FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Lamensdorf, I Hrycyna, C He, LP Nechushtan, A Tjurmina, O Harvey-White, J Eisenhofer, G Rojas, E Kopin, IJ AF Lamensdorf, I Hrycyna, C He, LP Nechushtan, A Tjurmina, O Harvey-White, J Eisenhofer, G Rojas, E Kopin, IJ TI Acidic dopamine metabolites are actively extruded from PC12 cells by a novel sulfonylurea-sensitive transporter SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE 3,4-dihydroxyphenylacetic acid; homovanillic acid; dopamine; transporter; sulfonylurea; PC12 cells; ATP-binding cassette (ABC) ID RESISTANCE-ASSOCIATED PROTEIN; BINDING CASSETTE TRANSPORTER; K-ATP CHANNELS; P-GLYCOPROTEIN; POTASSIUM CHANNEL; FUNCTIONAL EXPRESSION; SKELETAL-MUSCLE; RAT STRIATUM; BRAIN; GENE AB Incubation of PC 12 cells with the sulfonylurea drug. glipizide (1-100 mu M), increased intracellular levels of the acidic metabolites of dopamine, 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA). The levels of these acids in the medium were decreased, indicating the presence of a sulfonylurea-sensitive organic anion transporter. In the present study, we demonstrate that the sulfonylurea-sensitive transport of acidic dopamine metabolites is unidirectional, ATP dependent, unaffected by ouabain or by tetrodotoxin and blocked by drugs that interact with the multidrug-resistance protein-1 (MRP1). However, over-expression of MRP1 did not affect transport of the acid metabolites. The pharmacological profile and ion dependence of the transporter also differs from that of known ATP binding cassette (ABC) family members. Using microdialysis, we also demonstrated a sulfonylurea-sensitive transport process in the striatum of freely moving rats. These results show that acidic dopamine metabolites an actively secreted from dopaminergic cells into surrounding extracellular fluid by a previously undescribed transporter. C1 NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Lamensdorf, I (reprint author), NINDS, Clin Neurosci Branch, NIH, Bldg 10,Room 6N256, Bethesda, MD 20892 USA. NR 45 TC 9 Z9 9 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD JUN PY 2000 VL 361 IS 6 BP 654 EP 664 DI 10.1007/s002100000246 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 329AC UT WOS:000087883100012 PM 10882041 ER PT J AU Scortegagna, M Hanbauer, I AF Scortegagna, M Hanbauer, I TI Increased AP-1 DNA-binding activity and nuclear REF-1 accumulation in lead-exposed primary cultures of astrocytes SO NEUROCHEMICAL RESEARCH LA English DT Article DE activator protein-1; c-jun mRNA; redox factor-1 protein; lead; astrocyte primary cultures ID MESENCEPHALIC PRIMARY CULTURES; PROTEIN-KINASE-C; OXIDATIVE STRESS; REDOX REGULATION; REPAIR PROTEIN; MESSENGER-RNA; PC12 CELLS; RAT-BRAIN; TRANSCRIPTION; ENDONUCLEASE AB Pb was shown to perturb neuronal and glial function either directly by interacting with protein thiol groups or indirectly by mimicking Ca2+ and increasing oxidative stress. In view of the potential action of Pb on cellular redox homeostasis we studied the regulation of activator protein-1 (AP-1) DNA binding. A 1h incubation of astrocyte primary cultures with 10 mu M Pb caused a 2.5 fold increase in AP-1 DNA binding. An assessment of how Pb elicited this increase revealed the involvement of 1. transcriptional and 2. posttranslational processes. The first one was documented by an increase of c-jun mRNA content after 15 to 30 min of 10 mu M Pb exposure. The second one was suggested by an enhanced nuclear accumulation of redox factor-1 after 30 to 60 min of 10 mu M Pb exposure. The Pb-elicited increase of the reduction/oxidation-sensitive AP-1 signal transduction may regulate target genes operative in cell survival or cell death. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Hanbauer, I (reprint author), NHLBI, Biochem Lab, NIH, Bldg 10,Room 7N312, Bethesda, MD 20892 USA. NR 41 TC 10 Z9 10 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD JUN PY 2000 VL 25 IS 6 BP 861 EP 866 DI 10.1023/A:1007577710066 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 339FB UT WOS:000088466000014 PM 10944005 ER PT J AU Butera, RJ Johnson, SM DelNegro, CA Rinzel, J Smith, JC AF Butera, RJ Johnson, SM DelNegro, CA Rinzel, J Smith, JC TI Dynamics of excitatory networks of bursting pacemaking neurons: Modeling and experimental studies of the respiratory central pattern generator SO NEUROCOMPUTING LA English DT Article; Proceedings Paper CT 8th Annual Computational Neurosciences Meeting (CNS 99) CY JUL, 1999 CL PITTSBURGH, PA DE pre-Botzinger; medulla; respiration; pattern generation; frequency control ID PRE-BOTZINGER COMPLEX; RHYTHM GENERATION; NEURAL MECHANISMS; MEDULLARY SLICES; NEONATAL RAT; IN-VITRO; MAMMALS; GENESIS; INVITRO AB We have explored the dynamics of a computational model of an excitatory network of bursting pacemaker neurons with heterogeneous properties. The network generates synchronous bursts of activity, and the frequency of both single cells and the synaptically coupled pacemaker cell population may be controlled by varying the degree of depolarizing input (DI). The dynamic range of DI where stable bursting occurs is significantly larger for the coupled population than that of individual cells, suggesting a functional role of cellular heterogeneity in making biological rhythms more robust. Experimental evidence is presented from the pacemaker-network generating the respiratory rhythm in the mammalian brainstem. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Georgia Inst Technol, Sch Elect & Comp Engn, Atlanta, GA 30332 USA. Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA. NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Physiol & Biophys, Washington, DC 20059 USA. NYU, Ctr Neural Sci, New York, NY 10003 USA. NYU, Courant Inst Math Sci, New York, NY 10003 USA. RP Butera, RJ (reprint author), Georgia Inst Technol, Sch Elect & Comp Engn, Atlanta, GA 30332 USA. EM robert.butera@ece.gatech.edu OI Butera, Robert/0000-0002-1806-0621 NR 26 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-2312 J9 NEUROCOMPUTING JI Neurocomputing PD JUN PY 2000 VL 32 BP 323 EP 330 DI 10.1016/S0925-2312(00)00181-8 PG 8 WC Computer Science, Artificial Intelligence SC Computer Science GA 329GB UT WOS:000087897800046 ER PT J AU Dickerman, RD McConathy, WJ Smith, GH East, JW Rudder, L AF Dickerman, RD McConathy, WJ Smith, GH East, JW Rudder, L TI Middle cerebral artery blood flow velocity in elite power athletes during maximal weight-lifting SO NEUROLOGICAL RESEARCH LA English DT Article DE cerebral perfusion; stroke; baroreflex; Valsalva; ischemia; weight-lifting ID SLIDING HIATAL-HERNIA; VALSALVA MANEUVER; PRESSURE-OVERLOAD; INTRACRANIAL-PRESSURE; TRANSCRANIAL DOPPLER; RESISTANCE EXERCISE; AUTOREGULATION; CONTRACTION; CIRCULATION AB Cerebral blood flow velocity (CBFV) has been shown to significantly increase during dynamic exercise (running) secondary to increases in cardiac output. Static exercise (weight-lifting) induces supraphysiological arterial pressures up to 450/380 mmHg, and thus may alter CBFV. Catastrophic brain injuries such as stroke, cerebral hemorrhage, subarachnoid hemorrhage, retinal hemorrhage and retinal detachment have been associated with weight-lifting A recent study has shown that intra-ocular pressure (IOP) which is an indirect measure of intracranial pressure, elevates to pathophysiologic levels during weight-lifting. Recent CBFV studies instituting Valsalva have demonstrated decreases in CBFV from 21%-52%. To date, no studies have examined CBFV during maximal weight-lifting to elucidate the cerebrovascular responses to extreme pressure alterations. We recruited nine elite pou er athletes, including a multi-world record holder in powerlifting, for a transcranial Doppler study of middle cerebral artery blood flow velocity at rest and during maximal weight-lifting. All subjects' resting blood flow velocities were within normal ranges (mean 64.4 +/- 9.5 cm sec(2)). Blood flow velocities were significantly (p < 0.0001) decreased in all subjects during maximal lifting (mean 48.4 +/- 10.1 cm sec(2)). Linear regression analysis demonstrated a significant inverse linear relationship in the net change of blood velocities from rest to maximal lift for each subject (r = 0.8585, p < 0.001). This study demonstrates that blood flow velocities are significantly decreased during heavy resistance training. The drop in CBFV during weight-lifting was significantly less than previous Valsalva studies, which likely reveals the cardiovascular, baroreflex, and cerebrovascular system adaptations occurring in these elite power athletes. C1 Univ N Texas, Hlth Sci Ctr, Dept Surg, Ft Worth, TX USA. Univ N Texas, Hlth Sci Ctr, Dept Med, Ft Worth, TX USA. RP Dickerman, RD (reprint author), NIH, Surg Neurol Branch, 10 Ctr Dr,Bldg 10,Rm 5D37, Bethesda, MD 20892 USA. NR 41 TC 22 Z9 22 U1 1 U2 13 PU FOREFRONT PUBL GROUP PI WILTON PA C/O MARY J RAWLINS, 5 RIVER RD, STE 113, WILTON, CT 06897 USA SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD JUN PY 2000 VL 22 IS 4 BP 337 EP 340 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 328EC UT WOS:000087835100002 PM 10874679 ER PT J AU Berger, K Breteler, MMB Helmer, C Inzitari, D Fratiglioni, L Trenkwalder, C Hofman, A Launer, LJ AF Berger, K Breteler, MMB Helmer, C Inzitari, D Fratiglioni, L Trenkwalder, C Hofman, A Launer, LJ CA Neurologic Dis Elderly Res Grp TI Prognosis with Parkinson's disease in Europe: A collaborative study of population-based cohorts SO NEUROLOGY LA English DT Article DE PD; prognosis; mortality; institutionalization; elderly; epidemiology ID TO-DOOR SURVEY; LEVODOPA THERAPY; MORTALITY; PREVALENCE; DISORDERS; EPIDEMIOLOGY; OLDER; SURVIVAL; PROJECT; COUNTY AB Data are lacking on the prognosis (institutionalization and death) of PD cases identified in population-based studies. Data from five population-based European studies were compared and pooled, Each study used comparable two-step screening methods to identify cases and performed one or more follow-up examinations of their respective participants after defined periods of time. PD was classified on the basis of questionnaire and clinical data, The studies include 16,143 participants (252 with PD), The relative risk (RR) (95% CI) of death associated with PD was 2.3 (1.8 to 3.0). The risk for death in men with PD (RR 3.1 [2.1 to 4.4]) was higher than in women with PD (RR 1.8 [1.2 to 5.1]), The rate of institutionalization varied across studies, increased with age, and was considerably higher in PD cases compared to noncases. Women with PD had a fivefold higher risk to live in a care facility than did men with PD. These data on mortality and rate of institutionalization reflect the high burden of PD in the population. C1 Erasmus Med Ctr, Dept Epidemiol & Biostat, EURODEM, NL-3000 DR Rotterdam, Netherlands. Univ Munster, Inst Epidemiol & Social Med, D-4400 Munster, Germany. INSERM U330, Bordeaux, France. Univ Florence, Dept Neurol & Psychiat Sci, I-50121 Florence, Italy. Stockholm Gerontol Res Ctr, Karolinska Inst, NEUROTEC, Div Geriatr Med, Stockholm, Sweden. Max Planck Inst, Munich, Germany. NIA, Epidemiol Demog Biometry Program, Bethesda, MD 20892 USA. RP Berger, K (reprint author), Erasmus Med Ctr, Dept Epidemiol & Biostat, EURODEM, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI Breteler, Monique /J-5058-2014; HELMER, Catherine/I-6581-2015 OI HELMER, Catherine/0000-0002-5169-7421 NR 26 TC 40 Z9 43 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2000 VL 54 IS 11 SU 5 BP S24 EP S27 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 323ZP UT WOS:000087595700006 PM 10854358 ER PT J AU de Rijk, MC Launer, LJ Berger, K Breteler, MMB Dartigues, JF Baldereschi, M Fratiglioni, L Lobo, A Martinez-Lage, J Trenkwalder, C Hofman, A AF de Rijk, MC Launer, LJ Berger, K Breteler, MMB Dartigues, JF Baldereschi, M Fratiglioni, L Lobo, A Martinez-Lage, J Trenkwalder, C Hofman, A CA Neurologic Dis Elderly Res Grp TI Prevalence of Parkinson's disease in Europe: A collaborative study of population-based cohorts SO NEUROLOGY LA English DT Article DE PD; epidemiology; prevalence; elderly; collaboration study ID DISORDERS; DEMENTIA; DESIGN AB The results of seven population-based studies were examined separately and pooled to obtain age- and sex-specific estimates of the prevalence of PD, An in-person screening instrument and diagnostic clinical examination were used to detect potential PD cases, The overall prevalence (per 100 population) in persons 65 years of age and older was 1.8, with an increase from 0.6 for those age 65 to 69 years to 2.6 for those 85 to 89 years. There were no sex differences in prevalence of PD. C1 Erasmus MC, Dept Epidemiol & Biostat, EURODEM, NL-3000 DR Rotterdam, Netherlands. NIA, Epidemiol Demog Biometry Program, Bethesda, MD 20892 USA. Univ Munster, Inst Epidemiol & Social Med, D-4400 Munster, Germany. INSERM U330, Bordeaux, France. CNR, Italian Longitudinal Study, Florence, Italy. Stockholm Gerontol Res Ctr, Karolinska Inst, NEUROTEC, Div Geriatr Med, Stockholm, Sweden. Univ Zaragoza, Dept Psychiat, E-50009 Zaragoza, Spain. Univ Navarra, Dept Neurol, E-31080 Pamplona, Spain. Max Planck Inst Psychiat, D-80804 Munich, Germany. RP de Rijk, MC (reprint author), Erasmus MC, Dept Epidemiol & Biostat, EURODEM, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI Breteler, Monique /J-5058-2014 NR 13 TC 340 Z9 345 U1 0 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2000 VL 54 IS 11 SU 5 BP S21 EP S23 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 323ZP UT WOS:000087595700005 PM 10854357 ER PT J AU Di Carlo, A Launer, LJ Breteler, MMB Fratiglioni, L Lobo, A Martinez-Lage, J Schmidt, R Hofman, A AF Di Carlo, A Launer, LJ Breteler, MMB Fratiglioni, L Lobo, A Martinez-Lage, J Schmidt, R Hofman, A CA ILSA Working Grp Neurologic Dis Elderly Res Grp TI Frequency of stroke in Europe: A collaborative study of population-based cohorts SO NEUROLOGY LA English DT Article DE stroke; prevalence; incidence; elderly; epidemiology ID ACUTE CEREBROVASCULAR-DISEASE; PERTH COMMUNITY STROKE; CASE-FATALITY; PROJECT 1981-86; SECULAR TRENDS; GLOBAL BURDEN; PREVALENCE; MORTALITY; EPIDEMIOLOGY; EXPERIENCE AB The authors estimated stroke frequency in Europe using data from six population-based studies that were analyzed separately and also pooled. Overall, these surveys comprised 19,132 individuals age 55 years and older for the prevalence analyses, and 35,577 person-years for the incidence analyses. The overall prevalence of stroke, age- and sex-adjusted to the 1991 European population, was 4.84% (95% CI 4.47 to 5.21) in individuals age 65 to 84 years and 7.06% (95% CI 6.52 to 7.60) in those 75 years and older. Age- and sex-specific rates did not differ substantially across the studies. Incidence rates of first-ever stroke rose markedly with age, and the pooled results confirmed that incidence keeps increasing even at 90 years of age and older. The overall age- and sex-standardized incidence rates were 8.72 per 1000 person-years (95% CI 7.47 to 10.06) for individuals age 65 to 84 years, and 17.31 per 1000 person-years (95% CI 14.79 to 20.02) for those age 75 years and over. C1 Erasmus Med Ctr, Dept Epidemiol & Biostat, EURODEM, NL-3000 DR Rotterdam, Netherlands. Natl Res Council, CSFET, CNR, Italian Longitudinal Study, Florence, Italy. NIA, Epidemiol Demog Biometry Program, Bethesda, MD USA. Stockholm Gerontol Res Ctr, Karolinska Inst, NEUROTEC, Div Geriatr Med, Stockholm, Sweden. Univ Zaragoza, Dept Psychiat, E-50009 Zaragoza, Spain. Univ Navarra, Dept Neurol, E-31080 Pamplona, Spain. Karl Franzens Univ Graz, Dept Neurol, Graz, Austria. RP Di Carlo, A (reprint author), Erasmus Med Ctr, Dept Epidemiol & Biostat, EURODEM, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI Breteler, Monique /J-5058-2014 NR 44 TC 48 Z9 49 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2000 VL 54 IS 11 SU 5 BP S28 EP S33 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 323ZP UT WOS:000087595700007 PM 10854359 ER PT J AU Fratiglioni, L Launer, LJ Andersen, K Breteler, MMB Copeland, JRM Dartigues, JF Lobo, A Martinez-Lage, J Soininen, H Hofman, A AF Fratiglioni, L Launer, LJ Andersen, K Breteler, MMB Copeland, JRM Dartigues, JF Lobo, A Martinez-Lage, J Soininen, H Hofman, A CA Neurologic Dis Elderly Res Grp TI Incidence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts SO NEUROLOGY LA English DT Article DE dementia; AD; vascular dementia; incidence; epidemiology ID ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; SENILE DEMENTIA; PREVALENCE; METAANALYSIS; COMMUNITY; AGE; DISORDERS; PROJECT; MILD AB The authors examined the association of incident dementia and subtypes with age, sex, and geographic area in Europe. Incidence data from eight population-based studies carried out in seven European countries were compared and pooled. The pooled data included 835 mild to severe dementia cases and 42,996 person-years of follow-up. In all studies a higher proportion of cases were diagnosed with AD (60 to 70% of all demented cases) than vascular dementia (VaD). The incidence of dementia and AD continued to increase with age up to age 85 years, after which rates increased in women but not men. There was a large variation in VaD incidence across studies. In the pooled analysis, the incidence rates increased with age without any substantial difference between men and women. Surprisingly, higher incidence rates of dementia and AD were found in the very old in northwest countries than in southern countries. This study confirms that AD is the most frequent dementing disorder in all ages, and that there is a higher incidence of dementia, specifically AD, in women than men among the very old. Finally, there may be regional differences in dementia incidence. C1 Erasmus Med Ctr, Dept Epidemiol & Biostat, EURODEM, NL-3000 DR Rotterdam, Netherlands. Karolinska Inst, NEUROTEC, Stockholm Gerontol Res Ctr, S-10401 Stockholm, Sweden. Karolinska Inst, NEUROTEC, Div Geriatr Med, S-10401 Stockholm, Sweden. NIA, Epidemiol Demog Biometry Program, Bethesda, MD 20892 USA. Odense Univ, Dept Psychiat, DK-5230 Odense M, Denmark. Royal Liverpool Univ Hosp, Dept Psychiat, Liverpool, Merseyside, England. INSERM Unit 330, Bordeaux, France. Univ Zaragoza, Dept Psychiat, E-50009 Zaragoza, Spain. Univ Navarra, Dept Neurol, E-31080 Pamplona, Spain. Kuopio Univ Hosp, Dept Neurol, Kuopio, Finland. RP Fratiglioni, L (reprint author), Erasmus Med Ctr, Dept Epidemiol & Biostat, EURODEM, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI Breteler, Monique /J-5058-2014; Andersen, Kjeld/K-2169-2014 NR 34 TC 324 Z9 336 U1 0 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2000 VL 54 IS 11 SU 5 BP S10 EP S15 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 323ZP UT WOS:000087595700003 PM 10854355 ER PT J AU Jagger, C Andersen, K Breteler, MMB Copeland, JRM Helmer, C Baldereschi, M Fratiglioni, L Lobo, A Soininen, H Hofman, A Launer, LJ AF Jagger, C Andersen, K Breteler, MMB Copeland, JRM Helmer, C Baldereschi, M Fratiglioni, L Lobo, A Soininen, H Hofman, A Launer, LJ CA Neurologic Dis Elderly Res Grp TI Prognosis with dementia in Europe: A collaborative study of population-based cohorts SO NEUROLOGY LA English DT Article DE dementia; prognosis; mortality; institutionalization; elderly; epidemiology; collaborative study ID MINI-MENTAL STATE; ALZHEIMERS-DISEASE; FOLLOW-UP; COMMUNITY; SURVIVAL; INSTITUTIONALIZATION; PREDICTORS; PREVALENCE; INSTRUMENT; MORTALITY AB The effect of dementia on time to death and institutionalization in elderly populations is of importance to resource planning, as well as to patients and their carers, The authors report a collaborative reanalysis of nine population-based studies conducted in Europe to compare dementia cases and noncases in risk of and time to death and to institutionalization. Prevalent and incident cases were more likely than noncases to reside in an institution at baseline and were more likely to enter institutional care. Prevalent cases also had over twice the risk of death compared to noncases and survival for men with dementia was consistently lower than that for women with dementia of the same age group. C1 Erasmus Med Ctr, Dept Epidemiol & Biostat, EURODEM, NL-3000 DR Rotterdam, Netherlands. Univ Leicester, Dept Epidemiol & Publ Hlth, Leicester LE1 7RH, Leics, England. Odense Univ, Dept Psychiat, DK-5230 Odense, Denmark. Royal Liverpool Univ Hosp, Dept Psychiat, Liverpool, Merseyside, England. INSERM Unit 330, Bordeaux, France. Natl Res Council, CSFET, CNR, Italian Longitudinal Study Aging, Florence, Italy. Stockholm Gerontol Res Ctr, Karolinska Inst, NEUROTEC, Div Geriatr Med, Stockholm, Sweden. Univ Zaragoza, Dept Psychiat, E-50009 Zaragoza, Spain. Kuopio Univ Hosp, Dept Neurol, Kuopio, Finland. NIA, Epidemiol Demog Biometry Program, Bethesda, MD 20892 USA. RP Jagger, C (reprint author), Erasmus Med Ctr, Dept Epidemiol & Biostat, EURODEM, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI Breteler, Monique /J-5058-2014; HELMER, Catherine/I-6581-2015; Andersen, Kjeld/K-2169-2014 OI HELMER, Catherine/0000-0002-5169-7421; NR 26 TC 41 Z9 43 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2000 VL 54 IS 11 SU 5 BP S16 EP S20 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 323ZP UT WOS:000087595700004 PM 10854356 ER PT J AU Launer, LJ Hofman, A AF Launer, LJ Hofman, A TI Frequency and impact of neurologic diseases in the elderly of Europe: A collaborative study of population-based cohorts SO NEUROLOGY LA English DT Editorial Material ID PARKINSONS-DISEASE; PREVALENCE; DEMENTIA; COMMUNITY; DISORDERS; ZARAGOZA; STROKE; DESIGN C1 Erasmus Sch Ctr, Dept Epidemiol & Biostat, EURODEM, NL-3000 DR Rotterdam, Netherlands. NIA, Epidemiol Demog Biometry Program, Bethesda, MD USA. RP Launer, LJ (reprint author), Erasmus Sch Ctr, Dept Epidemiol & Biostat, EURODEM, POB 1738, NL-3000 DR Rotterdam, Netherlands. NR 17 TC 25 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2000 VL 54 IS 11 SU 5 BP S1 EP S3 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 323ZP UT WOS:000087595700001 PM 10854353 ER PT J AU Lobo, A Launer, LJ Fratiglioni, L Andersen, K Di Carlo, A Breteler, MMB Copeland, JRM Dartigues, JF Jagger, C Martinez-Lage, J Soininen, H Hofman, A AF Lobo, A Launer, LJ Fratiglioni, L Andersen, K Di Carlo, A Breteler, MMB Copeland, JRM Dartigues, JF Jagger, C Martinez-Lage, J Soininen, H Hofman, A CA Neurologic Dis Elderly Res Grp TI Prevalence of dementia and major subtypes in Europe: A collaborative study of population-based cohorts SO NEUROLOGY LA English DT Article DE dementia; prevalence; AD; vascular dementia; epidemiology; collaborative study; elderly ID MINI-MENTAL STATE; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; DIAGNOSTIC-CRITERIA; ELDERLY COMMUNITY; ZARAGOZA; RISK; AGE AB The last comparison of prevalence figures of dementia across European studies was 10 years ago. Using studies conducted in the 1990s, the authors compare the age- and sex-specific prevalence of dementia, AD, and vascular dementia (VaD) across European population-based studies of persons 65 years and older. Data from these studies were also pooled to obtain stable estimates of age- and sex-specific prevalence. A total of 2346 cases of mild to severe dementia were identified in 11 cohorts. Age-standardized prevalence was 6.4% for dementia tall causes), 4.4% for AD, and 1.6% for VaD. The prevalence of dementia increased continuously with age and was 0.8% in the group age 65 to 69 years and 28.5% at age 90 years and older. The corresponding figures for AD (53.7% of cases) were 0.6% and 22.2%, and for VaD (15.8% of cases), 0.3% and 5.2%. Variation of AD prevalence across studies was greatest for men. In the VaD subtype, a large variation across studies was observed, as well as a difference in prevalence between men and women that was age dependent. Dementia is more prevalent in women, and AD is the main contributor to the steep increase of prevalence with age. C1 Erasmus Sch Ctr, Dept Epidemiol & Biostat, EURODEM, NL-3000 DR Rotterdam, Netherlands. Univ Zaragoza, Dept Psychiat, E-50009 Zaragoza, Spain. NIA, Epidemiol Demog Biometry Program, Bethesda, MD USA. Stockholm Gerontol Res Ctr, Karolinska Inst, NEUROTEC, Div Geriatr Med, Stockholm, Sweden. Odense Univ, Dept Psychiat, DK-5230 Odense, Denmark. Natl Res Council, CSFET, CNR, Italian Longitudinal Study Aging, Florence, Italy. Royal Liverpool Univ Hosp, Dept Psychiat, Liverpool, Merseyside, England. INSERM Unit 330, Bordeaux, France. Univ Leicester, Dept Epidemiol & Publ Hlth, Leicester LE1 7RH, Leics, England. Univ Navarra, Dept Neurol, E-31080 Pamplona, Spain. Kuopio Univ Hosp, Dept Neurol, Kuopio, Finland. RP Lobo, A (reprint author), Erasmus Sch Ctr, Dept Epidemiol & Biostat, EURODEM, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI Breteler, Monique /J-5058-2014; Andersen, Kjeld/K-2169-2014; OI Lobo, Antonio/0000-0002-9098-655X NR 37 TC 496 Z9 520 U1 2 U2 48 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2000 VL 54 IS 11 SU 5 BP S4 EP S9 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 323ZP UT WOS:000087595700002 PM 10854354 ER PT J AU Schmidt, R Breteler, MMB Inzitari, D Fratiglioni, L Hofman, A Launer, LJ AF Schmidt, R Breteler, MMB Inzitari, D Fratiglioni, L Hofman, A Launer, LJ CA Neurologic Dis Elderly Res Grp TI Prognosis with stroke in Europe: A collaborative study of population-based cohorts SO NEUROLOGY LA English DT Article DE stroke; prognosis; mortality; institutionalization; elderly; epidemiology ID SURVIVAL; INSTITUTIONALIZATION; RECURRENCE; DEFINITION; MINNESOTA AB The authors pooled four population-based European studies to determine the risk for institutionalization and death after stroke. Risk for institutionalization was assessed in 13,095 subjects. Survival was calculated for prevalent stroke in 7929 individuals and incident stroke in 8550 individuals. The adjusted risk of long-term care for cases compared to noncases was 2.8 (95% CI 2.6 to 4.5). At 5 years, the excess risk of death in prevalent; cases was 1.6 (1.2 to 2.0), and the age- and sex-adjusted survival rate was 0.87 compared to 0.91 in noncases. The 5-year survival rate for incident cases was 0.84. C1 Erasmus Med Ctr, Dept Epidemiol & Biostat, EURODEM, NL-3000 DR Rotterdam, Netherlands. Karl Franzens Univ Graz, Dept Neurol, Graz, Austria. Univ Florence, Dept Neurol & Psychiat Sci, I-50121 Florence, Italy. Stockholm Gerontol Res Ctr, Karolinska Inst, NEUROTEC, Div Geriatr Med, Stockholm, Sweden. NIA, Epidemiol Demog Biometry Program, Bethesda, MD 20892 USA. RP Schmidt, R (reprint author), Erasmus Med Ctr, Dept Epidemiol & Biostat, EURODEM, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI Breteler, Monique /J-5058-2014 NR 24 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 2000 VL 54 IS 11 SU 5 BP S34 EP S37 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 323ZP UT WOS:000087595700008 PM 10854360 ER PT J AU Raben, N Nagaraju, K Lee, E Plotz, P AF Raben, N Nagaraju, K Lee, E Plotz, P TI Modulation of disease severity in mice with targeted disruption of the acid alpha-glucosidase gene SO NEUROMUSCULAR DISORDERS LA English DT Article DE acid alpha-glucosidase; glycogen storage disease type II; gene targeting; phenotype ID DUCHENNE MUSCULAR-DYSTROPHY; GLYCOGEN-STORAGE; POMPE-DISEASE; SKELETAL-MUSCLE; DEFICIENT MICE; EGF RECEPTOR; MOUSE MODEL; PHENOTYPE; ACCUMULATION; EXPRESSION AB Glycogen storage disease type II (GSDII) is a recessively inherited disorder caused by defects in lysosomal acid cr-glucosidase. In an attempt to reproduce the range of clinical manifestations of the human illness we have created null alleles at the acid ol-glucosidase locus (GAA) with several gene targeting strategies. In each knockout strain, enzyme activity was completely abolished and glycogen accumulated at indistinguishable rates. The phenotypes, however, differed strikingly. Acid or-glucosidase deficiency on a 129 x C57BL1/6 background resulted in a severe phenotype with progressive cardiomyopathy and profound muscle wasting similar to that in patients with glycogen storage disease type IL. On a 129/C57BL/6 x FVB background, homozygous mutants developed a milder phenotype with a later age of onset. Females were more affected than males irrespective of genetic background. As in humans with glycogen storage disease type II, therefore, other genetic loci affect the phenotypic expression of a single gene mutation. Published by Elsevier Science B.V. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Raben, N (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, 10-9N244,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 37 TC 26 Z9 26 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JUN PY 2000 VL 10 IS 4-5 BP 283 EP 291 DI 10.1016/S0960-8966(99)00117-0 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 324VE UT WOS:000087641400012 PM 10838256 ER PT J AU Reynolds, JH Pasternak, T Desimone, R AF Reynolds, JH Pasternak, T Desimone, R TI Attention increases sensitivity of V4 neurons SO NEURON LA English DT Article ID SPATIAL SELECTIVE ATTENTION; MONKEY VISUAL-CORTEX; STRIATE CORTEX; RESPONSE AMPLITUDE; NEURAL MECHANISMS; STIMULUS CONTRAST; CORTICAL-NEURONS; FEATURE BINDING; AREAS V1; ORIENTATION AB When attention is directed to a location in the visual field, sensitivity to stimuli at that location is increased. At the neuronal level, this could arise either through a multiplicative increase in firing rate or through an increase in the effective strength of the stimulus. To test conflicting predictions of these alternative models, we recorded responses of V4 neurons to stimuli across a range of luminance contrasts and measured the change in response when monkeys attended to them in order to discriminate a target stimulus from nontargets. Attention caused greater increases in response at low contrast than at high contrast, consistent with an increase in effective stimulus strength. On average, attention increased the effective contrast of the attended stimulus by a factor of 1.51, an increase of 51% of its physical contrast. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. Univ Rochester, Med Ctr, Dept Neurobiol & Anat, Rochester, NY 14642 USA. RP Desimone, R (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 9, Bethesda, MD 20892 USA. NR 40 TC 804 Z9 813 U1 3 U2 38 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN PY 2000 VL 26 IS 3 BP 703 EP 714 DI 10.1016/S0896-6273(00)81206-4 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 330ZH UT WOS:000087991600020 PM 10896165 ER PT J AU Klein, HG AF Klein, HG TI The prospects for red-cell substitutes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HEMOGLOBIN; EFFICACY; ANEMIA; TRIAL C1 NIH, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 47 Z9 51 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 1 PY 2000 VL 342 IS 22 BP 1666 EP 1668 DI 10.1056/NEJM200006013422211 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 319CE UT WOS:000087321600011 PM 10833216 ER PT J AU Nielsen, S Kwon, TH Frokiaer, J Knepper, MA AF Nielsen, S Kwon, TH Frokiaer, J Knepper, MA TI Key roles of renal aquaporins in water balance and water-balance disorders SO NEWS IN PHYSIOLOGICAL SCIENCES LA English DT Article ID CHANNEL EXPRESSION; COLLECTING DUCT; VASOPRESSIN; RAT; MEMBRANE AB The discovery of aquaporins by Agre and co-workers provided an answer to the long-standing biophysical question of how water can pass cell membranes. The identification and characterization of several aquaporins expressed in the kidney has allowed detailed insight, at the molecular level, into the fundamental physiology and pathophysiology of renal water metabolism. C1 Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus, Denmark. 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. FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 15 TC 15 Z9 19 U1 0 U2 2 PU NEWS IN PHYSIOLOGICAL SCIENCES PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0886-1714 J9 NEWS PHYSIOL SCI JI News Physiol. Sci. PD JUN PY 2000 VL 15 BP 136 EP 143 PG 8 WC Physiology SC Physiology GA 330MP UT WOS:000087966100006 PM 11390896 ER PT J AU Vaughan, TL Stewart, PA Teschke, K Lynch, CF Swanson, GM Lyon, JL Berwick, M AF Vaughan, TL Stewart, PA Teschke, K Lynch, CF Swanson, GM Lyon, JL Berwick, M TI Occupational exposure to formaldehyde and wood dust and nasopharyngeal carcinoma SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE occupational exposure; formaldehyde; wood dust ID UPPER RESPIRATORY-TRACT; SQUAMOUS-CELL CANCERS; UNITED-STATES; RISK-FACTORS; NONDIFFERENTIAL MISCLASSIFICATION; POOLED REANALYSIS; SINONASAL CANCER; NASAL CAVITY; MORTALITY; WORKERS AB Objectives-To investigate whether occupational exposures to formaldehyde and wood dust increase the risk of nasopharyngeal cancer (NPC). Methods-A multicentred, population based case-control study was carried out at five cancer registries in the United States participating in the National Cancer Institute's SEER program. Cases (n=196) with a newly diagnosed NPC between 1987 and 1993, and controls (n=244) selected over the same period from the general population through random digit dialing participated in structured telephone interviews which inquired about suspected risk factors for the disease, including a lifetime history of occupational and chemical exposure. Histological type of cancer was abstracted from clinical records of the registries. Potential exposure to formaldehyde and wood dust was assessed on a job by job basis by experienced industrial hygienists who were blinded as to case or control status. Results-For formaldehyde, after adjusting for cigarette use, race, and other risk factors, a trend of increasing risk of squamous and unspecified epithelial carcinomas was found for increasing duration (p=0.014) and cumulative exposure (p=0.033) but not for maximum exposure concentration. The odds ratio (OR) for people cumulatively exposed to >1.10 ppm-years was 3.0 (95% confidence interval (95% CI) 1.3 to 6.6) compared with those considered unexposed. In analyses limited to jobs considered definitely exposed, these trends became stronger. The associations were most evident among cigarette smokers. By contrast, there was no association between potential exposure to formaldehyde and undifferentiated and non-keratinising carcinomas. There was little evidence that exposure to wood dust increased risk of NPC, as modest crude associations essentially disappeared after control for potential exposure to formaldehyde. Conclusions-These results support the hypothesis that occupational exposure to formaldehyde, but not wood dust, increases risk of NPC. This association seems to be specific to squamous cell carcinomas. Established cohorts of workers exposed to formaldehyde and wood dust should continue to be monitored for NPC and other respiratory cancers. Future studies of NPC should take into account histological type in assessing risk from environmental and host factors. C1 Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, Bethesda, MD USA. Univ British Columbia, Dept Hlth Care & Epidemiol, Vancouver, BC V6T 1W5, Canada. Univ Iowa, Dept Epidemiol, Iowa City, IA USA. Michigan State Univ, Ctr Canc, E Lansing, MI 48824 USA. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. Univ Utah, Dept Family Med, Salt Lake City, UT USA. Mem Sloan Kettering Canc Res Ctr, New York, NY 10021 USA. RP Vaughan, TL (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, MP-474,1100 Fairview Ave,POB 19024, Seattle, WA 98109 USA. OI Berwick, Marianne/0000-0001-5062-2180 FU NCI NIH HHS [R29 CA 46552, N01 CN67009, R03 CA50256] NR 51 TC 74 Z9 81 U1 4 U2 14 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JUN PY 2000 VL 57 IS 6 BP 376 EP 384 DI 10.1136/oem.57.6.376 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 316CU UT WOS:000087150500003 PM 10810126 ER PT J AU Freedman, DM Dosemeci, H Alavanja, MCR AF Freedman, DM Dosemeci, H Alavanja, MCR TI Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case-control study based on death certificates SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE multiple sclerosis; aetiology; latitude; ultraviolet radiation; sunlight; occupation; residence; skin cancer ID UNITED-STATES VETERANS; RISK-FACTORS; SKIN-CANCER; US VETERANS; VITAMIN-D; EPIDEMIOLOGY; SUNLIGHT; LATITUDE AB Objectives-To explore whether mortality from multiple sclerosis is negatively associated with exposure to sunlight. Methods-Two case-control studies based on death certificates were conducted for mortality from multiple sclerosis and non-melanoma skin cancer (as a positive control) to examine associations with residential and occupational exposure to sunlight. Cases were all deaths from multiple sclerosis between 1984 and 1995 in 24 states of the United States. Controls, which were age frequency matched to a series of cases, excluded cancer and certain neurological deaths. The effects of occupational exposure to sunlight were assessed among subjects with usual occupations requiring substantial activity, so as to exclude those whose indoor jobs resulted from disabilities subsequent to the onset of the disease. Multiple logistic regression analyses were applied, with adjustment for age, sex, race, and socioeconomic status. Results-Unlike mortality from skin cancer, mortality from multiple sclerosis was negatively associated with residential exposure to sunlight (odds ratio (OR)=0.53 (multiple sclerosis) and OR=1.24 (skin cancer)). Odds ratios for the highest occupational exposure to sunlight were 0.74 (95% confidence interval (95% CI) 0.61 to 0.89) for mortality from multiple sclerosis, compared with 1.21 (1.09 to 1.34) for mortality from non-melanoma skin cancer. The OR was 0.24 for the combined effect of the highest levels of residential and occupational exposure to sunlight on multiple sclerosis, compared with an OR of 1.38 for skin cancer. Conclusions-In this exploratory study, mortality from multiple sclerosis, unlike mortality from skin cancer, was negatively associated with both residential and occupational exposure to sunlight. C1 NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. RP Freedman, DM (reprint author), NCI, Radiat Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. NR 27 TC 113 Z9 116 U1 1 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JUN PY 2000 VL 57 IS 6 BP 418 EP 421 DI 10.1136/oem.57.6.418 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 316CU UT WOS:000087150500009 PM 10810132 ER PT J AU Bies, J Feikova, S Bottaro, DP Wolff, L AF Bies, J Feikova, S Bottaro, DP Wolff, L TI Hyperphosphorylation and increased proteolytic breakdown of c-Myb induced by the inhibition of Ser/Thr protein phosphatases SO ONCOGENE LA English DT Article DE c-Myb; proteolysis; phosphorylation; 26S proteasome; Ser/Thr phosphatases ID NEGATIVE REGULATORY DOMAIN; INDUCED TRANSCRIPTION ACTIVATION; DNA-BINDING DOMAIN; KAPPA-B-ALPHA; V-MYB; PHOSPHORYLATION SITE; PROTEASOME PATHWAY; ONCOGENIC ACTIVATION; TRANS-ACTIVATION; TERMINAL REGION AB The c-myb proto-oncogene encodes a nuclear phosphoprotein that plays a crucial role in normal hematopoiesis. It is a short-lived transcription factor rapidly degraded by the 26S proteasome, Although it has been shown that instability determinants reside in its carboxyl terminus, the molecular mechanism of c-Myb degradation is unknown, Here, we report the first evidence that phosphorylation plays a role in targeting the protein to the proteasome, Inhibition of cellular serine/threonine protein phosphatase activity by okadaic acid resulted in hyperphosphorylation of c-Myb and extremely rapid turnover, The hyperphosphorylation resulted in a protein with altered properties that was indicative of conformational changes. Its mobility on gel electrophoresis was altered as well as its recognition by specific monoclonal antibody, The altered hyperphosphorylated protein still bound to DNA with an affinity similar to that of the hypophosphorylated form, Phosphorylation of three previously identified sites, serines 11, 12, and 528, does not appear to be involved in the proposed changes in conformation or stability, However, phosphoamino acid analyses of the hyperphosphorylated form of c-Myb revealed increased c-Myb phosphorylation mainly on threonine residues that correlated with other okadaic acid-induced alterations of c-Myb, These findings indicate that Ser/Thr phosphatases prevent conformational changes that may play an important role in controlled degradation of c-Myb. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Slovak Acad Sci, Canc Res Inst, Mol Virol Lab, Bratislava 83392, Slovakia. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wolff, L (reprint author), NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 44 TC 24 Z9 24 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 1 PY 2000 VL 19 IS 24 BP 2846 EP 2854 DI 10.1038/sj.onc.1203613 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 320LX UT WOS:000087403600006 PM 10851088 ER PT J AU Grem, JL AF Grem, JL TI The Damjanov/Meropol article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID 5-FLUOROURACIL; CANCER; TUMORS; TISSUE C1 NCI, Natl Naval Med Ctr, Med Branch, Bethesda, MD 20892 USA. RP Grem, JL (reprint author), NCI, Natl Naval Med Ctr, Med Branch, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUN PY 2000 VL 14 IS 6 BP 807 EP 808 PG 2 WC Oncology SC Oncology GA 368QP UT WOS:000090129300006 ER PT J AU Trimble, E Valmonte, CM Cheson, BD AF Trimble, E Valmonte, CM Cheson, BD TI Clinical trials - Referral resource SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Trimble, E (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUN PY 2000 VL 14 IS 6 BP 850 EP 850 PG 1 WC Oncology SC Oncology GA 368QP UT WOS:000090129300017 PM 10887635 ER PT J AU Yarchoan, R AF Yarchoan, R TI AIDS-related Kaposi's sarcoma: Current treatment options, future trends SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID HERPESVIRUS; KSHV C1 NCI, Malignancy Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Yarchoan, R (reprint author), NCI, Malignancy Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUN PY 2000 VL 14 IS 6 BP 887 EP 888 PG 2 WC Oncology SC Oncology GA 368QP UT WOS:000090129300022 ER PT J AU Trimble, CL Trimble, EL AF Trimble, CL Trimble, EL TI Update on low malignant potential ovarian tumors SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID SEROUS BORDERLINE TUMORS; BEHAVIOR; CANCER C1 Johns Hopkins Hosp, Dept Gynecol, Baltimore, MD 21287 USA. Johns Hopkins Hosp, Dept Obstet, Baltimore, MD 21287 USA. Johns Hopkins Hosp, Dept Oncol, Baltimore, MD 21287 USA. NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Trimble, CL (reprint author), Johns Hopkins Hosp, Dept Gynecol, Baltimore, MD 21287 USA. RI Trimble, Cornelia/B-5627-2012 OI Trimble, Cornelia/0000-0003-0397-5295 NR 11 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUN PY 2000 VL 14 IS 6 BP 907 EP 908 PG 2 WC Oncology SC Oncology GA 368QP UT WOS:000090129300027 ER PT J AU Mulligan, R Navazesh, M Komaroff, E Greenspan, D Redford, M Alves, M Phelan, J AF Mulligan, R Navazesh, M Komaroff, E Greenspan, D Redford, M Alves, M Phelan, J TI Salivary gland disease in human immunodeficiency virus-positive women from the WIHS study SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID INFILTRATIVE LYMPHOCYTOSIS SYNDROME; HIV-1 INFECTED PATIENTS; PAROTID-GLAND; ORAL MANIFESTATIONS; LYMPHOEPITHELIAL LESIONS; LYMPH-NODES; ENLARGEMENT; LYMPHADENOPATHIES AB Objective. To determine the prevalence of enlargement, tenderness, and absence of saliva on palpation as indicators of salivary gland disease in women who are human immunodeficiency virus (HIV)-positive. Study design. The study subjects are participants in the Women's Interagency HIV Study (WIHS), a multicenter study examining HIV-seropositive women and at-risk HIV-seronegative women. A total of 576 HIV-positive women and 152 HIV-negative women were examined at their baseline oral visit for clinical markers of salivary gland disease. Viral load levels, CD4 counts, and CD8 counts were obtained as part of the related core study. Results. HIV-positive women had higher rates of salivary gland enlargement (4.3%), tenderness (6.9%), and absence of saliva on palpation (26.6%) compared with HIV-negative women, who had rates of 1.3%, 4.6%, and 13.2%, respectively. Absence of saliva was significantly different (P = .001) between the 2 groups. When 2 of the 3 clinical findings were combined, comparisons between the HIV-positive women and HIV-negative women became significant at the P < .05 level for every combination, except for enlargement/tenderness for the submandibular/sublingual gland. For the HIV-positive women, the viral load was significantly related to enlargement (P = .019) and enlargement/absence of saliva on palpation (P = .037) for the parotids and enlargement (P = .046), absence of saliva (P = .043), and enlargement/absence of saliva (P = .022) for the submandibular/sublingual glands. Significant linear trends were Found for increasing viral load and enlargement (P = .013) and enlargement/tenderness (P = .024) for the submandibular/sublingual glands. Significance was present for submandibular/sublingual absence of saliva and tenderness/absence of saliva for CD4 and CD8 medians. Conclusions. Serostatus is related to salivary gland disease as assessed by glandular enlargement, tenderness, and absence of saliva on palpation. Furthermore, our findings indicate that a multidimensional approach to gland assessment may provide a more complete and perhaps more adequate description of glandular involvement with HIV infection. C1 Univ So Calif, Sch Dent, Dept Dent Med & Publ Hlth, Los Angeles, CA 90089 USA. Univ So Calif, Sch Dent, Sect Oral Med & Oral Diag, Los Angeles, CA 90089 USA. Univ Calif San Francisco, Dept Stomatol, San Francisco, CA 94143 USA. Univ Illinois, Coll Dent, Dept Periodont, Chicago, IL USA. New England Res Inst, Watertown, MA 02172 USA. Natl Inst Dent & Craniofacial Res, Chicago, IL USA. Dept Vet Affairs Med Ctr, Dent Serv, Northport, NY USA. RP Mulligan, R (reprint author), Univ So Calif, Sch Dent, Dept Dent Med & Publ Hlth, Los Angeles, CA 90089 USA. FU NIAID NIH HHS [U01AI35004, U01AI34994, U01AI31834] NR 41 TC 16 Z9 19 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JUN PY 2000 VL 89 IS 6 BP 702 EP 709 DI 10.1067/moe.2000.105328 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 324UC UT WOS:000087638900012 PM 10846124 ER PT J AU Barta, JR Tennyson, SA Schito, ML Danforth, HD Martin, DS AF Barta, JR Tennyson, SA Schito, ML Danforth, HD Martin, DS TI Partial characterization of a non-proteinaceous, low molecular weight antigen of Eimeria tenella SO PARASITOLOGY RESEARCH LA English DT Article ID CRYPTOSPORIDIUM-PARVUM SPOROZOITES; NEUTRALIZATION-SENSITIVE EPITOPES; TOXOPLASMA-GONDII; HYBRIDOMA ANTIBODIES; MONOCLONAL-ANTIBODY; INFECTION; ELECTROPHORESIS; IDENTIFICATION; SPECIFICITY; GEL AB A low molecular weight (LMW) antigen of Eimeria tenella, initially identified using a murine monoclonal antibody (mAb C(3)4F(1)) raised against E. tenella sporozoites, was partially characterized using enzymatic degradation, solvent extraction, and immunization into various inbred lines of mice. The LMW antigen could be isolated using Folch extraction (methanol/chloroform/water) and the epitope recognized by mAb C(3)4F(1) was resistant to degradation by alpha-amylase, pronase, and proteinase K, but was sensitive to sodium m-periodate treatment or digestion using mixed glycosidases (from Turbo cornutus). These observations suggest that the antigenic epitope recognized by mAb C3(4)F(1) is carbohydrate-dependent and, based on our ability to isolate the LMW antigen by Folch extraction, the epitope probably resides on a polar glycolipid. The inability of sporozoite-immunized nude mice to elicit a serum antibody response to this molecule indicates that it acts as a T-dependent antigen. Furthermore, sporozoite-immunized male CBA/N mice (with an X-linked immunodeficiency) also failed to elicit a serum antibody response to this molecule, which is consistent with a carbohydrate antigenic epitope. We propose that this antigenic molecule be designated ET-GL1 to reflect its origin and probable structure (E. tenella glycolipid 1). C1 Univ Guelph, Ontario Vet Coll, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. ARS, Parasite Biol & Epidemiol Lab, USDA, Beltsville, MD 20705 USA. RP Barta, JR (reprint author), Univ Guelph, Ontario Vet Coll, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. OI Barta, John/0000-0001-6896-2271 NR 25 TC 1 Z9 2 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0044-3255 J9 PARASITOL RES JI Parasitol. Res. PD JUN PY 2000 VL 86 IS 6 BP 461 EP 466 DI 10.1007/s004360050694 PG 6 WC Parasitology SC Parasitology GA 329AT UT WOS:000087884500004 PM 10894471 ER PT J AU Read, JS Rich, KC Korelitz, JJ Mofenson, LM Harris, R Moye, JH Meyer, WA Pahwa, SG Bethel, JW Nugent, RP AF Read, JS Rich, KC Korelitz, JJ Mofenson, LM Harris, R Moye, JH Meyer, WA Pahwa, SG Bethel, JW Nugent, RP CA Natl Inst Child Hlth Human Dev Int TI Quantification of human immunodeficiency virus type 1 p24 antigen and antibody rivals human immunodeficiency virus type 1 RNA and CD4(+) enumeration for prognosis SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article; Proceedings Paper CT 7th Conference on Retroviruses and Opportunistic Infections CY JAN 30-FEB 03, 2000 CL SAN FRANCISCO, CALIFORNIA DE human immunodeficiency virus; proteins; progression; pediatrics ID IMMUNE-COMPLEX DISSOCIATION; HEAT-DENATURED PLASMA; HIV-INFECTED CHILDREN; HIV-1-INFECTED CHILDREN; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; INFANTS; DIAGNOSIS; ASSAY; RISK AB Background. The sensitivity, specificity and positive predictive value of baseline serum concentrations of HIV-1 immune complex-dissociated (ICD) p24 antigen for predicting disease progression and mortality were assessed and compared with results obtained for HIV-1 ICD p24 antigen with HIV-1 p24 antibody and for HIV-1 RNA with CD4(+) lymphocyte percent. Methods. Data from HIV-infected children enrolled in a North American clinical trial (National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial) were analyzed. Disease progression was defined as growth failure, CD4(+) lymphocyte percent decline to <15% after study entry or development of an AIDS-defining opportunistic infection. Results. Baseline samples were available for ICD p24 antigen testing (median concentration, 319 pg/ml; range, <50 to 15 640) in 240 children. The combination of detectable ICD p24 antigen and low p24 antibody was more sensitive but less specific than the combination of high HIV-1 RNA and low CD4(+) lymphocyte percent in predicting disease progression and mortality. Using receiver operating characteristic curves, the specificity of ICD p24 antigen with p24 antibody for classifying children's disease progression or mortality was as great as, or greater than, HIV-1 RNA with CD4(+) lymphocyte percent at points on the curve corresponding to higher sensitivity, Conclusions, The use of ICD p24 antigen with p24 antibody to identify children at high risk of disease progression or mortality could be a viable alternative to the more expensive and technically difficult HIV-1 RNA and CD4(+) lymphocyte assays in resource-poor settings, including developing countries where the majority of children with HIV-1 infection reside. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL USA. Westat, Rockville, MD USA. Quest Diagnost Inc, Baltimore, MD USA. N Shore Univ Hosp, Manhasset, NY USA. RP Read, JS (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Execut Bldg,Room 4B11F,6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA. OI Mofenson, Lynne/0000-0002-2818-9808 FU NICHD NIH HHS [N01 HD 33162] NR 30 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUN PY 2000 VL 19 IS 6 BP 544 EP 551 DI 10.1097/00006454-200006000-00011 PG 8 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 324ZM UT WOS:000087651900011 PM 10877171 ER PT J AU Maloney, EM Hisada, M Palmer, P Brooks, K Pate, E Wiktor, SZ Lagrenade, L Manns, A AF Maloney, EM Hisada, M Palmer, P Brooks, K Pate, E Wiktor, SZ Lagrenade, L Manns, A TI Human T cell lymphotropic virus type I-associated infective dermatitis in Jamaica: a case report of clinical and biologic correlates SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE human T cell lymphotropic virus type I; pediatric; infective dermatitis; Jamaica ID TROPICAL SPASTIC PARAPARESIS; HTLV-I; POLYCLONAL INTEGRATION; PROVIRAL DNA; JAPAN; LEUKEMIA; CARRIERS; MYELOPATHY; ATL; LEUKEMIA/LYMPHOMA AB Infective dermatitis was first characterized in Jamaican children as an exudative and crusting eczema (involving the nostrils, ears and scalp) with frequent relapse after treatment.(1, 2) In 1990 a case series of infective dermatitis from Jamaica provided the first link with early life infection with human T cell lymphotropic virus type I (HTLV-I).(3) A subsequent case-control study confirmed this association and established criteria for diagnosis of HTLV-I-associated infective dermatitis.(4) The diagnostic criteria include HTLV-I seropositivity; eczema of at least two of seven sites (scalp, external ear, retroauricular areas, eyelid margins, paranasal skin. and/or neck, axillae, groin); chronic watery nasal discharge without other signs of rhinitis and/or crusting of the anterior nares; and either early childhood onset or chronic relapsing dermatitis.4 The prevalence of HTLV-I in the general population of Jamaica is 6.1%, and among women of reproductive age it is 3.8%.(5, 6) In Jamaica maternal-child transmission occur; at a rate of 18%, is primarily through breast-feeding and results in a HTLV-I prevalence of <2% among children younger than 10 years of (5, 6) Cases of infective dermatitis in HTLV-I-age. infected children have also been reported in Japan, Brazil, Colombia and Trinidad.(7-10) Infective dermatitis is the earliest disease manifestation of HTLV-I infection in children, whereas adult T cell leukemia/lymphoma and HTLV-I-associated myelopathy/tropical spastic paraparesis and HTLV-I-associated uveitis occur primarily among adults.(11) Linking these childhood and adult diseases are reports that patients with adult T cell leukemia/lymphoma and those with HTLV-I-associated myelopathy/tropical spastic paraparesis had been diagnosed with infective dermatitis 12 to 25 years earlier.(7, 12, 13) Thus infective dermatitis in childhood may be a harbinger of HTLVI-associated diseases in adult life. In this report we describe an infective dermatitis case that arose among 28 HTLV-I-infected Jamaican children prospectively followed for up to 9 years to elucidate events leading to the onset of disease and to identify potential markers for persons at risk for HTLV-I-associated disease in adulthood. C1 NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Univ W Indies, Kingston 7, Jamaica. RP Maloney, EM (reprint author), NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, 6120 Execut Blvd,PS-8006, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CP-40548] NR 38 TC 15 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUN PY 2000 VL 19 IS 6 BP 560 EP 565 DI 10.1097/00006454-200006000-00014 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 324ZM UT WOS:000087651900014 PM 10877174 ER PT J AU Vohr, BR Wright, LL Dusick, AM Mele, L Verter, J Steichen, JJ Simon, NP Wilson, DC Broyles, S Bauer, CR Delaney-Black, V Yolton, KA Fleisher, BE Papile, LA Kaplan, MD AF Vohr, BR Wright, LL Dusick, AM Mele, L Verter, J Steichen, JJ Simon, NP Wilson, DC Broyles, S Bauer, CR Delaney-Black, V Yolton, KA Fleisher, BE Papile, LA Kaplan, MD TI Neurodevelopmental and functional outcomes of extremely low birth weight infants in the National Institute of Child Health and Human Development Neonatal Research Network, 1993-1994 SO PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Pediatric-Research CY MAY 01-05, 1998 CL SAN FRANCISCO, CALIFORNIA SP Soc Pediat Res DE extremely low birth weight; neurologic outcome; developmental outcome; functional outcome; prematurity; cerebral palsy; Bayley ID GROSS MOTOR FUNCTION; SCHOOL-AGE OUTCOMES; PRETERM INFANTS; BRONCHOPULMONARY DYSPLASIA; CEREBRAL-PALSY; COGNITIVE-DEVELOPMENT; EXPOSURE; ENTRY; PERFORMANCE; SURFACTANT AB Objectives. The purposes of this study were to report the neurodevelopmental, neurosensory, and functional outcomes of 1151 extremely low birth weight (401-1000 g) survivors cared for in the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network, and to identify medical, social, and environmental factors associated with these outcomes. Study Design. A multicenter cohort study in which surviving extremely low birth weight infants born in 1993 and 1994 underwent neurodevelopmental, neurosensory, and functional assessment at 18 to 22 months' corrected age. Data regarding pregnancy and neonatal outcome were collected prospectively. Socioeconomic status and a detailed interim medical history were obtained at the time of the assessment. Logistic regression models were used to identify maternal and neonatal risk factors for poor neurodevelopmental outcome. Results. Of the 1480 infants alive at 18 months of age, 1151 (78%) were evaluated. Study characteristics included a mean birth weight of 796 +/- 135 g, mean gestation (best obstetric dates) 26 +/- 2 weeks, and 47% male. Birth weight distributions of infants included 15 infants at 401 to 500 g; 94 at 501 to 600 g; 208 at 601 to 700 g; 237 at 701 to 800 g; 290 at 801 to 900 g; and 307 at 901 to 1000 g. Twenty-five percent of the children had an abnormal neurologic examination, 37% had a Bayley II Mental Developmental Index <70, 29% had a Psychomotor Developmental Index <70, 9% had vision impairment, and 11% had hearing impairment. Neurologic, developmental, neurosensory, and functional morbidities increased with decreasing birth weight. Factors significantly associated with increased neurodevelopmental morbidity included chronic lung disease, grades 3 to 4 intraventricular hemorrhage/periventricular leukomalacia, steroids for chronic lung disease, necrotizing enterocolitis, and male gender. Factors significantly associated with decreased morbidity included increased birth weight, female gender, higher maternal education, and white race. Conclusion. ELBW infants are at significant risk of neurologic abnormalities, developmental delays, and functional delays at 18 to 22 months' corrected age. C1 Brown Univ, Women & Infants Hosp, Providence, RI 02905 USA. NICHHD, Bethesda, MD 20892 USA. Indiana Univ, Indianapolis, IN 46204 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Cincinnati, Cincinnati, OH USA. Emory Univ, Atlanta, GA 30322 USA. Case Western Reserve, Cleveland, OH USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Miami, Miami, FL 33152 USA. Wayne State Univ, Detroit, MI USA. Univ Tennessee, Memphis, TN USA. Stanford Univ, Stanford, CA 94305 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Yale Univ, New Haven, CT USA. RP Vohr, BR (reprint author), Brown Univ, Women & Infants Hosp, 101 Dudley St, Providence, RI 02905 USA. NR 59 TC 644 Z9 659 U1 8 U2 50 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 JUN PY 2000 VL 105 IS 6 BP 1216 EP 1226 DI 10.1542/peds.105.6.1216 PG 11 WC Pediatrics SC Pediatrics GA 321EA UT WOS:000087441400021 PM 10835060 ER PT J AU SanGiovanni, JP Parra-Cabrera, S Colditz, GA Berkey, CS Dwyer, JT AF SanGiovanni, JP Parra-Cabrera, S Colditz, GA Berkey, CS Dwyer, JT TI Meta-analysis of dietary essential fatty acids and long-chain polyunsaturated fatty acids as they relate to visual resolution acuity in healthy preterm infants SO PEDIATRICS LA English DT Article DE breast milk; docosahexaenoic acid; infant; meta-analysis; omega-3 fatty acids; visual acuity ID DOCOSAHEXAENOIC ACID; CEREBRAL-CORTEX; TERM INFANTS; SUPPLEMENTATION; ACCRETION; RETINA; BRAIN AB Objective. To derive combined estimates of visual resolution acuity differences between healthy preterm infants consuming different compositions and ratios of essential fatty acids (EFAs) and docosahexaenoic acid (DHA), an omega-3 (n-3) long-chain polyunsaturated fatty acid (LCPUFA). Data Sources. Electronic biomedical reference database (Medline and Health Star from 1965 to July 1999) searches with index terms omega-3, n-3, infant, vision, acuity, and human. Current review article, monograph, and book chapter bibliography/reference section hand searches. Study Selection. A total of 5 original articles and 4 review chapters were reviewed for details on study design, conduct, and outcome. Four prospective trials of EFA/LCPUFA supplementation were included in these analyses. For behaviorally based outcomes, there were 2 randomized comparisons each at less than or equal to 1, 2, 6, 9, and 12 months of corrected age and 4 randomized comparisons at 4 months of corrected age. For electrophysiologically based outcomes (visual-evoked potential), there were 2 randomized comparisons each at less than or equal to 1 and similar to 4 months of corrected age. Data Extraction. Dietary composition and EFA/LCPUFA balance, study design, and analytic characteristics (duration of feeding, source of EFAs/LCPUFAs, number of subjects in study population, number of subjects analyzed, and basis for estimating age), and experiment-based characteristics (location, number or sites, design, vision tests employed, testing protocol, and ophthalmic examination) were recorded independently by 2 researchers with a standardized protocol. Data Synthesis. The relative difference in visual resolution acuity between groups of infants who received a source of dietary EFAs/LCPUFAs and groups who did not was computed and then analyzed with the DerSimonian and Laird random-effects method. Results. Analysis of the randomized comparisons (DHA-supplemented formula vs DHA-free formula) showed significant differences in visual resolution acuity at 2 and 4 months of age. Combined estimates of behaviorally based visual resolution acuity differences at these ages were .47 +/- .14 octaves and .28 +/- .08 octaves, respectively. A 1-octave difference is a reduction in the width of the stimulus elements by 50%. Conclusion. These results support efficacy of n-3 LCPUFA intake in early visual system development, although supplementation safety issues still must be addressed through larger randomized trials. Whether n-3 intake confers lasting advantage in visually based process development across the life-span is still to be determined. C1 Harvard Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Boston, MA 02115 USA. Natl Publ Hlth Inst, Ctr Hlth Res, Cuernavaca, Morelos, Mexico. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA USA. Tufts Univ, New England Med Ctr, Sch Med, Frances Stern Nutr Ctr, Medford, MA 02155 USA. Tufts Univ, Sch Nutr Sci & Policy, Medford, MA 02155 USA. RP SanGiovanni, JP (reprint author), NEI, Div Biometry & Epidemiol, NIH Bldg 31,Room 6A52,31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. RI SanGiovanni, John Paul/A-7605-2008; Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Dwyer, Johanna/0000-0002-0783-1769 FU NIDDK NIH HHS [DK46200] NR 40 TC 138 Z9 140 U1 2 U2 20 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 JUN PY 2000 VL 105 IS 6 BP 1292 EP 1298 DI 10.1542/peds.105.6.1292 PG 7 WC Pediatrics SC Pediatrics GA 321EA UT WOS:000087441400032 PM 10835071 ER PT J AU Andrews, CW Bennett, L Yu, LX AF Andrews, CW Bennett, L Yu, LX TI Predicting human oral bioavailability of a compound: Development of a novel quantitative structure-bioavailability relationship SO PHARMACEUTICAL RESEARCH LA English DT Article DE bioavailability; quantitative structure-bioavailability relationship; Lipinski's Rule of Five ID DRUGS AB Purpose. The purpose of this investigation was to develop a quantitative structure-bioavailability relationship (QSBR) model for drug discovery and development. Methods. A database of drugs with human oral bioavailability was assembled in electronic form with structure in SMILES format. Using that database, a stepwise regression procedure was used to link oral bioavailability in humans and substructural fragments in drugs. The regression model was compared with Lipinski's Rule of Five. Results. The human oral bioavailability database contains 591 compounds. A regression model employing 85 descriptors was built to predict the human oral bioavailability of a compound based on its molecular structure. Compared to Lipinski's Rule of Five, the false negative predictions were reduced from 5% to 3% while the false positive predictions decreased from 78% to 53%. A set of substructural descriptors was identified to show which fragments tend to increase/ decrease human oral bioavailability. Conclusions. A novel quantitative structure-bioavailability relationship (QSBR) was developed. Despite a large degree of experimental error, the model was reasonably predictive and stood up to crossvalidation. When compared to Lipinski's Rule of Five, the QSBR model was able to reduce false positive predictions. C1 Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Yu, LX (reprint author), US FDA, Div Prod Qual Res, 5600 Fishers Lane,HFD-941,NLRC 2400B, Rockville, MD 20857 USA. EM yul@cder.fda.gov NR 9 TC 94 Z9 99 U1 1 U2 15 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD JUN PY 2000 VL 17 IS 6 BP 639 EP 644 DI 10.1023/A:1007556711109 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 342VF UT WOS:000088665300001 PM 10955834 ER PT J AU Sapone, A Peters, JM Sakai, S Tomita, S Papiha, SS Dai, RK Friedman, FK Gonzalez, FJ AF Sapone, A Peters, JM Sakai, S Tomita, S Papiha, SS Dai, RK Friedman, FK Gonzalez, FJ TI The human peroxisome proliferator-activated receptor a gene: identification and functional characterization of two natural allelic variants SO PHARMACOGENETICS LA English DT Article DE fibrate drugs; transfection; transactivation; Wy-14 643 ID DNA-BINDING DOMAIN; ALPHA-DEFICIENT MICE; LIGAND-BINDING; PPAR-ALPHA; GLUCOCORTICOID RECEPTOR; HORMONE RECEPTORS; BETA-OXIDATION; TARGETED DISRUPTION; SPECIES-DIFFERENCES; NUCLEAR RECEPTORS AB Peroxisome proliferator-activated receptor (PPAR)alpha-null mice have a defect in fatty acid metabolism but reproduce normally. The lack of a detrimental effect of the null phenotype in development and reproduction opens up the possibility for null or variant PPAR alpha gene (PPARA) alleles in humans. To search the coding region and splice junctions for mutant and variant PPAR alpha alleles, the human PPAR alpha gene was cloned and characterized, and sequencing by polymerase chain reaction was carried out. Two paint mutations in the human gene were found in the DNA binding domain at codons for amino acids 131 and 162. The allele containing the mutation in codon 162 (CTT to GTT, L162V) designated PPARA*3, was found at a high frequency in a Northern Indian population. Transfection assays of this mutant showed that the non-ligand dependent transactivation activity was less than one-half as active as the wild-type receptor, PPARA*3 was also unresponsive to low concentrations of ligand as compared to the wild-type PPARA*1 receptor. However, the difference is ligand concentration-dependent; at concentrations of the peroxisome proliferator Wy-14 643 > 25 mu M, induction activity was restored in this variant's transactivation activity to a level five-fold greater as compared with wild-type PPARA*1 with no ligand. The mutation in codon 131 (CGA to CAA, R131Q), designated PPARA*2 is less frequent than PPARA*3, and the constitutive ligand independent activity was slightly higher than PPARA*1, Increasing concentrations of Wy-14 643 activated PPARA*2 similar to that observed with PPARA*1. The biological significance of these novel PPAR alpha alleles remains to be established. It will be of great interest to determine whether these alleles are associated with differential response to fibrate therapy. Pharmacogenetics 10:321-333 (C) 2000 Lippincott Williams & Wilkins. C1 NCI, Lab Metab, Bethesda, MD 20892 USA. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. Univ Newcastle Upon Tyne, Sch Med, Dept Biochem & Genet, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Bldg 37,Room 3E-24, Bethesda, MD 20892 USA. RI Peters, Jeffrey/D-8847-2011; Sapone, Andrea/E-6704-2013; Friedman, Fred/D-4208-2016; OI Sapone, Andrea/0000-0001-8496-6977 NR 60 TC 86 Z9 88 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD JUN PY 2000 VL 10 IS 4 BP 321 EP 333 DI 10.1097/00008571-200006000-00006 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 321HP UT WOS:000087450300006 PM 10862523 ER PT J AU Elliot, EE White, JM AF Elliot, EE White, JM TI Precipitated and spontaneous withdrawal following administration of lorazepam but not zolpidem SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE zolpidem; lorazepam; radiotelemetry; tolerance; withdrawal ID BENZODIAZEPINE ANTAGONISTS; PHYSICAL-DEPENDENCE; SELF-INJECTION; TOLERANCE; RATS; DISCONTINUATION; FLUMAZENIL; DIAZEPAM; BABOONS; RO-15-1788 AB Radiotelemetry was utilized to compare zolpidem and lorazepam tolerance and withdrawal in rats. Locomotor activity, electromyographic activity (EMG), and body temperatures were used to assess the acute drug effects, and as measures of tolerance and withdrawal. Lorazepam, zolpidem, or vehicle was administered for 12 days, and data were recorded daily, immediately, after treatment. Data were also recorded immediately after flumazenil (25 mg/kg, IP) precipitated withdrawal and during 4 days of spontaneous withdrawal. Complete tolerance to the acute effects of lorazepam administration developed within 7 days of treatment and both flumazenil-precipitated and spontaneous withdrawal were observed. In contrast, there was no tolerance to the sedative actions of zolpidem administration after 12 days, but complete tolerance to the hypothermic and muscle relaxant effects was apparent after 8 days of treatment. Despite the presence of tolerance, no evidence of either spontaneous or flumazenil-induced withdrawal was recorded in these rats. In conclusion, this model suggests that as a sedative zolpidem has significant advantages over the classic benzodiazepines. (C) 2000 Elsevier Science Inc. C1 Univ Adelaide, Dept Clin & Expt Pharmacol, Adelaide, SA 5005, Australia. RP Elliot, EE (reprint author), NIDA, Dept Psychobiol, NIH, Baltimore, MD 21224 USA. RI White, Jason /A-2795-2011 OI White, Jason /0000-0001-6750-1078 NR 49 TC 18 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUN PY 2000 VL 66 IS 2 BP 361 EP 369 DI 10.1016/S0091-3057(00)00176-3 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 332FD UT WOS:000088062800019 PM 10880691 ER PT J AU Boguna, M Porra, JM Masoliver, J AF Boguna, M Porra, JM Masoliver, J TI Continued fraction solution for the radiative transfer equation in three dimensions SO PHYSICAL REVIEW E LA English DT Article ID ANISOTROPIC RANDOM-WALKS; PERSISTENT RANDOM-WALK; SCALING RELATIONSHIPS; PHOTON MIGRATION; MODEL; TIME AB Starting from the radiative transfer equation, we obtain an analytical solution for both the free propagator alone one of the awes and an arbitrary phase function in the Fourier-Laplace domain. Ne also find the effective absorption parameter, which turns out to be very different from the one provided by the diffusion approximation. We finally present an analytical approximation procedure and obtain a differential equation that accurately reproduces the transport process. We test our approximations by means of simulations that use the Henyey-Greenstein phase function with very satisfactory results. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Barcelona, Dept Fis Fonamental, E-08028 Barcelona, Spain. RP Boguna, M (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. RI Boguna, Marian/B-7795-2011; Masoliver, Jaume/F-7198-2016 OI Boguna, Marian/0000-0001-7833-3487; Masoliver, Jaume/0000-0002-5810-879X NR 15 TC 3 Z9 3 U1 0 U2 1 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD JUN PY 2000 VL 61 IS 6 BP 6248 EP 6254 DI 10.1103/PhysRevE.61.6248 PN A PG 7 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 323PZ UT WOS:000087575300029 ER PT J AU Gandjbakhche, AH Weiss, GH AF Gandjbakhche, AH Weiss, GH TI Descriptive parameter for photon trajectories in a turbid medium SO PHYSICAL REVIEW E LA English DT Article ID ANISOTROPIC RANDOM-WALKS; SCALING RELATIONSHIPS; TIME; PENETRATION; MIGRATION; MEDICINE; TISSUE; MODEL AB In many applications of laser techniques for diagnostic or therapeutic purposes it is necessary to be able to characterize photon trajectories to know which parts of the tissue are being interrogated. In this paper, we consider the cw reflectance experiment on a semi-infinite medium with uniform optical parameters and having a planar interface. The analysis is carried out in terms of a continuous-time random walk and the relation between the occupancy of a plane parallel to the surface to the maximum depth reached by the random walker is studied. The first moment of the ratio of average depth to the average maximum depth yields information about the volume of tissue interrogated as well as giving some indication of the region of tissue that gets the most light. We have also calculated the standard deviation of this random variable. It is not large enough to qualitatively affect information contained in the first moment. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Gandjbakhche, AH (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NR 17 TC 17 Z9 17 U1 0 U2 0 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD JUN PY 2000 VL 61 IS 6 BP 6958 EP 6962 DI 10.1103/PhysRevE.61.6958 PN B PG 5 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 323QA UT WOS:000087575400032 PM 11088388 ER PT J AU Loftus, SK Pavan, WJ AF Loftus, SK Pavan, WJ TI The use of expression profiling to study pigment cell biology and dysfunction SO PIGMENT CELL RESEARCH LA English DT Review DE melanocytes; regulation; intracellular signals; extracellular signals; neural crest; microarray ID NEURAL CREST DEVELOPMENT; GENE-EXPRESSION; TRANSCRIPTIONAL PROGRAM; DIFFERENTIAL DISPLAY; MICROARRAY ANALYSIS; PATTERNS; MELANOMA; CANCER; HYBRIDIZATION; SUPPRESSION AB Regulation of gene expression is a fundamental process by which cells respond to both intracellular and extracellular signals. For a pigment cell, alterations in gene expression regulate the processes of cell migration, lineage restriction, differentiation, type of pigment produced, and progression from a normal pigment cell to that of melanoma. To date, the identification of genes involved in normal pigment cell development has been accomplished by the cloning of individual mutant alleles, a single gene at a time. Current advances in technology have now made it possible to use expression profile analysis to investigate, on a genomic scale, the process of pigment cell development and function. This review compares and contrasts the methods of subtractive suppressive polymerase chain reaction (PCR) and differential display with that of cDNA microarray analysis. C1 NIH, Natl Ctr Human Genome Res, Genet Dis Res Branch, Mouse Embryol Sect, Bethesda, MD 20892 USA. RP Pavan, WJ (reprint author), NIH, Natl Ctr Human Genome Res, Genet Dis Res Branch, Mouse Embryol Sect, Bldg 49,Room 4A82, Bethesda, MD 20892 USA. NR 42 TC 12 Z9 12 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD JUN PY 2000 VL 13 IS 3 BP 141 EP 146 DI 10.1034/j.1600-0749.2000.130304.x PG 6 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 327PE UT WOS:000087769800003 PM 10885671 ER PT J AU Smith, MBK Lamb, ML Tirado-Rives, J Jorgensen, WL Michejda, CJ Ruby, SK Smith, RH AF Smith, MBK Lamb, ML Tirado-Rives, J Jorgensen, WL Michejda, CJ Ruby, SK Smith, RH TI Monte Carlo calculations on HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor 8-Cl TIBO: contribution of the L100I and Y181C variants to protein stability and biological activity SO PROTEIN ENGINEERING LA English DT Article DE HIV-1; inhibitor; reverse transcriptase; mutation; modeling ID IMMUNODEFICIENCY-VIRUS TYPE-1; LINEAR-RESPONSE METHOD; DRUG-RESISTANT MUTANT; NONNUCLEOSIDE INHIBITORS; BINDING AFFINITIES; FREE-ENERGY; SIMULATIONS; MECHANISM; PREDICTION; HYDRATION AB A computational model of the non-nucleoside inhibitor 8-Cl TIBO complexed with HIV-1 reverse transcriptase (RT) was constructed in order to determine the binding free energies. Using Monte Carlo simulations, both free energy perturbation and linear response calculations were carried out for the transformation of wild-type RT to two key mutants, Y181C and L100I. The newer linear response method estimates binding free energies based on changes in electrostatic and van der Waals energies and solvent-accessible surface areas. In addition, the change in stability of the protein between the folded and unfolded states was estimated for each of these mutations, which are known to emerge upon treatment with the inhibitor. Results from the calculations revealed that there is a large hydrophobic contribution to protein stability in the native, folded state. The calculated absolute free energies of binding from both the linear response, and also the more rigorous free energy perturbation method, gave excellent agreement with the experimental differences in activity. The success of the relatively rapid linear response method in predicting experimental activites holds promise for estimating the activity of the inhibitors not only against the wild-type RT, but also against key protein variants whose emergence undermines the efficacy of the drugs. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Yale Univ, Dept Chem, New Haven, CT 06520 USA. Western Maryland Coll, Westminster, MD 21157 USA. RP Lamb, ML (reprint author), NCI, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. RI Tirado-Rives, Julian/A-4992-2012 OI Tirado-Rives, Julian/0000-0001-7330-189X NR 35 TC 35 Z9 38 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 JUN PY 2000 VL 13 IS 6 BP 413 EP 421 DI 10.1093/protein/13.6.413 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 337AP UT WOS:000088335400006 PM 10877852 ER PT J AU Serio, D Singh, SP Cartas, MA Weber, IT Harrison, RW Louis, JM Srinivasan, A AF Serio, D Singh, SP Cartas, MA Weber, IT Harrison, RW Louis, JM Srinivasan, A TI Antiviral agent based on the non-structural protein targeting the maturation process of HIV-1: expression and susceptibility of chimeric Vpr as a substrate for cleavage by HIV-1 protease SO PROTEIN ENGINEERING LA English DT Article DE cleavage signal sequences; immature virus particle; mature virus particle; virion incorporation ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIRETROVIRAL THERAPY; FUSION PROTEINS; VIRAL PROTEASE; GAG; PARTICLES; VIRIONS; NEF; POLYPROTEINS; INFECTIVITY AB The processing of precursor proteins (Gag and Gag-pol) by the viral protease is absolutely required in order to generate infectious particles. This prompted us to consider novel strategies that target viral maturation. Towards this end, we have engineered an HIV-1 virion associated protein, Vpr, to contain protease cleavage signal sequences from Gag and Gag-pol precursor proteins. We previously reported that virus particles derived from HIV-1 proviral DNA, encoding chimeric Vpr, showed a lack of infectivity, depending on the fusion partner. As an extension of that work, the potential of chimeric Vpr as a substrate for HIV-1 protease was tested utilizing an epitope-based assay. Chimeric Vpr molecules were modified such that the Flag epitope is removed following cleavage, thus allowing us to determine the efficiency of protease cleavage. Following incubation with the protease, the resultant products were analyzed by radioimmunoprecipitation using antibodies directed against the Flag epitope, Densitometric analysis of the autoradiograms showed processing to be both rapid and specific. Further, the analysis of virus particles containing chimeric Vpr by immunoblot showed reactivities to antibodies against the Flag epitope similar to the data observed in vitro. These results suggest that the pseudosubstrate approach mag provide another avenue for developing antiviral agents. C1 Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Srinivasan, A (reprint author), Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. FU NIAID NIH HHS [AI 29306, AI41380]; NIGMS NIH HHS [R01 GM062920] NR 37 TC 2 Z9 2 U1 0 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 JUN PY 2000 VL 13 IS 6 BP 431 EP 436 DI 10.1093/protein/13.6.431 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 337AP UT WOS:000088335400008 PM 10877854 ER PT J AU Ginsburg, A Szczepanowski, RH Ruvinov, SB Nosworthy, NJ Sondej, M Umland, TC Peterkofsky, A AF Ginsburg, A Szczepanowski, RH Ruvinov, SB Nosworthy, NJ Sondej, M Umland, TC Peterkofsky, A TI Conformational stability changes of the amino terminal domain of enzyme I of the Escherichia coli phosphoenolpyruvate : sugar phosphotransferase system produced by substituting alanine or glutamate for the active-site histidine 189: Implications for phosphorylation effects SO PROTEIN SCIENCE LA English DT Article DE active-site mutants H189E and H189A; amino terminal domain; differential scanning calorimetry; enzyme I of the E. coli phosphoenolpyruvate : sugar phosphotransferase system; phosphorylation; secondary structure; thermal stability ID PHOSPHOCARRIER PROTEIN HPR; SCANNING CALORIMETRY; NMR; TRANSPORT; BINDING; COMPLEX; MODEL; FORM AB The amino terminal dom:lin of enzyme I (residues 1-258 + Arg; EIN) and full length enzyme I (575 residues; EI) harboring active-site mutations (H189E, expected to have properties of phosphorylated forms, and H189A) have been produced by protein bioengineering. Differential scanning calorimetry (DSC) and temperature-induced changes in ellipticity at 222 nm for monomeric wild-type and mutant EIN proteins indicate two-state unfolding. For EIN proteins in 10 mM K-phosphate (and 100 mM KCl) at pH 7.5, Delta H congruent to 140 +/- 10 (160) kcal mol(-1) and Delta C-p congruent to 2.7 (3.3) kcal K-1 mol(-1) Transition temperatures (T-m) are 57 (59), 55 (58), and 53 (56) degrees C for wild-type, H189A, and H189E forms of EIN, respectively. The order of conformational stability for dephospho-His189, phospho-His189, and H189 substitutions of EIN at pH 7.5 is: His > Ala > Glu > His-PO32- due to differences in conformational entropy. Although H189E mutants have decreased T-m values for overall unfolding the amino terminal domain, a small segment of structure (3 to 12%) is stabilized (T-m similar to 66-68 degrees C). This possibly arises from an ion pair interaction between the gamma-carboxyl of Glu189 and the epsilon-amino group of Lys69 in the docking region for the histidine-containing phosphocarrier protein HPr. However, the binding of HPr to wild-type and active-site mutants of EIN and EI is temperature-independent (entropically controlled) with about the same affinity constant at pH 7.5: K-A' = 3 +/- 1 x 10(5) M-1 for EIN and similar to 1.2 x 10(5) M-1 for EI. C1 NIH, Biochem Lab, Sect Prot Chem, Bethesda, MD 20892 USA. NHLBI, Macromol Sect, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ginsburg, A (reprint author), NIH, Biochem Lab, Sect Prot Chem, Bldg 3,Room 208, Bethesda, MD 20892 USA. NR 30 TC 11 Z9 12 U1 1 U2 5 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 JUN PY 2000 VL 9 IS 6 BP 1085 EP 1094 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 328NE UT WOS:000087856300005 PM 10892802 ER PT J AU Hu, ZJ Ma, BY Wolfson, H Nussinov, R AF Hu, ZJ Ma, BY Wolfson, H Nussinov, R TI Conservation of polar residues as hot spots at protein interfaces SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE protein-protein interfaces; hot spots; molecular recognition; protein folding and binding; residue conservation; polar residues ID MOLECULAR RECOGNITION; STRUCTURAL MOTIFS; FOLDING FUNNELS; LIGAND-BINDING; DOCKING; EVOLUTION; SURFACE; COMPLEMENTARITY; THERMODYNAMICS; COMPLEX AB A number of studies have addressed the question of which are the critical residues at protein-binding sites. These studies examined either a single or a few protein-protein interfaces. The most extensive study to date has been an. analysis of alanine-scanning mutagenesis. However, although the total number of mutations was large, the number of protein interfaces was small, with some of the interfaces closely related. Here we show that although overall binding sites are hydrophobic, they are studded with specific, conserved polar residues at specific locations, possibly serving as energy "hot spots." Our results confirm and generalize the alanine-scanning data analysis, despite its limited size, Previously Trp, Arg, and Tyr were shown to constitute energetic hot spots. These were rationalized by their polar interactions and by their surrounding rings of hydrophobic residues. However, there was no compelling reason as to why specifically these residues were conserved, Here we show that other polar residues are similarly conserved. These conserved residues have been detected consistently in all interface families that we have examined. Our results are based on an extensive examination of residues which are ill contact across protein interfaces. We utilize all clustered interface families with at least five members and with sequence similarity between the members in the range of 20-90%. There are 11 such clustered interface families, comprising a total of 97 crystal structures. Our three-dimensional superpositioning analysis of the occurrences of matched residues in each of the families identifies conserved residues at spatially similar environments. Additionally, in enzyme inhibitors, we observe that residues are more conserved at the interfaces than at other locations. On the other hand, antibody-protein interfaces have similar surface conservation as compared to their corresponding linear sequence alignment, consistent with the suggestion that evolution has optimized protein interfaces for function. (C) 2000 Wiley-Liss, Inc. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sch Math Sci, Dept Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. SAIC, Lab Expt & Computat Biol, Frederick, MD USA. RP Nussinov, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Bldg 469,Room 151, Frederick, MD 21702 USA. RI Wolfson, Haim/A-1837-2011; Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-56000] NR 42 TC 213 Z9 215 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD JUN 1 PY 2000 VL 39 IS 4 BP 331 EP 342 DI 10.1002/(SICI)1097-0134(20000601)39:4<331::AID-PROT60>3.0.CO;2-A PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 317FN UT WOS:000087215500006 PM 10813815 ER PT J AU Bower, CM Hyde, TM Zaka, M Hamid, EH Baca, SM Egan, MF AF Bower, CM Hyde, TM Zaka, M Hamid, EH Baca, SM Egan, MF TI Decreased mu-opioid receptor binding in the globus pallidus of rats treated with chronic haloperidol SO PSYCHOPHARMACOLOGY LA English DT Article DE autoradiography; mu-opioid receptor; [H-3]-DAMGO; haloperidol; VCM; rat ID VACUOUS CHEWING MOVEMENTS; LONG-TERM HALOPERIDOL; MESSENGER-RNA; TARDIVE-DYSKINESIA; BRAIN; NEURONS AB Rationale: Chronic neuroleptic treatment produces a movement disorder in rats characterized by vacuous chewing movements (VCMs). Neuroleptics also produce a variety of changes in opioid neurotransmission in several regions of the basal ganglia. Rats with the VCM syndrome show elevated mRNA for enkephalin in striatopallidal neurons, suggesting a possible role for enkephalin in the pathophysiology of VCMs. Objective: This study investigated the role of mu-opioid receptor density in the basal ganglia on the expression of VCMs. Methods: Rats were treated with haloperidol for 24 weeks and withdrawn for 9 weeks. Mu (mu) receptors were labeled with [H-3]-DAMGO. Results: Haloperidol treatment produced a significant reduction in mu-receptor binding in the globus pallidus (P<0.05). There was, however, no relationship between mu-opioid receptor density and VCMs in this or any other region of the basal ganglia. Conclusion: These results replicate prior findings of a neuroleptic-induced reduction in [H-3]-DAMGO binding in the globus pallidus. The lack of association between VCMs and [H-3]-DAMGO binding in the globus pallidus or any other region suggests that prior reports of enkephalinergic mRNA changes in the striatum are not accompanied by compensatory changes in postsynaptic neurons. C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20814 USA. RP Egan, MF (reprint author), NIMH, Clin Brain Disorders Branch, Bldg 10,Room 4 S 241,MSC1377,Ctr Dr, Bethesda, MD 20814 USA. NR 15 TC 10 Z9 10 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 JUN PY 2000 VL 150 IS 3 BP 260 EP 263 DI 10.1007/s002130000460 PG 4 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 334HQ UT WOS:000088181400004 PM 10923753 ER PT J AU Le, AD Harding, S Juzytsch, W Watchus, J Shalev, U Shaham, Y AF Le, AD Harding, S Juzytsch, W Watchus, J Shalev, U Shaham, Y TI The role of corticotrophin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE adrenalectomy; alcohol; corticosterone; corticotropin-releasing factor; reinstatement; relapse; stress ID ETHANOL-CONSUMPTION; 5-HYDROXYINDOLEACETIC ACID; NONPEPTIDE ANTAGONIST; PRIMING INJECTIONS; BETA-ENDORPHIN; HEROIN-SEEKING; DRUG-SEEKING; LONG-TERM; COCAINE; CORTICOSTERONE AB Rationale: Intermittent footshock stress reliably reinstates extinguished alcohol-taking behavior in drug-free rats, but the neurochemical events involved in this effect are not known. Objective: We studied here whether two main modulators of stress responses, corticotropin-releasing factor (CRF) and corticosterone, are involved in reinstatement of alcohol seeking induced by the intermittent footshock stressor. Methods: Rats were given alcohol in a two-bottle choice procedure (water versus alcohol) for 30 days and were then trained for 60 min per day to press a lever for alcohol (12% w/v) for 24-30 days in operant conditioning chambers. After stable drug-taking behavior was obtained, lever pressing for alcohol was extinguished by terminating drug delivery for 5-8 days. Reinstatement of alcohol seeking was then determined after exposure to intermittent footshock (0.8 mA; 10 min) in different groups of rats that were pretreated with CRF receptor antagonists or underwent adrenalectomy (ADX) to remove endogenous corticosterone from the body. Results: The CRF receptor antagonists, d-phe-CRF (0.3 or 1.0 mu g; ICV) and CP-154,526 (15, 30 or 45 mg/kg; IP) attenuated footshock-induced reinstatement of alcohol seeking in a dose dependent manner. In contrast, the removal of circulating corticosterone by ADX had no effect on footshock stress-induced reinstatement of alcohol-taking behavior. In addition, the prevention of the footshock-induced rise In corticosterone while maintaining basal levels of the hormone by providing adrenalectomized rats with corticosterone pellets (50 mg/kg per day), had no effect on stress-induced reinstatement. Conclusions: These data suggest that CRF contributes to stress-induced relapse to alcohol seeking via its actions on extra-hypothalamic sites. The present data, and previous data with heroin- and cocaine-trained rats, point to a general role of CRF in relapse to drugs induced by stressors. C1 Ctr Addict & Mental Hlth, Dept Neurosci, Toronto, ON M5S 2S1, Canada. Univ Toronto, Dept Pharmacol, Toronto, ON, Canada. NIDA, Behav Neurosci Branch, IRP, Baltimore, MD USA. RP Le, AD (reprint author), Ctr Addict & Mental Hlth, Dept Neurosci, 33 Russell St, Toronto, ON M5S 2S1, Canada. RI shaham, yavin/G-1306-2014 NR 63 TC 210 Z9 212 U1 3 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUN PY 2000 VL 150 IS 3 BP 317 EP 324 DI 10.1007/s002130000411 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 334HQ UT WOS:000088181400011 PM 10923760 ER PT J AU Shalev, Z Highfield, D Yap, J Shaham, Y AF Shalev, Z Highfield, D Yap, J Shaham, Y TI Stress and relapse to drug seeking in rats: studies on the generality of the effect SO PSYCHOPHARMACOLOGY LA English DT Article DE brain stimulation reward; drug self-administration; extinction; food deprivation; heroin; reinstatement; relapse; restraint; stress ID CORTICOTROPIN-RELEASING-FACTOR; CONTEXTUAL CONTROL; CONDITIONED FEAR; FOOD-DEPRIVATION; BETA-ENDORPHIN; HEROIN-SEEKING; BEHAVIOR; COCAINE; EXTINCTION; REINSTATEMENT AB Rationale: Intermittent footshock reinstates drug-taking behavior in rats, but not behaviors previously maintained by food reinforcers. Here we tested further the generality of this phenomenon by determining whether restraint and food deprivation stressors would reinstate heroin seeking, whether the environment in which footshock is given modulates footshock-induced reinstatement, and whether footshock would reinstate operant responding previously maintained by brain stimulation reward (BSR). Methods: Groups of rats were trained to self-administer for 10 days either heroin (0.05-0.1 mg/kg/infusion, IV, three 3-h sessions/day) or brain stimulation into the septal area (trains of monopolar cathodal pulses of 100 mu s for 500 ms, one 60-min session/day). After extinction of the heroin-reinforced behavior (10-13 days), the rats were tested for reinstatement after exposure to food deprivation (1 and 21 h), restraint given outside the self-administration environment (5, 15 and 30 min), or intermittent footshock (0.8 mA, 15 min) given in the self-administration environment or in a novel (non-drug) environment. For BSR-trained rats, the effect of footshock on reinstatement after extinction (6-10 days) was compared with that induced by noncontingent brain stimulation (three or six discrete stimulations at the start of the test sessions). Results: Food deprivation reinstated heroin seeking. Footshock reliably reinstated heroin seeking when given in the drug environment, but not when given in a non-drug environment. Similarly, restraint given outside the self-administration environment failed to reinstate heroin seeking. In addition, footshock was as effective as priming brain stimulation in reinstating operant responding previously maintained by BSR. Conclusions: The effect of footshock on reinstatement of heroin seeking generalizes to food deprivation, and appears to be dependent on the environment in which the stressor is given. The data with BSR indicate that the phenomenon of footshock-induced reinstatement is not selective for drug reinforcers. C1 NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI shaham, yavin/G-1306-2014 NR 61 TC 28 Z9 28 U1 3 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUN PY 2000 VL 150 IS 3 BP 337 EP 346 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 334HQ UT WOS:000088181400013 ER PT J AU Tseng, M DeVellis, RF Maurer, KR Khare, M Kohlmeier, L Everhart, JE Sandler, RS AF Tseng, Marilyn DeVellis, Robert F. Maurer, Kurt R. Khare, Meena Kohlmeier, Lenore Everhart, James E. Sandler, Robert S. TI Food intake patterns and gallbladder disease in Mexican Americans SO PUBLIC HEALTH NUTRITION LA English DT Article DE Cholelithiasis; Mexican Americans Diet; Factor analysis; NHANES III AB Objective: Results of previous studies on diet and gallbladder disease (GBD), de r ned as having gallstones or having had surgery for gallstones, have been inconsistent. This research examined patterns of food intake in Mexican Americans and their associations with GBD. Design: Cross-sectional. Subjects: who participated in the 1988-94 third National Health and Nutrition Examination Survey (NHANES III). GBD was diagnosed by ultrasound. Food intake patterns were identi r ed by principal components analysis based on food frequency questionnaire responses. Component scores representing the level of intake of each pattern were categorized into quartiles, and prevalence odds ratios (POR) were estimated relative to the lowest quartile along with 95% con r dence intervals (CI). Results: There were four distinct patterns in women (vegetable, high calorie, traditional, fruit) and three in men (vegetable, high calorie, traditional). After age adjustment, none were associated with GBD in women. However, men in the third (POR = 0.42, 95% CI 0.21-0.85) and fourth (POR = 0.53, 95% CI 0.28-1.01) quartiles of the traditional intake pattern were half as likely to have GBD as those in the lowest quartile. Conclusions: These r ndings add to a growing literature suggesting dietary intake patterns can provide potentially useful and relevant information on diet-disease associations. Nevertheless, methods to do so require further development and validation. C1 [Tseng, Marilyn; Kohlmeier, Lenore] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. [DeVellis, Robert F.] Univ N Carolina, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27599 USA. [Maurer, Kurt R.; Khare, Meena] Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Kohlmeier, Lenore] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. [Everhart, James E.] NIDDK, Bethesda, MD 20892 USA. [Sandler, Robert S.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. RP Tseng, M (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. EM m_tseng@fccc.edu RI Tseng, Marilyn/B-9334-2016 OI Tseng, Marilyn/0000-0002-9969-9055 FU National Institutes of Health [T32 DK07634, P30 DK34987] FX The authors thank Dr Matthew P. Longnecker for his useful comments on this manuscript. This research was supported in part by grants T32 DK07634 and P30 DK34987 from the National Institutes of Health. NR 68 TC 17 Z9 18 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 EI 1475-2727 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD JUN PY 2000 VL 3 IS 2 BP 233 EP 243 PG 11 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA V32XM UT WOS:000208983900013 PM 10948391 ER PT J AU Sher, L AF Sher, L TI Seasonal variation in coronary heart disease and seasonal mood changes SO QJM-MONTHLY JOURNAL OF THE ASSOCIATION OF PHYSICIANS LA English DT Letter ID ACUTE MYOCARDIAL-INFARCTION; AFFECTIVE-DISORDER C1 NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. RP Sher, L (reprint author), NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1460-2725 J9 QJM-MON J ASSOC PHYS JI QJM-Mon. J. Assoc. Physicians PD JUN PY 2000 VL 93 IS 6 BP 385 EP 386 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 325XJ UT WOS:000087701500012 PM 10873189 ER PT J AU Soyland, C Hassfjell, SP AF Soyland, C Hassfjell, SP TI A novel Po-210-based alpha-particle irradiator for radiobiological experiments with retrospective alpha-particle hit per cell determination SO RADIATION AND ENVIRONMENTAL BIOPHYSICS LA English DT Article ID MAMMALIAN-CELLS; SINGLE; MICROBEAM; SYSTEM; DESIGN AB A new experimental design for alpha-particle irradiation of cells in vitro is described where the alpha-particle irradiator is based on a Po-210 radioactive source. In the described set-up cells are grown directly on an alpha-particle detector and irradiation is done from below. For an irradiated cell dish the number of alpha-particle traversals through each individual cell is scored by using retrospective track etch dosimetry and an accurate technique for individual cell relocation. Calibration experiments characterizing the new irradiator system are presented. C1 Norwegian Radium Hosp, Dept Biophys, N-0310 Oslo, Norway. NCI, Radioimmune & Inorgan Chem Sect, ROB, NIH, Bethesda, MD 20892 USA. RP Soyland, C (reprint author), Norwegian Radium Hosp, Dept Biophys, N-0310 Oslo, Norway. NR 18 TC 13 Z9 14 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0301-634X J9 RADIAT ENVIRON BIOPH JI Radiat. Environ. Biophys. PD JUN PY 2000 VL 39 IS 2 BP 125 EP 130 DI 10.1007/s004110000050 PG 6 WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging GA 334TC UT WOS:000088200900007 PM 10929381 ER PT J AU Sullivan, DC AF Sullivan, DC TI Biomedical Imaging Symposium: Visualizing the future of biology and medicine SO RADIOLOGY LA English DT Article DE radiology and radiologists, research; special reports C1 NCI, Biomed Imaging Program, Bethesda, MD 20892 USA. RP Sullivan, DC (reprint author), NCI, Biomed Imaging Program, Execut Plaza N,Rm 800,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 0 TC 9 Z9 10 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 JUN PY 2000 VL 215 IS 3 BP 634 EP 638 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 317VE UT WOS:000087247000004 PM 10831677 ER PT J AU Kurdziel, KA AF Kurdziel, KA TI The panda sign SO RADIOLOGY LA English DT Article DE lacrimal gland and duct; nasopharynx; parotid gland, radionuclide studies; salivary glands, radionuclide studies; sarcoidosis; signs in imaging ID SARCOIDOSIS C1 NIH, Imaging Sci Training Program, Bethesda, MD 20892 USA. RP Kurdziel, KA (reprint author), NIH, Imaging Sci Training Program, Bldg 10,Rm 1C401,MSC 1C497, Bethesda, MD 20892 USA. NR 5 TC 27 Z9 29 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2000 VL 215 IS 3 BP 884 EP 885 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 317VE UT WOS:000087247000040 PM 10831715 ER PT J AU Chizhikov, V Patton, JT AF Chizhikov, V Patton, JT TI A four-nucleotide translation enhancer in the 3 '-terminal consensus sequence of the nonpolyadenylated mRNAs of rotavirus SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE gene expression; nonpolyadenylated mRNAs; rotavirus; translation enhancer ID NONSTRUCTURAL PROTEIN NSP3; MINUS-STRAND SYNTHESIS; HISTONE MESSENGER-RNA; BINDING-PROTEIN; MOSAIC-VIRUS; POLY(A) TAIL; 3' END; POLY(A)-BINDING PROTEIN; INITIATION-FACTORS; MOLECULAR-BIOLOGY AB The 5' cap and poly(A) tail of eukaryotic mRNAs work synergistically to enhance translation through a process that requires interaction of the cap-associated eukaryotic initiation factor, elF-4G, and the poly(A)-binding protein, PABP. Because the mRNAs of rotavirus, and other members of the Reoviridae, contain caps but lack poly(A) tails, their translation may be enhanced through a unique mechanism. To identify translation enhancement elements in the viral mRNAs that stimulate translation in vivo, chimeric RNAs were prepared that contained an open reading frame for luciferase and the 5' and 3' untranslated regions (UTRs) of a rotavirus mRNA or of a nonviral mRNA. Transfection of the chimeric RNAs into rotavirus-infected cells showed that the viral 3' UTR contained a translation-enhancement element that promoted gene expression. The element did not enhance gene expression In uninfected cells and did not affect the stability of the RNAs. Mutagenesis showed that the conserved sequence GACC located at the 3' end of rotavirus mRNAs operated as an enhancement element. The 3'-GACC element stimulated protein expression independently of the sequence of the 5' UTR, although efficient expression required the RNA to contain a cap. The results indicate that the expression of viral proteins in rotavirus-infected cells is specifically up-regulated by the activity of a novel 4-nt 3' translation enhancer (TE) common to the 11 nonpolyadenylated mRNAs of the virus. The 4-nt sequence of the rotavirus 3' TE represents by far the shortest of any of the sequence enhancers known to stimulate translation. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720,Room 117, Bethesda, MD 20892 USA. RI Patton, John/P-1390-2014 NR 42 TC 30 Z9 30 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD JUN PY 2000 VL 6 IS 6 BP 814 EP 825 DI 10.1017/S1355838200992264 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 322HA UT WOS:000087503100003 PM 10864041 ER PT J AU Engel, LS O'Meara, ES Schwartz, SM AF Engel, LS O'Meara, ES Schwartz, SM TI Maternal occupation in agriculture and risk of limb defects in Washington State, 1980-1993 SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE agriculture; birth defects; epidemiologic study; limb defects; pesticides ID BIRTH AB Objectives This study examined the association between maternal occupational exposure to agricultural chemicals and the risk of limb defects among offspring. Methods A retrospective cohort study was conducted using Washington State birth records for the years 1980 through 1993. The exposed group, consisting of 4466 births to mothers employed in agriculture, was compared with 2 reference groups: (i) 23 512 births in which neither parent worked in agriculture ("nonagricultural" group) and (ii) 5994 births in which only the father worked in agriculture ("paternal agriculture" group). The outcome of interest was limb defects [syndactyly, polydactyly, adactyly, and "other limb reductions" (as listed in the birth record)]. Results An elevated risk of limb defects was observed for the exposed group in comparison with both the nonagricultural and paternal agriculture groups, with ethnicity-adjusted prevalence ratios of 2.6 [95% confidence interval (95% CI) 1.1-5.8] and 2.6 (95% CI 0.7-9.5), respectively. Conclusions These results support the hypothesis that maternal occupational exposure to agricultural chemicals may increase the risk of giving birth to a child with limb defects. C1 Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Pacific NW Agr Safety & Hlth Ctr, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA. RP Engel, LS (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8111, Bethesda, MD 20892 USA. NR 10 TC 45 Z9 47 U1 2 U2 4 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD JUN PY 2000 VL 26 IS 3 BP 193 EP 198 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 329YN UT WOS:000087936200003 PM 10901110 ER PT J AU Grossman, Z Paul, WE AF Grossman, Z Paul, WE TI Self-tolerance: context dependent tuning of T cell antigen recognition SO SEMINARS IN IMMUNOLOGY LA English DT Review DE context-sensitivity; tuning; selection; activation; feedback ID IMMUNE-SYSTEM; PROLIFERATION; SELECTION; LIGANDS; MEMORY AB Physiological messages to cells are encoded in the magnitude, and in the time- and space-contingencies, of sets of stimuli. In particular individual T cells continuously integrate antigenic and other signals and respond differentially to the rate of change in the level of stimulation, translated intracellularly into 'metabolic perturbations'. The organization of the immune response at the cell-population level in space and time is also conductive to discriminating the magnitude of 'system perturbations'. In this way, the immune system was 'designed' to respond in a characteristic explosive way mainly to episodes of infection and not to the continuous presence of self-antigens. T cells are selected to be moderately autoreactive, and the degree of autoreactivity that they express is continuously controlled through activation-threshold tuning. Their level of autoreactivity is maintained in a range that facilitates survival and self-renewal and is probably used in performing some immunoregulatory functions and possibly other physiological functions. Autoreactivity and outward-directed immunity are regulated simultaneously and interactively through the interplay of selection, tuning, controlled activation and feedback. C1 Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Gulbenkian Inst Sci, Oeiras, Portugal. RP Grossman, Z (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. RI Grossman, Zvi/A-9643-2008 NR 29 TC 73 Z9 76 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD JUN PY 2000 VL 12 IS 3 BP 197 EP 203 DI 10.1006/smim.2000.0232 PG 7 WC Immunology SC Immunology GA 334HV UT WOS:000088181800007 PM 10910740 ER PT J AU Anderson, CC Matzinger, P AF Anderson, CC Matzinger, P TI Danger: the view from the bottom of the cliff SO SEMINARS IN IMMUNOLOGY LA English DT Review ID T-CELLS; IMMUNE PRIVILEGE; NONSELF; GAMMA; SELF; BETA C1 NIAID, Ghost Lab, LCMI, NIH, Bethesda, MD 20892 USA. RP Anderson, CC (reprint author), NIAID, Ghost Lab, LCMI, NIH, Bldg 4,Room 111, Bethesda, MD 20892 USA. NR 25 TC 49 Z9 55 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD JUN PY 2000 VL 12 IS 3 BP 231 EP 238 PG 8 WC Immunology SC Immunology GA 334HV UT WOS:000088181800011 PM 10910744 ER PT J AU Trimble, EL AF Trimble, EL TI Innovative therapies for advanced ovarian cancer SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT Workshop on Contemporary Issues in the Management of Ovarian Cancer CY SEP 28, 1999 CL ROME, ITALY ID GYNECOLOGIC-ONCOLOGY-GROUP; P53 GENE-THERAPY; PHASE-II TRIAL; INTRAPERITONEAL CISPLATIN; PLATINUM-RESISTANT; INTRAVENOUS CYCLOPHOSPHAMIDE; LIPOSOMAL DOXORUBICIN; BREAST-CANCER; CELL-LINES; HUMAN HEAD C1 NCI, Div Canc Treatment & Diagnos, Canc Therapy Evaluat Program, Rockville, MD 20852 USA. RP Trimble, EL (reprint author), NCI, Div Canc Treatment & Diagnos, Canc Therapy Evaluat Program, 6130 Execut Blvd,Suite 741,MSC 7436, Rockville, MD 20852 USA. NR 72 TC 17 Z9 17 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 2000 VL 27 IS 3 SU 7 BP 24 EP 30 PG 7 WC Oncology SC Oncology GA 344KV UT WOS:000088758200006 PM 10952123 ER PT J AU Wang, JTL Wang, X Shasha, D Shapiro, BA Zhang, KZ Ma, QC Weinberg, Z AF Wang, JTL Wang, X Shasha, D Shapiro, BA Zhang, KZ Ma, QC Weinberg, Z TI An approximate search engine for structural databases SO SIGMOD RECORD LA English DT Article; Proceedings Paper CT International Conference on Management of Data CY MAY 16-18, 2000 CL DALLAS, TEXAS SP Assoc Comp Machinery, Special Interest Grp Management Data C1 New Jersey Inst Technol, Dept Comp & Informat Sci, Newark, NJ 07102 USA. New Jersey Inst Technol, Dept CIS, Newark, NJ 07102 USA. NYU, Courant Inst Math Sci, New York, NY 10012 USA. Natl Canc Inst, Expt & Computat Biol Lab, Frederick, MD 21702 USA. Univ Western Ontario, Dept Comp Sci, London, ON N6A 5B7, Canada. Univ Washington, Dept Comp Sci & Engn, Seattle, WA 98195 USA. RP Wang, JTL (reprint author), New Jersey Inst Technol, Dept Comp & Informat Sci, Univ Hts, Newark, NJ 07102 USA. OI Weinberg, Zasha/0000-0002-6681-3624 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 1515 BROADWAY, NEW YORK, NY 10036 USA SN 0163-5808 J9 SIGMOD RECORD JI Sigmod Rec. PD JUN PY 2000 VL 29 IS 2 BP 584 EP 584 PG 1 WC Computer Science, Information Systems; Computer Science, Software Engineering SC Computer Science GA 328UA UT WOS:000087867500065 ER PT J AU Vogel, JC Udey, MC AF Vogel, JC Udey, MC TI Activation of skin dendritic cells by immunostimulatory DNA SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTRADERMAL GENE IMMUNIZATION; CADHERIN-MEDIATED ADHESION; LEISHMANIA-MAJOR INFECTION; BACTERIAL-DNA; PROTECTIVE IMMUNITY; FACTOR-ALPHA; CPG MOTIFS; IN-VIVO; T-CELL C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Vogel, JC (reprint author), NCI, Dermatol Branch, Bldg 10, Bethesda, MD 20892 USA. NR 49 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD JUN PY 2000 VL 22 IS 1-2 BP 45 EP 54 DI 10.1007/s002810000027 PG 10 WC Immunology; Pathology SC Immunology; Pathology GA 334DL UT WOS:000088170400005 PM 10944799 ER PT J AU Koch, CA Picken, C Clement, SC Azumi, N Sarlis, NJ AF Koch, CA Picken, C Clement, SC Azumi, N Sarlis, NJ TI Ectopic lingual thyroid: An otolaryngologic emergency beyond childhood SO THYROID LA English DT Article ID CLEFT-PALATE; DIAGNOSIS AB Ectopic thyroid is rare and occasionally presents suddenly in childhood. Adult patients with thyroid ectopy who develop local symptoms commonly have an enlarged ectopic gland and hypothyroidism. We describe the first case of an adult patient who sudden presented with sudden dysphagia and dyspnea caused by a large lingual thyroid in clinical and biochemical euthyroidism. Treatment consisted of surgical removal of the ectopic gland and thyroid hormone replacement therapy. C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Surg, Div Otolaryngol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Internal Med, Div Endocrinol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Pathol, Washington, DC 20007 USA. RP Sarlis, NJ (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bldg 10,Room 8D12C 10 Ctr Dr,MSC 1758, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 29 TC 12 Z9 14 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD JUN PY 2000 VL 10 IS 6 BP 511 EP 514 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 330PE UT WOS:000087969800011 PM 10907996 ER PT J AU Aframian, DJ Cukierman, E Nikolovski, J Mooney, DJ Yamada, KM Baum, BJ AF Aframian, DJ Cukierman, E Nikolovski, J Mooney, DJ Yamada, KM Baum, BJ TI The growth and morphological behavior of salivary epithelial cells on matrix protein-coated biodegradable substrata SO TISSUE ENGINEERING LA English DT Article ID IN-VIVO; GLAND; LINE; TISSUE; STIMULATION; XEROSTOMIA; EXPRESSION; SECRETION; RADIATION; LAMININ-1 AB The purpose of this study was to examine the growth and morphology of a salivary epithelial cell line (HSG) in vitro on several biodegradable substrata as an important step toward developing an artificial salivary gland. The substrates examined were poly-(L)-lactic acid (PLLA), polyglycolic acid (PGA), and two co-polymers, 85% and 50% PLGA, respectively. The substrates were formed into 20- to 25-mm disks, and the cells were seeded directly onto the polymers or onto polymers coated with specific extracellular matrix proteins. The two copolymer substrates became friable over time in aqueous media and proved not useful for these experiments. The purified matrix proteins examined included fibronectin (FN), laminin (LN), collagen I, collagen IV, and gelatin. In the absence of preadsorbed proteins, HSG cells did not attach to the polymer disks. The cells, in general, behaved similarly on both PLLA and PGA, although optimal results were obtained consistently in PLLA. On FN-coated PLLA disks, HSG cells were able to form a uniform monolayer, which was dependent on time and FN concentration. Coating of disks with LN, collagen I, and gelatin also promoted monolayer growth. This study defines the conditions necessary for establishing a monolayer organization of salivary epithelial cells with rapid proliferation on a biodegradable substrate useful for tissue engineering. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Baum, BJ (reprint author), NIDCR, GTTB, NIH, Bldg 10,Rm 1N113,MSC-1190, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 38 TC 79 Z9 83 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JUN PY 2000 VL 6 IS 3 BP 209 EP 216 DI 10.1089/10763270050044380 PG 8 WC Cell & Tissue Engineering SC Cell Biology GA 329BQ UT WOS:000087886600001 PM 10941215 ER PT J AU Dunson, DB Haseman, JK van Birgelen, APJM Stasiewicz, S Tennant, RW AF Dunson, DB Haseman, JK van Birgelen, APJM Stasiewicz, S Tennant, RW TI Statistical analysis of skin tumor data from Tg.AC mouse bioassays SO TOXICOLOGICAL SCIENCES LA English DT Article DE carcinogenicity; dose-response; drug safety; historical controls; papilloma; risk assessment; skin-painting study; transgenic mouse; tumorigenesis ID LINEAR MIXED MODELS; HA-RAS GENE; TRANSGENIC MICE; IDENTIFYING CARCINOGENS AB New strategies for identifying chemical carcinogens and assessing risk have been proposed based on the Tg.AC (zetaglobin promoted v-Ha-ras) transgenic mouse. Preliminary studies suggest that the Tg.AC mouse bioassay may be an effective means of quickly evaluating the carcinogenic potential of a test agent. The skin of the Tg,AC mouse is genetically initiated, and the induction of epidermal papillomas in response to dermal or oral exposure to a chemical agent acts as a reporter phenotype of the activity of the test chemical. In Tg.AC mouse bioassays, the test agent is typically applied topically for up to 26 weeks, and the number of papillomas in the treated area is counted weekly. Statistical analyses are complicated by within-animal and serial dependency in the papilloma counts, survival differences between animals, and missing data. In this paper, we describe a statistical model for the analysis of skin tumor data from a Tg.AC mouse bioassay, The model separates effects on papilloma latency and multiplicity and accommodates important features of the data, including variability in expression of the transgene and dependency in the tumor counts. Methods are described for carcinogenicity testing and risk assessment. We illustrate our approach using data from a study of the effect of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on tumorigenesis. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Operat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, POB 12233,MD A3-03, Res Triangle Pk, NC 27709 USA. NR 42 TC 15 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2000 VL 55 IS 2 BP 293 EP 302 DI 10.1093/toxsci/55.2.293 PG 10 WC Toxicology SC Toxicology GA 319JT UT WOS:000087338300008 PM 10828260 ER PT J AU Flynn, KM Ferguson, SA Delclos, KB Newbold, RR AF Flynn, KM Ferguson, SA Delclos, KB Newbold, RR TI Effects of genistein exposure on sexually dimorphic behaviors in rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE estrogen; phytoestrogen; isoflavone; endocrine disrupter; nutrition; chronic exposure ID SEX-DIFFERENCES; GONADAL-HORMONES; EARLY-LIFE; PLAY; PHYTOESTROGENS; ISOFLAVONES; DIFFERENTIATION; TESTOSTERONE; CHEMICALS; DAIDZEIN AB The phytoestrogen genistein, the principal isoflavone in soybeans, has adverse effects on animal reproduction. As adult physiology and behavior are sensitive to perturbation by developmental estrogens, exposure to genistein during development may produce behavioral alterations as well. Pregnant rats were fed soy-free diets containing 0, 25, 250, or 1250 ppm genistein (approximately 0, 2, 20, or 100 mg/kg/day) beginning on gestational day 7, and offspring continued on these diets through postnatal day (PND) 77. Male and female offspring were assessed for levels of sexually dimorphic behaviors: open field activity, play behavior, running wheel activity, and consumption of saccharin- and sodium chloride-flavored solutions. Consumption of the salt solution was affected by genistein, with animals in the 1250-ppm group drinking significantly more than controls; consumption of plain water was unaffected. Genistein treatment also significantly affected play behavior; although no treated group was significantly different from controls, and the effect was not sexually dimorphic. Running wheel activity and saccharin solution consumption showed significant sex differences, but no effects of genistein treatment. Gestational duration, total and live pups per litter, and total and live litter sex ratios were not significantly affected by genistein. However, average weight per live pup at birth and offspring body weights from PND 42-77 were significantly decreased in the 1250-ppm group. Body weight and food intake for the darns were also significantly decreased in the 1250-ppm group. These results indicate that developmental genistein treatment, at levels that decrease maternal and offspring body weight, causes subtle alterations in some sexually dimorphic behaviors. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Flynn, KM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd,HFT-132, Jefferson, AR 72079 USA. NR 39 TC 74 Z9 75 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2000 VL 55 IS 2 BP 311 EP 319 DI 10.1093/toxsci/55.2.311 PG 9 WC Toxicology SC Toxicology GA 319JT UT WOS:000087338300010 PM 10828262 ER PT J AU Liu, J Liu, YP Goyer, RA Achanzar, W Waalkes, MP AF Liu, J Liu, YP Goyer, RA Achanzar, W Waalkes, MP TI Metallothionein-I/II null mice are more sensitive than wild-type mice to the hepatotoxic and nephrotoxic effects of chronic oval or injected inorganic arsenicals SO TOXICOLOGICAL SCIENCES LA English DT Article DE arsenite; arsenate; chronic exposures; metallothionein-I/II null mice; nephrotoxicity; serum cytokines; hepatotoxicity; glutathione ID NONCIRRHOTIC PORTAL-HYPERTENSION; OXIDATIVE STRESS; SODIUM ARSENITE; HEPATIC METALLOTHIONEIN; GLUTATHIONE DEPLETION; HUMAN-FIBROBLASTS; TRANSGENIC MICE; OXIDANT STRESS; II GENES; TOXICITY AB Metallothionein (MT) is a low-molecular-weight, sulfhydryl-rich, metal-binding protein that can protect against the toxicity of cadmium, mercury, and copper. However, the role of MT in arsenic (As)-induced toxicity is less certain. To better define the ability of MT to modify As toxicity, MT-I/II knockout (MT-null) mice and the corresponding wild-type mice (WT) were exposed to arsenite [As(III)] or arsenate [As(V)] either through the drinking water for 48 weeks, or through repeated sc injections (5 days/week) for 15 weeks. Chronic As exposure increased tissue MT concentrations (2-5-fold) in the WT but not in MT-null mice. Arsenic by both routes produced damage to the liver (fatty infiltration, inflammation, and focal necrosis) and kidney (tubular cell vacuolization, inflammatory cell infiltration, and interstitial fibrosis) in both MT-null and WT mice. However, in MT-null mice, the pathological lesions were more frequent and severe when compared to WT mice. This was confirmed biochemically, in that, at the higher oral doses of As, blood urea nitrogen (BUN) levels were increased more in MT-null mice (60%) than in WT mice (30%). Chronic As exposures produced 2-10 fold elevation of serum interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha levels, with greater increases seen by repeated injections than by oral exposure, and again, MT-null mice had higher serum cytokines than WT mice after As exposure. Repeated As injections also decreased hepatic glutathione (GSH) by 35%, but GSH-peroxidase and GSH-reductase were minimally affected. MT-null mice were more sensitive than WT mice to the effect of GSH depletion by As(V). Hepatic caspase-3 activity was increased (2-3-fold) in both WT and MT-null mice, indicative of apoptotic cell death. In summary, chronic inorganic As exposure produced injuries to multiple organs, and MT-null mice are generally more susceptible than WT mice to As-induced toxicity regardless of route of exposure, suggesting that MT could be a cellular factor in protecting against chronic As toxicity. C1 NIEHS, NCI, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. NIEHS, Off Director, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), NIEHS, NCI, Comparat Carcinogenesis Lab, Mail Drop F0-09, Res Triangle Pk, NC 27709 USA. NR 56 TC 106 Z9 129 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2000 VL 55 IS 2 BP 460 EP 467 DI 10.1093/toxsci/55.2.460 PG 8 WC Toxicology SC Toxicology GA 319JT UT WOS:000087338300027 PM 10828279 ER PT J AU de Figueiredo, P Drecktrah, D Polizotto, RS Cole, NB Lippincott-Schwartz, J Brown, WJ AF de Figueiredo, P Drecktrah, D Polizotto, RS Cole, NB Lippincott-Schwartz, J Brown, WJ TI Phospholipase A(2) antagonists inhibit constitutive retrograde membrane traffic to the endoplasmic reticulum SO TRAFFIC LA English DT Article DE Golgi complex; membrane tubules; phospholipase A(2); retrograde transport ID TRANS-GOLGI NETWORK; YEAST COPI MUTANTS; BREFELDIN-A; RECYCLING PATHWAY; INTERMEDIATE COMPARTMENT; SIGNAL-TRANSDUCTION; ORGANELLE STRUCTURE; PROTEIN ERGIC-53; KDEL RECEPTOR; ER AB Eukaryotic cells contain a variety of cytoplasmic Ca2+-dependent and Ca2+-independent phospholipase A(2)s (PLA(2)s; EC 2.3.1.2.3). However, the physiological roles for many of these ubiquitously-expressed enzymes is unclear or not known. Recently, pharmacological studies have suggested a role for Ca2+-independent PLA(2) (iPLA(2)) enzymes in governing intracellular membrane trafficking events in general and regulating brefeldin A (BFA)-stimulated membrane tubulation and Golgi-to-endoplasmic reticulum (ER) retrograde membrane trafficking, in particular. Here, we extend these studies to show that membrane-permeant iPLA(2) antagonists potently inhibit the normal, constitutive retrograde membrane trafficking from the trans-Golgi network (TGN), Golgi complex, and the ERGIC-53-positive ER-Golgi-intermediate compartment (ERGIC), which occurs in the absence of BFA. Taken together, these results suggest that iPLA(2) enzymes play a general role in regulating, or directly mediating, multiple mammalian membrane trafficking events. C1 Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Brown, WJ (reprint author), Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. FU NIDDK NIH HHS [DK51596] NR 57 TC 45 Z9 46 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-9219 J9 TRAFFIC JI Traffic PD JUN PY 2000 VL 1 IS 6 BP 504 EP 511 DI 10.1034/j.1600-0854.2000.010608.x PG 8 WC Cell Biology SC Cell Biology GA 339TW UT WOS:000088494800008 PM 11208136 ER PT J AU Matsuo, K Procter, J Stroncek, D AF Matsuo, K Procter, J Stroncek, D TI Variations in genes encoding neutrophil antigens NA1 and NA2 SO TRANSFUSION LA English DT Article ID POLYMERASE CHAIN-REACTION; GAMMA RECEPTOR-III; SEQUENCE-SPECIFIC PRIMERS; NEONATAL NEUTROPENIA; FRENCH POPULATION; RIIIB DEFICIENCY; FREQUENCIES; SYSTEM; FORMS; POLYMORPHISM AB BACKGROUND: Neutrophil-specific antigens NAI and NA2 are located on Fc gamma receptor IIIb (Fc gamma RIIIb). NA1 and NA2 forms of Fc gamma RIIIb differ by four amino acids and the corresponding genes by five nucleotides. Variations in NA gene frequencies are encountered among ethnic groups. Altered forms of the genes are expected among individuals. STUDY DESIGN AND METHODS: RFLPs associated with four recognition sites were used to determine NA genotypes of 232 individuals. When atypical NA genotypes were identified, Fc gamma RIIIB and Fc gamma RIIIA regions were sequenced. RESULTS: NA I Fc gamma RIIIB frequency in 100 Japanese (0.66) was greater than that in 53 African Americans (blacks) (0.40; p < 0.01) and 79 whites (0.32; p < 0.001). Sequencing of atypical Fc gamma RIIIB in 16 people confirmed that four blacks had G --> A substitutions at 227; 7 blacks had A --> G substitutions at 277; and 1 Japanese person had C --> G at 141 and G --> T at 227. A at 227 and G at 277 represent expected nts of NA1 Fc gamma RIIIB. One black had an NA I Fc gamma RIIIB with a G --> A substitution at 349; A is normally found in NA2 Fc gamma RIIIB at 349. Sequencing atypical Fc gamma RIIIA in three persons revealed that two blacks had G --> A substitutions at 277 plus C --> A substitutions at 266 and 1 white had previously described T --> G at 230. Two blacks with atypical NA2 Fc gamma RIIIB had T --> G Fc gamma RIIIA at 230. One black was NA(null). CONCLUSION: NA2 Fc gamma RIIIB is more polymorphic in blacks than in whites or Japanese persons. Chimeric Fc gamma RIIIB alleles are most similar to NA2 Fc gamma RIIIB. One alternate allele of NA1 (NA1*02) and four alternate alleles of NA2 (NA2*02, NA2*03, NA2*04, and NA2*05) are described. C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Stroncek, D (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, 10 Ctr Dr,MSC 1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 35 TC 20 Z9 22 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2000 VL 40 IS 6 BP 645 EP 653 DI 10.1046/j.1537-2995.2000.40060645.x PG 9 WC Hematology SC Hematology GA 325JE UT WOS:000087671800007 PM 10864983 ER PT J AU Matsuo, K Lin, A Procter, JL Clement, L Stroncek, D AF Matsuo, K Lin, A Procter, JL Clement, L Stroncek, D TI Variations in the expression of granulocyte antigen NB1 SO TRANSFUSION LA English DT Article ID MONOCLONAL-ANTIBODIES; GENE-FREQUENCIES; NEUTROPHILS; PATHOGENESIS; NEUTROPENIA AB BACKGROUND: Between 87 and 97 percent of whites express NB1 alloantigen on some but not all of their granulocytes. The expression of NBI has not been compared among large groups of adults of different sexes, ages, and ethnic groups. Previous testing of whites suggests that the expression of NBI is variable. STUDY DESIGN AND METHODS: Serologic testing of granulocytes from 224 persons with two examples of MoAb to NB1 (1B5 and 7D8) was performed to distinguish phenotypic differences among age, sex, and ethnic groups and differences in reactivity to MoAbs. The donors were from 17 to 82 years of age, and 87 were female. They were from four ethnic backgrounds: 54 were African American (black), 10 were Asian, 9 Hispanic, and 152 white. Granulocytes were tested by flow cytometry. Parallel testing with MoAbs to CD16, CD11b, and CD45 served as controls. The size of the granulocyte population reacting with 1B5 and 7D8 and the respective mean, median, and peak cell fluorescence intensities were analyzed. RESULTS: The expression of 7D8 and 1B5 was greater on granulocytes from female donors. The expression of 7D8 fell in older women but not in men. There were no differences among the four racial groups in either the frequency of NBI as determined by 1B5 or 7D8 or in the size of the population of granulocytes reacting with either antibody. When the fluorescence intensities of the antibody reactions were compared among groups, there were no differences in reactivity with 1B5. However, reactions with 7D8 were all greater in blacks. Comparison of the size of the antigen-positive granulocyte population, as determined by antibody reactivity, showed that only 30 donors differed by more than 10 percent. These discordant results were more likely to occur in whites than in blacks (18% vs. 4%, p < 0.02). CONCLUSIONS: NB1 is composed of at least two epitopes as determined by serologic studies. The expression of both antigens is greater in females. The 7D8-reactive epitope appears to be more prevalent or more accessible on granulocytes of blacks. Variations in the expression of NBI are more likely to occur in whites. The biochemical and molecular basis of these variations are not known. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Hershey, PA 17033 USA. Univ So Calif, Los Angeles Cty Med Ctr, Div Allergy & Immunol, Los Angeles, CA 90033 USA. RP Stroncek, D (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, 10 Ctr Dr,MSC-1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 23 TC 37 Z9 38 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2000 VL 40 IS 6 BP 654 EP 662 DI 10.1046/j.1537-2995.2000.40060654.x PG 9 WC Hematology SC Hematology GA 325JE UT WOS:000087671800008 PM 10864984 ER PT J AU Stroncek, DF Confer, DL Leitman, SF AF Stroncek, DF Confer, DL Leitman, SF TI Peripheral blood progenitor cells for HPC transplants involving unrelated donors SO TRANSFUSION LA English DT Review ID COLONY-STIMULATING-FACTOR; BONE-MARROW DONORS; ACUTE ARTERIAL THROMBOSIS; STEM-CELLS; ALLOGENEIC TRANSPLANTATION; G-CSF; HEALTHY DONORS; HEMATOLOGIC MALIGNANCIES; FILGRASTIM MOBILIZATION; MYELOID-LEUKEMIA C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. Natl Marrow Donor Program, Minneapolis, MN USA. RP Stroncek, DF (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, 10 Ctr Dr,MSC 1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 62 TC 15 Z9 16 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2000 VL 40 IS 6 BP 731 EP 741 DI 10.1046/j.1537-2995.2000.40060731.x PG 11 WC Hematology SC Hematology GA 325JE UT WOS:000087671800021 PM 10864997 ER PT J AU Brown, P Cervenakova, L AF Brown, P Cervenakova, L TI Infectivity of buffy coat in variant CJD - Reply SO TRANSFUSION LA English DT Letter ID SPONGIFORM ENCEPHALOPATHY; COMPONENTS; PROTEIN; DISEASE; BLOOD C1 NINDS, CNS Studies Lab, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Jerome H Holland Lab, Rockville, MD USA. RP Brown, P (reprint author), NINDS, CNS Studies Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2000 VL 40 IS 6 BP 755 EP 755 PG 1 WC Hematology SC Hematology GA 325JE UT WOS:000087671800026 ER PT J AU Wang, YL Geer, LY Chappey, C Kans, JA Bryant, SH AF Wang, YL Geer, LY Chappey, C Kans, JA Bryant, SH TI Cn3D: sequence and structure views for Entrez SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID NEW-GENERATION C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Wang, YL (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RI Geer, Lewis/H-2714-2014 NR 6 TC 155 Z9 157 U1 1 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUN PY 2000 VL 25 IS 6 BP 300 EP 302 DI 10.1016/S0968-0004(00)01561-9 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 322UU UT WOS:000087528000012 PM 10838572 ER PT J AU Haxby, JV Hoffman, EA Gobbini, MI AF Haxby, JV Hoffman, EA Gobbini, MI TI The distributed human neural system for face perception SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; TEMPORAL CORTEX; FACIAL EXPRESSIONS; HUMAN AMYGDALA; OCCIPITOTEMPORAL CORTEX; FUNCTIONAL-ORGANIZATION; IMPAIRED RECOGNITION; VISUAL-ATTENTION; PARIETAL CORTEX AB Face perception, perhaps the most highly developed visual skill in humans, is mediated by a distributed neural system in humans that is comprised of multiple, bilateral regions. We propose a model for the organization of this system that emphasizes a distinction between the representation of invariant and changeable aspects of faces. The representation of invariant aspects of faces underlies the recognition of individuals, whereas the representation of changeable aspects of faces, such as eye gaze, expression, and lip movement, underlies the perception of information that facilitates social communication. The model is also hierarchical insofar as it is divided into a core system extended system. The core system is comprised of occipitotemporal regions in visual cortex that mediate the visual analysis of faces. In the core system, the representation of invariant aspects is mediated more by the face-responsive region fusiform gyrus, whereas the representation of changeable aspects is mediated more by the face-responsive region in the superior temporal sulcus. The extended system is comprised of regions from neural systems for other cognitive functions that, can be recruited to act in concert with the regions in the core system to extract meaning from faces. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Haxby, JV (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C104, Bethesda, MD 20892 USA. NR 96 TC 2180 Z9 2228 U1 37 U2 339 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD JUN PY 2000 VL 4 IS 6 BP 223 EP 233 DI 10.1016/S1364-6613(00)01482-0 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 321VZ UT WOS:000087476500004 ER PT J AU Wise, SP Murray, EA AF Wise, SP Murray, EA TI Arbitrary associations between antecedents and actions SO TRENDS IN NEUROSCIENCES LA English DT Review ID SUPPLEMENTARY EYE FIELD; INFEROTEMPORAL-FRONTAL DISCONNECTION; CONDITIONAL OCULOMOTOR ASSOCIATIONS; MEDIAL TEMPORAL-LOBE; NEURONAL-ACTIVITY; FORNIX TRANSECTION; PREMOTOR CORTEX; MONKEYS; LESIONS; MEMORY AB The arbitrary linkage of sensory cues to actions and goals represents one of the most-flexible capabilities in the behavioral repertoire of mammals. This ability has been termed 'conditional motor learning', 'conditional discrimination' or, more recently, 'arbitrary visuomotor mapping'. Unlike other forms of visuomotor guidance, in arbitrary mapping the location of the sensory cue lacks any systematic spatial relationship with the action or its goal. Recent work has identified much of the neural network that underlies this behavior. It consists of parts of the frontal cortex, hippocampal system and basal ganglia, each of which has neurons whose activity undergoes systematic evolution during learning. C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Wise, SP (reprint author), NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. OI Murray, Elisabeth/0000-0003-1450-1642 NR 40 TC 183 Z9 185 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUN PY 2000 VL 23 IS 6 BP 271 EP 276 DI 10.1016/S0166-2236(00)01570-8 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 318GL UT WOS:000087275500010 PM 10838597 ER PT J AU Krausz, KW Goldfarb, I Yang, TJ Gonzalez, FJ Gelboin, HV AF Krausz, KW Goldfarb, I Yang, TJ Gonzalez, FJ Gelboin, HV TI An inhibitory monoclonal antibody to human cytochrome P450 that specifically binds and inhibits P4502C9II, an allelic variant of P4502C9 having a single amino acid change Arg144 Cys SO XENOBIOTICA LA English DT Article ID CDNA-EXPRESSED HUMAN; HUMAN LIVER; GENETIC-ANALYSIS; METABOLISM; CYP2C9; TOLBUTAMIDE; ENZYMES; 7-ETHOXYCOUMARIN; POLYMORPHISM; BACULOVIRUS AB A monoclonal antibody (MAb 292-2-3) has been isolated that binds specifically to a single allele of three expressed human cytochrome P4502C9 alleles. The MAb binds to 2C9(Cys144) (II), and does not bind to the wild-type 2C9(Arg144) (I), or the third allele 2C9(Ile-->Leu359) (III) and thus the MAb detects an allele with > 99% homology and differing from the wild-type 2C9(Arg144) (I) by a single amino acid. The MAb 292-2-3 does not bind to the other 2C isoforms (2C8, 2C18, 2C19) or the other human cytochrome P450s, 1A1, 1A2, 2A6, 2B6, 2C8, 2D6, 2E1 or 3A4/5. MAb 292-2-3 inhibits the metabolism of tolbutamide, diclofenac and phenanthrene by the target 2C9(Cys144) (II) allele by > 90%, and does not inhibit the catalytic activity of the wild-type 2C9(Arg144) (I), or 2C9(Ile-->Leu359) (III) the other 2C isoforms 2C8, 2C18, 2C19, or the other non-2C human P450s listed above. The MAb 292-2-3 is thus a prototype of an ideal and extraordinarily specific reagent for the detection and measurement of the metabolic role of highly related isoforms and polymorphic alleles of human cytochrome P450s. MAbs of high specificity can also determine the amount of phenotypic expression of polymorphic alleles and their metabolic role in drug and non-drug xenobiotic metabolism in heterozygote individuals. The inhibitory MAb might also identify allele-specific substrates of polymorphic human cytochrome P450s. C1 NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gelboin, HV (reprint author), NCI, Mol Carcinogenesis Lab, NIH, 37 Convent Dr,Bldg 37,Rm 3E24, Bethesda, MD 20892 USA. NR 31 TC 7 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD JUN PY 2000 VL 30 IS 6 BP 619 EP 625 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 332KL UT WOS:000088072800006 PM 10923863 ER PT J AU Smith, SKF Anderson, HA Yu, G Robertson, AGS Allen, SJ Tyler, SJ Naylor, RL Mason, G Wilcock, GW Roche, PA Fraser, PE Dawbarn, D AF Smith, SKF Anderson, HA Yu, G Robertson, AGS Allen, SJ Tyler, SJ Naylor, RL Mason, G Wilcock, GW Roche, PA Fraser, PE Dawbarn, D TI Identification of syntaxin 1A as a novel binding protein for presenilin-1 SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Alzheimer's disease; presenilin 1; syntaxin; thioredoxin ID FAMILIAL ALZHEIMERS-DISEASE; MISSENSE MUTATIONS; GENE; EXPRESSION; MICE; DEFECTS; NOTCH1; BRAIN; DII1 AB Mutations in the presenilin 1 gene have been shown to result in Alzheimer's disease. Presenilin 1 is a multi-transmembrane protein with a large hydrophilic loop near the C-terminus. This region is required for known functions of presenilin 1. We have constrained this loop within the active site of the bacterial protein, thioredoxin, to mimic its native conformational state. This hybrid protein was used as bait in a yeast two hybrid screen in an attempt to identify presenilin binding proteins. By this method syntaxin 1A, a synaptic plasma membrane protein, was identified as a novel binding protein for presenilin 1. In vitro experiments confirm the two-hybrid results suggesting that PSI binds syntaxin under physiological conditions. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Bristol, Dept Med Care Elderly, Mol Neurobiol Unit, Bristol BS2 8HW, Avon, England. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Toronto, Dept Med, Toronto, ON M5S 3H2, Canada. Univ Toronto, Ctr Res Neurodegenerat Dis, Dept Med Biophys, Toronto, ON M5S 3H2, Canada. Univ Bristol, Frenchay Hosp, Dept Care Elderly, Bristol BS16, Avon, England. RP Dawbarn, D (reprint author), Univ Bristol, Dept Med Care Elderly, Mol Neurobiol Unit, Bristol BS2 8HW, Avon, England. NR 25 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY 31 PY 2000 VL 78 IS 1-2 BP 100 EP 107 DI 10.1016/S0169-328X(00)00079-6 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 337AB UT WOS:000088334200010 ER PT J AU Vasquez, DA Nyaga, SG Lloyd, RS AF Vasquez, DA Nyaga, SG Lloyd, RS TI Purification and characterization of a novel UV lesion-specific DNA glycosylase/AP lyase from Bacillus sphaericus SO MUTATION RESEARCH-DNA REPAIR LA English DT Article DE pyrimidine dimer; glycosylase/AP lyase; Bacillus sphaericus ID T4 ENDONUCLEASE-V; BASE EXCISION-REPAIR; PYRIMIDINE DIMER; CATALYTIC MECHANISM; MICROCOCCUS-LUTEUS; ABASIC LYASE; CIS-SYN; SITE; T4-ENDONUCLEASE-V; ENZYME AB The purification and characterization of a pyrimidine dimer-specific glycosylase/AP lyase from Bacillus sphaericus (Bsp-pdg) are reported. Bsp-pdg is highly specific for DNA containing the cis-syn cyclobutane pyrimidine dimer, displaying no detectable activity on oligonucleotides with trans-syn I, trans-syn II, (6-4), or Dewar photoproducts. Like other glycosylase/AP lyases that sequentially cleave the N-glycosyl bond of the 5' pyrimidine of a cyclobutane pyrimidine dimer, and the phosphodiester backbone, this enzyme appears to utilize a primary amine as the attacking nucleophile. The formation of a covalent enzyme-DNA imino intermediate is evidenced by the ability to trap this protein-DNA complex by reduction with sodium borohydride. Also consistent with its AP lyase activity, Bsp-pdg was shown to incise an AP site-containing oligonucleotide, yielding beta- and delta-elimination products. N-terminal amino acid sequence analysis of this 26 kDa protein revealed little amino acid homology to any previously reported protein. This is the first report of a glycosylase/AP lyase enzyme from Bacillus sphaericus that is specific for ris-syn pyrimidine dimers. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA. Univ Texas, Med Branch, Sch Med, Galveston, TX 77555 USA. NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. RP Lloyd, RS (reprint author), Univ Texas, Med Branch, Sealy Ctr Mol Sci, Med Res Bldg,Room 5-142,301 Univ Blvd, Galveston, TX 77555 USA. FU NIEHS NIH HHS [ES06676, ES04091] NR 23 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD MAY 31 PY 2000 VL 459 IS 4 BP 307 EP 316 DI 10.1016/S0921-8777(00)00009-4 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 324FC UT WOS:000087610300005 PM 10844244 ER PT J AU Li, YL Li, HM Smith-Gill, SJ Mariuzza, RA AF Li, YL Li, HM Smith-Gill, SJ Mariuzza, RA TI Three-dimensional structures of the free and antigen-bound Fab from monoclonal antilysozyme antibody HyHEL-63 SO BIOCHEMISTRY LA English DT Article ID EGG-WHITE LYSOZYME; INFLUENZA-VIRUS NEURAMINIDASE; PROTEIN-PROTEIN RECOGNITION; SITE-DIRECTED MUTAGENESIS; DOUBLE MUTANT CYCLES; X-RAY-DIFFRACTION; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; ANGSTROM RESOLUTION; MUTATIONAL ANALYSIS AB Antigen-antibody complexes provide useful models for studying the structure and energetics of protein-protein interactions. We report the cloning, bacterial expression, and crystallization of the antigen-binding fragment (Fab) of the anti-hen egg white lysozyme (HEL) antibody HyHEL-63 in both free and antigen-bound forms. The three-dimensional structure of Fab HyHEL-63 complexed with I-IEL was determined to 2.0 Angstrom resolution, while the structure of the unbound antibody was determined in two crystal forms, to 1.8 and 2.1 Angstrom resolution. In the complex, 19 HyHEL-63 residues from all six complementarity-determining regions (CDRs) of the antibody contact 21 HEL residues from three discontinuous polypeptide segments of the antigen. The interface also includes 11 bound water molecules, 3 of which are completely buried in the complex. Comparison of the structures of foe and bound Fab HyHEL-63 reveals that several of the ordered water molecules in the free antibody-combining site are retained and that additional waters are added upon complex formation. The interface waters serve to increase shape and chemical complementarity by filling cavities between the interacting surfaces and by contributing to the hydrogen bonding network linking the antigen and antibody. Complementarity is further enhanced by small (<3 Angstrom) movements in the polypeptide backbones of certain antibody CDR loops, by rearrangements of side chains in the interface, and by a slight shift in the relative orientation of the VL and VH domains. The combining site residues of complexed Fab HyHEL-63 exhibit reduced temperature factors compared with those of the free Fab, suggesting a loss in conformational entropy upon binding. To probe the relative contribution of individual antigen residues to complex stabilization, single alanine substitutions were introduced in the epitope of HEL recognized by HyHEL-63, and their effects on antibody affinity were measured using surface plasmon resonance. In agreement with the crystal structure, HEL residues at the center of the interface that are buried in the complex contribute most to the binding energetics (Delta G(mutant) - Delta G(wild type) > 3.0 kcal/mol), whereas the apparent contributions of solvent-accessible residues at the periphery are much less pronounced (<1.5 kcal/mol). In the latter case, the mutations may be partially compensated by local rearrangements in solvent structure that help preserve shape complementarity and the interface hydrogen bonding network. C1 Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Mariuzza, RA (reprint author), Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. OI Li, Hongmin/0000-0002-8684-5308 FU NIGMS NIH HHS [GM5280] NR 60 TC 70 Z9 70 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 30 PY 2000 VL 39 IS 21 BP 6296 EP 6309 DI 10.1021/bi000054l PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 319YP UT WOS:000087374100004 PM 10828942 ER PT J AU Balajee, AS Bohr, VA AF Balajee, AS Bohr, VA TI Genomic heterogeneity of nucleotide excision repair SO GENE LA English DT Review DE cancer susceptibility and genomic instability; chromatin organization; cockayne syndrome; neurodegeneration; repair heterogeneity; transcription coupled repair; Xeroderma pigmentosum ID RNA-POLYMERASE-II; TRANSCRIPTION-COUPLED REPAIR; HAMSTER OVARY CELLS; CYCLOBUTANE PYRIMIDINE DIMERS; PIGMENTOSUM GROUP-C; COCKAYNES-SYNDROME CELLS; INDUCED DNA-DAMAGE; B GENE-PRODUCT; XERODERMA-PIGMENTOSUM; ESCHERICHIA-COLI AB Nucleotide excision repair (NER) is one of the major cellular pathways that removes bulky DNA adducts and helix-distorting lesions. The biological consequences of defective NER in humans include UV-light-induced skin carcinogenesis and extensive neurodegeneration. Understanding the mechanism of the NER process is of great importance as the number of individuals diagnosed with skin cancer has increased considerably in recent years, particularly in the United States. Rapid progress made in the DNA repair field since the early 1980s has revealed the complexity of NER, which operates differently in different genomic regions. The genomic heterogeneity of repair seems to be governed by the functional compartmentalization of chromatin into transcriptionally active and inactive domains in the nucleus. Two sub-pathways of NER remove UV-induced photolesions: (I) Global Genome Repair (GGR) and (II) Transcription Coupled Repair (TCR). GGR is a random process that occurs slowly, while the TCR, which is lightly linked to RNA polymerase II transcription, is highly specific and efficient. The efficiency of these pathways is important in avoiding cancer and genomic instability. Studies with cell lines derived from Cockayne syndrome (CS) and Xeroderma pigmentosum (XP) group C patients, that are defective in the NER sub-pathways, have yielded valuable information regarding the genomic heterogeneity of DNA repair. This review deals with the complexity of repair heterogeneity, its mechanism and interacting molecular pathways as well as its relevance in the maintenance of genomic integrity. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIA, Mol Genet Lab, Baltimore, MD 21224 USA. Columbia Univ Coll Phys & Surg, Dept Radiat Oncol, Ctr Radiol Res, New York, NY 10032 USA. RP Balajee, AS (reprint author), NIA, Mol Genet Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 160 TC 99 Z9 102 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 30 PY 2000 VL 250 IS 1-2 BP 15 EP 30 DI 10.1016/S0378-1119(00)00172-4 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 327PF UT WOS:000087769900002 PM 10854775 ER PT J AU Annab, LA Kouprina, N Solomon, G Cable, PL Hill, DE Barrett, JC Larionov, V Afshari, CA AF Annab, LA Kouprina, N Solomon, G Cable, PL Hill, DE Barrett, JC Larionov, V Afshari, CA TI Isolation of a functional copy of the human BRCA1 gene by transformation-associated recombination in yeast SO GENE LA English DT Article DE expression vectors; TAR cloning; tumor suppressor; YAC retrofitting ID CELL-CYCLE; ARTIFICIAL CHROMOSOMES; DNA-DAMAGE; CANCER CELLS; CLONING; EXPRESSION; BREAST; PHOSPHORYLATION; LOCALIZATION; INDUCTION AB The BRCA1 gene, mutations of which contribute significantly to hereditary breast cancer, was not identified in the existing YAC and BAC libraries. The gene is now available only as a set of overlapping fragments that form a contig. In this work we describe direct isolation of a genomic copy of BRCA1 from human DNA by transformation-associated recombination (TAR) cloning. Despite the presence of multiple repeats, most of the primary BRCA1 YAC isolates did not contain detectable deletions and could be stably propagated in a host strain with conditional RAD52. Similar to other circular YACs, similar to 90 kb BRCA1 YACs were efficiently and accurately retrofitted into bacterial artificial chromosomes (BACs) with the Neo(R) mammalian selectable marker and transferred as circular BAC/YACs in E. coli cells. The BRCA1 BAC/YAC DNAs were isolated from bacterial cells and were used to transfect mouse cells using the Neo(R) gene as selectable marker. Western blot analysis of transfectants showed that BRCA1 YACs isolated by a TAR cloning contained a functional gene. The advantage of this expression vector is that the expression of BRCA1 is generated from its own regulatory elements and does not require additional promoter elements that may result in overexpression of the protein. In contrast to the results with cDNA expression vectors, the level of BRCA1 expression from this TAR vector is stable, does not induce cell death, maintains serum regulation, and approximates the level of endogenously expressed BRCA1 in human cells. The entire isolation procedure of BRCA1 described in this paper can be accomplished in approximately 10 days and can be applied to isolation of gene from clinical material. We propose that the opportunity to directly isolate normal and mutant forms of BRCA1 will greatly facilitate analysis of the gene and its contribution to breast cancer: (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Oncogene Res Prod, Cambridge, MA 02142 USA. RP Larionov, V (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RI Hill, David/B-6617-2011 NR 30 TC 16 Z9 17 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 30 PY 2000 VL 250 IS 1-2 BP 201 EP 208 DI 10.1016/S0378-1119(00)00180-3 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 327PF UT WOS:000087769900020 PM 10854793 ER PT J AU Chandrasekhar, D Van Houten, B AF Chandrasekhar, D Van Houten, B TI In vivo formation and repair of cyclobutane pyrimidine dimers and 6-4 photoproducts measured at the gene and nucleotide level in Escherichia coli SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE gene-specific repair; strand-specific repair; DNA repair; Escherichia coli; cyclobutane pyramidine dimers; 6-4 photoproducts; UV light; QPCR; UV-induced mutations ID EXCISION-REPAIR; DNA DAMAGE; LACI GENE; ULTRAVIOLET-LIGHT; UV LIGHT; MUTAGENIC SPECIFICITY; MUTATION HOTSPOTS; MAMMALIAN-CELLS; ACTIVE GENE; DHFR GENE AB In vivo formation and repair of the major UV-induced DNA photoproducts, cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidone photoproducts (6-4 PPs), have been examined at the gene and nucleotide level in Escherichia coli. Each type of DNA photoproduct has individually been studied using photoreactivation and two newly developed assays; the multiplex QPCR assay for damage detection at the gene level and the reiterative primer extension (PE) assay for damage detection at the nucleotide level, In the E. coli lacI and lacZ genes, CPDs and 6-4 PPs form in a 2:1 ratio, respectively, during UV irradiation. Repair of 6-4 PPs is more efficient than repair of CPDs since, on the average, 42% of 6-4 PPs are repaired in both genes in the first 40 min following 200 J/m(2) UV irradiation, while 1% of CPDs are repaired. The location, relative frequency of formation, and efficiency of repair of each type of photoproduct was examined in the first 52 codons of the E. coli lacI gene at the nucleotide level. Hotspots of formation were found for each type of lesion. Most photoproducts are at sites where both CPDs and 6-4 PPs are formed. Allowing 40 min of recovery following 200 J/m(2) shows that in vivo repair of 6-4 PPs is about fourfold more efficient than the repair of CPDs. Comparison of the lesion-specific photoproduct distribution of the lad gene with a UV-induced mutation spectrum from wild-type cells shows that most mutational hotspots are correlated with sites of a majority of CPD formation. However, 6-4 PPs are also formed at some of these sites with relatively high frequency. This information, taken together with the observation that 6-4 PPs are repaired faster than CPDs, suggest that the cause of mutagenic hotspots in wild-type E. coli is inefficient repair of CPDs. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Van Houten, B (reprint author), NIEHS, Mol Genet Lab, NIH, 111 Alexander Dr,Box 12233, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [ES07218, ES07122] NR 49 TC 32 Z9 32 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 30 PY 2000 VL 450 IS 1-2 SI SI BP 19 EP 40 DI 10.1016/S0027-5107(00)00014-2 PG 22 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 323DL UT WOS:000087549500003 PM 10838132 ER PT J AU Canella, KA Seidman, MM AF Canella, KA Seidman, MM TI Mutation spectra in supF: approaches to elucidating sequence context effects SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE mutation; custom marker genes; sequence context; supF shuttle vector ID SHUTTLE VECTOR PLASMID; XERODERMA-PIGMENTOSUM VARIANT; THYMINE-THYMINE DIMER; ESCHERICHIA-COLI PLASMID; TRIPLE-HELIX FORMATION; SIMPLEX VIRUS TYPE-1; YEAST DNA-POLYMERASE; TRANSFER-RNA GENE; MAMMALIAN-CELLS; IN-VIVO AB Shuttle vectors carrying the supF suppressor tRNA gene were originally developed for mutagenesis experiments in primate and human cells. Since then, the supF gene has been used as a mutation reporter in other mammalian cells, yeast, Escherichia coli, and transgenic mice. The widespread use of the vector for studies of many DNA reactive agents has produced a large database of mutation spectra. These provide primary information on the kinds and distribution of mutations provoked by many agents and, in many instances, allow comparisons between related agents or the same agent in different cell backgrounds. In this review we will discuss some of these data with a primary focus on the interpretation of UV mutation spectra. We will also describe our development and application of custom supF marker genes as an approach to studying the effect of sequence context on mutation hotspots and cold spots. Our studies suggest that C-C photoproducts are not mutagenic in certain sequence contexts in which T-C photoproducts are mutation hotspots. In addition, we have found several examples of sequence context effects acting as much as 80 bases away from the site of mutation. We will consider some of the problems raised by these studies and the possible resolution of some of them offered by the newly discovered family of damage bypass DNA polymerases. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Seidman, MM (reprint author), NIA, Mol Genet Lab, NIH, Rm 2E18,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 127 TC 47 Z9 48 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 30 PY 2000 VL 450 IS 1-2 SI SI BP 61 EP 73 DI 10.1016/S0027-5107(00)00016-6 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 323DL UT WOS:000087549500005 PM 10838134 ER PT J AU Bigger, CAH Ponten, I Page, JE Dipple, A AF Bigger, CAH Ponten, I Page, JE Dipple, A TI Mutational spectra for polycyclic aromatic hydrocarbons in the supF target gene SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE pS189; pSP189; supF; shuttle vector; sequence specificity; polymerase stop assay; site-specific mutagenesis; dihydrodiol epoxide; DNA adduct; benzo[c]phenanthrene; benzo[a]pyrene; 5-methychrysene; 5,6-dimethylchrysene; 7-methylbenz[a]anthracene; benzo[g]chrysene; 7-bromomethylbenz[a]anthracene; 7-bromomethyl-12-methylbenz[a]anthracene ID BENZOPHENANTHRENE DIHYDRODIOL EPOXIDES; (+)-ANTI-BENZOPYRENE DIOL EPOXIDE; SITE-SPECIFIC MUTAGENESIS; SINGLE-STRANDED VECTOR; EMBRYO CELL-CULTURES; ESCHERICHIA-COLI; SEQUENCE CONTEXT; SHUTTLE-VECTOR; DNA-ADDUCTS; 1,2-DIHYDRODIOL 3,4-EPOXIDE AB An SV40-based shuttle vector system was used to identify the types of mutational changes and the sites of mutation within the supF DNA sequence generated by the four stereoisomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide (B[c]PhDE), by racemic mixtures of bay or fjord region dihydrodiol epoxides (DE) of 5-methylchrysene, of 5,6-dimethylchrysene, of benzo[g]chrysene and of 7-methylbenz[a]anthracene and by two direct acting polycyclic aromatic hydrocarbon carcinogens, 7-bromomethylbenz[a]anthracene (7-BrMeBA) and 7-bromomethyl-12-methylbenz[a]anthracene (7-BrMe-12- MeBA). The results of these studies demonstrated that the predominant type of mutation induced by these compounds is the base substitution. The chemical preference for reaction at deoxyadenosine (dAdo) or deoxyguanosine (dGuo) residues in DNA, which is in general correlated with the spatial structure (planar or non-planar) of the reactive polycyclic aromatic hydrocarbon, is reflected in the preference for mutation at A . T or G . C pairs. In addition, if the ability to react with DNA in vivo is taken into account, the relative mutagenic potencies of the B[c]PhDE stereoisomers are consistent with the higher tumorigenic activity associated with non-planar polycyclic aromatic hydrocarbons and their extensive reaction with dAdo residues in DNA. Comparison of the types of mutations generated by polycyclic aromatic hydrocarbons and other bulky carcinogens in this shuttle vector system suggests that all bulky lesions may be processed by a similar mechanism related to that involved in replication past apurinic sites. However, inspection of the distribution of mutations over the target gene induced by the different compounds' demonstrated that individual polycyclic aromatic hydrocarbons induce unique patterns of mutational hotspots within the target gene. A polymerase arrest assay was used to determine the sequence specificity of the interaction of reactive polycyclic aromatic hydrocarbons with the shuttle vector DNA. The results of these assays revealed a divergence between mutational hotspots and polymerase arrest sites for all compounds investigated, i.e., sites of mutational hotspots do not correspond to sites where high levels of adduct formation occur, and suggested that some association between specific adducts and sequence context may be required to constitute a premutagenic lesion. A site-specific mutagenesis system employing a single-stranded vector (M13mp7L2) was used to investigate the mutational events a single benzo[a]pyrene or benzo[c]phenanthrene dihydrodiol epoxide-DNA adduct elicits within specific sequence contexts. These studies showed that sequence context can cause striking differences in mutagenic frequencies for given adducts. In addition, these sequence context effects do not originate only from nucleotides immediately adjacent to the adduct, but are also modulated by more distal nucleotides. The implications of these results for mechanisms of polycyclic aromatic hydrocarbon-induced mutagenesis and carcinogenesis are discussed. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NCI, Chem Carcinogenesis Lab, Basic Res Program, Adv Biosci Labs,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Bigger, CAH (reprint author), US FDA, Ctr Drug Evaluat & Res HFD530, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 77 TC 24 Z9 25 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 30 PY 2000 VL 450 IS 1-2 SI SI BP 75 EP 93 DI 10.1016/S0027-5107(00)00017-8 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 323DL UT WOS:000087549500006 PM 10838135 ER PT J AU Berger, VW AF Berger, VW TI Pros and cons of permutation tests in clinical trials SO STATISTICS IN MEDICINE LA English DT Article ID ENRICHMENT; DESIGN AB Hypothesis testing, in which the null hypothesis specifies no difference between treatment groups, is an important tool in the assessment of new medical interventions. For randomized clinical trials, permutation tests that reflect the actual randomization are design-based analyses for such hypotheses. This means that only such design-based permutation tests can ensure internal validity, without which external validity is irrelevant. However, because of the conservatism of permutation tests, the virtues of permutation tests continue to be debated in the literature, and conclusions are generally of the type that permutation tests should always be used or permutation tests should never be used. A better conclusion might be that there are situations in which permutation tests should be used, and other situations in which permutation tests should not be used. This approach opens the door to broader agreement, but begs the obvious question of when to use permutation tests. We consider this issue from a variety of perspectives, and conclude that permutation tests are ideal to study efficacy in a randomized clinical trial which compares, in a heterogeneous patient population, two or more treatments, each of which may be most effective in some patients, when the primary analysis does not adjust for covariates. We propose the p-value interval as a novel measure of the conservatism of a permutation test that can be defined independently of the significance level. This p-value interval can be used to ensure that the permutation test have both good global power and an acceptable degree of conservatism. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Div Canc Prevent, Execut Plaza N,Suite 344, Bethesda, MD 20892 USA. FU DRS NIH HHS [RSR-96-004A] NR 28 TC 68 Z9 72 U1 1 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 30 PY 2000 VL 19 IS 10 BP 1319 EP 1328 DI 10.1002/(SICI)1097-0258(20000530)19:10<1319::AID-SIM490>3.3.CO;2-S PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 314NN UT WOS:000087062300005 PM 10814980 ER PT J AU Park, E Lee, YJ AF Park, E Lee, YJ TI Non-parametric test of ordered alternatives in incomplete blocks SO STATISTICS IN MEDICINE LA English DT Article AB Often in medical studies, study subjects become a natural block of observations repeated over a time period. Some subjects miss observations, thus becoming incomplete blocks of observations. We are interested in testing an ordered alternative (or time trend), and propose a non-parametric method to detect a trend in incomplete blocks. Our approach is to estimate the trend by the linear regression method within each block and apply the one-sample Wilcoxon test to the estimated linear trends. The one-sample Wilcoxon test will be sensitive to the trend if it exists. The proposed test statistic is asymptotically normal and consistent. We can also estimate the overall magnitude of the linear trend and its confidence interval by a proper non-parametric method. By Monte Carlo studies, we compare the performance of the proposed test against extended Page and Jonckheere tests. Published in 2000 by John Wiley & Sons, Ltd. C1 NIH, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. RP Lee, YJ (reprint author), Hanyang Univ, Sungdong Ku, 17 Hangdang Dong, Seoul 133791, South Korea. NR 8 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 30 PY 2000 VL 19 IS 10 BP 1329 EP 1337 DI 10.1002/(SICI)1097-0258(20000530)19:10<1329::AID-SIM483>3.0.CO;2-S PG 9 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 314NN UT WOS:000087062300006 PM 10814981 ER PT J AU Shields, DC Ramsbottom, D Donoghue, C Pinjon, E Kirke, PN Molloy, AM Edwards, YH Mills, JL Mynett-Johnson, L Weir, DG Scott, JM Whitehead, AS AF Shields, DC Ramsbottom, D Donoghue, C Pinjon, E Kirke, PN Molloy, AM Edwards, YH Mills, JL Mynett-Johnson, L Weir, DG Scott, JM Whitehead, AS TI Association between historically high frequencies of neural tube defects and the human T homologue of mouse T (Brachyury) SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE genetics; folate; MTHFR; spina bifida ID METHYLENETETRAHYDROFOLATE REDUCTASE; THERMOLABILE VARIANT; SPINA-BIFIDA; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; FOLATE STATUS; GENES; RISK; T(BRACHYURY); PREGNANCIES; METABOLISM AB The human T developmental gene has been implicated in the etiology of neural tube defects (NTDs) on the basis both of mouse studies of its homologue, T (Brachyury), and of allelic association in a Caucasian population. We have investigated the frequency of the T allelic variant TIVS7-2 in 218 Irish NTD case-parent triads, This population showed the same trend as previously reported, with an excess of the TIVS7-2 allele among cases. Log-linear modeling of case and maternal genotypic effects within families indicated that TIVS7-2 was elevated in cases (relative risk, RR = 1.36) but not in mothers (RR = 0,91), The TIVS7-2 allele is markedly associated with cases born before 1980 (RR = 2.09; CI = 1.23-3.55; corrected p = 0.030), but not with more recent cases (RR = 0.92). Cases carrying a TIVS7-2 allele did not show any increased tendency to be homozygous for the thermolabile variant of the folate-dependent enzyme 5,10-methylene tetrahydrofolate reductase, which is an established genetic risk factor for NTDs. Since the incidence of NTDs has declined markedly in Ireland over the last few decades, we suggest that the T-associated risk is potentiated by nutritional or environmental risk factor(s), the impact of which have been diminishing over time. Am. J, Med, Genet. 92:206-211, 2000, (C) 2000 Wiley-Liss, Inc. C1 Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Pharmacogenet, Philadelphia, PA 19104 USA. Royal Coll Surgeons Ireland, Dept Clin Pharmacol, Dublin 2, Ireland. Trinity Coll Dublin, Dept Genet, Dublin, Ireland. Hlth Res Board, Dublin, Ireland. Trinity Coll Dublin, Dept Clin Med, Dublin, Ireland. UCL, MRC, Human Biochem Genet Unit, London, England. NICHHD, Bethesda, MD 20892 USA. Trinity Coll Dublin, Dept Biochem, Dublin, Ireland. RP Whitehead, AS (reprint author), Univ Penn, Sch Med, Dept Pharmacol, 153 Johnson Pavil,3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM aswhitehead@pharm.med.upenn.edu NR 31 TC 17 Z9 18 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 29 PY 2000 VL 92 IS 3 BP 206 EP 211 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 307VM UT WOS:000086674900009 PM 10817656 ER PT J AU Mori, I Yasuhara, K Hayashi, S Nonoyama, T Nomura, T Mitsumori, K AF Mori, I Yasuhara, K Hayashi, S Nonoyama, T Nomura, T Mitsumori, K TI Carcinogen dose-dependent variation in the transgene mutation spectrum in urethane-induced lung tumors in transgenic mice carrying the human prototype c-Ha-ras gene SO CANCER LETTERS LA English DT Article DE rasH2 mice; urethane; human prototype c-Ha-ras; mouse c-Ki-ras ID ETHYL CARBAMATE URETHANE; CHEMICALLY-INDUCED LUNG; VINYL CARBAMATE; B6C3F1 MOUSE; A/J MICE; ACTIVATION; PROTOONCOGENE; ONCOGENES; DNA; METABOLITE AB Urethane-induced lung tumors and their genetic changes were investigated in transgenic (Tg) mice carrying a human prototype c-Ha-ras gene (rasH2 mice). Male and female rasH2 mice and non-transgenic (non-Tg) littermates were injected intraperitoneally with 1000 mg/kg of urethane once or three times at 2-day intervals. Hyperplasias and adenomas of the lung were observed in all animals of each group from week 10, and carcinomas were observed in male and female rasH2 mice of the triple injection group from week 10 and female non-Tg mice of the single injection group at 15/20 weeks. The multiplicities of lung proliferative lesions including hyperplasias. adenomas and carcinomas, in treated rasH2 mice were significantly higher than those in treated non-Tg mice. CAG to CTG transversions were observed in the c-Ha-ras gene in these lung proliferative lesions of rasH2 mice of the single injection group at high incidence (male: 58.3%. female: 62.5%), but no mutations of the mouse c-Ki-ras gene were evident in either rasH2 or non-Tg mice. In the triple injection group, transgene mutations were detected at a relatively low incidence, and mouse c-Ki-ras gene mutations(CAA to CGA) were observed in both rasH2 and non-Tg mice, These results suggest that the variation of the lesions induced by different doses of urethane was not the cause of the variation of the mutation spectrum and mutations of both transgene and mouse c-K-ras gene are not principal genetic events in urethane-induced lung proliferative lesions in rasH2 mice, (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Takeda Chem Ind Ltd, Drug Anal & Pharmacokinet Res Labs, Yodogawa Ku, Osaka 5328686, Japan. Natl Inst Hlth Sci, Div Pathol, Setagaya Ku, Tokyo 1588501, Japan. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Takeda Chem Ind Ltd, Drug Safety Res Labs, Yodogawa Ku, Osaka 5328686, Japan. Cent Inst Expt Anim, Kawasaki, Kanagawa 2160001, Japan. RP Mori, I (reprint author), Takeda Chem Ind Ltd, Drug Anal & Pharmacokinet Res Labs, Yodogawa Ku, C-81,2-17-85 Juso Honmachi, Osaka 5328686, Japan. NR 34 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 29 PY 2000 VL 153 IS 1-2 BP 199 EP 209 DI 10.1016/S0304-3835(00)00372-4 PG 11 WC Oncology SC Oncology GA 396WV UT WOS:000166661600028 PM 10779650 ER PT J AU Shen, WP Proost, P Li, BQ Gong, WH Le, YY Sargeant, R Murphy, PM Van Damme, J Wang, JM AF Shen, WP Proost, P Li, BQ Gong, WH Le, YY Sargeant, R Murphy, PM Van Damme, J Wang, JM TI Activation of the chemotactic peptide receptor FPRL1 in monocytes phosphorylates the chemokine receptor CCR5 and attenuates cell responses to selected chemokines SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE FPRL1; CCR5; desensitization; phosphorylation; V3 peptide; chemotaixs; Ca2+ flux ID LIPOXIN A(4) RECEPTOR; PROTEIN-COUPLED RECEPTOR; SERUM AMYLOID-A; V3 LOOP; IDENTIFICATION; HIV-1; GP120; 7-TRANSMEMBRANE; MOBILIZATION; PHAGOCYTES AB FPRL1 is a seven-transmembrane (STM), G-protein coupled receptor which was originally identified as a low affinity receptor for the bacterial chemotactic formyl peptide and a high affinity receptor for the Lipid metabolite lipoxin A4. me recently discovered that a number of peptides, including several synthetic domains of the HIV-1 envelope proteins and the serum amyloid A, use FPRL1 to induce migration and calcium mobilization in human monocytes and neutrophils. In this study, we report that a synthetic peptide domain of the V3 region of the HIV-1 envelope gp120, activates the FPRL1 receptor in monocytes and neutrophils. Furthermore, monocytes prestimulated with V3 peptide showed reduced response to several chemokines that use multiple cell receptors. This is associated with a rapid phosphorylation of the chemokine receptor CCR5 on the serine residues. Our study suggests that FPRL1, as a classical chemoattractant receptor, may play an important role in modulating monocyte activation in the presence of multiple stimuli. (C) 2000 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Mol Immunoregulat Lab, Frederick, MD 21701 USA. Katholieke Univ Leuven, Rega Inst, Lab Mol Immunol, Louvain, Belgium. NCI, Frederick Canc Res & Dev Ctr, SAIC, Intramural Res Support Program, Frederick, MD 21702 USA. ProSci Inc, Prod Dev, Poway, CA 92064 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Wang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Mol Immunoregulat Lab, Bldg 560,Room 31-40, Frederick, MD 21701 USA. FU NCI NIH HHS [N01-CO-56000] NR 34 TC 37 Z9 39 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 27 PY 2000 VL 272 IS 1 BP 276 EP 283 DI 10.1006/bbrc.2000.2770 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 320AM UT WOS:000087378900046 PM 10872839 ER PT J AU Qiu, CY Sora, I Ren, K Uhl, G Dubner, R AF Qiu, CY Sora, I Ren, K Uhl, G Dubner, R TI Enhanced delta-opioid receptor-mediated antinociception in mu-opioid receptor-deficient mice (vol 387, pg 163, 2000) SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Correction C1 Univ Maryland, Sch Dent, Dept Oral & Craniofacial Biol Sci, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sch Med, NIDA, IRP, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol & Neurosci, Baltimore, MD 21224 USA. RP Dubner, R (reprint author), Univ Maryland, Sch Dent, Dept Oral & Craniofacial Biol Sci, Room 5E-08,666 W Baltimore St, Baltimore, MD 21201 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAY 26 PY 2000 VL 397 IS 1 BP 227 EP 227 DI 10.1016/S0014-2999(00)00203-X PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 320VL UT WOS:000087421500027 ER PT J AU Itkes, A Allegra, CJ Zajac-Kaye, M AF Itkes, A Allegra, CJ Zajac-Kaye, M TI Multiprotein complexes present at the MIF motifs flanking the promoter of the human c-myc gene SO FEBS LETTERS LA English DT Article DE transcription; c-myc; intron; myc intron binding polypeptide; RFX1 ID HEPATITIS-B VIRUS; DNA-BINDING PROTEIN; ENHANCER-I; SV40 ENHANCER; RFX1; INTRON; TRANSACTIVATOR; ORGANIZATION; ELEMENT; REGIONS AB The activated C-myc allele in Burkitt's lymphoma is associated,vith a clustering of somatic mutations within a discrete domain of intron I that define protein recognition sequences, designated as myc intron factors (MIF-1, MIF-2 and MIF-3). We have previously shown that MIF-1 binding activity consists of two polypeptides, myc intron binding polypeptide (MIBP1) and RFX1, In the present study we identified two polypeptides, p105 and p115, and showed that these proteins give rise to a DNA-protein complex at the MIF-2 as well as the adjacent MIF-1 site. In addition, we demonstrated that all four proteins interact with a navel MIF-I like motif upstream from the c-myc promoter region, designated 5'MTF, These data suggest a model, where the interactions of MIBP1/RFX1 and p105/p115 with the MIF-like sites may play a role in the promoter topology of the c-myc gene. (C) 2000 Federation of European Biochemical Societies. C1 Naval Hosp, NCI, Navy Oncol Branch, Div Clin Sci,Med Branch,Dept Dev Therapeut, Bethesda, MD 20889 USA. RP Zajac-Kaye, M (reprint author), Naval Hosp, NCI, Navy Oncol Branch, Div Clin Sci,Med Branch,Dept Dev Therapeut, Bldg 8,R 5101, Bethesda, MD 20889 USA. EM kayem@exchange.nih.gov NR 27 TC 4 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 26 PY 2000 VL 474 IS 1 BP 23 EP 28 DI 10.1016/S0014-5793(00)01562-3 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 320YB UT WOS:000087427500005 PM 10828444 ER PT J AU Hanada, K Hara, T Nishijima, M AF Hanada, K Hara, T Nishijima, M TI D-Serine inhibits serine palmitoyltransferase, the enzyme catalyzing the initial step of sphingolipid biosynthesis SO FEBS LETTERS LA English DT Article DE D-serine; serine palmitoyltransferase; sphingolipid ID CLONING; LCB1; GENE; SACCHAROMYCES; RACEMASE; LIVER AB Serine palmitoyltransferase (SPT), responsible for the initial step of sphingolipid biosynthesis, catalyzes condensation of palmitoyl coenzyme A and L-serine to produce 3-ketodihydrosphingosine (KDS), For determination of the stereochemical specificity of the amino acid substrate, a competition analysis of the production of [H-3]KDS from L-[H-3]serine was performed using purified SPT, D-Serine inhibited [H-3]KDS production as effectively as non-radioactive L-serine, whereas neither D-alanine nor D-threonine showed any significant effect. Incubation of purified SPT with [palmitoyl 1-C-14]palmitoyl coenzyme A and D-serine did not produce [C-14]KDS, while the control incubation with L-serine did. These results suggest that D-serine competes with L-serine for the amino acid recognition site of SPT, but that D-serine is not utilized by this enzyme to produce KDS, (C) 2000 Federation of European Biochemical Societies. C1 NIAID, Dept Biochem & Cell Biol, Shinjuku Ku, Tokyo 1628640, Japan. NIAID, Japan Sci & Technol Corp, CREST, Shinjuku Ku, Tokyo 1628640, Japan. RP Hanada, K (reprint author), NIAID, Dept Biochem & Cell Biol, Shinjuku Ku, 1-23-1 Toyama, Tokyo 1628640, Japan. NR 17 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 26 PY 2000 VL 474 IS 1 BP 63 EP 65 DI 10.1016/S0014-5793(00)01579-9 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 320YB UT WOS:000087427500013 PM 10828452 ER PT J AU Zhang, M Zhao, X Chen, HC Catt, KJ Hunyady, L AF Zhang, M Zhao, X Chen, HC Catt, KJ Hunyady, L TI Activation of the AT(1) angiotensin receptor is dependent on adjacent apolar residues in the carboxyl terminus of the third cytoplasmic loop SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; MUSCARINIC ACETYLCHOLINE-RECEPTOR; HUMAN BETA-2-ADRENERGIC RECEPTOR; 3RD INTRACELLULAR LOOP; II TYPE-1 RECEPTOR; SIGNAL-TRANSDUCTION; AMINO-ACID; CONSTITUTIVE ACTIVATION; BINDING-SITE; RAT AT(1A) AB The C-terminal region of the third intracellular loop of the AT(1) angiotensin receptor (AT(1)-R) is an important determinant of G protein coupling. The roles of individual residues in agonist-induced activation of G(q/11)-dependent phosphoinositide hydrolysis were determined by mutational analysis of the amino acids in this region. Functional studies on mutant receptors transiently expressed in COS-7 cells showed that alanine substitutions of the amino acids in positions 232-240 of the third loop had no major effect on signal generation. However, deletion mutations that removed Ile(238) or affected its position relative to transmembrane helix VI significantly impaired angiotensin II-induced inositol phosphate responses. Substitution of Ile(238) with an acidic residue abolished the ability of the receptor to mediate inositol phosphate production, whereas its replacement with basic or polar residues reduced the amplitude of inositol phosphate responses. Substitutions of Phe(239) with polar residues had relatively minor effects on inositol phosphate signal generation, but its replacement by aspartic acid reduced, and by positively charged residues (Lys, Arg) significantly increased, angiotensin II-induced inositol phosphate responses. The internalization kinetics of the Ile(238) and Phe239 mutant receptors were impaired in parallel with the reduction in their signaling responses. These findings have identified Ile238 and Phe239 as the critical residues in the C-terminal region of the third intracellular loop of the AT(1)-R for receptor activation. They also suggest that an apolar amino acid corresponding to Ile(238) of the AT(1)-R is a general requirement for activation of other G protein-coupled receptors by their agonist ligands. C1 Semmelweis Univ, Sch Med, Dept Physiol, H-1444 Budapest, Hungary. NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Hunyady, L (reprint author), Semmelweis Univ, Sch Med, Dept Physiol, POB 259, H-1444 Budapest, Hungary. NR 43 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 26 PY 2000 VL 275 IS 21 BP 15782 EP 15788 DI 10.1074/jbc.M000198200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 318NX UT WOS:000087291400026 PM 10747880 ER PT J AU Rausch, JW Sathyanarayana, BK Bona, MK Le Grice, SFJ AF Rausch, JW Sathyanarayana, BK Bona, MK Le Grice, SFJ TI Probing contacts between the ribonuclease H domain of HIV-1 reverse transcriptase and nucleic acid by site-specific photocross-linking SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; C-TERMINAL DOMAIN; CROSS-LINKING; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; FOOTPRINT ANALYSIS; STRAND TRANSFER; DNA COMPLEX; PRIMER GRIP; PROTEIN AB Cys(38) and Cys(280) Of p66/p51 human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) can be converted to Ser without affecting enzyme function. We have exploited this feature to construct and purify "monocysteine" RT derivatives for site-specific modification with the photoactivable cross-linking agent, p-azidophenacyl bromide. Acylation of a unique cysteine residue introduced at the extreme C terminus of the p66 subunit (C-561) With an azidophenacyl group allowed us to probe contacts between residues C-terminal to alpha-helix E' of the RNase H domain and structurally divergent nucleic acid duplexes. In a binary complex of RT and template-primer, we demonstrate efficient cross-linking to primer nucleotides -21 to -24/-25, and template nucleotides -18 to -21, Cross-linking specificity was confirmed by an analogous evaluation following limited primer extension, where the profile is displaced by the register of DNA synthesis. Finally, contact with a DNA primer hybridized to an isogenic RNA or DNA template indicates subtle alterations in cross-linking specificity, suggesting differences in nucleic acid geometry between duplex DNA and RNA/DNA hybrids at the RNase H domain. These data exemplify how site-specific acylation of HIV-1 RT can be used to provide high resolution structural data to complement crystallographic studies. C1 Natl Canc Inst, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Frederick, MD 21072 USA. Natl Canc Inst, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21072 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Le Grice, SFJ (reprint author), Natl Canc Inst, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Frederick, MD 21072 USA. FU NIGMS NIH HHS [GM 52263] NR 40 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 26 PY 2000 VL 275 IS 21 BP 16015 EP 16022 DI 10.1074/jbc.M909808199 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 318NX UT WOS:000087291400056 PM 10748161 ER PT J AU Gong, DW Monemdjou, S Gavrilova, O Leon, LR Marcus-Samuels, B Chou, CJ Everett, C Kozak, LP Li, CL Deng, CX Harper, ME Reitman, ML AF Gong, DW Monemdjou, S Gavrilova, O Leon, LR Marcus-Samuels, B Chou, CJ Everett, C Kozak, LP Li, CL Deng, CX Harper, ME Reitman, ML TI Lack of obesity and normal response to fasting and thyroid hormone in mice lacking uncoupling protein-3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BROWN-ADIPOSE-TISSUE; SKELETAL-MUSCLE; MITOCHONDRIAL CARRIER; PROTON TRANSPORT; UP-REGULATION; BODY-WEIGHT; EXPRESSION; FAT; THERMOGENESIS; GENE AB Uncoupling protein-3 (UCP3) is a mitochondrial protein that can diminish the mitochondrial membrane potential. Levels of muscle Ucp3 mRNA are increased by thyroid hormone and fasting. Ucp3 has been proposed to influence metabolic efficiency and is a candidate obesity gene. We have produced a Ucp3 knockout mouse to test these hypotheses. The Ucp3 (-/-) mice had no detectable immunoreactive UCP3 by Western blotting. In mitochondria from the knockout mice, proton leak was greatly reduced in muscle, minimally reduced in brown fat, and not reduced at all in liver. These data suggest that UCP3 accounts for much of the proton leak in skeletal muscle. Despite the lack of UCP3, no consistent phenotypic abnormality was observed. The knockout mice were not obese and had normal serum insulin, triglyceride, and leptin levels, with a tendency toward reduced free fatty acids and glucose. Knockout mice showed a normal circadian rhythm in body temperature and motor activity and had normal body temperature responses to fasting, stress, thyroid hormone, and cold exposure. The base-line metabolic rate and respiratory exchange ratio were the same in knockout and control mice, as were the effects of fasting, a beta 3-adrenergic agonist (CL316243), and thyroid hormone on these parameters. The phenotype of Ucp1/Ucp3 double knockout mice was indistinguishable from Ucp1 single knockout mice. These data suggest that Ucp3 is not a major determine. These data suggest that Ucp3 is not a major determinant of metabolic rate but, rather, has other functions. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada. Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. NIDDK, Mammalian Genet Sect, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Harper, ME (reprint author), NIDDK, Diabet Branch, NIH, Bldg 10,Rm 8N-250, Bethesda, MD 20892 USA. RI Reitman, Marc/B-4448-2013; deng, chuxia/N-6713-2016; OI Reitman, Marc/0000-0002-0426-9475; Harper, Mary-Ellen/0000-0003-3864-5886; Monemdjou, Shadi/0000-0002-5809-595X NR 56 TC 298 Z9 301 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 26 PY 2000 VL 275 IS 21 BP 16251 EP 16257 DI 10.1074/jbc.M910177199 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 318NX UT WOS:000087291400087 PM 10748195 ER PT J AU Yun, CW Tiedeman, JS Moore, RE Philpott, CC AF Yun, CW Tiedeman, JS Moore, RE Philpott, CC TI Siderophore-iron uptake in Saccharomyces cerevisiae - Identification of ferrichrome and fusarinine transporters SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAJOR FACILITATOR SUPERFAMILY; FET3 GENE; YEAST; PROTEIN; MECHANISMS; PATHWAYS; PERMEASE; ENCODES; FUNGI; CYCLE AB A family of four putative transporters (Arn1p-4p) in Saccharomyces cerevisiae is expressed under conditions of iron deprivation and is regulated by Aft1p, the major iron-dependent transcription factor in yeast. One of these, Arn3p/Sit1p, facilitates the uptake of ferrioxamine B, a siderophore of the hydroxamate class. Here we report that ARN family members facilitated the uptake of iron from the trihydroxamate siderophores ferrichrome, ferrichrome A, and triacetylfusarinine C. Uptake of siderophore-bound iron was dependent on either the high-affinity ferrous iron transport system or the ARN family of transporters. The specificity of each siderophore for individual transporters was determined. Uptake of ferrichrome and ferrichrome A was facilitated by both Arn1p and Arn3p. Uptake of triacetylfusarinine C was facilitated by Arn2p, although small amounts of uptake also occurred through Arn1p and Arn3p. In contrast to the trihydroxamates, uptake of iron from the dihydroxamate rhodotorulic acid occurred only via the high-affinity ferrous iron system. Epitope-tagged Arn1p was expressed in intracellular vesicles in a pattern that was indistinguishable from that of Arn3p, whereas Ftr1p, a component of the high-affinity ferrous system, was expressed on the plasma membrane. These data indicate that S. cerevisiae maintains two systems of siderophore uptake, only one of which is located on the plasma membrane. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Chem, Oshkosh, WI 54901 USA. RP NIDDK, Liver Dis Sect, NIH, Bldg 10,Rm 9B16,10 Ctr Dr, Bethesda, MD 20892 USA. EM carolinep@intra.niddk.nih.gov NR 36 TC 109 Z9 113 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 26 PY 2000 VL 275 IS 21 BP 16354 EP 16359 DI 10.1074/jbc.M001456200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 318NX UT WOS:000087291400101 PM 10748025 ER PT J AU Debrabant, A Ghedin, E Dwyer, DM AF Debrabant, A Ghedin, E Dwyer, DM TI Dissection of the functional domains of the Leishmania surface membrane 3 '-nucleotidase/nuclease, a unique member of the class I nuclease family SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DONOVANI PROMASTIGOTES; GENE; 5'-NUCLEOTIDASE; LOCALIZATION; PURIFICATION; TRYPANOSOMA; AMASTIGOTES; EXPRESSION; RESOLUTION; CLONING AB Class I nucleases are a family of enzymes that specifically hydrolyze single-stranded nucleic acids. Recently, we characterized the gene encoding a new member of this family, the 3'-nucleotidase/nuclease (Ld3'NT/NU) of the parasitic protozoan Leishmania donovani. The Ld3'NT/NU is unique as it is the only class I nuclease that is a cell surface membrane-anchored protein. Currently, we used a homologous episomal expression system to dissect the functional domains of the Ld3'NT/NU. Our results showed that its N-terminal signal peptide targeted this protein into the endoplasmic reticulum, Using Ld3'NT/NU-green fluorescent protein chimeras, we showed that the C-terminal domain of the Ld3'NT/NU functioned to anchor this protein into the parasite cell surface membrane. Further, removal of the Ld3'NT/NU C-terminal domain resulted in its release/secretion as a fully active enzyme. Moreover, deletion of its single N-linked glycosylation site showed that such glycosylation was not required for the enzymatic functions of the Ld3'NT/NU. Thus, using the fidelity of a homologous expression system, we have defined some of the functional domains of this unique member of the class I nuclease family. C1 NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Dwyer, DM (reprint author), NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. NR 25 TC 41 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 26 PY 2000 VL 275 IS 21 BP 16366 EP 16372 DI 10.1074/jbc.M908725199 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 318NX UT WOS:000087291400103 PM 10748102 ER PT J AU Hu, HM Tian, Q Baer, M Spooner, CJ Williams, SC Johnson, PF Schwartz, RC AF Hu, HM Tian, Q Baer, M Spooner, CJ Williams, SC Johnson, PF Schwartz, RC TI The C/EBP bZIP domain can mediate lipopolysaccharide induction of the proinflammatory cytokines interleukin-6 and monocyte chemoattractant protein-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; ENHANCER-BINDING-PROTEIN; LYMPHOBLASTIC CELL-LINE; LEUCINE-ZIPPER; TRANSCRIPTIONAL ACTIVATION; MESSENGER-RNA; GROWTH-FACTOR; BETA ISOFORM; GENE; EXPRESSION AB C/EBP alpha, beta, and delta are all expressed by bone marrow-derived macrophages, Ectopic expression of any of these transcription factors is sufficient to confer lipopolysaccharide (LPS)-inducible expression of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) to a B lymphoblast cell line, which normally lacks C/EBP factors and does not display LPS induction of proinflammatory cytokines. Thus, the activities of C/EBP alpha, beta, and delta are redundant in regard to expression of IL-6 and MCP-1. Surprisingly, the bZIP region of C/EBP beta, which lacks any previously described activation domains, can also confer LPS-inducible expression of IL-6 and MCP-1 in stable transfectants, Transient transfections reveal that the bZIP regions of C/EBP beta, C/EBP delta, and, to a lesser extent, C/EBP alpha can activate the IL-6 promoter and augment its induction by LPS. Furthermore, the transdominant inhibitor, LIP, can activate expression from the IL-6 promoter. The ability of the C/EBP beta bZIP region to activate the IL-6 promoter in transient transfections is completely dependent upon an intact NF-kappa B-binding site, supporting a model where the bZIP protein primarily functions to augment the activity of NF-kappa B. Replacement of the leucine zipper of C/EBP beta with that of GCN4 yields a chimeric protein that can dimerize and specifically bind to a C/EBP consensus sequence, but shows a markedly reduced ability to activate IL-6 and MCP-1 expression. These results implicate the leucine zipper domain in some function other than dimerization with known C/EBP family members, and suggest that C/EBP redundancy in regulating cytokine expression may result from their highly related bZIP regions. C1 Michigan State Univ, Dept Microbiol, E Lansing, MI 48824 USA. NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Eukaryot Transcript Regulat Sect, Ft Detrick, MD 21702 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Biochem & Cell Biol, Lubbock, TX 79430 USA. RP Schwartz, RC (reprint author), Michigan State Univ, Dept Microbiol, E Lansing, MI 48824 USA. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 44 TC 76 Z9 78 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 26 PY 2000 VL 275 IS 21 BP 16373 EP 16381 DI 10.1074/jbc.M910269199 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 318NX UT WOS:000087291400104 PM 10748205 ER PT J AU Hu, JX Hauache, O Spiegel, AM AF Hu, JX Hauache, O Spiegel, AM TI Human Ca2+ receptor cysteine-rich domain - Analysis of function of mutant and chimeric receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM-SENSING RECEPTOR; CELL-SURFACE EXPRESSION; METABOTROPIC GLUTAMATE RECEPTORS; TERMINAL EXTRACELLULAR DOMAIN; PUTATIVE PHEROMONE RECEPTORS; CA2+-SENSING RECEPTOR; SIGNAL-TRANSDUCTION; LIGAND-BINDING; MOLECULAR-CLONING; GABA(B) RECEPTOR AB The 612-residue extracellular domain of the human Ca2+ receptor (hCaR) has been speculated to consist of a Venus's-flytrap domain (VFT) and a cysteine-rich domain. We studied the function of the hCaR Cys-rich domain by using mutagenesis and chimera approaches. A chimeric hCaR with the sequence from residues 540-601 replaced by the corresponding sequence from the Fugu CaR remained fully functional. Another chimeric hCaR with the same region of sequence replaced by the corresponding sequence from metabotropic glutamate receptor subtype 1 (mGluR1) still was activated by extracellular Ca2+ ([Ca2+](o)), but its function was severely compromised. Chimeric receptors with the hCaR VFT and mGluR1 seven-transmembrane domain plus C-tail domain retained good response to [Ca2+](o) whether the Cys-rich domain was from hCaR or from mGluR1, Mutant hCaR with the Cys-rich domain deleted failed to respond to [Ca2+](o), although it was expressed at the cell surface and capable of dimerization. Our results indicate that the hCaR Cys-rich domain plays a critical role in signal transmission from VFT to seven-transmembrane domain. This domain tolerates a significant degree of amino acid substitution and may not be directly involved in the binding of [Ca2+](o). C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Hu, JX (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Rm 8C-101, Bethesda, MD 20892 USA. NR 33 TC 77 Z9 78 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 26 PY 2000 VL 275 IS 21 BP 16382 EP 16389 DI 10.1074/jbc.M000277200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 318NX UT WOS:000087291400105 PM 10747888 ER PT J AU Shneyvays, V Jacobson, KA Li, AH Nawrath, H Zinman, T Isaac, A Shainberg, A AF Shneyvays, V Jacobson, KA Li, AH Nawrath, H Zinman, T Isaac, A Shainberg, A TI Induction of apoptosis in rat cardiocytes by A(3) adenosine receptor activation and its suppression by isoproterenol SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE adenosine receptors; apoptosis; image analysis; light and electron microscopy; immunohistochemistry; isoproterenol ID CELL-DEATH; CARDIAC MYOCYTES; A(2B) RECEPTORS; ADRENERGIC REGULATION; MUSCLE CELLS; ACTIN GENE; HEART; MITOCHONDRIA; NECROSIS; GROWTH AB The purpose of the present study was to investigate the mechanisms involved in the induction of apoptosis in newborn cultured cardiomyocytes by activation of adenosine (ADO) A(3) receptors and to examine the protective effects of beta-adrenoceptors, The selective agonist for A(3) ADO receptors Cl-IB-MECA (2-chloro-N-6-iodobenzyl-5-N-methylcarboxamidoadenosine) and the antagonist MRS1523 (5-propyl-2-ethyl-4-propyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridin-5-carboxylate) were used. High concentrations of the Cl-IBMECA (greater than or equal to 10 mu M) agonist induced morphological modifications of myogenic cells, such as rounding and retraction of cell body and dissolution of contractile filaments, followed by apoptotic death. In addition, Cl-IB-MECA caused a sustained and reversible increase in [Ca2+](i), which was prevented by the selective antagonist MRS1523. Furthermore, MRS1523 protected the cardiocytes if briefly exposed to CI-IBMECA and partially protected from prolonged (48 h) agonist exposure. Apoptosis induced by Cl-IB-MECA was not redox-dependent, since the mitochondrial membrane potential remained constant until the terminal stage of cell death. Cl-IB-MECA activated caspase-3 protease in a concentration-dependent manner after 7 h of treatment and more effectively after 18 h of exposure. Bcl-2 protein was readily detected in control cells, and its expression was significantly decreased after 24 and 48 h of treatment with Cl-IB-MECA. beta-Adrenergic stimulation antagonized the pro-apoptotic effects of Cl-IB-MECA, probably through a cAMP/protein kinase A-independent mechanism, since addition of dibutyryl-cAMP did not abolish the apoptosis induced by Cl-IB-MECA. Incubation of cultured myocytes with isoproterenol (5 mu M) for 3 or 24 h almost completely abolished the increase in [Ca2+]i. Prolonged incubation of cardiomyocytes with isoproterenol and Cl-IB-MECA did not induce apoptosis, Our data suggest that the apoptosis-inducing signal from activation of adenosine A(3) receptors (or counteracting beta-adrenergic signal) leads to the activation of the G-protein-coupled enzymes and downstream pathways to a self-amplifying cascade. Expression of different genes within this cascade is responsible for orchestrating either cardiomyocyte apoptosis or its protection. (C) 2000 Academic Press. C1 Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Med Diagnost Res Ctr, IL-52900 Ramat Gan, Israel. NIH, Mol Recognit Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Univ Mainz, Inst Pharmacol, D-6500 Mainz, Germany. RP Shainberg, A (reprint author), Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Med Diagnost Res Ctr, IL-52900 Ramat Gan, Israel. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 54 TC 62 Z9 63 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 25 PY 2000 VL 257 IS 1 BP 111 EP 126 DI 10.1006/excr.2000.4882 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 317JL UT WOS:000087222200011 PM 10854059 ER PT J AU Kwon, TK Baek, SH Kim, JH Lee, SJ Park, YK Park, JW Kwun, KB Buchholz, MA Nordin, AA AF Kwon, TK Baek, SH Kim, JH Lee, SJ Park, YK Park, JW Kwun, KB Buchholz, MA Nordin, AA TI Cdk7-and cdc25A-independent dephosphorylation of cdk2 during phorbol ester-mediated cell cycle arrest in U937 cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID PROTEIN-KINASE-C; MYELOMONOCYTIC LEUKEMIA-CELLS; DEPENDENT KINASES; PHOSPHATASE-ACTIVITY; G(1)/S TRANSITION; MAMMALIAN-CELLS; ACTIVATION; EXPRESSION; INHIBITORS; PHOSPHORYLATION AB The molecular mechanism underlying protein kinase C (PKC)-mediated cell cycle arrest is poorly understood, We undertook to characterize phorbol ester-activated PKC-mediated cell cycle arrest. Treatment with phorbol ester inhibited cell growth of human histiocytic lymphoma U937 cells with 83% of the cells arrested in G1 phase. Reduced activity of cdk2 correlated with cdk2 dephosphorylation and accumulation of cdk2 inhibitor p21(Waf) in phorbol ester-treated cells. Dephosphorylation of cdk2 was not associated with cdk7 and cdc25A activity in phorbol ester-treated cells. Protein phosphatase inhibitor assays suggest that the dephosphorylation of cdk2 results in the activation of a specific protein tyrosine phosphatase. Thus, dephosphorylation of cdk2 as well as accumulation of cdk2 inhibitor is likely to contribute to the G1 phase arrest in phorbol ester-treated in U937 cells. (C) 2000 Academic Press. C1 Keimyung Univ, Coll Med, Sch Med,Dept Immunol, Jung Gu, Taegu 704701, South Korea. Yeungnam Univ, Coll Med, Taegu 705717, South Korea. NIA, Immunol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Kwon, TK (reprint author), Keimyung Univ, Coll Med, Sch Med,Dept Immunol, Jung Gu, 194 Dong San Dong, Taegu 704701, South Korea. NR 39 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 25 PY 2000 VL 257 IS 1 BP 145 EP 151 DI 10.1006/excr.2000.4880 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 317JL UT WOS:000087222200014 PM 10854062 ER PT J AU Ebert, AD Wechselberger, C Nees, M Clair, T Schaller, G Martinez-Lacaci, I Wallace-Jones, B Bianco, C Weitzel, HK Salomon, DS AF Ebert, AD Wechselberger, C Nees, M Clair, T Schaller, G Martinez-Lacaci, I Wallace-Jones, B Bianco, C Weitzel, HK Salomon, DS TI Cripto-1-induced increase in vimentin expression is associated with enhanced migration of human Caski cervical carcinoma cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Cripto-1; vimentin; cDNA gene expression array; migration; cervical carcinoma; human ID KERATIN INTERMEDIATE FILAMENTS; MAMMARY EPITHELIAL-CELLS; EPITHELIOMESENCHYMAL TRANSFORMATION; PHOSPHATIDYLINOSITOL 3-KINASE; EXPERIMENTAL COEXPRESSION; TYROSINE PHOSPHORYLATION; CANCER CELLS; MOUSE EMBRYO; CRIPTO; GROWTH AB Cripto-1 (CR-1), a member of the EGF-CFC peptide family, plays an essential role during mesoderm formation in vertebrates as well as in cancer development, Using cDNA gene expression array, Western blot, and indirect immunofluorescence, an increase in vimentin expression was demonstrated in CR-1-transfected human Caski cervical carcinoma cells compared to control vector-transfected cells, In parental Caski cells, recombinant CR-1 induced a dose-dependent increase of vimentin protein expression within 24 h, Since vimentin expression has been demonstrated to correlate with a more aggressive phenotype in human cervical cancer, the migration capacity of CR-1-transfected or CR-1-treated Caski cells was studied in the Boyden chamber assay, Compared to the vector-transfected or untreated Caski cells, CR-1-transfected cells or cells treated with recombinant CR-1 exhibit enhanced migration, both through collagen- and through gelatin-coated membranes, Additionally, CR-1 can function as a chemoattractant for Caski cells, These findings are of biological significance since CR-1 is overexpressed in several types of human carcinomas, The present data demonstrate that CR-1 can increase vimentin expression and modulate migration in human cervical carcinoma cells. C1 NCI, Tumor Immunol & Biol Lab, NIH, Growth Factors Sect, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Free Univ Berlin, Med Ctr Benjamin Franklin, Dept Obstet & Gynecol, D-12200 Berlin, Germany. RP Salomon, DS (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Growth Factors Sect, Bldg 10,Room 5B39,10 Ctr Dr MSC-1750, Bethesda, MD 20892 USA. NR 42 TC 39 Z9 40 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 25 PY 2000 VL 257 IS 1 BP 223 EP 229 DI 10.1006/excr.2000.4881 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 317JL UT WOS:000087222200023 PM 10854071 ER PT J AU Rankin, T Soyal, S Dean, J AF Rankin, T Soyal, S Dean, J TI The mouse zona pellucida: folliculogenesis, fertility and pre-implantation development SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Workshop on Early Folliculogenesis and Oocyte Development - Basic and Clinical Aspects CY JUN 10-11, 1999 CL ROYAL COLL PHYSICIANS, LONDON, ENGLAND SP Ares Serono Fdn HO ROYAL COLL PHYSICIANS DE zona pellucida (mouse); infertility; folliculogenesis; transgenesis; ZP1; ZP2; ZP3 ID EGG VITELLINE ENVELOPE; GLYCOPROTEIN ZP3; SPERM RECEPTOR; XENOPUS-LAEVIS; MICE; BINDING; EXPRESSION; ADHESION; FERTILIZATION; LACKING AB Perinatally, oocytes within the mouse ovary become surrounded by a layer of flattened granulosa cells and form primordial follicles. The subsequent accretion of the zona pellucida between the oocytes and granulosa cells provides a biochemical marker of folliculogenesis. In mice, the zona matrix is composed of three proteins (ZP1: ZP2, ZP3). Mouse lines lacking either ZP1 or ZP3 have been established and have abnormal folliculogenesis. Without ZP1, structurally defective zonae are formed resulting in decreased fecundity due to early embryonic loss. More strikingly, without ZP3, the zona matrix is absent, no 2-cell embryos are formed and females are infertile. The structural integrity of the zona matrix can be restored by substituting human homologues for the missing mouse protein and these 'humanized' zona matrices should prove useful in investigating the molecular basis of fertilization. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rankin, T (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 6,Room B1-26,6 Ctr Dr MSC 2715, Bethesda, MD 20892 USA. NR 25 TC 31 Z9 35 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAY 25 PY 2000 VL 163 IS 1-2 BP 21 EP 25 DI 10.1016/S0303-7207(99)00236-1 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 346UK UT WOS:000088889300004 PM 10963869 ER PT J AU Monget, P Bondy, C AF Monget, P Bondy, C TI Importance of the IGF system in early folliculogenesis SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Workshop on Early Folliculogenesis and Oocyte Development - Basic and Clinical Aspects CY JUN 10-11, 1999 CL ROYAL COLL PHYSICIANS, LONDON, ENGLAND SP Ares Serono Fdn HO ROYAL COLL PHYSICIANS DE IGFs; ovarian folliculogenesis; mammals ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-2; OVARIAN FOLLICULAR DEVELOPMENT; MESSENGER RIBONUCLEIC-ACIDS; RECEPTOR GENE-EXPRESSION; PRIMATE OVARY; CELLULAR-LOCALIZATION; PROTEOLYTIC ACTIVITY; PORCINE OVARY; OVINE OVARY AB In the primate ovary, androgens promote oocyte insulin-like growth factor (IGF) I expression as well as initiation of follicle development. In most other mammals, IGFs do not appear to be required for the entry of follicles into the pool of growing follicles and for their gonadotropin-independent development. In contrast, IGFs are involved in the increase in FSH-responsiveness of granulosa cells when follicles enter into the gonadotropin-dependent stages of follicular development (200 mu m in mouse, 2 mm in sheep, 5 mm diameter in cattle). In the late stages of folliculogenesis, the decrease in IGFBPs participates in the increase in IGF bioavailability, leading to a further amplification of FSH action. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 INRA, Physiol Reprod Mammiferes Domest, URA CNRS 1291, F-37380 Nouzilly, France. NICHD, NIH, Bethesda, MD 20892 USA. RP Monget, P (reprint author), INRA, Physiol Reprod Mammiferes Domest, URA CNRS 1291, F-37380 Nouzilly, France. NR 33 TC 59 Z9 63 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAY 25 PY 2000 VL 163 IS 1-2 BP 89 EP 93 DI 10.1016/S0303-7207(99)00244-0 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 346UK UT WOS:000088889300014 PM 10963879 ER PT J AU Bell, AC Felsenfeld, G AF Bell, AC Felsenfeld, G TI Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene SO NATURE LA English DT Article ID MOUSE H19 GENE; BECKWITH-WIEDEMANN-SYNDROME; WILMS-TUMOR; EPIGENETIC CHANGES; CONTROL ELEMENT; REGION; INSULATOR; UPSTREAM; DOMAIN; LOCUS AB The expression of the insulin-like growth factor 2 (Igf2) and H19 genes is imprinted. Although these neighbouring genes share an enhancer(1), H19 is expressed only from the maternal allele, and Igf2 only from the paternally inherited allele(2,3). A region of paternal-specific methylation upstream of H19 appears to be the site of an epigenetic mark that is required for the imprinting of these genes(4,5). A deletion within this region results in loss of imprinting of both H19 and Igf2 (ref. 5). Here we show that this methylated region contains an element that blocks enhancer activity. The activity of this element is dependent upon the vertebrate enhancer-blocking protein CTCF. Methylation of CpGs within the CTCF-binding sites eliminates binding of CTCF in vitro, and deletion of these sites results in loss of enhancer-blocking activity in vivo, thereby allowing gene expression. This CTCF-dependent enhancer-blocking element acts as an insulator. We suggest that it controls imprinting of Igf 2. The activity of this insulator is restricted to the maternal allele by specific DNA methylation of the paternal allele. Our results reveal that DNA methylation can control gene expression by modulating enhancer access to the gene promoter through regulation of an enhancer boundary. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI jia, xu/A-8386-2016 NR 30 TC 1013 Z9 1040 U1 8 U2 76 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 25 PY 2000 VL 405 IS 6785 BP 482 EP 485 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 317DX UT WOS:000087212000054 PM 10839546 ER PT J AU Means-Markwell, M Burgess, T DeKeratry, D O'Neil, K Mascola, J Fleisher, T Lucey, D AF Means-Markwell, M Burgess, T DeKeratry, D O'Neil, K Mascola, J Fleisher, T Lucey, D TI Eosinophilia with aberrant T cells and elevated serum levels of interleukin-2 and interleukin-15 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; KILLER-CELLS; IN-VITRO; IL-15; CYTOKINE; PROLIFERATION; CYTOTOXICITY; ACTIVATION; EXPRESSION; EXPANSION C1 Washington Hosp Ctr, Infect Dis Serv, Washington, DC 20010 USA. Natl Naval Med Ctr, Dept Med, Bethesda, MD USA. Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Lucey, D (reprint author), Washington Hosp Ctr, Infect Dis Serv, Rm 2A-56,110 Irving St NW, Washington, DC 20010 USA. NR 17 TC 19 Z9 21 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 25 PY 2000 VL 342 IS 21 BP 1568 EP 1571 DI 10.1056/NEJM200005253422104 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 316XJ UT WOS:000087193100004 PM 10824075 ER PT J AU Engels, EA Frisch, M Biggar, RJ Goedert, JJ AF Engels, EA Frisch, M Biggar, RJ Goedert, JJ TI AIDS-related opportunistic illness and potent antiretroviral therapy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NCI, Rockville, MD USA. RP Engels, EA (reprint author), NCI, Rockville, MD USA. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 NR 3 TC 2 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 24 PY 2000 VL 283 IS 20 BP 2653 EP 2653 DI 10.1001/jama.283.20.2653 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 314FP UT WOS:000087046000019 PM 10819935 ER PT J AU Ross, GW Abbott, RD Petrovitch, H Morens, DM Grandinetti, A Tung, KH Tanner, CM Masaki, KH Blanchette, PL Curb, JD Popper, JS White, LR AF Ross, GW Abbott, RD Petrovitch, H Morens, DM Grandinetti, A Tung, KH Tanner, CM Masaki, KH Blanchette, PL Curb, JD Popper, JS White, LR TI Association of coffee and caffeine intake with the risk of Parkinson disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY HEART-DISEASE; JAPANESE ANCESTRY; MEN; HAWAII; EPIDEMIOLOGY; RECEPTORS; SMOKING; ALCOHOL; SYSTEM AB Context The projected expansion in the next several decades of the elderly population at highest risk for Parkinson disease (PD) makes identification of factors that promote or prevent the disease an important goat. Objective To explore the association of coffee and dietary caffeine intake with risk of PD. Design, Setting, and Participants Data were analyzed from 30 years of fallow-up of 8004 Japanese American men (aged 45-68 years) enrolled in the prospective longitudinal Honolulu Heart Program between 1965 and 1968. Main Outcome Measure Incident PD, by amount of coffee intake (measured at study enrollment and 6-year follow-up) and by total dietary caffeine intake (measured at enrollment). Results During follow-up, 102 men were identified as having PD. Age-adjusted incidence of PD declined consistently with increased amounts of coffee intake, from 10.4 per 10000 person-years in men who drank no coffee to 1.9 per 10000 person-years in men who drank at least 28 oz/d (P<.001 for trend). Similar relationships were observed with total caffeine intake (P<.001 for trend) and caffeine from noncoffee sources (P = .03 for trend). Consumption of increasing amounts of coffee was also associated with lower risk of PD in men who were never, past, and current smokers at baseline (P = .049, P = .22, and P = .02, respectively, for trend). Other nutrients in coffee, including niacin, were unrelated to PD incidence. The relationship between caffeine and PD was unaltered by intake of milk and sugar. Conclusions Our findings indicate that higher coffee and caffeine intake is associated with a significantly lower incidence of PD, This effect appears to be independent of smoking. The data suggest that the mechanism is related to caffeine intake and not to other nutrients contained in coffee. C1 Dept Vet Affairs, Honolulu, HI 96850 USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Univ Hawaii, John A Burns Sch Med, Pacific Biomed Res Ctr, Honolulu, HI 96822 USA. Univ Virginia, Sch Med, Dept Hlth Evaluat Sci, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA. Pacific Hlth Res Inst, Honolulu, HI USA. NIAID, NIH, Bethesda, MD 20892 USA. Parkinsons Inst, Sunnyvale, CA USA. Kuakini Med Ctr Honolulu Asia Aging Study, Honolulu, HI USA. Univ Hawaii, Sch Publ Hlth, Honolulu, HI 96822 USA. RP Ross, GW (reprint author), Dept Vet Affairs, Honolulu 151,POB 50188, Honolulu, HI 96850 USA. FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 31 TC 349 Z9 355 U1 6 U2 53 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 24 PY 2000 VL 283 IS 20 BP 2674 EP 2679 DI 10.1001/jama.283.20.2674 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 314FP UT WOS:000087046000035 PM 10819950 ER PT J AU Emanuel, EJ Wendler, D Grady, C AF Emanuel, EJ Wendler, D Grady, C TI What makes clinical research ethical? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID CISPLATIN-INDUCED NAUSEA; DEVELOPING-COUNTRIES; INFORMED CONSENT; PROTECTING COMMUNITIES; ONDANSETRON GR-38032F; SEROTONIN ANTAGONIST; ROTAVIRUS VACCINE; CONTROLLED TRIALS; HUMAN-RIGHTS; PREVENTION AB Many believe that informed consent makes clinical research ethical. However, informed consent is neither necessary nor sufficient for ethical clinical research. Drawing on the basic philosophies underlying major codes, declarations, and other documents relevant to research with human subjects, we propose 7 requirements that systematically elucidate a coherent framework for evaluating the ethics of clinical research studies: (1) value-enhancements of health or knowledge must be derived from the research; (2) scientific validity-the research must be methodologically rigorous; (3) fair subject selection-scientific objectives, not vulnerability or privilege, and the potential for and distribution of risks and benefits, should determine communities selected as study sites and the inclusion criteria for individual subjects; (4) favorable risk-benefit ratio-within the context of standard clinical practice and the research protocol, risks must be minimized, potential benefits enhanced, and the potential benefits to individuals and knowledge gained for society must outweigh the risks; (5) independent review-unaffiliated individuals must review the research and approve, amend, or terminate it; (6) informed consent-individuals should be informed about the research and provide their voluntary consent; and (7) respect for enrolled subjects-subjects should have their privacy protected, the opportunity to withdraw, and their well-being monitored. Fulfilling all 7 requirements is necessary and sufficient to make clinical research ethical. These requirements are universal, although they must be adapted to the health, economic, cultural, and technological conditions in which clinical research is conducted. C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 128 TC 869 Z9 900 U1 13 U2 127 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 24 PY 2000 VL 283 IS 20 BP 2701 EP 2711 DI 10.1001/jama.283.20.2701 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 314FP UT WOS:000087046000040 PM 10819955 ER PT J AU Baber, JL Levens, D Libutti, D Tjandra, N AF Baber, JL Levens, D Libutti, D Tjandra, N TI Chemical shift mapped DNA-binding sites and N-15 relaxation analysis of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K SO BIOCHEMISTRY LA English DT Article ID FRAGILE-X-SYNDROME; ROTATIONAL DIFFUSION ANISOTROPY; HETERONUCLEAR NMR-SPECTROSCOPY; MAGNETIC-RESONANCE RELAXATION; MODEL-FREE APPROACH; RNA-BINDING; IN-VITRO; HNRNP-K; PHOSPHOTRANSFERASE SYSTEM; MULTIDIMENSIONAL NMR AB The K homology (KH) motif is one of the major classes of nucleic acid binding proteins. Some members of this family have been shown to interact with DNA while others have RNA targets. There have been no reports containing direct experimental evidence regarding the nature of KH module-DNA interaction. In this study, the interaction of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K (KH3) with it's cognate single-stranded DNA (ssDNA) are investigated. Chemical shift perturbation mapping indicates that the first two helices, the conserved GxxG loop, beta 1, and beta 2, are the primary regions involved in DNA binding for KH3. The nature of the KH3-ssDNA interaction is further illuminated by a comparison of backbone N-15 relaxation data for the bound and unbound KH3. Relaxation data are also used to confirm that the backbone of wild-type KH3 is structurally identical to that of the G26R mutant KH3, which was previously published. Amide proton exchange experiments indicate that the two helices involved in DNA binding are less stable than other regions of secondary structure and that a large portion of KH3 backbone amide hydrogens are protected in some manner upon ssDNA binding. The major backbone dynamics features of KH3 are similar to these of the structurally comparable human papillomavirus-31 E2 DNA binding domain. Secondary structure information for ssDNA-bound wild-type KH3 is also presented and shows that binding results in no global changes in the protein fold. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 74 TC 19 Z9 19 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 23 PY 2000 VL 39 IS 20 BP 6022 EP 6032 DI 10.1021/bi000105e PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 320KE UT WOS:000087399700012 PM 10821674 ER PT J AU Shi, GB Gong, YC Savchenko, A Zeikus, JG Xiao, B Ji, XH Yan, HG AF Shi, GB Gong, YC Savchenko, A Zeikus, JG Xiao, B Ji, XH Yan, HG TI Dissecting the nucleotide binding properties of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase with fluorescent 3 '(2)'-o-anthraniloyladenosine 5 '-triphosphate SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article ID RNA-POLYMERASE; RESISTANCE; 7,8-DIHYDRO-6-HYDROXYMETHYLPTERIN-PYROPHOSPHOKINASE; EXPRESSION; ENTHALPY; KINASE AB 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin, the first reaction in the folate biosynthetic pathway. Like other enzymes in the folate pathway, HPPK is an ideal target for development of antimicrobial agents because the enzyme is essential for microorganisms but is absent from humans and animals. Using 3'(2')-o-anthraniloyladenosine 5'-triphosphate as a fluorescent probe, a fluorometric competitive binding assay has been developed for measuring the dissociation constants of various compounds that bind to the ATP site of HPPK. The fluorometric assay has been used to determine the nucleotide specificity and dissect the energetics of the binding of MgATP. The order of affinity of various nucleoside triphosphates for HPPK is MgATP > MgGTP > MgITP > MgXTP approximate to MgUTP approximate to MgCTP. The affinity of MgATP for HPPK (K-d = 2.6 +/- 0.06 mu M) is 260-fold higher than that of MgGTP and more than 1000-fold higher than those of the other nucleoside triphosphates, indicating that HPPK is highly specific with respect to the base moiety of the nucleotide. The affinity of ATP for HPPK in the presence of Mg2+ is 15 times that in the absence of Mg2+, indicating that the metal ion is important for the binding of the nucleotide. Removal of the gamma-phosphate from MgATP reduces its affinity for HPPK by a factor of similar to 21. The affinity of AMP for HPPK is about one third that of ADP and almost the same as that of adenosine. The result suggests that among the three phosphoryl groups of MgATP, the gamma-phosphoryl group is most critical for binding to HPPK and the alpha-phosphoryl group contributes little to the binding of the nucleotide. The affinity of MgATP is 18 times that of MgdATP, indicating that the 2'-hydroxyl group of MgATP is also important for binding. van't Hoff analysis suggests that binding of MgATP is mainly driven by enthalpy at 25 degrees C and the entropy of binding is also in favor of the formation of the HPPK MgATP complex. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Michigan State Univ, Dept Biochem, E Lansing, MI 48824 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Yan, HG (reprint author), Michigan State Univ, Dept Biochem, E Lansing, MI 48824 USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NIGMS NIH HHS [GM51901] NR 30 TC 31 Z9 32 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD MAY 23 PY 2000 VL 1478 IS 2 BP 289 EP 299 DI 10.1016/S0167-4838(00)00043-1 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 320WG UT WOS:000087423400012 PM 10825540 ER PT J AU Prasad, A Tupas-Habib, T Schenke, WH Mincemoyer, R Panza, JA Waclawin, MA Ellahham, S Quyyumi, AA AF Prasad, A Tupas-Habib, T Schenke, WH Mincemoyer, R Panza, JA Waclawin, MA Ellahham, S Quyyumi, AA TI Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis SO CIRCULATION LA English DT Article DE atherosclerosis; angiotensin; nitric oxide; endothelium; receptors; losartan ID CORONARY-ARTERY DISEASE; CONVERTING ENZYME-INHIBITION; NITRIC-OXIDE; MYOCARDIAL-INFARCTION; REACTIVE HYPEREMIA; HYPERTENSION; LOSARTAN; CELLS; RISK; ACTIVATION AB Background-The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The present study was performed to determine whether angiotensin-1 (AT(1)) receptor inhibition improves endothelial dysfunction. Methods and Results-In the femoral circulation of 19 patients with atherosclerosis and of 9 control subjects, we studied microvascular responses to reactive hyperemia, angiotensin II, acetylcholine, and sodium nitroprusside before and after the administration of intra-arterial losartan (10 mg), Femoral artery flow velocity was measured with a Doppler flow wire, and the femoral vascular resistance index (FVRI) was calculated as mean arterial pressure divided by flow velocity. Losartan induced a minor (5.9+/-2%, P=0.02) reduction in FVRI and inhibited angiotensin II-mediated vasoconstriction in both patient groups (P<0.01). After the administration of losartan, acetylcholine-mediated vasodilation was augmented in patients (44+/-5% to 58+/-4% reduction in FVRI with infusion at a rate of 150 mu g/min, P<0.001) but not control subjects. Vasodilation during reactive hyperemia was also greater after AT(1) receptor inhibition (P=0.03) in patients, but the response to sodium nitroprusside remained unchanged. In a separate group of 31 patients with atherosclerosis, we investigated the effect of 8 weeks of oral losartan therapy on brachial artery flow-mediated vasodilation with the use of high-resolution ultrasound. Oral losartan therapy improved flow-mediated brachial artery dilation (1.4+/-0.9% to 3.2+/-0.8%, P=0.03) but had no effect on the nitroglycerin response. Serum nitrogen oxide levels increased from 21.6+/-1.7 to 26.7+/-2.4 mu mol/L (P=0.008). Conclusions-The results of the present study indicate that inhibition of the AT(1) receptor in patients with atherosclerosis reverses endothelial dysfunction by improving NO availability and therefore may have long-term therapeutic benefits. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. Washington Hosp Ctr, Dept Internal Med, Div Cardiol, Washington, DC 20010 USA. RP Quyyumi, AA (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. NR 37 TC 148 Z9 154 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 23 PY 2000 VL 101 IS 20 BP 2349 EP 2354 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 316EY UT WOS:000087155700006 PM 10821809 ER PT J AU Rapoport, SI AF Rapoport, SI TI Functional brain imaging to identify affected subjects genetically at risk for Alzheimer's disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; APOLIPOPROTEIN-E; CHOLINERGIC STIMULATION; EPSILON-4 ALLELE; SENILE DEMENTIA; DOWNS-SYNDROME; TYPE-4 ALLELE; BLOOD-FLOW; MYOINOSITOL C1 NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Sect Brain Physiol & Metab, NIH, Bldg 10,Room 6C103, Bethesda, MD 20892 USA. NR 43 TC 17 Z9 17 U1 3 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 23 PY 2000 VL 97 IS 11 BP 5696 EP 5698 DI 10.1073/pnas.120178897 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319BG UT WOS:000087318700006 PM 10811924 ER PT J AU Horiuchi, M Priola, SA Chabry, J Caughey, B AF Horiuchi, M Priola, SA Chabry, J Caughey, B TI Interactions between heterologous forms of prion protein: Binding, inhibition of conversion, and species barriers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; SCRAPIE-ASSOCIATED FORM; CELL-FREE CONVERSION; RESISTANT STATE; NEUROBLASTOMA-CELLS; TRANSGENIC MICE; CULTURED-CELLS; PRP; AGENT; BSE AB The self-induced formation of the disease-associated, protease-resistant prion protein (PrP-res) from the normal protease-sensitive isoform (PrP-sen) appears to be a key event in the pathogenesis of transmissible spongiform encephalopathies. The amino acid sequence specificity of PrP-res formation correlates with, and may account for, the species specificity in transmission of transmissible spongiform encephalopathy agents in vivo. To analyze the mechanism controlling the sequence specificity of PrP-res formation, we compared the binding of PrP-sen to PrP-res with its subsequent acquisition of protease resistance by using cell-free systems consisting of heterologous versus homologous mouse and hamster PrP isoforms, Our studies showed that heterologous PrP-sen can bind to PrP-res with little conversion to the protease-resistant state and, in doing so, can interfere with the conversion of homologous PrP-sen, The interference occurred with molar ratios of homologous to heterologous PrP-sen molecules as low as 1:1. The interference was due primarily to the inhibition of conversion, but not the binding, of the homologous PrP-sen to PrP-res, The results provide evidence that the sequence specificity of PrP-res formation in this model is determined more by the conversion to protease resistance than by the initial binding step. These findings also imply that after the initial binding, further intermolecular interactions between PrP-sen and PrP-res are required to complete the process of conversion to the protease-resistant state. C1 NIAID, Lab Persistant Viral Dis, Rocky Mt Labs, NIH, Hamilton, ON 59840, Canada. Obihiro Univ Agr & Vet Med, Dept Vet Publ Hlth, Obihiro, Hokkaido 0808555, Japan. Obihiro Univ Agr & Vet Med, Res Ctr Protozoan Mol Immunol, Obihiro, Hokkaido 0808555, Japan. RP Caughey, B (reprint author), NIAID, Lab Persistant Viral Dis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, ON 59840, Canada. RI Chabry, Joelle/O-2101-2016 NR 35 TC 115 Z9 119 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 23 PY 2000 VL 97 IS 11 BP 5836 EP 5841 DI 10.1073/pnas.110523897 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319BG UT WOS:000087318700032 PM 10811921 ER PT J AU Yu, DG Ellis, HM Lee, EC Jenkins, NA Copeland, NG Court, DL AF Yu, DG Ellis, HM Lee, EC Jenkins, NA Copeland, NG Court, DL TI An efficient recombination system for chromosome engineering in Escherichia coli SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STRAND-BREAK REPAIR; BACTERIOPHAGE-LAMBDA RECOMBINATION; PHAGE-LAMBDA; SACCHAROMYCES-CEREVISIAE; GENETIC-ANALYSIS; BETA-PROTEIN; RED-PATHWAY; DNA; DELETION; CLONING AB A recombination system has been developed for efficient chromosome engineering in Escherichia coli by using electroporated linear DNA. A defective lambda prophage supplies functions that protect and recombine an electroporated linear DNA substrate in the bacterial cell. The use of recombination eliminates the requirement for standard cloning as all novel joints are engineered by chemical synthesis in vitro and the linear DNA is efficiently recombined into place in vivo. The technology and manipulations required are simple and straight forward. A temperature-dependent repressor tightly controls prophage expression, and, thus, recombination functions can be transiently supplied by shifting cultures to 42 degrees C for 15 min. The efficient prophage recombination system does not require host RecA function and depends primarily on Exo, Beta, and Gam functions expressed from the defective lambda prophage, The defective prophage can be moved to other strains and can be easily removed from any strain. Gene disruptions and modifications of both the bacterial chromosome and bacterial plasmids are possible. This system will be especially useful for the engineering of large bacterial plasmids such as those from bacterial artificial chromosome libraries. C1 NCI, Div Basic Sci, Frederick Canc Res & Dev Ctr, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. NCI, Div Basic Sci, Frederick Canc Res & Dev Ctr, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP NCI, Div Basic Sci, Frederick Canc Res & Dev Ctr, Gene Regulat & Chromosome Biol Lab, Bldg 539,Room 243, Frederick, MD 21702 USA. EM court@ncifcrf.gov NR 37 TC 1017 Z9 1082 U1 14 U2 94 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 23 PY 2000 VL 97 IS 11 BP 5978 EP 5983 DI 10.1073/pnas.100127597 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319BG UT WOS:000087318700056 PM 10811905 ER PT J AU Vereb, G Matko, J Vamosi, G Ibrahim, SM Magyar, E Varga, S Szollosi, J Jenei, A Gaspar, R Waldmann, TA Damjanovich, S AF Vereb, G Matko, J Vamosi, G Ibrahim, SM Magyar, E Varga, S Szollosi, J Jenei, A Gaspar, R Waldmann, TA Damjanovich, S TI Cholesterol-dependent clustering of IL-2R alpha and its colocalization with HLA and CD48 on T lymphoma cells suggest their functional association with lipid rafts SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IL-2 receptor; HLA glycoproteins; transferrin receptor; receptor clustering; electron microscopy ID RESONANCE ENERGY-TRANSFER; GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED PROTEINS; HUMAN LYMPHOBLASTOID-CELLS; CLASS-I MOLECULES; PLASMA-MEMBRANE; IL-2 RECEPTOR; SIGNAL-TRANSDUCTION; OPTICAL MICROSCOPY; SURFACE; ACTIVATION AB Immunogold staining and electron microscopy show that IL-2 receptor alpha-subunits exhibit nonrandom surface distribution on human T lymphoma cells, Analysis of interparticle distances reveals that this clustering on the scale of a few hundred nanometers is independent of the presence of IL-2 and of the expression of the IL-2R beta-subunit. Clustering of IL-2R alpha is confirmed by confocal microscopy, yielding the same average cluster size, approximate to 600-800 nm, as electron microscopy. HLA class I and II and CD48 molecules also form clusters of the same size. Disruption of cholesterol-rich lipid rafts with filipin or depletion of membrane cholesterol with methyl-beta-cyclodextrin results in the blurring of cluster boundaries and an apparent dispersion of clusters for all four proteins. Interestingly, the transferrin receptor which is thought to be located outside lipid rafts, exhibits clusters that are only 300 nm in size and are less affected by modifying the membrane cholesterol content. Furthermore, transferrin receptor clusters hardly colocalize with IL-2R alpha, HLA, and CD48 molecules (crosscorrelation coefficient is 0.05), whereas IL-2R alpha colocalizes with both HLA and CD48 (crosscorrelation coefficient is between 0.37 and 0.46), This coclustering is confirmed by electron microscopy. The submicron clusters of IL-2R alpha chains and their coclustering with HLA and CD48, presumably associated with lipid rafts, could underlie the efficiency of signaling in lymphoid cells. C1 Univ Debrecen, Med & Hlth Sci Ctr, Dept Biophys & Cell Biol, H-4012 Debrecen, Hungary. Univ Debrecen, Med & Hlth Sci Ctr, Cell Biophys Res Grp, Hungarian Acad Sci, H-4012 Debrecen, Hungary. Univ Debrecen, Med & Hlth Sci Ctr, Cent Res Serv Lab, H-4012 Debrecen, Hungary. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Univ Debrecen, Med & Hlth Sci Ctr, Dept Biophys & Cell Biol, POB 39, H-4012 Debrecen, Hungary. EM dami@jaguar.dote.hu RI Vamosi, Gyorgy/C-9351-2009; Damjanovich, Sandor/A-9284-2011; Matko, Janos/C-9008-2013; Vereb, Gyorgy/A-4241-2008 OI Matko, Janos/0000-0001-9434-934X; Vereb, Gyorgy/0000-0003-2157-3265 NR 46 TC 123 Z9 124 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 23 PY 2000 VL 97 IS 11 BP 6013 EP 6018 DI 10.1073/pnas.97.11.6013 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319BG UT WOS:000087318700062 PM 10823948 ER PT J AU Mi, QS Zhou, L Schulze, DH Fischer, RT Lustig, A Rezanka, LJ Donovan, DM Longo, DL Kenny, JJ AF Mi, QS Zhou, L Schulze, DH Fischer, RT Lustig, A Rezanka, LJ Donovan, DM Longo, DL Kenny, JJ TI Highly reduced protection against Streptococcus pneumoniae after deletion of a single heavy chain gene in mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNE-DEFICIENT MICE; PHOSPHOCHOLINE-SPECIFIC ANTIBODIES; PNEUMOCOCCAL INFECTION; REPERTOIRE DIVERSITY; BACTERIAL-ANTIGENS; AGED MICE; PHOSPHORYLCHOLINE-ANTIBODY; MONOCLONAL-ANTIBODIES; SOMATIC MUTATION; SELF-BINDING AB Phosphocholine (PC) is the immunodominant epitope found on the surface of Streptococcus pneumoniae (SPn). T15-idiotype Abs, whose heavy (H) chain variable region is encoded by the V1 gene, are dominant in the anti-PC response in adult mice and protect mice from lethal pneumococcal infection. The ability of anti-PC Abs using H chains other than the V1 H chain to protect against pneumococcal infection remains controversial. We generated V1(-/-) knockout mice to determine whether protective anti-PC Abs could be produced in the absence of the V1 gene. No anti-PC Abs were produced in V1(-/-) mire immunized with avirulent SPn; however, PC-BSA binding Abs were induced after immunization with PC-keyhole limpet hemocyanin but at significantly lower levels than those in wild-type mice. These Abs provided poor protection aga inst virulent SPn; th us, <25% of V1(-/-) mice survived challenge with 10(4) bacteria as compared with 100% survival of V1(+/+) mice. The anti-PC Abs in V1(-/-) mice were heteroclitic, binding to nitrophenyl-PC better than to PC. None of nine hybridomas produced from V1(-/-) mice provided passive protection. However, the V1(-/-) mice produced normal amounts of Ab to SPn proteins that can partially protect mice against SPn. These data indicate that the V1 gene is critical for the production of anti-PC Abs providing optimum protection against infection with SPn, and the V1(-/-) mice could be useful in unmasking epitopes other than the immunodominant PC epitope on SPn capable of providing cross protection. C1 NIA, Immunol Lab, Cell Dev Sect B, NIH, Baltimore, MD 21224 USA. NIA, Transgen & Knockout Facil Sect, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. Taishan Med Coll, Clin Immunol Lab, Taian 271000, Shandong, Peoples R China. Taishan Med Coll, Dept Dermatol, Taian 271000, Shandong, Peoples R China. RP Kenny, JJ (reprint author), NIA, Immunol Lab, Cell Dev Sect B, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 45 TC 32 Z9 32 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 23 PY 2000 VL 97 IS 11 BP 6031 EP 6036 DI 10.1073/pnas.110039497 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319BG UT WOS:000087318700065 PM 10811914 ER PT J AU Habib, KE Weld, KP Rice, KC Pushkas, J Champoux, M Listwak, S Webster, EL Atkinson, AJ Schulkin, J Contoreggi, C Chrousos, GP McCann, SM Suomi, SJ Higley, JD Gold, PW AF Habib, KE Weld, KP Rice, KC Pushkas, J Champoux, M Listwak, S Webster, EL Atkinson, AJ Schulkin, J Contoreggi, C Chrousos, GP McCann, SM Suomi, SJ Higley, JD Gold, PW TI Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; RHESUS-MONKEYS; STIMULATION TEST; DEPRESSION; INFLAMMATION; INHIBITION; DISORDERS; ANXIETY; ANTALARMIN; IMPACT AB We evaluated the effects of the lipophilic nonpeptide corticotropin-releasing hormone (CRH) type 1 receptor antagonist antalarmin on the behavioral, neuroendocrine, and autonomic components of the stress response in adult male rhesus macaques. After oral administration, significant antalarmin concentrations were detected in the systemic circulation and the cerebrospinal fluid by a mass spectrometry-gas chromatography assay developed specifically for this purpose. Pharmacokinetic and dose response studies suggested that an oral dose of 20 mg/kg was optimal for behavioral and endocrine effects. We then administered this dose in a double-blind, placebo-controlled fashion to monkeys exposed to an intense social stressor: namely, placement of two unfamiliar males in adjacent cages separated only by a transparent Plexiglas screen. Antalarmin significantly inhibited a repertoire of behaviors associated with anxiety and fear such as body tremors, grimacing, teeth gnashing, urination, and defecation. In contrast, antalarmin increased exploratory and sexual behaviors that are normally suppressed during stress. Moreover, antalarmin significantly diminished the increases in cerebrospinal fluid CRH as well as the pituitary-adrenal, sympathetic, and adrenal medullary responses to stress. We conclude that CRH plays a broad role in the physiological responses to psychological stress in primates and that a CRH type 1 receptor antagonist may be of therapeutic value in human psychiatric, reproductive, and cardiovascular disorders associated with CRH system hyperactivity. C1 NIMH, Clin Neuroendocrinol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NIDDKD, Med Chem Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NIH, Clin Ctr Pharm, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, Primate Unit, Intramural Res Program, Poolesville, MD 20837 USA. NICHHD, Comparat Ethol Lab, Intramural Res Program, NIH,Anim Ctr, Poolesville, MD 20837 USA. NIDA, Brain Imaging Unit, Intramural Res Program, Baltimore, MD 21224 USA. Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. RP Habib, KE (reprint author), NIH, Ctr Clin, Room 2D-45,10 Ctr Dr, Bethesda, MD 20892 USA. NR 49 TC 274 Z9 280 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 23 PY 2000 VL 97 IS 11 BP 6079 EP 6084 DI 10.1073/pnas.97.11.6079 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 319BG UT WOS:000087318700073 PM 10823952 ER PT J AU Trovato, R Cereseto, A Takemoto, S Gessain, A Watanabe, T Waldmann, T Franchini, G AF Trovato, R Cereseto, A Takemoto, S Gessain, A Watanabe, T Waldmann, T Franchini, G TI Deletion of the p16(INK4A) gene in ex vivo acute adult T cell lymphoma/leukemia cells and methylation of the p16(INK4A) promoter in HTLV type I-infected T cell lines SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID LYMPHOBLASTIC-LEUKEMIA; CDKN2 GENE; P16; INACTIVATION; MALIGNANCIES; CYCLE; HYPERMETHYLATION; INHIBITORS; FREQUENT; LYMPHOMA AB The stoichiometry of the p16(INK4A) and p15(INK4B) proteins bound to the cyclin D-CDK4/6 complex regulates the entry of cells into the G(1) phase of the cell cycle. Thus, their level of expression is essential in maintaining regulated cell growth. In several tumors, deletion of these genes has been reported and, more recently, promoter methylation has been suggested as an alternative mechanism to decrease the expression of these cell cycle inhibitor proteins. Here, we studied the methylation status and the integrity of the p16(INK4A) and p15(INK4B) genes in 8 chronically HTLV-I-infected T cell lines and in ex vivo cells from 14 ATLL patients. Deletion of the locus carrying both genes was not found in the HTLV-I-infected T cell lines but was found in seven of eight acute ATLL cases and in none of the PBMCs from the chronic cases or the affected lymph nodes of the lymphoma type. In contrast, partial or complete methylation of one or both genes was found only in chronically HTLV-I T cells, Thus, HTLV-I infection targets the p16(INK4A) and p15(INK4B) loci both in vitro and in vivo, although the mechanisms may differ. C1 NCI, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Inst Pasteur, F-75724 Paris, France. Univ Tokyo, Inst Med Sci, Dept Pathol, Tokyo 1088639, Japan. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Basic Res Lab, Div Basic Sci, NIH, Bldg 41,Room D804,41 Library Dr, Bethesda, MD 20892 USA. OI Takemoto, Shigeki/0000-0003-4130-074X NR 22 TC 16 Z9 17 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 20 PY 2000 VL 16 IS 8 BP 709 EP 713 DI 10.1089/088922200308701 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 315AF UT WOS:000087089900002 PM 10826477 ER PT J AU Lee, MK Martin, MA Cho, MW AF Lee, MK Martin, MA Cho, MW TI Higher Western blot immunoreactivity of glycoprotein 120 from R5 HIV type 1 isolates compared with X4 and X4R5 isolates SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; CHEMOKINE RECEPTORS; V3 LOOP; ANTIBODY-RESPONSE; FUSION COFACTORS; RNA-POLYMERASE; AIDS RESEARCH; LOW-RISK; INFECTION AB The envelope glycoprotein of human immunodeficiency virus 1 (HIV-1) plays important roles in viral life cycle and pathogenesis. Understanding the immune responses the protein elicits during the course of a viral infection in patients is important in designing an effective vaccine candidate against the virus or for better diagnosis of the disease. In this study, we report that gp120 of R5 isolates have higher Western blot (WB) immunoreactivity to antibodies elicited against the protein in virus-infected human patients compared with that of X4 and X4R5 isolates. Analyses of WE immunoreactivity of chimeric gp120s constructed between R5 (AD8) and X4R5 (DH12) HIV-1 isolates indicate that there are complex tertiary interdomain interactions even after a complete denaturation of the protein. Our data suggest that the determinant(s) responsible for the high WE immunoreactivity might be present in all gp120s, but are accessible to antibodies only for R5 gp120s in the WE assay. The V1/V2 and/or V3 regions of X4 and X4R5 gp120s likely interfere with either the formation or surface exposure of the WE immunoreactive determinant, Supplementing HIV-1 WE diagnosis kits with purified R5 gp120 could improve their sensitivity and facilitate earlier diagnosis of virus infection. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Cho, MW (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 339,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 57 TC 14 Z9 14 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 20 PY 2000 VL 16 IS 8 BP 765 EP 775 DI 10.1089/088922200308765 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 315AF UT WOS:000087089900008 PM 10826483 ER PT J AU Buckley , NE McCoy, KL Mezey, E Bonner, T Zimmer, A Felder, CC Glass, M Zimmer, A AF Buckley , NE McCoy, KL Mezey, E Bonner, T Zimmer, A Felder, CC Glass, M Zimmer, A TI Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB2 receptor SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE knockout mouse; cannabinoid receptor; Delta(9)tetrahydrocannabinol; macrophage ID HEAT-STABLE ANTIGEN; T-CELL RESPONSES; COSTIMULATORY MOLECULES; INFECTED MACROPHAGES; HUMAN-LEUKOCYTES; INVERSE AGONIST; KNOCKOUT MICE; EXPRESSION; MODULATION; DELTA(9)-TETRAHYDROCANNABINOL AB Cannabinoids have immunomodulatory as well as psychoactive effects, Because the central cannabinoid receptor (cannabinoid CB2 receptor) is highly expressed in many neuronal tissues and the peripheral cannabinoid receptor (cannabinoid CB2 receptor) is highly expressed in immune cells, it has been suggested that the central nervous system effects of cannabinoids are mediated by cannabinoid CB2 receptors and that the immune effects are mediated by cannabinoid CB2 receptors. To test this hypothesis, we have generated the first mouse strain with a targeted mutation in the cannabinoid CB2 receptor gene. Binding studies using the highly specific synthetic cannabinoid receptor agonist (-)-cis-3-[2-Hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol ([H-3]CP 55,940) revealed no residual cannabinoid binding sites in the spleen of the cannabinoid CB2 receptor knockout mice, while binding in the central nervous system was unchanged. Cannabinoid CB2 receptor knockout mice, which appear healthy, are fertile and care for their offspring. Fluorescence activated cell sorting (FACS) analysis showed no differences in immune cell populations between cannabinoid CB2 receptor knockout and wildtype mice. We investigated the immunomodulatory effects of cannabinoids in cannabinoid CB2 receptor deficient mice using a T cell co-stimulation assay. Delta(9)Tetrahydrocannabinol inhibits helper T cell activation through macrophages derived from wild type, but not from knockout mice, thus indicating that this effect is mediated by the cannabinoid CB2 receptor. In contrast, central nervous system effects of cannabinoids were not altered in these mice. Our results suggest that cannabinoid CB2 receptor-specific ligands may be clinically useful in the modulation of macrophage immune function while exhibiting no central nervous system activity. Furthermore, we conclude that the cannabinoid CB2 receptor knockout mouse is a useful animal model in which to study the role of the cannabinoid system in immunoregulation. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NINDS, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Microbiol & Immunol, Richmond, VA 23298 USA. NIMH, Genet Lab, Bethesda, MD 20892 USA. Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Natl Inst DCD, Cell Biol Lab, Rockville, MD 20850 USA. RP Buckley , NE (reprint author), Calif State Polytech Univ Pomona, Dept Sci Biol, 3801 W Temple Ave, Pomona, CA 91768 USA. EM nebuckley@csupomona.edu; zimmer@codon.nih.gov RI Zimmer, Andreas/B-8357-2009; OI Glass, Michelle/0000-0002-5997-6898 FU NIDA NIH HHS [P50DA05274] NR 39 TC 320 Z9 337 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAY 19 PY 2000 VL 396 IS 2-3 BP 141 EP 149 DI 10.1016/S0014-2999(00)00211-9 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 317JJ UT WOS:000087222000013 PM 10822068 ER PT J AU Shao, W Lee, AY Gulnik, S Gustchina, E Liu, YL Kung, HF Erickson, JW AF Shao, W Lee, AY Gulnik, S Gustchina, E Liu, YL Kung, HF Erickson, JW TI A novel putative transcription factor protein MYT2 that preferentially binds supercoiled DNA and induces DNA synthesis in quiescent cells SO FEBS LETTERS LA English DT Article DE myelin transcription factor 2; DNA-binding protein; topoisomer-like pattern; DNA replicase; DNA synthesis; microinjection ID REPLICATION INITIATOR PROTEIN; SEQUENCE SPECIFICITY; HUMAN FIBROBLASTS; SUPERHELICAL DNA; NUCLEAR-PROTEIN; IN-VITRO; PROMOTER; SITES; TRANSFORMATION; MICROINJECTION AB Myelin transcription factor 2 (MYT2), a putative transcription factor found in the human central nervous system, was cloned from an expression cDNA library from human T-cells, MYT2 shares weak similarity to bacterial type I topoisomerases and shares 63% sequence identity to a replicase from Leuconostoc mesenteroides. MYT2 preferentially binds supercoiled DNA (scDNA), Incubation of MYT2 and scDNA at or above equal molar ratios generated topoisomer-like patterns that were abolished by deproteination. Thus, MYT2 appears to relax scDNA via a non-enzymatic mechanism. The banding pattern of MYT2-scDNA complexes was shown to be quantisized, saturable and sequence-independent. Microinjection of MYT2 mRNA induced G(0) growth-arrested NIH 3T3 cells to enter the S phase of the cell cycle, (C) 2000 Federation of European Biochemical Societies. C1 NCI, Struct Biochem Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Lab Biochem Physiol, Frederick, MD 21702 USA. Univ Hong Kong, Inst Mol Biol, Hong Kong, Hong Kong, Peoples R China. RP Shao, W (reprint author), Celera Genom, 45 W Gude Dr, Rockville, MD 20850 USA. FU NCI NIH HHS [N01-CO-56000] NR 34 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 19 PY 2000 VL 473 IS 3 BP 363 EP 369 DI 10.1016/S0014-5793(00)01536-2 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 318AX UT WOS:000087262300018 PM 10818241 ER PT J AU Danilkovitch-Miagkova, A Angeloni, D Skeel, A Donley, S Lerman, M Leonard, EJ AF Danilkovitch-Miagkova, A Angeloni, D Skeel, A Donley, S Lerman, M Leonard, EJ TI Integrin-mediated RON growth factor receptor phosphorylation requires tyrosine kinase activity of both the receptor and c-Src SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MACROPHAGE-STIMULATING PROTEIN; FOCAL ADHESION KINASE; PDGF-BETA-RECEPTORS; ALPHA(V)BETA(3) INTEGRIN; CELL-ADHESION; ACTIVATION; MIGRATION; IDENTIFICATION; FIBROBLASTS; MODULATION AB Cooperation between integrins and growth factor receptors plays an important role in the regulation of cell growth, differentiation, and survival. The function of growth factor receptor tyrosine kinases (RTKs) can be regulated by cell adhesion to extracellular matrix (ECM) even in the absence of ligand, We investigated the pathway involved in integrin-mediated RTK activation, using RON, the receptor for macrophage-stimulating protein. Adhesion of RON-expressing epithelial cells to ECM caused phosphorylation of RON, which depended on the kinase activity of both RON itself and c-Src. This conclusion is based on these observations: 1) ECM-induced RON phosphorylation was inhibited in cells expressing kinase-inactive c-Src; 2) active c-Src could phosphorylate immunoprecipitated RON from ECM-stimulated cells but not from unstimulated cells; and 3) ECM did not cause RON phosphorylation in cells expressing kinase-dead RON, nor could active c-Src phosphorylate RON immunoprecipitated from these cells. The data fit a pathway in which ECM-induced integrin aggregation causes both c-Src activation and RON oligomerization followed by RON kinase-dependent autophosphorylation; this results in RON becoming a target for activated c-Src, which phosphorylates additional tyrosines on RON. Integrin-induced epidermal growth factor receptor (EGFR) phosphorylation also depended on both EGFR and c-Src kinase activities. This sequence appears to be a general pathway for integrin-dependent growth factor RTK activation. C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. RP Danilkovitch-Miagkova, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Bldg 560,Rm 1246, Frederick, MD 21702 USA. NR 31 TC 65 Z9 65 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2000 VL 275 IS 20 BP 14783 EP 14786 DI 10.1074/jbc.C000028200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315TD UT WOS:000087128300002 PM 10747844 ER PT J AU Basrur, V Song, YS Mazur, SJ Higashimoto, Y Turpin, JA Rice, WG Inman, JK Appella, E AF Basrur, V Song, YS Mazur, SJ Higashimoto, Y Turpin, JA Rice, WG Inman, JK Appella, E TI Inactivation of HIV-1 nucleocapsid protein P7 by pyridinioalkanoyl thioesters - Characterization of reaction products and proposed mechanism of action SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ZINC FINGERS; TYPE-1; RESISTANCE; INHIBITORS; INFECTIVITY; REPLICATION; ZIDOVUDINE; MUTATIONS; PEPTIDES AB The synthesis and antiviral properties of pyridinioalkanoyl thioester (PATE) compounds that target nucleocapsid p7 protein (NCp7) of the human immunodeficiency virus type 1 (HIV-1) have been described previously (Turpin, J. A., Song, Y., Inman, J. K., Huang, M., Wallqvist, k, Maynard, A., Covell, D. G,, Rice, W, G., and Appella, E. (1999) J. Med. Chem, 42, 67-86), In the present study, fluorescence and electrospray ionization-mass spectrometry were employed to determine the mechanism of modification of NCp7 by two lead compounds, N-[2-(5-pyridiniovaleroylthio)benzoyl] sulfacetamide bromide and N-12-(5-pyridiniovaleroylthio)benzoyll-4-(4-nitrophenylsulfonyl) aniline bromide (compounds 45 and 47, respectively). Although both compounds exhibit antiviral activity in cell-based assays, we failed to detect appreciable ejection of zinc from NCp7 under conditions in which previously described NCp7-active disulfides readily eject zinc. However, upon "activation" by Ag+, compound 45 reacted with NCp7 resulting in the zinc ejection from both zinc fingers. The reaction followed a two-step mechanism in which zinc was ejected from the carboxyl-terminal zinc finger faster than from the amino-terminal zinc finger. Both compounds covalently modified the protein with pyridinioalkanoyl groups. Compound 45 modified cysteines 36 and 49 of the carboxyl-terminal zinc finger. The results obtained herein demonstrate that FATE compounds can be constructed that selectively target only one of the two zinc fingers of NCp7, thus providing an impetus to pursue development of highly selective zinc finger inhibitors. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Serquest, Antiviral Res Lab, Frederick, MD 21702 USA. Achill Pharmaceut, Frederick, MD 21701 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Appella, E (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 24 TC 26 Z9 30 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2000 VL 275 IS 20 BP 14890 EP 14897 DI 10.1074/jbc.275.20.14890 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315TD UT WOS:000087128300018 PM 10809733 ER PT J AU Latham, GJ Forgacs, E Beard, WA Prasad, R Bebenek, K Kunkel, TA Wilson, SH Lloyd, RS AF Latham, GJ Forgacs, E Beard, WA Prasad, R Bebenek, K Kunkel, TA Wilson, SH Lloyd, RS TI Vertical-scanning mutagenesis of a critical tryptophan in the "minor groove binding track" of HIV-1 reverse transcriptase - Major groove DNA adducts identify specific protein interactions in the minor groove SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RAS CODON-61 SEQUENCE; DOUBLE-STRANDED DNA; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; OXIDE ADDUCTS; TRANSLESION SYNTHESIS; THUMB SUBDOMAIN; TEMPLATE-PRIMER; IN-VITRO AB Biochemical and molecular modeling studies of human immunodeficiency virus type 1 reverse transcriptase (RT) have revealed that a structural element, the minor groove binding track (MGBT), is important for both replication frameshift fidelity and processivity, The MGBT interactions occur in the DNA minor groove from the second through sixth base pair from the primer 3'-terminus where the DNA undergoes a structural transition from A-like to B-form DNA Alanine-scanning mutagenesis had previously demonstrated that Gly(262) and Trp(266) of the MGBT contributes important DNA interactions. To probe the molecular interactions occurring in this critical region, eight mutants of RT were studied in which alternate residues were substituted for Trp(266) These enzymes were characterized in primer extension assays in which the template DNA was adducted at a single adenine by either R- or S-enantiomers of styrene oxide. These lesions failed to block DNA polymerization by wild-type RT, yet the Trp(266) mutants and an alanine mutant of Gly(262) terminated synthesis on styrene oxide-adducted templates. Significantly, the sites of termination occurred primarily 1 and 3 bases following adduct bypass, when the lesion was positioned in the major groove of the template-primer stem. These results indicate that residue 266 serves as a "protein sensor" of altered minor groove interactions and identifies which base pair interactions are altered by these lesions. In addition, the major groove lesion must alter important structural transitions in the template-primer stem, such as minor groove widening, that allow RT access to the minor groove. C1 Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Lloyd, RS (reprint author), Amb Inc, 2130 Woodward St, Austin, TX 78744 USA. FU NIEHS NIH HHS [ES06492, ES05355, ES06766] NR 36 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2000 VL 275 IS 20 BP 15025 EP 15033 DI 10.1074/jbc.M000279200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315TD UT WOS:000087128300037 PM 10747890 ER PT J AU Ellison, PA Sellers, JR Cremo, CR AF Ellison, PA Sellers, JR Cremo, CR TI Kinetics of smooth muscle heavy meromyosin with one thiophosphorylated head SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHORYLATION-DEPENDENT REGULATION; LIGHT-CHAIN KINASE; 2 HEADS; ADENOSINE-TRIPHOSPHATASE; ATPASE ACTIVITY; SCALLOP MYOSIN; GIZZARD MYOSIN; ACTIN; COOPERATIVITY; CONFORMATION AB Actin-activated MgATPase of smooth muscle heavy meromyosin is activated by thiophosphorylation of two regulatory light chains, one on each head domain. To understand cooperativity between heads, we examined the kinetics of heavy meromyosin (HMM) with one thiophosphorylated head, Proteolytic gizzard heavy meromyosin regulatory light chains were partially exchanged with recombinant thiophosphorylated His-tagged light chains, and HMM with one thiophosphorylated head was isolated by nickel-affinity chromatography, In vitro motility was observed By steady-state kinetic analysis, one-head thiophosphorylated heavy meromyosin had a similar K-m value for actin but a V-max value of similar to 50% of the fully thiophosphorylated molecule. However, single turnover analysis, which is not sensitive to small amounts of active heads, showed that one-head thiophosphorylated heavy meromyosin was 46-120 times more active than unphosphorylated HMM but only 7-19% as active as the fully thiophosphorylated molecule. Discrepancy between the single turnover and steady-state values could be explained by a small fraction of rigor heads. These rigor heads would have a large effect on the steady-state kinetics of one-head thiophosphorylated HMM. In summary, thiophosphorylation of one head leads to a molecule with unique intermediate kinetics suggesting that thiophosphorylation of one head cooperatively alters the kinetics of the partner head and vice versa. C1 Univ Nevada, Dept Biochem, Reno, NV 89557 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Cremo, CR (reprint author), Univ Nevada, 1664 N Virginia St, Reno, NV 89503 USA. FU NIAMS NIH HHS [AR40917] NR 47 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2000 VL 275 IS 20 BP 15142 EP 15151 DI 10.1074/jbc.275.20.15142 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315TD UT WOS:000087128300052 PM 10809750 ER PT J AU Zhang, ZS Torii, N Furusaka, A Malayaman, N Hu, ZY Liang, TJ AF Zhang, ZS Torii, N Furusaka, A Malayaman, N Hu, ZY Liang, TJ TI Structural and functional characterization of interaction between hepatitis B virus X protein and the proteasome complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TATA-BINDING PROTEIN; RNA-POLYMERASE-II; HBX PROTEIN; DNA-BINDING; 20S PROTEASOME; SACCHAROMYCES-CEREVISIAE; TRANSACTIVATION FUNCTION; TRANSCRIPTION MACHINERY; REGULATORY COMPLEX; ACTIVATION DOMAINS AB Hepatitis B virus (HBV) has a unique fourth open reading frame coding for a 16.5-kDa protein known as hepatitis B virus X protein (HBX), The importance of HEX in the life cycle of HBV has been well established, but the underlying molecular function of HEX remains controversial. We previously identified a proteasome subunit PSMA7 that interacts specifically with HEX in the Saccharomyces cerevisiae two-hybrid system. Here we demonstrate that PSMC1, an ATPase-like subunit of the 19 S proteasome component, also interacts with HEX and PSMA7. Analysis of the interacting domains among PSMA7, PSMC1, and HEX by deletion and site-directed mutagenesis suggested a mutually competitive structural relationship among these polypeptides. The competitive nature of these interactions is further demonstrated using a modified yeast two-hybrid dissociator system. The crucial HEX sequences involved in interaction with PSMA7 and PSMC1 are important for its function as a transcriptional coactivator. HEX, while functioning as a coactivator of AP-1 and acidic activator VP-16 in mammalian cells, had no effect on the transactivation function of their functional orthologs GCN4 and Ga14 in yeast. Overexpression of PSMC1 seemed to suppress the expression of various reporters in mammalian cells; this effect, however, was overcome by coexpression of HEX. In addition, HEX expression inhibited the cellular turnover of c-Jun and ubiquitin-Arg-P-galactosidase, two well known substrates of the ubiquitin-proteasome pathway. Thus, interaction of HEX with the proteasome complex in metazoan cells may underlie the functional basis of proteasome as a cellular target of HEX. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Rm 9B16, Bethesda, MD 20892 USA. NR 56 TC 100 Z9 112 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2000 VL 275 IS 20 BP 15157 EP 15165 DI 10.1074/jbc.M910378199 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315TD UT WOS:000087128300054 PM 10748218 ER PT J AU Padilla, PI Wada, A Yahiro, K Kimura, M Niidome, T Aoyagi, H Kumatori, A Anami, M Hayashi, T Fujisawa, J Saito, H Moss, J Hirayama, T AF Padilla, PI Wada, A Yahiro, K Kimura, M Niidome, T Aoyagi, H Kumatori, A Anami, M Hayashi, T Fujisawa, J Saito, H Moss, J Hirayama, T TI Morphologic differentiation of HL-60 cells is associated with appearance of RPTP beta and induction of Helicobacter pylori VacA sensitivity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROMYELOCYTIC LEUKEMIA-CELLS; PROTEIN-TYROSINE-PHOSPHATASE; VACUOLATING CYTOTOXIN; TERMINAL DIFFERENTIATION; RETINOIC ACID; HL60 CELLS; LINE; EXPRESSION; TOXIN; PROLIFERATION AB Phorbol la-myristate Is-acetate (PMA) induces differentiation of human leukemic HL-60 cells into cells with macrophage-like characteristics and enhances the susceptibility of HL-60 cells to the Helicobacter pylori VacA toxin (de Bernard, M., Moschioni., M., Papini, E., Telford, J. L., Rappuoli, Il., and Montecucco, C. (1998) FEES Lett. 436, 218-222). We examined the mechanism by which HL-60 cells acquire sensitivity to VacA, in particular, looking for expression of RPTP beta, a VacA-binding protein postulated to be the VacA receptor (Yahiro, K., Niidome, T., Kimura, M., Hatakeyama, T., Aoyagi, H., Kurazono, H., Imagawa, K., Wads, A, Moss, J., and Hirayama, T. (1999) J. BioL Chem, 274, 36693-36699). PMA induced expression of RPTP beta mRNA and protein as determined by RNase protection assay and indirect immunofluorescence studies, respectively. Vitamin D-3 and interferon-gamma, which stimulate differentiation of HL-60 cells into monocyte-like cells, also induced VacA sensitivity and expression of RPTP beta mRNA, whereas 1.2% Me,SO and retinoic acid, which stimulated the maturation of HL-60 into granulocyte-like cells, did not. RPTP beta antisense oligonucleotide inhibited induction of VacA sensitivity and expression of RPTP beta. Double immunostaining studies also indicated that newly expressed RPTP beta colocalized with VacA in PMA-treated HL-60 cells. In agreement with these data, BHK-21 cells, which are insensitive to VacA, when transfected with the RPTP beta cDNA, acquired VacA sensitivity. All data are consistent with the conclusion that acquisition of VacA sensitivity by PMA-treated HL-60 cells results from induction of RPTP beta, a protein that functions as the VacA receptor. C1 Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 852, Japan. Nagasaki Univ, Inst Trop Med, Dept Biochem, Nagasaki 8528523, Japan. Nagasaki Univ, Fac Engn, Dept Appl Chem, Nagasaki 8528523, Japan. Nagasaki Univ Hosp, Dept Pathol, Nagasaki 8528501, Japan. Kansai Med Univ, Dept Microbiol, Moriguchi, Osaka 5708506, Japan. Dana Farber Canc Inst, Dept Tumor Immunol, Boston, MA 02115 USA. NHKBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Hirayama, T (reprint author), Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 852, Japan. RI Niidome, Takuro/F-1508-2010 OI Niidome, Takuro/0000-0002-8070-8708 NR 37 TC 50 Z9 55 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2000 VL 275 IS 20 BP 15200 EP 15206 DI 10.1074/jbc.275.20.15200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315TD UT WOS:000087128300059 PM 10809755 ER PT J AU Fertala, J Vance, JR Pourquier, P Pommier, Y Bjornsti, MA AF Fertala, J Vance, JR Pourquier, P Pommier, Y Bjornsti, MA TI Substitutions of Asn-726 in the active site of yeast DNA topoisomerase I define novel mechanisms of stabilizing the covalent enzyme-DNA intermediate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CAMPTOTHECIN SENSITIVITY; CLEAVABLE COMPLEXES; REPLICATION FORKS; CELLS; RESISTANCE; DRUGS; PHOSPHORYLATION; TOXICITY; POISONS; BINDING AB Eukaryotic DNA topoisomerase I (Top1p) catalyzes changes in DNA topology and is the cellular target of camptothecin, Recent reports of enzyme structure highlight the importance of conserved amino acids N-terminal to the active site tyrosine and the involvement of Asn-726 in mediating Top1p sensitivity to camptothecin, To investigate the contribution of this residue to enzyme catalysis, we evaluated the effect of substituting His, Asp, or Ser for Asn-726 on yeast Top1p, Top1N726S and Top1N726D mutant proteins were resistant to camptothecin, although the Ser mutant was distinguished by a lack of detectable changes in activity. Thus, a basic residue immediately N-terminal to the active site tyrosine is required for camptothecin cytotoxicity. However, replacing Asn-726 with Asp or His interfered with distinct aspects of the catalytic cycle, resulting in cell lethality. In contrast to camptothecin, which inhibits enzyme-catalyzed religation of DNA, the His substituent enhanced the rate of DNA scission, whereas the Asp mutation diminished the enzyme binding of DNA. Yet, these effects on enzyme catalysis were not mutually exclusive as the His mutant was hypersensitive to camptothecin. These results suggest distinct mechanisms of poisoning DNA topoisomerase I may be explored in the development of antitumor agents capable of targeting different aspects of the Top1p catalytic cycle. C1 St Jude Childrens Res Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. Thomas Jefferson Univ, Dept Mol Pharmacol & Biochem, Philadelphia, PA 19107 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Bjornsti, MA (reprint author), St Jude Childrens Res Hosp, Dept Mol Pharmacol, 332 N Lauderdale St, Memphis, TN 38105 USA. FU NCI NIH HHS [CA09137, CA09346, CA58755] NR 42 TC 28 Z9 28 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2000 VL 275 IS 20 BP 15246 EP 15253 DI 10.1074/jbc.275.20.15246 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315TD UT WOS:000087128300065 PM 10809761 ER PT J AU Jang, SI Karaman-Jurukovska, N Morasso, MI Steinert, PM Markova, NG AF Jang, SI Karaman-Jurukovska, N Morasso, MI Steinert, PM Markova, NG TI Complex interactions between epidermal POU domain and activator protein 1 transcription factors regulate the expression of the profilaggrin gene in normal human epidermal keratinocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INVOLUCRIN PROMOTER ACTIVITY; DNA-BINDING; TERMINAL DIFFERENTIATION; RESPONSE ELEMENT; FLEXIBILITY; FAMILY; OCT-1; AP-1; CELLS; RECOGNITION AB The human profilaggrin gene is expressed in the granular layer during the late stages of the epidermal differentiation. The proximal promoter region of the gene confers high levels of keratinocyte-specific transcription via interactions with c-Jun/c-Fos heterodimers, Here we provide evidence for another level of complexity in the regulation of the profilaggrin promoter activity. The POU domain proteins Oct1, Skn1a/i, and Oct6, which are abundantly expressed in the epidermal cells, act to both stimulate and repress transcription in a general and a cell type-specific mode. While binding to specific recognition elements within the promoter region, they exert their effects by either stimulating or antagonizing the c-Jun-dependent activity of the promoter. The response of the promoter to forced expression of the POU domain proteins reflects the effect of these transcription factors on the endogenous profilaggrin mRNA synthesis and suggests that the latter requires a fine balance in the amounts and the activities of the individual activator protein 1 and POU domain proteins. C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Living Skin Bank, Stony Brook, NY 11794 USA. RP Markova, NG (reprint author), SUNY Stony Brook, Sch Dent Med, Dept Oral Biol & Pathol, Living Skin Bank, Westchester Hall,Rm 1112, Stony Brook, NY 11790 USA. NR 59 TC 29 Z9 31 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2000 VL 275 IS 20 BP 15295 EP 15304 DI 10.1074/jbc.275.20.15295 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315TD UT WOS:000087128300071 PM 10809764 ER PT J AU Yu, CD Wang, F Kan, M Jin, CL Jones, RB Weinstein, M Deng, CX McKeehan, WL AF Yu, CD Wang, F Kan, M Jin, CL Jones, RB Weinstein, M Deng, CX McKeehan, WL TI Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; MESSENGER-RNA LEVELS; HMG-COA REDUCTASE; LIVER DEVELOPMENT; NUCLEAR RECEPTOR; OXYSTEROL 7-ALPHA-HYDROXYLASE; COORDINATE REGULATION; HEPARAN-SULFATE; BINDING PROTEIN; FACTOR FAMILY AB Heparan sulfate-regulated transmembrane tyrosine kinase receptor FGFR4 is the major FGFR isotype in mature hepatocytes. Fibroblast growth factor has been implicated in the definition of liver from foregut endoderm where FGFR4 is expressed and stimulation of hepatocyte DNA synthesis in vitro, Here we show that livers of mice lacking FGFR4 exhibited normal morphology and regenerated normally in response to partial hepatectomy, However, the FGFR4 (-/-) mice exhibited depleted gallbladders, an elevated bile acid pool and elevated excretion of bile acids. Cholesterol- and bile acid-controlled liver cholesterol 7 alpha-hydroxylase, the limiting enzyme for bile acid synthesis, was elevated, unresponsive to dietary cholesterol, but repressed normally by dietary cholate, Expression pattern and cholate-dependent, cholesterol-induced hepatomegaly in the FGFR4 (-/-) mice suggested that activation of receptor interacting protein 140, a co-repressor of feed-forward activator liver X receptor alpha, may mediate the negative regulation of cholesterol- and bile acid-controlled liver cholesterol 7 alpha-hydroxylase transcription by FCFR4 and cholate, The results demonstrate that transmembrane sensors interface with metabolite-controlled transcription networks and suggest that pericellular matrix-controlled liver FGFR4 in particular may ensure adequate cholesterol for cell structures and signal transduction. C1 Texas A&M Univ, Inst Biosci & Technol, Syst Hlth Sci Ctr, Ctr Canc Biol & Nutr, Houston, TX 77030 USA. Texas A&M Univ, Dept Biochem & Biophys, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Grad Sch Biomed Sci, Houston, TX 77030 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP McKeehan, WL (reprint author), Texas A&M Univ, Inst Biosci & Technol, Syst Hlth Sci Ctr, Ctr Canc Biol & Nutr, 2121 W Holcombe Blvd, Houston, TX 77030 USA. RI Yu, C/G-4626-2010; deng, chuxia/N-6713-2016 FU NCI NIH HHS [CA59971]; NIDDK NIH HHS [DK35310, DK47039] NR 50 TC 218 Z9 227 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2000 VL 275 IS 20 BP 15482 EP 15489 DI 10.1074/jbc.275.20.15482 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315TD UT WOS:000087128300095 PM 10809780 ER PT J AU Herrmann, H Strelkov, SV Feja, B Rogers, KR Brettel, M Lustig, A Haner, M Parry, DAD Steinert, PM Burkhard, P Aebi, U AF Herrmann, H Strelkov, SV Feja, B Rogers, KR Brettel, M Lustig, A Haner, M Parry, DAD Steinert, PM Burkhard, P Aebi, U TI The intermediate filament protein consensus motif of helix 2B: Its atomic structure and contribution to assembly SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE intermediate filament protein; assembly; atomic structure; vimentin; desmin ID NEMATODE CAENORHABDITIS-ELEGANS; NUCLEAR LAMIN; COILED-COIL; IF PROTEINS; IN-VITRO; MOLECULAR CHARACTERISTICS; MASS DETERMINATION; ESCHERICHIA-COLI; SIZED FILAMENTS; TAIL DOMAIN AB Nearly all intermediate filament proteins exhibit a highly conserved amino acid motif (YRKLLEGEE) at the C-terminal end of their central alpha-helical rod domain. We have analyzed its contribution to the various stages of assembly by using truncated forms of Xenopus vimentin and mouse desmin, VimIAT and DesIAT, which terminate exactly before this motif, by comparing them with the wild-type and tailless proteins. It is surprising that in buffers of low ionic strength and high pH where the full-length proteins form tetramers, both VimIAT and DesIAT associated into various high molecular weight complexes. After initiation of assembly, both VimIAT and DesIAT aggregated into unit-length-type filaments, which rapidly longitudinally annealed to yield filaments of around 20 nm in diameter. Mass measurements by scanning transmission electron microscopy revealed that both VimIAT and DesIAT filaments contained considerably more subunits per cross-section than standard intermediate filaments. This indicated that the YRKLLEGEE-motif is crucial for the formation of authentic tetrameric complexes and also for the control of filament width, rather than elongation, during assembly. To determine the structure of the YRKLLEGEE domain, we grew crystals of peptides containing the last 28 amino acid residues of coil 2B, chimerically fused at its amino-terminal end to the 31 amino acid-long leucine zipper domain of the yeast transcription factor GCN4 to facilitate appropriate coiled-coil formation. The atomic structure shows that starting from Tyr400 the two helices gradually separate and that the coiled coil terminates with residue Glu405 while the downstream residues fold away from the coiled-coil axis. (C) 2000 Academic Press. C1 German Canc Res Ctr, Div Cell Biol, D-69120 Heidelberg, Germany. Univ Basel, Biozentrum, Maurice E Miller Inst, CH-4056 Basel, Switzerland. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Herrmann, H (reprint author), German Canc Res Ctr, Div Cell Biol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. RI Strelkov, Sergei/G-7425-2014 NR 81 TC 104 Z9 109 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 19 PY 2000 VL 298 IS 5 BP 817 EP 832 DI 10.1006/jmbi.2000.3719 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 330UX UT WOS:000087980500008 PM 10801351 ER PT J AU Liotta, LA Clair, T AF Liotta, LA Clair, T TI Cancer - Checkpoint for invasion SO NATURE LA English DT Editorial Material ID CELL-MIGRATION; PROTEIN C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. NR 8 TC 27 Z9 32 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 18 PY 2000 VL 405 IS 6784 BP 287 EP 288 DI 10.1038/35012728 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 314YT UT WOS:000087085700025 PM 10830943 ER PT J AU Schiffman, M Hildesheim, A Herrero, R Bratti, C AF Schiffman, M Hildesheim, A Herrero, R Bratti, C TI Human papillomavirus testing as a screening tool for cervical cancer - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. Int Agcy Res Canc, F-69372 Lyon, France. Costa Rican Social Secur Adm, San Jose, Costa Rica. RP Schiffman, M (reprint author), NCI, Bethesda, MD 20892 USA. NR 5 TC 8 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 17 PY 2000 VL 283 IS 19 BP 2525 EP 2526 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 312VL UT WOS:000086964600028 PM 10815111 ER PT J AU Iribarren, C Sidney, S Bild, DE Liu, K Markovitz, JH Roseman, JM Matthews, K AF Iribarren, C Sidney, S Bild, DE Liu, K Markovitz, JH Roseman, JM Matthews, K TI Association of hostility with coronary artery calcification in young adults - The CARDIA study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Meeting of the Conference on Cardiovascular Disease, Epidemiology, and Prevention CY MAR 24-27, 1999 CL ORLANDO, FLORIDA ID DENSITY-LIPOPROTEIN-CHOLESTEROL; ACUTE MYOCARDIAL-INFARCTION; ELECTRON-BEAM CT; HEART-DISEASE; CAROTID ATHEROSCLEROSIS; POSTMENOPAUSAL WOMEN; ADRENALINE INFUSION; TOTAL MORTALITY; RISK-FACTORS; A BEHAVIOR AB Context Psychosocial factors, including personality and character traits, may play a role in the development and expression of coronary artery disease. Objective To evaluate whether hostility, a previously reported predictor of clinical coronary artery disease, is associated with coronary calcification, which is a marker of subclinical atherosclerosis. Design Prospective cohort study. Setting and Participants Volunteer subsample from Chicago, ill, and Oakland, Calif, consisting of 374 white and black men and women, aged 18 to 30 years at baseline, who participated in the Coronary Artery Risk Development in You ng Adults (CARDIA) study. Cook-Medley hostility assessment data were collected at baseline from 1985 to 1986 and at year 5 examinations from 1990 to 1992. After the 10-year examinations in the 1995-1996 year, electron-beam computed tomographic scans were performed. Main Outcome Measures Presence of any detectable coronary artery calcification (coronary calcium score >0), and coronary artery calcium scores of 20 or higher. Results In logistic regression analysis adjusting for age, sex, race, and field center comparing those with hostility scores above and below the median of the distribution of the present sample, the odds ratio of having any coronary calcification was 2.57 (95% confidence interval, 1.31-5.22), and the odds ratio of having a calcium score of 20 or higher was 9.56 (95% confidence interval. 2.29-65.9) for calcium scores of 20 or higher. The associations with any coronary artery calcification persisted after adjusting for demographic, lifestyle, and physiological variables. Results using a cynical distrust subscale were somewhat weaker than for those using the global hostility score. Power was inadequate to perform sex- or race-specific analyses. Conclusion These results suggest that a high hostility level may predispose young adults to coronary artery calcification. C1 Kaiser Permanente Med Care Program, Oakland, CA 94611 USA. NHLBI, Dept Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Dept Family & Community Med, Chicago, IL USA. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Iribarren, C (reprint author), Kaiser Permanente Div Res, 3505 Broadway, Oakland, CA 94611 USA. FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049] NR 51 TC 145 Z9 149 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 17 PY 2000 VL 283 IS 19 BP 2546 EP 2551 DI 10.1001/jama.283.19.2546 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 312VL UT WOS:000086964600035 PM 10815118 ER PT J AU Bernard, GR Sopko, G Cerra, F Demling, R Edmunds, H Kaplan, S Kessler, L Masur, H Parsons, P Shure, D Webb, C Weidemann, H Weinmann, G Williams, D AF Bernard, GR Sopko, G Cerra, F Demling, R Edmunds, H Kaplan, S Kessler, L Masur, H Parsons, P Shure, D Webb, C Weidemann, H Weinmann, G Williams, D TI Pulmonary artery catheterization and clinical outcomes - National Heart, Lung, and Blood Institute and Food and Drug Administration workshop report SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CRITICALLY ILL PATIENTS; CARE; KNOWLEDGE; TIME AB Objective The efficacy and safety of the pulmonary artery catheter are under scrutiny because of its association with increased morbidity and mortality in observational studies. In response, the National Heart, Lung, and Blood Institute (NHLBI) and the US Food and Drug Administration (FDA) conducted the Pulmonary Artery Catheterization and Clinical Outcomes workshop in Alexandria, Va, on August 25 and 26, 1997, to develop recommendations regarding actions to improve pulmonary artery catheter utility and safety. Participants The NHLBI and FDA planning task force selected a workshop chairperson, subcommittee chairs, and participants. Approximately 85 participants were selected for their collective expertise in critical care, pulmonary medicine, cardiovascular medicine and surgery, pediatrics, nursing, biostatistics,and medical economics. The meeting was open to industry representatives and other government and lay observers. This workshop was funded by the NHLBI an the FDA's Division of Devices. Evidence Published reports relating to the efficacy and safety of the pulmonary artery catheter, especially consensus documents developed by professional societies. Consensus Process The planning task force disseminated materials, held teleconferences, and developed draft position papers prior to the workshop. These were modified during the workshop and thereafter in the course of several teleconferences, and presented to the entire group for final modifications and approval. Conclusions A need exists for collaborative education of physicians and nurses in performing, obtaining, and interpreting information from the use of pulmonary artery catheters. This effort should be led by professional societies, in collaboration with federal agencies, with the purpose of developing and disseminating standardized educational programs. Areas given high priority for clinical trials were pulmonary artery catheter use in persistent/refractory congestive heart failure, acute respiratory distress syndrome, severe sepsis and septic shock, and low-risk coronary artery bypass graft surgery. C1 Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA. NHLBI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Los Angeles, CA USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. Univ Colorado, Denver, CO 80202 USA. Washington Univ, St Louis, MO USA. Cleveland Clin, Cleveland, OH 44106 USA. Brown Univ, Providence, RI 02912 USA. RP Bernard, GR (reprint author), Vanderbilt Univ, Sch Med, Room T-1219 Med Ctr N, Nashville, TN 37232 USA. OI Wiedemann, Herbert/0000-0002-4587-4401 NR 33 TC 106 Z9 114 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 17 PY 2000 VL 283 IS 19 BP 2568 EP 2572 DI 10.1001/jama.283.19.2568 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 312VL UT WOS:000086964600038 PM 10815121 ER PT J AU Smith, LE Denissenko, MF Bennett, WP Li, HY Amin, S Tang, MS Pfeifer, GP AF Smith, LE Denissenko, MF Bennett, WP Li, HY Amin, S Tang, MS Pfeifer, GP TI Targeting of lung cancer mutational hotspots by polycyclic aromatic hydrocarbons SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID REGION DIOL-EPOXIDES; HUMAN P53 GENE; TUMOR-SUPPRESSOR GENE; FJORD-REGION; ESCHERICHIA-COLI; NEWBORN MICE; DNA-ADDUCTS; MOUSE SKIN; METABOLIC-ACTIVATION; SLOW REPAIR AB Background: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in combustion products of organic matter, including cigarette smoke. Metabolically activated diol epoxides of these compounds, including benzo[a]pyrene diol epoxide (B[a]PDE), have been suggested as causative agents in the development of lung cancer. We previously mapped the distribution of B[a]PDE adducts within the p53 tumor suppressor gene (also known as TP53), which is mutated in 60% of human lung cancers, and found that B[a]PDE adducts preferentially form at lung cancer mutational hotspots (codons 154, 157, 158, 245, 248, and 273). Other PAHs may be important in lung cancer as well, Methods: Here we have mapped the distribution of adducts induced by diol epoxides of additional PAHs: chrysene (CDE), 5-methylchrysene (5-MCDE), 6-methylchrysene (6-MCDE), benzo[c]phenanthrene (B[c]PDE), and benzo[g]chrysene (B[g]CDE) within exons 5, 7, and 8 of the p53 gene in human bronchial epithelial cells. Results: CDE exposure produced only low levels of adducts. Exposure of cells to the other activated PAHs resulted in DNA damage patterns similar to those previously observed with B[a]PDE but with some distinct differences, 5-MCDE, 6-MCDE, B[g]CDE, and B[c]PDE efficiently induced adducts at guanines within codons 154, 156, 157, 158, and 159 of exon 5, codons 237, 245 and 248 of exon 7, and codon 273 of exon 8, but the relative levels of adducts at each site varied for each compound. B[g]CDE, B[c]PDE, and 5-MCDE induced damage at codon 158 more selectively than 6-MCDE or B[a]PDE. The sites most strongly involved in PAH adduct formation were also the sites of highest mutation frequency (codons 157, 158, 245, 248, and 273), Conclusion: The data suggest that PAHs contribute to the mutational spectrum in human lung cancer. C1 NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Pfeifer, GP (reprint author), NIH, Div Canc Epidemiol & Genet, Execut Plaza S,Rm 8049, Bethesda, MD 20892 USA. FU NIEHS NIH HHS [ES03124] NR 60 TC 225 Z9 231 U1 1 U2 27 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 17 PY 2000 VL 92 IS 10 BP 803 EP 811 DI 10.1093/jnci/92.10.803 PG 9 WC Oncology SC Oncology GA 313DP UT WOS:000086985300010 PM 10814675 ER PT J AU Jemal, A Devesa, SS Fears, TR Hartge, P AF Jemal, A Devesa, SS Fears, TR Hartge, P TI Cancer surveillance series: Changing patterns of cutaneous malignant melanoma mortality rates among whites in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SKIN-CANCER; ULTRAVIOLET-RADIATION; TRENDS; CANADA; AGE; MASSACHUSETTS; POPULATION; SUNSCREEN; MIGRATION; REGISTRY AB Background: Mortality from melanoma among whites is still increasing in the United States. In this study, we describe the changing patterns of melanoma mortality rates among whites by demographic factors and geography and further assess the relationship between the geographic patterns and the UV radiation (UV-B) level. Methods: Age-adjusted incidence and mortality rates were computed by use of the 1970 U.S. population standard, Annual percent changes of mortality were estimated by filling regression lines to the logarithm of rates, The relationships between melanoma mortality rates and UV-B level over time were assessed by weighted regressions. All statistical tests were two-sided. Results: From 1950-1954 through 1990-1994, melanoma mortality rates increased by 191% and 84% among males and females, respectively. Mortality rates peaked in the 1930 through 1950 birth cohorts for females and in the 1935 through 1950 birth cohorts for males. In the 1950 through 1969 study period, melanoma mortality rates showed a strong North-South gradient, but the gradient weakened in recent periods, The absolute change in mortality for a 10% increase in UV-B among females decreased from 0.08 additional deaths per 100 000 person-years in 1950-1959 to 0.01 additional deaths in 1990-1995, In contrast, the absolute change in mortality among males showed little change over time; additional deaths increased from 0.11 to 0.12 per 100 000 person-years. Conclusions: Melanoma mortality in the United States reflects the complex interplay of UV radiation levels in each geographic region, the sun-protection behaviors of each generation of males and females in childhood and adulthood, the geographic mobility of the population, and the risk awareness and early detection. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Jemal, A (reprint author), NIH, Execut Plaza S,Room 8049, Bethesda, MD 20892 USA. NR 41 TC 88 Z9 91 U1 0 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 17 PY 2000 VL 92 IS 10 BP 811 EP 818 DI 10.1093/jnci/92.10.811 PG 8 WC Oncology SC Oncology GA 313DP UT WOS:000086985300011 PM 10814676 ER PT J AU Velie, E Kulldorff, M Schairer, C Block, G Albanes, D Schatzkin, A AF Velie, E Kulldorff, M Schairer, C Block, G Albanes, D Schatzkin, A TI Dietary fat, fat subtypes, and breast cancer in postmenopausal women: A prospective cohort study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NATIONAL-HEALTH; AMERICAN WOMEN; FOLLOW-UP; RISK; QUESTIONNAIRE; ASSOCIATION; RECORDS; EPIDEMIOLOGY; CAUSATION AB Background: The intake of total dietary fat and of certain fat subtypes has been shown to be strongly associated with breast cancer in international comparisons and in animal experiments. However, observational epidemiologic studies have generally reported either weak positive or no associations. To extend the prospective epidemiologic evidence on this question, we examined the association between adult dietary intake of fat, fat subtypes, and breast cancer in a large, prospective cohort of postmenopausal women, Methods: Participants were selected from a national breast cancer mammography screening program conducted from 1973 through 1981 at 29 centers throughout the United States. From 1987 through 1989, 40022 postmenopausal women satisfactorily completed a mailed, self-administered questionnaire that included a 60-item National Cancer Institute/Block food-frequency questionnaire. Women were then followed for an average of 5.3 years; 996 women developed breast cancer. Risk was assessed by use of Cox: proportional hazard regression, with age as the underlying time metric. All statistical tests were two-sided. Results: Compared with women in the lowest quintile (Q1) of percentage of energy from total fat, the adjusted risk ratio (RR) and 95% confidence interval (CI) for women in the highest quintile (Q5) was 1.07 (95% CI = 0.86-1.32). In analyses stratified by history of benign breast disease (BBD), a positive association was observed among only women with no history of BED (RR (Q5) (versus) (Q1) = 2.20; 95% CI = 1.41-3.42; test for trend, P = .0003). The increased risk in these women appeared to be attributable to unsaturated fat intake and oleic acid in particular. Conclusions: In this study, there was no overall association between fat intake during adulthood and breast cancer risk; however, among women with no history of BED, there appeared to be a positive association between total and unsaturated fat intake and breast cancer risk. C1 NCI, Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Evironm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Canc Prevent Studies Branch, Div Clin Sci, Bethesda, MD 20892 USA. Univ Connecticut, Sch Med, Dept Community Med & Hlth Care, Div Biostat, Farmington, CT USA. Univ Calif Berkeley, Dept Publ Hlth Nutr, Berkeley, CA 94720 USA. RP Velie, E (reprint author), NIH, 6120 Execut Blvd,MSC 7232,EPS,Rm 7026, Bethesda, MD 20892 USA. RI Block, Gladys/E-3304-2010; Kulldorff, Martin/H-4282-2011; Albanes, Demetrius/B-9749-2015; OI Kulldorff, Martin/0000-0002-5284-2993 NR 43 TC 66 Z9 70 U1 2 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 17 PY 2000 VL 92 IS 10 BP 833 EP 839 DI 10.1093/jnci/92.10.833 PG 7 WC Oncology SC Oncology GA 313DP UT WOS:000086985300014 PM 10814679 ER PT J AU Wistow, G Sardarian, L Gan, WN Wyatt, MK AF Wistow, G Sardarian, L Gan, WN Wyatt, MK TI The human gene for gamma S-crystallin: Alternative transcripts and expressed sequences from the first intron SO MOLECULAR VISION LA English DT Article ID LENS DEVELOPMENT; BETA-CRYSTALLIN; EYE LENS; C-MAF; DIFFERENTIATION; FAMILY; INVOLVEMENT; SUPERFAMILY; RECRUITMENT; ACTIVATION AB Purpose: gamma S-crystallins are major components of adult vertebrate lenses. Here we examine the population of gamma S transcripts in adult human lens and the structure of the human CRYGS genes. Methods: Adult lens human transcripts were obtained from NEIBANK, an Expressed Sequence Tag (EST) analysis of human eye tissues. The human CRYGS gene was isolated as a PAC clone and sequenced by direct and PCR-based methods. Results: As judged by EST frequency, gamma S is one of the most abundant transcripts in the adult human lens, ranking just behind beta B2-, alpha B- and alpha A-crystallins. EST analysis reveals two transcript sizes resulting from alternative AATAAA and ATTAAA polyadenylation signals. In addition, one cDNA clone was found to contain a novel insert sequence that disrupted the open reading frame. Gene sequencing confirmed that this insert comes from intron 1 and is part of a sequence corresponding to a cluster of unidentified human transcripts in dbEST. Human and mouse gamma S gene proximal promoter sequences were compared and showed a high degree of evolutionary conservation, including consensus binding sites for transcription factors of the maf and SOX families. Conclusions: The human CRYGS gene can give rise to at least two transcripts through alternative polyadenylation. A minor transcript results from alternative splicing into sequences in intron 1. These sequences form part of a transcription unit (Mys) expressed in several non-lens tissues. The identity and function Mys of is not yet known, however, the cryptic splicing of CRYGS could produce a defective protein product, with potentially deleterious results for the adult human lens. C1 NEI, Sect Mol Struct & Funct, NIH, Bethesda, MD 20892 USA. NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA. RP Wistow, G (reprint author), NEI, Sect Mol Struct & Funct, NIH, Bldg 6,Rm 331, Bethesda, MD 20892 USA. NR 31 TC 17 Z9 21 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD MAY 17 PY 2000 VL 6 IS 9 BP 79 EP 84 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 320DE UT WOS:000087385600001 PM 10837510 ER PT J AU Smith, SV Koley, AP Dai, RK Robinson, RC Leong, H Markowitz, A Friedman, FK AF Smith, SV Koley, AP Dai, RK Robinson, RC Leong, H Markowitz, A Friedman, FK TI Conformational modulation of human cytochrome P450 2E1 by ethanol and other substrates: A CO flash photolysis study SO BIOCHEMISTRY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; ENDOPLASMIC-RETICULUM; BINDING-KINETICS; CYP2E1; PURIFICATION; DEGRADATION; ACIDS; SUBSTITUTION; EXPRESSION; INHIBITION AB The alcohol-inducible cytochrome P450 2E1 is a major human hepatic P450 which metabolizes a broad array of endogenous and exogenous compounds, including ethanol, low-molecular weight toxins, and fatty acids. Several substrates are known to stabilize this P450 and inhibit its cellular degradation. Furthermore, ethanol is a known modulator of P450 2E1 substrate metabolism. We examined the CO binding kinetics of P450 2E1 after laser flash photolysis of the heme-CO bond, to probe the effects of ethanol and other substrates on protein conformation and dynamics. Ethanol had an effect on the two kinetic parameters that describe CO binding: it decreased the rate of CO binding, suggesting a decrease in the protein's conformational flexibility, and increased the photosensitivity, which indicates a local effect in the active site region such as strengthening of the heme-CO bond. Other substrates decreased the CO binding rate to varying degrees. Of particular interest is the effect of arachidonic acid, which abolished photodissociation in the absence of ethanol but had no effect in the presence of ethanol. These results are consistent with a model of P450 2E1 whereby arachidonic acid binds along a long hydrophobic binding pocket and blocks exit of CO from the heme region. C1 NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NIH, Bioengn & Phys Sci Program, Bethesda, MD 20892 USA. RP Friedman, FK (reprint author), NCI, Mol Carcinogenesis Lab, NIH, Bldg 37,Room 3E-24, Bethesda, MD 20892 USA. RI Friedman, Fred/D-4208-2016 NR 39 TC 21 Z9 22 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 16 PY 2000 VL 39 IS 19 BP 5731 EP 5737 DI 10.1021/bi000129l PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313ME UT WOS:000087002800012 PM 10801323 ER PT J AU Devereux, RB Roman, MJ Paranicas, M O'Grady, MJ Lee, ET Welty, TK Fabsitz, RR Robbins, D Rhoades, ER Howard, BV AF Devereux, RB Roman, MJ Paranicas, M O'Grady, MJ Lee, ET Welty, TK Fabsitz, RR Robbins, D Rhoades, ER Howard, BV TI Impact of diabetes on cardiac structure and function - The strong heart study SO CIRCULATION LA English DT Article DE diabetes mellitus; echocardiography; hypertrophy; ventricles ID LEFT-VENTRICULAR HYPERTROPHY; PRESSURE-OVERLOAD HYPERTROPHY; IMPAIRED GLUCOSE-TOLERANCE; M-MODE ECHOCARDIOGRAPHY; DISEASE RISK-FACTORS; CARDIOVASCULAR-DISEASE; AMERICAN-INDIANS; ARTERIAL-HYPERTENSION; POPULATION; MORTALITY AB Background-Whether diabetes mellitus (DM) adversely affects left ventricular (LV) structure and function independently of increases in body mass index (BMI) and blood pressure is controversial. Methods and Results-Echocardiography was used in the Strong Heart Study, a study of cardiovascular disease in American Indians, to compare LV measurements between 1810 participants with DM and 944 with normal glucose tolerance. Participants with DM were older (mean age, 60 versus 59 years), had higher BMI (32.4 versus 28.9 kg/m(2)) and systolic blood pressure (133 versus 124 mm Hg), and were more likely to be female, to be on antihypertensive treatment, and to live in Arizona (all P<0.001). In analyses adjusted for covariates, women and men with DM had higher LV mass and wall thicknesses and lower LV fractional shortening, midwall shortening, and stress-corrected midwall shortening (all P<0.002), Pulse pressure/stroke volume, a measure of arterial stiffness, was higher in participants with DM (P<0.001 independent of confounders). Conclusions-Non-insulin-dependent DM has independent adverse cardiac effects, including increased LV mass and wall thicknesses, reduced LV systolic chamber and myocardial function, and increased arterial stiffness. These findings identify adverse cardiovascular effects of DM, independent of associated increases in BMI and arterial pressure, that may contribute to cardiovascular events in diabetic individuals. C1 Cornell Univ, Med Ctr, New York Hosp, New York, NY 10021 USA. Univ Oklahoma, Hlth Sci Ctr, Sch Publ Hlth, Oklahoma City, OK USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. NHLBI, Bethesda, MD 20892 USA. Medstar Res Inst, Washington, DC USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. RP Devereux, RB (reprint author), New York Presbyterian Hosp, Div Cardiol, Box 222,525 East 68th St, New York, NY 10021 USA. EM rbdevere@mail.med.cornell.edu FU NHLBI NIH HHS [UO1-HL-41642, UO1-HL-41652, UO1-HL-41654] NR 34 TC 450 Z9 480 U1 0 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 16 PY 2000 VL 101 IS 19 BP 2271 EP 2276 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 314VK UT WOS:000087078100009 PM 10811594 ER PT J AU Koch, KS Aoki, T Wang, Y Atkinson, AE Gleiberman, AS Glebov, OK Leffert, HL AF Koch, KS Aoki, T Wang, Y Atkinson, AE Gleiberman, AS Glebov, OK Leffert, HL TI Site-specific integration of targeted DNA into animal cell genomes SO GENE LA English DT Article DE co-transfection; FRT inverted repeats; retroviral vectors; yeast FLP recombinase ID IMMUNOGLOBULIN RECEPTOR GENE; ADULT-RAT HEPATOCYTES; MAMMALIAN-CELLS; FLP RECOMBINASE; CRE RECOMBINASE; YEAST PLASMID; 2-MU CIRCLE; EXPRESSION; SYSTEM; SEQUENCES AB Novel genetically engineered retroviral vectors and targeting plasmids are described that enable the site-specific targeting of exogenous DNA into the genomes of cultured animal cells. The protocol involves the transduction of competent cells by a chimeric retroviral vector containing a transcription unit composed of two linked cassettes: an upstream marker gene under the control of the viral 5' LTR; and a downstream reporter trap containing a strong promoter 5' to a 48 bp yeast FRT element. When cells containing such integrated units are co-transfected with a plasmid encoding yeast FLP recombinase and a promoterless targeting plasmid containing a reporter cDNA tract 3' to an homologous FRT element, the targeting plasmid recombines at the chromosomally preconfigured FRT site, and a new hemizygous function is introduced into the downstream cassette. These reagents provide a new portable system for site-specific targeting of chemically modified genes into uniform and unique sites in genomically integrated transcription units. