis, and global expression level monitoring of ail human genes. In this review we will describe the fundamental principles behind nucleic acid array-based assays, while focusing on their applications towards genome-wide DNA and RNA analysis. The current capabilities and limitations of these technologies will be discussed, with a focus on areas where future development will be needed for DNA chip-based assays to achieve their full potential. C1 NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NIH, Natl Human Genome Res Inst, Bldg 49-3A14, Bethesda, MD 20892 USA. EM fc23a@nih.gov NR 48 TC 29 Z9 30 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 1998 VL 3 IS 6 BP 483 EP 492 DI 10.1038/sj.mp.4000475 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 134UR UT WOS:000076762500008 PM 9857973 ER PT J AU Mezey, E Dehejia, AM Harta, G Suchy, SF Nussbaum, RL Brownstein, MJ Polymeropoulos, MH AF Mezey, E Dehejia, AM Harta, G Suchy, SF Nussbaum, RL Brownstein, MJ Polymeropoulos, MH TI Alpha synuclein is present in Lewy bodies in sporadic Parkinson's disease SO MOLECULAR PSYCHIATRY LA English DT Article DE Parkinson's disease; Lewy body; alpha-synuclein; ubiquitin; diffuse Lewy body disease (DLBD); Alzheimer's disease; Pick's disease ID ALZHEIMERS-DISEASE; NEUROPIL THREADS; BODY DISEASE; HUMAN-BRAIN; PLAQUES; IMMUNOCYTOCHEMISTRY; PROTEINS AB A missense mutation in the human alpha synuclein gene was recently identified in some cases of familial Parkinson's disease (FPD). We have developed an antibody that recognizes the C-terminal 12 amino acids of the human alpha synuclein protein and have demonstrated that alpha synuclein is an abundant component of the Lewy bodies found within the degenerating neurons of patients with Parkinson's disease (PD). The presence of alpha synuclein in Lewy bodies of sporadic PD patients suggests a central role for alpha synuclein in the pathogenesis of PD. C1 NIH, Genet Dis Res Branch, NHGRI, Bethesda, MD 20892 USA. RP Polymeropoulos, MH (reprint author), NIH, Genet Dis Res Branch, NHGRI, Bldg 49,Rm 4A66, Bethesda, MD 20892 USA. RI Brownstein, Michael/B-8609-2009 NR 23 TC 81 Z9 82 U1 1 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 1998 VL 3 IS 6 BP 493 EP 499 DI 10.1038/sj.mp.4000446 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 134UR UT WOS:000076762500009 PM 9857974 ER PT J AU Wolozin, B Maheshwari, S Jones, C Dukoff, R Wallace, W Racchi, M Nagula, S Shulman, NR Sunderland, T Bush, A AF Wolozin, B Maheshwari, S Jones, C Dukoff, R Wallace, W Racchi, M Nagula, S Shulman, NR Sunderland, T Bush, A TI beta-amyloid augments platelet aggregation: reduced activity of familial angiopathy-associated mutants SO MOLECULAR PSYCHIATRY LA English DT Article DE amyloid precursor protein; Alzheimer's disease; focal adhesion kinase; tyrosine phosphorylation; adenosine diphosphate ID HEREDITARY CEREBRAL-HEMORRHAGE; ALZHEIMERS-DISEASE; TYROSINE PHOSPHORYLATION; PRECURSOR PROTEIN; DUTCH-TYPE; PEPTIDE; INTEGRIN; NEUROTOXICITY; RECEPTORS; ADHESION AB The beta-amyloid (A beta) peptide is present both in serum and in platelets, however it is unclear whether A beta plays a role in platelet function. We have now investigated the effects of soluble A beta on platelet function and have found that low levels (0.1-1 nM) of soluble A beta augment ADP-dependent platelet aggregation and translocation of focal adhesion kinase to the platelet cytoskeleton. Addition of A beta to gel-filtered platelets along with concentrations of adenosine diphosphate (ADP) producing submaximal aggregation responses increased the aggregation response by over 2-fold depending on the ADP:A beta ratios. The structure activity requirements for A beta activity showed intriguing constraints. Only full length A beta has significant activity. Truncated A beta peptides, such as A beta(1-16) or A beta(25-35), or reverse A beta(40-1) all show little or no activity. We also examined the activity of mutant A beta peptides, corresponding with the APP(692A-->G) and APP(693E-->Q) (at A beta 21 and A beta 22, respectively) which are found in familiar Alzheimer's disease and hereditary cerebral hemorrhagic amyloidosis, Dutch type (HCHWA-D), and found that these peptides showed little or no activity. These results suggest that A beta interacts with platelets in a highly specific manner and may play a role in regulating platelet function. C1 NIMH, Sect Geriatr Psychiat, Bethesda, MD 20892 USA. NIDDK, Clin Hematol Branch, Bethesda, MD 20892 USA. NIA, Mol Neurobiol Unit, Bethesda, MD 20892 USA. Sacred Heart Hosp, Alzheimer Dept, Mol & Cellular Neurobiol Lab, Brescia, Italy. Univ Milan, Inst Pharmacol Sci, Milan, Italy. Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA USA. RP Wolozin, B (reprint author), Loyola Univ, Med Ctr, Dept Pharmacol, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 27 TC 10 Z9 10 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 1998 VL 3 IS 6 BP 500 EP 507 DI 10.1038/sj.mp.4000451 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 134UR UT WOS:000076762500010 PM 9857975 ER PT J AU Palliyath, S Hallett, M Thomas, SL Lebiedowska, MK AF Palliyath, S Hallett, M Thomas, SL Lebiedowska, MK TI Gait in patients with cerebellar ataxia SO MOVEMENT DISORDERS LA English DT Article DE cerebellum; degeneration; gait; ataxia; multijoint coordination ID LOCOMOTION; KINEMATICS AB The gait pattern in 10 patients with cerebellar degenerations was studied and the results were compared with 10 matched normal subjects, seeking the principal patterns in this disorder. Gait at natural speed was studied in a biomechanics laboratory using a video-based kinematic data acquisition system for measuring body movements. Patients showed a reduced step and stride length with a trend to reduced cadence. Heel off time, toe off time, and time of peak flexion of the knee in swing were all delayed. Range of motion of ankle, knee, and hip were all reduced, but only ankle range of motion reached significance. Multijoint coordination was impaired, as indicated by a relatively greater delay of planter flexion of the ankle compared with flexion of the knee and a relatively late knee flexion compared with hip flexion at the onset of swing. The patients also showed increased variability of almost all measures. Although some of the deviations from normal were simply the result of slowness of walking, the gait pattern of patients with cerebellar degeneration shows incoordination similar to that previously described for their multijoint limb motion. C1 Vet Adm Med Ctr, New Orleans, LA 70146 USA. So Illinois Univ, Sch Med, Dept Orthoped & Rehabil, Springfield, IL USA. RP Hallett, M (reprint author), NINDS, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 13 TC 76 Z9 77 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 1998 VL 13 IS 6 BP 958 EP 964 DI 10.1002/mds.870130616 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 134VQ UT WOS:000076764700015 PM 9827622 ER PT J AU Samii, A Luciano, CA Dambrosia, JM Hallett, M AF Samii, A Luciano, CA Dambrosia, JM Hallett, M TI Central motor conduction time: Reproducibility and discomfort of different methods SO MUSCLE & NERVE LA English DT Article DE transcranial magnetic stimulation; central motor conduction; reproducibility; discomfort; human ID CERVICAL MAGNETIC STIMULATION; BRAIN-STIMULATION; CLINICAL-APPLICATIONS; NERVE-CONDUCTION; DISEASE; VARIABILITY; PROPAGATION; EXPERIENCE; MECHANISMS; CORTEX AB Central motor conduction time, a useful measure for studying central motor pathways, is calculated by determining the difference between the latency of motor-evoked potentials and peripheral conduction time. The intraindividual trial-to-trial variability of central motor conduction time and the discomfort associated with three methods of measuring peripheral motor conduction time (F-wave latency, cervical magnetic stimulation, and cervical needle stimulation) were studied in 5 healthy subjects with the use of transcranial magnetic stimulation to elicit motor-evoked potentials. Central motor conduction time was calculated by using measurements, made on 3 separate days, from the same three muscles on each hand. A visual analog pain scale was used to determine the level of discomfort for each method. Intraindividual trial-to-trial variability of central motor conduction time was similar for all methods, with coefficients of variation of 13% for the F-wave latency, 15% for cervical magnetic stimulation, and 11% for cervical needle stimulation. The last method was significantly more painful than the other two methods; there was no significant difference in discomfort between the F-wave method and cervical magnetic stimulation. To assess peripheral motor conduction time, when determining central motor conduction time, either the F-wave method or cervical magnetic stimulation is preferable to cervical needle stimulation. (C) 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1445-1450, 1998. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NINDS, EMG Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. NR 32 TC 24 Z9 24 U1 1 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD NOV PY 1998 VL 21 IS 11 BP 1445 EP 1450 DI 10.1002/(SICI)1097-4598(199811)21:11<1445::AID-MUS12>3.0.CO;2-# PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 124EJ UT WOS:000076168200012 PM 9771668 ER PT J AU Miller, AC Fuciarelli, AF Jackson, WE Ejnik, EJ Emond, C Strocko, S Hogan, J Page, N Pellmar, T AF Miller, AC Fuciarelli, AF Jackson, WE Ejnik, EJ Emond, C Strocko, S Hogan, J Page, N Pellmar, T TI Urinary and serum mutagenicity studies with rats implanted with depleted uranium or tantalum pellets SO MUTAGENESIS LA English DT Article ID WATER-TREATMENT WORKERS; ALPHA-PARTICLES; EXPOSURE; RADON; INHIBITOR; MUTATIONS; STRAINS; DRUGS; CELLS; P53 AB During the 1991 Persian Gulf War several US military personnel were wounded by shrapnel fragments consisting of depleted uranium. These fragments were treated as conventional shrapnel and were not surgically removed to spare excessive tissue damage. Uranium bioassays conducted over a year after the initial uranium injury indicated a significant increase in urine uranium levels above natural background levels. The potential mutagenic effects of depleted uranium are unknown. To assess the potential mutagenic effects of long-term exposure to internalized depleted uranium, Sprague-Dawley rats were implanted with depleted uranium and their urine and serum were evaluated for mutagenic potential at various times after pellet implantation using the Ames Salmonella reversion assay. Tantalum, an inert metal widely used in prosthetic devices was used for comparison. Enhancement of mutagenic activity in Salmonella typhiurium strain TA98 and the Ames II(TM) mixed strains (TA7001-7006) was observed in urine samples from animals implanted with depleted uranium pellets. In contrast, urine samples from animals implanted with tantalum did not show a significant enhancement of mutagenic activity in these strains. In depleted uranium-implanted animals, urine mutagenicity increased in a dose- and time-dependent manner demonstrating a strong positive correlation with urine uranium levels (r = 0.995, P < 0.001). There was no mutagenic enhancement of any bacterial strain detected in the sera of animals implanted with either depleted uranium or tantalum pellets. The results suggest that uranium content in the urine is correlated with urine mutagenicity and that urinary mutagenicity might be used as a biomarker to detect exposure to internalized uranium. C1 Armed Forces Radiobiol Res Inst, Appl Cellular Radiobiol Dept, Bethesda, MD 20889 USA. Armed Forces Radiobiol Res Inst, Radiat Pathophysiol Dept, Bethesda, MD 20889 USA. EMP Dept, Pacific NW Lab, Richland, WA USA. NCI, Div Canc Treatment, NIH, Bethesda, MD 20892 USA. RP Miller, AC (reprint author), Armed Forces Radiobiol Res Inst, Appl Cellular Radiobiol Dept, Bethesda, MD 20889 USA. NR 33 TC 55 Z9 61 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD NOV PY 1998 VL 13 IS 6 BP 643 EP 648 DI 10.1093/mutage/13.6.643 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 140HY UT WOS:000077082900015 PM 9862198 ER PT J AU Erexson, GL Cunningham, ML Tindall, KR AF Erexson, GL Cunningham, ML Tindall, KR TI Cytogenetic characterization of the transgenic Big Blue (R) Rat2 and Big Blue (R) mouse embryonic fibroblast cell lines SO MUTAGENESIS LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; SISTER-CHROMATID EXCHANGES; CHROMOSOMAL-ABERRATIONS; MUTATIONS; CHEMICALS; MICE AB The transgenic Big Blue(R) Rat2 and Big Blue(R) mouse embryonic fibroblast cell lines have been used to complement the transgenic Big Blue(R) rat and mouse in vivo mutagenesis assays, However, limited information is available regarding the karyology of these cell lines. Therefore, we have characterized the ploidy, mitotic index, spontaneous frequencies of chromosome and chromatid aberrations and rate of micronucleus (MN) formation in both cell lines. We have also characterized the frequency of sister chromatid exchange (SCE) in transgenic Big Blue(R) mouse cells. Big Blue(R) Rat2 cells are hyperploid and have extremely high baseline frequencies of cytogenetic damage. In addition, Big Blue(R) Rat2 cells are BrdU-resistant, therefore, SCE frequencies cannot be assessed in these cells, We conclude that Big Blue(R) Rat2 cells are not useful for routine cytogenetic toxicology studies. The transgenic Big Blue(R) mouse cell line is polyploid and consistently yields a low mitotic index (similar to 1%) in untreated cells, These mouse cells also exhibited moderately high baseline frequencies of chromosome and chromatid aberrations, however, baseline frequencies of SCE and of MN were not elevated. Transgenic Big Blue(R) mouse embryonic fibroblasts were further studied for MN induction following treatment with N-ethyl-N-nitrosourea (ENU) for 0.5 h at concentrations of 0.425, 0.85 and 1.7 mM, Concentration-dependent increases in MN were observed in these cells, Thus, while an ENU-induced cytogenetic response using transgenic Big Blue(R) mouse cells demonstrates that this cellular model could be used to cytogenetically complement the mutagenesis assays, the low mitotic index and the high spontaneous frequency of chromosome damage confounds its use for routine genetic toxicology studies. C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Mol Mutagenesis Grp, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Tindall, KR (reprint author), NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Mol Mutagenesis Grp, POB 12233, Res Triangle Pk, NC 27709 USA. EM tindall@niehs.nih.gov NR 21 TC 14 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD NOV PY 1998 VL 13 IS 6 BP 649 EP 653 DI 10.1093/mutage/13.6.649 PG 5 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 140HY UT WOS:000077082900016 PM 9862199 ER PT J AU Flax, JD Aurora, S Yang, CH Simonin, C Wills, AM Billinghurst, LL Jendoubi, M Sidman, RL Wolfe, JH Kim, SU Snyder, EY AF Flax, JD Aurora, S Yang, CH Simonin, C Wills, AM Billinghurst, LL Jendoubi, M Sidman, RL Wolfe, JH Kim, SU Snyder, EY TI Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes SO NATURE BIOTECHNOLOGY LA English DT Article DE cell therapy; progenitor cell; gene therapy; Tay-Sachs disease; transplantation; differentiation ID CENTRAL-NERVOUS-SYSTEM; REGION-SPECIFIC DIFFERENTIATION; FIBROBLAST GROWTH-FACTOR; PROGENITOR CELLS; MOUSE-BRAIN; PRECURSORS; LINES; CNS; TRANSPLANTATION; FOREBRAIN AB Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. These self-renewing clones give rise to all fundamental neural lineages in vitro, Following transplantation into germinal zones of the newborn mouse brain they participate in aspects of normal development, including migration along established migratory pathways to disseminated central nervous system regions, differentiation into multiple developmentally and regionally appropriate cell types, and nondisruptive interspersion with host progenitors and their progeny. These human NSCs can be genetically engineered and are capable of expressing foreign transgenes in vivo. Supporting their gene therapy potential, secretory products from NSCs can correct a prototypical genetic metabolic defect in neurons and glia in vitro, The human NSCs can also replace specific deficient neuronal populations, Cryopreservable human NSCs may be propagated by both epigenetic and genetic means that are comparably safe and effective, By analogy to rodent NSCs, these observations may allow the development of NSC transplantation for a range of disorders. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. NEI, NIH, Bethesda, MD 20892 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Ctr Comparat Med Genet, Philadelphia, PA 19104 USA. Univ British Columbia, Univ Hosp, Dept Med, Div Neurol, Vancouver, BC V5Z 1M9, Canada. RP Snyder, EY (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. EM Snyder@A1.TCH.Harvard.edu FU NIDDK NIH HHS [DK42707, DK46637]; NINDS NIH HHS [NS33852] NR 41 TC 560 Z9 602 U1 3 U2 17 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 1998 VL 16 IS 11 BP 1033 EP 1039 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 136QF UT WOS:000076870100024 PM 9831031 ER PT J AU Brustle, O Choudhary, K Karram, K Huttner, A Murray, K Dubois-Dalcq, M McKay, RDG AF Brustle, O Choudhary, K Karram, K Huttner, A Murray, K Dubois-Dalcq, M McKay, RDG TI Chimeric brains generated by intraventricular transplantation of fetal human brain cells into embryonic rats SO NATURE BIOTECHNOLOGY LA English DT Article DE stem cell; neural progenitor cell; cell therapy ID CENTRAL-NERVOUS-SYSTEM; PROGENITOR CELLS; STEM-CELLS; NEURAL PROGENITORS; GROWTH-FACTOR; PRECURSORS; OLIGODENDROCYTES; MYELINATION; FOREBRAIN; PROTEIN AB Limited experimental access to the central nervous system (CNS) is a key problem in the study of human neural development, disease, and regeneration. We have addressed this problem by generating neural chimeras composed of human and rodent cells. Fetal human brain cells implanted into the cerebral ventricles of embryonic rats incorporate individually into all major compartments of the brain, generating widespread CNS chimerism. The human cells differentiate into neurons, astrocytes, and oligodendrocytes, which populate the host fore-, mid-, and hindbrain. These chimeras provide a unique model to study human neural cell migration and differentiation in a functional nervous system. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Bonn, Med Ctr, Dept Neuropathol, D-53105 Bonn, Germany. Inst Pasteur, Unite Neurovirol & Regenerat Syst Nerveux, F-75724 Paris, France. RP Brustle, O (reprint author), NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 37 TC 209 Z9 228 U1 1 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 1998 VL 16 IS 11 BP 1040 EP 1044 DI 10.1038/3481 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 136QF UT WOS:000076870100025 PM 9831032 ER PT J AU Lauro, D Kido, Y Castle, AL Zarnowski, MJ Hayashi, H Ebina, Y Hayashi, H Accili, D AF Lauro, D Kido, Y Castle, AL Zarnowski, MJ Hayashi, H Ebina, Y Hayashi, H Accili, D TI Impaired glucose tolerance in mice with a targeted impairment of insulin action in muscle and adipose tissue SO NATURE GENETICS LA English DT Article ID TRANSGENIC MICE; DIABETES-MELLITUS; BETA-CELL; RECEPTOR; RESISTANCE; NIDDM; GENE; EXPRESSION AB Type 2 diabetes is a complex metabolic disorder characterized by peripheral insulin resistance and impaired beta cell function(1,2) Insulin resistance is inherited as a non-mendelian trait(3). In genetically predisposed individuals, resistance of skeletal muscle and adipose tissue to insulin action precedes the onset of clinical diabetes, and is thought to contribute to hyperglycaemia by leading to impaired beta cell function and increased hepatic glucose production(4,5). It is not clear whether beta cell and liver defects are also genetically determined(2). To test the hypothesis that insulin resistance in muscle and fat is sufficient to cause type 2 diabetes in the absence of intrinsic beta cell and liver abnormality, we generated transgenic mice that were insulin-resistant in skeletal muscle and adipose tissue. These mice developed all the prodromal features of type 2 diabetes hut, despite the compounded effect of peripheral insulin resistance and a mild impairment of beta cell function, failed to become diabetic. These findings indicate the need for a critical re-examination of the primary site(s) of insulin resistance in diabetes. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Univ Tokushima, Inst Enzyme Res, Tokushima 770, Japan. RP Accili, D (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. OI Lauro, Davide/0000-0002-8597-4415 NR 23 TC 93 Z9 97 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1998 VL 20 IS 3 BP 294 EP 298 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 133QW UT WOS:000076698100027 PM 9806552 ER PT J AU Morris, L Martin, DJ Quinn, TC Chaisson, RE AF Morris, L Martin, DJ Quinn, TC Chaisson, RE TI The importance of doing HIV research in developing countries SO NATURE MEDICINE LA English DT Editorial Material ID VIRAL LOAD; VIRUS LOAD; INFECTION; TRANSMISSION; HYDROXYUREA; DIDANOSINE; DISEASES; THERAPY; AFRICA; IMPACT C1 Natl Inst Virol, AIDS Virus Res Unit, Johannesburg, South Africa. NIAID, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Morris, L (reprint author), Natl Inst Virol, AIDS Virus Res Unit, Johannesburg, South Africa. OI , Lynn/0000-0003-3961-7828 NR 20 TC 1 Z9 1 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 1998 VL 4 IS 11 BP 1228 EP 1229 DI 10.1038/3206 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 134EY UT WOS:000076731000020 PM 9809535 ER PT J AU Miller, LH Smith, JD AF Miller, LH Smith, JD TI Motherhood and malaria SO NATURE MEDICINE LA English DT Editorial Material ID FALCIPARUM-INFECTED ERYTHROCYTES; PLASMODIUM-FALCIPARUM; CHONDROITIN SULFATE; ADHERENCE; RECEPTOR; SURFACE C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Miller, LH (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 13 TC 19 Z9 19 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 1998 VL 4 IS 11 BP 1244 EP 1245 DI 10.1038/3223 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 134EY UT WOS:000076731000030 PM 9809545 ER PT J AU Studer, L Tabar, V McKay, R AF Studer, L Tabar, V McKay, R TI Survival of expanded dopaminergic precursors is critical for clinical trials - Reply SO NATURE NEUROSCIENCE LA English DT Letter C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Studer, L (reprint author), NINDS, Mol Biol Lab, NIH, 36 Convent Dr,Bldg 36,Room SA29, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 1 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 1998 VL 1 IS 7 BP 537 EP 537 DI 10.1038/2774 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 146NL UT WOS:000077437100003 ER PT J AU Toth, K McBain, CJ AF Toth, K McBain, CJ TI Afferent-specific innervation of two distinct AMPA receptor subtypes on single hippocampal interneurons SO NATURE NEUROSCIENCE LA English DT Article ID GUINEA-PIG HIPPOCAMPUS; MOSSY FIBER SYNAPSES; GLUTAMATE RECEPTORS; RAT HIPPOCAMPUS; CA2+ PERMEABILITY; SUBUNIT COMPOSITION; KAINATE RECEPTORS; SYNAPTIC TRANSMISSION; INWARD RECTIFICATION; SELECTIVE ANTAGONISM AB Using the polyamine toxin philanthotoxin, which selectively blocks calcium-permeable AMPA receptors, we show that synaptic transmission onto single hippocampal interneurons occurs by afferent-specific activation of philanthotoxin-sensitive and -insensitive AMPA receptors, Calcium-permeable AMPA receptors are found exclusively at synapses from mossy fibers. In contrast, synaptic responses evoked by stimulation of CA3 pyramidal neurons are mediated by calcium-impermeable AMPA receptors. Both pathways converge onto single interneurons and can be discriminated with Group II mGluR agonists. Thus, single interneurons target AMPA receptors of different subunit composition to specific postsynaptic sites, providing a mechanism to increase the synapse-specific computational properties of hippocampal interneurons. C1 NICHD, Lab Cellular & Mol Neurophysiol, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, Rm 5A72,Bldg 49,49 Convent Dr, Bethesda, MD 20892 USA. NR 50 TC 185 Z9 187 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 1998 VL 1 IS 7 BP 572 EP 578 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 146NL UT WOS:000077437100012 PM 10196564 ER PT J AU Agodoa, L AF Agodoa, L TI Patterns of end-stage renal disease in US African-Americans SO NEPHROLOGY LA English DT Article DE African-Americans; diabetes mellitus; end-stage renal disease; hypertension AB Although African-Americans constitute only about 12.4% of the population of the United States of America (USA), they comprise over 30% of the end-stage renal disease (ESRD) patient population. Diabetes mellitus (predominantly type 2) is the most frequently reported cause of ESRD in all racial and ethnic groups in the USA. However, hypertensive renal disease is reported as the dominant cause of ESRD in African-Americans. In general, all racial and ethnic minority group in the USA have greater incidence and prevalence rates of ESRD than Caucasians, However, survival probabilities in all ESRD patients, dialysis patients, and cadaveric renal allograft recipients are greater in African-Americans than in Caucasians. The suggested reasons for these racial and ethnic disparities are discussed. C1 NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Agodoa, L (reprint author), NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD NOV PY 1998 VL 4 SU S BP S12 EP S16 DI 10.1111/j.1440-1797.1998.tb00464.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 172AZ UT WOS:000078900300005 ER PT J AU Fogo, A Breyer, JA Smith, MC Cleveland, WH Agodoa, L Kirk, KA Glassock, R AF Fogo, A Breyer, JA Smith, MC Cleveland, WH Agodoa, L Kirk, KA Glassock, R CA AASK Pilot Study Investigators TI Renal histopathology in US African-Americans with presumed hypertensive nephrosclerosis SO NEPHROLOGY LA English DT Article DE African-Americans; hypertension; hypertensive nephrosclerosis; renin-angiotensin system ID ANGIOTENSIN-CONVERTING ENZYME; UNITED-STATES; DISEASE; DIAGNOSIS; GENE; RISK AB African-Americans have, in comparison with Caucasians, excess hypertension and end-stage renal disease, which has been presumed to be due to hypertension. However, systematic renal biopsy assessment of lesions in this population and verification of this clinical impression have not been done. During the pilot phase of the AASK trial, 46 hypertensive (diastolic BP > 95 mmHg) non-diabetic African-American patients between the ages of 18-70 years, with glomerular filtration rate (GFR) between 25 and 70 mL/min per 1.73m(2) and without marked proteinuria were therefore biopsied to assess underlying lesions. Adequate biopsy material was obtained in 39 (29 men and 10 women), on average 53.0 +/- 11.0 years old, with MAP of 109 +/- 15 mmHg and GFR 51.7 +/- 13.6 mL/min per 1.73 m(2). Of these 39 biopsies, 38 showed arteriosclerosis and/or arteriolosclerosis, severity on average 1.5 +/- 0.9 and 1.5 +/- 0.8, respectively, on a 0-3+ scale. Interstitial fibrosis was moderate, 1.3 +/- 0.9 (0-3+ scale). Segmental glomerulosclerosis was present in five biopsies, and in one patient, biopsy and clinical findings were consistent with idiopathic focal segmental glomerulosclerosis. Additional lesions included mesangiopathic glomerulonephritis in one patient, basement membrane thickening suggestive of diabetic nephropathy in one, and cholesterol emboli in two cases. Arteriolar and arterial sclerosis were tightly linked, and correlated with interstitial fibrosis and the reciprocal of serum creatinine. Global glomerulosclerosis was extensive, involving on average 43 +/- 26% of glomeruli. The extent of this lesion did not correlate with degree of arteriolar or arterial thickening, but did correlate with systolic blood pressure (P = 0.0174), the reciprocal of serum creatinine (P = 0.0009), serum cholesterol (P = 0.0129) and interstitial fibrosis (P < 0.0001). These data underscore that the clinical diagnosis of hypertensive nephrosclerosis based on strict clinical criteria in non-diabetic African-Americans with mild to moderate renal insufficiency without marked proteinuria is strongly correlated with renal biopsy vascular lesions consistent with this clinical diagnosis. However, the mechanism(s) for this clinicopathologic constellation remains undetermined. Current studies are focused on possible genetic contributions to the development of hypertension and renal lesions in this population. C1 Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Div Nephrol, Nashville, TN 37232 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH USA. Moorehouse Sch Med, Atlanta, GA USA. NIDDKD, Div Kidney Urol & Hematol Dis, Bethesda, MD USA. Univ Alabama, Birmingham, AL USA. Univ Kentucky, Dept Med, Lexington, KY 40506 USA. RP Fogo, A (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, MCN C-3310, Nashville, TN 37232 USA. NR 18 TC 3 Z9 3 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD NOV PY 1998 VL 4 SU S BP S54 EP S58 DI 10.1111/j.1440-1797.1998.tb00473.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 172AZ UT WOS:000078900300014 ER PT J AU Imperatore, G Nelson, RG AF Imperatore, G Nelson, RG TI Genetic susceptibility to nephropathy in Pima Indians with type 2 diabetes mellitus SO NEPHROLOGY LA English DT Article DE diabetic nephropathy; genetics; linkage analysis; Pima Indians ID CONVERTING-ENZYME GENE; ALDOSE REDUCTASE GENE; URINARY ALBUMIN EXCRETION; STAGE RENAL-DISEASE; PROLIFERATIVE RETINOPATHY; ANGIOTENSINOGEN GENE; OVERT NEPHROPATHY; IDDM PATIENTS; POLYMORPHISM; NIDDM AB In Pima Indians, the incidence of end-stage renal disease, nearly all of which is attributable to type 2 diabetes mellitus, is more than 20 times that in the general United States population. Studies in the Pimas indicate that factors other than diabetes per se enhance susceptibility tu the development of diabetic nephropathy. Aggregation of renal disease in families, a relationship between parental blood pressure and diabetic nephropathy in the offspring, and an association between higher prediabetic blood pressure and the occurrence of renal disease after the onset of diabetes all point to individual differences in susceptibility. Although clustering of environmental exposures may be responsible for these findings, they may also represent genetic transmission of susceptibility to renal disease. Recently, linkage analyses were performed in 98 diabetic sib-pairs, both affected by diabetic nephropathy. Two adjacent markers on chromosome 7 met the criteria for suggestive linkage with two-point analysis. Positioned between these markers is the gene coding for aldose reductase. Polymorphisms of this locus are associated with diabetic microvascular complications in other populations. Linkage studies provide evidence that familial aggregation of diabetic renal disease reflects, in part, genetic transmission of susceptibility that appears to be independent uf thr transmission of diabetes. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. RP Nelson, RG (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Nelson, Robert/B-1470-2012 NR 50 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD NOV PY 1998 VL 4 SU S BP S34 EP S39 DI 10.1111/j.1440-1797.1998.tb00470.