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA. Hlth Sci Univ Hokkaido, Fac Pharmaceut Sci, Dept Biochem, Ishikari, Hokkaido 0610293, Japan. Third Mil Med Coll, SW Hosp, Dept Infect Dis, Chongqing 400038, Peoples R China. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. NCI, Dept Genet, NNMC, Bethesda, MD 20889 USA. Univ Calif San Diego, Sch Med, Ctr Mol Genet, La Jolla, CA 92093 USA. RP Leffert, HL (reprint author), Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA. FU NCI NIH HHS [CA71390] NR 37 TC 15 Z9 18 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 16 PY 2000 VL 249 IS 1-2 BP 135 EP 144 DI 10.1016/S0378-1119(00)00153-0 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 320JL UT WOS:000087398000014 PM 10831847 ER PT J AU Chen, L Chen, MH Larson, MG Evans, J Benjamin, EJ Levy, D AF Chen, L Chen, MH Larson, MG Evans, J Benjamin, EJ Levy, D TI Risk factors for syncope in a community-based sample (The Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HYPERTROPHIC CARDIOMYOPATHY; DIAGNOSING SYNCOPE; SUDDEN-DEATH; MANAGEMENT; FAILURE AB The epidemiology of syncope has not been well described. Prior studies have examined risk factors for syncope in hospital-based or other acute or long-term core settings. To determine risk factors for syncope in a community-based sample, we performed a nested case-control study. We examined reports of syncope in Framingham Heart Study participants who underwent routine clinic visits from 1971 to 1990. For each syncope case (n = 543) 2 controls were matched for age, sex, and examination period. Mean age of subjects was 67 years (range 25 to 95); 59% were women. History of stroke or transient ischemic attack, history of myocardial infarction, high blood pressure, use of antihypertensive medication, use of other cardiac medication, smoking, alcohol intake, body moss index, systolic blood pressure, diastolic blood pressure, heart rate, atrial fibrillation, PR interval prolongation, interventricular block, and diabetes or elevated glucose level were examined as potential predictors. Using conditional logistic regression analysis, the predictors of syncope included a history of stroke or transient ischemic attack (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.62 to 4.04), use of cardiac medication (OR 1.67, 95% CI 1.21 to 2.30), and high blood pressure (OR 1.46, 95% CI 1.14 to 1.88). Lower body mass index was marginally associated with syncope (OR per 4 kg/m(2) decrement 1.10, 95% CI 0.99 to 1.22), as were increased alcohol intake (OR per 5 oz/week 1.11, 95% CI 0.99 to 1.26), and diabetes or on elevated glucose level (OR 1.29, 95% CI 0.96 to 1.75). To our knowledge, this study represents the first community-based study of risk factors for syncope. (C) 2000 by Excerpta Medica, Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Boston Med Ctr, Div Cardiol & Prevent Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Clin Epidemiol, Boston, MA USA. VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Field Program, Seattle, WA USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-38038]; NINDS NIH HHS [5-R01-NS-17950-16] NR 28 TC 17 Z9 21 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2000 VL 85 IS 10 BP 1189 EP 1193 DI 10.1016/S0002-9149(00)00726-8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 312LV UT WOS:000086945500006 PM 10801999 ER PT J AU Connor, RJ Boer, R Prorok, PC Weed, DL AF Connor, RJ Boer, R Prorok, PC Weed, DL TI Investigation of design and bias issues in case-control studies of cancer screening using microsimulation SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE bias; cancer (epidemiology); case-control studies; neoplasms ID CERVICAL-CANCER; BREAST-CANCER; EFFICACY; DEFINITION; MORTALITY; PROJECT; PROGRAM; IMPACT AB Using a microsimulation approach, the authors examined design and bias issues in case-control studies of cancer screening. Specifically, they looked at the impact on the odds ratio of the way in which exposure to screening is defined, the type of age matching, the time scale used, and the criteria used to determine control eligibility. The results showed that defining exposure as "ever/never" screened produced, as expected, a serious bias in favor of screening. Defining exposure as being screened no later than the time the case's cancer is diagnosed has a serious bias against screening. An alternative exposure definition-screening can occur no later than the time the case would have been clinically diagnosed-eliminates the bias against screening. Further, the results showed that the type of age matching and the time scale used can produce a bias against screening and that this bias can be quite strong when case-control studies are performed in populations with a periodic screening program that is the only source of screening. Finally, control eligibility criteria had little effect. C1 NCI, Div Canc Prevent, Biometry Branch, Bethesda, MD 20892 USA. Erasmus Univ, Dept Publ Hlth & Social Med, NL-3000 DR Rotterdam, Netherlands. NCI, Prevent Oncol Branch, Div Canc Prevent, Bethesda, MD 20892 USA. RP Prorok, PC (reprint author), NCI, Div Canc Prevent, Biometry Branch, EPN 344-MSC 7354,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Boer, Rob/E-6473-2015 OI Boer, Rob/0000-0003-0680-001X NR 27 TC 28 Z9 28 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 15 PY 2000 VL 151 IS 10 BP 991 EP 998 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 313JL UT WOS:000086996500009 PM 10853638 ER PT J AU Kim, G Selengut, J Levine, RL AF Kim, G Selengut, J Levine, RL TI Carbonic anhydrase III: The phosphatase activity is extrinsic SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE carbonic anhydrase; phosphatase; glutathionylation ID OXIDATIVELY MODIFIED PROTEINS; TYROSINE PHOSPHATASES; GLUTAMINE-SYNTHETASE; MUSCLE; IDENTIFICATION; RESIDUES AB The carbonic anhydrases reversibly hydrate carbon dioxide to yield bicarbonate and hydrogen ion. They have a variety of physiological functions, although the specific roles of each of the 10 known isozymes are unclear. Carbonic anhydrase isozyme III is particularly rich in skeletal muscle and adipocytes, and it is unique among the isozymes in also exhibiting phosphatase activity. Previously published studies provided evidence that the phosphatase activity was intrinsic to carbonic anhydrase III, that it had specificity for tyrosine phosphate, and that activity was regulated by reversible glutathionylation of cysteine-186. To study the mechanism of this phosphatase, we cloned and expressed the rat liver carbonic anhydrase III. The purified recombinant had the same specific activity as the carbonic anhydrase purified from rat liver, but it had virtually no phosphatase activity. We attempted to identify an activator of the phosphatase in rat liver and found a protein of similar to 14 kDa, the amount of which correlated with the phosphatase activity of the carbonic anhydrase III fractions. It was identified as liver fatty acid binding protein, which was then purified to test for activity as an activator of the phosphatase and for protein-protein interaction, but neither binding nor activation could be demonstrated. Immunoprecipitation experiments established that carbonic anhydrase III could be separated from the phosphatase activity. Finally, adding additional purification steps completely separated the phosphatase activity from the carbonic anhydrase activity. We conclude that the phosphatase activity previously considered to be intrinsic to carbonic anhydrase III is actually extrinsic. Thus, this isozyme exhibits only the carbon dioxide hydratase and esterase activities characteristic of the other mammalian isozymes, and the phosphatase previously shown to be activated by glutathionylation is not carbonic anhydrase III. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 29 TC 24 Z9 25 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 15 PY 2000 VL 377 IS 2 BP 334 EP 340 DI 10.1006/abbi.2000.1793 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 318XV UT WOS:000087310700016 PM 10845711 ER PT J AU Mandler, R Dadachova, E Brechbiel, JK Waldmann, TA Brechbiel, MW AF Mandler, R Dadachova, E Brechbiel, JK Waldmann, TA Brechbiel, MW TI Synthesis and evaluation of antiproliferative activity of a geldanamycin-Herceptin (TM) immunoconjugate SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID HUMAN-BREAST-CANCER; MONOCLONAL-ANTIBODY; IN-VIVO; ERBB-2 GENE; GELDANAMYCIN; EXPRESSION; ONCOGENE; THERAPY; AMPLIFICATION; PROTEIN AB Geldanamycin was modified with 1,4-diaminobutane to introduce a primary amine that was subsequently employed to provide a maleimide for protein linkage. Monoclonal antibody Herceptin(TM) was then derivatized to generate thiol groups that reacted with the maleimide derivative to produce the immunoconjugate. The product showed antiproliferative activity greater than native Herceptin(TM). (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20982 USA. NCI, Metab Branch, NIH, Bethesda, MD 20982 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20982 USA. RI Dadachova, Ekaterina/I-7838-2013 NR 27 TC 11 Z9 12 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 15 PY 2000 VL 10 IS 10 BP 1025 EP 1028 DI 10.1016/S0960-894X(00)00155-4 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 317HD UT WOS:000087219200007 PM 10843208 ER PT J AU Patterson, JMM Johnson, MH Zimonjic, DB Graubert, TA AF Patterson, JMM Johnson, MH Zimonjic, DB Graubert, TA TI Characterization of Ly-6M, a novel member of the Ly-6 family of hematopoietic proteins SO BLOOD LA English DT Article ID THYMIC SHARED ANTIGEN-1; CELL-CELL ADHESION; STEM-CELLS; DIFFERENTIATION ANTIGEN; MULTIGENE FAMILY; LYMPHOCYTES-T; GENE FAMILY; BONE-MARROW; EXPRESSION; IDENTIFICATION AB The Ly-6 family includes a number of highly homologous, low molecular weight glycophosphatidylinositol-linked proteins expressed on hematopoietic and lymphoid cells, The best characterized family member is Sca-1 (Ly-6A/E), an antigen commonly used for purification of murine pluripotent hematopoietic cells. We sought to characterize the genomic locus surrounding the Sca-1 gene. We identified several overlapping P1 artificial chromosomes containing the Sca-1 gene and mapped one of these to mouse chromosome 15D3.1-3.3, the region previously shown to contain members of the murine Ly-6 gene family, We then mapped this clone and found that the Sca-2 gene lies 35.4 kilobase (kb) downstream of Sca-1 in the opposite transcriptional orientation, This is the first direct demonstration of physical linkage of Ly-6 genes; A novel gene, highly homologous to Sca-1 was identified and localized 13.4 kb downstream of Sca-1. This gene, which we designated Ly-GM, shares several structural features conserved among members of the Ly-6 family, Ly-GM messenger RNA (mRNA) is easily detectable in hematopoietic tissue (bone marrow, spleen, thymus, peritoneal macrophages) as well as kidney and lung. No mRNA expression was detected in heart, stomach, liver, small intestine, brain, or skin, Ly-GM protein is detectable on 10% to 15% of peripheral blood leukocytes, including monocytes and a subpopulation of B220(+) cells, Ly-GM is broadly distributed in the bone marrow, with prominent expression on monocytes and myeloid precursors, The identification and characterization of Ly-GM adds a new member to a complex family of homologous, tightly linked genes that have proven extremely useful reagents for defining populations within the hematopoietic system. (C) 2000 by The American Society of Hematology. C1 Washington Univ, Sch Med, Div Bone Marrow Transplantat & Stem Cell Biol, St Louis, MO 63110 USA. NCI, Mol Cytogenet Sect, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Graubert, TA (reprint author), Washington Univ, Sch Med, Div Bone Marrow Transplantat & Stem Cell Biol, Campus Box 8007,660 S Euclid Ave, St Louis, MO 63110 USA. OI Graubert, Timothy/0000-0002-7710-1171 FU NHLBI NIH HHS [K08 HL03872-01] NR 40 TC 19 Z9 21 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2000 VL 95 IS 10 BP 3125 EP 3132 PG 8 WC Hematology SC Hematology GA 312PE UT WOS:000086951000018 PM 10807778 ER PT J AU Ebinu, JO Stang, SL Teixeira, C Bottorff, DA Hooton, J Blumberg, PM Barry, M Bleakley, RC Ostergaard, HL Stone, JC AF Ebinu, JO Stang, SL Teixeira, C Bottorff, DA Hooton, J Blumberg, PM Barry, M Bleakley, RC Ostergaard, HL Stone, JC TI RasGRP links T-cell receptor signaling to Ras SO BLOOD LA English DT Article ID PROTEIN-KINASE-C; NUCLEOTIDE EXCHANGE FACTOR; TYROSINE KINASE; ANTIGEN RECEPTOR; ZETA-CHAIN; ADAPTER PROTEIN; PHOSPHOLIPASE-C; ACTIVATION; TCR; PATHWAY AB Stimulation of the T-cell receptor (TCR) alters a number of intracellular signaling pathways including one that involves protein tyrosine kinases, phospholipase C-gamma 1 (PLC-gamma 1), diacylglycerol (DAG), and calcium messengers, By a divergent pathway, TCR-stimulated protein tyrosine kinase activity is thought to result independently in recruitment of the Ras activator Sos to the plasma membrane, leading to Has activation. Here we show that Ras- GRP, a Has activator that contains calcium-binding EF hands and a DAG-binding domain, is expressed in T cells, A PLC-gamma 1 inhibitor diminished activation of Ras following TCR stimulation. Membranes from TCR-stimulated Jurkat T cells exhibited increased RasGRP and increased Ras-guanyl nucleotide association activity that was inhibited by antibodies directed against RasGRP. Overexpression of RasGRP in T cells enhanced TCR-Ras-Erk signaling and augmented interleukin-2 secretion in response to calcium ionophore plus DAG analogues phorbol ester myristate or bryostatin-1. Thus, RasGRP links TCR and PLC-gamma 1 to Ras-Erk signaling, a pathway amenable to pharmacologic manipulation. (C) 2000 by The American Society of Hematology. C1 Univ Alberta, Dept Biochem, Edmonton, AB T6G 2H7, Canada. Univ Alberta, Dept Immunobiol, Edmonton, AB T6G 2H7, Canada. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP Stone, JC (reprint author), Univ Alberta, Dept Biochem, Edmonton, AB T6G 2H7, Canada. NR 46 TC 234 Z9 239 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2000 VL 95 IS 10 BP 3199 EP 3203 PG 5 WC Hematology SC Hematology GA 312PE UT WOS:000086951000028 PM 10807788 ER PT J AU Centola, M Wood, G Frucht, DM Galon, J Aringer, M Farrell, C Kingma, DW Horwitz, ME Mansfield, E Holland, SM O'Shea, JJ Rosenberg, HF Malech, HL Kastner, DL AF Centola, M Wood, G Frucht, DM Galon, J Aringer, M Farrell, C Kingma, DW Horwitz, ME Mansfield, E Holland, SM O'Shea, JJ Rosenberg, HF Malech, HL Kastner, DL TI The gene for familial Mediterranean fever, MEFV, is expressed in early leukocyte development and is regulated in response to inflammatory mediators SO BLOOD LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; NECROSIS-FACTOR-ALPHA; INTERFERON-ALPHA; BINDING PROTEIN; BEHCETS-DISEASE; RETINOIC ACID; IFN-GAMMA; CELL LINE; DIFFERENTIATION; TRANSCRIPTION AB Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever and neutrophil-mediated serosal inflammation. We recently identified the gene causing FMF, designated MEFV, and found it to be expressed in mature neutrophils, suggesting that it functions as an inflammatory regulator. To facilitate our understanding of the normal function of MEFV, we extended our previous studies, MEFV messenger RNA was detected by reverse transcriptase-polymerase chain reaction in bone marrow leukocytes, with differential expression observed among cells by in situ hybridization. CD34 hematopoietic stem-cell cultures induced toward the granulocytic lineage expressed MEFV at the myelocyte stage, concurrently with lineage commitment. The prepromyelocytic cell line HL60 expressed MEFV only at granulocytic and monocytic differentiation. MEN was also expressed in the monocytic cell lines U937 and THP-1. Among peripheral blood leukocytes, MEFV expression was detected in neutrophils, eosinophils, and to varying degrees, monocytes. Consistent with the tissue specificity of expression, complete sequencing and analysis of upstream regulatory regions of MEN revealed homology to myeloid-specific promoters and to more broadly expressed inflammatory promoter elements. In vitro stimulation of monocytes with the proinflammatory agents interferon (IFN) gamma, tumor necrosis factor, and lipopolysaccharide induced MEFV expression, whereas the antiinflammatory cytokines interleukin (IL) 4, 11-10, and transforming growth factor beta inhibited such expression. Induction by IFN-gamma occurred rapidly and was resistant to cycloheximide, IFN-alpha also induced MEFV expression. In granulocytes, MEN was up-regulated by IFN-gamma and the combination of IFN-alpha and colchicine. These results refine understanding of MEFV by placing the gene in the myelomonocytic-specific proinflammatory pathway and identifying it as an IFN-gamma immediate early gene. (C) 2000 by The American Society of Hematology. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Vienna, Dept Rheumatol Internal Med 3, A-1010 Vienna, Austria. RP Centola, M (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N210, Bethesda, MD 20892 USA. NR 82 TC 252 Z9 263 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2000 VL 95 IS 10 BP 3223 EP 3231 PG 9 WC Hematology SC Hematology GA 312PE UT WOS:000086951000033 PM 10807793 ER PT J AU Leach, FS Hsieh, JT Molberg, K Saboorian, MH McConnell, JD Sagalowsky, AI AF Leach, FS Hsieh, JT Molberg, K Saboorian, MH McConnell, JD Sagalowsky, AI TI Expression of the human mismatch repair gene hMSH2 - A potential marker for urothelial malignancy SO CANCER LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Urological-Association CY MAY 01-06, 1999 CL DALLAS, TEXAS SP Amer Urol Assoc DE hMSH2; immunohistochemistry; mismatch repair; reverse transcription-polymerase chain reaction (RT-PCR); urothelial malignancy ID NONPOLYPOSIS COLORECTAL-CANCER; BLADDER-CANCER; MICROSATELLITE INSTABILITY; URINARY-BLADDER; TUMOR-CELLS; ALTERED EXPRESSION; SOMATIC MUTATIONS; GROWTH-FACTORS; MSH2; CARCINOMA AB BACKGROUND. The human mismatch repair (MMR) gene hMSH2 (human mutS homolog-2) is a DNA repair gene that has been reported to be mutated in 40% of hereditary nonpolyposis colon cancer (HNPCC) kindreds and a small percentage of sporadic tumors. HNPCC is a cancer predisposition syndrome with an increased risk of carcinoma of the colon, endometrium, stomach, small intestine, ovary, ureter, and renal pelvis. Immunohistochemical analysis demonstrated increased hMSH2 expression in sporadic colon carcinoma and in the replicative compartment of normal epithelium. A recent immunohistochemical analysis of hMSH2 in bladder tumors correlated reduced hMSH2 expression with recurrence and higher tumor grade. In the current study, we examined hMSH2 expression in urothelial malignancy using immunohistochemical analysis and developed a molecular assay for the detection of hMSH2 expression in bladder washes. METHODS. Immunohistochemical analysis of 17 tumors from the genitourinary tract and reverse transcription coupled with polymerase chain reaction (RT-PCR) of 40 bladder washes were used to investigate hMSH2 expression in noninvasive and invasive urothelial malignancies. RESULTS. Increased expression of hMSH2 was detected in all tumors examined using immunohistochemical analysis independent of grade or stage. Reverse transcription-PCR of hMSH2 mRNA from bladder washes detected 17 of 21 patients with primary or recurrent urothelial neoplasms or tumors involving the urothelial system. Four patients with urothelial malignancies without detectable hMSH2 expression from their bladder washes had high grade lesions. Ten of 13 patients without pathologic or cystoscopic evidence of bladder tumors were negative for hMSH2 expression in bladder washes. Two patients with bladder tumors and bladder washes that were positive for hMSH2 subsequently were found to be negative for hMSH2 after treatment of their tumors and at last follow-up had remained recurrence free for at least 1 year. CONCLUSIONS. The results of the current study suggest that hMSH2 expression is increased in low and high grade urothelial neoplasms, similar to the expression pattern in sporadic colon carcinoma. However, a fraction of high grade lesions may not express hMSH2 as detected by RT-PCR from bladder washes. The ability to detect hMSH2 expression in bladder washes may allow the use of hMSH2 expression as a marker for urothelial malignancy. In addition, the ability to define hMSH2 deficient tumors using bladder washes may have prognostic significance in the treatment of patients with urothelial carcinoma. Cancer 2000;88:2333-41. (C) 2000 American Cancer Society. C1 Univ Texas, SW Med Ctr, Dept Urol, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX USA. RP Leach, FS (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 2B47, Bethesda, MD 20892 USA. FU NCI NIH HHS [T32-CA66187-01A1]; NIDDK NIH HHS [DK47657] NR 40 TC 22 Z9 34 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 MAY 15 PY 2000 VL 88 IS 10 BP 2333 EP 2341 PG 9 WC Oncology SC Oncology GA 310DD UT WOS:000086810500018 PM 10820356 ER PT J AU Ries, LAG Wingo, PA Miller, DS Howe, HL Weir, HK Rosenberg, HM Vernon, SW Cronin, K Edwards, BK AF Ries, LAG Wingo, PA Miller, DS Howe, HL Weir, HK Rosenberg, HM Vernon, SW Cronin, K Edwards, BK TI The annual report to the nation on the status of cancer, 1973-1997, with a special section on colorectal cancer SO CANCER LA English DT Article DE neoplasm; incidence rate; mortality; race; surveillance; colon; rectum; joinpoint; screening ID FATAL COLON-CANCER; BREAST-CANCER; UNITED-STATES; REDUCED RISK; MORTALITY; THERAPY; TRENDS; RATES; PREVENTION; SURVIVAL AB BACKGROUND. This annual report to the nation addresses progress in cancer prevention and control in the U.S. with a special section on colorectal cancer. This report is the joint effort of the American Cancer Society, the National Cancer Institute (NCI), the North American Association of Central Cancer Registries (NAACCR), and the Centers for Disease Control and Prevention (CDC), including the National Center for Health Statistics (NCHS). METHODS. Age-adjusted rates were based on cancer incidence data from the NCI and NAACCR and underlying cause of death as compiled by NCHS. Joinpoint analysis was based on NCI Surveillance, Epidemiology, and End Results (SEER) program incidence rates and NCHS death rates for 1973-1997. The prevalence of screening examinations for colorectal cancer was obtained from the CDC's Behavioral Risk Factor Surveillance System and the NCHS's National Health Interview Survey. RESULTS. Between 1990-1997, overall cancer incidence and death rates declined. Joinpoint analyses of cancer incidence and death rates confirmed the declines described in earlier reports. The incidence trends for colorectal cancer have shown recent steep declines for whites in contrast to a leveling off of the rates for blacks. State-to-state variations occurred in colorectal cancer screening prevalence as well as incidence and death rates. CONCLUSIONS. The continuing declines in overall cancer incidence and death rates are encouraging. However, a few of the top ten incidence or mortality cancer sites continued to increase or remained level. For many cancer sites, whites had lower incidence and mortality rates than blacks but higher rates than Hispanics, Asian and Pacific Islanders, and American Indians/Alaska Natives. The variations in colorectal cancer incidence and death rates by race/ethnicity, gender, age, and geographic area may be related to differences in risk factors, demographic characteristics, screening, and medical practice. New efforts currently are underway to increase awareness of screening benefits and treatment for colorectal cancer. Cancer 2000;88:2398-424. (C) 2000 American Cancer Society. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. N Amer Assoc Cent Canc Registries, Springfield, IL USA. Ctr Dis Control & Prevent, Div Vital Stat, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. RP Ries, LAG (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 343J, Rockville, MD 20852 USA. NR 66 TC 533 Z9 550 U1 1 U2 10 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 MAY 15 PY 2000 VL 88 IS 10 BP 2398 EP 2424 DI 10.1002/(SICI)1097-0142(20000515)88:10<2398::AID-CNCR26>3.0.CO;2-I PG 27 WC Oncology SC Oncology GA 310DD UT WOS:000086810500026 PM 10820364 ER PT J AU Zhou, Q Fukushima, P DeGraff, W Mitchell, JB Stetler-Stevenson, M Ashkenazi, A Steeg, PS AF Zhou, Q Fukushima, P DeGraff, W Mitchell, JB Stetler-Stevenson, M Ashkenazi, A Steeg, PS TI Radiation and the Apo2L/TRAIL apoptotic pathway preferentially inhibit the colonization of premalignant human breast cells overexpressing cyclin D1 SO CANCER RESEARCH LA English DT Article ID CARCINOMA IN-SITU; CANCER; HYPERPLASIA; GROWTH; FAMILY; AMPLIFICATION; PROTEIN; MEMBER; LINE AB The role of cyclin D1 overexpression in human breast premalignancy was investigated using immortal, nontumorigenic MCF-10A cells. Previous work documented that cyclin D1 overexpression promoted in vitro anchorage-independent colonization. We now report that the colonization of MCF-10A cyclin D1 transfectants was preferentially inhibited by gamma-radiation and specific classes of apoptosis inducers [Apo-2 Ligand (Apo-2L), but not tumor necrosis factor ct]. Antibody inhibition studies and semiquantitative PCR indicated that radiation inhibition of colonization was partially mediated via the Apo2L/TRAIL pathway. The apoptotic removal of cyclin D1-overexpressing, colonization-competent premalignant breast cells by Apo2L/TRAIL or other biologicals may represent a novel approach to the prevention of breast cancer. C1 NCI, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. NCI, Womens Canc Sect, Bethesda, MD 20892 USA. NCI, Flor Cytometry Unit, Bethesda, MD 20892 USA. Genentech Inc, Dept Mol Oncol, S San Francisco, CA 94080 USA. RP Steeg, PS (reprint author), NIH, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. NR 20 TC 31 Z9 31 U1 0 U2 2 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 MAY 15 PY 2000 VL 60 IS 10 BP 2611 EP 2615 PG 5 WC Oncology SC Oncology GA 314MJ UT WOS:000087059600011 PM 10825131 ER PT J AU Saitoh, N Bell, AC Recillas-Targa, F West, AG Simpson, M Pikaart, M Felsenfeld, G AF Saitoh, N Bell, AC Recillas-Targa, F West, AG Simpson, M Pikaart, M Felsenfeld, G TI Structural and functional conservation at the boundaries of the chicken beta-globin domain SO EMBO JOURNAL LA English DT Article DE chromatin domains; CTCF; globin genes; insulators; odorant receptors ID PUTATIVE OLFACTORY RECEPTOR; ENHANCER-BLOCKING ACTIVITY; LOCUS-CONTROL REGION; CHROMATIN DOMAIN; TRANSCRIPTIONAL ACTIVITY; HISTONE ACETYLATION; CHROMOSOMAL DOMAIN; ODORANT RECEPTOR; ERYTHROID-CELLS; PROTEIN CTCF AB We show that the 3' boundary of the chicken P-globin locus bears striking structural similarities to the 5' boundary. In erythroid cells a clear transition in DNase I sensitivity of chromatin at the 3' end of the locus is observed, the location of this transition is marked by a constitutive DNase I hypersensitive site (HS), and DNA spanning this site has the enhancer-blocking capacity of an insulator. This HS contains a binding site for the transcription factor CTCF, As in the case of the 5' insulator, the CTCF site is both necessary and sufficient for the enhancer-blocking activity of the 3' boundary. The position of this insulator is consistent with our proposal that it may function to maintain the distinct regulatory programs of the globin genes and their closely appended 3' neighbor, an odorant receptor gene. We conclude that both boundaries of the chicken P-globin domain are capable of playing functionally similar roles and that the same protein is a necessary component of the molecular mechanism through which these boundaries are defined. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. OI West, Adam/0000-0003-3502-7804 NR 46 TC 118 Z9 122 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 15 PY 2000 VL 19 IS 10 BP 2315 EP 2322 DI 10.1093/emboj/19.10.2315 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 315YP UT WOS:000087140800018 PM 10811622 ER PT J AU Wang, WG Caldwell, MC Lin, SK Furneaux, H Gorospe, M AF Wang, WG Caldwell, MC Lin, SK Furneaux, H Gorospe, M TI HuR regulates cyclin A and cyclin B1 mRNA stability during cell proliferation SO EMBO JOURNAL LA English DT Article DE cyclin A; cyclin B1; HuR; proliferation; mRNA stability ID RNA-BINDING PROTEIN; AU-RICH ELEMENT; MESSENGER-RNA; 3'-UNTRANSLATED REGION; POSTTRANSCRIPTIONAL REGULATION; CYTOPLASMIC POLYADENYLATION; DEPENDENT REGULATION; SERUM STIMULATION; ELAV PROTEINS; EXPRESSION AB Colorectal carcinoma RKO cells expressing reduced levels of the RNA-binding protein HuR (ASHuR) displayed markedly reduced growth. In synchronous RKO populations, HuR was almost exclusively nuclear during early G(1), increasing in the cytoplasm during late G(1), S and G(2). The expression and half-life of mRNAs encoding cyclins A and B1 similarly increased during S and G(2), then declined, indicating that mRNA stabilization contributed to their cell cycle-regulated expression. In gel-shift assays using radiolabeled cyclin RNA transcripts and RKO protein extracts, only those transcripts corresponding to the 3'-untranslated regions of cyclins A and B1 formed RNA-protein complexes in a cell cycle-dependent fashion. HuR directly bound mRNAs encoding cyclins A and B1, as anti-HuR antibodies supershifted such RNA-protein complexes. Importantly, the expression and half-life of mRNAs encoding cyclins A and B1 were reduced in ASHuR RKO cells. Our results indicate that HuR may play a critical role in cell proliferation, at least in part by mediating cell cycle-dependent stabilization of mRNAs encoding cyclins A and B1. C1 NIA, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol & Therapeut, New York, NY 10021 USA. RP Gorospe, M (reprint author), NIA, Biol Chem Lab, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 78 TC 302 Z9 304 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 15 PY 2000 VL 19 IS 10 BP 2340 EP 2350 DI 10.1093/emboj/19.10.2340 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 315YP UT WOS:000087140800021 PM 10811625 ER PT J AU Fitzhugh, AL Keefer, LK AF Fitzhugh, AL Keefer, LK TI Diazeniumdiolates: Pro- and antioxidant applications of the "NONOates" SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE diazeniumdiolates; NONOates; nitric oxide; free radicals ID NITRIC-OXIDE-DONOR; VASCULAR RELAXATION; BIOLOGICAL-SYSTEMS; CEREBRAL VASOSPASM; IN-VIVO; NO; PEROXYNITRITE; DECOMPOSITION; CYTOTOXICITY; PROTECTION AB Diazeniumdiolates are compounds containing the X-[N(O)NO](-) structural unit that as a class offer many advantages as tools for probing the roles of nitric oxide (NO) in biological redox processes. Available examples in which X is a secondary amine group spontaneously generate up to two molecules of NO per [N(O)NO](-) unit when dissolved in aqueous media; their half-lives range from 2 s (for X = L-prolyl) to 20 h [for X = (H2NCH2CH2)(2)N] at pH 7.4 and 37 degrees C, and are in general relatively little influenced by medium effects or metabolism. When X = O- (Angeli's salt), first-order dissociation produces NO- rather than NO, but the ion becomes an NO source on 1-electron oxidation; diazeniumdiolate-derived NO can also be used to generate reactive nitrogen/oxygen species with higher nitrogen oxidation states (+3 and +4) in the presence of selected oxidizing agents. The advantages of diazeniumdiolates in biomedical research are briefly illustrated with examples from the recent literature probing NO's role in inhibiting oxidative drug metabolism, radical-induced lipid oxidation, the cytotoxicity of reactive oxygen species, and ischemia-induced vascular reoxygenation injury. Future work with this compound class should provide further insight into the mechanisms of NO's involvement in pro- and antioxidant processes, and may well lead to important medicinal advances, including reversal of cerebral vasospasm and radiosensitization of hypoxic tumors. (C) 2000 Elsevier Science Inc. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Fitzhugh, AL (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bldg 538,Room 228, Frederick, MD 21702 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-56000] NR 33 TC 96 Z9 96 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY 15 PY 2000 VL 28 IS 10 BP 1463 EP 1469 DI 10.1016/S0891-5849(00)00251-3 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 343ZG UT WOS:000088732700004 PM 10927170 ER PT J AU Srivastava, M Hsieh, S Grinberg, A Williams-Simons, L Huang, SP Pfeifer, K AF Srivastava, M Hsieh, S Grinberg, A Williams-Simons, L Huang, SP Pfeifer, K TI H19 and Igf2 monoallelic expression is regulated in two distinct ways by a shared cis acting regulatory region upstream of H19 SO GENES & DEVELOPMENT LA English DT Article DE genomic imprinting; conditional deletion; DMR; H19; Igf2 ID HISTONE DEACETYLASE COMPLEX; CREATINE-KINASE GENE; DNA METHYLATION; IMPRINTED EXPRESSION; MOUSE; CHROMATIN; DELETION; ELEMENT; MECHANISMS; DROSOPHILA AB H19 and Igf2 are expressed in a monoallelic fashion from the maternal and paternal chromosomes, respectively. A region upstream of H19 has been shown to regulate such imprinted expression of both genes in cis. We have taken advantage of a loxP/cre recombinase-based strategy to delete this region in mice in a conditional manner to determine the temporal requirement of the upstream region in initiating and maintaining the imprinted expression of H19 and Igf2. Analysis of allele-specific expression of H19 and Igf2 and DNA methylation at the H19 promoter demonstrates that this region controls the monoallelic expression of the two genes in different ways, suggesting that it harbors two functionally distinct regulatory elements. Continued presence of the region is required to silence maternal Igf2 in accordance with its proposed role as an insulator. However, it does not have a direct role in keeping the paternal H19 promoter silenced. Instead, on the paternal chromosome, the upstream element mediates epigenetic modifications of the H19 promoter region during development, leading to transcriptional silencing of H19. Thereafter, its presence is redundant for preventing transcription. Presently, this temporal requirement of the silencing element appears to be a unique cis activity in the mammalian system. However, it is likely that other cis-acting elements, positive and negative, have the ability to effect stable changes in the chromatin structure and are not constantly required to give signals to the transcriptional machinery. C1 NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. RP Pfeifer, K (reprint author), NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. OI Pfeifer, Karl/0000-0002-0254-682X NR 43 TC 99 Z9 103 U1 0 U2 2 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 MAY 15 PY 2000 VL 14 IS 10 BP 1186 EP 1195 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 316YT UT WOS:000087196400003 PM 10817754 ER PT J AU Gray, TA Hernandez, L Carey, AH Schaldach, MA Smithwick, MJ Rus, K Graves, JAM Stewart, CL Nicholls, RD AF Gray, TA Hernandez, L Carey, AH Schaldach, MA Smithwick, MJ Rus, K Graves, JAM Stewart, CL Nicholls, RD TI The ancient source of a distinct gene family encoding proteins featuring RING and C3H zinc-finger motifs with abundant expression in developing brain and nervous system SO GENOMICS LA English DT Article ID PRE-MESSENGER-RNA; TRANSLATIONAL CONTROL; POXVIRUS PROTEIN; DNA RECOGNITION; BINDS; MOUSE; TRISTETRAPROLIN; VIRULENCE; COMPLEX; REGION AB Intronless genes can arise by germline retrotransposition of a cDNA originating as mRNA from an intron-containing source gene. Previously, we described several members of a family of intronless mammalian genes encoding a novel class of zinc-finger proteins, including one that shows imprinted expression and one that escapes X-inactivation. We report here the identification and characterization of the Makorin ring finger protein 1 gene (MKRN1), a highly transcribed, intron-containing source for this family of genes. Phylogenetic analyses clearly indicate that the MKRN1 gene is the ancestral founder of this gene family. We have identified MKRN1 orthologs from human, mouse, wallaby, chicken, fruitfly, and nematode, underscoring the age and conservation of this gene. The MKRN gene family encodes putative ribonucleoproteins with a distinctive array of zinc-finger motifs, including two to four C3H zinc-fingers, an unusual Cys/ His arrangement that may represent a novel zinc-finger structure, and a highly conserved RING zinc-finger. To date, we have identified nine MKRN family loci distributed throughout the human genome. The human and mouse MKRN1 loci map to a conserved syntenic group near the T-cell receptor beta cluster (TCRB) in chromosome 7q34-q35 and chromosome 6A, respectively. MKRN1 is widely transcribed in mammals, with high levels in murine embryonic nervous system and adult testis. The ancient origin of MKRN1, high degree of conservation, and expression pattern suggest important developmental and functional roles for this gene and its expressed family members. (C) 2000 Academic Press. C1 Univ Hosp Cleveland, Ctr Human Genet, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. NCI, Canc & Dev Biol Lab DBS, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. La Trobe Univ, Dept Genet, Melbourne, Vic 3083, Australia. John Carroll Univ, Dept Biol, Cleveland, OH 44118 USA. RP Carey, AH (reprint author), Case Western Reserve Univ, Sch Med, Dept Genet, 10900 Euclid Ave, Cleveland, OH 44106 USA. RI Graves, Jennifer/A-1387-2008 FU NICHD NIH HHS [HD36079, HD31491]; NIGMS NIH HHS [GM18306] NR 35 TC 53 Z9 58 U1 1 U2 1 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 MAY 15 PY 2000 VL 66 IS 1 BP 76 EP 86 DI 10.1006/geno.2000.6199 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 318AQ UT WOS:000087261500009 PM 10843807 ER PT J AU Schueler, MG Higgins, AW Nagaraja, R Tentler, D Dahl, N Gustashaw, K Willard, HF AF Schueler, MG Higgins, AW Nagaraja, R Tentler, D Dahl, N Gustashaw, K Willard, HF TI Large-insert clone/STS contigs in Xq11-q12, spanning deletions in patients with androgen insensitivity and mental retardation SO GENOMICS LA English DT Article ID FLUORESCENCE INSITU HYBRIDIZATION; HUMAN X-CHROMOSOME; YAC-CONTIG; RECEPTOR GENE; TRANSCRIPT MAP; YEAST; DNA; CONSTRUCTION; CENTROMERE; RESOLUTION AB An integrated large-insert clone map of the region Xq11-q12 is presented. A physical map containing markers within a few hundred kilobases of the centromeric locus DXZ1 to DXS1125 spans nearly 5 Mb in two contigs separated by a gap estimated to be similar to 100-250 kb. The contigs combine 75 yeast artificial chromosome clones, 12 bacterial artificial chromosome clones, and 17 P1-derived artificial chromosome clones with 81 STS or EST markers. Overall marker density across this region is similar to 1 STS/60 kb. Mapped within the contigs are 12 ESTs as well as 5 known genes, moesin (MSN), hephaestin (HEPH), androgen receptor (AR), oligophrenin-1 (OPHN1), and Eph ligand-2 (EPLG2). Orientation of the contigs on the X chromosome, as well as marker order within the contigs, was unambiguously determined by reference to a number of X chromosome breakpoints. In addition, the distal contig spans deletions from chromosomes of three patients exhibiting either complete androgen insensitivity (CAI) or a contiguous gene syndrome that includes CAI, impaired vision, and mental retardation. (C) 2000 Academic Press. C1 Case Western Reserve Univ, Sch Med, Dept Genet, Ctr Human Genet, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Res Inst, Cleveland, OH 44106 USA. NIA, Genet Lab, Baltimore, MD 21224 USA. Univ Uppsala, Childrens Hosp, Clin Genet Sect, Uppsala, Sweden. RP Willard, HF (reprint author), Case Western Reserve Univ, Sch Med, Dept Genet, Ctr Human Genet, 2109 Adelbert Rd, Cleveland, OH 44106 USA. FU NHGRI NIH HHS [HG000107]; NICHD NIH HHS [HD26202] NR 35 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 0888-7543 J9 GENOMICS JI Genomics PD MAY 15 PY 2000 VL 66 IS 1 BP 104 EP 109 DI 10.1006/geno.2000.6180 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 318AQ UT WOS:000087261500013 PM 10843811 ER PT J AU Tirnauer, JS Bierer, BE AF Tirnauer, JS Bierer, BE TI EB1 proteins regulate microtubule dynamics, cell polarity, and chromosome stability SO JOURNAL OF CELL BIOLOGY LA English DT Review ID CYTOPLASMIC DYNEIN; TUMOR-SUPPRESSOR; DROSOPHILA HOMOLOG; DYNACTIN COMPLEX; BINDING PROTEIN; MITOTIC SPINDLE; BETA-CATENIN; GENE FAMILY; IN-VIVO; APC C1 NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Bierer, BE (reprint author), NHLBI, Lab Lymphocyte Biol, NIH, 10 Ctr Dr,Bldg 10-5D49, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [K08 DK 02578] NR 50 TC 158 Z9 163 U1 1 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 15 PY 2000 VL 149 IS 4 BP 761 EP 766 DI 10.1083/jcb.149.4.761 PG 6 WC Cell Biology SC Cell Biology GA 315DQ UT WOS:000087097700002 PM 10811817 ER PT J AU He, XP Yang, F Xie, ZP Lu, B AF He, XP Yang, F Xie, ZP Lu, B TI Intracellular Ca2+ and Ca2+/calmodulin-dependent kinase II mediate acute potentiation of neurotransmitter release by neurotrophin-3 SO JOURNAL OF CELL BIOLOGY LA English DT Article DE ryanodine receptors; inositol 1,4,5-trisphosphate receptors acetylcholine; neuromuscular junction; synaptic transmission ID DEVELOPING NEUROMUSCULAR SYNAPSES; LONG-TERM POTENTIATION; CULTURED HIPPOCAMPAL-NEURONS; SQUID GIANT SYNAPSE; DEVELOPING MOTONEURONS; SIGNAL-TRANSDUCTION; QUANTAL SECRETION; DENDRITIC GROWTH; BDNF; PLASTICITY AB Neurotrophins have been shown to acutely modulate synaptic transmission in a variety of systems, but the underlying signaling mechanisms remain unclear. Here we provide evidence for an unusual mechanism that mediates synaptic potentiation at the neuromuscular junction (NMJ) induced by neurotrophin-3 (NT3), using Xenopus nerve-muscle co-culture. Unlike brain-derived neurotrophic factor (BDNF), which requires Ca2+ influx for its acute effect, NT3 rapidly enhances spontaneous transmitter release at the developing NMJ even when Ca2+ influx is completely blocked, suggesting that the NT3 effect is independent of extracellular Ca2+. Depletion of intracellular Ca2+ stores, or blockade of inositol 1,4,5-trisphosphate (IP3) or ryanodine receptors, prevents the NT3-induced synaptic potentiation. Blockade of IP3 receptors can not prevent BDNF-induced potentiation, suggesting that BDNF and NT3 use different mechanisms to potentiate transmitter release. Inhibition of Ca2+/calmodulin-dependent kinase II (CaMKII) completely blocks the acute effect of NT3, Furthermore, the NT3-induced potentiation requires a continuous activation of CaMKII, because application of the CaMKII inhibitor KN62 reverses the previously established NT3 effect. Thus, NT3 potentiates neurotransmitter secretion by stimulating Ca2+ release from intracellular stores through IP3 and/or ryanodine receptors, leading to an activation of CaMKII. C1 NICHHD, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHHD, Unit Synapse Dev & Plast, NIH, Bldg 49,Rm 6A80,49 Convent Dr,MSC4480, Bethesda, MD 20892 USA. RI Yang, Feng/C-9530-2011; Lu, Bai/A-4018-2012 NR 49 TC 58 Z9 58 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 15 PY 2000 VL 149 IS 4 BP 783 EP 791 DI 10.1083/jcb.149.4.783 PG 9 WC Cell Biology SC Cell Biology GA 315DQ UT WOS:000087097700005 PM 10811820 ER PT J AU Leissring, MA Akbari, Y Fanger, CM Cahalan, MD Mattson, MP LaFerla, FM AF Leissring, MA Akbari, Y Fanger, CM Cahalan, MD Mattson, MP LaFerla, FM TI Capacitative calcium entry deficits and elevated luminal calcium content in mutant presenilin-1 knockin mice SO JOURNAL OF CELL BIOLOGY LA English DT Article DE Alzheimer's disease; endoplasmic reticulum; phosphoinositide signaling; store-operated calcium channel; store-operated calcium entry ID FAMILIAL ALZHEIMERS-DISEASE; AMYLOID-BETA-PEPTIDE; FIBROBLASTS; MUTATIONS; CELLS; HOMEOSTASIS; GENE; EXPRESSION; NEURONS; RELEASE AB Dysregulation of calcium signaling has been causally implicated in brain aging and Alzheimer's disease. Mutations in the presenilin genes (PS1, PS2), the leading cause of autosomal dominant familial Alzheimer's disease (FAD), cause highly specific alterations in intracellular calcium signaling pathways that may contribute to the neurodegenerative and pathological lesions of the disease. To elucidate the cellular mechanisms underlying these disturbances, we studied calcium signaling in fibroblasts isolated from mutant PS1 knockin mice. Mutant PS1 knockin cells exhibited a marked potentiation in the amplitude of calcium transients evoked by agonist stimulation. These cells also showed significant impairments in capacitative calcium entry (CCE, also known as store-operated calcium entry), an important cellular signaling pathway wherein depletion of intracellular calcium stores triggers influx of extracellular calcium into the cytosol. Notably, deficits in CCE were evident after agonist stimulation, but nor if intracellular calcium stores were completely depleted with thapsigargin. Treatment with ionomycin and thapsigargin revealed that calcium levels within the ER were significantly increased in mutant PS1 knockin cells. Collectively, our findings suggest that the overfilling of calcium stores represents the fundamental cellular defect underlying the alterations in calcium signaling conferred by presenilin mutations. C1 Univ Calif Irvine, Dept Neurobiol & Behav, Ctr Neurobiol Learning & Memory, Lab Mol Neuropathogenesis, Irvine, CA 92697 USA. Univ Calif Irvine, Inst Brain Aging & Dementia, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP LaFerla, FM (reprint author), Univ Calif Irvine, Dept Neurobiol & Behav, Ctr Neurobiol Learning & Memory, Lab Mol Neuropathogenesis, 1109 Gillespie Neurosci Res Facil, Irvine, CA 92697 USA. RI Mattson, Mark/F-6038-2012 FU NIA NIH HHS [AG16573, P50 AG016573] NR 25 TC 227 Z9 235 U1 1 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 15 PY 2000 VL 149 IS 4 BP 793 EP 797 DI 10.1083/jcb.149.4.793 PG 5 WC Cell Biology SC Cell Biology GA 315DQ UT WOS:000087097700006 PM 10811821 ER PT J AU Freeman, L Aragon-Alcaide, L Strunnikov, A AF Freeman, L Aragon-Alcaide, L Strunnikov, A TI The condensin complex governs chromosome condensation and mitotic transmission of rDNA SO JOURNAL OF CELL BIOLOGY LA English DT Article DE SMC; condensin; chromosome condensation; chromosome segregation; chromatin ID YEAST SACCHAROMYCES-CEREVISIAE; SISTER-CHROMATID COHESION; UBIQUITOUS PROTEIN FAMILY; DOSAGE COMPENSATION; FISSION YEAST; BUDDING YEAST; 13S CONDENSIN; X-CHROMOSOME; NUCLEOTIDE-SEQUENCE; MUTATIONAL ANALYSIS AB We have characterized five genes encoding condensin components in Saccharomyces cerevisiae. All genes are essential for cell viability and encode proteins that form a complex in vivo. We characterized new mutant alleles of the genes encoding the core subunits of this complex, smc2-8 and smc4-1. Both SMC2 and SMC4 are essential for chromosome transmission in anaphase. Mutations in these genes cause defects in establishing condensation of unique (chromosome VIII arm) and repetitive (rDNA) regions of the genome but do not impair sister chromatid cohesion. In vivo localization of Smc4p fused to green fluorescent protein showed that, unexpectedly, in S. cerevisiae the condensin complex concentrates in the rDNA region at the G2/M phase of the cell cycle, rDNA segregation in mitosis is delayed and/or stalled in smc2 and smc4 mutants, compared with separation of pericentromeric and distal arm regions. Mitotic transmission of chromosome III carrying the rDNA translocation is impaired in smc2 and smc4 mutants. Thus, the condensin complex in S. cerevisiae has a specialized function in mitotic segregation of the rDNA locus. Chromatin immunoprecipitation (ChIP) analysis revealed that condensin is physically associated with rDNA in vivo. Thus, the rDNA array is the first identified set of DNA sequences specifically bound by condensin in vivo. The biological role of higher-order chromosome structure in S. cerevisiae is discussed. C1 NICHHD, Mol Embryol Lab, NIH, Unit Chromosome Struct & Funct, Bethesda, MD 20892 USA. RP Strunnikov, A (reprint author), NICHHD, Mol Embryol Lab, NIH, Unit Chromosome Struct & Funct, 18T Lib Dr,Room 106, Bethesda, MD 20892 USA. OI Strunnikov, Alexander/0000-0002-9058-2256 NR 50 TC 198 Z9 205 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 15 PY 2000 VL 149 IS 4 BP 811 EP 824 DI 10.1083/jcb.149.4.811 PG 14 WC Cell Biology SC Cell Biology GA 315DQ UT WOS:000087097700008 PM 10811823 ER PT J AU Lauwers, K Saunders, R Vogels, R Vandenbussche, E Orban, GA AF Lauwers, K Saunders, R Vogels, R Vandenbussche, E Orban, GA TI Impairment in motion discrimination tasks is unrelated to amount of damage to superior temporal sulcus motion areas SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE cerebral cortex; primate; motion perception; just noticeable differences; MT/V5; ablation ID PERCEPTION FOLLOWING LESIONS; UNILATERAL CEREBRAL-LESIONS; HUMAN VISUAL-CORTEX; MACAQUE MONKEY; ORIENTATION DISCRIMINATION; TOPOGRAPHIC ORGANIZATION; DIRECTIONAL DEFECTS; RESPONSE PROPERTIES; 2ND-ORDER MOTION; RECEPTIVE-FIELDS AB The behavioral role of the middle temporal (MT/V5) area and its satellites in motion processing is still unclear, particularly the degree to which MT/V5 proper is critical for different types of motion processing. Therefore, effects of small and large lesions in the caudal part of the superior temporal sulcus of macaque monkeys were compared for two tasks requiring different types of motion processing: a direction and a kinetic orientation discrimination. The small lesion was restricted to the peripheral representation of MT/V5 but included V4t, whereas the large lesion included all of MT/V5 and the medial superior temporal (MST) area as well as substantial parts of the floor of the superior temporal (FST) area. Both lesions resulted in significant and long-lasting impairment of direction discrimination but had a lesser effect on kinetic orientation discrimination. Thus the effects of small STS lesions on motion perception are much stronger than expected. (C) 2000 Wiley-Liss, Inc. C1 Katholieke Univ Leuven, Lab Neuro Psychofysiol, B-3000 Louvain, Belgium. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Orban, GA (reprint author), Katholieke Univ Leuven, Lab Neuro Psychofysiol, Campus Gasthuisberg,Herestr 49, B-3000 Louvain, Belgium. NR 54 TC 23 Z9 23 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 15 PY 2000 VL 420 IS 4 BP 539 EP 557 DI 10.1002/(SICI)1096-9861(20000515)420:4<539::AID-CNE10>3.0.CO;2-3 PG 19 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 309AL UT WOS:000086745000010 PM 10805926 ER PT J AU Nanki, T Lipsky, PE AF Nanki, T Lipsky, PE TI Cutting edge: Stromal cell-derived factor-1 is a costimulator for CD4(+) T cell activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; SIGNALING PATHWAYS; MOLECULAR-CLONING; PERIPHERAL-BLOOD; PROTEIN-KINASE; LYMPHOCYTES; CHEMOTAXIS; EXPRESSION; MECHANISM; SDF-1 AB Stromal cell-derived factor (SDF)-1 is a chemoattractant for T cells, precursor B cells, monocytes, and neutrophils. SDF-1 alpha was also found to up-regulate expression of early activation markers (CD69, CD25, and CD154) by anti-CD3-activated CD4(+) T cells. In addition, SDF-1 alpha costimulated proliferation of CD4(+) T cells and production of IL-2, IFN-gamma, IL-4, and IL-10, Stimulation with SDF-1 alpha alone did not induce activation marker expression, proliferation, or cytokine production by the CD4(+) T cells. SDF-1 alpha-mediated costimulation was blocked by anti-CXC chemokine receptor-4 mAb, RANTES also increased activation marker expression by anti-CD3-stimulated peripheral CD4(+) T cells, but less effectively than SDF-1 alpha did, and did not up-regulate IL-2 production and proliferation. These results indicate that SDF-1 and CXC chemokine receptor-4 interactions not only play a role in T cell migration but also provide potent costimulatory signals to Ag-stimulated T cells. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Harold C Simmons Arthrit Res Ctr, Dallas, TX 75235 USA. RP Lipsky, PE (reprint author), NIAMSD, Bldg 10,Room 9N228,10 Ctr Dr MSC 1820, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR-39169] NR 29 TC 132 Z9 143 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2000 VL 164 IS 10 BP 5010 EP 5014 PG 5 WC Immunology SC Immunology GA 312MW UT WOS:000086947900005 PM 10799853 ER PT J AU van der Veen, RC Dietlin, TA Hofman, FM Pen, L Segal, BH Holland, SM AF van der Veen, RC Dietlin, TA Hofman, FM Pen, L Segal, BH Holland, SM TI Superoxide prevents nitric oxide-mediated suppression of helper T lymphocytes: Decreased autoimmune encephalomyelitis in nicotinamide adenine dinucleotide phosphate oxidase knockout mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; LOW-DENSITY-LIPOPROTEIN; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; IFN-GAMMA; PERITONEAL-MACROPHAGES; SYNTHASE INHIBITORS; CELL PROLIFERATION; IN-VITRO; PEROXYNITRITE AB NO, which suppresses T cell proliferation, may be inactivated by superoxide (O-2(-)) due to their strong mutual affinity. To examine this possibility, preactivated Th clones were cocultured with stimulated macrophages. PMA neutralized the inhibitory activity of NO, which aas dependent on extracellular O-2(-) production. In contrast, macrophages from p47(phox -/-) (pKO) mice, which lack functional NADPH oxidase, retained their NO-dependent inhibition of T cell proliferation upon stimulation with PMA, indicating that NADPH oxidase is the major source of NO-inactivating O-2(-) in this system. To examine the NO-O-2(-) interaction in vivo, the role of NADPH oxidase in experimental autoimmune encephalomyelitis was studied in pKO mice. No clinical or histological signs were observed in the pKO mice. Neither a bias in Th subsets nor a reduced intensity of T cell responses could account for the disease resistance. Although spleen cells from pKO mice proliferated poorly in response to the immunogen, inhibition of NO synthase uncovered a normal proliferative response, These results indicate that NO activity may play a critical role in T cell responses in pKO mite and that in normal spleens inhibition of T cell proliferation by NO may be prevented by simultaneous NADPH oxidase activity. C1 Univ So Calif, Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. RP van der Veen, RC (reprint author), Univ So Calif, Sch Med, Dept Neurol, 1333 San Pablo St,MCH 142, Los Angeles, CA 90033 USA. NR 45 TC 69 Z9 72 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2000 VL 164 IS 10 BP 5177 EP 5183 PG 7 WC Immunology SC Immunology GA 312MW UT WOS:000086947900028 PM 10799876 ER PT J AU Kubota, R Soldan, SS Martin, R Jacobson, S AF Kubota, R Soldan, SS Martin, R Jacobson, S TI An altered peptide ligand antagonizes antigen-specific T cells of patients with human T lymphotropic virus type I-associated neurological disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; MYELIN BASIC-PROTEIN; AUTOIMMUNE ENCEPHALOMYELITIS; RECEPTOR ANTAGONISTS; VIRAL PEPTIDES; HTLV-1 TAX; MYELOPATHY; LYMPHOCYTES; HETEROGENEITY; RECOGNITION AB Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurologic disease associated with HTLV-I infection, in which chronically activated, HTLV-I-specific CD8(+) CTL have been suggested to be immunopathogenic. In HLA-A2 HAM/TSP patients, CD8(+) HTLV-I-specific CTLs recognize an immunodominant peptide of the HTLV-I Tax protein, Tax(11-19). We examined the functional outcome on activation of both cloned peripheral blood and cerebrospinal spinal fluid-derived CTL and bulk PBMC from HAM/TSP patients by altered peptide ligands (APL) derived from HTLV-I Tax(11-19). In CTL clones generated from PBMC and CSF of HLA-A2 HAM/TSP patients, an APL substituted at position 5 significantly decreased CTL responses when compared with the native peptide. Moreover, these ligands were also shown to inhibit CTL responses to the native peptide in bulk PBMC of HLA-A2 HAM/TSP patients. These data suggest that a modification of an antigenic peptide at the central position can manipulate the T cell responses in bulk PBMC from different individuals,vith an inflammatory disease. Additionally, these results have implications for the potential use of APL-based immunotherapy in this T cell-mediated CNS disease. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Jacobson, S (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 51 TC 12 Z9 13 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 MAY 15 PY 2000 VL 164 IS 10 BP 5192 EP 5198 PG 7 WC Immunology SC Immunology GA 312MW UT WOS:000086947900030 PM 10799878 ER PT J AU Suzuki, Y Sher, A Yap, G Park, D Neyer, LE Liesenfeld, O Fort, M Kang, H Gufwoli, E AF Suzuki, Y Sher, A Yap, G Park, D Neyer, LE Liesenfeld, O Fort, M Kang, H Gufwoli, E TI IL-10 is required for prevention of necrosis in the small intestine and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice following peroral infection with Toxoplasma gondii SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; NATURAL-KILLER-CELLS; INTERFERON-GAMMA; IFN-GAMMA; IMMUNE-RESPONSE; FACTOR-ALPHA; INTERLEUKIN-12; ENCEPHALITIS; LYMPHOCYTES; ANTIBODY AB The role for IL-10 in the immunopathogenesis of acute toxoplasmosis following peroral infection was examined in both genetically susceptible C57BL/6 and resistant BALB/c mice. C57BL/6-background IL-10-targeted mutant (IL-10(-/-)) mice all died in 2 wk after infection with 20 cysts of the ME49 strain, whereas only 20% of control mice succumbed. Histological studies revealed necrosis in the small and large intestines and livers of infected IL-10(-/-) mice, The necrosis in the small intestine was the most severe pathologic response and was not observed in control mice. Treatment of infected IL-10(-/-) mice with either anti-CD4 or anti-IFN-gamma mAb prevented intestinal pathology and significantly prolonged time to death. Treatment of these animals with anti-IL-12 mAb also prevented the pathology. Significantly greater amounts of IFN-gamma, mRNA were detected in the lamina propria lymphocytes obtained from the small intestine of infected IL-10(-/-) mice than those from infected control mice, In common with C57BL/6-background IL-10(-/-) mice, BALB/c-background IL-10(-/-) mice all died developing intestinal pathology after infection. Control BALB/c mice all survived even after infection with 100 cysts and did not develop the intestinal lesions. Treatment with anti-IFN-gamma mAb prevented the pathology and prolonged time to death of the infected n-10(-/-) mice, These results strongly suggest that IL-10 plays a critical role in down-regulating IFN-gamma production in the small intestine following sublethal peroral infection with Toxaplasma gondii and that this do,vn-regulatory effect of IL-10 is required for prevention of development of IFN-gamma-mediated intestinal pathology and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice. C1 Palo Alto Med Res Fdn, Res Inst, Dept Immunol & Infect Dis, Palo Alto, CA 94301 USA. Stanford Univ, Dept Med, Div Infect Dis & Geog Med, Sch Med, Stanford, CA 94305 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. DNAX Res Inst Mol & Cellular Biol Inc, Dept Immunol, Palo Alto, CA 94304 USA. RP Suzuki, Y (reprint author), Palo Alto Med Res Fdn, Res Inst, Dept Immunol & Infect Dis, 860 Bryant St, Palo Alto, CA 94301 USA. FU NIAID NIH HHS [AI04717, AI38260] NR 37 TC 138 Z9 145 U1 0 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 MAY 15 PY 2000 VL 164 IS 10 BP 5375 EP 5382 PG 8 WC Immunology SC Immunology GA 312MW UT WOS:000086947900053 PM 10799901 ER PT J AU Nagaraju, K Casciola-Rosen, L Rosen, A Thompson, C Loeffler, L Parker, T Danning, C Rochon, PJ Gillespie, J Plotz, P AF Nagaraju, K Casciola-Rosen, L Rosen, A Thompson, C Loeffler, L Parker, T Danning, C Rochon, PJ Gillespie, J Plotz, P TI The inhibition of apoptosis in myositis and in normal muscle cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY MYOPATHIES; T-CELLS; MUSCULAR-DYSTROPHIES; DNA-FRAGMENTATION; FAS LIGAND; EXPRESSION; DEATH; COMPLEX; ANTIGEN; FIBERS AB The mechanism of injury and death of muscle cells in the inflammatory myopathies (dermatomyositis, polymyositis, and inclusion body myositis) remains obscure, We and others have not detected apoptosis in the muscle biopsies from patients with myositis despite clear evidence of cell damage and loss. We provide evidence in this study that Fas ligand (FasL) as well as Fas is present on muscle cells and inflammatory cells in myositis biopsies: Fas is present on most muscle cells and lymphocytes, and Fast is present on degenerating muscle cells and many infiltrating mononuclear cells, The expression of both Pas and Fast in the inflamed tissue makes the absence of apoptosis more striking. To address the mechanisms of this resistance to classical apoptosis in muscle cells, we have investigated the expression of the antiapoptotic molecule FLICE (Fas-associated death domain-like IL-1-converting enzyme)-inhibitory protein (FLIP) in muscle biopsies of myositis patients and in cultured human skeletal muscle cells. Using laser capture microscopy, we have shown that FLIP is expressed in the muscle fibers and on infiltrating lymphocytes of myositis biopsies. Furthermore, we have shown that FLIP, but not Bcl-2, is expressed in cultured human skeletal muscle cells stimulated with proinflammatory cytokines, and inhibition of FLIP with antisense oligonucleotides promotes significant cleavage of poly(ADP-ribose) polymerase autoantigen, a sensitive indicator of apoptosis. These studies strongly suggest that the resistance of muscle to Fas-mediated apoptosis is due to the expression of FLIP in muscle cells in the inflammatory environment in myositis. C1 NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Dermatol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Cell Biol & Anat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Plotz, P (reprint author), NIAMSD, Arthritis & Rheumatism Branch, NIH, Bldg 10,Room 9N-244, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR44684] NR 32 TC 59 Z9 63 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2000 VL 164 IS 10 BP 5459 EP 5465 PG 7 WC Immunology SC Immunology GA 312MW UT WOS:000086947900065 PM 10799913 ER PT J AU Muraro, PA Pette, M Bielekova, B McFarland, HF Martin, R AF Muraro, PA Pette, M Bielekova, B McFarland, HF Martin, R TI Human autoreactive CD4(+) T cells from naive CD45RA(+) and memory CD45RO(+) subsets differ with respect to epitope specificity and functional antigen avidity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; MULTIPLE-SCLEROSIS PATIENTS; RESTING B-CELLS; LYMPHOCYTE-T; HEALTHY-INDIVIDUALS; FINE SPECIFICITY; PERIPHERAL-BLOOD; CD45; EXPRESSION; ACTIVATION AB T cells with specificity for self-Ags are normally present in the peripheral blood, and, upon activation, may target tissue Ags and become involved in the pathogenesis of autoimmune processes. In multiple sclerosis, a demyelinating disease of the CNS, it is postulated that inflammatory damage is initiated by CD4(+) T cells reactive to myelin Ags, To investigate the potential naive vs memory origin of circulating myelin-reactive cells, we have generated myelin basic protein (MBP)- and tetanus toroid-specific T cell clones from CD45RA(+)/RO- and CD45RO(+)/RA(-) CD4(+) T cell subsets from the peripheral blood of multiple sclerosis patients and controls. Our results show that 1) the response to MBP, different from that to TT, predominantly emerges from the CD45RA(+) subset; 2) the reactivity to immunodominant MBP epitopes mostly resides in the CD45RA(+) subset; 3) in each individual, the recognition of single MBP epitopes is skewed to either subset, with no overlap in the Ag fine specificity; and 4) in spite of a lower expression of costimulatory and adhesion molecules, CD45RA(+) subset-derived clones recognize epitopes with higher functional Ag avidity. These findings point to a central role of the naive CD45RA(+) T cell subset as the source for immunodominant, potentially pathogenic effector CD4(+) T cell responses in humans. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Chieti, Sch Med, Dept Oncol & Neurosci, Chieti, Italy. Tech Univ Dresden, Klinikum Carl Gustav Carus, Neurol Klin, Dresden, Germany. RP Martin, R (reprint author), NINDS, Neuroimmunol Branch, NIH, 10 Ctr Dr MSC 1400, Bethesda, MD 20892 USA. NR 49 TC 50 Z9 51 U1 0 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 MAY 15 PY 2000 VL 164 IS 10 BP 5474 EP 5481 PG 8 WC Immunology SC Immunology GA 312MW UT WOS:000086947900067 PM 10799915 ER PT J AU Scamurra, RW Miller, DJ Dahl, L Abrahamsen, M Kapur, V Wahl, SM Milner, ECB Janoff, EN AF Scamurra, RW Miller, DJ Dahl, L Abrahamsen, M Kapur, V Wahl, SM Milner, ECB Janoff, EN TI Impact of HIV-1 infection on V(H)3 gene repertoire of naive human B cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SUPERANTIGEN-BINDING-SITE; INFLUENZAE TYPE-B; IMMUNODEFICIENCY-VIRUS-INFECTION; V-H FAMILY; CAPSULAR POLYSACCHARIDE; HUMAN-ANTIBODIES; SOMATIC HYPERMUTATION; PNEUMOCOCCAL VACCINE; HOMOSEXUAL MEN; USAGE AB B tells of the largest Ig variable heavy chain gene (V-H) family, V(H)3, are reportedly decreased in patients with late stage HIV-1 disease, This deficit may contribute to their impaired responses to infections and vaccines. We confirmed that the V(H)3 family was underrepresented in serum IgM proteins, with a 45% decrease in patients with advanced HIV-1 disease. However, the proportion of V(H)3 within V-H(1-6) IgM mRNA from peripheral B cells did not differ from that of control subjects (mean +/- SD, 57.1 +/- 9.7 vs 61.1 +/- 8.7%), Similarly, within V-H(1-6) IgD mRNA, which even more closely represents the unstimulated naive repertoire, the relative expression of V(H)3 mRNA was comparable in the two groups. Moreover, the frequency of individual genes within the V(H)3 family for IgD, particularly genes which encode putative HIV-1 gp120 binding sites, also was normal in HIV-1-infected patients, However, V(H)3 family expression for IgG mRNA was significantly decreased (17%) and V(H)4 IgG was increased (33%) relative to other V-H families in advanced HIV-1-infected patients. Thus, the changes in V-H family expression were more readily apparent in previously activated IgG "memory" B cell populations and, likely, in cells actively producing IgM rather than in resting naive cells. The presence of a relatively normal naive V(H)3 IgM and IgD mRNA repertoire in resting cells supports the prospect that with proper stimulation, particularly in conjunction with effective antiviral therapy, vigorous humoral immune responses to infections and vaccines may be elicited in this high-risk population. C1 Univ Minnesota, Sch Med, Vet Affairs Med Ctr, Infect Dis Sect 111F,Ctr Mucosal & Vaccine Biol, Minneapolis, MN 55417 USA. Univ Minnesota, Coll Vet Med, Dept Vet Pathobiol, St Paul, MN 55108 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Virginia Mason Res Ctr, Seattle, WA 98101 USA. RP Janoff, EN (reprint author), Univ Minnesota, Sch Med, Vet Affairs Med Ctr, Infect Dis Sect 111F,Ctr Mucosal & Vaccine Biol, 1 Vet Dr, Minneapolis, MN 55417 USA. RI Kapur, Vivek/F-7610-2013; OI Kapur, Vivek/0000-0002-9648-0138 FU NIAID NIH HHS [AI39445]; NIDCR NIH HHS [DE72621, DE42600] NR 58 TC 38 Z9 40 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2000 VL 164 IS 10 BP 5482 EP 5491 PG 10 WC Immunology SC Immunology GA 312MW UT WOS:000086947900068 PM 10799916 ER PT J AU Glazner, GW Chan, SL Lu, CB Mattson, MP AF Glazner, GW Chan, SL Lu, CB Mattson, MP TI Caspase-mediated degradation of AMPA receptor subunits: A mechanism for preventing excitotoxic necrosis and ensuring apoptosis SO JOURNAL OF NEUROSCIENCE LA English DT Article DE calcium; excitotoxicity; glutamate receptors; hippocampus; kainate; neurotrophic factor; NMDA ID FIBROBLAST GROWTH-FACTOR; HUMAN CORTICAL-NEURONS; HIPPOCAMPAL-NEURONS; CELL-DEATH; SYNAPTIC PLASTICITY; CALCIUM HOMEOSTASIS; GLUTAMATE RECEPTORS; PARKINSONS-DISEASE; OXIDATIVE STRESS; PROTEOLYSIS AB Activation of ionotropic glutamate receptors of the AMPA and NMDA subtypes likely contributes to neuronal injury and death in various neurodegenerative disorders. Excitotoxicity can manifest as either apoptosis or necrosis, but the mechanisms that determine the mode of cell death are not known. We now report that levels of AMPA receptor subunits GluR-1 and GluR-4 are rapidly decreased in cultured rat hippocampal neurons undergoing apoptosis in response to withdrawal of trophic support (WTS), whereas levels of NMDA receptor subunits NR1, NR2A, and NR2B are unchanged. Exposure of isolated synaptosomal membranes to "apoptotic" cytosolic extracts resulted in rapid degradation of AMPA receptor subunits. Treatment of cells and synaptosomal membranes with the caspase inhibitors prevented degradation of AMPA receptor subunits, demonstrating a requirement for caspases in the process. Calcium responses to AMPA receptor activation were reduced after withdrawal of trophic support and enhanced after treatment with caspase inhibitors. Vulnerability of neurons to excitotoxic necrosis was decreased after withdrawal of trophic support and potentiated by treatment with caspase inhibitors. Our data indicate that caspase-mediated degradation of AMPA receptor subunits occurs during early periods of cell stress and may serve to ensure apoptosis by preventing excitotoxic necrosis. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, GRC 4F01,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 64 TC 109 Z9 111 U1 0 U2 1 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 MAY 15 PY 2000 VL 20 IS 10 BP 3641 EP 3649 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 312JK UT WOS:000086940000020 PM 10804206 ER PT J AU Tsai, RYL McKay, RDG AF Tsai, RYL McKay, RDG TI Cell contact regulates fate choice by cortical stem cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cortical stem cell; density; cell contact; cell-fate determination; smooth muscle; astrocyte ID CENTRAL-NERVOUS-SYSTEM; LEUKEMIA INHIBITORY FACTOR; SMOOTH-MUSCLE ACTIN; RECOMBINANT RETROVIRUS; PROGENITOR CELLS; CEREBRAL-CORTEX; MAMMALIAN NUMB; RAT-BRAIN; IN-VITRO; DIFFERENTIATION AB Cell fate is determined by intrinsic programs and external cues, such as soluble signals and cell-cell contact. Previous studies have demonstrated the roles of soluble factors in the proliferation and differentiation of cortical stem cells and cell-cell contact in maintaining stem cells in a proliferative state. In the present study, we focused on the effect of cell-cell interaction on cell-fate determination. We found that density could exert a strong influence on the cell-type composition when cortical stem cells differentiate. Multipotent stem cells, which normally gave rise to neurons, astrocytes, and oligodendrocytes under high-density culture condition, differentiated almost exclusively into smooth muscle at low density. Clonal analysis indicated that smooth muscle and astrocytes were derived from a common precursor and that the density effect on cell types used an instructive mechanism on the choice of fate rather than an effect of selective survival and/or proliferation. This instructive mechanism depended on the local and not the average density of the cells. This local signal could be mimicked by membrane extract. These findings demonstrate the importance of membrane-bound signals in specifying lineage and provide the first evidence for a short-range regulatory mechanism in cortical stem cell differentiation. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP McKay, RDG (reprint author), NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 56 TC 154 Z9 160 U1 0 U2 2 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 MAY 15 PY 2000 VL 20 IS 10 BP 3725 EP 3735 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 312JK UT WOS:000086940000028 PM 10804214 ER PT J AU Lamensdorf, I Eisenhofer, G Harvey-White, J Hayakawa, Y Kirk, K Kopin, IJ AF Lamensdorf, I Eisenhofer, G Harvey-White, J Hayakawa, Y Kirk, K Kopin, IJ TI Metabolic stress in PC12 cells induces the formation of the endogenous dopaminergic neurotoxin, 3,4-dihydroxyphenylacetaldehyde SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE DOPAL; 3,4-dihydroxyphenylethanol; dopamine; complex I; Parkinson's disease ID NERVE GROWTH-FACTOR; PARKINSONS-DISEASE; IN-VITRO; INHIBITION; RELEASE; DEPLETION; TERMINALS; APOPTOSIS; ALCOHOL; STORAGE AB 3,4-Dihydroxyphenylacetaldehyde (DOPAL) has been reported to be a toxic metabolite formed by the oxidative-deamination of dopamine (DA) catalyzed by monoamine oxidase. This aldehyde is either oxidized to 3,4-dihydroxyphenylacetic acid (DOPAC) by aldehyde dehydrogenase, an NAD-dependent enzyme or reduced to 3,4-dihydroxyphenylethanol (DOPET) by aldehyde or aldose reductase. In the present study we examined whether levels of DOPAL are elevated by inhibition of the mitochondrial respiratory chain. Using inhibitors of mitochondrial complexes I, II, III and IV we found that inhibition of complex I and III increased levels of DOPAL and DOPET. Nerve growth factor-induced differentiation of PC12 cells markedly potentiated DOPAL and DOPET accumulation in response to metabolic stress. DOPAL was toxic to differentiated PC12 as well as to SK-N-SH cell lines. Because complex I dysfunction has been implicated in the pathogenesis of Parkinson's disease, the accumulation of DOPAL may explain the vulnerability of the dopaminergic system to complex I inhibition. The rapid appearance of DOPAL and DOPET after inhibition of complex I may be a useful early index of oxidative stress in DA-forming neurons. Published 2000 Wiley-Liss, Inc.