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 172AZ UT WOS:000078900300011 ER PT J AU Lippa, CF Flanders, KC Kim, ES Croul, S AF Lippa, CF Flanders, KC Kim, ES Croul, S TI TGF-beta receptors-I and -II immunoexpression in Alzheimer's disease: A comparison with aging and progressive supranuclear palsy SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; cytokine; dementia; glia; receptor; TGF-beta ID GROWTH-FACTOR-BETA; MIDBRAIN DOPAMINERGIC-NEURONS; TRANSIENT FOREBRAIN ISCHEMIA; RAT-BRAIN; TRANSFORMING GROWTH-FACTOR-BETA-1; MESSENGER-RNA; SERINE/THREONINE KINASE; HIPPOCAMPAL-NEURONS; CEREBRAL-ISCHEMIA; SENSORY NEURONS AB The transforming growth factor-ps (TGF-Ps) influence cell survival, and TGF-beta 2 shows increased immunoexpression in neurofibrillary tangle-bearing neurons and reactive glia in Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). We compared immunohistochemical expression of TGF-beta type I (RI) and type II (RII) receptors in eight patients with AD, eight controls and three cases of progressive supranuclear palsy. Mild intraneuronal immunoreactivity for the RI receptor was observed in all cases. Intraneuronal TGF-beta RII receptor immunoexpression was more common in all groups, and its frequency did not differ between groups. We observed increased immunoreactivity for both RI and RII subtypes in reactive glia in the AD frontal cortex (RI: U = 0.5,p = 0.002; and RII: U = 9.000, p = 0.006) and parahippocampal gyrus (RI: U = 9.500, p = 0.013; RII: U = 14.5, p = 0.05) compared to control cases. We conclude that TGF-beta RI and II immunoreactivity is increased in reactive glia In AD and progressive supranuclear palsy, and RI immunoreactivity may occasionally be increased in neurons in cases with advanced AD. (C) 1999 Elsevier Science Inc. C1 Med Coll Penn & Hahnemann Univ, Dept Neurol, Philadelphia, PA 19129 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Med Coll Penn & Hahnemann Univ, Dept Pathol, Philadelphia, PA USA. RP Lippa, CF (reprint author), Med Coll Penn & Hahnemann Univ, Dept Neurol, 3300 Henry Ave,9th Floor,Room 556C, Philadelphia, PA 19129 USA. EM LIPPA@AUHS.edu FU PHS HHS [13623] NR 52 TC 18 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1998 VL 19 IS 6 BP 527 EP 533 DI 10.1016/S0197-4580(98)00089-X PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 175RJ UT WOS:000079108500004 PM 10192211 ER PT J AU Calhoun, ME Kurth, D Phinney, AL Long, JM Hengemihle, J Mouton, PR Ingram, DK Jucker, M AF Calhoun, ME Kurth, D Phinney, AL Long, JM Hengemihle, J Mouton, PR Ingram, DK Jucker, M TI Hippocampal neuron and synaptophysin-positive bouton number in aging C57BL/6 mice SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; CNS; brain; mouse; hippocampus; neurons; synapses; stereology; maze learning; memory; behavior; synaptophysin ID UNBIASED STEREOLOGICAL ESTIMATION; RADIAL MAZE PERFORMANCE; IMPAIRED AGED RATS; ALZHEIMERS-DISEASE; MOUSE STRAINS; DENTATE GYRUS; OLD MICE; MEMORY; BRAIN; SYNAPSES AB A loss of hippocampal neurons and synapses had been considered a hallmark of normal aging and, furthermore, to br: a substrate of age-related learning and memory deficits. Recent stereological studies in humans have shown that only a relatively minor neuron loss occurs with aging and that this loss is restricted to specific brain regions, including hippocampal subregions. Here, we investigate these age-related changes in C57BL/6J mice, one of thr must commonly used laboratory mouse strains. Twenty-five mice (groups at 2, 14, and 28-31 months of age) were assessed for Morris water-maze performance, and modern stereological techniques were used to estimate total neuron and synaptophysin-positive bouton number in hippocampal subregions at the light microscopic level. Results revealed that performance in the water maze was largely maintained with aging. No age-related decline was observed in number of dentate gyrus granule cells or CAI pyramidal cells. In addition, no age-related change in number of synaptophysin-positive boutons was observed in the molecular layer of the dentate gyrus or CAI region of hippocampus. We observed a significant correlation between dentate gyrus synaptophysin-positive bouton number and water-maze performance. These results demonstrate that C57BL/6J mice do not exhibit major age-related deficits in spatial learning or hippocampal structure, providing a baseline for further study of mouse brain aging. (C) 1999 Elsevier Science Inc. C1 Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Jucker, M (reprint author), Univ Basel, Inst Pathol, Schonbeinstr 40, CH-4003 Basel, Switzerland. NR 53 TC 160 Z9 168 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1998 VL 19 IS 6 BP 599 EP 606 DI 10.1016/S0197-4580(98)00098-0 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 175RJ UT WOS:000079108500013 PM 10192220 ER PT J AU Grady, CL McIntosh, AR Bookstein, F Horwitz, B Rapoport, SI Haxby, JV AF Grady, CL McIntosh, AR Bookstein, F Horwitz, B Rapoport, SI Haxby, JV TI Age-related changes in regional cerebral blood flow during working memory for faces SO NEUROIMAGE LA English DT Article DE aging; cerebral blood how memory; neuroimaging; human ID POSITRON EMISSION TOMOGRAPHY; BRAIN GLUCOSE-UTILIZATION; PARTIAL LEAST-SQUARES; PREFRONTAL CORTEX; NEURAL SYSTEMS; FRONTAL-CORTEX; FUNCTIONAL-ORGANIZATION; DOUBLE DISSOCIATION; SEX-DIFFERENCES; VISUAL MEMORY AB Young and old adults underwent positron emission tomography during the performance of a working memory task for faces (delayed match-to-sample), in which the delay between the sample and choice faces was varied from 1 to 21 s. Reaction time was slower and accuracy lower in the old group, but not markedly so. Values of regional cerebral blood how (rCBF) were analyzed for sustained activity across delay conditions, as well as for changes as delay increased, Many brain regions showed similar activity during these tasks in both young and old adults, including left anterior prefrontal carter, which had increased rCBF with delay, and ventral extrastriate cortex, which showed decreased rCBF with delay. However, old adults had less activation overall and less modulation of rCBF across delay in right ventrolateral prefrontal cortex than did the young adults. Old adults also showed greater rCBF activation in left dorsolateral prefrontal cortex across all WM delays and increased rCBF at short delays in left occipitoparietal cortex compared to young adults. Activity in many of these regions was differentially related to performance in that it was associated with decreasing response times in the young group and increasing response times in the older individuals. Thus despite the finding that performance on these memory tasks and associated activity in a number of brain areas are relatively preserved in old adults, differences elsewhere in the brain suggest that different strategies or cognitive processes are used by the elderly to maintain memory representations over short periods of time. (C) 1998 Academic Press. C1 Rotman Res Inst, Baycrest Ctr Geriatr Care, Toronto, ON, Canada. NIA, Neurosci Lab, Bethesda, MD 20892 USA. Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Grady, CL (reprint author), Rotman Res Inst, Baycrest Ctr Geriatr Care, Toronto, ON, Canada. RI McIntosh, Anthony/G-4955-2011; OI McIntosh, Anthony/0000-0002-1784-5662 NR 62 TC 167 Z9 170 U1 1 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV PY 1998 VL 8 IS 4 BP 409 EP 425 DI 10.1006/nimg.1998.0376 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 144GV UT WOS:000077306700009 PM 9811558 ER PT J AU Chrousos, GP Harris, AG AF Chrousos, GP Harris, AG TI Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy - 1. General principles SO NEUROIMMUNOMODULATION LA English DT Review DE hypothalamic-pituitary-adrenal axis; HPA axis, structure and function; HPA axis, testing; adrenal insufficiency; asthma; inhaled corticosteroids ID CORTICOTROPIN-RELEASING HORMONE; FLUTICASONE PROPIONATE; HEALTHY-VOLUNTEERS; BETA-ENDORPHIN; ASTHMA; BUDESONIDE; INSUFFICIENCY; SECRETION; CHILDREN; ADRENOCORTICOTROPIN AB The safety of long-term inhaled corticosteroid therapy at commonly prescribed doses is an issue of growing concern to physicians and international regulatory bodies. This is so because long-term use of these drugs has become the mainstay of chronic asthma management and their introduction now is widely recommended in official treatment guidelines at the 'mild persistent' stage of asthma, where regular daily therapy is first begun. In addition to more frequent use of inhaled corticosteroids, there is a further trend to use higher doses of existing inhaler therapies and to use the newer and more potent compounds that have recently become available. At the same time as these developments have been taking place, there has not been a concurrent move to a more rigorous examination of the safety profile of these inhaled corticosteroid treatments - especially to assess their effects on the hypothalamic-pituitary-adrenal (HPA) axis. Most safety data with respect to HPA axis effects have been derived from testing methods that are limited in their ability to detect HPA system impairment and, more seriously, that can give the impression of functional integrity in the HPA axis when there may be moderate (or even greater) impairment. In this first part of a two-part review of the HPA axis effects of inhaled corticosteroids and of how these effects should be assessed, we examine the currently used and the currently available testing methodologies and also review the present state of knowledge concerning the structure and function of the HPA axis and the effects of its suppression. It is clear that there are state-of-the-art tests to assess in a discriminating manner the safety profile of inhaled corticosteroids. These tests have been insufficiently employed, including during the drug development process, yet they are readily available, relatively inexpensive and can detect adrenal suppression before the appearance of clinical effects. In part 2 of this review we examine what can be learned about the effects of inhaled corticosteroid therapy on the HPA axis from the limited amount of reliable published information from clinical and pharmacological studies describing their use and safety. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD USA. Schering Plough Corp, Phase 4 Res Unit, Kenilworth, NJ 07033 USA. RP Chrousos, GP (reprint author), NICHHD, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 2862, Bethesda, MD 20892 USA. OI Harris, Alan/0000-0002-6618-2092 NR 60 TC 30 Z9 31 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PD NOV-DEC PY 1998 VL 5 IS 6 BP 277 EP 287 DI 10.1159/000026348 PG 11 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 132AR UT WOS:000076607900001 PM 9762010 ER PT J AU Chrousos, GP Harris, AG AF Chrousos, GP Harris, AG TI Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy - 2. Review of the literature SO NEUROIMMUNOMODULATION LA English DT Review DE hypothalamic-pituitary-adrenal axis; HPA axis, structure and function; HPA axis, testing; adrenal insufficiency; asthma; inhaled corticosteroids ID ADULT ASTHMATIC-PATIENTS; BECLOMETHASONE DIPROPIONATE; FLUTICASONE PROPIONATE; BRONCHIAL-ASTHMA; MODERATE ASTHMA; HEALTHY-VOLUNTEERS; CORTISOL SECRETION; DOSING FREQUENCY; MILD ASTHMA; HPA-AXIS AB In the first part of this two-part review it was noted that inhaled corticosteroids had become the mainstay of treatment for chronic asthma and yet the effects of long-term use of these compounds on the hypothalamic-adrenal-pituitary (HPA) axis were largely being determined by testing methods of limited reliability, especially by morning plasma cortisol measurements. It was established in our examination of the published literature and in our presentation of current knowledge of the structure and function of the HPA axis that safe, accurate and discriminating techniques to assess the functional status of the HPA axis were available. It was concluded that two state-of-the-art tests that have been insufficiently used were the ACTH stimulation test and measurement of the 24-hour integrated serial plasma cortisol concentrations. These two tests can detect adrenal suppression before the appearance of clinical effects. For part 2 of this review we conducted an exhaustive search of the English language clinical and pharmacological literature on the use of inhaled corticosteroids from 1988 until the present time to identify studies in which one or both of these testing methods have been used. We present our analysis of this limited number of studies to determine what accurately can be known of the HPA axis safety profile of three of the most commonly used and investigated inhaled corticosteroids - beclomethasone dipropionate, budesonide and fluticasone propionate. The first finding of significance was that only 50 reports were identified in which information on the HPA axis safety effects of orally inhaled steroids in asthma patients or in clinical pharmacological studies met our inclusion requirements. By analysis of the data presented in these reports we were able to reach the following conclusions: (1) inhaled corticosteroids administered chronically, and prudently, within recommended dose ranges do not endanger the functioning of the HPA axis, (2) the increasing tendency to use higher doses of inhaled corticosteroids on the assumption that there are clear dose-response benefits and no adverse HPA axis effects from long-term high-dose regimens is misguided and not supported by reliable published information, (3) the corollary - that higher corticosteroid potencies (as measured, for example, by skin-blanching activity) can have greater therapeutic effect in lung tissue without greater concomitant systemic activity - is a flawed concept, and (4) the limited clinical and pharmacological data support our part 1 conclusions that discriminating techniques to assess the functional HPA axis status should be an integral part of the drug development process and that further HPA axis function studies are required on existing inhaled corticosteroids - if they lack a rigorous testing history or long-term record of clinical safety. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD USA. Schering Plough Corp, Phase 4 Res Unit, Kenilworth, NJ 07033 USA. RP Chrousos, GP (reprint author), NICHHD, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 2862, Bethesda, MD 20892 USA. EM chrousog@cc1.nichd.nih.gov OI Harris, Alan/0000-0002-6618-2092 NR 68 TC 33 Z9 33 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PD NOV-DEC PY 1998 VL 5 IS 6 BP 288 EP 308 DI 10.1159/000026349 PG 21 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 132AR UT WOS:000076607900002 PM 9762011 ER PT J AU Uttl, B Santacruz, P Litvan, I Grafman, J AF Uttl, B Santacruz, P Litvan, I Grafman, J TI Caregiving in progressive supranuclear palsy SO NEUROLOGY LA English DT Article ID RICHARDSON-OLSZEWSKI-SYNDROME; NATURAL-HISTORY; DEMENTIA; BURDEN; INTERVENTIONS; PREDICTORS; CRITERIA; BEHAVIOR AB Background: Basic issues regarding factors influencing progressive supranuclear palsy (PSP) patient caregiver burden remain unresolved, including whether and how disease severity and duration influence caregiver burden. Objective: To examine the relation between PSP patient caregiver burden and disease severity, describe the time course of caregiver burden in relation to disease progression, and identify the contribution of other factors (e.g., patient memory and behavioral problems, caregiver gender) to caregiver burden. Methods: Mail survey of 180 caregivers of PSP patients (living at home and cared for by nonprofessionals) who were members of the Society for Progressive Supranuclear Palsy. The survey included the Burden Interview, an instrument measuring caregiver burden by inquiring how they feel about different aspects and demands of caregiving. Results: Caregiver burden was related to both PSP disease severity (r = 0.40) and disability/need for assistance (r = 0.43). The relation between burden and disease duration was nonlinear, following the same time course as disease severity; the burden increased during the first 18 months postdiagnosis and leveled off thereafter. Women reported more burden than men (caregiver sex Delta r(2) = 0.05), even after controlling for disease severity and duration (Delta r(2) = 0.22) and patient gender (Delta r(2) < 0.01; NS), patient depression (Delta r(2) = 0.09), and aggressiveness (Delta r(2) = 0.02). Conclusion: Burden in PSP is related to disease severity, disease duration, and caregiver gender (even after controlling for patient's memory, patient depression, and aggression). C1 NINDS, Cognit Neurosci Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Henry M Jackson Fdn, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neuropharmacol Unit, Henry M Jackson Fdn, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, Med Neurol Branch, NIH, Bldg 10,Room 5C205,10 Ctr Dr, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457; Litvan, Irene/0000-0002-3485-3445 NR 22 TC 9 Z9 10 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1998 VL 51 IS 5 BP 1303 EP 1309 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 137GP UT WOS:000076906600015 PM 9818850 ER PT J AU Ziemann, U Chen, R Cohen, LG Hallett, M AF Ziemann, U Chen, R Cohen, LG Hallett, M TI Dextromethorphan decreases the excitability of the human motor cortex SO NEUROLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; AMYOTROPHIC-LATERAL-SCLEROSIS; LONG-TERM POTENTIATION; CORTICAL EXCITABILITY; HORIZONTAL CONNECTIONS; SOMATOSENSORY CORTEX; SYNAPTIC PLASTICITY; NMDA RECEPTORS; INHIBITION; FACILITATION AB Objective: To assess the acute effects of dextromethorphan (DM) on human motor cortical excitability. Background: DM, a noncompetitive N-methyl-D-aspartate receptor antagonist, has recently attracted clinical interest for its potential as a neuroprotective agent in various models of excitotoxicity. We were interested in learning whether this drug can modulate the excitability of the motor cortex in healthy subjects. Methods: The effects of DM on the excitability of the normal human motor cortex were studied in eight healthy volunteers by means of focal transcranial magnetic stimulation before and 1.5, 4, 6.5, and 24 hours after a single oral dose of 150 mg DM. Motor evoked potentials (MEPs) were recorded from the relaxed abductor digiti minimi muscle. Measures of motor cortical excitability were motor threshold, MEP recruitment, duration of the cortical silent period, and intracortical inhibition and facilitation. In addition, the authors explored spinal and neuromuscular excitability by means of F waves, duration of the peripheral silent period, and maximum NI wave. Results: Intracortical inhibition increased temporarily, intracortical facilitation decreased, and the cortical silent period lengthened slightly. Motor threshold, MEP recruitment, and spinal and peripheral motor excitability were not affected significantly. Conclusions: Our findings suggest that DM can exert a significant suppression of the excitatory drive in the normal human cortex, which may be relevant for its potential therapeutic use in excitotoxicity-related neurologic disease. Furthermore, the noninvasive technique described may prove useful in preclinical studies to assess the effects on motor cortical excitability induced by new modulators of glutamatergic transmission currently under development. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Ziemann, U (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bldg 10,Room 5N234,10 Ctr Dr, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 33 TC 229 Z9 230 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1998 VL 51 IS 5 BP 1320 EP 1324 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 137GP UT WOS:000076906600018 PM 9818853 ER PT J AU Teipel, SJ Hampel, H Alexander, GE Schapiro, MB Horwitz, B Teichberg, D Daley, E Hippius, H Moller, HJ Rapoport, SI AF Teipel, SJ Hampel, H Alexander, GE Schapiro, MB Horwitz, B Teichberg, D Daley, E Hippius, H Moller, HJ Rapoport, SI TI Dissociation between corpus callosum atrophy and white matter pathology in Alzheimer's disease SO NEUROLOGY LA English DT Article ID RESONANCE-IMAGING HYPERINTENSITIES; MULTIPLE-SCLEROSIS; METABOLISM; DEMENTIA; LESIONS AB Objective: To determine whether the size of the corpus callosum is related to the extent of white matter pathology in patients with AD and age-matched healthy control subjects. Methods: White matter hyperintensity load and corpus callosum size were compared between 20 clinically diagnosed AD patients and 21 age-matched healthy control subjects. We investigated the effect of age and disease severity on corpus callosum size and white matter hyperintensity, in addition to the relation between corpus callosum areas and white matter hyperintensity load. Results: We found significant regional atrophy of the corpus callosum in AD when compared with control subjects, although the groups did not differ in their white matter hyperintensity load. We further showed a region-specific correlation between corpus callosum size and white matter hyperintensity in the control group but not in AD patients. In the AD group, corpus callosum size correlated with age and dementia severity, whereas white matter hyperintensity correlated only with age. Conclusion: Corpus callosum atrophy in AD can occur independent of white matter degeneration, likely reflecting specific AD pathology in projecting neurons. C1 Univ Munich, Sch Med, Dept Psychiat, Res Unit D2,Geriatr Psychiat Branch, D-80336 Munich, Germany. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Teipel, SJ (reprint author), Univ Munich, Sch Med, Dept Psychiat, Res Unit D2,Geriatr Psychiat Branch, Nussnbaumstr 7, D-80336 Munich, Germany. NR 35 TC 60 Z9 62 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1998 VL 51 IS 5 BP 1381 EP 1385 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 137GP UT WOS:000076906600029 PM 9818864 ER PT J AU Chen, R Karp, BI Hallett, M AF Chen, R Karp, BI Hallett, M TI Botulinum toxin type F for treatment of dystonia: Long-term experience SO NEUROLOGY LA English DT Article ID DOUBLE-BLIND; TORTICOLLIS; RESISTANT AB The authors analyzed retrospectively the results of open-labeled botulinum toxin type F (BTXF) treatment for 1 year or longer in 18 BTXA-resistant patients. All patients except one primary nonresponder to BTXA improved initially with BTXF. Most patients continued to respond to BTXF for 1 year or longer, but four patients became resistant to BTXF. BTXF-resistant patients received a higher dose per treatment and a higher cumulative dose than BTXF-responsive patients. BTXF can he used for longterm treatment of dystonia. It seems prudent to limit BTX doses of all serotypes to the lowest necessary for clinical efficacy. C1 NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 10 TC 34 Z9 35 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1998 VL 51 IS 5 BP 1494 EP 1496 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 137GP UT WOS:000076906600060 PM 9818895 ER PT J AU Naruse, S Thinakaran, G Luo, JJ Kusiak, JW Tomita, T Iwatsubo, T Qian, XZ Ginty, DD Price, DL Borchelt, DR Wong, PC Sisodia, SS AF Naruse, S Thinakaran, G Luo, JJ Kusiak, JW Tomita, T Iwatsubo, T Qian, XZ Ginty, DD Price, DL Borchelt, DR Wong, PC Sisodia, SS TI Effects of PS1 deficiency on membrane protein trafficking in neurons SO NEURON LA English DT Article ID AMYLOID-BETA-PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; COPII-COATED VESICLES; PRECURSOR PROTEIN; HIPPOCAMPAL-NEURONS; IN-VIVO; ENDOPLASMIC-RETICULUM; GOLGI TRANSPORT; MAMMALIAN-CELLS; NERVOUS-SYSTEM AB We have examined the trafficking and metabolism of the beta-amyloid precursor protein (APP), an APP homolog (APLP1), and TrkB in neurons that lack PS1. We report that PS1-deficient neurons fail to secrete A beta, and that the rate of appearance of soluble APP derivatives in the conditioned medium is increased. Remarkably, carboxyl-terminal fragments (CTFs) derived from APP and APLP1 accumulate in PS1-deficient neurons. Hence, PS1 plays a role in promoting intramembrane cleavage and/or degradation of membrane-bound CTFs. Moreover, the maturation of TrkB and BDNF-inducible TrkB autophosphorylation is severely compromised in neurons lacking PS1. We conclude that PS1 plays an essential role in modulating trafficking and metabolism of a selected set of membrane and secretory proteins in neurons. C1 Univ Chicago, Dept Pharmacol & Physiol Sci, Chicago, IL 60637 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Neuropathol, Baltimore, MD 21205 USA. NIA, Baltimore, MD 21224 USA. Univ Tokyo, Fac Pharmaceut Sci, Dept Neuropathol & Neurosci, Tokyo 113, Japan. RP Sisodia, SS (reprint author), Univ Chicago, Dept Pharmacol & Physiol Sci, 947 E 58Th St, Chicago, IL 60637 USA. EM ssisodia@drugs.bsd.uchicago.edu RI Tomita, Taisuke/L-5427-2015 OI Tomita, Taisuke/0000-0002-0075-5943 FU NIA NIH HHS [1PO1 AG14248, AG05146]; NINDS NIH HHS [NS 20471] NR 45 TC 320 Z9 322 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1998 VL 21 IS 5 BP 1213 EP 1221 DI 10.1016/S0896-6273(00)80637-6 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 145RX UT WOS:000077386100030 PM 9856475 ER PT J AU Shoaf, SE Carson, R Hommer, D Williams, W Higley, JD Schmall, B Herscovitch, P Eckelman, W Linnoila, M AF Shoaf, SE Carson, R Hommer, D Williams, W Higley, JD Schmall, B Herscovitch, P Eckelman, W Linnoila, M TI Brain serotonin synthesis rates in rhesus monkeys determined by [C-11]alpha-methyl-L-tryptophan and positron emission tomography compared to CSF 5-hydroxyindole-3-acetic acid concentrations SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin; positron emission tomography; rhesus monkeys; pharmacokinetics; brain; alpha-methyl-L-tryptophan ID DIMINISHED SOCIAL COMPETENCE; NONHUMAN PRIMATE MODEL; NEUTRAL AMINO-ACIDS; TRYPTOPHAN DEPLETION; HEALTHY-VOLUNTEERS; SYNTHESIS INVIVO; AGGRESSION; AVAILABILITY; METABOLITES; STABILITY AB Twelve male,fasted, anesthetized rhesus monkeys were studied with positron emission tomography (PET) and [C-11]alpha-methyl-L-tryptophan (alpha MTP) to determine serotonin synthesis rates as described by Diksic et al. (1991). It tons expected that the serotonin synthesis rates determined for the whole brain would be correlated with CSF 5-hydroxyindole-3-acetic acid concentrations, a measure of central serotonin turnover, because both measures were obtained at steady state. However, no significant correlation was found. During data analysis, it was noticed that the calculated serotonin synthesis rates were significantly correlated to free plasma tryptophan (TP) concentrations (r = 0.88, p < .001). From repeat scans conducted in six monkeys, if was determined that day-to-day variability in free plasma TP and the percentage of protein binding (average percent difference was 48 and 37%, respectively) produced most of the variability in the calculated serotonin synthesis rates (50%); repeat K images, obtained from the PET data alone, differed by only 11%. Calculated serotonin synthesis rates reported for [C-11]alpha MTP PET studies of humans (Nishizawa et al. 1997) and dogs (Diksic et al. 1991) were also highly correlated to reported differences in pIasma free TP concentrations. It seems that the [C-11]alpha MTP model for the computation of serotonin synthesis rates is very dependent on plasma free TP concentration and that it may not accurately determine actual serotonin synthesis rates. [Neuropsychopharmacology 19:345-353, 1998] Published by Elsevier Science Inc. C1 NIAAA, Clin Studies Lab, Bethesda, MD 20892 USA. Natl Inst Hlth Clin Ctr, PET Dept, Bethesda, MD USA. RP Shoaf, SE (reprint author), 10 Ctr Dr,MSC-1256, Bethesda, MD 20892 USA. NR 44 TC 32 Z9 32 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 1998 VL 19 IS 5 BP 345 EP 353 DI 10.1016/S0893-133X(98)00032-3 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 120LT UT WOS:000075958400001 PM 9778657 ER PT J AU Malhotra, AK Breier, A Goldman, D Picken, L Pickar, D AF Malhotra, AK Breier, A Goldman, D Picken, L Pickar, D TI The apolipoprotein E epsilon 4 allele is associated with blunting of ketamine-induced psychosis in schizophrenia - A preliminary report SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ketamine; N-methyl-d-aspartate; psychosis; APOE; genotype ID NOVELTY SEEKING; HEALTHY-VOLUNTEERS; POLYMORPHISM; GENE; ANTAGONIST AB Interindividual differences in the psychotomimetic response to the N-methyl-d-aspartate receptor antagonist ketamine are commonly observed. The apolipoprotein E (APOE) epsilon 4 allele has been associated with reduced severity of positive psychotic symptoms in schizophrenia. In this study, we sought to determine if the APOE epsilon 4 allele influences the psychotomimetic response to ketamine in schizophrenics. Eighteen patients genotyped at the APOE locus underwent a double-blind infusion of ketamine and of placebo. Ketamine-induced alterations in the brief psychiatric rating scale factors were compared between schizophrenics with and without the APOE epsilon 4 allele. APOE epsilon 4+ schizophrenics displayed significantly reduced ketamine-induced psychosis, as compared to epsilon 4- patients. These preliminary data indicate that the psychotomimetic response to ketamine may be genetically influenced and may provide additional evidence that APOE may modify expression of the positive symptoms in schizophrenia. [Neuropsychopharmacology 19:445-448, 1998] Published by Elsevier Science Inc. C1 NIMH, Expt Therapeut Branch, NIH, Bethesda, MD USA. NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Malhotra, AK (reprint author), Hillside Hosp, 75-59 263rd St, Glen Oaks, NY 11004 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 17 TC 14 Z9 14 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 1998 VL 19 IS 5 BP 445 EP 448 DI 10.1016/S0893-133X(98)00031-1 PG 4 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 120LT UT WOS:000075958400010 PM 9778666 ER PT J AU Borlongan, CV Fujisaki, T Watanabe, S AF Borlongan, CV Fujisaki, T Watanabe, S TI Chronic cyclosporine-A injection in rats with damaged blood-brain barrier does not impair retention of passive avoidance SO NEUROSCIENCE RESEARCH LA English DT Article DE cyclosporine-A; immunosuppression; blood-brain barrier; memory retention; passive avoidance; neural transplantation ID DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; SURVIVAL; TRANSPLANTATION; 6-HYDROXYDOPAMINE; MODULATION; GRAFTS; FK506; DRUGS AB Recently, we demonstrated that chronic administration of immunosuppressant drug, cyclosporine-A (CsA), does not produce impairment in memory retention of a passive avoidance task in normal adult rats. Since CsA has been used as an adjunctive therapy to avoid xenograft rejection inherent in neural transplantation therapy for neurodegenerative disorders, we replicated our previous study in animals with damaged blood-brain barrier (BBB) simulating that of the neural transplantation protocol. Adult rats with damaged BBB that received either chronic CsA (5, 10, and 20 mg/kg) or vehicle injection did not differ significantly in their memory retention of the passive avoidance task that rewarded 'less mobile activity', in that animals avoided electric shock when they restrained their movements within the safe compartment. General spontaneous locomotor activity also was not altered by CsA, except in animals that received 20 mg/kg, which displayed significant hypoactivity at later post-injection periods of CsA. The absence of potentiation of retention of the passive avoidance task in all CsA-treated animals, including the hypoactive ones, suggests that locomotor activity did not interfere with cognitive behavior. The present results confirm our previous findings that the therapeutic dosage (10 mg/kg) of CsA used for neural transplantation does not produce visible deleterious effects on the performance of memory retention task in immunosuppressed rats with damaged BBB. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NIDA, Dept Cellular Neurophysiol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Keio Univ, Dept Psychol, Minato Ku, Tokyo 108, Japan. RP Borlongan, CV (reprint author), NIDA, Dept Cellular Neurophysiol, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Borlongan, Cesar/0000-0002-2966-9782 NR 27 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD NOV PY 1998 VL 32 IS 3 BP 195 EP 200 DI 10.1016/S0168-0102(98)00088-1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 148QW UT WOS:000077544300002 PM 9875561 ER PT J AU Schmall, B Conti, PS Schaeffer, DJ Kleinert, EL AF Schmall, B Conti, PS Schaeffer, DJ Kleinert, EL TI Radiotracer-derived biochemical profiles via a mathematical model: Implications for therapeutic intervention SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Letter C1 NIH, PET Dept, Bethesda, MD 20892 USA. Univ So Calif, Sch Med, Dept Radiol, PET Imaging Sci Ctr, Los Angeles, CA 90033 USA. Univ Illinois, Dept Vet Biosci, Urbana, IL 61801 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Schmall, B (reprint author), NIH, PET Dept, Bldg 10,Rm 1C-401, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD NOV PY 1998 VL 25 IS 8 BP 799 EP 801 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 137HB UT WOS:000076907700019 PM 9863569 ER PT J AU Hacia, JG Woski, SA Fidanza, J Edgemon, K Hunt, N McGall, G Fodor, SPA Collins, FS AF Hacia, JG Woski, SA Fidanza, J Edgemon, K Hunt, N McGall, G Fodor, SPA Collins, FS TI Enhanced high density oligonucleotide array-based sequence analysis using modified nucleoside triphosphates SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ENZYMATIC INCORPORATION; DNA; RNA; HYBRIDIZATION; PAIR AB Pairs of high density oligonucleotide arrays (DNA chips) consisting of >96 000 oligonucleotides were designed to screen the entire 5.53 kb coding region of the hereditary breast and ovarian cancer BRCA1 gene for all possible sequence changes in the homozygous and heterozygous states. Single-stranded RNA targets were generated by PCR amplification of individual BRCA1 exons using primers containing T3 and T7 RNA polymerase promoter tails followed by in vitro transcription and partial fragmentation reactions. Fluorescent hybridization signals from targets containing the four natural bases to >5592 different fully complementary 25mer oligonucleotide probes an the chip varied over two orders of magnitude. To examine the thermodynamic contribution of rU.dA and rA.dT target.probe base pairs to this variability, modified uridine [5-methyluridine and 5-(1-propynyl)-uridine)] and modified adenosine (2,6-diaminopurine riboside) 5'-triphosphates were incorporated into BRCA1 targets. Hybridization specificity was assessed based upon hybridization signals from >33 200 probes containing centrally localized single base pair mismatches relative to target sequence. Targets containing 5-methyluridine displayed promising localized enhancements in hybridization signal, especially in pyrimidine-rich target tracts, while maintaining single nucleotide mismatch hybridization specificities comparable with those of unmodified targets. C1 Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. Affymetrix, Santa Clara, CA 95051 USA. RP Collins, FS (reprint author), Natl Human Genome Res Inst, NIH, Bldg 31,Room 4B09,31 Ctr Dr, Bethesda, MD 20892 USA. FU NHGRI NIH HHS [5POLHGO1323-03] NR 31 TC 48 Z9 55 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 1 PY 1998 VL 26 IS 21 BP 4975 EP 4982 DI 10.1093/nar/26.21.4975 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 136EJ UT WOS:000076845300027 PM 9776762 ER PT J AU Grady, PA AF Grady, PA TI News from NINR SO NURSING OUTLOOK LA English DT News Item C1 NINR, NIH, Bethesda, MD 20892 USA. RP Grady, PA (reprint author), NINR, NIH, 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 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD NOV-DEC PY 1998 VL 46 IS 6 BP 289 EP 289 DI 10.1016/S0029-6554(98)90086-0 PG 1 WC Nursing SC Nursing GA 153EU UT WOS:000077798800009 ER PT J AU Yunmbam, MK AF Yunmbam, MK TI Inhibition of breast cancer in nude mouse model by anti-angiogenesis SO ONCOLOGY REPORTS LA English DT Article DE inhibition; breast cancer; nude mice; anti-angiogenesis; pentosan polysulfate; difluoromethylornithine ID ALPHA-DIFLUOROMETHYLORNITHINE; ORNITHINE DECARBOXYLASE; TUMOR ANGIOGENESIS; POLYAMINE METABOLISM; PENTOSAN POLYSULFATE; CELL-PROLIFERATION; GROWTH-FACTORS; DFMO; MICE; DIFFERENTIATION AB The mechanism by which DL-a-difluoromethylornithine (DFMO) inhibits angiogenesis is generally thought to involve the inhibition of the rate-limiting enzyme, ornithine decarboxylase (ODC), leading to polyamine depletion in cells and the ultimate cytostatic effect on proliferating endothelial cells. Another mechanism for inhibiting tumor growth involves pentosan polysulfate (PPS) which binds heparin-binding growth factors, known to be crucial for tumor angiogenesis. To quantitate the combined anti-angiogenic effect of DFMO and PPS on tumors, blood vessels were stained using monoclonal antibodies against the platelet endothelial cell adhesion molecule (PECAM). When compared to untreated mice, DFMO/PPS-treated mice exhibited significantly lower (6-fold) blood vessel counts. Furthermore, mice receiving the combination drug treatment had prolonged life compared to untreated tumor-bearing mice, but less than normal tumor-free mice. The prolonged life span of drug treated tumor-bearing mice also correlated with reduced tumor burden in these mice. The use of single drug treatment results in rapid tumor growth and eventual death of tumor-bearing mice. We have demonstrated that there was significant difference in survival time which correlated to less tumor burden in treated groups of mice as compared to the controls. Inhibition of tumor angiogenesis by the drug combinations suggest that these compounds are anti-angiogenic agents for potential use in clinical trial. C1 Georgetown Univ, Vincent T Lombardi Canc Ctr, Washington, DC 20007 USA. RP Yunmbam, MK (reprint author), NCI, Med Branch, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NCI NIH HHS [P50-CA58185] NR 35 TC 6 Z9 6 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD NOV-DEC PY 1998 VL 5 IS 6 BP 1431 EP 1437 PG 7 WC Oncology SC Oncology GA 129HR UT WOS:000076458200022 PM 9769382 ER PT J AU Walton, RC Nussenblatt, RB Whitcup, SM AF Walton, RC Nussenblatt, RB Whitcup, SM TI Cyclosporine therapy for severe sight-threatening uveitis in children and adolescents SO OPHTHALMOLOGY LA English DT Article ID LOW-DOSE METHOTREXATE; INFLAMMATORY OCULAR DISEASE; RHEUMATOID-ARTHRITIS; IMMUNOSUPPRESSIVE DRUGS; CORTICOSTEROID-THERAPY; NONINFECTIOUS UVEITIS; AUTOIMMUNE-DISEASES; CHANGING PATTERNS; COMPLICATIONS; NEPHROPATHY AB Objective: To review the safety and efficacy of cyclosporine in the treatment of children with severe bilateral sight-threatening intermediate uveitis or panuveitis. Design/Participants: A retrospective chart review was performed on all children younger than 18 years of age with chronic bilateral sight-threatening uveitis who were treated with cyclosporine. Main Outcome Measures: Assessment of the therapeutic efficacy and development of adverse effects of cyclosporine after 6 months, 2 years, and 4 years of therapy was performed. Results: Between 1983 and 1992, 15 children and adolescents were treated with cyclosporine. After 6 months, visual acuity improved or stabilized in 82.1% of eyes, while median vitreous inflammation decreased from 2.0 to 0.5. After 2 and 4 years, visual acuity improved or stabilized in 64% and 75% of eyes, respectively. Median vitreous inflammation remained 0.5 after 2 and 4 years of therapy. Mean creatinine clearance and hemoglobin values decreased and serum creatinine increased after 6 months. After 2 years, only mean hemoglobin values remained decreased. After 4 years, no significant differences were noted in any of the laboratory studies. The most frequently noted side effects included transient increases in serum creatinine in 53%, gingival hyperplasia in 40%, and hirsutism in 20% of patients. Conclusions: The authors' results suggest that cyclosporine is a safe and effective therapy for the treatment of children with severe bilateral sight-threatening intermediate uveitis or panuveitis. C1 Univ Tennessee, Dept Ophthalmol, Coll Med, Memphis, TN 38163 USA. NEI, Clin Branch, NIH, Bethesda, MD 20892 USA. RP Walton, RC (reprint author), Univ Tennessee, Dept Ophthalmol, Coll Med, 956 Court Ave,Site D228, Memphis, TN 38163 USA. NR 44 TC 36 Z9 38 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 1998 VL 105 IS 11 BP 2028 EP 2034 DI 10.1016/S0161-6420(98)91120-4 PG 7 WC Ophthalmology SC Ophthalmology GA 135YX UT WOS:000076831500020 PM 9818601 ER PT J AU Biesecker, LG Ondrey, E AF Biesecker, LG Ondrey, E TI Pallister-Hall syndrome SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Letter C1 Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness Other Commun Disorders, NIH, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NR 3 TC 3 Z9 3 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 1998 VL 119 IS 5 BP 556 EP 556 PG 1 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 137JR UT WOS:000076912000031 PM 9807095 ER PT J AU Smith, WB Gracely, RH Safer, MA AF Smith, WB Gracely, RH Safer, MA TI The meaning of pain: cancer patients' rating and recall of pain intensity and affect SO PAIN LA English DT Article DE pain; memory; recall; pain memory; pain measurement; pain dimensions ID SCALES; MEMORY; VALIDITY; MODEL AB The present study investigated the influence of an increase in present pain intensity on the rating and recall of the intensity and affective dimensions of clinical pain. Thirty-two cancer patients who reported that movement caused or exacerbated their pain rated their present pain intensity and affect before and after a session of physical therapy. Subjects also rated their usual, highest and lowest pain intensity and pain affect for the previous 3 days, and were randomly assigned to make these ratings either before or after the physical therapy session. Physical therapy increased the intensity (P < 0.01) but not the unpleasantness of the pain (P > 0.05), thus demonstrating a dissociation between pain intensity and pain affect. Beliefs about pain etiology also influenced post-therapy pain ratings. Subjects (N = 11) who believed that their pain was due to cancer, rated their post-therapy pain intensity and pain affect significantly higher than those subjects (N = 21) who did not believe their pain was due to cancer (both P < 0.05). For all subjects, recall of past pain intensity and affect was positively correlated with present levels of pain intensity and pain affect (P < 0.01). Thus, recall was assimilated to present pain levels. The results demonstrate the importance of rating both the intensity and affective dimensions of pain, and suggest that the significance of clinical pain influences pain ratings. These results also suggest that research on the rating and recall of pain, particularly the affective dimension of pain, should use actual patients who are experiencing changes in their naturally occurring pain. (C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V. C1 NIDR, Neurobiol & Anesthesiol Branch, NIH, Bethesda, MD 20892 USA. Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA. RP Smith, WB (reprint author), NIDR, Neurobiol & Anesthesiol Branch, NIH, Willco Bldg,Suite 505,6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. NR 20 TC 44 Z9 45 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 1998 VL 78 IS 2 BP 123 EP 129 DI 10.1016/S0304-3959(98)00122-5 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 139RJ UT WOS:000077042900005 PM 9839822 ER PT J AU Lujan, HD Mowatt, MR Nash, TE AF Lujan, HD Mowatt, MR Nash, TE TI The molecular mechanisms of Giardia encystation SO PARASITOLOGY TODAY LA English DT Review ID FIELD-EMISSION SEM; CYST WALL PROTEIN; PRIMITIVE EUKARYOTE; LIPID UPTAKE; LAMBLIA; INVITRO; GROWTH; DIFFERENTIATION; EXPRESSION; IDENTIFICATION AB The protozoan parasite Giardia lamblia is transmitted as an environmentally resistant cyst. The encystation process is attracting attention not only from the viewpoint of disease transmission, but also as a model for differentiation. Here, Hugo Lujan, Michael Mowatt and Theadore Nash discuss molecular events underlying this process, including the induction of expression and transport of cyst wall proteins and the induction of Golgi-like activity. They also propose that the signal for encystation derives from cholesterol deprivation in the towel small intestine. C1 Univ Nacl Cordoba, Fac Ciencias Med, Catedra Quim Biol, RA-5000 Cordoba, Argentina. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Nash, TE (reprint author), Univ Nacl Cordoba, Fac Ciencias Med, Catedra Quim Biol, RA-5000 Cordoba, Argentina. NR 35 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD NOV PY 1998 VL 14 IS 11 BP 446 EP 450 DI 10.1016/S0169-4758(98)01333-7 PG 5 WC Parasitology SC Parasitology GA 135KH UT WOS:000076800500005 PM 17040845 ER PT J AU Hediger, ML Overpeck, MD Kuczmarski, RJ McGlynn, A Maurer, KR Davis, WW AF Hediger, ML Overpeck, MD Kuczmarski, RJ McGlynn, A Maurer, KR Davis, WW TI Muscularity and fatness of infants and young children born small- or large-for-gestational-age SO PEDIATRICS LA English DT Article DE small-for-gestational-age; large-for-gestational-age; muscularity; fatness; growth; infants ID BIRTH-WEIGHT; CHILDHOOD GROWTH; FAT DISTRIBUTION; BODY-COMPOSITION; FETAL GROWTH; APPROPRIATE; ADULTHOOD; DISEASE; PRETERM; LIFE AB Objective. There is growing interest in the extent to which body composition, both short- and long-term, differs in infants and children born at the extremes of birth weight. This is because a growing number of studies have linked low birth weight and fetal growth restriction to the chronic diseases in adulthood that often are obesity-related, and there is also evidence to suggest that heavy infants may be at increased risk for obesity in later life, again with the attendant obesity-related chronic diseases. Our objective was to compare anthropometric indices of body composition of infants and young children born small-for-gestational-age (SGA, <10th percentile) or large-for-gestational age (LGA, greater than or equal to 90th percentile) with those of normal birth weight status (appropriate-for-gestational-age, AGA) in a US sample. Design. National sample of US-born non-Hispanic white, non-Hispanic black, and Mexican-American infants and young children, 2 to 47 months of age, examined in the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), for whom birth certificates were obtained. The primary outcomes were normalized anthropometric indices (z scores or standard deviation units [SDU]) of nutritional status and body composition (mid-upper arm circumference, triceps and subscapular skinfolds, mid-upper arm muscle and mid-upper arm fat areas (UFA), and the arm fat index). The outcomes thus were scaled to permit comparison across chronologic ages. Results. The prevalence of SGA was 8.6%, appropriate-for-gestational-age 80.9%, and LGA 10.5%. From ages 2 to 47 months, for infants and young children born SGA, there was a persistent overall deficit in muscularity (mid-upper arm circumference and mid-upper arm muscle area) of approximately -0.50 SDU, but less of a deficit in fatness, particularly at the youngest ages. For infants and young children born LGA, there was a surfeit in muscularity of similar to 0.45 SDU, with less of a surfeit in fatness, particularly at the youngest ages. Across all ages, the mean UFA showed a statistically significant deficit for SGA children (-0.27 +/- 0.10 SDU) and surfeit for LGA children (0.24 +/- 0.08 SDU). At individual ages for UFA and at individual and all ages combined for skinfold thicknesses, there were no significant differences in level of subcutaneous fatness in the three birth-weight-for-gestational-age groups. There was a tendency in the first year for the arm fat index (% arm fat) to be significantly higher for SGA infants, but the effect did not persist after the first year. Conclusion. SGA infants remain smaller and LGA infants larger in size through early childhood, but the discrepancies in weight are primarily attributable to differences in lean body mass (muscularity). Fatness is less affected. Thus, based on the fatness indicators used, at any given weight for infants and children 2 to 47 months of age, percent body fat appears to be relatively higher for children who were SGA at birth and lower in those who were LGA at birth. These differences in body composition for SGA infants support the evidence documenting a link between disturbances in intrauterine growth and chronic disease associated with subsequent adiposity in adulthood. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Klemm Anal Grp, Hyattsville, MD USA. Westat Corp, Rockville, MD USA. RP Overpeck, MD (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bldg 6100,Rm 7B03, Bethesda, MD 20892 USA. NR 34 TC 146 Z9 150 U1 2 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 1998 VL 102 IS 5 AR e60 DI 10.1542/peds.102.5.e60 PG 7 WC Pediatrics SC Pediatrics GA 134ZT UT WOS:000076774600012 PM 9794990 ER PT J AU Kimm, SYS Payne, GH Stylianou, MP Waclawiw, MA Lichtenstein, C AF Kimm, SYS Payne, GH Stylianou, MP Waclawiw, MA Lichtenstein, C TI National trends in the management of cardiovascular disease risk factors in children: Second NHLBI survey of primary care physicians SO PEDIATRICS LA English DT Article DE children; physician practice; cholesterol; blood pressure; screening; treatment ID CORONARY HEART-DISEASE; BLOOD CHOLESTEROL; PREVENTION; FAT; PEDIATRICIANS; INTERVENTION; ATTITUDES; CHILDHOOD; ADULTS; HEALTH AB Background. The evidence that atherosclerosis begins during adolescence has led to the belief that primary prevention of cardiovascular disease (CHD) should commence in childhood. Although several national guidelines have been issued for the defection and treatment of CHD risk factors in children, concerns continue to be expressed regarding what constitutes appropriate measures and when to institute such measures in children. A 1988 national survey of primary care physicians revealed variation in the management of CHD risk factors in children by physician categories, which suggested the underlying quandary among physicians regarding CHD risk factors in children. Objective. To assess current clinical management of pediatric CHD risk factors in the primary care setting and also to evaluate time trends between the current and 1988 surveys. Methods. A 25-minute telephone survey was conducted with 1036 of eligible physicians tie, >20 hours per week direct patient care including at least five pediatric patient contacts) selected from a national probability sample in three practice categories (family practitioners, pediatricians, and general practitioners). The questionnaire assessed the current practice of these physicians in the primary care setting regarding cholesterol and blood pressure (BP) screening and treatment, both nonpharmacologic and pharmacologic, and physician attitude and knowledge. Results. Cholesterol screening in children was performed by 75.7% of all physicians. Nonscreening was highest among general practitioners (38%) and lowest among pediatricians (12%). BP was measured by almost all physicians. The majority of physicians (71%) prescribed diet as the first cholesterol-lowering step, but similar to 16% also used pharmacologic therapy. Cholesterol synthesis inhibitors and bile acid sequestrants were the drugs used most commonly. Approximately 25% of physicians have used drugs in children to treat high BP. Diuretics and beta-blockers were used most frequently. More than one fourth of the physicians had some concern about identifying and treating children for CHD risk factors. There was slightly less cholesterol measurement in 1995 compared with 1988, and no notable increase in the knowledge regarding major CHD risk factors. Conclusion. The results of the second National Heart, Lung, and Blood Institute survey of primary care physicians suggest that additional inroads need to be made in the dissemination of the national guidelines for the management of CHD risk factors in children, including appropriate use of pharmacologic agents. C1 Univ Pittsburgh, Sch Med, Dept Family Med & Clin Epidemiol, Pittsburgh, PA 15261 USA. NHLBI, Div Epidemiol, NIH, Bethesda, MD 20892 USA. CODA Inc, Silver Spring, MD USA. RP Kimm, SYS (reprint author), Univ Pittsburgh, Sch Med, Dept Family Med & Clin Epidemiol, M-200 Scaife Hall, Pittsburgh, PA 15261 USA. FU NHLBI NIH HHS [N01-HC-35132] NR 38 TC 17 Z9 21 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 1998 VL 102 IS 5 AR e50 DI 10.1542/peds.102.5.e50 PG 8 WC Pediatrics SC Pediatrics GA 134ZT UT WOS:000076774600002 PM 9794980 ER PT J AU Long, RM AF Long, RM TI Part II. What do reviewers consider when evaluating institutional research training program grant applications (T32s) to the NIGMS? SO PHARMACEUTICAL RESEARCH LA English DT News Item C1 NIH, Pharmacol & Physiol Sci PPS Branch, Div Pharmacol Physiol & Biol Chem, PPBC,NIGMS, Bethesda, MD 20892 USA. RP Long, RM (reprint author), NIH, Pharmacol & Physiol Sci PPS Branch, Div Pharmacol Physiol & Biol Chem, PPBC,NIGMS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD NOV PY 1998 VL 15 IS 11 BP 1647 EP 1648 PG 2 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 138VR UT WOS:000076994500001 PM 9833981 ER PT J AU Piscitelli, SC Vogel, S Figg, WD Raje, S Forrest, A Metcalf, JA Baseler, M Falloon, J AF Piscitelli, SC Vogel, S Figg, WD Raje, S Forrest, A Metcalf, JA Baseler, M Falloon, J TI Alteration in indinavir clearance during interleukin-2 infusions in patients infected with the human immunodeficiency virus SO PHARMACOTHERAPY LA English DT Article ID HEPATIC CYTOCHROME-P-450; XANTHINE-OXIDASE; INTERFERON; HEPATOCYTES; DEPRESSION; INDUCTION; EXPRESSION; HIV AB Study Objective. To evaluate the effect of interleukin-2 (IL-2) infusions on the pharmacokinetics of indinavir in patients infected with the human immunodeficiency virus. Design. Observational, noncontrolled trial and prospective, open-label, nonrandomized, pharmacokinetic study. Setting. Government research hospital. Patients. Seventeen patients receiving indinavir 800 mg every 8 hours and a 5-day continuous infusion of recombinant IL-2. Interventions. Observational study: trough indinavir concentrations were measured on day 1 and day 5 of IL-2 as part of a clinical trial. Prospective study: serial plasma samples were collected on days 1 and 5 of IL-2 to determine indinavir concentrations. Samples were also collected over the study period to determine IL-6 concentrations. The data were fit by a one compartment model that allowed clearance to change based on IL-6 production and by standard noncompartmental equations. Measurements and Main Results. The area under the curve of indinavir increased in eight of nine patients by a mean of 88% (range -29-215%) between days 1 and 5 of IL-2 infusion. Over this period, IL-6 concentrations also increased in all patients and indinavir clearance significantly decreased. Observational data in eight patients from the clinical trial showed significantly increased indinavir trough concentrations from 264 +/- 493 to 670 +/- 677 ng/ml in the presence of IL-2. Conclusion. Indinavir concentrations were altered during IL-2 infusions, possibly by induction of IL-6. Investigation into the effects of other proinflammatory cytokines is warranted. C1 NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Sch Pharm, Amherst, NY USA. Sci Applicat Int Corp, Frederick, MD USA. RP Piscitelli, SC (reprint author), NIH, Ctr Clin, Dept Pharm, Bldg 10,Room 1N257, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 20 TC 15 Z9 15 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV-DEC PY 1998 VL 18 IS 6 BP 1212 EP 1216 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 140AX UT WOS:000077064600004 PM 9855318 ER PT J AU Knebel, W Davis, JC Sanders, WD Fessler, B Yarboro, C Pucino, F Boumpas, DT AF Knebel, W Davis, JC Sanders, WD Fessler, B Yarboro, C Pucino, F Boumpas, DT TI The pharmacokinetics and pharmacodynamics of fludarabine in rheumatoid arthritis SO PHARMACOTHERAPY LA English DT Article ID PHOSPHATE AB Study Objective. To describe the pharmacokinetics and pharmacodynamics of fludarabine in patients with rheumatoid arthritis (RA). Design. Open-label, staggered trial conducted in conjunction with a phase III clinical trial. Setting. Government research hospital. Patients. Twenty-six patients with refractory RA. Intervention. Fludarabine 20 or 30 mg/m(2)/day was administered as a 0.5-hour infusion for 3 consecutive days (1 cycle) for 6 months (1 cycle/mo). Measurements and Main Results. Serial plasma samples were collected for pharmacokinetic analysis on day 2 of the first cycle of therapy. Relationships between pharmacokinetic parameters and hematologic and efficacy parameters were examined. The disposition of fludarabine was characterized by a two-compartment model. There were no differences in pharmacokinetics between the low- and high-dose groups. The mean +/- SD total clearance, volume of distribution at steady state, and P-half-life were 13.68 +/- 5.1 L/hour, 170.08 +/- 86.5 L, and 10.9 +/- 3.1 hours, respectively. The volume of the peripheral compartment was approximately twice as large as the volume of the central compartment, indicating a significant amount of tissue distribution. No significant pharmacodynamic relationships were observed between pharmacokinetic parameters and hematologic and efficacy parameters. Conclusion. Fludarabine pharmacokinetics in patients with RA are characterized by an intermediate-length distribution phase (similar to 40 min), terminal half-life of 10.9 hours, and significant amount of tissue distribution. C1 NIH, Ctr Clin, Clin Pharmacokinet Res Lab, Dept Pharm, Bethesda, MD 20892 USA. NIH, Ctr Clin, Clin Sect, Dept Pharm, Bethesda, MD 20892 USA. NIAMSD, Clin Invest Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Knebel, W (reprint author), NIH, Ctr Clin, Clin Pharmacokinet Res Lab, Dept Pharm, Bldg 10,Room 1N-257,10 Ctr Dr,MSC 1196, Bethesda, MD 20892 USA. NR 21 TC 6 Z9 7 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV-DEC PY 1998 VL 18 IS 6 BP 1224 EP 1229 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 140AX UT WOS:000077064600006 PM 9855320 ER PT J AU Bilski, P Kukielczak, BM Chignell, CF AF Bilski, P Kukielczak, BM Chignell, CF TI Photoproduction and direct spectral detection of singlet molecular oxygen (O-1(2)) in keratinocytes stained with rose bengal SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID CATIONIC SURFACTANT; CELLS; EOSIN; PHOTOSENSITIZATION; PHOSPHORESCENCE; PHOTOPROCESSES; DIFFUSION; 1-DELTA-G; SOLVENT AB In vivo, keratinocyte skin cells are exposed to photooxidative processes, some of which can be mediated by singlet molecular oxygen (O-1(2)), a species that is very difficult to detect spectrally in cells. We photosensitized O-1(2) in cultured HaCaT keratinocytes stained with rose bengal (RB) that localizes exclusively inside the keratinocyte hydrophobic regions, as evidenced by strongly red-shifted absorbance and intense fluorescence. We used keratinocytes grown in a monolayer on a plastic coverslip and in suspension. The phosphorescence spectrum (1200-1350 nm) from O-1(2) was strongest when the coverslip containing RE-stained keratinocytes was irradiated in air. The spectral intensity decreased when the coverslip was immersed in D2O during irradiation and was almost completely quenched when it was irradiated while immersed in water. Water not only shortens the O-1(2) lifetime but also reabsorbs part of the O-1(2) phosphorescence, processes that do not occur when O-1(2) is produced in a keratinocyte layer exposed to air. Because the RE was inside keratinocytes, singlet oxygen must also be produced inside the keratinocytes. However, the sensitivity to the extracellular environment suggests that most of the detectable O-1(2) phosphorescence originates from those O-1(2) molecules that escaped from the cell through its membrane into D2O or into the air, where O-1(2) has longer lifetimes. Our results confirm directly that O-1(2) is indeed photosensitized in living cells by RE. They also suggest that keratinocyte monolayers may be a good cell model to examine in vitro the production of O-1(2) by other photosensitizers of environmental and photomedical interest. C1 NIEHS, Environm Toxicol Program, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Technol Planning & Management Corp, Res Triangle Pk, NC USA. RP Chignell, CF (reprint author), NIEHS, Environm Toxicol Program, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 17 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD NOV PY 1998 VL 68 IS 5 BP 675 EP 678 DI 10.1111/j.1751-1097.1998.tb02528.x PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 141PH UT WOS:000077152000012 PM 9825697 ER PT J AU Weiss, GH Porra, JM Masoliver, J AF Weiss, GH Porra, JM Masoliver, J TI Statistics of the depth probed by cw measurements of photons in a turbid medium SO PHYSICAL REVIEW E LA English DT Article ID MIGRATION; TISSUE; MODEL; TIME; ABSORPTION; SCATTERING; MEDICINE AB Photon migration in a turbid medium has been modeled in many different ways. The motivation for such modeling is based on technology that can be used to probe potentially diagnostic optical properties of biological tissue. Surprisingly, one of the more effective models is also one of the simplest. It is based on statistical properties of a nearest-neighbor lattice random walk. Here we develop a theory allowing one to calculate the number of visits by a photon to a given depth, if it is eventually detected at an absorbing surface. This mimics cw measurements made on biological tissue and is directed towards characterizing the depth reached by photons injected at the surface. Our development of the theory uses formalism based on the theory of a continuous-time random walk (CTRW). Formally exact results are given in the Fourier-Laplace domain, which, in turn, are used to generate approximations for parameters of physical interest. [S1063-651X(98)15411-9]. C1 NIH, Bethesda, MD 20892 USA. Univ Barcelona, Dept Fis Fonamental, E-08028 Barcelona, Spain. RP NIH, Bethesda, MD 20892 USA. RI Masoliver, Jaume/F-7198-2016 OI Masoliver, Jaume/0000-0002-5810-879X NR 31 TC 11 Z9 11 U1 1 U2 2 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2470-0045 EI 2470-0053 J9 PHYS REV E JI Phys. Rev. E PD NOV PY 1998 VL 58 IS 5 BP 6431 EP 6439 DI 10.1103/PhysRevE.58.6431 PN B PG 9 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 139VV UT WOS:000077052300046 ER PT J AU Suchy, SF Lin, T Horwitz, JA O'Brien, WE Nussbaum, RL AF Suchy, SF Lin, T Horwitz, JA O'Brien, WE Nussbaum, RL TI First report of prenatal biochemical diagnosis of Lowe syndrome SO PRENATAL DIAGNOSIS LA English DT Article DE Lowe syndrome; prenatal diagnosis; phosphatidylinositol 4,5-bisphosphate 5-phosphatase; amniocentesis; chorionic villus sampling ID OCULOCEREBRORENAL SYNDROME; GENE; MUTATIONS; OCRL1 AB The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked disorder with a severe phenotype characterized by congenital cataracts, renal tubular dysfunction and neurological deficits. The gene has been characterized and mutations have been identified in patients. Owing to the allelic heterogeneity exhibited by this gene, prenatal diagnosis by molecular analysis is limited to families in which the mutation is already known or in which linkage is informative. A more generally applicable diagnostic test would be valuable for families at risk for Lowe syndrome. Since ocrl1 is now known to encode a phosphatidylinositol 4,5-bisphosphate 5-phosphatase (Ptdlns(4,5)P-2 phosphatase), we assessed whether biochemical testing could be used for prenatal diagnosis. We report here the first case of prenatal diagnosis for Lowe syndrome by measuring phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity in cultured amniocytes. (C) 1998 John Wiley & Sons, Ltd. C1 Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. Genzyme Genet, Santa Fe, NM 87505 USA. Baylor Coll Med, Biochem Genet Lab, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Suchy, SF (reprint author), Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bldg 49,Room 4B67,49 Convent Dr MSC 4470, Bethesda, MD 20892 USA. NR 9 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD NOV PY 1998 VL 18 IS 11 BP 1117 EP 1121 DI 10.1002/(SICI)1097-0223(199811)18:11<1117::AID-PD413>3.0.CO;2-Q PG 5 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 143PJ UT WOS:000077264300002 PM 9854717 ER PT J AU Phelan, MC Blackburn, W Rogers, RC Crawford, EC Cooley, NR Schrock, E Ning, Y Ried, T AF Phelan, MC Blackburn, W Rogers, RC Crawford, EC Cooley, NR Schrock, E Ning, Y Ried, T TI Fish analysis of a complex chromosome rearrangement involving nine breakpoints on chromosomes 6, 12, 14 and 16 SO PRENATAL DIAGNOSIS LA English DT Article DE complex chromosome rearrangement; prenatal diagnosis; fluorescence in situ hybridization (FISH); spectral karyotyping (SKY) ID IN-SITU HYBRIDIZATION; PRENATAL-DIAGNOSIS; MOLECULAR ANALYSIS; FOLLOW; CHILD AB We report the prenatal diagnosis of an apparently balanced de novo complex chromosome rearrangement (CCR) which involved nine breakpoints on four different chromosomes. Fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY) were performed as an adjunct to G-banding for characterization of the abnormal chromosomes. The 22-week female fetus showed minor dysmorphic features including dolichocephaly, broad fingernails, tibial bowing, clubfoot, thoracolumbar scoliosis and hypoplastic toenails. Autopsy revealed gall-bladder hypoplasia and an atrial septal defect. Chromosome analysis of fetal tissue confirmed the presence of the complex rearrangement. (C) 1998 John Wiley & Sons, Ltd. C1 Greenwood Genet Ctr, Greenwood, SC 29646 USA. NHGRI, NIH, Bethesda, MD 20893 USA. George Washington Univ, Gene Care Wilson Genet Lab, Washington, DC 20037 USA. RP Phelan, MC (reprint author), Greenwood Genet Ctr, 1 Gregor Mendel Circle, Greenwood, SC 29646 USA. EM kphelan@ggc.org NR 20 TC 21 Z9 21 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD NOV PY 1998 VL 18 IS 11 BP 1174 EP 1180 DI 10.1002/(SICI)1097-0223(199811)18:11<1174::AID-PD411>3.0.CO;2-H PG 7 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 143PJ UT WOS:000077264300013 PM 9854728 ER PT J AU Hickman, TB Briefel, RR Carroll, MD Rifkind, BM Cleeman, JI Maurer, KR Johnson, CL AF Hickman, TB Briefel, RR Carroll, MD Rifkind, BM Cleeman, JI Maurer, KR Johnson, CL TI Distributions and trends of serum lipid levels among United States children and adolescents ages 4-19 years: Data from the third National Health and Nutrition Examination Survey SO PREVENTIVE MEDICINE LA English DT Article DE lipids; cholesterol; low-density lipoproteins (LDL); high-density lipoproteins (HDL); triglycerides; National Health and Nutrition Examination; Survey (NHANES); children; adolescents ID CHOLESTEROL LEVELS; ADULTHOOD; PLASMA AB Background. Atherosclerosis beans in childhood and progresses into adulthood. The reduction of cardiovascular risk factors, such as elevated serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, in childhood may reduce cardiovascular morbidity and mortality in adulthood. Lipid distributions among children and adolescents were examined using the most recent nationally representative data. Methods. Data from 7,499 examinees in NHANES III (1988-1994) were used to estimate mean and percentile distributions of serum total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides in children and adolescents aged 4 to 19 years. The estimates were analyzed by age, sex, and race/ethnic groups. Trends in mean total cholesterol were examined for 12- to 17-year-olds using data from NHES III (1966-1970), NHANES I (1971-1974), and NHANES III (1988-1994). Results. For children and adolescents 4 to 19 years of age, the 95th percentile for serum total cholesterol was 216 mg/dL and the 75th percentile was 181 mg/dL. Mean age-specific total cholesterol levels peaked at 171 mg/dL at 9-11 years of age and fell thereafter. Females Bad significantly higher mean total cholesterol and LDL-C levels than did males (P < 0.005). Non-Hispanic black children and adolescents had significantly higher mean total cholesterol, LDL-C, and HDL-C levels compared to non-Hispanic white and Mexican American children and adolescents. The mean total cholesterol level among 12- to 17-year-olds decreased by 7 mg/dL from 1966-1970 to 1988-1994 and is consistent with, but less than, observed trends in adults. Black females have experienced the smallest decline between surveys. Conclusions. The findings provide a picture of the lipid distribution among U.S. children and adolescents and indicate that, like adults, adolescents have experienced a fall in total cholesterol levels. Total cholesterol levels in U.S. adolescents declined from the late 1960s to the early 1990s by an average of 7 mg/dL. This information is useful for planning programs targeting the prevention of cardiovascular disease beginning with the development of heathy lifestyles in childhood. (C) 1998 American Health Foundation and Academic Press. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Briefel, RR (reprint author), 6525 Belcrest Rd, Hyattsville, MD 20782 USA. EM rrb1@cdc.gov NR 29 TC 224 Z9 235 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD NOV-DEC PY 1998 VL 27 IS 6 BP 879 EP 890 DI 10.1006/pmed.1998.0376 PG 12 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 147RJ UT WOS:000077579700017 PM 9922071 ER PT J AU Anderson, KM Seed, T Vos, M Mulshine, J Meng, J Alrefai, W Ou, D Harris, JE AF Anderson, KM Seed, T Vos, M Mulshine, J Meng, J Alrefai, W Ou, D Harris, JE TI 5-lipoxygenase inhibitors reduce PC-3 cell proliferation and initiate nonnecrotic cell death SO PROSTATE LA English DT Article DE PC-3 cells; 5-lipoxygenase inhibitors; programmed cell death ID ARACHIDONIC-ACID; IN-VIVO; C-FOS; APOPTOSIS; BCL-2; PROSTATE; NECROSIS; LINE; ACTIVATION; PREVENTION AB BACKGROUND. Products of the arachidonic acid-metabolizing enzyme, 5-lipoxygenase, stimulate the growth of several cell types. Selective inhibitors of the enzyme, including SC41661A and MK886, reduce PC-3 prostate cell proliferation. With continued culture, cells die, but the mode of death, necrotic or nonnecrotic, has not been established. METHODS. Flow cytometry, laddering after agarose electrophoresis of DNA from inhibitor-treated cells, and light and electron microscopy were employed to examine the type of death in PC-3 prostate cells cultured with either 5-lipoxygenase inhibitor. RESULTS. The inhibitors induced nonnecrotic, programmed cell death. SC41661A-treated cells exhibited "foamy," vacuolated cytoplasm and mitochondria with disrupted cristae and limiting membranes, while some cells contained numerous polysomes and extended hyper trophic Golgi and secretory cisternal networks. A proportion of the treated cells detached and the nuclei of these cells were characteristic of type 1 "apoptotic" programmed cell death. MK886, a 5-lipoxygenase- inhibitor with a different mechanism of action, induced nonnecrotic changes largely confined to the cytoplasm, most consistent with type 2 "autophagic" programmed cell death. In preliminary studies of mechanism, we demonstrated that PC-3 cells express mRNA for 5-lipoxygenase and for 5-lipoxygenase-activating protein. The less active inhibitor, SC45662 neither reduced proliferation nor induced DNA laddering. The antioxidant, N-acetyl-1-cysteine but not butylated hydroxy toluene or alpha tocopherol, partially reduced the inhibition of proliferation from SC41661A. CONCLUSIONS. SC41661A and MK886 inhibit PC-3 cell proliferation and induce a form of type 1 or type 2 programmed cell death, respectively. PC-3 cells contain messenger RNA for 5-lipoxygenase and 5-lipoxygenase-activating proteins. Drug-induced changes included altered redox potential, inferred from the increased survival due to the antioxidant and glutathione precursor, N-acetyl.-1-cysteine. PC-3 cells are an appropriate model for studying the mechanism responsible for 5-lipoxygenase inhibitor-induced cellular suicide. (C) 1998 Wiley-Liss, Inc. C1 Rush Med Coll, Sect Med Oncol, Dept Med, Chicago, IL 60612 USA. Rush Med Coll, Dept Biochem, Chicago, IL 60612 USA. TechMicro Serv, Glen Ellyn, IL USA. Natl Canc Inst, Biomarkers Prevent Branch, Rockville, MD USA. W Side VA, Dept Clin Immunol, Chicago, IL USA. RP Anderson, KM (reprint author), Rush Med Coll, Sect Med Oncol, Dept Med, 1753 W Harrison, Chicago, IL 60612 USA. NR 38 TC 81 Z9 85 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-4137 J9 PROSTATE JI Prostate PD NOV 1 PY 1998 VL 37 IS 3 BP 161 EP 173 DI 10.1002/(SICI)1097-0045(19981101)37:3<161::AID-PROS5>3.0.CO;2-D PG 13 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 130HN UT WOS:000076514400005 PM 9792133 ER PT J AU Wallqvist, A Smythers, GW Covell, DG AF Wallqvist, A Smythers, GW Covell, DG TI A cooperative folding unit in HIV-1 protease. Implications for protein stability and occurrence of drug-induced mutations SO PROTEIN ENGINEERING LA English DT Article DE autonomous folding unit; drug-resistance; HIV-1 protease; HIV-1 reverse transcriptase; mutation ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; HYDROGEN-EXCHANGE; 3-DIMENSIONAL STRUCTURE; RESISTANCE PATTERNS; CROSS-RESISTANCE; 2.3-A RESOLUTION; INHIBITOR DESIGN; MUTANT; MECHANISM AB We investigated the HIV-1 protease molecule for the occurrence of cooperative folding units, i.e. structural units that exhibit a relatively stronger protection against unfolding than do other parts of the molecule, Calculated unfolding penalties are used to delineate folding units. This procedure identifies a folding core in HIV-1 protease, based on an ensemble of denatured states derived from native structures, comprising a spatially close unit of residues 84-91, 74-78 and 22-32, the last of which contains the active site residues D25, T26 and G27, Observed enzyme mutations of HIV-1 protease, either naturally occurring or induced by drug therapy, are found in regions that are not structurally designed to withstand unfolding. These mutations are especially likely to occur in the flap region, a part of the protein which is not essential for the stability of the protein, but does contribute significantly to the stability of protease-drug complexes. A similar avoidance of structurally protected regions in the reverse transcriptase enzyme is also observed. C1 NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. NR 43 TC 23 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD NOV PY 1998 VL 11 IS 11 BP 999 EP 1005 DI 10.1093/protein/11.11.999 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 148MP UT WOS:000077509400006 PM 9876920 ER PT J AU Murray, MB Tadaki, DK Campion, SR Lamerdin, JA Serpersu, EH Bradrick, TD Niyogi, SK AF Murray, MB Tadaki, DK Campion, SR Lamerdin, JA Serpersu, EH Bradrick, TD Niyogi, SK TI Structure-function analysis of a conserved aromatic cluster in the N-terminal domain of human epidermal growth factor SO PROTEIN ENGINEERING LA English DT Article DE aromatic cluster of human EGF; circular dichroism; mutagenesis; NMR analysis; receptor binding ID SITE-DIRECTED MUTAGENESIS; NUCLEAR-MAGNETIC-RESONANCE; TYROSINE KINASE-ACTIVITY; FACTOR-ALPHA; RECEPTOR-BINDING; H-1-NMR ASSIGNMENTS; MUTATIONAL ANALYSIS; FACTOR HEGF; BETA-SHEET; PROTEIN AB The importance of a cluster of conserved aromatic residues of human epidermal growth factor (hEGF) to the receptor binding epitope is suggested by the interaction of His10 and Tyr13 of the A-loop with Tyr22 and Tyr29 of the N-terminal beta-sheet to form a hydrophobic surface on the hEGF protein. Indeed, Tyr13 has previously been shown to contribute a hydrophobic determinant to receptor binding. The roles of His10, Tyr22 and Tyr29 were investigated by structure-function analysis of hEGF mutant analogues containing individual replacements of each residue. Substitutions with aromatic residues or a leucine at position 10 retained receptor affinities and agonist activities similar to wild-type indicating that an aromatic residue is not essential. Variants with polar, charged or aliphatic substitutions altered in size and/or hydrophobicity exhibited reduced binding and agonist activities, 1-Dimensional H-1 NMR spectra of high, moderate and low-affinity analogues at position 10 suggested only minor alterations in hEGF native structure. In contrast, a variety of replacements were tolerated at position 22 or 29 indicating that neither aromaticity nor hydrophobicity of Tyr22 and Tyr29 is required for receptor binding, CD spectra of mutant analogues at position 22 or 29 indicated a correlation between loss of receptor affinity and alterations in hEGF structure. The results indicate that similar to Tyr13, His10 of hEGF contributes hydrophobicity to the receptor binding epitope, whereas Tyr22 and Tyr29 do not appear to be directly involved in receptor interactions. The latter conclusion, together with previous studies, suggests that hydrophobic residues on only one face of the N-terminal P-sheet of hEGF are important in receptor recognition. C1 Prot Engn & Mol Mutagenesis Program, Oak Ridge, TN 37831 USA. Univ Tennessee, Oak Ridge Grad Sch Biomed Sci, Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN 37831 USA. Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Niyogi, SK (reprint author), Prot Engn & Mol Mutagenesis Program, Oak Ridge, TN 37831 USA. FU NCI NIH HHS [CA 09336]; NIGMS NIH HHS [R29 GM42661] NR 61 TC 7 Z9 8 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD NOV PY 1998 VL 11 IS 11 BP 1041 EP 1050 DI 10.1093/protein/11.11.1041 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 148MP UT WOS:000077509400011 PM 9876925 ER PT J AU McCord, M Stahl, SJ Mueser, TC Hyde, CC Vora, AC Grandgenett, DP AF McCord, M Stahl, SJ Mueser, TC Hyde, CC Vora, AC Grandgenett, DP TI Purification of recombinant Rous sarcoma virus integrase possessing physical and catalytic properties similar to virion-derived integrase SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID MURINE LEUKEMIA-VIRUS; VIRAL-DNA ENDS; IN-VITRO; RETROVIRAL DNA; CONCERTED INTEGRATION; HIV-1 INTEGRASE; BINDING PROPERTIES; TYPE-1 INTEGRASE; PROTEIN; INVITRO AB Recombinant Rous sarcoma virus integrase cloned from the Prague A (PrA) virus strain was expressed in Escherichia coli. Here we report the detailed purification procedure resulting in an apparently homogeneous integrase. Recombinant PrA integrase was compared at both the protein structural and the catalytic levels to avian myeloblastosis virus integrase purified from virions. Both proteins exist minimally in a dimeric state at low nanomolar concentrations as analyzed by glycerol gradient sedimentation and protein crosslinking studies, Likewise, both proteins have similar specific activities for full-site (concerted integration reaction) and half-site strand transfer activities using linear 480-bp retrovirus-like donor substrates that contain wild-type or mutant termini, They respond similarly to high NaCl concentrations (similar to 350 mM) as well as aprotic solvents for efficient full-site strand transfer. The data suggest that recombinant integrase proteins with physical and catalytic properties similar to the virion counterpart can be purified using these techniques and will faithfully and efficiently promote the full-site integration reaction in vitro, (C) 1998 Academic Press. C1 St Louis Univ, Hlth Sci Ctr, Inst Mol Virol, St Louis, MO 63110 USA. NIAMSD, Bethesda, MD 20892 USA. RP Grandgenett, DP (reprint author), St Louis Univ, Hlth Sci Ctr, Inst Mol Virol, St Louis, MO 63110 USA. EM Grandgdp@SLU.EDU FU NCI NIH HHS [CA16312] NR 40 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD NOV PY 1998 VL 14 IS 2 BP 167 EP 177 DI 10.1006/prep.1998.0954 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 133RD UT WOS:000076698800003 PM 9790878 ER PT J AU Kervinen, J Lubkowski, J Zdanov, A Bhatt, D Dunn, BM Hui, KY Powell, DJ Kay, J Wlodawer, A Gustchina, A AF Kervinen, J Lubkowski, J Zdanov, A Bhatt, D Dunn, BM Hui, KY Powell, DJ Kay, J Wlodawer, A Gustchina, A TI Toward a universal inhibitor of retroviral proteases: Comparative analysis of the interactions of LP-130 complexed with proteases from HIV-I, FIV, and EIAV SO PROTEIN SCIENCE LA English DT Article DE drug design; drug resistance; HIV; proteases; retroviruses ID FELINE IMMUNODEFICIENCY VIRUS; X-RAY-DIFFRACTION; PROTEINASE; BINDING; SUSCEPTIBILITY; SENSITIVITY; RESISTANT; SEQUENCES; VARIANTS; PEPTIDES AB One of the major problems encountered in antiviral therapy against AIDS is the emergence of viral variants that exhibit drug resistance. The sequences of proteases (PRs) from related retroviruses sometimes include, at structurally equivalent positions, amino acids identical to those found in drug-resistant forms of HIV-1 PR. The statine-based inhibitor LP-130 was found to be a universal, nanomolar-range inhibitor against all tested retroviral PRs. We solved the crystal structures of LP-130 in complex with retroviral PRs from HIV-1. feline immunodeficiency virus, and equine infectious anemia virus and compared the structures to determine the differences in the interactions between the inhibitor and the active-site residues of the enzymes. This comparison shows an extraordinary similarity in the binding modes of the inhibitor molecules. The only exceptions are the different conformations of naphthylalanine side chains at the P3/P3' positions, which might be responsible for the variation in the K-i, values. These findings indicate that successful inhibition of different retroviral PRs by LP-130 is achieved because this compound can be accommodated without serious conformational differences, despite the variations in the type of residues forming the active site region. Although strong, specific interactions between the ligand and the enzyme might improve the potency of the inhibitor, the absence of such interactions seems to favor the universality of the compound. Hence, the ability of potential anti-AIDS drugs to inhibit multiple retroviral PRs might indicate their likelihood of not eliciting drug resistance. These studies may also contribute to the development of a small-animal model for preclinical testing of antiviral compounds. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol Struct Lab, Frederick, MD 21702 USA. Univ Florida, J Hillis Miller Hlth Ctr, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Wales Coll Cardiff, Sch Mol & Med Biosci, Cardiff CF1 3US, S Glam, Wales. RP Gustchina, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol Struct Lab, Frederick, MD 21702 USA. EM alla@orion.ncifcrf.gov FU NIAID NIH HHS [AI28571]; NIGMS NIH HHS [P01 GM48870] NR 39 TC 30 Z9 31 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD NOV PY 1998 VL 7 IS 11 BP 2314 EP 2323 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 134WE UT WOS:000076766100008 PM 9827997 ER PT J AU Blazer, DG Landerman, LR Hays, JC Simonsick, EM Saunders, WB AF Blazer, DG Landerman, LR Hays, JC Simonsick, EM Saunders, WB TI Symptoms of depression among community-dwelling elderly African-American and White older adults SO PSYCHOLOGICAL MEDICINE LA English DT Article ID BLACKS; SCALE AB Background. Few studies have explored the variance in individual symptoms by race in older adults. Methods. Data were analysed from the Duke site of the Established Populations for Epidemiologic Studies of the Elderly (EPESE), a community sample of persons 65 years-of-age and older, 54 % of whom were African-Americans. Of the 3401 subjects with adequate data on depressive symptomatology, confirmatory factor analysis and LISREL were first used to confirm the presence of the factor structure previously reported for the CES-D. Next, bivariate analysis was performed to determine the prevalence of individual symptoms by race. Finally, LISREL analysis was performed to control for potential confounding variables. Results. When bivariate comparisons of specific symptoms by race were explored, African-Americans were more likely to report less hope about the future, poor appetite, difficulty concentrating, requiring more effort for usual activities, less talking, feeling people were unfriendly, feeling disliked by others and being more 'bothered' than usual. When LISREL analyses were applied to these data (controlling for education, income, cognitive impairment, chronic health problems and disability and other factors) racial differences in somatic complaints and life satisfaction disappeared, yet differences in interpersonal relations persisted. Conclusions. This study confirms earlier findings of minimal overall differences in symptom frequency between African-American and non-African-American community-dwelling older adults in controlled studies. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. Glaxo Wellcome Inc, Worldwide Epidemiol, NIA, Epidemiol Demog & & Biometry Program, Res Triangle Pk, NC 27709 USA. RP Blazer, DG (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Box 3005, Durham, NC 27710 USA. FU NIA NIH HHS [N01 AG 1 2102] NR 30 TC 137 Z9 137 U1 1 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD NOV PY 1998 VL 28 IS 6 BP 1311 EP 1320 DI 10.1017/S0033291798007648 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 145GL UT WOS:000077362600006 PM 9854272 ER PT J AU Knox, SS Uvnas-Moberg, K AF Knox, SS Uvnas-Moberg, K TI Social isolation and cardiovascular disease: An atherosclerotic pathway? SO PSYCHONEUROENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Wenner Gren Symposium - Is There a Neurobiology of Love CY AUG 28-31, 1996 CL STOCKHOLM, SWEDEN DE social isolation; atherosclerosis; oxytocin; pituitary; sympathetic ID CORONARY-ARTERY DISEASE; PLATELET BETA-ADRENOCEPTORS; FEMALE CYNOMOLGUS MONKEYS; BLOOD-PRESSURE; MEN BORN; MYOCARDIAL-INFARCTION; PERSONALITY-TRAITS; FOLLOW-UP; LABORATORY MODEL; OXYTOCIN LEVELS AB This paper outlines two pathways through which social support can influence the prevention or progression of cardiovascular disease: health behaviors and neuroendocrine mechanisms. Its primary focus is on neuroendocrine pathways, reviewing data which suggest that lack of social support is etiologically related to coronary artery lesion development through two mechanisms: sympathetic-adrenomedullary influences on platelet function, heart rate and blood pressure in the initial endothelial injury; and pituitary-adrenal cortical factors involved in smooth muscle cell proliferation during progression of the lesion after injury has taken place. It hypothesizes that the buffering effect of social support on the cardiovascular system is mediated primarily through mechanisms associated with the release of oxytocin. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NHLBI, Div Epidemiol & Clin Applicat, Rockledge Ctr II 8120, Bethesda, MD 20892 USA. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. RP Knox, SS (reprint author), NHLBI, Div Epidemiol & Clin Applicat, Rockledge Ctr II 8120, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA. EM sarah_knox@nih.gov NR 84 TC 91 Z9 91 U1 6 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD NOV PY 1998 VL 23 IS 8 BP 877 EP 890 DI 10.1016/S0306-4530(98)00061-4 PG 14 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 156LD UT WOS:000078001800008 PM 9924742 ER PT J AU Marley, RJ Arros, DM Henricks, KK Marley, ME Miner, LL AF Marley, RJ Arros, DM Henricks, KK Marley, ME Miner, LL TI Sensitivity to cocaine and amphetamine among mice selectively bred for differential cocaine sensitivity SO PSYCHOPHARMACOLOGY LA English DT Article DE behavioral genetics; cocaine; amphetamine; psychomotor stimulant; selective breeding ID OPEN-FIELD ACTIVITY; INDIVIDUAL-DIFFERENCES; GENETIC-DIFFERENCES; DOPAMINE; RECEPTORS; ETHANOL; LINES; SENSITIZATION; GENERATIONS; BRAIN AB Selective breeding of mice for differences in response to a drug offers a powerful means for testing hypotheses regarding underlying mechanisms and relationships between drug-induced behaviors. Starting from a heterogeneous stock of mice, we have selectively bred lines of mice for extreme differences in their locomotor response to 10 mg/kg cocaine HCl. Selection pressure has been maintained for 12 generations and has resulted in two cocaine sensitive (CAHI) and two cocaine insensitive (CALO) lines. Across the generations of selection, the CAHI lines showed progressively greater amounts of cocaine-induced locomotion, with mice from the S12 generation traveling over 21,000 cm/30 min. following 10 mg/kg cocaine. The CALO lines, in contrast, did not substantially diverge from control values until the S8 generation. By generation 12, however, the LO lines traveled no further following 10 mg/kg cocaine (7000 cm/30 min), than they did following an initial saline injection. Cocaine and amphetamine dose-response analyses were conducted on drug-naive mice from the tenth generation, The CAHI lines were extremely sensitive to the locomotor activating effects of all doses of cocaine, displaying from 2- to 6-fold greater amounts of cocaine-induced locomotion than the CALO lines. The CALO lines, in contrast, were completely insensitive to the psychomotor stimulant effects of cocaine. The CAHI lines were also more sensitive to the locomotor activating effects of amphetamine. Both lines showed dose-dependent amphetamine-induced locomotion that peaked at 3 mg/kg. However, at all doses, the CAHI lines showed a 2- to 4-fold greater amount of locomotion than CALO lines. Thus, the sensitivity to cocaine developed through selection using a single dose of cocaine has generalized to a range of doses of cocaine and to at least one other psychostimulant. C1 SUNY Albany, Dept Psychol, Albany, NY 12222 USA. Taconic Farms, Germantown, NY USA. NIDA, Sci Policy Branch, Rockville, MD 20857 USA. RP Marley, RJ (reprint author), SUNY Albany, Dept Psychol, 1400 Washington Ave, Albany, NY 12222 USA. NR 35 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 1998 VL 140 IS 1 BP 42 EP 51 DI 10.1007/s002130050737 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 141PE UT WOS:000077151700006 PM 9862401 ER PT J AU Ron, E AF Ron, E TI Ionizing radiation and cancer risk: Evidence from epidemiology SO RADIATION RESEARCH LA English DT Review ID ATOMIC-BOMB SURVIVORS; CANADIAN FLUOROSCOPY COHORT; CHERNOBYL CLEANUP WORKERS; BREAST-CANCER; LUNG-CANCER; THYROID-CANCER; CHILDHOOD LEUKEMIA; OCCUPATIONAL EXPOSURE; NUCLEAR-FACILITIES; RESIDENTIAL RADON AB Epidemiological studies provide the primary data on the carcinogenic effects of radiation in humans. Much of what is known has come from studies of the atomic bomb survivors, and to a lesser extent from patients receiving radiotherapy. These studies demonstrate that exposure to moderate to high doses of radiation increases the risk of cancer in most organs. For all solid cancers combined, cancers of the thyroid, breast and lung, and leukemia, risk estimates are fairly precise, and associations have been found at relatively low doses (<0.2 Gy). Associations between radiation and cancers of the salivary glands, stomach, colon, bladder, ovary, central nervous system and skin have also been reported, but the relationships are not as well quantified. Associations between radiation and cancers of the liver and esophagus, and to a lesser extent multiple myeloma and non-Hodgkin's lymphoma, have been reported in a few studies, but results are inconsistent. Chronic lymphocytic leukemia, Hodgkin's disease, and cancers of the pancreas, prostate, testis and cervix have rarely been linked to radiation exposure. A linear no-threshold model adequately describes the dose-response relationship for solid cancers, although at extremely high doses the risk appears to flatten out. Because few populations have been followed until the end of life, the temporal patterns of risk are not completely known. An increased risk, however, does continue for several decades. In contrast, radiation-related leukemias begin to occur shortly (2-3 years) after exposure and, at least in the A-bomb survivors, a linear-quadratic dose response seems to fit the data better than a pure linear model. Radiation does not act entirely in isolation. It can interact with other carcinogens, e.g. tobacco or chemotherapeutic agents, and with host factors such as age at exposure, gender or reproductive history. Interactions with medical interventions or with certain heritable mutations have also been suggested. While the studies of high-dose exposures are essential for understanding the overall biological consequences of radiation exposure, the public is more concerned about the long-term health effects from protracted exposures at low doses. Unfortunately, the inherent limitations of epidemiology make it extremely difficult to directly quantify health risks from these exposures. While most epidemiological data are compatible with linear extrapolations from exposures at high doses or high dose rates, they cannot entirely exclude other possibilities. As the field of epidemiology advances, understanding more about the health effects of prolonged and low-dose exposures will be the next challenge. (C) 1998 by Radiation Research Society. C1 Natl Canc Inst, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Natl Canc Inst, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NR 112 TC 76 Z9 77 U1 0 U2 14 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD NOV PY 1998 VL 150 IS 5 SU S BP S30 EP S41 DI 10.2307/3579806 PG 12 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 133QY UT WOS:000076698300005 PM 9806607 ER PT J AU Manzone, TA Malkowicz, SB Tomaszewski, JE Schnall, MD Langlotz, CP AF Manzone, TA Malkowicz, SB Tomaszewski, JE Schnall, MD Langlotz, CP TI Use sf endorectal MR imaging to predict prostate carcinoma recurrence after radical prostatectomy SO RADIOLOGY LA English DT Article; Proceedings Paper CT 83rd Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 30-DEC 05, 1997 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE prostate, MR; prostate, neoplasms; prostate, surgery ID SURFACE COIL; MULTIVARIATE-ANALYSIS; PATHOLOGICAL STAGE; ANTIGEN FAILURE; CANCER; ADENOCARCINOMA; UTILITY AB Purpose: To determine the ability of endorectal magnetic resonance (MR) imaging to help predict postprostatectomy disease recurrence and, thereby, patient outcome. Materials and methods: The authors evaluated 116 patients for prostate MR imaging during 1991 and 1992 who subsequently underwent radical prostatectomy and for whom follow-up data through 1996 could be obtained. The MR reports, clinic charts, and pathology reports were reviewed. Disease recurrence was established by means of detectable levels or serum prostate-specific antigen (PSA) after surgery. Results: Thirty-four patients (29%) had postoperative disease recurrence. Patients with recurrence had higher preoperative PSA values (P < .0001). These patients also more frequently had positive surgical margins (P = .0005), transcapsular tumor spread (P <. 001) and high grade (P = .0058). Of 13 patients whose MR examinations showed definite extracapsular disease, eight (65%) had disease recurrence. The recurrence rate when MR imaging indicated limited disease (24%) was similar to that when MR imaging showed possible microscopic extension (27%). An MR finding of definite extracapsular disease was 24% sensitive and 94% specific for the prediction of disease recurrence. Conclusion: MR imaging findings of definite extracapsular spread of disease helped predict prostate tumor recurrence with high specificity, although with low sensitivity. C1 Univ Penn, Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Urol, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. RP Langlotz, CP (reprint author), NCI, Diagnost Imaging Program, 6130 Execut Blvd,EPN 800, Rockville, MD 20892 USA. RI Schnall, Mitchell/D-1149-2009 NR 25 TC 17 Z9 17 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1998 VL 209 IS 2 BP 537 EP 542 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 132EU UT WOS:000076618000039 PM 9807586 ER EF