(dagger) C1 NINDS, Clin Neurosci Branch, NIH, CNS, Bethesda, MD 20892 USA. NINDS, LMMN, NIH, Bethesda, MD 20892 USA. NIDDKD, LBC, NIH, Bethesda, MD USA. RP Lamensdorf, I (reprint author), NINDS, Clin Neurosci Branch, NIH, CNS, Bldg 10,Room 6N256, Bethesda, MD 20892 USA. NR 36 TC 67 Z9 69 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY 15 PY 2000 VL 60 IS 4 BP 552 EP 558 DI 10.1002/(SICI)1097-4547(20000515)60:4<552::AID-JNR14>3.0.CO;2-U PG 7 WC Neurosciences SC Neurosciences & Neurology GA 310ME UT WOS:000086831300014 PM 10797558 ER PT J AU Toth, K McBain, CJ AF Toth, K McBain, CJ TI Target-specific expression of pre- and postsynaptic mechanisms SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article; Proceedings Paper CT Journal of Physiology Symposium on Neuronal Compartmentalization - Channels, Receptors and Signalling CY OCT 23, 1999 CL MIAMI BEACH, FLORIDA ID METABOTROPIC GLUTAMATE-RECEPTOR; CEREBELLAR GRANULE CELLS; LONG-TERM POTENTIATION; GABAA-BENZODIAZEPINE RECEPTORS; RAT HIPPOCAMPAL-NEURONS; AMPA RECEPTORS; TRANSMITTER RELEASE; MONOCLONAL-ANTIBODIES; SYNAPTIC PLASTICITY; EXCITATORY SYNAPSES AB Target-specific expression of pre- and postsynaptic mechanisms of synaptic transmission has been shown in a variety of central neurons log a number of laboratories. These data have demonstrated that synaptic transmission between single axons diverging onto distinct target neurons can behave independently, differentially influencing activity in the target neuron. Similarly, single neurons are capable of manufacturing molecularly distinct ligand-gated receptors and targeting them to synapses innervated by distinct converging afferent projections. A picture is emerging consistent with a role for both pre- and postsynaptic mechanisms in influencing the: target-specific nature of transmission at numerous diverse synapses throughout the mammalian CNS. This target specificity adds another level of complexity in unravelling the roles played by individual neurons within a computational network. To begin to understand the coordinated activity of large ensembles of neurons it is becoming clear that the nature of transmission between individual pre- and postsynaptic elements within a circuit must first Lt understood for each and every neural element involved. C1 NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, NIH, Rm 5A72,49 Convent Dr, Bethesda, MD 20892 USA. NR 84 TC 62 Z9 62 U1 0 U2 0 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 MAY 15 PY 2000 VL 525 IS 1 BP 41 EP 51 DI 10.1111/j.1469-7793.2000.00041.x PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 320FQ UT WOS:000087391500005 PM 10811723 ER PT J AU Pozzo-Miller, LD Connor, JA Andrews, SB AF Pozzo-Miller, LD Connor, JA Andrews, SB TI Microheterogeneity of calcium signalling in dendrites SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article; Proceedings Paper CT Journal of Physiology Symposium on Neuronal Compartmentalization - Channels, Receptors and Signalling CY OCT 23, 1999 CL MIAMI BEACH, FL ID HIPPOCAMPAL PYRAMIDAL NEURONS; SMOOTH ENDOPLASMIC-RETICULUM; GATED CA2+ CHANNELS; INTRACELLULAR CALCIUM; SYNAPTIC ACTIVATION; MITOCHONDRIAL CALCIUM; SYMPATHETIC NEURONS; ACTION-POTENTIALS; NMDA RECEPTORS; PROBE ANALYSIS AB Transient changes in the intracellular concentration of free Ca2+ ([Ca2+](i)) originating from voltage- or ligand-gated influx and by ligand- or Ca2+-gated release from intracellular stores, trigger or modulate many fundamental neuronal processes, including neurotransmitter release and synaptic plasticity. Of the intracellular compartments involved in Ca2+ clearance, the endoplasmic reticulum (ER) has received the most attention because it expresses Ca2+ pumps and Ca2+ channels, thus endowing it with the potential to act as both an intracellular calcium sink and store. We review here our ongoing work on the role of calcium sequestration into, and release from, En cisterns and the role that this plays in the generation and termination of free [Ca2+](i) transients in dendrites of pyramidal neurons in hippocampal slices during and after synaptic activity. These studies have been approached by combining parallel microfluorometric measurements of free cytosolic [Ca2+](i) transients with energy-dispersive X-ray microanalytical measurements of total Ca content within specific dendritic compartments at the electron microscopy level. Our observations support the emerging realization that specific subsets of dendritic ER cisterns provide spatial and temporal microheterogeneity of Ca2+ signalling, acting not only as a major intracellular Ca sink involved in active clearance mechanisms after voltage- and ligand-gated Ca2+ influx, but also as an intracellular Ca2+ source that can be mobilized by a signal cascade originating at activated synapses. C1 Marine Biol Lab, Woods Hole, MA 02543 USA. Univ Alabama Birmingham, Dept Neurobiol, Civitan Int Res Ctr 429 A2, Birmingham, AL 35294 USA. Univ New Mexico, Dept Neurosci, Albuquerque, NM 87131 USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Univ Alabama Birmingham, Dept Neurobiol, Civitan Int Res Ctr 429 A2, 1719 6th Ave S, Birmingham, AL 35294 USA. EM pozzomiller@nrc.uab.edu FU NINDS NIH HHS [NS35644, R01 NS035644] NR 54 TC 37 Z9 38 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAY 15 PY 2000 VL 525 IS 1 BP 53 EP 61 DI 10.1111/j.1469-7793.2000.t01-1-00053.x PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 320FQ UT WOS:000087391500006 PM 10811724 ER PT J AU Corthout, E Uttl, B Walsh, V Hallet, M Cowey, A AF Corthout, E Uttl, B Walsh, V Hallet, M Cowey, A TI Plasticity revealed by transcranial magnetic stimulation of early visual cortex SO NEUROREPORT LA English DT Article DE plasticity; transcranial magnetic stimulation (TMS); visual cortex; visual perception ID INTRACORTICAL MICROSTIMULATION; OCCIPITAL CORTEX; PERCEPTION; SUPPRESSION; DISCRIMINATION; FIELD AB We applied single-pulse transcranial magnetic stimulation (TMS) to the occipital pole of healthy subjects while they performed a forced-choice visual letter-identification task. We found three separate periods when TMS suppressed performance; the first period is best explained by TMS-induced blinking whereas the last two periods are best explained by TMS-induced disruption of letter-processing in the early visual cortex. Unexpectedly, we also found that TMS-induced suppression progressively disappeared during three weeks of repeated TMS experiments. However, it was only suppression during the last two periods that disappeared; suppression during the first period remained undiminished. When subjects were then presented with dimmer letters, suppression reappeared. The most likely explanation is a practice-induced increase in neuronal activity in the early visual cortex. NeuroReport 11:1565-1569 (C) 2000 Lippincott Williams & Wilkins. C1 Dept Expt Psychol, Oxford OX1 3UD, England. Oregon State Univ, Dept Psychol, Corvallis, OR 97331 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Corthout, E (reprint author), Dept Expt Psychol, S Pk Rd, Oxford OX1 3UD, England. NR 23 TC 18 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 15 PY 2000 VL 11 IS 7 BP 1565 EP 1569 DI 10.1097/00001756-200005150-00039 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 316WN UT WOS:000087191200042 PM 10841378 ER PT J AU Marintchev, A Robertson, A Dimitriadis, EK Prasad, R Wilson, SH Mullen, GP AF Marintchev, A Robertson, A Dimitriadis, EK Prasad, R Wilson, SH Mullen, GP TI Domain specific interaction in the XRCC1-DNA polymerase beta complex SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BASE-EXCISION-REPAIR; DNA-LIGASE-III; STRAND BREAK REPAIR; PROTEIN SECONDARY STRUCTURE; N-TERMINAL DOMAIN; POLY(ADP-RIBOSE) POLYMERASE; IN-VITRO; GENE; REQUIREMENT; RECONSTITUTION AB XRCC1 (X-ray cross-complementing group 1) is a DNA repair protein that forms complexes with DNA polymerase beta (beta-Pol), DNA ligase III and poly-ADP-ribose polymerase in the repair of DNA single strand breaks. The domains in XRCC1 have been determined, and characterization of the domain-domain interaction in the XRCC1-beta-Pol complex has provided information on the specificity and mechanism of binding, The domain structure of XRCC1, determined using limited proteolysis, was found to include an N-terminal domain (NTD), a central BIRCT-I (breast cancer susceptibility protein-1) domain and a C-terminal BRCT-II domain. The BRCT-I-linker-BRCT-II C-terminal fragment and the linker-BRCT-II C-terminal fragment were relatively stable to proteolysis suggestive of a non-random conformation of the linker, A predicted inner domain was found not to be stable to proteolysis, Using cross-linking experiments, XRCC1 was found to bind intact beta-Pol and the beta-Pol 31 kDa domain, The XRCC1-NTD1-183 (residues 1-183) was found to bind beta-Pol, the beta-Pol 31 kDa domain and the beta-Pol C-terminal palm-thumb (residues 140-335), and the interaction was further localized to XRCC1-NTD1-157 (residues 1-157), The XRCC1-NTD1-183-beta-Pol 31 kDa domain complex was stable at high salt (1 M NaCl) indicative of a hydrophobic contribution, Using a yeast two-hybrid screen, polypeptides expressed from two XRCC1 constructs, which Included residues 36-355 and residues 1-159, were found to interact with beta-Pol, the beta-Pol31 kDa domain, and the beta-Pol C-terminal thumb-only domain polypeptides expressed from the respective beta-Pol constructs. Neither the XRCC1-NTD1-159 nor the XRCC1(36-355) polypeptide was found to interact with a beta-Pol thumbless polypeptide, A third XRCC1 polypeptide (residues 75-212) showed no Interaction with beta-Pol, In quantitative gel filtration and analytical ultracentrifugation experiments, the XRCC1-NTD1-183, was found to bind beta-Pol and its 31 kDa domain in a 1:1 complex with high affinity (K-d of 0.4-2.4 mu M). The combined results indicate a thumb-domain specific 1:1 interaction between the XRCC1-NTD1-159 and beta-Pol that is of an affinity comparable to other binding interactions involving beta-Pol. C1 Univ Connecticut, Ctr Hlth, Dept Biochem, Farmington, CT 06032 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIH, Biomed Engn & Phys Sci Program, Bethesda, MD 20892 USA. RP Mullen, GP (reprint author), Univ Connecticut, Ctr Hlth, Dept Biochem, 263 Farmington Ave, Farmington, CT 06032 USA. FU NIGMS NIH HHS [GM52738] NR 48 TC 70 Z9 74 U1 0 U2 1 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 MAY 15 PY 2000 VL 28 IS 10 BP 2049 EP 2059 DI 10.1093/nar/28.10.2049 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 316CM UT WOS:000087149900005 PM 10773072 ER PT J AU Lin, JX Leonard, WJ AF Lin, JX Leonard, WJ TI The role of Stat5a and Stat5b in signaling by IL-2 family cytokines SO ONCOGENE LA English DT Review DE IL-2 family cytokines; Jak kinases; Stat5; signal transduction; phosphorylation; gene regulation ID RECEPTOR-BETA-CHAIN; HUMAN INTERLEUKIN-2 RECEPTOR; SEVERE COMBINED IMMUNODEFICIENCY; T-CELL PROLIFERATION; PROTEIN-TYROSINE-PHOSPHATASE; DNA-BINDING ACTIVITY; JAK-3 JANUS KINASE; MICE LACKING JAK3; P70 S6 KINASE; GAMMA-CHAIN AB The activation of Stat5 proteins (Stat5a and Stat5b) is one of the earliest signaling events mediated by IL-2 family cytokines, allowing the rapid delivery of signals from the membrane to the nucleus. Among STAT family proteins, Stat5a and Stat5b are the two most closely related STAT proteins. Together with other transcription factors and co-factors, they regulate the expression of the target genes in a cytokine-specific fashion. In addition to their activation by cytokines, activities of Stat5a and Stat5b, as well as other STAT proteins, are negatively controlled by CIS/SOCS/SSI family proteins. The outcome of Stat5 activation in regulating expression of target genes varies, depending upon the complexity of the promoter region of target genes and the other signaling pathways that are activated by each cytokine as well. Here, we mainly focus on the IL2-/IL-2 receptor system, as it is one of the best-studied systems that depend on Stat5-mediated signals, We will summarize what we have learned about the molecular mechanisms of how Stat5 is activated by IL-2 family cytokines from in vitro biochemical studies as well as the role that is played by Stat5 in each of the cytokine signaling pathways from in vivo gene-targeting analyses. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7N252,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 158 TC 204 Z9 222 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 15 PY 2000 VL 19 IS 21 BP 2566 EP 2576 DI 10.1038/sj.onc.1203523 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 321MN UT WOS:000087459400012 PM 10851055 ER PT J AU Park, G Ye, N Rogers, RD Brechbiel, MW Planalp, RP AF Park, G Ye, N Rogers, RD Brechbiel, MW Planalp, RP TI Effect of metal size on coordination geometry of N,N ',N ''-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane: synthesis and structure of [(ML)-L-II] (ClO4)(2) (M = Zn, Cd and Hg) SO POLYHEDRON LA English DT Article DE Cd(II); Hg(II); tachpyr; torsion angles; twist angles; Zn(II) ID IRON COMPLEXES; LIGAND; CADMIUM(II); 1,4,7-TRIAZACYCLONONANE-N,N',N''-TRIACETATE; CIS,CIS-1,3,5-TRIAMINOCYCLOHEXANE; MERCURY(II); ZINC(II); GALLIUM AB The hexadentate ligand N,N',N'-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane (tachpyr) forms stable metal complexes from the salts M(ClO4)(2) . 6H(2)O (M = Zn2+ and Cd2+) and Hg(ClO4)(2) in methanol or ethanol. The complexes [Zn(tachpyr)] (ClO4)(2) . CH3OH (1 . CH3OH), [Cd(tachpyr)] (ClO4)(2) (2) and [Hg(tachpyr)] (ClO4)(2) (3) have been isolated. and their solid state structures have been determined and analyzed. The coordination sphere changes from octahedral to trigonal-prismatic geometry with increasing metal radius. The trigonal twist angles (alpha) are 43.7(2)degrees in compound 1 . CH3OH, range between 11.0(4)degrees and 21.7(2)degrees in compound 2 and range between 3.1 (3)degrees and 5.5(2)degrees in compound 3. To accommodate larger metal ions there is also a slight outward expansion of the triaminocyclohexane nitrogens, which leads to a reduction in the average cyclohexyl ring C-C-C-C torsion angles (beta) with concomitant flattening of the ring. The torsion angles (beta) in 1 . CH3OH are 52.3(6)degrees and 52.4(6)degrees, range between 46.1(9)degrees and 52.7(9)degrees in compound 2 and range between 45.1 (6)degrees and 52.9(7)degrees in compound 3. (C) 2000 Elsevier Science Ltd All rights reserved. C1 Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. NIH, Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Planalp, RP (reprint author), Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 24 TC 19 Z9 19 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-5387 J9 POLYHEDRON JI Polyhedron PD MAY 15 PY 2000 VL 19 IS 9 BP 1155 EP 1161 DI 10.1016/S0277-5387(00)00380-6 PG 7 WC Chemistry, Inorganic & Nuclear; Crystallography SC Chemistry; Crystallography GA 325RT UT WOS:000087690700019 ER PT J AU Deacon, AM Ni, YS Coleman, WG Ealick, SE AF Deacon, AM Ni, YS Coleman, WG Ealick, SE TI The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist SO STRUCTURE WITH FOLDING & DESIGN LA English DT Article DE ADP-L-glycero-D-mannoheptose; epimerase; lipopolysaccharide core biosynthesis; multiwavelength anomalous diffraction ID ESCHERICHIA-COLI K-12; UDP-GALACTOSE 4-EPIMERASE; PROTEIN; BINDING; ENZYME; BIOSYNTHESIS; DIFFRACTION; BACTERIA; FUCOSE; MAD AB Background: ADP-L-glycero-D-mannoheptose 6-epimerase (AGME) is required for lipopolysaccharide (LPS) biosynthesis in most genera of pathogenic and non-pathogenic Gram-negative bacteria. It catalyzes the interconversion of ADP-D-glycero-D-mannoheptose and ADP-L-glycero-D-mannoheptose, a precursor of the seven-carbon sugar L-glycero-D-mannoheptose (heptose). Heptose is an obligatory component of the LPS core domain; its absence results in a truncated LPS structure resulting in susceptibility to hydrophobic antibiotics. Heptose is not found in mammalian cells, thus its biosynthetic pathway in bacteria presents a unique target for the design of novel antimicrobial agents. Results: The structure of AGME, in complex with NADP and the catalytic inhibitor ADP-glucose, has been determined at 2.0 Angstrom resolution by multiwavelength anomalous diffraction (MAD) phasing methods. AGME is a homopentameric enzyme, which crystallizes with two pentamers in the asymmetric unit. The location of 70 crystallographically independent selenium sites was a key step in the structure determination process. Each monomer comprises two domains: a large N-terminal domain, consisting of a modified seven-stranded Rossmann fold that is associated with NADP binding; and a smaller alpha/beta C-terminal domain involved in substrate binding. Conclusions: The first structure of an LPS core biosynthetic enzyme leads to an understanding of the mechanism of the conversion between ADP-D-glycero-D-mannoheptose and ADP-L-glycero-D-mannoheptose. On the basis of its high structural similarity to UDP-galactose epimerase and the three-dimensional positions of the conserved residues Ser116, Tyr140 ana Lys144, AGME was classified as a member of the short-chain dehydrogenase/reductase (SDR) superfamily. This study should prove useful in the design of mechanistic and structure-based inhibitors of the AGME catalyzed reaction. C1 Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA. NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Coleman, WG (reprint author), Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA. NR 33 TC 64 Z9 66 U1 1 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0969-2126 J9 STRUCT FOLD DES JI Struct. Fold. Des. PD MAY 15 PY 2000 VL 8 IS 5 BP 453 EP 462 DI 10.1016/S0969-2126(00)00128-3 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 316AR UT WOS:000087145600003 PM 10896473 ER PT J AU Ping, PP Murphy, E AF Ping, PP Murphy, E TI Role of p38 mitogen-activated protein kinases in preconditioning - A detrimental factor or a protective kinase? SO CIRCULATION RESEARCH LA English DT Editorial Material DE cardioprotection; kinases; signal transduction C1 Univ Louisville, Dept Med, Div Cardiol & Physiol & Biophys, Louisville, KY 40202 USA. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. Jewish Hosp, Heart & Lung Inst, Louisville, KY USA. RP Ping, PP (reprint author), Univ Louisville, Dept Med, Div Cardiol & Physiol & Biophys, 570 S Preston St,1st Floor N,Room 122, Louisville, KY 40202 USA. NR 19 TC 74 Z9 79 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAY 12 PY 2000 VL 86 IS 9 BP 921 EP 922 PG 2 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 317RY UT WOS:000087241800004 PM 10807861 ER PT J AU Kajava, AV AF Kajava, AV TI alpha-Helical solenoid model for the human involucrin SO FEBS LETTERS LA English DT Article DE modeling; repetitive sequence; skin; structural prediction; three-dimensional ID CROSS-LINKING; 3-DIMENSIONAL STRUCTURE; CELL-ENVELOPE; PROTEINS; BINDING; GENE; TRANSGLUTAMINASE-1; EVOLUTION; PROGRAM; DOMAINS AB Involucrin is a key component of the cross-linked envelope of terminally differentiated keratinocytes, The human molecule largely consists of 10 residue repeats and forms a thin 460 Angstrom long rod. Summarized experimental data and a detailed stereochemical analysis made with computer modeling resulted in a structural model for the involucrin molecule. The suggested structure is a left-handed alpha-helical solenoid built of a tandem array of helix-turn-helix folds. The structure enables us to explain the whole set of experimental data and residue conservations within the repeats. It is ideally suited to serve as a scaffold for cell envelope assembly and proposes a possible mode of the intermolecular interactions of involucrin during cell cornification. (C) 2000 Federation of European Biochemical Societies. C1 NIH, Ctr Mol Modeling CIT, Bethesda, MD 20892 USA. RP Kajava, AV (reprint author), NIH, Ctr Mol Modeling CIT, Bldg 12A, Bethesda, MD 20892 USA. RI Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 NR 28 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 12 PY 2000 VL 473 IS 2 BP 127 EP 131 DI 10.1016/S0014-5793(00)01502-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 315RM UT WOS:000087126800001 PM 10812058 ER PT J AU Kowaltowski, AJ Vercesi, AE Rhee, SG Netto, LES AF Kowaltowski, AJ Vercesi, AE Rhee, SG Netto, LES TI Catalases and thioredoxin peroxidase protect Saccharomyces cerevisiae against Ca2+-induced mitochondrial membrane permeabilization and cell death SO FEBS LETTERS LA English DT Article DE mitochondrion; yeast; antioxidant; mitochondriai permeability transition; cell death ID CYTOCHROME-C; YEAST MITOCHONDRIA; OXIDATIVE STRESS; TRANSITION PORE; IN-SITU; HYDROGEN-PEROXIDE; APOPTOSIS; BCL-2; ANTIOXIDANT; CALCIUM AB The involvement of reactive oxygen species in Ca2+-induced mitochondrial membrane permeabilization and cell viability was studied using yeast cells in which the thioredoxin peroxidase (TPx) gene was disrupted and/or catalase was inhibited by 3-amino-1,2,4-triazole (ATZ) treatment. Wild-type Saccharomyces cerevisiae cells were very resistant to Ca2+ and inorganic phosphate or t-butyl hydroperoxide-induced mitochondrial membrane permeabilization, but suffered an immediate decrease in mitochondrial membrane potential when treated with Ca2+ and the dithiol binding reagent phenylarsine oxide. In contrast, S, cerevisiae spheroblasts lacking the TPx gene and/or treated with ATZ suffered a decrease in mitochondrial membrane potential, generated higher amounts of hydrogen peroxide and had decreased viability under these conditions. In all cases, the decrease in mitochondrial membrane potential could be inhibited by ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid, dithiothreitol or ADP, but not by cyclosporin A. We conclude that TPx and catalase act together, maintaining cell viability and protecting S, cerevisiae mitochondria against Ca2+-promoted membrane permeabilization, which presents similar characteristics to mammalian permeability transition. (C) 2000 Federation of European Biochemical Societies. C1 Univ Sao Paulo, Inst Biociencias, Dept Biol, BR-05508900 Sao Paulo, Brazil. Univ Estadual Campinas, Fac Ciencias Med, Dept Patol Clin, BR-13083970 Campinas, SP, Brazil. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Netto, LES (reprint author), Univ Sao Paulo, Inst Biociencias, Dept Biol, Rua Matao,Travessa 14 321, BR-05508900 Sao Paulo, Brazil. RI Netto, Luis/A-3783-2008; Vercesi, Anibal /C-8767-2012; Kowaltowski, Alicia/H-8698-2012 OI Netto, Luis/0000-0002-4250-9177; NR 49 TC 47 Z9 49 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 12 PY 2000 VL 473 IS 2 BP 177 EP 182 DI 10.1016/S0014-5793(00)01526-X PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 315RM UT WOS:000087126800013 PM 10812070 ER PT J AU Moskovitz, J Poston, JM Berlett, BS Nosworthy, NJ Szczepanowski, R Stadtman, ER AF Moskovitz, J Poston, JM Berlett, BS Nosworthy, NJ Szczepanowski, R Stadtman, ER TI Identification and characterization of a putative active site for peptide methionine sulfoxide reductase (MsrA) and its substrate stereospecificity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEINS; DEGRADATION; EXPRESSION; RESIDUES; GENE; RADICALS; DAMAGE AB Peptide methionine sulfoxide reductases (MsrA) from many different organisms share a consensus amino acid sequence (GCFWG) that could play an important role in their active site. Site-directed single substitution of each of these amino acids except glycines in the yeast MsrA resulted in total loss of enzyme activity, Nevertheless, all the recombinant MsrA mutants and native proteins had a very similar circular dichroism spectrum. The demonstration that either treatment with iodoacetamide or replacement of the motif cysteine with serine leads to inactivation of the enzyme underscores the singular importance of cysteine residues in the activity of MsrA. The recombinant yeast MsrA was used for general characterization of the enzyme. Its K-m value was similar to the bovine MsrA and appreciably lower than the K-m of the bacterial enzyme. Also, it was shown that the enzymatic activity increased dramatically with increasing ionic strength. The recombinant yeast MsrA activity and the reduction activity of free methionine sulfoxide(s) were stereoselective toward the L-methionine S-sulfoxide and S-methyl p-tolyl sulfoxide. It was established that a methionine auxotroph yeast strain could grow on either form of L-methionine sulfoxide. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20982 USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD USA. RP Moskovitz, J (reprint author), NHLBI, Biochem Lab, NIH, Bethesda, MD 20982 USA. NR 22 TC 134 Z9 137 U1 1 U2 14 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 12 PY 2000 VL 275 IS 19 BP 14167 EP 14172 DI 10.1074/jbc.275.19.14167 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313NZ UT WOS:000087006900023 PM 10799493 ER PT J AU Oshima, Y Joshi, BH Puri, RK AF Oshima, Y Joshi, BH Puri, RK TI Conversion of interleukin-13 into a high affinity agonist by a single amino acid substitution SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARCINOMA CELL-LINES; RECEPTOR-GAMMA CHAIN; HUMAN GLIOMA-CELLS; HUMAN B-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; SIGNAL-TRANSDUCTION; IL-13 RECEPTOR; SARCOMA-CELLS; TUMOR-CELLS AB We created a novel mutated form of human interleukin-13 (IL-13) in which a positively charged arginine (R) at position 112 was substituted to a negatively charged aspartic acid (D). This mutant, termed IL-13R112D, was expressed in Escherichia coli and purified to near homogeneity. IL-13R112D was found to be a potent IL-13 agonist with 5-10-fold improved binding affinity to IL-13 receptors compared with wild-type IL-13 (wtIL-13). The conclusion of IL-13 agonist activity was drawn on the basis of approximately 10-fold improved activity over wtIL-13 in several assays: (a) inhibition of CD14 expression in primary monocytes; (b) proliferation of TF-1 and B9 cell lines; and (c) activation of STAT6 in Epstein-Barr virus-immortalized B cells, primary monocytes, and THP-1 monocytic cell line. Furthermore, mutant IL-13R112D neutralized the cytotoxic activity of a chimeric fusion protein composed of wtIL-13 and a Pseudomonas exotoxin A (IL-13-PE38) approximately 10 times better than wtIL-13. Based on these results, it was concluded that IL-13R112D interacts with much stronger affinity than wtIL-13 on all cell types tested and that Arg-112 plays an important role in the interaction with its receptors (IL-13R). Thus, these results suggest that IL-13R112D may be a useful ligand for the study of IL-13 interaction with its receptors or, alternatively, in designing specific targeted agents for IL-13R-positive malignancies. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, 29 Lincoln Dr,NIH Bldg 29B,Rm 2NN10, Bethesda, MD 20892 USA. NR 40 TC 34 Z9 38 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 12 PY 2000 VL 275 IS 19 BP 14375 EP 14380 DI 10.1074/jbc.275.19.14375 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313NZ UT WOS:000087006900051 PM 10799519 ER PT J AU Nielsen, PK Gho, YS Hoffman, MP Watanabe, H Makino, M Nomizu, M Yamada, Y AF Nielsen, PK Gho, YS Hoffman, MP Watanabe, H Makino, M Nomizu, M Yamada, Y TI Identification of a major heparin and cell binding site in the LG4 module of the laminin alpha 5 chain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TERMINAL GLOBULAR DOMAIN; DYSTROGLYCAN BINDING; SYNTHETIC PEPTIDES; BASEMENT-MEMBRANES; CRYSTAL-STRUCTURE; SKELETAL-MUSCLE; ADHESION; PERLECAN; AGRIN; MICE AB The G domain of the laminin alpha chains consists of five homologous G modules (LG1-5) and has been implicated in various biological functions. In this study, we identified an active site for cell and heparin binding within the laminin alpha 5 G domain using recombinant proteins and synthetic peptides. Recombinant LG4, LG5, and LG4-5 modules were generated using a mammalian expression system. The LG4 and LG4-5 modules were highly active for cell binding, whereas the LG5 module alone showed only weak binding. Heparin inhibited cell binding to the LG4-5 module, whereas no inhibition was observed with EDTA or antibodies against the integrin beta(1) subunit. These results suggest that the LG4-5 module interacts with a cell surface receptor containing heparan sulfate but not with integrins. Solid-phase assays and surface plasmon resonance measurements demonstrated strong binding of the LG4 and LG4-5 modules to heparin with K-D values in the nanomolar range, whereas a 16-fold lower value was determined for the LG5 module. Treatment with glycosidases demonstrated that N-linked carbohydrates on the LG5 module are complex-type oligosaccharides. The LG4-5 module, devoid of N-linked carbohydrates, exhibited similar binding kinetics toward heparin. Furthermore, cell binding was unaffected by removal of N-linked glycosylation. To localize active sites on the LG4 module, various synthetic peptides were used to compete with binding of the tandem module to heparin and cells. Peptide F4 (AGQWHRVSVRWG) inhibited binding, whereas a scrambled peptide of F4 failed to compete binding. Alanine replacements demonstrated that one arginine residue within F4 was important for cell and heparin binding. Our results suggest a critical role of the LG4 module for heparan sulfate-containing receptor binding within the laminin alpha 5 chain. C1 NIDCR, Mol Biol Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. NIDCR, Cell Biol Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Hokkaido Univ, Grad Sch Environm Earth Sci, Kita Ku, Sapporo, Hokkaido 0600810, Japan. RP Yamada, Y (reprint author), NIDCR, Mol Biol Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Rm 405,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. NR 24 TC 40 Z9 40 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 12 PY 2000 VL 275 IS 19 BP 14517 EP 14523 DI 10.1074/jbc.275.19.14517 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313NZ UT WOS:000087006900069 PM 10799535 ER PT J AU Wang, XT McCullough, KD Franke, TF Holbrook, NJ AF Wang, XT McCullough, KD Franke, TF Holbrook, NJ TI Epidermal growth factor receptor-dependent Akt activation by oxidative stress enhances cell survival SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-B; NF-KAPPA-B; INSULIN-LIKE GROWTH-FACTOR-1; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; SIGNALING PATHWAY; INDUCED APOPTOSIS; HEAT-SHOCK; C-AKT; TRANSCRIPTION FACTOR AB The serine/threonine kinase Akt (also known as protein kinase B) is activated in response to various stimuli by a mechanism involving phosphoinositide 3-kinase (PI3-K). Akt provides a survival signal that protects cells from apoptosis induced by growth factor withdrawal, but its function in other forms of stress is less clear. Here we investigated the role of PI3-K/Akt during the cellular response to oxidant injury. H2O2 treatment elevated Akt activity in multiple cell types in a time- (5-30 min) and dose (400 mu M-2 mM)-dependent manner. Expression of a dominant negative mutant of p85 (regulatory component of PI3-K) and treatment with inhibitors of PB-K (wortmannin and LY294002) prevented H2O2-induced Akt activation. Akt activation by H2O2 also depended on epidermal growth factor receptor (EGFR) signaling; H2O2 treatment led to EGFR phosphorylation, and inhibition of EGFR activation prevented Akt activation by H2O2. As H2O2 causes apoptosis of HeLa cells, we investigated whether alterations of PI3-K/Akt signaling would affect this response. Wortmannin and LY294002 treatment significantly enhanced H2O2-induced apoptosis, whereas expression of exogenous myristoylated Akt tan activated form) inhibited cell death. Constitutive expression of v-Akt likewise enhanced survival of H2O2-treated NHH3T3 cells. These results suggest that H2O2 activates Akt via an EGFR/PI3-K-dependent pathway and that elevated Akt activity confers protection against oxidative stress-induced apoptosis. C1 NIA, Biol Chem Lab, Cell Stress & Aging Sec, Baltimore, MD 21224 USA. Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. RP Holbrook, NJ (reprint author), NIA, Biol Chem Lab, Cell Stress & Aging Sec, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 52 TC 325 Z9 336 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 12 PY 2000 VL 275 IS 19 BP 14624 EP 14631 DI 10.1074/jbc.275.19.14624 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313NZ UT WOS:000087006900083 PM 10799549 ER PT J AU Zhao, XH Bondeva, T Balla, T AF Zhao, XH Bondeva, T Balla, T TI Characterization of recombinant phosphatidylinositol 4-kinase beta reveals auto- and heterophosphorylation of the enzyme SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 3-KINASE SERINE KINASE; PROTEIN-KINASE; PHOSPHOINOSITIDE 3-KINASE; SACCHAROMYCES-CEREVISIAE; WORTMANNIN; PI-3-KINASE; CLONING; PATHWAY; GENE AB Phosphatidylinositol (PI) 4-kinases catalyze the synthesis of PI 4-phosphate, an important intermediate for the synthesis of membrane polyphosphoinositides, regulators of multiple cellular functions. Two mammalian PI 4-kinases have been cloned, a 230-kDa enzyme (alpha-form) and a 110-kDa (beta-form), both of which are inhibited by >0.1 mu M concentrations of the PI 3-kinase inhibitor, wortmannin (WT), In the present study, we created a glutathione S-transferase-PI4K beta fusion protein for expression in Escherichia coli. The purified protein was biologically active and phosphorylated PI in its 4-position with WT sensitivity and kinetic parameters that were identical to those of purified bovine brain PI4K beta, In addition to its lipid kinase activity, the enzyme exhibited autophosphorylation that was enhanced by Mn2+ ions and inhibited by WT and another PI 3-kinase inhibitor, LY 294002. The recombinant protein was unable to transphosphorylate, but its isolated C-terminal catalytic domain still displayed autophosphorylation, suggesting that the autophosphorylation site resides within the C-terminal catalytic domain of the protein and is held in position by intramolecular interactions. Autophosphorylation inhibited subsequent lipid kinase activity, which was reversed upon dephosphorylation, by protein phosphatases, PPI and PP2A(1), suggesting that it may represent a regulatory mechanism for the enzyme. Phosphorylation of endogenous or overexpressed PI4K beta was also observed in COS-7 cells; how ever, the in vivo phosphorylation of the expressed protein was only partially inhibited by WT and also occurred in a catalytically inactive form of the enzyme, indicating the presence of additional phosphorylation site(s). Successful bacterial expression of PI4K beta should aid research on the structure-function relationships of this protein as well as of other, structurally related enzymes. C1 NICHD, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. RP Balla, T (reprint author), NICHD, Endocrinol & Reprod Res Branch, Bldg 49,Rm 6A35,49 Convent Dr, Bethesda, MD 20892 USA. OI Balla, Tamas/0000-0002-9077-3335 NR 29 TC 21 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 12 PY 2000 VL 275 IS 19 BP 14642 EP 14648 DI 10.1074/jbc.275.19.14642 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 313NZ UT WOS:000087006900085 PM 10799551 ER PT J AU Phillips, LR Bramhall, C Buckley, J Wolfe, T House, TL Stinson, SF AF Phillips, LR Bramhall, C Buckley, J Wolfe, T House, TL Stinson, SF TI Identification of the principal circulating metabolite of a synthetic 5,4 '-diaminoflavone (NSC 686288), an antitumor agent, in the rat SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE retro-Diels-Alder fragmentation; 5,4 '-diaminoflavone; NSC 686288 AB During the course of our study to develop analytical methodology for quantitating the investigative antitumor agent 5-amino-2-(4-amino-3-fluorophenyl)-6,8-difluoro-7-methyl-4H-1-benzopyran-4-one (DAF; NSC 686288) in plasma, a significant concentration of a metabolite was observed in a post-dosed rat. The results of electron-ionization (EI) mass spectrometric analysis of the metabolite suggested that N-acetylation had occurred, brit, interestingly, that only one of the compound's two primary amino groups had been transformed. Comparing the mass spectra and gas chromatographic retention times of a mono-acetylated sample of DAF and that of the metabolite showed both to be the same. A retro-Diels-Alder (RDA) fragmentation of the B ring of DAF results in formation of two abundant product ions, each retaining one of the amino groups. The EI mass spectrum of mono-N-acetamido-d(3) DAF shows loss of ketene-d(2), leading to formation of an -NHD group. The ensuing RDA fragmentation easily identifies which of the two product ions contains the deuterium, thereby allowing us to assign the site of N-acetylation as the amino group on ring C (the 4' position) of DAF. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment Diag & Ctr, Frederick, MD 21701 USA. SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Phillips, LR (reprint author), NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment Diag & Ctr, Frederick, MD 21701 USA. FU NCI NIH HHS [N01-CO-56000] NR 10 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAY 12 PY 2000 VL 741 IS 2 BP 205 EP 211 DI 10.1016/S0378-4347(00)00094-3 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 317TG UT WOS:000087242600010 PM 10872590 ER PT J AU Hobby, P Wyatt, MK Gan, WN Bernstein, S Tomarev, S Slingsby, C Wistow, G AF Hobby, P Wyatt, MK Gan, WN Bernstein, S Tomarev, S Slingsby, C Wistow, G TI Cloning, modeling, and chromosomal localization for a small leucine-rich repeat proteoglycan (SLRP) family member expressed in human eye SO MOLECULAR VISION LA English DT Article ID PROTEINS C1 NEI, Sect Mol Struct & Funct, NIH, Bethesda, MD 20892 USA. Birkbeck Coll, Dept Crystallog, London, England. NIH Intramural Sequencing Ctr, Gaithersburg, MD USA. Univ Maryland, Sch Med, Dept Ophthalmol, Baltimore, MD 21201 USA. RP Wistow, G (reprint author), NEI, Sect Mol Struct & Funct, NIH, Bldg 6,Rm 331, Bethesda, MD 20892 USA. EM graeme@helix.nih.gov NR 15 TC 26 Z9 28 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD MAY 12 PY 2000 VL 6 IS 8 BP 72 EP 78 PG 7 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 320DC UT WOS:000087385400001 PM 10837509 ER PT J AU Ahmad, F Tang, JR Brandt, D Holst, LS Degerman, E Manganiello, VC AF Ahmad, F Tang, JR Brandt, D Holst, LS Degerman, E Manganiello, VC TI Potential functional co-localization of cyclic nucleotide phosphodiesterase 3B (PDE3B) and PKB beta in 3T3-L1 adipocytes SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Lund, S-22100 Lund, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1525 BP A1578 EP A1578 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401555 ER PT J AU Andoh, T Lee, SY Chiueh, CC AF Andoh, T Lee, SY Chiueh, CC TI S-nitrosoglutathione (GSNO) increases bcl-2 and prevents neurotoxicity induced by oxidative stress in SH-SY5Y cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Unit Neurodegenerat & Neuroprotect, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1086 BP A1500 EP A1500 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401115 ER PT J AU Aymerich, MS Schwartz, JP Becerra, SP AF Aymerich, MS Schwartz, JP Becerra, SP TI Pigment epithelium-derived factor (PEDF) activates the MEK-ERK signal transduction pathway on cerebellar granule cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 314 BP A1364 EP A1364 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400345 ER PT J AU Bae, MA Soh, Y Pie, JE Song, BJ AF Bae, MA Soh, Y Pie, JE Song, BJ TI Selective activation or the c-Jun N-terminal protein kinase pathway during acetaminophen-induced apoptosis SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA, Rockville, MD 20852 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1167 BP A1516 EP A1516 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401197 ER PT J AU Bar-Noy, S Gorlatov, SN AF Bar-Noy, S Gorlatov, SN TI Over expression of wild type and seCys/Cys mutant of human thioredoxin reductase in E-coli: The essential role of selenocysteine in catalytic activity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 610 BP A1418 EP A1418 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400643 ER PT J AU Basanez, G Shinnar, AE Zimmerberg, J AF Basanez, G Shinnar, AE Zimmerberg, J TI Pore formation by hagfish intestinal antimicrobial peptides: Biophysical studies on mechanism of action SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD, LCMB, NIH, Bethesda, MD 20892 USA. Columbia Univ Barnard Coll, Dept Chem, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 852 BP A1460 EP A1460 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400883 ER PT J AU Boye, SE Tramontini, N Mobley, J Holland, SM Kilgore, KS AF Boye, SE Tramontini, N Mobley, J Holland, SM Kilgore, KS TI Requirement of functional NADPH oxidase for alterations in pulmonary function and inflammatory changes in a murine model of acute lung injury. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Warner Lambert Parke Davis, Parke Davis Pharmaceut Res, Ann Arbor, MI 48105 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 276 BP A1358 EP A1358 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400305 ER PT J AU Camitta, MGW Bradbury, JA Yang, B Gabel, SA Chulada, PC Langenbach, R Murphy, E Zeldin, DC AF Camitta, MGW Bradbury, JA Yang, B Gabel, SA Chulada, PC Langenbach, R Murphy, E Zeldin, DC TI Reduced functional recovery after global cardiac ischemia in prostaglandin H synthase-1 and -2 deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1460 BP A1566 EP A1566 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401489 ER PT J AU Cissel, DS Beayen, MA AF Cissel, DS Beayen, MA TI Loss of heat shock proteins from the multimeric Raf-1 complex and rat signaling in dexamethasone-treated mast cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, LMI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 273 BP A1357 EP A1357 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400303 ER PT J AU Corchero, J Pimprale, S Krausz, K Gelboin, HV Gonzalez, J AF Corchero, J Pimprale, S Krausz, K Gelboin, HV Gonzalez, J TI CYP2D6 "humanized" mice: A model for in vivo pharmacokinetics and drug-drug interactions SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 719 BP A1437 EP A1437 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400750 ER PT J AU Cragg, GM AF Cragg, GM TI Medicinals for the millennia. The historical record SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA D2 BP A1308 EP A1308 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400019 ER PT J AU Deng, CX AF Deng, CX TI BRCA1 and its functions in genetic stability and tumorigenesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, GDDB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1132 BP A1510 EP A1510 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401165 ER PT J AU Edwards, S Kuehl, P Zhang, J Li, J Driscoll, M Ewing, B Boguski, M AF Edwards, S Kuehl, P Zhang, J Li, J Driscoll, M Ewing, B Boguski, M TI A new pharmacogenomics information resource on the world wide web. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Johns Hopkins Univ, Human Genet Program, Baltimore, MD USA. Univ Washington, Dept Mol Biotechnol, Seattle, WA 98195 USA. Natl Inst Gen Med Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 912 BP A1470 EP A1470 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400941 ER PT J AU Felici, A Bottaro, DP AF Felici, A Bottaro, DP TI Gab1 expression mediates HGF-induced mitogenicity and differentiation in 32D cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Cellular & Mol Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1044 BP A1493 EP A1493 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401076 ER PT J AU Finkel, T AF Finkel, T TI Signaling role of mitochondrial-generated hydrogen peroxide SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1114 BP A1506 EP A1506 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401145 ER PT J AU Gasior, M Ungard, JT Witkin, JM AF Gasior, M Ungard, JT Witkin, JM TI Efficacy of chlormethiazole against toxic effects of cocaine in mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDA, Drug Dev Grp, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1376 BP A1551 EP A1551 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401406 ER PT J AU Gilfillan, AM Metcalfe, DD Tkaczyk, C AF Gilfillan, AM Metcalfe, DD Tkaczyk, C TI Fc epsilon RI-dependent tyrosine phosphorylation in human mast cells (HuMC's): Comparison to RBL 2H3 cells and mouse bone marrow derived mast cells (BMMC's). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, LAD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 278A BP A1358 EP A1358 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400309 ER PT J AU Gonzalez, FJ AF Gonzalez, FJ TI Mouse models of genetic deficiencies in xenobiotic-metabolizing enzymes SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Lab Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA C17 BP A1308 EP A1308 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400020 ER PT J AU Greener, T Eisenberg, E Greene, L AF Greener, T Eisenberg, E Greene, L TI Auxilin and GAK have a unique clathrin binding domain that enables C-terminal 20 kDa recombinant fragments of these proteins to support uncoating of clathrin baskets by Hsc70 but not to induce clathrin polymerization SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, LCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1042 BP A1493 EP A1493 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401075 ER PT J AU Han, C Gruschus, J Greener, T Green, L Ferretti, J Eisenberg, E AF Han, C Gruschus, J Greener, T Green, L Ferretti, J Eisenberg, E TI NMR structure of a recombinant fragment of auxilin, the J-domain protein required for uncoating of clathrin-coated vesicles by hsc70 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1045 BP A1493 EP A1493 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401074 ER PT J AU Hayashi, T Su, TP AF Hayashi, T Su, TP TI Structural coupling of sigma-1 receptors to inositol 1,4,5-trisphosphte receptors (IP3R) and ankyrin B in NG-108 cells: Relationship to Ca2+ signaling. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDA, Cellular Pathobiol Unit, IRP, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1500 BP A1573 EP A1573 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401531 ER PT J AU Holaday, SK Martin, BM Fletcher, PL Krishna, NR AF Holaday, SK Martin, BM Fletcher, PL Krishna, NR TI NMR structure of butantoxin from the scorpion Tityus serrulatus. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL 35294 USA. NIMH, NIH, Bethesda, MD 20892 USA. E Carolina Univ, Sch Med, Greenville, NC 27858 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 433 BP A1385 EP A1385 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400462 ER PT J AU Hong, HL Devereux, TR Melnick, RL Boorman, GA Sills, RC AF Hong, HL Devereux, TR Melnick, RL Boorman, GA Sills, RC TI Mutations of ras protooncogenes and p53 tumor suppressor gene in cardiac hemangiosarcomas from B6C3F1 mice exposed to 1,3-butadiene for 2 years. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1338 BP A1545 EP A1545 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401371 ER PT J AU Houshyar, H Rice, KC Woods, JH AF Houshyar, H Rice, KC Woods, JH TI Body temperature and pituitary-adrenal effects of antalarmin, a nonpeptide CRH antagonist, in rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. NIDDK, Med Chem Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 47 BP A1319 EP A1319 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400077 ER PT J AU Hrvevna, CA Litman, T Mickley, L Gottesman, MM Fojo, T Bates, SE AF Hrvevna, CA Litman, T Mickley, L Gottesman, MM Fojo, T Bates, SE TI Functional expression and characterization of the mitoxantrone resistance-associated transporter MXR1 in human cells using a vaccinia virus transient expression system. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, DBS, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, DCS, Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 166 BP A1339 EP A1339 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400195 ER PT J AU Hundley, TR Beaven, MA AF Hundley, TR Beaven, MA TI Studies of the role of the MAP kinases in the regulation of the expression of eicosanoid metabolizing enzymes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 821 BP A1454 EP A1454 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400850 ER PT J AU Hurley, JH Misra, S Rao, V Burden, L Tsujishita, Y Kunz, J Anderson, RA AF Hurley, JH Misra, S Rao, V Burden, L Tsujishita, Y Kunz, J Anderson, RA TI Of FVYEs, flounders, and flattened folds: Structural biology of phosphoinositide signaling SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 570 BP A1411 EP A1411 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400603 ER PT J AU Hutter, D Liu, P Barnes, J Liu, Y AF Hutter, D Liu, P Barnes, J Liu, Y TI Structural domains of MAP kinase phosphatase-1 (MKP-1) required for the inactivation of MAP kinases SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, Biol Chem Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 829 BP A1456 EP A1456 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400860 ER PT J AU Katz, JL AF Katz, JL TI Discriminative stimulus effects of D1-like dopamine receptor agonists in squirrel monkeys trained to discriminate cocaine from saline SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDA, IRP, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1369 BP A1550 EP A1550 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401398 ER PT J AU Kawamoto, T Negishi, M AF Kawamoto, T Negishi, M TI Activation of mouse nuclear receptor CAR by estrogens and the repression by androgens and progesterone SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RI Kawamoto, Takeshi/D-7938-2015 OI Kawamoto, Takeshi/0000-0003-3337-1775 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 695 BP A1433 EP + PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400726 ER PT J AU King, LM Ma, JX Srettabunjong, S Li, LP Zeldin, DC AF King, LM Ma, JX Srettabunjong, S Li, LP Zeldin, DC TI Cloning of the CYP2J2 gene and identification of polymorphisms SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 721 BP A1437 EP A1437 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400751 ER PT J AU Kristof, AS Konczalik, JM Moss, J AF Kristof, AS Konczalik, JM Moss, J TI Mitogen-activated protein kinases mediate AP-1-dependent human inducible nitric oxide synthase promoter activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 371 BP A1374 EP A1374 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400402 ER PT J AU Kumaraswamy, E Malykh, A Korotkov, K Kozyavkin, S Hu, Y Berry, M Lee, B Hatfield, D Diamond, A Gladyshev, V AF Kumaraswamy, E Malykh, A Korotkov, K Kozyavkin, S Hu, Y Berry, M Lee, B Hatfield, D Diamond, A Gladyshev, V TI Structure and expression of the 15 kDa selenoprotein gene: Possible role of the protein in cancer? SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, BRL, Bethesda, MD 20892 USA. Fidel Syst Inc, Gaithersburg, MD USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. Univ Illinois, Chicago, IL 60612 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Seoul Natl Univ, LMG, Seoul 151742, South Korea. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1409 BP A1557 EP A1557 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401437 ER PT J AU Kumari, D Usdin, K AF Kumari, D Usdin, K TI Interplay of transcription factors at the FMR1 promoter SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Cellular & Mol Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 117 BP A1331 EP A1331 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400147 ER PT J AU Lee, CH Um, PY Park, MH AF Lee, CH Um, PY Park, MH TI Structure-function studies of deoxyhypusine synthase: Binding of spermidine and NAD SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 82 BP A1325 EP A1325 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400114 ER PT J AU Lee, SY Davis, DA Andoh, T Hawkins, V Yarchoan, R Chiueh, CC AF Lee, SY Davis, DA Andoh, T Hawkins, V Yarchoan, R Chiueh, CC TI S-nitrosoglutathione (GSNO): An inhibitor of HIV-1 protease. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 728 BP A1438 EP A1438 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400757 ER PT J AU Liu, P Hutter, D Kenny, JJ Longo, DL Liu, Y AF Liu, P Hutter, D Kenny, JJ Longo, DL Liu, Y TI Tyrosine phosphorylation of phospholipase C-gamma 2 required Bruton's tyrosine kinase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, Biol Chem Lab, Baltimore, MD 21224 USA. NIA, Immunobiol Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 835 BP A1457 EP A1457 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400866 ER PT J AU London, SJ AF London, SJ TI Pharmacogenetics and cancer risk. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA C16 BP A1308 EP A1308 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400017 ER PT J AU Moskovitz, J Poston, JM Berlett, BS Nosworthy, NJ Stadtman, ER AF Moskovitz, J Poston, JM Berlett, BS Nosworthy, NJ Stadtman, ER TI Identifying and characterization of a putative active site of peptide-methionine sulfoxide reductase (MSRA). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 611 BP A1418 EP A1418 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400641 ER PT J AU Nam, SW Clair, T Liotta, LA Stracke, ML AF Nam, SW Clair, T Liotta, LA Stracke, ML TI A sensitive screening assay for secreted motility-stimulating factor, autotaxin SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 911 BP A1470 EP A1470 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400943 ER PT J AU Nam, SW Clair, T McMarlin, A Liotta, LA Stracke, ML AF Nam, SW Clair, T McMarlin, A Liotta, LA Stracke, ML TI Autotaxin, a potent tumor cell motility-stimulating factor, promotes in vivo neovascularization and stimulates smooth muscle cell migration SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 628 BP A1421 EP A1421 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400658 ER PT J AU Negishi, M AF Negishi, M TI Nuclear receptor CAR as a phenobarbital induction signal of CYP2B genes SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA C6 BP A1306 EP A1306 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400007 ER PT J AU Oin, S Chock, PB AF Oin, S Chock, PB TI Regulation of oxidative stress-induced calcium release by phosphatidylinositol 3-kinase and Bruton's tyrosine kinase in B cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 836 BP A1457 EP A1457 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400869 ER PT J AU Onda, M Kreitman, RJ Vincent, JJ Wang, QC Lee, B Pastan, I AF Onda, M Kreitman, RJ Vincent, JJ Wang, QC Lee, B Pastan, I TI Lowering the isoelectric point of the Fv portion of immunotoxin anti-Tac(Fv)-PE38 reduces nonspecific animal toxicity SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 264 BP A1356 EP A1356 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400293 ER PT J AU Pacheco-Rodriguez, G Vitale, N Ferrans, VJ Riemenschneider, W Moss, J Vaughan, M AF Pacheco-Rodriguez, G Vitale, N Ferrans, VJ Riemenschneider, W Moss, J Vaughan, M TI Specific functional interaction of human cytohesin-1 and ADP-ribosylation factor domain protein (ARD1) SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, 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 FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 988 BP A1484 EP A1484 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401019 ER PT J AU Reddy, DS Rogawski, MA AF Reddy, DS Rogawski, MA TI Enhanced anticonvulsant activity of ganaxolone following neurosteroid withdrawal in a rat model of catamenial epilepsy. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 588 BP A1414 EP A1414 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400618 ER PT J AU Rhee, SG Bae, YS Lee, SR Lee, C Kwon, J Yang, KS AF Rhee, SG Bae, YS Lee, SR Lee, C Kwon, J Yang, KS TI Hydrogen peroxide in peptide growth factor signaling SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea. NR 0 TC 3 Z9 3 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1112 BP A1505 EP A1505 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401142 ER PT J AU Schetz, JA Sibley, DR AF Schetz, JA Sibley, DR TI Three distinct allosteric sites on a G-protein coupled receptor modulate the pharmacology of the binding site crevice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Mississippi, University, MS 38677 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 180 BP A1342 EP A1342 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400210 ER PT J AU Selengut, JD Levine, RL AF Selengut, JD Levine, RL TI MDP-1 is a member of the had-family of aspartate-dependent phosphatases. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 612 BP A1418 EP A1418 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400644 ER PT J AU Sierra, ML Lesniak, MA Taylor, SI Haft, CR AF Sierra, ML Lesniak, MA Taylor, SI Haft, CR TI Cloning and characterization of human orthologs of yeast Vps26p, Vps29p, and Vps35p, three molecules involved in protein traffic from endosomes to trans-Golgi network SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 641 BP A1423 EP A1423 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400673 ER PT J AU Song, Y Goel, A Basrur, V Mazur, SJ Higashimoto, Y Mikovits, J Turpin, JA Rice, WG Inman, JK Appella, E AF Song, Y Goel, A Basrur, V Mazur, SJ Higashimoto, Y Mikovits, J Turpin, JA Rice, WG Inman, JK Appella, E TI Studies of pyridinioalkanoyl thioesthers (PATEs) that target HIV-1 nueleocapsid protein zinc fingers SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, LCB, NIH, Bethesda, MD 20892 USA. NCI, LADM, NIH, Bethesda, MD 20892 USA. So Res Inst, Birmingham, AL 35255 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 490 BP A1395 EP A1395 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400521 ER PT J AU Su, TP Tsao, LI Hayashi, T AF Su, TP Tsao, LI Hayashi, T TI Delta opioid peptide blocks serum deprivation-induced apoptosis in PC12 cells via map kinases. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDA, Cellular Pathobiol Unit, Mol Neuropsychiat Sect, Intramural Res Program,NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1188 BP A1519 EP A1519 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401219 ER PT J AU Tang, JR Manganiello, VC AF Tang, JR Manganiello, VC TI Characterization of promoter elements in the 5-flanking region of the mouse phosphodiesterase 3B (MPDE3B) gene SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1518 BP A1576 EP A1576 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401548 ER PT J AU Tsao, CC Coulter, SJ Chanas, B Goldstein, JA AF Tsao, CC Coulter, SJ Chanas, B Goldstein, JA TI Identification of critical residues of human CYP2C19 as key determinants of S-mephenytoin hydroxylase activity SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 718 BP A1436 EP A1436 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400749 ER PT J AU Tsao, CC Foley, J Coulter, SJ Maronpot, R Zeldin, DC Goldstein, JA AF Tsao, CC Foley, J Coulter, SJ Maronpot, R Zeldin, DC Goldstein, JA TI CYP2C40, a unique arachidonic acid 16-hydroxylase, is the major CYP2C in murine intestinal tract SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 707 BP A1435 EP + PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400738 ER PT J AU Tsao, LI Hayashi, T Su, TP AF Tsao, LI Hayashi, T Su, TP TI Delta opioid peptide blocks the loss of dopamine transporter (DAT) and tyrosine hydroxylase (Th) caused by methamphetamine (METH): Altered biochemical properties of DAT and TH. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDA, Cellular Pathobiol Unit, Instramural Res Program, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 933 BP A1474 EP A1474 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400963 ER PT J AU Wan, J Shoaf, SE AF Wan, J Shoaf, SE TI Chlorzoxazone metabolism is increased in fasted Sprague-Dawley rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 713 BP A1436 EP + PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400744 ER PT J AU Wang, T Chock, PB Yang, DCH AF Wang, T Chock, PB Yang, DCH TI Expression of biotinylated ubiquitin fusion protein in E-coli SO FASEB JOURNAL LA English DT Meeting Abstract C1 Georgetown Univ, Dept Chem, Washington, DC 20057 USA. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RI Yang, David/A-7294-2009 NR 0 TC 1 Z9 1 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1259 BP A1531 EP A1531 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401288 ER PT J AU Witkin, JM Gaisor, M Zapata, A Slusher, BS Shippenberg, TS AF Witkin, JM Gaisor, M Zapata, A Slusher, BS Shippenberg, TS TI Inhibition of NAALADase: A novel strategy for preventing sensitization to convulsant stimuli. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Guilford Pharmaceut Inc, Dept Res, Baltimore, MD 21224 USA. NIDA, Behav Neurosci Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 589 BP A1414 EP A1414 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400621 ER PT J AU Wolff, EC Wolff, J Park, MH AF Wolff, EC Wolff, J Park, MH TI Fluorescence of bound NADH generated by deoxyhypusine synthase: Demonstration of a transient hydride transfer mechanism SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDCR, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 72 BP A1323 EP A1323 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400103 ER PT J AU Wu, C AF Wu, C TI ATP-driven chromatin remodeling complexes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Mol Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1543 BP A1581 EP A1581 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401573 ER PT J AU Yeagley, DA Moll, J Vinson, CA Quinn, PG AF Yeagley, DA Moll, J Vinson, CA Quinn, PG TI CREB and C/EBP, but not AP-1, are required for induction of PEPCK transcription by PKA, but do not mediate insulin inhibition. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Penn State Coll Med, Hershey, PA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 679 BP A1430 EP A1430 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400712 ER PT J AU Yoshinari, K Sueyoshi, T Moore, R Negishi, M AF Yoshinari, K Sueyoshi, T Moore, R Negishi, M TI Nuclear receptor CAR as a regulatory factor for the sexually dimorphic induction of CYP2B1 gene by phenobarbital in rat livers SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 137 BP A1334 EP A1334 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400166 ER PT J AU Zelko, I Kobayashi, R Negishi, M AF Zelko, I Kobayashi, R Negishi, M TI Repression of phenobarbital-responsive enhancer module in the Cyp2b10 gene by estrogen receptor-related receptor ERR. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Pharmacogenet Sect, LRDT, NIH, Res Triangle Pk, NC 27709 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RI Zelko, Igor/L-2673-2013 OI Zelko, Igor/0000-0003-3976-3884 NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 696 BP A1433 EP A1433 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400729 ER PT J AU Zhang, X Young, HA AF Zhang, X Young, HA TI Up-regulation of interleukin-8 by 15-deoxy-Delta(12,14)-PGJ(2) in human monocytes and THP-1 cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, FCRDC, Expt Immunol Lab, DBS, Ft Detrick, MD 21702 USA. RI Zhang, Xia/B-8152-2008 OI Zhang, Xia/0000-0002-9040-1486 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 260 BP A1355 EP A1355 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400288 ER PT J AU Zhang, Y Dufau, ML AF Zhang, Y Dufau, ML TI Differential transcriptional regulation of human and rat luteinizing hormone receptor gene by nuclear orphan receptors SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, Sect Mol Endocrinol, ERRB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 684 BP A1431 EP A1431 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005400715 ER PT J AU Zhang, Z Abernethy, DR Soldatov, NM AF Zhang, Z Abernethy, DR Soldatov, NM TI Age-dependent switch in expression of human Ca2+ channel alpha(1C) subunit isoforms. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 11 PY 2000 VL 14 IS 8 MA 1068 BP A1497 EP A1497 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 313NH UT WOS:000087005401097 ER PT J AU Kawasaki, H Schiltz, L Chiu, R Itakura, K Taira, K Nakatani, Y Yokoyama, KK AF Kawasaki, H Schiltz, L Chiu, R Itakura, K Taira, K Nakatani, Y Yokoyama, KK TI ATF-2 has intrinsic histone acetyltransferase activity which is modulated by phosphorylation SO NATURE LA English DT Article ID AMP RESPONSE ELEMENT; COACTIVATORS P300; TRANSCRIPTIONAL ACTIVATION; GENOTOXIC AGENTS; RETINOIC-ACID; DNA-BINDING; ACETYLATION; PROTEIN; CBP; NUCLEAR AB Transcription factors carry functional domains, which are often physically distinct, for sequence-specific DNA binding, transcriptional activation and regulatory functions. The transcription factor ATF-2 is a DNA-binding protein that binds to cyclic AMP-response elements (CREs), forms a homodimer or heterodimer with c-Jun, and stimulates CRE-dependent transcription(1-3). Here we report that ATF-2 is a histone acetyltransferase (HAT), which specifically acetylates histones H2B and H4 in vitro. Motif A, which is located in the HAT domain, is responsible for the stimulation of CRE-dependent transcription; moreover, in response to ultraviolet irradiation, phosphorylation of ATF-2 is accompanied by enhanced HAT activity of ATF-2 and CRE-dependent transcription. These results indicate that phosphorylation of ATF-2 controls its intrinsic HAT activity and its action on CRE-dependent transcription. ATF-2 may represent a new class of sequence-specific factors, which are able to activate transcription by direct effects on chromatin components. C1 RIKEN, Inst Phys & Chem Res, Tsukuba Life Sci Ctr, Tsukuba, Ibaraki 3050074, Japan. MITI, Agcy Ind Sci & Technol, Natl Inst Adv Interdisciplianry Res, Tsukuba, Ibaraki 3050006, Japan. MITI, Agcy Ind Sci & Technol, Natl Inst Biosci & Human Technol, Tsukuba, Ibaraki 3050006, Japan. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Sch Dent Surg Oncol Oral Biol & Med, Los Angeles, CA 90095 USA. City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Genet, Duarte, CA 91010 USA. Univ Tokyo, Grad Sch Engn, Dept Chem & Biotechnol, Tokyo 1138656, Japan. RP Yokoyama, KK (reprint author), RIKEN, Inst Phys & Chem Res, Tsukuba Life Sci Ctr, Tsukuba, Ibaraki 3050074, Japan. NR 29 TC 176 Z9 182 U1 0 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 11 PY 2000 VL 405 IS 6783 BP 195 EP 200 DI 10.1038/35012097 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 314WG UT WOS:000087080100054 PM 10821277 ER PT J AU Kovacs, JA Masur, H AF Kovacs, JA Masur, H TI Drug therapy: Prophylaxis against opportunistic infections in patients with human immunodeficiency virus infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID PNEUMOCYSTIS-CARINII PNEUMONIA; MYCOBACTERIUM-AVIUM COMPLEX; ACTIVE ANTIRETROVIRAL THERAPY; PLACEBO-CONTROLLED TRIAL; RANDOMIZED TRIAL; TRIMETHOPRIM-SULFAMETHOXAZOLE; ACQUIRED-IMMUNODEFICIENCY; CYTOMEGALOVIRUS RETINITIS; MAINTENANCE THERAPY; TOXOPLASMIC ENCEPHALITIS C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Masur, H (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 110 TC 135 Z9 144 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 11 PY 2000 VL 342 IS 19 BP 1416 EP 1429 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 312JR UT WOS:000086940600007 PM 10805828 ER PT J AU Mills, JL AF Mills, JL TI Fortification of foods with folic acid - How much is enough? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID NEURAL-TUBE DEFECTS; COBALAMIN DEFICIENCY; PERNICIOUS-ANEMIA; FOLATE; PREVENTION; SUPPLEMENTATION C1 NICHHD, Bethesda, MD 20892 USA. RP Mills, JL (reprint author), NICHHD, Bethesda, MD 20892 USA. NR 28 TC 65 Z9 67 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 11 PY 2000 VL 342 IS 19 BP 1442 EP 1445 DI 10.1056/NEJM200005113421911 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 312JR UT WOS:000086940600011 PM 10805832 ER PT J AU Firon, M Shaharabany, M Altstock, RT Horev, J Abramovici, A Resau, JH Vande Woude, GF Tsarfaty, I AF Firon, M Shaharabany, M Altstock, RT Horev, J Abramovici, A Resau, JH Vande Woude, GF Tsarfaty, I TI Dominant negative Met reduces tumorigenicity-metastasis and increases tubule formation in mammary cells SO ONCOGENE LA English DT Article DE Met; HGF/SF; dominant negative; tubulogenesis; breast cancer cells ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; HUMAN BREAST-CANCER; C-MET; TYROSINE KINASE; EPITHELIAL-CELLS; FACTOR-RECEPTOR; FACTOR/SCATTER FACTOR; TUMOR PROGRESSION; MET/HGF RECEPTOR AB Activation of the Met tyrosine kinase growth factor receptor by its ligand HGF/SF has been shown to increase in vitro invasiveness in epithelial cell lines. To study the effect of Met-HGF/SF signaling in breast cancer cells, we transfected met, hgf/sf and dominant negative (DN) forms of met into the poorly differentiated metastatic murine mammary adenocarcinoma cell line DA3, These cells express moderate levels of endogenous Met, which is rapidly phosphorylated in response to HGF/SF treatment. Met+hgf/sf transfection results in significantly increased tumorigenic and metastatic activity in vivo accompanied by reduced tubule formation. DA3 cells transfected with DN forms of Met (DN-DA3) exhibit reduced Met phosphorylation following exposure to HGF/SF, Furthermore, as compared to the parental cells, the DN-DA3 cells exhibit diminished in vitro scattering and invasiveness, while in vitro they display greatly reduced tumorigenicity and spontaneous metastasis, Tumors emanating from DN-DA3 cells injected to BALB/C mice are highly differentiated and display extensive tubule formation. These results suggest that Met-HGF/SF signaling is a determining factor in the delicate balance between differentiation/tubule formation and tumorigenicity-metastasis. C1 Tel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Pathol, IL-69978 Tel Aviv, Israel. NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Tel Aviv Univ, Sackler Sch Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel. NR 62 TC 46 Z9 48 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD MAY 11 PY 2000 VL 19 IS 20 BP 2386 EP 2397 DI 10.1038/sj.onc.1203557 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 313UV UT WOS:000087018400003 PM 10828880 ER PT J AU Roos, MD Hanover, JA AF Roos, MD Hanover, JA TI Structure of O-linked GlcNAc transferase: Mediator of glycan-dependent signaling SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Editorial Material ID N-ACETYLGALACTOSAMINYLTRANSFERASE FAMILY; TETRATRICOPEPTIDE REPEATS; INSULIN-RESISTANCE; PROTEIN INTERACTIONS; RAT-1 FIBROBLASTS; GLUCOSE-TRANSPORT; GENE-EXPRESSION; UDP-GALNAC; GLYCOSYLATION; NUCLEAR C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NR 39 TC 38 Z9 40 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 10 PY 2000 VL 271 IS 2 BP 275 EP 280 DI 10.1006/bbrc.2000.2600 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 313LH UT WOS:000087000800001 PM 10799287 ER PT J AU Vartanian, T Goodearl, A Lefebvre, S Park, SK Fischbach, G AF Vartanian, T Goodearl, A Lefebvre, S Park, SK Fischbach, G TI Neuregulin induces the rapid association of focal adhesion kinase with the erbB2-erbB3 receptor complex in Schwann cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GLIAL GROWTH-FACTOR; NEUROMUSCULAR-JUNCTIONS; SIGNAL-TRANSDUCTION; PROLIFERATION; LOCALIZATION; APOPTOSIS; NERVE; ARIA AB Neuregulins signal cells by binding to an activating hetero- and homodimeric forms of the neuregulin receptors HER2 (erbB2), HER3 (erbB3), and HER4 (erbB4). Axonally derived neuregulin signals myelin forming cells of the central and peripheral nervous systems through different receptor complexes: oligodendrocytes through erbB2/erbB4 heterodimers and Schwann cells through erbB2/erbB3 heterodimers. Since the leading edge of myelinating cells interacts directly with the axonal surface, we were interested in determining if signaling molecules localized at the leading edge associate with activated neuregulin receptors. We found a novel association between neuregulin receptors and focal adhesion kinase (FAK) in primary cultures of Schwann cells. Following stimulation with ligand, maximal binding of FAK to HER2 occurred by 1 min whereas maximal binding to HER3 was delayed to similar to 7 min. FAK is localized in focal adhesions of Schwann cells. We have previously shown HER2 and HER3 are distributed evenly throughout the plasmalemma. Neuregulins thus use FAK to transmit intracellular signals and the differential kinetics of FAK association with individual neuregulin receptors, as well as its restricted subcellular localization, may play a role in specifying biologic responses. (C) 2000 Academic Press. C1 Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Beth Israel Deaconess Hosp, Boston, MA USA. Millennium Pharmaceut, Cambridge, MA USA. NINDS, Bethesda, MD 20892 USA. RP Vartanian, T (reprint author), Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. FU NINDS NIH HHS [NS02028, NS18458] NR 22 TC 26 Z9 29 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 10 PY 2000 VL 271 IS 2 BP 414 EP 417 DI 10.1006/bbrc.2000.2624 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 313LH UT WOS:000087000800025 PM 10799311 ER PT J AU Roden, RBS Yutzy, WH Fallon, R Inglis, S Lowy, DR Schiller, JT AF Roden, RBS Yutzy, WH Fallon, R Inglis, S Lowy, DR Schiller, JT TI Minor capsid protein of human genital papillomaviruses contains subdominant, cross-neutralizing epitopes SO VIROLOGY LA English DT Article ID COTTONTAIL RABBIT PAPILLOMAVIRUS; VIRUS-LIKE PARTICLES; BOVINE PAPILLOMAVIRUS; N-TERMINUS; L2; IMMUNIZATION; VACCINATION; TYPE-16; L1; ANTIBODIES AB Vaccination with virus-like particles (VLP), comprising both L1 and L2 of human papillomavirus (HPV) genital types 6, 16, and 18, induces predominantly type-specific neutralizing antibodies. L2 polypeptide vaccines protect animals against experimental challenge with homologous papillomavirus and cross-reactive epitopes are present in HPV L2. To assess L2-specific cross-neutralization of HPV genotypes, sheep were immunized with purified, bacterially expressed HPV6, 16, or 18 L2. in addition to neutralizing the homologous HPV type in vitro, antisera to each HPV L2 also cross-neutralized both heterologous HPV types. This suggests that unlike VLP-based prophylactic HPV vaccines, an L2 polypeptide vaccine may provide broad-spectrum protection. (C) 2000 Academic Press. C1 Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. Cantab Pharmaceut Res Ltd, Cambridge CB4 4GN, England. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Roden, RBS (reprint author), Johns Hopkins Univ, Dept Pathol, Room 656,Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. NR 22 TC 148 Z9 158 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 10 PY 2000 VL 270 IS 2 BP 254 EP 257 DI 10.1006/viro.2000.0272 PG 4 WC Virology SC Virology GA 317LP UT WOS:000087227100002 PM 10792983 ER PT J AU Guschin, D Wade, PA Kikyo, N Wolffe, AP AF Guschin, D Wade, PA Kikyo, N Wolffe, AP TI ATP-dependent histone octamer mobilization and histone deacetylation mediated by the Mi-2 chromatin remodeling complex SO BIOCHEMISTRY LA English DT Article ID METASTASIS-ASSOCIATED GENE; HORMONE RESPONSE ELEMENT; YEAST SWI/SNF COMPLEX; NUCLEOSOMAL DNA; TRANSCRIPTIONAL REPRESSION; RNA-POLYMERASE; SACCHAROMYCES-CEREVISIAE; CORE HISTONES; N-TERMINI; ACETYLTRANSFERASE AB The Mi-2 complex has been implicated in chromatin remodeling and transcriptional repression associated with histone deacetylation. Here, we use a purified Mi-2 complex containing six components, Mi-2, Mta 1-like, p66, RbAp48, RPD3, and MBD3, to investigate the capacity of this complex to destabilize histone-DNA interactions and deacetylate core histones. The Mi-2 complex has ATPase activity that is stimulated by nucleosomes but not by free histones or DNA. This nucleosomal ATPase is relatively inefficient, yet is essential to facilitate both translational movement of histone octamers relative to DNA and the efficient deacetylation of the core histones within a mononucleosome. Surprisingly, ATPase activity had no effect on deacetylation of nucleosomal arrays. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. NR 61 TC 67 Z9 68 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 9 PY 2000 VL 39 IS 18 BP 5238 EP 5245 DI 10.1021/bi000421t PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 312PD UT WOS:000086950900002 PM 10819992 ER PT J AU Deng, HB Yu, YK Pak, Y O'Dowd, BF George, SR Surratt, CK Uhl, GR Wang, JB AF Deng, HB Yu, YK Pak, Y O'Dowd, BF George, SR Surratt, CK Uhl, GR Wang, JB TI Role for the C-terminus in agonist-induced mu opioid receptor phosphorylation and desensitization SO BIOCHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; RAT LOCUS-COERULEUS; RHODOPSIN PHOSPHORYLATION; OPIATE RECEPTOR; AMINO-ACIDS; IN-VIVO; SITES; IDENTIFICATION; DELTA; INTERNALIZATION AB Determining which domains and amino acid residues of the mu opioid receptor are phosphorylated is critical for understanding the mechanism of mu opioid receptor phosphorylation. The role of the C-terminus of the receptor was investigated by examining the C-terminally truncated or point-mutated mu opioid receptors in receptor phosphorylation and desensitization. Both wild-type and mutated receptors were stably expressed in Chinese hamster ovary (CHO) cells. The receptor expression was confirmed by receptor radioligand binding and immunoblotting. After exposure to 5 mu M of DAMGO, phosphorylation of the C-terminally truncated receptor and the mutant receptor T394A was reduced to 30 and 10% of that of the wild-type receptor, respectively. Mutation effects on agonist-induced desensitization were studied using adenylyl cyclase inhibition assays. The C-terminally truncated receptor and mutant receptor T394A both showed complete loss of DAMGO-induced desensitization, while the mutant T/S-7A receptor only lost part of its ability to desensitize. Taken together, these results suggest that the C-terminus of the mu opioid receptor participates in receptor phosphorylation and desensitization with threonine 394, a crucial residue for both features. DAMGO-induced mu opioid receptor phosphorylation and desensitization are associated and appear to involve both the mu opioid receptor C-terminus and other domains of the receptor. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada. Addict Res Fdn, Toronto, ON M5S 2S1, Canada. Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10461 USA. NIDA, Mol Neurobiol Branch, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21224 USA. RP Wang, JB (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. FU NIDA NIH HHS [DA11925] NR 40 TC 45 Z9 47 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 9 PY 2000 VL 39 IS 18 BP 5492 EP 5499 DI 10.1021/bi991938b PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 312PD UT WOS:000086950900032 PM 10820022 ER PT J AU Booth, CL Pulaski, L Gottesman, MM Pastan, L AF Booth, CL Pulaski, L Gottesman, MM Pastan, L TI Analysis of the properties of the N-terminal nucleotide-binding domain of human P-glycoprotein SO BIOCHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANCE GENE; ATP-BINDING; SALMONELLA-TYPHIMURIUM; DEPENDENT TRANSPORT; ESCHERICHIA-COLI; LINKER REGION; ACTIVE-SITE; PURIFICATION; OVEREXPRESSION; EXPRESSION AB Human P-glycoprotein, the MDR1 gene product, requires both Mg2+-ATP binding and hydrolysis to function as a drug transporter; however, the mechanism(s) defining these events is not understood. In the present study, we explored the nature of Mg2+-ATP binding in the N-terminal nucleotide-binding domain of human P-glycoprotein and identified the minimal functional unit required for specific ATP binding. Recombinant proteins encompassing amino acids within the region beginning at 348 and ending at 707 were expressed in Escherichia coli, purified from inclusion bodies under denaturing conditions, and renatured by rapid dilution. The ability of ATP to interact with these proteins was examined by use of the photoactive ATP analogue [alpha-P-32]-8-azido-ATP. Photoaffinity labeling of recombinant proteins identified the region between amino acids 375 and 635 as the region necessary to obtain specific ATP-binding properties. Specific protein labeling was saturable, enhanced by Mg2+, and inhibited by ATP. Recombinant proteins confined within the region beginning at amino acid 392 and ending at amino acid 590 demonstrated nonspecific [alpha-P-32]-8-azido-ATP labeling. Nonspecific labeling was not enhanced by Mg2+ and was inhibited only by high concentrations of ATP. Using a D555N mutated protein, we found that the conserved aspartate residue in the Walker B motif plays a role in magnesium-enhanced ATP-binding. Taken together, these data define the region of the N-terminal nucleotide-binding domain of P-glycoprotein that is required for specific ATP binding and suggest that magnesium may play a role in stabilizing the ATP-binding site. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, L (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 41 TC 21 Z9 21 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 9 PY 2000 VL 39 IS 18 BP 5518 EP 5526 DI 10.1021/bi992931x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 312PD UT WOS:000086950900035 PM 10820025 ER PT J AU Wang, F Harvey, EV Conti, MA Wei, DF Sellers, JR AF Wang, F Harvey, EV Conti, MA Wei, DF Sellers, JR TI A conserved negatively charged amino acid modulates function in human nonmuscle myosin IIA SO BIOCHEMISTRY LA English DT Article ID FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; HEAVY-CHAIN GENE; BETA-MYOSIN; ACANTHAMOEBA MYOSIN; CHIMERIC SUBSTITUTIONS; UNCONVENTIONAL MYOSIN; ACTIN; SUBFRAGMENT-1; PHOSPHORYLATION; EXPRESSION AB A myosin surface loop (amino acids 391-404) is postulated to be an important actin binding site. In human P-cardiac myosin, mutation of arginine-403 to a glutamine or a tryptophan causes hypertrophic cardiomyopathy. There is a phosphorylatable serine or threonine residue present on this loop in some lower eukaryotic myosin class I and myosin class VI molecules. Phosphorylation of the myosin I molecules at this site regulates their enzymatic activity. In almost all other myosins, the homologous residue is either a glutamine or an aspartate, suggesting that a negative charge at this location is important for activity. To study the function of this loop, we have used site-directed mutagenesis and baculovirus expression of a heavy meromyosin-(HMM-) like fragment of human nonmuscle myosin IIA. An R393Q mutation (equivalent to the R403Q mutation in human beta-cardiac muscle myosin) has essentially no effect on the actin-activated MgATPase or in vitro motility of the expressed HMM-like fragment. Three mutations, D399K, D399A, and a deletion mutation that removes residues 393-402, all decrease both the V-max of the actin-activated MgATPase by 8-10-fold and the rate of in vitro motility by a factor of 2-3. The K-ATPase of the actin-activated MgATPase activity and the affinity constant for binding of HMM to actin in the presence of ADP are affected by less than a factor of 2. These data support an important role for the negative charge at this location but show that it is not critical to enzymatic activity. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Sellers, JR (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Room 8N202, Bethesda, MD 20892 USA. NR 39 TC 41 Z9 41 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 9 PY 2000 VL 39 IS 18 BP 5555 EP 5560 DI 10.1021/bi000133x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 312PD UT WOS:000086950900039 PM 10820029 ER PT J AU Blum, A Hathaway, L Mincemoyer, R Schenke, WH Kirby, M Csako, G Waclawiw, MA Panza, JA Cannon, RO AF Blum, A Hathaway, L Mincemoyer, R Schenke, WH Kirby, M Csako, G Waclawiw, MA Panza, JA Cannon, RO TI Oral L-arginine in patients with coronary artery disease on medical management SO CIRCULATION LA English DT Article DE atherosclerosis; coronary disease; endothelium; nitric oxide ID CHOLESTEROL-LOWERING THERAPY; NITRIC-OXIDE SYNTHASE; RISK-FACTORS; ENDOTHELIAL DYSFUNCTION; ANGINA-PECTORIS; VASOMOTOR TONE; ATHEROSCLEROSIS; ACETYLCHOLINE; SUPPLEMENTATION; HYPERCHOLESTEROLEMIA AB Background-Vascular nitric oxide (NO) bioavailability is reduced in patients with coronary artery disease (CAD). We investigated whether oral L-arginine, the substrate for NO synthesis, improves homeostatic functions of the vascular endothelium in patients maintained on appropriate medical therapy and thus might be useful as adjunctive therapy. Methods and Results-Thirty CAD patients (29 men; age, 67+/-8 years) on appropriate medical management were randomly assigned to L-arginine (9 g) or placebo daily for 1 month, with crossover to the alternate therapy after 1 month off therapy, in a double-blind study. Nitrogen oxides in serum las an index of endothelial NO release), flow-mediated brachial artery dilation las an index of vascular NO bioactivity), and serum cell adhesion molecules las an index of NO-regulated markers of inflammation) were measured at the end of each treatment period. L-Arginine significantly increased arginine levels in plasma (130+/-53 versus 70+17 mu mol/L, P<0.001) compared with placebo. However, there was no effect of L-arginine on nitrogen oxides (19.3+/-7.9 versus 18.6+/-6.7 mu mol/L, P=0.546), on flow-mediated dilation of the brachial artery (11.9+/-6.3% versus 11.4+/-7.9%, P=0.742), or on the cell adhesion molecules E-selectin (47.8+/-15.2 versus 47.2+/-14.4 ng/mL, P=0.601), intercellular adhesion molecule-1 (250+/-57 versus 249+/-57 ng/mL, P=0.862), and vascular cell adhesion molecule-1 (567+/-124 versus 574+/-135 ng/mL, P=0.473). Conclusions-Oral L-arginine therapy does not improve NO bioavailability in CAD patients on appropriate medical management and thus may not benefit this group of patients. C1 NHLBI, Cardiol Branch, Ctr Clin, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Ctr Clin, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Ctr Clin, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Cardiol Branch, Ctr Clin, NIH, Bldg 10,Room 7B15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. NR 32 TC 106 Z9 110 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 9 PY 2000 VL 101 IS 18 BP 2160 EP 2164 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 311TV UT WOS:000086902500019 PM 10801756 ER PT J AU Reinlib, L Field, L AF Reinlib, L Field, L TI Cell transplantation as future therapy for cardiovascular disease? A workshop of the National Heart, Lung, and Blood Institute SO CIRCULATION LA English DT Editorial Material DE cardiovascular diseases; cells; grafting; myocytes ID SKELETAL MYOBLAST TRANSPLANTATION; MYOCARDIAL SCAR TISSUE; CARDIOMYOCYTE GRAFTS; INTRACARDIAC GRAFTS; SYSTEMIC DELIVERY; EMBRYONIC HEART; CARDIAC-MUSCLE; FETAL; EXPRESSION; DIFFERENTIATION AB Despite the development of improved therapies and the significant advances in the understanding of the basis of disease pathogenesis, millions of Americans continue to live with life-threatening cardiovascular diseases. Recent breakthroughs' suggest exciting directions that are likely to produce more effective therapies for the treatment of cardiovascular disease. One such area, cell transplantation (grafting of healthy cells into the diseased heart), holds enormous potential as an approach to cardiovascular pathophysiology. Once thought to be a scientific long shot, cell transplantation is becoming recognized as a viable strategy to strengthen weak hearts and limit infarct growth. The technology could also be used for the long-term delivery of beneficial recombinant proteins to the heart, which is a strategy to complement molecular biology advances and provide an alternative strategy for gene therapy. On August 24, 1998, the National Heart, Lung, and Blood Institute convened a workshop to discuss the current status of this fast-moving line of research and to explore its promise for treating cardiovascular disease. The participants included basic and clinical researchers, with representatives from academic and commercial research settings. The workshop was designed to establish the state-of-the-art and to equate current research with practical clinical application. The group recommended short- and long-term goals to assist in realizing, in the most expedient manner, the potential utility of cell transplantation for the treatment of cardiovascular disease. A summary of the meeting discussions and recommendations for future areas of research is presented. C1 NHLBI, Div Heart & Vasc Dis, Rockledge Ctr 2, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN USA. Indiana Univ, Sch Med, Herman B Wells Ctr Pediat Res, Indianapolis, IN USA. RP Reinlib, L (reprint author), NHLBI, Div Heart & Vasc Dis, Rockledge Ctr 2, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM lr25v@nih.gov NR 38 TC 96 Z9 106 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 9 PY 2000 VL 101 IS 18 BP E182 EP E187 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 311TV UT WOS:000086902500001 PM 10801766 ER PT J AU Siegel, H Sonies, BC Graham, B McCutchen, C Hunter, K Vega-Bermudez, F Sato, S AF Siegel, H Sonies, BC Graham, B McCutchen, C Hunter, K Vega-Bermudez, F Sato, S TI Obstructive sleep apnea: A study by simultaneous polysomnography and ultrasonic imaging SO NEUROLOGY LA English DT Article DE obstructive sleep apnea; polysomnography; ultrasonic imaging C1 NINCDS, Off Clin Director, EEG Sect, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Rehabil Med, Speech Language Pathol Sect, Bethesda, MD 20892 USA. RP Sato, S (reprint author), NINCDS, Off Clin Director, EEG Sect, NIH, Bldg 10,Room 5C-101,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 7 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 9 PY 2000 VL 54 IS 9 BP 1872 EP 1872 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 311WC UT WOS:000086908000032 PM 10802805 ER PT J AU Anderson, J Phan, L Hinnebusch, AG AF Anderson, J Phan, L Hinnebusch, AG TI The Gcd10p/Gcd14p complex is the essential two-subunit tRNA(1-methyladenosine) methyltransferase of Saccharomyces cerevisiae SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSFER-RNA-SYNTHETASES; METHIONYL-TRANSFER-RNA; YEAST; INITIATOR; TRANSLATION; RESISTANCE; DISCRIMINATION; IDENTIFICATION; METHYLATION; MATURATION AB The modified nucleoside 1-methyladenosine (m(1)A) is found at position 58 in the T Psi C loop of many eukaryotic tRNAs. The absence of m(1)A from ail tRNAs in Saccharomyces cerevisiae mutants lacking Gcd10p elicits severe defects in processing and stability of initiator methionine tRNA (tRNA(i)(Met)). Gcd10p is found in a complex with Gcd14p, which contains conserved motifs for binding S-adenosyl-methionine (AdoMet). These facts, plus our demonstration that gcd14 Delta cells lacked m(1)A, strongly suggested that Gcd10p/Gcd14p complex is the yeast tRNA(m(1)A)methyltransferase [(m(1)A)MTase]. Supporting this prediction, affinity-purified Gcd10p/Gcd14p complexes used AdoMet as a methyl donor to synthesize m(1)A in either total tRNA or purified tRNA(i)(Met) lacking only this modification. Kinetic analysis of the purified complex revealed KM values for AdoMet or tRNA(i)(Met) Of 5.0 mu M and 2.5 nM, respectively. Mutations in the predicted AdoMet-binding domain destroyed GCD14 function in vivo and (m(1)A)MTase activity in vitro. Purified Flag-tagged Gcd14p alone had no enzymatic activity and was severely impaired for tRNA-binding compared with the wild-type complex, suggesting that Gcd10p is required for tight binding of the tRNA substrate. Our results provide a demonstration of a two-component tRNA MTase and suggest that binding of AdoMet and tRNA substrates depends on different subunits of the complex. C1 NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. NR 31 TC 82 Z9 85 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 9 PY 2000 VL 97 IS 10 BP 5173 EP 5178 DI 10.1073/pnas.090102597 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 313KH UT WOS:000086998500033 PM 10779558 ER PT J AU Slattery, JP Sanner-Wachter, L O'Brien, SJ AF Slattery, JP Sanner-Wachter, L O'Brien, SJ TI Novel gene conversion between X-Y homologues located in the nonrecombining region of the Y chromosome in Felidae (Mammalia) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PHYLOGENETIC RECONSTRUCTION; MEIOTIC RECOMBINATION; MOLECULAR EVOLUTION; RIBOSOMAL-RNA; CYTOCHROME-B; SEQUENCES; YEAST; TRANSPOSITION; DIVERGENCE; PATTERNS AB Genes located on the mammalian Y chromosome outside of the pseudoautosomal region do not recombine with those on the X and are predicted to either undergo selection for male function or gradually degenerate because of an accumulation of deleterious mutations. Here, phylogenetic analyses of X-Y homologues, Zfx and Zfy, among 26 felid species indicate two ancestral episodes of directed genetic exchange (ectopic gene conversion) from X to Y: once during the evolution of pallas cat and once in a common predecessor of ocelot lineage species. Replacement of the more rapidly evolving Y homologue with the evolutionarily constrained X copy may represent a mechanism for adaptive editing of functional genes on the nonrecombining region of the mammalian Y chromosome. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. RP Slattery, JP (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. NR 43 TC 57 Z9 59 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 9 PY 2000 VL 97 IS 10 BP 5307 EP 5312 DI 10.1073/pnas.97.10.5307 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 313KH UT WOS:000086998500056 PM 10805789 ER PT J AU Kashiwaya, Y Takeshima, T Mori, N Nakashima, K Clarke, K Veech, RL AF Kashiwaya, Y Takeshima, T Mori, N Nakashima, K Clarke, K Veech, RL TI D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMYLOID PRECURSOR PROTEIN; DOPAMINERGIC-NEURONS; KETONE-BODIES; METABOLISM; INSULIN; POPULATION; PHENOTYPE; INJURY; BRAIN; HEART AB The heroin analogue 1-methyl-4-phenylpyridinium, MPP+, both in vitro and in vivo, produces death of dopaminergic substantia nigral cells by inhibiting the mitochondrial NADH dehydrogenase multienzyme complex, producing a syndrome indistinguishable from Parkinson's disease. Similarly, a fragment of amyloid protein, A beta(1-42) is lethal to hippocampal cells, producing recent memory deficits characteristic of Alzheimer's disease. Here we show that addition of 4 mM D-beta-hydroxybutyrate protected cultured mesencephalic neurons from MPP+ toxicity and hippocampal neurons from A beta(1-42) toxicity. Our previous work in heart showed that ketone bodies, normal metabolites, can correct defects in mitochondrial energy generation. The ability of ketone bodies to protect neurons in culture suggests that defects in mitochondrial energy generation contribute to the pathophysiology of both brain diseases. These findings further suggest that ketone bodies may play a therapeutic role in these most common forms of human neurodegeneration. C1 NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. Tottori Univ, Fac Med, Div Neurol, Yonago, Tottori 6838503, Japan. Univ Oxford, Dept Biochem, Oxford OX1 3QU, England. RP Veech, RL (reprint author), NIAAA, Lab Membrane Biochem & Biophys, 12501 Washington Ave, Rockville, MD 20852 USA. NR 33 TC 208 Z9 211 U1 1 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 9 PY 2000 VL 97 IS 10 BP 5440 EP 5444 DI 10.1073/pnas.97.10.5440 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 313KH UT WOS:000086998500079 PM 10805800 ER PT J AU Xiang, R Lode, HN Chao, TH Ruehlmann, JM Dolman, CS Rodriguez, F Whitton, JL Overwijk, WW Restifo, NP Reisfeld, RA AF Xiang, R Lode, HN Chao, TH Ruehlmann, JM Dolman, CS Rodriguez, F Whitton, JL Overwijk, WW Restifo, NP Reisfeld, RA TI An autologous oral DNA vaccine protects against murine melanoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOTOXIC T-LYMPHOCYTES; ANTIVIRAL PROTECTION; REJECTION ANTIGEN; IN-VIVO; INDUCTION; IDENTIFICATION; IMMUNIZATION; DEGRADATION; CELLS AB We demonstrated that peripheral T cell tolerance toward murine melanoma self-antigens gp100 and TRP-2 can be broken by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to minigenes encoding peptide epitopes gp100(25-33) and TRP-2(181-188). These epitopes contain dominant anchor residues for MHC class I antigen alleles H-2D(b) and H-2K(b), respectively. The DNA vaccine was delivered by oral gavage by using an attenuated strain of Salmonella typhimurium as carrier. Tumor-protective immunity was mediated by MHC class I antigen-restricted CD8(+) T cells that secreted T(H)1 cytokine IFN-gamma and induced tumor rejection and growth suppression after a lethal challenge with B16G3.26 murine melanoma cells. Importantly, the protective immunity induced by this autologous DNA Vaccine against murine melanoma cells was at least equal to that achieved through xenoimmunization with the human gp100(25-33) peptide, which differs in its three NH2-terminal amino acid residues from its murine counterpart and was previously reported to be clearly superior to an autologous vaccine in inducing protective immunity. The presence of ubiquitin upstream of the minigene proved to be essential for achieving this tumor-protective immunity, suggesting that effective antigen processing and presentation may make it possible to break peripheral T cell tolerance to a self-antigen. This vaccine design might prove useful for future rational designs of other recombinant DNA vaccines targeting tissue differentiation antigens expressed by tumors. C1 NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. NCI, NIH, Metab Branch, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA. RP Reisfeld, RA (reprint author), NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999]; NCI NIH HHS [CA42508]; NIAID NIH HHS [AI-37186] NR 22 TC 126 Z9 139 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 9 PY 2000 VL 97 IS 10 BP 5492 EP 5497 DI 10.1073/pnas.090097697 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 313KH UT WOS:000086998500088 PM 10779556 ER PT J AU McBride, AA Dlugosz, A Baker, CC AF McBride, AA Dlugosz, A Baker, CC TI Production of infectious bovine papillomavirus from cloned viral DNA by using an organotypic raft/xenograft technique SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COTTONTAIL RABBIT PAPILLOMAVIRUS; HUMAN FORESKIN XENOGRAFTS; EPITHELIAL RAFT CULTURES; IN-VITRO; MOUSE CELLS; LIFE-CYCLE; TYPE-31; EXPRESSION; BINDING; E7 AB Bovine papillomavirus type 1 (BPV-1) induces fibropapillomas in its natural host and can transform fibroblasts in culture. The Viral genome is maintained as an episome within fibroblasts, which has allowed extensive genetic analyses of the viral functions required for DNA replication, gene expression, and transformation. Much less is known about BPV-1 gene expression and replication in bovine epithelial cells because the study of the complete viral life cycle requires an experimental system capable of generating a fully differentiated stratified bovine epithelium. Using a combination of organotypic raft cultures and xenografts on nude mice, we have developed a system in which BPV-1 can replicate and produce infectious viral particles, Organotypic cultures were established with bovine keratinocytes plated on a collagen raft containing BPV-1-transformed fibroblasts. These keratinocytes were infected with virus particles isolated from a bovine wart or were transfected with cloned BPV-1 DNA, Several days after the rafts were lifted to the air interface,they were grafted on nude mice. After 6-8 weeks, large xenografts were produced that exhibited a hyperplastic: and hyperkeratotic epithelium overlying a large dermal fibroma. These lesions were strikingly similar to a fibropapilloma caused by BPV-I in the natural host Amplified viral DNA and capsid antigens were detected in the suprabasal cells of the epithelium. Moreover, infectious virus particles could be isolated from these lesions and quantitated by a focus formation assay on mouse cells in culture. Interestingly, analysis of grafts produced with infected and uninfected fibroblasts indicated that the fibroma component was not required for productive infection or morphological changes characteristic of papillomavirus-infected epithelium. This system will be a powerful tool for the genetic analysis of the roles of the Viral gene products in the complete viral life cycle. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 137,4 Ctr Dr MSC 0445, Bethesda, MD 20892 USA. OI McBride, Alison/0000-0001-5607-5157 NR 30 TC 10 Z9 10 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 9 PY 2000 VL 97 IS 10 BP 5534 EP 5539 DI 10.1073/pnas.97.10.5534 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 313KH UT WOS:000086998500095 PM 10805809 ER PT J AU Akhmedov, NB Piriev, NI Chang, B Rapoport, AL Hawes, NL Nishina, PM Nusinowitz, S Heckenlively, JR Roderick, TH Kozak, CA Danciger, M Davisson, MT Farber, DB AF Akhmedov, NB Piriev, NI Chang, B Rapoport, AL Hawes, NL Nishina, PM Nusinowitz, S Heckenlively, JR Roderick, TH Kozak, CA Danciger, M Davisson, MT Farber, DB TI A deletion in a photoreceptor-specific nuclear receptor mRNA causes retinal degeneration in the rd7 mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECESSIVE RETINITIS-PIGMENTOSA; BETA-SUBUNIT; ROD PHOSPHODIESTERASE; GENE; MUTATIONS; IDENTIFICATION; TULP1; TUBBY AB The rd7 mouse, an animal model for hereditary retinal degeneration, has some characteristics similar to human flecked retinal disorders. Here we report the identification of a deletion in a photoreceptor-specific nuclear receptor (mPNR) mRNA that is responsible for hereditary retinal dysplasia and degeneration in the rd7 mouse. mPNR was isolated from a pool of photoreceptor-specific cDNAs originally created by subtractive hybridization of mRNAs from normal and photoreceptorless rd mouse retinas. Localization of the gene corresponding to mPNR to mouse Chr 9 near the rd7 locus made it a candidate for the site of the rd7 mutation. Northern analysis of total RNA isolated from rd7 mouse retinas revealed no detectable signal after hybridization with the mPNR cDNA probe. However, with reverse transcription-PCR, we were able to amplify different fragments of mPNR from rd7 retinal RNA and to sequence them directly. We found a 380-nt deletion in the coding region of the rd7 mPNR message that creates a frame shift and produces a premature stop codon. This deletion accounts for more than 32% of the normal protein and eliminates a portion of the DNA-binding domain. In addition, it may result in the rapid degradation of the rd7 mPNR message by the nonsense-mediated decay pathway, preventing the synthesis of the corresponding protein. Our findings demonstrate that mPNR expression is critical for the normal development and function of the photoreceptor cells. C1 Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NIAID, Bethesda, MD 20892 USA. Loyola Marymount Univ, Dept Biol, Los Angeles, CA 90045 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. RP Farber, DB (reprint author), Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. FU NEI NIH HHS [EY08285, EY07758, EY11996, R01 EY007758, R01 EY008285, R01 EY011996] NR 31 TC 139 Z9 141 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 9 PY 2000 VL 97 IS 10 BP 5551 EP 5556 DI 10.1073/pnas.97.10.5551 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 313KH UT WOS:000086998500098 PM 10805811 ER PT J AU Zhou, J Reich, S Brooks, BR AF Zhou, J Reich, S Brooks, BR TI Elastic molecular dynamics with self-consistent flexible constraints SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID SYMPLECTIC INTEGRATORS; HAMILTONIAN-SYSTEMS; POLARIZABLE WATER; SIMULATIONS; ALGORITHMS; LANGEVIN; MOMENTUM; MODELS; ENERGY AB A new algorithm for constrained molecular dynamics is proposed. In contrast to the standard approach, the constrained bond-length/bond-angle value is adjusted at each time step so that total energy is minimized with respect to the constrained distances. This can be viewed as modifying the equilibrium bond-length/bond-angle according to external and centripetal forces. Two approaches are constructed to implement the algorithm. Method I includes all energy terms, but it is neither holonomic nor symplectic. Method II neglects a rotational kinetic energy term, resulting in a more expensive symplectic integrator. Both integrators are reversible and well conserve total energy. Due to the iterative nature of the optimization, which requires an energy evaluation at each iteration, these methods are intended for use in conjunction with other integration techniques that require an optimization at each time step iteration, such as the self-consistent electronic polarization methods or iterative combined quantum mechanics/molecular mechanics (QM/MM) hybrid simulations. Simulation results for collisions between two diatomic molecules, two water molecules, and for a periodic water box are compared and contrasted with fully constrained and free dynamics. These results demonstrate the utility and efficacy of these new methods. (C) 2000 American Institute of Physics. [S0021-9606(00)50906-4]. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Surrey, Dept Math & Stat, Guildford GU2 5XH, Surrey, England. RP NHLBI, Biophys Chem Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Reich, Sebastian/0000-0002-5336-8904 NR 34 TC 22 Z9 22 U1 2 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD MAY 8 PY 2000 VL 112 IS 18 BP 7919 EP 7929 DI 10.1063/1.481393 PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 307DH UT WOS:000086617600019 ER PT J AU Lodmell, DL Ewalt, LC AF Lodmell, DL Ewalt, LC TI Rabies vaccination: comparison of neutralizing antibody responses after priming and boosting with different combinations of DNA, inactivated virus, or recombinant vaccinia virus vaccines SO VACCINE LA English DT Article DE rabies virus; recombinant vaccinia virus (RVV) vaccine; DNA vaccine; human diploid cell vaccine (HDCV); neutralizing antibody; booster ID HUMAN ADENOVIRUS VACCINE; T-CELL INDUCTION; PROTECTIVE IMMUNITY; GLYCOPROTEIN; IMMUNIZATION; INFECTION; EFFICACY; MALARIA; MICE; IMMUNOGENICITY AB Long-term levels of neutralizing antibody were evaluated in mice after a single immunization with experimental DNA or recombinant vaccinia virus (RW) vaccines encoding the rabies virus glycoprotein (Cr), or the commercially available inactivated virus human diploid cell vaccine (HDCV). Anamnestic antibody titers were also evaluated after two booster immunizations with vaccines that were identical to or different from the priming vaccine. Five hundred and forty days (1.5 year) after a single immunization with any of the three vaccines, neutralizing antibody titers remained greater than the minimal acceptable human level of antibody titer (0.5 International Units (IU)/ml). In addition, either an HDCV or DNA booster elicited early and elevated anamnestic antibody responses in mice that had been primed with any of the three vaccines. In contrast, RVV boosters failed to elevate titers in mice that had been previously primed with RVV, and elicited slowly rising titers in mice that had been primed with either DNA or HDCV. Thus, a single vaccination with any of the three different vaccines elicited long-term levels of neutralizing antibody that exceeded 0.5 IU/ml. In contrast, different prime-booster vaccine combinations elicited anamnestic neutralizing antibody responses that increased quickly, increased slowly or failed to increase, Published by Elsevier Science Ltd. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Lodmell, DL (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, 903 S Forth St, Hamilton, MT 59840 USA. NR 30 TC 30 Z9 34 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 8 PY 2000 VL 18 IS 22 BP 2394 EP 2398 DI 10.1016/S0264-410X(00)00005-0 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 313BN UT WOS:000086978600012 PM 10738096 ER PT J AU Durbin, AP Elkins, WR Murphy, BR AF Durbin, AP Elkins, WR Murphy, BR TI African green monkeys provide a useful nonhuman primate model for the study of human parainfluenza virus types-1,-2, and-3 infection SO VACCINE LA English DT Article ID TYPE-3 VACCINE; RHESUS-MONKEYS; HEMAGGLUTININ-NEURAMINIDASE; ATTENUATION PHENOTYPES; SURFACE GLYCOPROTEINS; FUSION GLYCOPROTEINS; PARA-INFLUENZA; PIV TYPE-3; LIVE; CHIMPANZEES AB Human parainfluenza virus (HPIV) types-1, -2, and -3 are significant causes of both upper and Lower respiratory tract disease in infants and children. Although there are two live attenuated vaccines for the prevention of HPIV-3 disease in phase 1 clinical trials, vaccines are not currently available for prevention of HPIV-1 or -2 disease. Our laboratory is developing candidate vaccines for the prevention of HPIV-1, -2, and -3 disease, and a suitable nonhuman primate model is needed for evaluation of these vaccine candidates prior to administration to humans. We evaluated the replication of HPIV-1 and -2 in six different species of nonhuman primates and found both viruses to replicate most efficiently in African green monkeys and chimpanzees. We then compared the replication of HPIV-3 in African green monkeys to that in rhesus macaques, which we have used previously, and found that HPIV-3 replicated to higher titer in African green monkeys. In summary, African green monkeys provide a very useful nonhuman primate for the evaluation of HPIV-1, -2, and -3 vaccine candidates, especially for the evaluation of various combinations of these PIV vaccines and for vaccine strategies that employ sequential immunization. Published by Elsevier Science Ltd. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Durbin, AP (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI-000087] NR 37 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 8 PY 2000 VL 18 IS 22 BP 2462 EP 2469 DI 10.1016/S0264-410X(99)00575-7 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 313BN UT WOS:000086978600020 PM 10738104 ER PT J AU O'Brien, TR McDermott, DH Ioannidis, JPA Carrington, M Murphy, PM Havlir, DV Richman, DD AF O'Brien, TR McDermott, DH Ioannidis, JPA Carrington, M Murphy, PM Havlir, DV Richman, DD TI Effect of chemokine receptor gene polymorphisms on the response to potent antiretroviral therapy SO AIDS LA English DT Article DE AIDS; antiretroviral therapy; CC-chemokine receptor 5; genotype; HIV; HIV RNA; protease inhibitors; treatment response ID HIV-1 DISEASE PROGRESSION; INFECTION; CCR5; AIDS; RESISTANCE; VARIANTS; PLASMA; CCR5-DELTA-32; RESTRICTION; INDIVIDUALS AB Background: Both the natural history of HIV infection and the response to antiretroviral therapy are heterogeneous. Polymorphisms in chemokine receptor genes modulate the natural history of HIV-1 infection. In comparison with subjects with other genotypes, the prognosis for HIV-1-infected CCR5-Delta 32 heterozygotes is more favorable and that for CCR5 promoter allele 59029A homozygotes is less favorable. Methods: HIV-1-infected adults with a CD4+ lymphocyte count greater than or equal to 200 cells x 10(6)/l and a plasma HIV RNA level greater than or equal to 1000 copies/ml were treated with indinavir, zidovudine and lamivudine for 6 months. HIV RNA levels were measured at 4-week intervals. Genotyping for chemokine receptor gene polymorphisms (CCR5-Delta 32, CCR5 59029A/G, CCR2-64l) was performed. We examined whether the time to first HIV RNA < 200 copies/ml, frequency of viral suppression failure (HIV RNA greater than or equal to 200 copies/ mi between weeks 16 and 28 of therapy), or reduction from the pre-treatment HIV RNA level differed by genotype. Results: Time to first HIV RNA < 200 copies/ml was not predicted by genotype. Among 272 Caucasian patients, viral suppression failure was more common among patients with the CCR5 +/+ / CCR2+/+ \ CCR5-59029 A/A genotype (28%) than among all other subjects combined (relative risk, 2.0; P = 0.06). After 24 weeks of therapy, genotype groups differed in the reduction of the HIV RNA level from baseline (P = 0.02); patients with the CCR5 +/+ / CCR2+/+ \ CCR5-59029 A/A genotype had a mean reduction of 2.12 log(10) copies/ml compared to 2.64 log(10) copies/ml among all other groups combined. Conclusion: Polymorphisms in chemokine receptor genes may explain some of the heterogeneity in sustaining viral suppression observed among patients receiving potent antiretroviral therapy. (C) 2000 Lippincott Williams & Wilkins. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD USA. San Diego Vet Affairs Med Ctr, San Diego, CA USA. RP O'Brien, TR (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8016, Rockville, MD 20852 USA. RI Ioannidis, John/G-9836-2011; OI McDermott, David/0000-0001-6978-0867 FU NIAID NIH HHS [AI 27670, AI 36214, AI 38858] NR 24 TC 74 Z9 74 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 5 PY 2000 VL 14 IS 7 BP 821 EP 826 DI 10.1097/00002030-200005050-00008 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 312XK UT WOS:000086969100008 PM 10839590 ER PT J AU Feldman, JG Burns, DN Gange, SJ Bacchetti, P Cohen, M Anastos, K Nowicki, M Delapena, R Miotti, P AF Feldman, JG Burns, DN Gange, SJ Bacchetti, P Cohen, M Anastos, K Nowicki, M Delapena, R Miotti, P TI Serum albumin as a predictor of survival in HIV-infected women in the Women's Interagency HIV Study SO AIDS LA English DT Article DE proportional hazards; serum albumin; survival ID DISEASE; RISK; ASSOCIATION; MORTALITY; COUNT AB Background: The level of serum albumin is associated with mortality in a wide variety of chronic diseases. However, few studies have examined the relationship between serum albumin and survival in HIV-1 infection. Objectives: To determine whether the serum albumin level is associated with survival in HIV-1 infected women. Design: Prospective cohort study. Patients were interviewed and examined at 6 month intervals. Setting: A North American multi-institutional cohort of HIV-infected women from five geographical areas. Participants: A total of 2056 HIV-infected women at various stages of disease. Measurements: Mortality during the first 3 years of follow-up. The relative risk of death by serum albumin level was estimated using a proportional hazards ratio adjusted for CD4 cell count, HIV-1-RNA level and other relevant covariates. Result: Three year mortality for women in the lowest serum albumin category (< 35/l) was 48% compared with 11% in the highest category (greater than or equal to 42 g/l; P<0.001). The adjusted relative hazard (RH) of death was 3.1 times greater for those in the lowest albumin category (P < 0.01). The excess risk associated with lower serum albumin levels remained when subjects with moderate to severe immunosuppression and abnormal kidney and liver function were excluded (P < 0.01). Conclusion: The baseline serum albumin level is an independent predictor of mortality in HIV-l-infected women. The serum albumin level may be a useful additional marker of HIV-1 disease progression, particularly among asymptomatic women with little or no evidence of immunosuppression. (C) 2000 Lippincott Williams & Wilkins. C1 SUNY, Brooklyn, NY USA. NICHHD, Bethesda, MD 20892 USA. Johns Hopkins Sch Hyg & Publ Hlth, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Cook Cty Hosp, Chicago, IL 60612 USA. Catholic Med Ctr, New York, NY USA. Univ So Calif, Los Angeles, CA USA. Howard Univ, Washington, DC 20059 USA. NIAID, Bethesda, MD 20892 USA. RP Feldman, JG (reprint author), SUNY Hlth Sci Ctr, Dept Prevent Med, Box 43,450 Clarkson Ave, Brooklyn, NY 11203 USA. EM jfeldman@netmail.hscbklyn.edu OI Gange, Stephen/0000-0001-7842-512X FU NIAID NIH HHS [U01-AI-31834, U01-AI-35004, U01-AI-34989] NR 14 TC 35 Z9 35 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 5 PY 2000 VL 14 IS 7 BP 863 EP 870 DI 10.1097/00002030-200005050-00013 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 312XK UT WOS:000086969100013 PM 10839595 ER PT J AU Leno, M Kowalski, M Robert-Guroff, M AF Leno, M Kowalski, M Robert-Guroff, M TI CD8 T cell anti-HIV activity as a complementary protective mechanism in vaccinated chimpanzees SO AIDS LA English DT Letter ID IMMUNODEFICIENCY-VIRUS; IMMUNIZATION; INFECTION; MACAQUES C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. RP Leno, M (reprint author), NCI, Basic Res Lab, Bethesda, MD 20892 USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 5 PY 2000 VL 14 IS 7 BP 893 EP 894 DI 10.1097/00002030-200005050-00017 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 312XK UT WOS:000086969100017 PM 10839598 ER PT J AU Dezzutti, CS Guenthner, PC Green, TA Cohen, OJ Spira, TJ Lal, RB AF Dezzutti, CS Guenthner, PC Green, TA Cohen, OJ Spira, TJ Lal, RB TI Stromal-derived factor-1 chemokine gene variant is associated with the delay of HIV-1 disease progression in two longitudinal cohorts SO AIDS LA English DT Letter ID CCR5; INFECTION; HETEROZYGOSITY; POLYMORPHISMS; PATHOGENESIS; CXCR4 C1 Ctr Dis Control & Prevent, HIV & Retrovirol Branch, Div AIDS STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Off Director, Div AIDS STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, HIV Immunol & Diagnost Branch, Div AIDS STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Dezzutti, CS (reprint author), Ctr Dis Control & Prevent, HIV & Retrovirol Branch, Div AIDS STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. NR 16 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 5 PY 2000 VL 14 IS 7 BP 894 EP 896 DI 10.1097/00002030-200005050-00018 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 312XK UT WOS:000086969100018 PM 10839599 ER PT J AU Noronha, SB Yeh, HJC Spande, TF Shiloach, J AF Noronha, SB Yeh, HJC Spande, TF Shiloach, J TI Investigation of the TCA cycle and the glyoxylate shunt in Escherichia coli BL21 and JM109 using C-13-NMR/MS SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE metabolic flux; E. coli; acetate; glyoxylate; TCA cycles; C-13; NMR; MS ID RECOMBINANT PROTEIN-PRODUCTION; ORIENTATION-CONSERVED TRANSFER; FLUX ANALYSIS; ACETATE ACCUMULATION; METABOLIC NETWORKS; CORYNEBACTERIUM-GLUTAMICUM; DENSITY FERMENTATION; MAPPING MATRICES; CULTURES; PHOSPHORYLATION AB Acetate accumulation is a common problem observed in aerobic high cell density Escherichia coli cultures. A previous report has hypothesized that the glyoxylate shunt is active in a low acetate producer, E. coli BL21, and inactive in a high acetate producer, JM109. To further investigate this hypothesis, we now develop a model for the incorporation of C-13 from uniformly labeled glucose into key TCA cycle intermediates. The C-13 isotopomer distributions of oxaloacetate and acetyl-CoA are first determined using NMR and MS techniques. These distributions are next validated by predicting the NMR spectrum of glutamate, Under steady state isotopic conditions, and with knowledge of the full isotopomer distributions of oxaloacetate and acetyl-CoA, the flux ratios through the TCA cycle and the glycoxylate shunt are obtained with respect to the flux through the PPC anaplerotic shunt. We conclude that in BL21, the glyoxylate shunt is active at 22% of the flux through the TCA cycle, and is inactive in JM109. Further, in BL21, the flux through the TCA cycle equals the flux through the PPC shunt, while in JM109 the TCA cycle flux is only third of the flux through the PPC shunt. (C) 2000 John Wiley & Sons, Inc. C1 NIDDK, Biotechnol Unit, LCDB, NIH, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Unit, LCDB, NIH, Bldg 6,Rm BI-33, Bethesda, MD 20892 USA. NR 39 TC 54 Z9 57 U1 0 U2 12 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD MAY 5 PY 2000 VL 68 IS 3 BP 316 EP 327 DI 10.1002/(SICI)1097-0290(20000505)68:3<316::AID-BIT10>3.0.CO;2-2 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 304UA UT WOS:000086501500010 PM 10745200 ER PT J AU Suzukawa, K Miura, K Mitsushita, J Resau, J Hirose, K Crystal, R Kamata, T AF Suzukawa, K Miura, K Mitsushita, J Resau, J Hirose, K Crystal, R Kamata, T TI Nerve growth factor-induced neuronal differentiation requires generation of Rac1-regulated reactive oxygen species SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYDROGEN-PEROXIDE; TRANSFORMING GROWTH-FACTOR-BETA-1; SIGNAL-TRANSDUCTION; NITRIC-OXIDE; PC12 CELLS; FIBROBLASTS; SUPEROXIDE; SPECIFICITY; INVOLVEMENT; EXPRESSION AB Nerve growth factor (NGF) stimulation of pheochromocytoma PC12 cells transiently increased the intracellular concentration of reactive oxygen species (ROS). This increase was blocked by the chemical antioxidant N-acetylcysteine and a flavoprotein inhibitor, diphenylene iodonium. NGF responses of PC12 cells, including neurite outgrowth, tyrosine phosphorylation, and AP-1 activation, was inhibited when ROS production was prevented by N-acetylcysteine and diphenylene iodonium. The expression of dominant negative Rac1N17 blocked induction of both ROS generation and morphological differentiation by NGF. The ROS produced appears to be H2O2, because the introduction of catalase into the cells abolished NGF-induced neurite outgrowth, ROS production, and tyrosine phosphorylation, These results suggest that the ROS, perhaps H2O2, acts as an intracellular signal mediator for NGF-induced neuronal differentiation and that NGF-stimulated ROS production is regulated by Rac1 and a flavoprotein-binding protein similar to the phagocytic NADPH oxidase. C1 NCI, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. NCI, Analyt Microscopy Lab, Adv Biosci Labs,Basic Res Program, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. Cornell Univ, Med Ctr, New York, NY 10021 USA. Kureha Chem, Inst Biomed Res, Tokyo 160, Japan. Shinshu Univ, Sch Med, Dept Mol Biol & Biochem, Nagano 3908621, Japan. RP Kamata, T (reprint author), Shinshu Univ, Sch Med, Dept Mol Biol & Biochem, Asahi 3-1-1, Nagano 3908621, Japan. RI Mitsushita, Junji/D-7688-2016 OI Mitsushita, Junji/0000-0001-9402-4318 NR 26 TC 185 Z9 188 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 2000 VL 275 IS 18 BP 13175 EP 13178 DI 10.1074/jbc.275.18.13175 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 312CH UT WOS:000086925300004 PM 10788420 ER PT J AU Vann, LR Twitty, S Spiegel, S Milstien, S AF Vann, LR Twitty, S Spiegel, S Milstien, S TI Divergence in regulation of nitric-oxide synthase and its cofactor tetrahydrobiopterin by tumor necrosis factor-alpha - Ceramide potentiates nitric oxide synthesis without affecting GTP cyclohydrolase I activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-KAPPA-B; VASCULAR SMOOTH-MUSCLE; VEIN ENDOTHELIAL-CELLS; GENE-EXPRESSION; PROINFLAMMATORY CYTOKINES; INDUCED APOPTOSIS; BINDING SITES; GLIAL-CELLS; ACTIVATION; INDUCTION AB Synthesis of 6(R)-5,6,7,8-tetrahydrobiopterin (BH4), a required cofactor for inducible nitric-oxide synthase (iNOS) activity, is usually coordinately regulated with iNOS expression. In C6 glioma cells, tumor necrosis factor-cu (TNF-cu) concomitantly potentiated the stimulation of nitric oxide (NO) and BH4 production induced by IFN-gamma and interleukin-1 beta. Expression of both iNOS and GTP cyclohydrolase I (GTPCH), the rate-limiting enzyme in the BH4 biosynthetic pathway, was also markedly increased, as were their activities and protein levels. Ceramide, a sphingolipid metabolite, may mediate some of the actions of TNF-alpha. Indeed, we found that bacterial sphingomyelinase, which hydrolyzes sphingomyelin and increases endogenous ceramide, or the cell permeable ceramide analogue, C-2-ceramide, but not C-2-dihydroceramide (N-acetylsphinganine), significantly mimicked the effects of TNF-alpha on NO production and iNOS expression and activity in C6 cells. Surprisingly, although TNF-alpha increased BH4 synthesis and GTPCH activity, neither BH4 nor GTPCH expression was affected by C-2-ceramide or sphingomyelinase in IFN-gamma- and interleukin-1 beta-stimulated cells. It is likely that increased BH4 levels results from increased GTPCH protein and activity in vivo rather than from reduced turnover of BH4, because the GTPCH inhibitor, 2,4-diamino-6-hydroxypyrimidine, blocked cytokine-stimulated BH4 accumulation. Moreover, expression of the GTPCH feedback regulatory protein, which if decreased might increase GTPCH activity, was not affected by TNF-alpha or ceramide. Treatment with the antioxidant pyrrolidine dithiocarbamate, which is known to inhibit NF-kappa B and sphingomyelinase in C6 cells, or with the peptide SN-50, which blocks translocation of NF-kappa B to the nucleus, inhibited TNF-alpha-dependent iNOS mRNA expression without affecting GTPCH mRNA levels. This is the first demonstration that cytokine-stimulated iNOS and GTPCH expression, and therefore NO and BH4 biosynthesis, may be regulated by discrete pathways. As BH4 is also a cofactor for the aromatic amino acid hydroxylases, discovery of distinct mechanisms for regulation of BH4 and NO has important implications for its specific functions. C1 NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. RP Milstien, S (reprint author), NIMH, Lab Cellular & Mol Regulat, NIH, Bldg 36,Rm 2A-11, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM43880] NR 57 TC 33 Z9 34 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 2000 VL 275 IS 18 BP 13275 EP 13281 DI 10.1074/jbc.275.18.13275 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 312CH UT WOS:000086925300019 PM 10788433 ER PT J AU Nelson, SA Aris, JP Patel, BKR LaRochelle, WJ AF Nelson, SA Aris, JP Patel, BKR LaRochelle, WJ TI Multiple growth factor induction of a murine early response gene that complements a lethal defect in yeast ribosome biogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION; CELLS; PDGF; RNA; FIBROBLASTS; ACTIVATION; EXPRESSION; REGULATOR; COMPONENT; PROTEIN AB Identification of the transcriptionally activated targets of receptor tyrosine kinases is critical to understanding biologic programs directing both normal and neoplastic growth. To elucidate these molecular processes, we identified genes induced by a potent mesenchymal mitogen, platelet-derived growth factor (PDGF), Using differential display reverse transcription-polymerase chain reaction technology, we isolated a novel growth factor-induced cDNA, San5. San5 transcript induction occurred within 60 min in NIH 3T3 fibroblasts and proceeded in the presence of cycloheximide. Maximal induction of the San5 transcript occurred between 8 and 16 h, concurrent with passage of fibroblasts through G(1). San5 message was potently induced by PDGF AA and BB and acidic and basic fibroblast growth factors, all strong activators of fibroblast proliferation, but not by epidermal growth factor and interleukin-4. In a murine hematopoietic progenitor cell line, San5 transcript induction strictly correlated with [H-3]thymidine uptake. Isolation and sequencing of the murine San5 cDNA revealed amino acid sequence homology to yeast Nop5p, a nucleolar protein required for pre-rRNA processing and ribosome assembly. Strikingly, SAN5 was able to rescue a nop5 null mutant, implicating SAN5 in the process of ribosome biogenesis. Consistent with this result, SAN5 was localized to the nucleolus in both yeast and mouse. Thus, San5 may provide a link between growth factor receptor activation and the cellular translational machinery. C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Hlth Sci Ctr, Dept Anat & Cell Biol, Gainesville, FL 32610 USA. RP LaRochelle, WJ (reprint author), NCI, Cellular & Mol Biol Lab, NIH, Bldg 37,Rm 1E24, Bethesda, MD 20892 USA. OI Aris, John/0000-0002-6475-064X FU NIGMS NIH HHS [R01 GM048586-05] NR 41 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 2000 VL 275 IS 18 BP 13835 EP 13841 DI 10.1074/jbc.275.18.13835 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 312CH UT WOS:000086925300093 PM 10788506 ER PT J AU Rausch, JW Bona-Le Grice, MK Nymark-McMahon, MH Miller, JT Le Grice, SFJ AF Rausch, JW Bona-Le Grice, MK Nymark-McMahon, MH Miller, JT Le Grice, SFJ TI Interaction of p55 reverse transcriptase from the Saccharomyces cerevisiae retrotransposon Ty3 with conformationally distinct nucleic acid duplexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRIMER-BINDING-SITE; RNASE-H-DOMAIN; STRAND DNA-SYNTHESIS; ESCHERICHIA-COLI; RIBONUCLEASE-H; ANGSTROM RESOLUTION; FOOTPRINT ANALYSIS; CRYSTAL-STRUCTURE; POLYPURINE TRACT AB The 55-kDa reverse transcriptase (RT) domain of the Ty3 POL3 open reading frame was purified and evaluated on conformationally distinct nucleic acid duplexes. Purified enzyme migrated as a monomer by size exclusion chromatography. Enzymatic footprinting indicate Ty3 RT protects template nucleotides +7 through -21 and primer nucleotides -1 through -24, Contrary to previous data with retroviral enzymes, a 4-base pair region of the template-primer duplex remained nuclease accessible. The C-terminal portion of Ty3 RT encodes a functional RNase H domain, although the hydrolysis profile suggests an increased spatial separation between the catalytic centers. Despite conservation of catalytically important residues in the RNase H domain, Fe2+ fails to replace Mg2+ in the RNase H catalytic center for localized generation of hydroxyl radicals, again suggesting this domain may be structurally distinct from its retroviral counterparts. RNase H Specificity was investigated using a model system challenging the enzyme to select the polypurine tract primer from within an RNA/DNA hybrid, extend this into (+) DNA, and excise the primer from nascent DNA, purified RT catalyzed each of these three steps but was almost inactive on a non-polypurine tract RNA primer. Our studies provide the first detailed characterization of the enzymatic activities of a retrotransposon reverse transcriptase. C1 NCI, HIV Drug Resistance Program, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Sci Applicat Int Corp, Frederick, MD 21702 USA. Univ Calif Irvine, Coll Med, Dept Biol Chem, Irvine, CA 92697 USA. RP Rausch, JW (reprint author), NCI, HIV Drug Resistance Program, Div Basic Sci, Frederick Canc Res & Dev Ctr, Bldg 535, Frederick, MD 21702 USA. FU NIGMS NIH HHS [GM33281, GM 52263] NR 55 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 2000 VL 275 IS 18 BP 13879 EP 13887 DI 10.1074/jbc.275.18.13879 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 312CH UT WOS:000086925300099 PM 10788512 ER PT J AU Vitale, N Patton, WA Moss, J Vaughan, M Lefkowitz, RJ Premont, RT AF Vitale, N Patton, WA Moss, J Vaughan, M Lefkowitz, RJ Premont, RT TI GIT proteins, a novel family of phosphatidylinositol 3,4,5-trisphosphate-stimulated GTPase-activating proteins for ARF6 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLATION FACTOR; NUCLEOTIDE-EXCHANGE PROTEIN; KDEL RECEPTOR; GOLGI-COMPLEX; HYDROLYSIS; DOMAIN; IDENTIFICATION; PURIFICATION; PATHWAY; BINDS AB ADP-ribosylation factor (ARF) proteins are key players in numerous vesicular trafficking events ranging from the formation and fusion of vesicles in the Golgi apparatus to exocytosis and endocytosis. To complete their GTPase cycle, ARFs require a guanine nucleotide-exchange protein to catalyze replacement of GDP by GTP and a GTPase-activating protein (GAP) to accelerate hydrolysis of bound GTP. Recently numerous guanine nucleotide-exchange proteins and GAP proteins have been identified and partially characterized. Every ARF GAP protein identified to date contains a characteristic zinc finger motif. GIT1 and GIT2, two members of a new family of G protein-coupled receptor kinase-interacting proteins, also contain a putative zinc finger motif and display ARF GAP activity. Truncation of the amino-terminal region containing the zinc finger motif prevented GAP activity of GIT1, One zinc molecule was found associated per molecule of purified recombinant ARF-GAP1, GIT1, and GIT2 proteins, suggesting the zinc finger motifs of ARF GAPs are functional and should play an important role in their GAP activity. Unlike ARF-GAP1, GIT1 and GIT2 stimulate hydrolysis of GTP bound to ARF6. Accordingly we found that the phospholipid dependence of the GAP activity of ARF-GAP1 and GIT proteins was quite different, as the GIT proteins are stimulated by phosphatidylinositol 3,4,5-trisphosphate whereas ARF-GAP1 is stimulated by phosphatidylinositol 4,5-bisphosphate and diacylglycerol, These results suggest that although the mechanism of GTP hydrolysis is probably very similar in these two families of ARF GAPs, GIT proteins might specifically regulate the activity of ARF6 in cells in coordination with phosphatidylinositol 3-kinase signaling pathways. C1 Duke Univ, Med Ctr, Dept Med Gastroenterol, Howard Hughes Med Inst, Durham, NC 27710 USA. Ctr Neurochim, INSERM, U338, F-67084 Strasbourg, France. Duke Univ, Med Ctr, Dept Med Cardiol, Howard Hughes Med Inst, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Howard Hughes Med Inst, Durham, NC 27710 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Premont, RT (reprint author), Duke Univ, Med Ctr, Dept Med Gastroenterol, Howard Hughes Med Inst, Box 3083, Durham, NC 27710 USA. RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 FU NHLBI NIH HHS [HL16037] NR 34 TC 114 Z9 115 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 2000 VL 275 IS 18 BP 13901 EP 13906 DI 10.1074/jbc.275.18.13901 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 312CH UT WOS:000086925300102 PM 10788515 ER PT J AU Parker, RMC Copeland, NG Eyre, HJ Liu, M Gilbert, DJ Crawford, J Couzens, M Sutherland, GR Jenkins, NA Herzog, H AF Parker, RMC Copeland, NG Eyre, HJ Liu, M Gilbert, DJ Crawford, J Couzens, M Sutherland, GR Jenkins, NA Herzog, H TI Molecular cloning and characterisation of GPR74 a novel G-protein coupled receptor closest related to the Y-receptor family SO MOLECULAR BRAIN RESEARCH LA English DT Article DE neuropeptide Y; cell-surface expression; green fluorescence protein; gene structure; chromosomal localisation ID NEUROPEPTIDE-Y; PANCREATIC-POLYPEPTIDE; PEPTIDE YY; RAT-BRAIN; EXPRESSION; SUBTYPES; ORGANIZATION; SEQUENCE; GENES AB A novel gene product, GPR74, with homology to the seven transmembrane-domain receptor superfamily, has been cloned. GPR74 has been identified from the expressed sequence tags (EST) database. Subsequent PCR amplification of that sequence and screening of a human heart cDNA library led to the isolation of a 1.7-kb cDNA clone encoding a protein of 408 amino acids. GPR74 shows highest amino acid identity (33%) to the human neuropeptide Y-receptor subtype Y2. The human and mouse genes for GPR74 have been isolated and their exon-intron structures determined. In both species the gene consists of four exons spanning around 20 kb with the exon-intron borders being 100% conserved. Northern analysis of various human tissues reveals highest levels of mRNA expression in brain and heart. In situ hybridisation analysis of rat brain tissue confirms this result and identifies the hippocampus and amygdala nuclei as the brain areas with particular high expression of GPR74 mRNA. Fluorescence in situ hybridisation, PCR analysis on a radiation hybrid panel and interspecific mouse backcross mapping have localised the genes to human chromosome 4q21 and mouse chromosome 5. Expression of the human GPR74 cDNA as a GFP-fusion protein in various cell lines reveals the inability of the recombinant receptor protein to reach the cell surface. This is consistent with the lack of NPY specific binding in these cells and suggests that unknown factors are required for a full functional receptor complex. (C) 2000 Elsevier Science B.V. All rights reserved. C1 St Vincents Hosp, Neurobiol Program, Garvan Inst Med Res, Sydney, NSW 2010, Australia. Womens & Childrens Hosp, Dept Cytogenet & Mol Genet, Ctr Med Genet, Adelaide, SA 5006, Australia. NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Herzog, H (reprint author), St Vincents Hosp, Neurobiol Program, Garvan Inst Med Res, 384 Victoria St, Sydney, NSW 2010, Australia. RI Sutherland, Grant/D-2606-2012; Crawford, Joanna /F-9135-2013 OI Crawford, Joanna /0000-0003-0786-6889 NR 24 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY 5 PY 2000 VL 77 IS 2 BP 199 EP 208 DI 10.1016/S0169-328X(00)00052-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 322MX UT WOS:000087514300005 ER PT J AU Namboodiri, MAA Corigliano-Murphy, A Jiang, G Rollag, M Provencio, I AF Namboodiri, MAA Corigliano-Murphy, A Jiang, G Rollag, M Provencio, I TI Murine aspartoacylase: cloning, expression and comparison with the human enzyme SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Canavan disease; N-acetylaspartate; amide hydrolysis; human aspartoacylase; acetate deficiency hypothesis; acetate supplementation therapy ID N-ACETYL-ASPARTATE; DIFFERENTIAL DISTRIBUTION; CANAVAN-DISEASE; NERVOUS-SYSTEM; BOVINE BRAIN; RAT-BRAIN; ACETYLASPARTATE; LOCALIZATION; TRANSPORT AB Canavan disease is caused by mutations in aspartoacylase, the enzyme that degrades N-acetylaspartate (NAA) into acetate and aspartate, Murine aspartoacylase (mASPA) was cloned using sequence information from mouse expressed sequence tags homologous to the human cDNA. The open reading frame was cloned into a thioredoxin fusion vector, overexpressed in bacteria, and the protein was purified using affinity chromatography to near homogeneity. Recombinant human ASPA (hASPA) was prepared by a similar method. Both recombinant enzymes were highly specific to NAA, with about 10% of the NAA activity toward N-acetylasparagine. More interestingly, the product of N-acetylasparagine was aspartate but not asparagine, indicating that ASPA catalyzed deacetylation as well as hydrolysis of the beta acid amide. Our success in preparing the recombinant ASPA in high purity should permit multiple lines of investigations to understand the pathogenic mechanisms of Canavan disease and the functional roles of NAA. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NICHD, Dev Neurobiol Lab, Sect Neuroendocrinol, Bethesda, MD 20892 USA. NIH, Cell Biol Lab, NHLBI, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Physiol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Anat & Cell Biol, Bethesda, MD 20814 USA. RP Namboodiri, MAA (reprint author), NICHD, Dev Neurobiol Lab, Sect Neuroendocrinol, Bethesda, MD 20892 USA. NR 25 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAY 5 PY 2000 VL 77 IS 2 BP 285 EP 289 DI 10.1016/S0169-328X(00)00068-1 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 322MX UT WOS:000087514300015 ER PT J AU Yang, Y Fang, SY Jensen, JP Weissman, AM Ashwell, JD AF Yang, Y Fang, SY Jensen, JP Weissman, AM Ashwell, JD TI Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli SO SCIENCE LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; PROGRAMMED CELL-DEATH; BACULOVIRUS INHIBITOR; C-CBL; E3; FINGER; P53 AB To determine why proteasome inhibitors prevent thymocyte death, we examined whether proteasomes degrade anti-apoptotic molecules in cells induced to undergo apoptosis, The c-IAP1 and XIAP inhibitors of apoptosis were selectively lost in glucocorticoid- or etoposide-treated thymocytes in a proteasome-dependent manner before death. IAPs catalyzed their own ubiquitination in vitro, an activity requiring the RING domain. Overexpressed wild-type c-IAP1, but not a RING domain mutant, was spontaneously ubiquitinated and degraded, and stably expressed XIAP lacking the RING domain was relatively resistant to apoptosis-induced degradation and, correspondingly, more effective at preventing apoptosis than wild-type XIAP. Autoubiquitination and degradation of IAPs may be a key event in the apoptotic program. C1 NCI, Lab Immune Cell Biol, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Fang, Shengyun/H-3802-2011; Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 23 TC 751 Z9 775 U1 0 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 5 PY 2000 VL 288 IS 5467 BP 874 EP 877 DI 10.1126/science.288.5467.874 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 311DN UT WOS:000086869600043 PM 10797013 ER PT J AU Maronpot, RR Mitsumori, K Mann, P Takaoka, M Yamamoto, S Usui, T Okamiya, H Nishikawa, S Nomura, T AF Maronpot, RR Mitsumori, K Mann, P Takaoka, M Yamamoto, S Usui, T Okamiya, H Nishikawa, S Nomura, T TI Interlaboratory comparison of the CB6F1-Tg rasH2 rapid carcinogenicity testing model SO TOXICOLOGY LA English DT Article DE cancer bioassays; animal models; carcinogenicity; transgenic mice; hazard identification ID TRANSGENIC MICE; VINYL CARBAMATE; TUMORS; GENE; SUSCEPTIBILITY; TABLES AB Several genetically engineered mouse models are currently being examined for potential use in cancer hazard identification. We have undertaken an interlaboratory comparison of the performance of the CB6F1-Tg rasH2 transgenic mouse in cancer bioassays concurrently conducted in the United States and Japan. Chemicals selected for study included known human carcinogens (melphalan and cyclosporin A) and known rodent carcinogens (p-cresidine and vinyl carbamate) tested at carcinogenic doses, and non-carcinogens (p-anisidine and resorcinol) tested at appropriate high doses. Because of abdominal adhesions caused by the intraperitoneal dosing vehicle, melphalan was excluded from the study results. The remaining five studies showed similar results between the two laboratories conducting each study. Vinyl carbamate gave the strongest positive response inducing lung adenomas and carcinomas and splenic hemangiosarcomas. p-Cresidine was considered positive for urinary bladder transitional neoplasia, Cyclosporin A, p-anisidine, and resorcinol were negative in all studies. Although only five chemicals were successfully tested in this interlaboratory comparison, there was good concordance in outcome for the strong carcinogens and for the non-carcinogens. Successful testing of chemicals with less carcinogenic potential may require modifications in study design to include more animals and longer study duration. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Natl Inst Hlth Sci, Tokyo 158, Japan. Expt Pathol Labs, Res Triangle Pk, NC USA. Sankyo Co, Shizuoka, Japan. Keio Univ, Sch Med, Tokyo, Japan. Cent Inst Expt Anim, Kawasaki, Kanagawa, Japan. Yamanouchi Pharmaceut Co Ltd, Tokyo, Japan. Kyowa Hakko Kogyo Co Ltd, Ube, Yamaguchi, Japan. RP Maronpot, RR (reprint author), NIEHS, Lab Expt Pathol, POB 12233,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 18 TC 17 Z9 19 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD MAY 5 PY 2000 VL 146 IS 2-3 BP 149 EP 159 DI 10.1016/S0300-483X(00)00168-2 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 322NQ UT WOS:000087516000007 PM 10814847 ER PT J AU Lohrum, MAE Ashcroft, M Kubbutat, MHG Vousden, KH AF Lohrum, MAE Ashcroft, M Kubbutat, MHG Vousden, KH TI Contribution of two independent MDM2-binding domains in p14(ARF) to p53 stabilization SO CURRENT BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR; MDM2; P19(ARF); PRODUCT; LOCUS; DEGRADATION AB The MDM2 protein targets the p53 tumor suppressor for ubiquitin-dependent degradation [1], and can function both as an E3 ubiquitin ligase [2] and as a regulator of the subcellular localization of p53 [3]. Oncogene activation stabilizes p53 through expression of the ARF protein (p14(ARF) in humans, p19(ARF) in the mouse) [4], and loss of ARF allows tumor development without loss of wild type p53 [5,6], ARF binds directly to MDM2, and prevents MDM2 from targeting p53 for degradation [6-9] by inhibiting the E3 ligase activity of MDM2 [2] and preventing nuclear export of MDM2 and p53 [10,11]. Interaction between ARF and MDM2 results in the localization of both proteins to the nucleolus [12-14] through nucleolar localization signals (NoLS) in ARF and MDM2 [11-14], Here, we report a new NoLS within the highly conserved amino terminal 22 amino acids of p14(ARF), a region that we found could interact with MDM2, relocalize MDM2 to the nucleolus and inhibit the ability of MDM2 to degrade p53, In contrast, the carboxy-terminal fragment of p14(ARF), which contains the previously described NoLS [11], did not drive nucleolar localization of MDM2, although this region could bind MDM2 and weakly inhibit its ability to degrade p53, Our results support the importance of nucleolar sequestration for the efficient inactivation of MDM2, The inhibition of MDM2 by a small peptide from the amino terminus of pl4ARF might be exploited to restore p53 function in tumors. C1 NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Frederick, MD 21702 USA. RP Vousden, KH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Bldg 560,Room 22-96,W 7th St, Frederick, MD 21702 USA. NR 16 TC 69 Z9 70 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 4 PY 2000 VL 10 IS 9 BP 539 EP 542 DI 10.1016/S0960-9822(00)00472-3 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 348GZ UT WOS:000088978300020 PM 10801444 ER PT J AU Chaudhary, A King, WG Mattaliano, MD Frost, JA Diaz, B Morrison, DK Cobb, MH Marshall, MS Brugge, JS AF Chaudhary, A King, WG Mattaliano, MD Frost, JA Diaz, B Morrison, DK Cobb, MH Marshall, MS Brugge, JS TI Phosphatidylinositol 3-kinase regulates Raf1 through Pak phosphorylation of serine 338 SO CURRENT BIOLOGY LA English DT Article ID PROTEIN-KINASE; GUANOSINE TRIPHOSPHATASES; ACTIVATION; RAC; IDENTIFICATION; FAMILY; CELLS; AKT AB We have previously shown that inhibition of phosphatidylinositol (PI) 3 kinase severely attenuates the activation of extracellular signal-regulated kinase (Erk) following engagement of integrin/fibronectin receptors and that Raf is the critical target of PI 3-kinase regulation [I], To investigate how PI 3-kinase regulates Raf, we examined sites on Raf1 required for regulation by PI 3-kinase and explored the mechanisms involved in this regulation. Serine 338 (Ser338), which was critical for fibronectin stimulation of Raf1, was phosphorylated in a PI 3-kinase-dependent manner following engagement of fibronectin receptors. In addition, fibronectin activation of a Raf1 mutant containing a phospho-mimic mutation (S338D) was independent of PI 3-kinase. Furthermore, integrin-induced activation of the serine/threonine kinase Pak-l,which has been shown to phosphorylate Raf1 Ser338, was also dependent on PI 3-kinase activity and expression of a kinase-inactive Pak-1 mutant blocked phosphorylation of Raf1 Ser338. These results indicate that PI 3-kinase regulates phosphorylation of Raf1 Ser338 through the serine/threonine kinase Pak. Thus, phosphorylation of Raf1 Ser338 through PI 3-kinase and Pak provides a co-stimulatory signal which together with Pas leads to strong activation of Raf1 kinase activity by integrins. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, Dallas, TX 75235 USA. Indiana Univ, Sch Med, Dept Med & Biochem, Indianapolis, IN 46202 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res, Mol Basis Carcinogenesis Lab, Frederick, MD 21702 USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. OI Cobb, Melanie/0000-0003-0833-5473 FU NCI NIH HHS [CA78873]; NIGMS NIH HHS [GM53032] NR 18 TC 172 Z9 177 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 4 PY 2000 VL 10 IS 9 BP 551 EP 554 DI 10.1016/S0960-9822(00)00475-9 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 348GZ UT WOS:000088978300023 PM 10801448 ER PT J AU Wickner, RB Taylor, KL Edskes, HK Maddelein, ML AF Wickner, RB Taylor, KL Edskes, HK Maddelein, ML TI Prions: Portable prion domains SO CURRENT BIOLOGY LA English DT Article ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; SACCHAROMYCES-CEREVISIAE; PODOSPORA-ANSERINA; YEAST PRION; IN-VITRO; PROTEIN; SUP35; PROPAGATION; DETERMINANT; URE2P AB Self-propagating abnormal proteins, prions, have been identified in yeast; asparagine/glutamine rich 'prion domains' within these proteins can inactivate the linked functional domains; new prion domains and reporters have been used to make 'synthetic prions', leading to discoveries of new natural prions. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RI MADDELEIN, Marie-Lise/G-5395-2010 NR 36 TC 9 Z9 10 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 4 PY 2000 VL 10 IS 9 BP R335 EP R337 DI 10.1016/S0960-9822(00)00460-7 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 348GZ UT WOS:000088978300007 PM 10801430 ER PT J AU Vgontzas, AN Bixler, EO Papanicolaou, DA Chrousos, GP AF Vgontzas, AN Bixler, EO Papanicolaou, DA Chrousos, GP TI Chronic systemic inflammation in overweight and obese adults SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID SLEEP C1 Penn State Univ, Coll Med, Hershey, PA 17033 USA. NICHHD, Bethesda, MD 20892 USA. RP Vgontzas, AN (reprint author), Penn State Univ, Coll Med, Hershey, PA 17033 USA. NR 5 TC 40 Z9 42 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 3 PY 2000 VL 283 IS 17 BP 2235 EP 2235 DI 10.1001/jama.283.17.2235 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 307UB UT WOS:000086671600015 PM 10807374 ER PT J AU Visser, M Harris, TB AF Visser, M Harris, TB TI Chronic systemic inflammation in overweight and obese adults - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID RISK C1 Vrije Univ Amsterdam, Amsterdam, Netherlands. NIH, Bethesda, MD 20892 USA. RP Visser, M (reprint author), Vrije Univ Amsterdam, Amsterdam, Netherlands. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 3 PY 2000 VL 283 IS 17 BP 2236 EP 2236 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 307UB UT WOS:000086671600017 ER PT J AU Gail, MH Costantino, JP Bryant, J Croyle, R Freedman, L Helzlsouer, K Vogel, V AF Gail, MH Costantino, JP Bryant, J Croyle, R Freedman, L Helzlsouer, K Vogel, V TI Re: Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Pittsburgh, Magee Womens Hosp, Inst Canc, Pittsburgh, PA 15260 USA. Bar Ilan Univ, Ramat Gan, Israel. Johns Hopkins Sch Hyg & Publ Hlth, Baltimore, MD USA. RP Gail, MH (reprint author), NIH, Execut Plaza S,Rm 8032, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 3 PY 2000 VL 92 IS 9 BP 758 EP 758 DI 10.1093/jnci/92.9.758 PG 1 WC Oncology SC Oncology GA 310GL UT WOS:000086818100023 ER PT J AU Bennet, WP Alavanja, MCR Harris, CC AF Bennet, WP Alavanja, MCR Harris, CC TI Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 City Hope Canc Ctr, Div Mol Med, Duarte, CA 91010 USA. Beckman Res Inst, Duarte, CA 91010 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Bethesda, MD 20892 USA. RP Bennet, WP (reprint author), City Hope Canc Ctr, Div Mol Med, Fox Plaza S,Rm 1001A,1500 E Duarte Rd, Duarte, CA 91010 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 3 PY 2000 VL 92 IS 9 BP 760 EP 761 PG 2 WC Oncology SC Oncology GA 310GL UT WOS:000086818100027 ER PT J AU Tanner, FC Boehm, M Akyurek, LM San, H Yang, ZY Tashiro, J Nabel, GJ Nabel, EG AF Tanner, FC Boehm, M Akyurek, LM San, H Yang, ZY Tashiro, J Nabel, GJ Nabel, EG TI Differential effects of the cyclin-dependent kinase inhibitors p27(Kip1), p21(Cip1), and p16(Ink4) on vascular smooth muscle cell proliferation SO CIRCULATION LA English DT Article DE cell cycle; cell division; cyclin-dependent kinases ID PROTEIN; P21; PROGRESSION; EXPRESSION AB Background-The cyclin-dependent kinase inhibitors (CKIs) have different patterns of expression in vascular diseases. The Kip/Cip CKIs, p27(Kip1) and p21(Cip1), are upregulated during arterial repair and negatively regulate the growth of vascular smooth muscle cells (VSMCs). In contrast, the Ink CKI, p16(Ink4), is not expressed in vascular lesions. We hypothesized that a variation in the inactivation of cdk3 and cdk4 during the G(1) phase of the cell cycle by p27(Kip1), p21(Cip1) and p16(Ink4) leads to different effects on VSMC growth in vitro and in vivo. Methods and Results-The expression of p27(Kip1) and p21(Cip1), serum-stimulated VSMCs inactivated cdk2 and cdk4, leading to G(1) growth arrest, p16(Ink4) inhibited cdk4, but not cdk2, kinase activity, producing partial inhibition of VSMC growth in vitro. In an in vivo model of vascular injury, overexpression of p27(Kip1) reduced intimal VSMC proliferation by 52% (P<0.01) and the intima/media area ratio by 51% (P<0.005) after vascular injury and gene transfer to pig arteries, when compared with control arteries. p16(Ink4) was a weak inhibitor of intimal VSMC proliferation in injured arteries (P=NS), and it did not significantly reduce intima/media area ratios (P=NS), which is consistent with its minor effects on VSMC growth in vitro. Conclusions-p27(Kip1) and p21(Cip1) are potent inhibitors of VSMC growth compared with p16(Ink4) because of their different molecular mechanisms of cyclin-dependent kinase inhibition in the G(1) phase of the cell cycle. These findings have important implications for our understanding of the pathophysiology of vascular proliferative diseases and for the development of molecular therapies. C1 NHLBI, Bethesda, MD 20892 USA. NIH, Vaccine Res Ctr, Bethesda, MD USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Physiol, Ann Arbor, MI 48109 USA. RP Nabel, EG (reprint author), NHLBI, Bldg 10,Room 8C103, Bethesda, MD 20892 USA. NR 16 TC 187 Z9 198 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 2 PY 2000 VL 101 IS 17 BP 2022 EP 2025 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 310EH UT WOS:000086813200002 PM 10790340 ER PT J AU Vasan, RS Levy, D AF Vasan, RS Levy, D TI Defining diastolic heart failure - A call for standardized diagnostic criteria SO CIRCULATION LA English DT Editorial Material DE heart failure; diastole; echocardiography; imaging; diagnosis ID VENTRICULAR EJECTION FRACTION; SYSTOLIC FUNCTION; POPULATION; PREVALENCE; ECHOCARDIOGRAPHY; DYSFUNCTION; PROGNOSIS; COMMUNITY; DISEASE; IMPACT C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Beth Israel Hosp, Div Cardiol, Boston, MA USA. Beth Israel Hosp, Div Clin Epidemiol, Boston, MA USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. NHLBI, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. RI Tay, Wee Beng/B-1095-2010; OI Ramachandran, Vasan/0000-0001-7357-5970 NR 36 TC 402 Z9 432 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 2 PY 2000 VL 101 IS 17 BP 2118 EP 2121 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 310EH UT WOS:000086813200018 PM 10790356 ER PT J AU Liu, YP Yang, X Xu, XL Deng, JX Cheng, X Huang, CF AF Liu, YP Yang, X Xu, XL Deng, JX Cheng, X Huang, CF TI Expression of Smad4 gene in Pichia pastoris and identification of the protein SO ACTA BIOCHIMICA ET BIOPHYSICA SINICA LA Japanese DT Article DE Smad4; Pichia pastoris; yeast expression AB Smad4 is a novel tumor suppressor gene which is mutated or deleted in about 50% of pancreatic carcinoma and 30% of colon cancer. SMAD4 was expressed in Pichia pastoris and was characterized. The molecular weight of the expression product was shown to be about 67 kD, and 13 amino acids in N terminal were determined and were identical with the putative sequence from Smad4 cDNA, and it was able to specifically react with the antibody against SMAD4. C1 Acad Mil Med Sci, Inst Biotechnol, Beijing 100071, Peoples R China. Guangzhou Inst Mil Med Sci, Guangzhou 510507, Peoples R China. NIDDKD, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 4 PU SHANGHAI INST BIOCHEMISTRY, ACADEMIA SINICA PI SHANGHAI PA 320 YUE-YANG ROAD, SHANGHAI 20031, PEOPLES R CHINA SN 0582-9879 J9 ACTA BIOCH BIOPH SIN JI Acta Biochim. Biophys. Sin. PD MAY PY 2000 VL 32 IS 3 BP 239 EP 242 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 316EF UT WOS:000087154100008 ER PT J AU Gerschenson, M Erhart, SW Paik, CY Claire, MCS Nagashima, K Skopets, B Harbaugh, SW Harbaugh, JW Quan, W Poirier, MC AF Gerschenson, M Erhart, SW Paik, CY Claire, MCS Nagashima, K Skopets, B Harbaugh, SW Harbaugh, JW Quan, W Poirier, MC TI Fetal mitochondrial heart and skeletal muscle damage in Erythrocebus patas monkeys exposed in utero to 3 '-azido-3 '-deoxythymidine SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL NUCLEOSIDE ANALOGS; ZIDOVUDINE-INDUCED MYOPATHY; DNA-POLYMERASE-GAMMA; CARDIAC STRUCTURE; HIV-INFECTION; AZT; THERAPY; AIDS; DYSFUNCTION AB 3'-azido-3'-deoxythymidine (AZT) is given to pregnant women positive for the human immunodeficiency virus type 1 (HIV-1) to reduce maternal-fetal viral transmission, To explore fetal mitochondrial consequences of this exposure, pregnant Erythrocebus patas monkeys were given daily doses of 1.5 mg (21% of the human daily dose) and 6.0 mg (86% of the human daily dose) of AZT/kg body weight (bw), for the second half of gestation. At term, electron microscopy of fetal cardiac and skeletal muscle showed abnormal and disrupted sarcomeres with myofibrillar loss. Some abnormally shaped mitochondria with disrupted cristae were observed in skeletal muscle myocytes, Oxidative phosphorylation (OXPHOS) enzyme assays showed dose-dependent alterations. At the human-equivalent dose of AZT (6 mg of AZT/kg bw), there was an similar to 85% decrease in the specific activity of NADH dehydrogenase (complex I) and three- to sixfold increases in specific activities of succinate dehydrogenase (complex II) and cytochrome-e oxidase (complex IV). Furthermore, a dose-dependent depletion of mitochondrial DNA levels was observed in both tissues. The data demonstrate that transplacental AZT exposure causes cardiac and skeletal muscle mitochondrial myopathy in the patas monkey fetus. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD 20850 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Cell & Mol Struct, SAIC, Frederick, MD 21702 USA. RP Gerschenson, M (reprint author), NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 40 TC 67 Z9 68 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 1 PY 2000 VL 16 IS 7 BP 635 EP 644 DI 10.1089/088922200308864 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 309QX UT WOS:000086781700004 PM 10791874 ER PT J AU Miley, WJ Suryanarayana, K Manns, A Kubota, R Jacobson, S Lifson, JD Waters, D AF Miley, WJ Suryanarayana, K Manns, A Kubota, R Jacobson, S Lifson, JD Waters, D TI Real-time polymerase chain reaction assay for cell-associated HTLV type I DNA viral load SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRUS TYPE-I; SIMIAN IMMUNODEFICIENCY VIRUS; CYTOTOXIC T-LYMPHOCYTES; LEUKEMIA-VIRUS; HIV-1 INFECTION; NUCLEOTIDE-SEQUENCE; SPASTIC PARAPARESIS; PLASMA; PCR; PROVIRUS AB We have developed a quantitative real-time PCR assay for HTLV-I DNA, This assay approach uses real-time monitoring of fluorescent signal generation as a consequence of Tag-mediated amplification of specific target sequences to allow real-time kinetic analysis of amplicon production. This kinetic approach yields excellent sensitivity and an extremely broad linear dynamic range, and ensures that quantitation is based on analysis during the exponential phase of amplification, regardless of the input template copy number. The HTLV-I DNA assay has a nominal threshold sensitivity of 10 copy Eq/reaction, although single-copy plasmid template can be detected at frequencies consistent with statistical prediction. The linear dynamic range is in excess of 5 logs, Interassay reproducibility averages 14% (coefficient of variation) for control templates over a range of 10(1) to 10(6) copy Eq/reaction and 25%, based on studies of extraction and analysis of replicate aliquots of PBMC specimens from HTLV-I-infected subjects. The primer/probe combination targets tax sequences conserved across described HTLV-I and HTLV-II isolates. Parallel quantitation in the same samples of an endogenous sequence present at a known copy number per cell allows normalization of results for potential variation in DNA recovery. Availability of this assay should facilitate studies of basic pathogenesis and clinical evaluation of HTLV-I and HTLV-II infection, as well as assessment of therapeutic approaches. C1 NCI, Frederick Canc Res & Dev Ctr, Human Retrovirus Sect, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Retroviral Pathogenesis,AIDS Vaccine Program, Frederick, MD 21702 USA. NCI, Viral Epidemiol Branch, NIH, Rockville, MD 20852 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Waters, D (reprint author), NCI, Frederick Canc Res & Dev Ctr, Human Retrovirus Sect, SAIC Frederick, Frederick, MD 21702 USA. RI Kubota, Ryuji/A-7139-2009 FU NCI NIH HHS [N01-CO-56000] NR 53 TC 30 Z9 30 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 1 PY 2000 VL 16 IS 7 BP 665 EP 675 DI 10.1089/088922200308891 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 309QX UT WOS:000086781700007 PM 10791877 ER PT J AU Fahlke, C Lorenz, JG Long, J Champoux, M Suomi, SJ Higley, JD AF Fahlke, C Lorenz, JG Long, J Champoux, M Suomi, SJ Higley, JD TI Rearing experiences and stress-induced plasma cortisol as early risk factors for excessive alcohol consumption in nonhuman primates SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE rhesus macaques; alcohol consumption; cortisol; social separation; rearing condition ID MONKEYS MACACA-MULATTA; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; DIMINISHED SOCIAL COMPETENCE; CSF MONOAMINE METABOLITE; RHESUS-MONKEYS; PARAVENTRICULAR NUCLEUS; MESSENGER-RNA; RAT-BRAIN; DRINKING; RECEPTOR AB Background: The purpose of this study was to assess the impact of early rearing and stress-induced rise of plasma cortisol collected during infancy as a biological predictors of adult alcohol consumption in nonhuman primates. Methods: Ninety-seven female and male rhesus macaques (Macaca mulatta) were investigated. They were reared for their first 6 months of life either without mothers or other adults but with constant access to same-aged peers (peer-reared), or as controls with their mothers (mother-reared). When subjects reached 6 months of age, they underwent a series of four sequential weeks of 4-day social separations. Blood was drawn 1 and 2 hr after initiation of the 4-day separation periods, and the plasma was assayed for plasma cortisol concentrations. When the subjects were young adults (approximately 50 months of age), they were tested for voluntary intake of alcohol for 1 hr per day, 4 days a week, during a period of 5 to 7 weeks under normal living conditions. Results: The social separation challenge increased infant plasma cortisol concentrations, with peer-reared subjects exhibiting higher stress-induced cortisol concentrations than mother-reared animals. Subjects that responded to the social separation challenge with high cortisol levels consumed significantly more alcohol per kilogram of body weight as adults than subjects with a low cortisol response to the separation challenge, regardless of rearing condition. In addition, male and peer-reared subjects consumed significantly more alcohol than female and mother-reared subjects, respectively. Conclusions: These findings suggest that early rearing experiences, such as adult absence, and high plasma cortisol concentrations early in life after a social separation stressor, are useful psychobiological predictors of future high alcohol consumption among nonhuman primates. C1 NIAAA, Clin Studies Lab, Primate Unit, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA. NICHHD, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD USA. RP Fahlke, C (reprint author), Univ Gothenburg, Dept Psychol, Box 500, SE-40530 Gothenburg, Sweden. NR 43 TC 128 Z9 128 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2000 VL 24 IS 5 BP 644 EP 650 DI 10.1111/j.1530-0277.2000.tb02035.x PG 7 WC Substance Abuse SC Substance Abuse GA 317FU UT WOS:000087216000008 PM 10832905 ER PT J AU Cohen, SG Rizzo, PL AF Cohen, SG Rizzo, PL TI Asthma among the famous - A continuing series - Thomas Dylan (1914-1953) Welsh poet and author SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Biographical-Item C1 NIAID, Natl Lib Med, NIH, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, Natl Lib Med, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAY-JUN PY 2000 VL 21 IS 3 BP 185 EP 195 DI 10.2500/108854100778148918 PG 11 WC Allergy SC Allergy GA 327UA UT WOS:000087810900013 PM 10892522 ER PT J AU Lloyd-Jones, DM Camargo, CA Giugliano, RP O'Donnell, CJ AF Lloyd-Jones, DM Camargo, CA Giugliano, RP O'Donnell, CJ TI Effect of leukocytosis at initial examination on prognosis in patients with primary unstable angina SO AMERICAN HEART JOURNAL LA English DT Article ID C-REACTIVE PROTEIN; ACUTE MYOCARDIAL-INFARCTION; BLOOD-CELL COUNT; CORONARY HEART-DISEASE; TROPONIN-T; MORTALITY; PECTORIS; PREDICTORS; FIBRINOGEN; INSIGHTS AB Background Leukocytosis with acute myocardial infarction at initial examination predicts adverse prognosis, but it is unknown whether it predicts outcome in patients with primary unstable angina. Methods and Results We studied 414 consecutive patients with unstable angina admitted through the emergency department to telemetry and intensive care units of an urban academic hospital. To study primary unstable angina, we excluded 134 patients with precipitants (eg, urosepsis, pneumonia) that may cause leukocytosis. Of 280 patients, 96 (34%) had leukocytosis (leukocyte count >10,000 per mu L) at initial examination. A total of 30 patients (11%) died and 47 (17%) died or had nonfatal myocardial infarction within 12 months of initial examination. In a univariate Cox model, patients with leukocytosis had a hazard ratio (HR) of 2.6 (95% confidence interval [CI] 1.3-5.4) for death by 1 year. In a multivariate Cox model the only significant predictors of 1-year death were congestive heart failure at initial examination (HR 7.8; 95% CI 2.8-22) and elevated creatinine (HR 2.7; 95% CI 1.3-5.7); in this model, the relation between leukocytosis and prognosis was markedly attenuated (HR 1.4, 95% CI 0.6-2.9). The adjusted HR for leukocytosis was 1.3 (95% CI 0.7-2.3) for death or nonfatal MI by 1 year. Conclusions Leukocytosis at initial examination is associated with adverse prognosis in patients with primary unstable angina. However, the association is confounded by other important predictors of prognosis. Leukocytosis may be a marker of stress associated with more severe cases of unstable angina or comorbid conditions. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Lloyd-Jones, DM (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [HL03533, HL07575] NR 32 TC 10 Z9 11 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2000 VL 139 IS 5 BP 867 EP 873 DI 10.1016/S0002-8703(00)90019-X PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 312XZ UT WOS:000086970400020 PM 10783221 ER PT J AU Goff, DC Howard, G Wang, CH Folsom, AR Rosamond, WD Cooper, LS Chambless, LE AF Goff, DC Howard, G Wang, CH Folsom, AR Rosamond, WD Cooper, LS Chambless, LE CA ARIC Study Investigators TI Trends in severity of hospitalized myocardial infarction: The Atherosclerosis Risk in Communities (ARIC) Study, 1987-1994 SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY HEART-DISEASE; CASE-FATALITY; MORTALITY; RATES; SURVEILLANCE; EXPERIENCE; MORBIDITY; SURVIVAL; REGISTER; HISTORY AB Background Declining mortality rates of coronary heart disease in the United States could be attributable to declining incidence, declining severity, and/or improvements in treatment. Methods We examined trends in severity of patients hospitalized for myocardial infarction to characterize its contribution to this decline by using data from the Atherosclerosis Risk in Communities (ARIC) study. Results No significant change in the proportion having systolic blood pressure <100 mm Hg or an abnormal pulse at presentation was noted. The proportion with ST-segment elevation on the initial electracardiogram increased 10% per year (P <.001), and the proportion with a diagnostic or evolving diagnostic electrocardiogram abnormality increased 4% per year (P <.01); the proportion that had a new Q-wave infarction develop remained unchanged. The mean peak creatine kinase level decreased 5% per year (P <.001), the proportion with abnormal enzyme levels decreased 10% per year (P <.001), and the proportion that met criteria for definite myocardial infarction decreased 4% per year (P <.05). The proportion that had cardiogenic shock decreased 10.9% per year (P <.01), but the proportion that had an acute episode of congestive heart failure was stable. Conclusions With stable hemodynamic indicators, worsening electrocardiographic indicators, and improving enzymatic indicators, these results provide mixed support for decreases in the severity of myocardial infarction. C1 Wake Forest Univ, Sch Med, Ultrasound Reading Ctr, Winston Salem, NC 27157 USA. Univ Minnesota, Minneapolis, MN USA. Univ N Carolina, Chapel Hill, NC USA. NHLBI, Bethesda, MD 20892 USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Texas, Sch Med, Houston, TX USA. Methodist Hosp, Atherosclerosis Clin Lab, Houston, TX 77030 USA. RP Goff, DC (reprint author), Wake Forest Univ, Sch Med, Ultrasound Reading Ctr, Med Ctr Blvd, Winston Salem, NC 27157 USA. FU NHLBI NIH HHS [N01HC55018, N01HC55016, N01HC55015] NR 23 TC 28 Z9 29 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2000 VL 139 IS 5 BP 874 EP 880 DI 10.1016/S0002-8703(00)90020-6 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 312XZ UT WOS:000086970400021 PM 10783222 ER PT J AU Bittner, V Olson, M Kelsey, SF Rogers, WJ Merz, CNB Armstrong, K Reis, SE Boyette, A Sopko, G AF Bittner, V Olson, M Kelsey, SF Rogers, WJ Merz, CNB Armstrong, K Reis, SE Boyette, A Sopko, G CA WISE Investigators TI Effect of coronary angiography on use of lipid-lowering agents in women: A report from the Women's Ischemia Syndrome Evaluation (WISE) study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; ARTERY DISEASE; HEART-DISEASE; CHOLESTEROL; HYPERCHOLESTEROLEMIA; ATHEROSCLEROSIS; PROGRESSION; REGRESSION; ADHERENCE; TRENDS AB We sought to assess the impact of coronary angiography results on use; of lipid-lowering agents among women enrolled in the Women's Ischemia Syndrome Evaluation [WISE] study. WISE is a multicenter study designed to evaluate new diagnostic modalities among women undergoing angiography for suspected coronary artery disease (CAD). History of atherosclerosis, risk factors for CAD, and low-density lipoprotein (LDL) cholesterol are determined at baseline. The percentage of women at LDL cholesterol goal, use of lipid-lowering agents, and eligibility for lipid-lowering therapy were determined based on National Cholesterol Education Program II guidelines at baseline and 6-week follow-up. Among the 212 women for whom angiographic data were available, 84 had known atherosclerosis, 80 had no history of atherosclerosis but greater than or equal to 2 risk factors (high risk), and 48 had no history of atherosclerosis and <2 risk factors (low risk). At baseline, LDL cholesterol goals were met in 24% women with atherosclerosis, in 56% high-risk women, and in 88% low-risk women. Angiography revealed previously undiagnosed CAD in 70% of the high-risk and in 42% of the low-risk women, After angiography results were available, 6 women started lipid-lowering therapy and 2 stopped. Based on National Cholesterol Education Program II guidelines, 63 additional women would have been eligible for pharmacologic lipid-lowering therapy. Intensification of lipid-lowering therapy was not apparent 6 weeks after coronary angiography in women with newly diagnosed CAD or among women whose diagnosis was confirmed. (C) 2000 by Excerpta Medica, Inc. C1 Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Div Cardiol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Florida, Gainesville, FL USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Bittner, V (reprint author), Univ Alabama, Div Cardiovasc Dis, LHRB 310-UAB Stn, Birmingham, AL 35294 USA. RI Reis, Steven/J-3957-2014 FU NHLBI NIH HHS [N01-HV-68161, N01-HV-68162, N01-HV-68163] NR 20 TC 9 Z9 9 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2000 VL 85 IS 9 BP 1083 EP 1088 DI 10.1016/S0002-9149(00)00700-1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 308PA UT WOS:000086721000007 PM 10781756 ER PT J AU Padayatty, SJ Levine, M AF Padayatty, SJ Levine, M TI Vitamin C and myocardial infarction: the heart of the matter SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID ASCORBIC-ACID C1 NIH, Mol & Clin Nutr Sect, Digest Dis Branch, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Levine, M (reprint author), NIH, Mol & Clin Nutr Sect, Digest Dis Branch, Bldg 10,Room 4D52,MSC 1372, Bethesda, MD 20892 USA. RI Padayatty, Sebastian/A-8581-2012 OI Padayatty, Sebastian/0000-0001-8758-3170 NR 12 TC 11 Z9 13 U1 1 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 2000 VL 71 IS 5 BP 1027 EP 1028 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 306HH UT WOS:000086590900003 PM 10799361 ER PT J AU Booth, SL Tucker, KL Chen, HL Hannan, MT Gagnon, DR Cupples, LA Wilson, PWF Ordovas, J Schaefer, EJ Dawson-Hughes, B Kiel, DP AF Booth, SL Tucker, KL Chen, HL Hannan, MT Gagnon, DR Cupples, LA Wilson, PWF Ordovas, J Schaefer, EJ Dawson-Hughes, B Kiel, DP TI Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE vitamin K; phylloquinone; osteoporosis; osteocalcin; apo E genotype; hip fracture; bone mineral density; elderly ID SERUM UNDERCARBOXYLATED OSTEOCALCIN; FOOD FREQUENCY QUESTIONNAIRE; APOLIPOPROTEIN-E; PHYLLOQUINONE VITAMIN-K-1; HEMODIALYSIS-PATIENTS; PHYSICAL-ACTIVITY; FRAMINGHAM; RISK; OSTEOPOROSIS; POPULATION AB Background: Vitamin K has been associated with bone mineral density (BMD) and risk of hip fracture. The apolipoprotein (apo) E4 allele (APOE*E4) has been associated with bone fracture through a putative effect on vitamin K transport in blood. Objective: The objective was to determine the associations between vitamin K intake, apo E genotype, BMD, and hip fracture in a population-based cohort of elderly men and women. Design: Dietary vitamin K intake was assessed with a food-frequency questionnaire in 335 men and 553 women (average age: 75.2 y) participating in the Framingham Heart Study in 1988-1989. Incidence of hip fractures was recorded from 1988 to 1995. BMD at the hip, spine, and arm was assessed on 2 separate occasions (1988-1989 and 1992-1993). Comparisons between apo E genotype and BMD were made relative to E4 allele status (at least 1 epsilon 4 allele compared with no epsilon 4 allele). Results: Individuals in the highest quartile of vitamin K intake (median: 254 mu g/d) had a significantly lower fully adjusted relative risk (0.35; 95% CI: 0.13, 0.94) of hip fracture than did those in the lowest quartile of intake (median: 56 mu g/d). There were no associations between vitamin K intake and BMD in either men or women. No association was found between the E4 allele and BMD, and there were no significant interactions between the E4 allele and phylloquinone intake and BMD or hip fracture. Conclusions: Low vitamin K intakes were associated with an increased incidence of hip fractures in this cohort of elderly men and women. Neither low vitamin K intake nor E4 allele status was associated with low BMD. C1 Tufts Univ, JM USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Harvard Univ, Sch Med, Hebrew Rehabil Ctr Aged Res, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Training Inst, Div Aging, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. NHLBI, Framingham, MA USA. RP Booth, SL (reprint author), Tufts Univ, JM USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. RI Tucker, Katherine/A-4545-2010; OI Kiel, Douglas/0000-0001-8474-0310; Tucker, Katherine/0000-0001-7640-662X; Ordovas, Jose/0000-0002-7581-5680; Chen, Honglei/0000-0003-3446-7779 FU NHLBI NIH HHS [N01-HC-38038]; NIAMS NIH HHS [R01 AR/AG 41398] NR 44 TC 205 Z9 219 U1 0 U2 9 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 2000 VL 71 IS 5 BP 1201 EP 1208 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 306HH UT WOS:000086590900026 PM 10799384 ER PT J AU Tornwall, ME Virtamo, J Haukka, JK Aro, A Albanes, D Huttunen, JK AF Tornwall, ME Virtamo, J Haukka, JK Aro, A Albanes, D Huttunen, JK TI Prospective study of diet, lifestyle, and intermittent claudication in male smokers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE antioxidants; cohort studies; diet; intermittent claudication; smoking ID CORONARY HEART-DISEASE; PERIPHERAL ARTERIAL-DISEASE; VITAMIN-E CONSUMPTION; ALPHA-TOCOPHEROL; RISK-FACTORS; MYOCARDIAL-INFARCTION; FATTY-ACIDS; DENSITY-LIPOPROTEIN; SERUM-CHOLESTEROL; UNITED-STATES AB The association between dietary and lifestyle factors and intermittent claudication was investigated in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cohort comprised 26,872 male smokers aged 50-69 years who were free of claudication at study entry. At baseline (1985-1988), subjects completed a diet history questionnaire. During a median follow-up period of 4 years (ending in spring 1993), 2,578 men reported symptoms of claudication on the Rose questionnaire, which was administered annually. Smoking status was assessed every 4 months. Smoking, systolic blood pressure, serum total cholesterol, and diabetes mellitus were positively associated with risk for claudication, whereas serum high density lipoprotein cholesterol, education, and leisure time exercise were inversely associated with risk. Dietary carbohydrates, fiber, and n-6 polyunsaturated fatty acids were inversely associated with risk for claudication, as were some dietary and serum antioxidants: dietary vitamin C (highest quartile vs. lowest: relative risk (RR) - 0.86; 95% confidence interval (CI): 0.77, 0.97), dietary gamma-tocopherol (RR = 0.89; 95% CI: 0.79, 1.00), dietary carotenoids (RR = 0.82; 95% CI: 0.73, 0.92), serum alpha-tocopherol (RR = 0.88; 95% CI: 0.77, 1.00), and serum beta-carotene (RR = 0.77; 95% CI: 0.68, 0.86). Smoking cessation reduced subsequent risk for claudication (RR = 0.86; 95% CI: 0.75, 0.99). The authors conclude that classical risk factors for atherosclerosis are associated with claudication. High intakes of antioxidant vitamins may be protective. Further research is needed before antioxidants can be recommended for the prevention of intermittent claudication. C1 Natl Publ Hlth Inst, Dept Nutr, SF-00300 Helsinki, Finland. NCI, Bethesda, MD 20892 USA. RP Tornwall, ME (reprint author), Natl Publ Hlth Inst, Dept Nutr, Mannerheimintie 166, SF-00300 Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015; Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [N0I-CN-45165] NR 46 TC 24 Z9 24 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 2000 VL 151 IS 9 BP 892 EP 901 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 308ER UT WOS:000086698000006 PM 10791562 ER PT J AU Bai, Y Sherman, S Khoury, MJ Flanders, WD AF Bai, Y Sherman, S Khoury, MJ Flanders, WD TI Bias associated with study protocols in epidemiologic studies of disease familial aggregation SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article ID CONGENITAL HEART-DISEASE; BREAST-CANCER; ALZHEIMERS-DISEASE; RISK; HISTORY; RECURRENCE; RELATIVES; MOTHERS AB The effect of selection bias has not been well evaluated in epidemiologic studies which focus on familial aggregation. The authors illustrate this type of bias for a reconstructed cohort study, With the reconstructed cohort design, cases and controls are first selected from the population and their relatives form the exposed and unexposed cohorts, respectively. The recurrence risk ratio (RRR) is calculated to assess and measure familial aggregation. The ways of utilizing information from relatives affects the estimate of RRR, and the authors show that a traditional method used in epidemiologic studies can yield a severely biased estimate of the RRR, However, this traditional approach can give approximately unbiased estimates under special conditions. A novel selection approach is proposed which yields an unbiased estimate of RRR. In conclusion, when relatives are identified through cases or controls, they should be included and counted in the study cohorts each time a case or control is selected, even if they or other family members have already been included. C1 Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Genet, Atlanta, GA USA. Ctr Dis Control & Prevent, Off Genet & Dis Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Bai, Y (reprint author), NCI, Genet Epidemiol Branch, Execut Plaza S,Room 7106,6120 Execut Blvd,MSC 723, Rockville, MD 20852 USA. NR 23 TC 24 Z9 24 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 2000 VL 151 IS 9 BP 927 EP + PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 308ER UT WOS:000086698000010 PM 10791566 ER PT J AU Sarosiek, J Jensen, RT Maton, PN Peura, DA Harlow, D Feng, TQ McCallum, RW Pisegna, JR AF Sarosiek, J Jensen, RT Maton, PN Peura, DA Harlow, D Feng, TQ McCallum, RW Pisegna, JR TI Salivary and gastric epidermal growth factor in patients with Zollinger-Ellison Syndrome: Its protective potential SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL REFLUX DISEASE; HELICOBACTER-PYLORI; ESOPHAGEAL MUCOSA; ACID; SECRETION; RELEASE; HUMANS; ESOPHAGOPROTECTION; CYTOPROTECTION; PROSTAGLANDINS AB OBJECTIVE: Evidence is accumulating that epidermal growth factor (EGF) is a major molecule contributing to the maintenance of the integrity of the upper alimentary tract mucosa before and after injury by acid and pepsin. Patients with Zollinger-Ellison Syndrome (ZES) typically have hypersecretion of acid and pepsin; however, the concentration and rate of secretion of salivary and gastric EGF that could counteract these potentially aggressive factors are unknown. Accordingly, this study was conducted to determine whether EGF affords mucosal protection in ZES patients. METHODS: The concentration and output of salivary (sEGF) and gastric epidermal growth factor (gEGF) were measured in eight patients with ZES and the results compared to those in 17 patients with nonulcer dyspepsia (NUD), serving as a control group. All patients had normal esophageal and gastric mucosa as determined by endoscopy. Total saliva was collected during l-h parafilm- and l-h pentagastrin/parafilm-stimulated conditions, as well as basal and pentagastrin-stimulated gastric juice. The concentration and output of EGF were determined by radioimmunoassay. RESULTS: The concentration of EGF in saliva collected from ZES patients after parafilm chewing was significantly higher compared to that in NUD patients (4.61 +/- 0.59 vs 2.75 +/- 0.50 ng/ml, p < 0.05). The concentration of EGF in saliva collected after pentagastrin stimulation in ZES patients was also significantly higher than in NUD patients (4.37 +/- 0.73 vs 2.22 +/- 0.37 ng/ml, p < 0.05). Salivary EGF output during parafilm chewing in ZES and NUD were similar (68 +/- 6.4 vs 109 +/- 25.2 ng/h). Salivary EGF output after administration of pentagastrin in ZES and NUD was also similar (66 +/- 6.1 vs 132 +/- 45.4 ng/h). Basal EGF output in the gastric juice of patients with ZES was 3-fold higher than in patients with NUD (801 +/- 73 la 271 +/- 32 ng/h, p < 0.01). Pentagastrin-stimulated EGF output was similar in both groups (705 +/- 92 Is 675 +/- 168 ng/h). CONCLUSIONS: Patients with ZES have a significantly higher EGF concentration in saliva and EGF output in basal gastric juice. This elevated content of salivary and gastric EGF in ZES patients may ploy a protective role in preventing the development of reflux esophagitis and gastric ulcer under the impact of gastric acid and pepsin hypersecretion. (C) 2000 by Am. Cell. of Gastroenterology. C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Training Program Gastroenterol, Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. NIH, Digest Dis Branch, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22903 USA. RP Pisegna, JR (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Training Program Gastroenterol, Vet Affairs Greater Los Angeles Hlth Care Syst, Bldg 115,Room 316, Los Angeles, CA 90073 USA. NR 42 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2000 VL 95 IS 5 BP 1158 EP 1165 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 310WW UT WOS:000086853300010 PM 10811321 ER PT J AU Stroncek, D Procter, JL Johnson, J AF Stroncek, D Procter, JL Johnson, J TI Drug-induced hemolysis: Cefotetan-dependent hemolytic anemia mimicking an acute intravascular immune transfusion reaction SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE cefotetan; cephalosporins; penicillin; drug-dependent antibodies; hemolytic anemia AB Numerous cases of drug-induced hemolytic anemia have been described in patients treated with penicillin or cephalosporin. Second and third generation cephalosporins are more commonly implicated in hemolytic reactions than first generation cephalosporins. We report a case of severe cefotetan-induced hemolytic anemia in a previously healthy 46-year-old woman undergoing an elective hysterectomy. The patient received 2 g of intravenous cefotetan intraoperatively and subsequently at 12 and 24 h post-operatively. She complained of diarrhea and fever on the third post-operative day and was seen in her gynecologist's office on the fifth post-operative day (hemoglobin = 10.5 g/dL). On the seventh post-operative day, she complained of fever and soreness around the suprapubic catheter site and was given a prescription for 500 mg oral cephalexin four times a day. The next day she was seen in the gynecologist's office and reported feeling better. Ten days after the operation her fatigue worsened and her hemoglobin was 4.8 g/dL, She was transfused with 3 units of packed red blood cells (PRBC) and was given 1 g of cefotetan intravenously, During the transfusion of the second unit of PRBC nursing staff observed gross hemoglobinuria and she subsequently developed acute renal failure. Laboratory chemistry parameters were consistent with severe acute hemolysis, The patient's direct antiglobulin test was reactive and her serum reacted with cefotetan-coated red blood cells (RBCs) and serum plus soluble cefotetan reacted with untreated RBCs, The titration endpoint of the serum against cefotetan-coated RBCs was 40,960, while the serum plus soluble cefotetan against uncoated RBCs was 2,560, This case of severe cefotetan-induced hemolysis was complicated by an acute hemolytic event that occurred during the transfusion of PRBC. Clinical and transfusion service staff must consider drug-induced hemolysis in the differential diagnosis of acute anemia. Am. J. Hematol. 64:67-70, 2000, Published 2000 Wiley-Liss, Inc.dagger C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. St Marys Hosp, Richmond, VA USA. RP Stroncek, D (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, 10 Ctr Dr,MSC-1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 8 TC 9 Z9 9 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2000 VL 64 IS 1 BP 67 EP 70 DI 10.1002/(SICI)1096-8652(200005)64:1<67::AID-AJH12>3.3.CO;2-Q PG 4 WC Hematology SC Hematology GA 306HB UT WOS:000086590300012 PM 10815791 ER PT J AU Hagan, DM Ross, AJ Strachan, T Lynch, SA Ruiz-Perez, V Wang, YM Scambler, P Custard, E Reardon, W Hassan, S Muenke, M Nixon, P Papapetrou, C Winter, RM Edwards, Y Morrison, K Barrow, M Cordier-Alex, MP Correia, P Galvin-Parton, PA Gaskill, S Gaskin, KJ Garcia-Minaur, S Gereige, R Hayward, R Homfray, T McKeown, C Murday, V Plauchu, H Shannon, N Spitz, L Lindsay, S AF Hagan, DM Ross, AJ Strachan, T Lynch, SA Ruiz-Perez, V Wang, YM Scambler, P Custard, E Reardon, W Hassan, S Muenke, M Nixon, P Papapetrou, C Winter, RM Edwards, Y Morrison, K Barrow, M Cordier-Alex, MP Correia, P Galvin-Parton, PA Gaskill, S Gaskin, KJ Garcia-Minaur, S Gereige, R Hayward, R Homfray, T McKeown, C Murday, V Plauchu, H Shannon, N Spitz, L Lindsay, S TI Mutation analysis and embryonic expression of the HLXB9 Currarino syndrome gene SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MOTOR-NEURON IDENTITY; SACRAL AGENESIS; HOMEOBOX GENE; HOMEODOMAIN; HB9; MALFORMATIONS; REQUIREMENT; PANCREAS; HEDGEHOG; COMPLEX AB The HLXB9 homeobox gene was recently identified as a locus for autosomal dominant Currarino syndrome, also known as hereditary sacral agenesis (HSA), This gene specifies a 403-amino acid protein containing a homeodomain preceded by a very highly conserved 82-amino acid domain of unknown function; the remainder of the protein is not well conserved. Here we report an extensive mutation survey that has identified mutations in the HLXB9 gene in 20 of 21 patients tested with familial Currarino syndrome. Mutations were also detected in two of seven sporadic Currarino syndrome patients; the remainder could be explained by undetected mosaicism for an HLXB9 mutation or by genetic heterogeneity in the sporadic patients. Of the mutations identified in the 22 index patients, 19 were intragenic and included 11 mutations that could lead to the introduction of a premature termination codon, The other eight mutations were missense mutations that were significantly clustered in the homeodomain, resulting, in each patient, in nonconservative substitution of a highly conserved amino acid. All of the intragenic mutations were associated with comparable phenotypes. The only genotype-phenotype correlation appeared to be the occurrence of developmental delay in the case of three patients with microdeletions. HLXB9 expression was analyzed during early human development in a period spanning Carnegie stages 12-21, Signal was detected in the basal plate of the spinal cord and hindbrain and in the pharynx, esophagus, stomach, and pancreas, Significant spatial and temporal expression differences were evident when compared with expression of the mouse Hlxb9 gene, which may partly explain the significant human-mouse differences in mutant phenotype. C1 Univ Newcastle Upon Tyne, Sch Biochem & Genet, Human Genet Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Inst Child Hlth, Mol Med Unit, London, England. Inst Child Hlth, Dept Clin Genet & Fetal Med, London, England. UCL, MRC Human Biochem Genet Unit, London, England. Great Ormond St Hosp Sick Children, Dept Neurosurg, London WC1N 3JH, England. Great Ormond St Hosp Sick Children, Nuffield Dept Surg, London WC1N 3JH, England. St George Hosp, Sch Med, Dept Med Genet, London, England. Natl Human Genome Res Inst, Bethesda, MD USA. Leicester Royal Infirm, Dept Clin Genet, Leicester, Leics, England. Hop Hotel Dieu, Lyon, France. IFF Fiocruz, Rio De Janeiro, Brazil. SUNY Stony Brook, Dept Pediat, Stony Brook, NY 11794 USA. Royal Alexandra Hosp Sick Children, Camperdown, NSW, Australia. Hosp Crices, Clin Materno Infantil, Baracaldo, Spain. All Childrens Hosp, St Petersburg, FL USA. Birmingham Womens Hosp, Clin Genet Unit, Birmingham, W Midlands, England. Ctr Human Genet, Sheffield, S Yorkshire, England. RP Strachan, T (reprint author), Univ Newcastle Upon Tyne, Sch Biochem & Genet, Human Mol Genet Unit, Ridley Bldg,Claremont Pl, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. EM tom.strachan@ncl.ac.uk; s.lindsay@newcastle.ac.uk RI Scambler, Peter/C-4998-2008; Ruiz-Perez, Victor /K-6066-2014 OI Scambler, Peter/0000-0002-1487-4628; Ruiz-Perez, Victor /0000-0003-0635-3619 FU Medical Research Council [G9900837, G9826762] NR 41 TC 80 Z9 85 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 2000 VL 66 IS 5 BP 1504 EP 1515 DI 10.1086/302899 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 337QT UT WOS:000088373700004 PM 10749657 ER PT J AU Wilson, AF Sorant, AJM AF Wilson, AF Sorant, AJM TI Equivalence of single- and multilocus markers: Power to detect linkage with composite markers derived from biallelic loci SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SIB-PAIR TEST; QUANTITATIVE TRAITS; REGIONAL INFERENCE AB The reintroduction of biallelic markers, now in the form of single-nucleotide polymorphisms (SNPs), has again raised concerns about the practicality of the use of markers with low heterozygosity for genomic screening for complex traits, even if thousands of such markers are available. Like the early blood-group markers (e.g., Rh and MNS), tightly linked biallelic SNPs can be combined into composite markers with heterozygosity similar to that of short-tandem-repeat polymorphisms. The assumptions that underlie the equivalence between single-locus multiallelic and composite markers are presented. We used computer simulation to determine the power of the Haseman-Elston test for linkage with composite markers when not all of these assumptions hold. The Genometric Analysis Simulation Program was used to simulate continuous and discrete traits, one single-locus four-allele marker, and six biallelic markers. We studied composite markers created from pairs, trios, and quartets of biallelic markers in nuclear families and in independent sib pairs. The power to detect linkage with a two-point approach for composite markers and with a multipoint approach that incorporated all six biallelic markers was compared with that for a single-locus, four-allele reference marker. Although the power to detect linkage with a single biallelic marker was considerably less than that of the reference marker, the power to detect linkage with two- and three-locus composite markers was quite similar to that of the reference marker. The power to detect linkage with four-locus composite markers was similar to that of a multipoint approach. C1 Natl Human Genome Res Inst, NIH, Genometr Sect, Inherited Dis Res Branch, Baltimore, MD 21224 USA. RP Wilson, AF (reprint author), Natl Human Genome Res Inst, NIH, Genometr Sect, Inherited Dis Res Branch, 333 Cassell Dr,Suite 2000, Baltimore, MD 21224 USA. RI Wilson, Alexander/C-2320-2009 FU NCRR NIH HHS [1P41RR03655] NR 17 TC 20 Z9 21 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 2000 VL 66 IS 5 BP 1610 EP 1615 DI 10.1086/302889 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 337QT UT WOS:000088373700015 PM 10762546 ER PT J AU Collins, FS AF Collins, FS TI The sequence of the human genome: coming a lot sooner than you thought. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 2000 VL 66 IS 5 BP 1723 EP 1723 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 337QT UT WOS:000088373700033 ER PT J AU Jemal, A Grauman, D Devesa, S AF Jemal, A Grauman, D Devesa, S TI Recent geographic patterns of lung cancer and mesothelioma mortality rates in 49 shipyard counties in the United States, 1970-94 SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE asbestos; lung cancer; mesothelioma; shipyard; shipbuilding ID WORLD-WAR-II; MALIGNANT MESOTHELIOMA; CHRYSOTILE ASBESTOS; COASTAL VIRGINIA; EXPOSURE; WORKERS; RISK; EMPLOYMENT; OCCUPATION; SMOKING AB Background Lung cancer mortality rates among white males in the United States were observed to be elevated during 1950-69 in counties with shipbuilding industries during World War II; risk was found to be associated with asbestos exposure. We evaluated the geographic patterns in more recent years, 1970-94, for whites and compared them with the 1950-69 patterns, Methods We calculated age-adjusted rates and estimated rate ratios between comparison groups. Results Rates generally were higher in shipyard counties than in all nonshipyard counties and in coastal nonshipyard counties for both sexes and time periods. Rates increased markedly from 1950-69 to 1970-94 in all groups, with the changes more pronounced in females than males. Pleural mesothelioma mortality rates were also significantly higher in shipyard counties than coastal nonshipyard counties in all regions among males but not among females, Conclusion The more pronounced changes in lung cancer mortality rates among females in shipyard counties may be attributed to the combined effects of low asbestos exposures and changes in smoking behavior Am. J, Ind, Med. 37:512-521, 2000. Published 2000 Wiley-Liss, Inc.dagger. C1 NCI, Div Canc Epidemiol & Genet, EPS Biostat Branch 8049, Bethesda, MD 20892 USA. RP Jemal, A (reprint author), NCI, Div Canc Epidemiol & Genet, EPS Biostat Branch 8049, Bethesda, MD 20892 USA. NR 40 TC 16 Z9 16 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAY PY 2000 VL 37 IS 5 BP 512 EP 521 DI 10.1002/(SICI)1097-0274(200005)37:5<512::AID-AJIM7>3.0.CO;2-M PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 300MT UT WOS:000086257300007 PM 10723045 ER PT J AU Hamann, HA Croyle, RT Venne, VL Baty, BJ Smith, KR Botkin, JR AF Hamann, HA Croyle, RT Venne, VL Baty, BJ Smith, KR Botkin, JR TI Attitudes toward the genetic testing of children among adults in a Utah-based kindred tested for a BRCA1 mutation SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE ethics; patients' attitudes; BRCA1 testing; children ID BREAST-OVARIAN CANCER; DECISION-MAKING; ASHKENAZI JEWS; EVENT SCALE; SUSCEPTIBILITY; FAMILIES; RISK; PREDISPOSITION; ADOLESCENTS; PENETRANCE AB Advances in molecular biology and genetics have led to the identification of the breast/ ovarian cancer susceptibility genes BRCA1 and BRCA2, along with tests to detect mutations in these genes. Although the appropriateness of BRCA1/2 genetic testing for children has been debated in the literature, little is known about the attitudes of individuals who have undergone cancer susceptibility testing. The present study focused on attitudes toward BRCA1 testing for children among 218 adults from a Utah-based kindred who had received BRCA1 test results. Results indicated that approximately one-fourth of the participants would permit BRCA1 testing for children under the age of 18, General attitudes about genetic testing were predictive of attitudes toward the testing of children. In addition, men and individuals without a BRCA1 mutation were more likely to agree that miners should be allowed BRCA1 testing. Individuals whose mother had been affected with breast cancer were less likely to permit testing for miners. Among parents of minor children, less than one-fifth indicated that they would want BRCA1 testing for their own children; carrier status was not predictive of attitudes toward testing their own children. As breast/ovarian cancer susceptibility testing continues to be disseminated into clinical settings, there may be an increase in the number of test requests for miners. The findings of the present study represent an important step in exploring attitudes about genetic testing of children among individuals who have received cancer susceptibility test results. Am. J, Med. Genet, 92:25-32, 2000, (C) 2000 Wiley-Liss, Inc. C1 Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Univ Utah, Dept Pediat, Salt Lake City, UT USA. Univ Utah, Dept Family & Consumer Studies, Salt Lake City, UT 84112 USA. RP Hamann, HA (reprint author), Univ Utah, Dept Psychol, 1530 E 390 S,Rm 502, Salt Lake City, UT 84112 USA. FU NCI NIH HHS [CA63681]; NCRR NIH HHS [MO1-RR00064]; PHS HHS [5-T32-NG00042-05] NR 40 TC 33 Z9 33 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 1 PY 2000 VL 92 IS 1 BP 25 EP 32 DI 10.1002/(SICI)1096-8628(20000501)92:1<25::AID-AJMG5>3.0.CO;2-Y PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 303UV UT WOS:000086444000005 PM 10797419 ER PT J AU Wyszynski, DF Diehl, SR AF Wyszynski, DF Diehl, SR TI Infant C677T mutation in MTHFR, maternal periconceptional vitamin use, and risk of nonsyndromic cleft lip SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter ID OROFACIAL CLEFTS; ORAL CLEFTS; FOLIC-ACID; SUPPLEMENTATION; MULTIVITAMINS; PREVENTION C1 Boston Univ, Sch Med, Genet Program, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Natl Inst Dent & Cranofacial Res, NIH, Bethesda, MD USA. RP Wyszynski, DF (reprint author), Boston Univ, Sch Med, Genet Program, 715 Albany St,L320, Boston, MA 02118 USA. NR 15 TC 20 Z9 22 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 1 PY 2000 VL 92 IS 1 BP 79 EP 80 DI 10.1002/(SICI)1096-8628(20000501)92:1<79::AID-AJMG14>3.0.CO;2-H PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 303UV UT WOS:000086444000014 PM 10797428 ER PT J AU Fraenkel, L Tofler, GH Zhang, YQ Silbershatz, H D'Agostino, RB Wilson, PWF Felson, DT AF Fraenkel, L Tofler, GH Zhang, YQ Silbershatz, H D'Agostino, RB Wilson, PWF Felson, DT TI The associations between plasma levels of von Willebrand factor and fibrinogen with Raynaud's phenomenon in men and women SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID VONWILLEBRAND-FACTOR ANTIGEN; SYSTEMIC-SCLEROSIS; DIAGNOSIS; MARKERS; BLOOD C1 Yale Univ, Dept Internal Med, Rheumatol Sect, New Haven, CT 06520 USA. Royal N Shore Hosp, Dept Cardiol, St Leonards, NSW 2065, Australia. Boston Univ, Ctr Arthritis, Boston, MA 02215 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Bethesda, MD USA. RP Fraenkel, L (reprint author), Yale Univ, Dept Internal Med, Rheumatol Sect, POB 208031,333 Cedar St, New Haven, CT 06520 USA. NR 20 TC 2 Z9 2 U1 0 U2 202 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2000 VL 108 IS 7 BP 583 EP 586 DI 10.1016/S0002-9343(00)00350-8 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 312LQ UT WOS:000086945100010 PM 10806290 ER PT J AU Barequet, IS Li, Q Wang, Y O'Brien, TP Hooks, JJ Stark, WJ AF Barequet, IS Li, Q Wang, Y O'Brien, TP Hooks, JJ Stark, WJ TI Herpes simplex virus DNA identification from aqueous fluid in Fuchs heterochromic iridocyclitis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CYCLITIS; UVEITIS AB PURPOSE: To report the presence of herpes simplex virus DNA in the aqueous humor of an eye with Fuchs heterochromic iridocyclitis. METHODS: In an eye with a clinical diagnosis of Fuchs heterochromic iridocyclitis, samples of aqueous humor and anterior capsule of the lens were obtained during cataract surgery. Polymerase chain reaction was per formed on the samples to detect the presence of viral DNA including herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Serologic analysis was also performed for antiviral immunoglobulins, RESULTS: Herpes simplex virus DNA was identified in the aqueous humor but not in the anterior capsule, Serum immunoglobulin G was positive for herpes simplex virus, varicella-zoster virus, and cytomegalovirus, CONCLUSIONS: The presence of herpes simplex virus DNA in the aqueous humor of an eye with Fuchs heterochromic iridocyclitis suggests that herpes simplex virus infection may play a role in the pathogenesis of Fuchs heterochromic iridocyclitis. (C) 2000 by Elsevier Science Inc, All rights reserved. C1 Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA. NEI, NIH, Bethesda, MD 20892 USA. RP Li, Q (reprint author), Johns Hopkins Hosp, Wilmer Eye Inst, Ocular Microbiol & Immunol Lab, Woods 259,600 N Wolfe, Baltimore, MD 21287 USA. NR 5 TC 28 Z9 29 U1 0 U2 1 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 MAY PY 2000 VL 129 IS 5 BP 672 EP 673 DI 10.1016/S0002-9394(00)00409-8 PG 2 WC Ophthalmology SC Ophthalmology GA 318JU UT WOS:000087281200021 PM 10844066 ER PT J AU Slavkin, H AF Slavkin, H TI Toward understanding the molecular basis of craniofacial growth and development SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS LA English DT Editorial Material RP Slavkin, H (reprint author), NIDR, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0889-5406 J9 AM J ORTHOD DENTOFAC JI Am. J. Orthod. Dentofac. Orthop. PD MAY PY 2000 VL 117 IS 5 BP 538 EP 539 DI 10.1016/S0889-5406(00)70191-0 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 314TJ UT WOS:000087073400008 PM 10799106 ER PT J AU Zolyomi, A Zhao, XH Downing, GJ Balla, T AF Zolyomi, A Zhao, XH Downing, GJ Balla, T TI Localization of two distinct type III phosphatidylinositol 4-kinase enzyme mRNAs in the rat SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE inositol lipids; calcium; phospholipase C; wortmannin ID RECEPTOR MESSENGER-RNAS; PHOSPHOLIPASE-C; BOVINE BRAIN; PHOSPHOINOSITIDE 3-KINASE; SACCHAROMYCES-CEREVISIAE; INSITU HYBRIDIZATION; MOLECULAR-CLONING; WORTMANNIN; EXPRESSION; KINASE AB Inositol lipid kinases generate polyphosphoinositides, important regulators of several cellular functions. We have recently cloned two distinct phosphatidylinositol (PI) 4-kinase enzymes, the 210-kDa PI4KIII alpha and the 110-kDa PI4KIII beta, from bovine tissues. In the present study, the distribution of mRNAs encoding these two enzymes was analyzed by in situ hybridization histochemistry in the rat. PI4KIIIa was found predominantly expressed in the brain, with low expression in peripheral tissues. PI4KIII beta was more uniformly expressed being also present in various peripheral tissues. Within the brain, PI4KIII beta showed highest expression in the gray matter, especially in neurons of the olfactory bulb and the hippocampus, but also gave a signal in the white matter indicating its presence in glia. PI4KIII alpha was highly expressed in neurons, but lacked a signal in the white matter and the choroid plexus. Both enzymes showed expression in the pigment layer and nuclear layers as well as in the ganglion cells of the retina. In a 17-day-old rat fetus, PI4KIII beta was found to be more widely distributed and PI4KIII alpha was primarily expressed in neurons. These results indicate that PI4KIII beta is more widely expressed than PI4KIII alpha, and that the two enzymes are probably coexpressed in many neurons. Such expression pattern and the conservation of these two proteins during evolution suggest their nonredundant functions in mammalian cells. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Balla, T (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A35,49 Convent Dr, Bethesda, MD 20892 USA. NR 39 TC 8 Z9 8 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 MAY PY 2000 VL 278 IS 5 BP C914 EP C920 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 313LN UT WOS:000087001300009 PM 10794665 ER PT J AU Penninx, BWJH Guralnik, JM Ferrucci, L Fried, LP Allen, RH Stabler, SP AF Penninx, BWJH Guralnik, JM Ferrucci, L Fried, LP Allen, RH Stabler, SP TI Vitamin B-12 deficiency and depression in physically disabled older women: Epidemiologic evidence from the Women's Health and Aging Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SERUM METHYLMALONIC ACID; COBALAMIN DEFICIENCY; NEUROPSYCHIATRIC DISORDERS; REPLACEMENT THERAPY; FOLATE DEFICIENCIES; ELDERLY WOMEN; PREVALENCE; HOMOCYSTEINE; OUTPATIENTS; POPULATION AB Objective: It has been hypothesized that adequate concentrations of vitamin B-12 and folate are essential to maintain the integrity of the neurological systems involved in mood regulation, but epidemiologic evidence for such a link in the general population is unavailable. This study examined whether community-dwelling older women with metabolically significant vitamin B-12 or folate deficiency are particularly prone to depression. Method: Serum levels of vitamin B-12, Folate, methylmalonic acid, and total homocysteine were assayed in 700 disabled, nondemented women aged 65 years and over living in the community. Depressive symptoms were measured by means of the Geriatric Depression Scale and categorized as no depression, mild depression, and severe depression. Results: Serum homocysteine levels, serum folate levels, and the prevalences folate deficiency and anemia were not associated with depression status. The depressed subjects, especially those with severe depression, had a significantly higher serum methylmalonic acid level and a nonsignificantly lower serum vitamin B-12 level than the nondepressed subjects. Metabolically significant vitamin B-12 deficiency was present in 14.9% of the 478 nondepressed subjects, 17.0% of the 700 mildly depressed subjects, and 27.0% of the 122 severely depressed women. After adjustment for sociodemographic characteristics and health status, the subjects with vitamin B-12 deficiency were 2.05 times as likely to be severely depressed as were nondeficient subjects. Conclusions: In community-dwelling older women, metabolically significant vitamin B-12 deficiency is associated with a twofold risk of severe depression. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Inst Res Extramural Med, Amsterdam, Netherlands. Johns Hopkins Med Inst, Sch Med, Dept Med, Baltimore, MD USA. Johns Hopkins Med Inst, Sch Med, Dept Epidemiol, Baltimore, MD USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Hematol, Denver, CO USA. RP Guralnik, JM (reprint author), NIA, Epidemiol Demog & Biometry Program, Room 3C-309,Gateway Bldg,7201 Wisconsin Ave, Bethesda, MD 20892 USA. FU NIA NIH HHS [AG12112, AG09834] NR 34 TC 141 Z9 148 U1 1 U2 8 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2000 VL 157 IS 5 BP 715 EP 721 DI 10.1176/appi.ajp.157.5.715 PG 7 WC Psychiatry SC Psychiatry GA 309QY UT WOS:000086781800009 PM 10784463 ER PT J AU Elvevag, B Weinberger, DR Suter, JC Goldberg, TE AF Elvevag, B Weinberger, DR Suter, JC Goldberg, TE TI Continuous performance test and schizophrenia: A test of stimulus-response compatibility, working memory, response readiness, or none of the above? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SUSTAINED ATTENTION; TIME; DOPAMINE; DEFICITS; CONTEXT; CORTEX AB Objective: Abnormalities of attention are considered the fundamental deficits in cognitive function manifested by patients with schizophrenia. The authors administered variations of two types of cognitive tasks to patients with schizophrenia (N=20) and normal comparison subjects (N=30) to test four possible cognitive mechanisms that might account for such abnormalities. Method: Variations of the Continuous Performance Test were used to test the four mechanisms. Stimulus-response mapping was explored by comparing results on a task in which subjects were to make a response if the word "nine" was preceded by the word "one" with results on a task in which the required response was made explicit by the stimulus (the word "ready" followed by the word "press"). The building up of a prepotent response tendency was tested by manipulating the probability with which the cue and imperative stimulus appeared (17% or 50%). The amount of working memory required to maintain contextual information was tested by using different delay intervals (1000 msec and 3000 msec). The extent to which problems in vigilance might be attributable to problems in the "motoric" component of response readiness was operationalized by having subjects perform a secondary motor task concurrent with the attentional task. Results: Patients with schizophrenia performed significantly worse than the normal comparison subjects on all tasks. However, none of the four manipulations of the Continuous Performance Test tasks had a differential impact on the patients' performance speed or accuracy. In contrast, there was a significant interaction of group, delay interval, and target probability in which patients made disproportionately more omission errors at short delay intervals and at low target probabilities. Conclusions: The findings may call into question the explanatory power of certain well-known contemporary mechanistic accounts of performance on the Continuous Performance Test in patients with schizophrenia. The findings suggest that a difficulty in rapidly encoding information (i.e., constructing a representation) in certain "unengaging" situations may be at the core of deficits on tasks associated with this attentional test. C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, 10 Ctr Dr,Rm 4C215,MSC 1373, Bethesda, MD 20892 USA. NR 27 TC 45 Z9 45 U1 2 U2 6 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2000 VL 157 IS 5 BP 772 EP 780 DI 10.1176/appi.ajp.157.5.772 PG 9 WC Psychiatry SC Psychiatry GA 309QY UT WOS:000086781800017 PM 10784471 ER PT J AU Nicolson, R Lenane, M Singaracharlu, S Malaspina, D Giedd, JN Hamburger, SD Gochman, P Bedwell, J Thaker, GK Fernandez, T Wudarsky, M Hommer, DW Rapoport, JL AF Nicolson, R Lenane, M Singaracharlu, S Malaspina, D Giedd, JN Hamburger, SD Gochman, P Bedwell, J Thaker, GK Fernandez, T Wudarsky, M Hommer, DW Rapoport, JL TI Premorbid speech and language impairments in childhood-onset schizophrenia: Association with risk factors SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 12-18, 1998 CL LAS CROABAS, PUERTO RICO SP Amer Coll Neuropsychopharmacol ID ROSCOMMON FAMILY; EYE-TRACKING; AFFECTIVE-DISORDERS; SCHOOL PERFORMANCE; BIRTH COHORT; FOLLOW-UP; CHILDREN; RELATIVES; COMPLICATIONS; PERSONALITY AB Objective: As both premorbid neurodevelopmental impairments and familiar risk factors for schizophrenia are prominent in childhood-onset cases (with on set of psychosis by age 12), their relationship was examined. Method: Premorbid language, motor, and social impairments were assessed in a cohort of 49 patients with childhood-onset schizophrenia. Familiar loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications were assessed without knowledge of premorbid abnormalities and were compared in the patients with and without developmental impairments. Results: Over one-half of the patients in this group had developmental dysfunction in each domain assessed. The patients with premorbid speech and language impairments had higher familial loading scores for schizophrenia spectrum disorders and more obstetrical complications, and their relatives had worse smooth-pursuit eye movements. The boys had more premorbid motor abnormalities, but early language and social impairments did not differ significantly between genders. There were no other significant relationships between premorbid social or motor abnormalities and the risk factors assessed here. Conclusions: Premorbid developmental impairments are common in childhood-onset schizophrenia. The rates of three risk factors for schizophrenia (familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications) were increased for the probands with premorbid speech and language impairments, suggesting that the pathophysiology of schizophrenia involves the abnormal development of language-related brain regions. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, Bethesda, MD USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. RP Nicolson, R (reprint author), NIMH, Child Psychiat Branch, Room 3N202,10 Ctr Dr, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Fernandez, Thomas/D-4295-2009; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Fernandez, Thomas/0000-0003-0830-022X; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 44 TC 67 Z9 70 U1 2 U2 8 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2000 VL 157 IS 5 BP 794 EP 800 DI 10.1176/appi.ajp.157.5.794 PG 7 WC Psychiatry SC Psychiatry GA 309QY UT WOS:000086781800020 PM 10784474 ER PT J AU Fee, E Brown, TM AF Fee, E Brown, TM TI The past and future of public health practice SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. Univ Rochester, Med Ctr, Dept Community & Prevent Med, Rochester, NY 14642 USA. RP Fee, E (reprint author), Natl Lib Med, Hist Med Div, Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 4 TC 6 Z9 6 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2000 VL 90 IS 5 BP 690 EP 691 DI 10.2105/AJPH.90.5.690 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 308VN UT WOS:000086733700002 PM 10800411 ER PT J AU Wang, YZ Bonner, JC AF Wang, YZ Bonner, JC TI Mechanism of extracellular signal-regulated kinase (ERK)-1 and ERK-2 activation by vanadium pentoxide in rat pulmonary myofibroblasts SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; PROTEIN-TYROSINE-PHOSPHATASE; SMOOTH-MUSCLE CELLS; HYDROGEN-PEROXIDE; FACTOR RECEPTOR; PATHWAY; H2O2; PHOSPHORYLATION; INDUCTION; EXPOSURE AB Vanadium pentoxide (V2O5) is a cause of occupational asthma and chronic bronchitis, yet the molecular mechanisms through which V2O5 exerts its effects on cell function are unclear. In this study we investigated the potential of V2O5 to activate the extracellular signal-regulated kinases 1 and 2 (ERK-1/2) in rat pulmonary myofibroblasts. Treatment of myofibroblasts with V2O5 resulted in the activation of ERK-1/2 yet the inert metal titanium dioxide had no effect on ERK-I/2 activation. V2O5-induced ERK-1/2 activation was abolished by pretreatment with forskolin or PD98059, indicating a dependence on Raf and mitogen-activated protein (MAP) kinase kinase, respectively. Depletion of conventional protein kinase C activity with phorbol 12-myristate 13-acetate did not inhibit V2O5-induced ERK-1/2 activation. ERK-1/2 activation by V2O5 was inhibited > 70% with the epidermal growth factor receptor (EGF-R) tyrosine kinase inhibitor AG1478. Phosphorylation of the 170-kD EGF-R by V2O5 was detected after immunoprecipitation with an anti-EGF-R antibody followed by phosphotyrosine Western blotting. V2O5 strongly tyrosine-phosphorylated a 115-kD protein (p115) and activation of p115 was inhibited 60 to 70% by AG1478, indicating that this protein was an EGF-R substrate. Phosphorylation of p115 was also observed in EGF-stimulated cells. Immunoprecipitation of V2O5- or EGF-treated cell lysates with an antibody against Src homology 2 protein tyrosine phosphatase (SH-PTP2) identified p115 as a SH-PTP2-binding protein. Pretreatment of cells with the antioxidant N-acetyl-L-cysteine blocked V2O5-induced MAP kinase activation and p115 phosphorylation > 90%. These data suggest that V2O5 activation of ERK-1/2 is oxidant-dependent and mediated through tyrosine phosphorylation of EGF-R and an EGF-R substrate which we identified as a 115-kD SH-PTP2-binding protein. C1 NIEHS, Airway Inflammat Sect, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Bonner, JC (reprint author), NIEHS, Airway Inflammat Sect, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 38 TC 31 Z9 31 U1 1 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 2000 VL 22 IS 5 BP 590 EP 596 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 313EC UT WOS:000086986500013 PM 10783131 ER PT J AU Engelthaler, DM Hinnebusch, BJ Rittner, CM Gage, KL AF Engelthaler, DM Hinnebusch, BJ Rittner, CM Gage, KL TI Quantitative competitive PCR as a technique for exploring flea - Yersina pestis dynamics SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID POLYMERASE-CHAIN-REACTION; PLAGUE BACILLUS; TRANSMISSION; GENE AB We used a quantitative competitive polymerase chain reaction assay to quantify Yersinia pestis loads in fleas and bacteremia levels in mice that were used as sources of infectious blood meals for feeding the fleas. Xenopsylla cheopis, the Oriental rat flea, achieved higher infection rates, developed greater bacterial loads, and became infectious more rapidly than Oropsylla montana, a ground squirrel flea. Both flea species required about 10(6) Y. pestis cells per flea to be able to transmit to mice. Most fleas that achieved these levels, however, were incapable of transmitting. Our results suggest that at the time of flea feeding, host blood must contain greater than or equal to 10(6) bacteria/ml to result in detectable Y. pestis infections in these fleas, and greater than or equal to 10(7) bacteria/mL to cause infection levels sufficient for both species to eventually become capable of transmitting Y. pestis to uninfected mice. Yersinia pestis colonies primarily developed in the midguts of O. montana, whereas infections in X. cheopis often developed simultaneously in the proventriculus and the midgut. These findings were visually confirmed by infecting fleas with a strain of Y. pestis that had been transformed with the green fluorescent protein gene. C1 NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, Hamilton, MT 59840 USA. Arizona Dept Hlth Serv, Bur Epidemiol & Dis Control Serv, Phoenix, AZ 85015 USA. Ctr Dis Control, Bacterial Zoonoses Branch, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, Ft Collins, CO 80522 USA. RP Engelthaler, DM (reprint author), Arizona Dept Hlth Serv, Bur Epidemiol & Dis Control Serv, 3815 N Black Canyon Highway, Phoenix, AZ 85015 USA. NR 38 TC 47 Z9 49 U1 1 U2 6 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2000 VL 62 IS 5 BP 552 EP 560 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 412HP UT WOS:000167549200003 PM 11289663 ER PT J AU Lin, FYC Ho, VA Bay, PV Nguyen, TTT Bryla, D Thanh, TC Khiem, HB Trach, DD Robbins, JB AF Lin, FYC Ho, VA Bay, PV Nguyen, TTT Bryla, D Thanh, TC Khiem, HB Trach, DD Robbins, JB TI The epidemiology of typhoid fever in the Dong Thap Province, Mekong Delta region of Vietnam SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID RESISTANT SALMONELLA-TYPHI; CHILDREN; BACTEREMIA AB A population-based surveillance for typhoid fever was conducted in three rural communes of Dong Thap Province in southern Vietnam (population 28,329) for a 12-month-period starting on December 4, 1995. Cases of typhoid fever were detected by obtaining blood for culture from residents with fever greater than or equal to 3 days. Among 658 blood cultures, 56 (8.5%) were positive for Salmonella typhi with an overall incidence of 198 per 10(5) population per year. The peak occurrence was at the end of the dry season in March and April. The attack rate was highest among 5-9 year-olds (531/10(5)/year), and lowest in > 30 year-olds (39/10(5)/year). The attack rate was 358/10(5)/year in 2-4 year-olds. The isolation of S. typhi from blood cultures was highest (17.4%) in patients with 5 to 6 days of fever. Typhoid fever is highly endemic in Vietnam and is a significant disease in both preschool and school-aged children. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Dong Thap Prov Hosp, Cao Lanh, Dong Thap Prov, Vietnam. Inst Pasteur, Ho Chi Minh, Vietnam. Minist Hlth, Natl Inst Hyg & Epidemiol, Hanoi, Vietnam. RP Lin, FYC (reprint author), NICHHD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU NICHD NIH HHS [N01-HD-5-3225] NR 24 TC 92 Z9 94 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2000 VL 62 IS 5 BP 644 EP 648 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 412HP UT WOS:000167549200018 PM 11289678 ER PT J AU Cidlowski, JA Bortner, CD Gomez-Angelats, M Mann, C Scoltock, A Huang, J Evans-Storms, R AF Cidlowski, JA Bortner, CD Gomez-Angelats, M Mann, C Scoltock, A Huang, J Evans-Storms, R TI The cell and molecular biology of apoptosis in T-lymphocytes SO ANNALES D ENDOCRINOLOGIE LA English DT Article; Proceedings Paper CT 1999 SFE Congress CY 1999 CL BORDEAUX, FRANCE SP SFE ID ACTIVATION; K+ C1 NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. RI Huang, Se-Te/F-6881-2013 NR 5 TC 3 Z9 3 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0003-4266 J9 ANN ENDOCRINOL-PARIS JI Ann Endocrinol. PD MAY PY 2000 VL 61 IS 2 BP 138 EP 138 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 339MF UT WOS:000088480300008 PM 10960327 ER PT J AU Zalenski, RJ Selker, HP Cannon, CP Farin, HM Gibler, WB Goldberg, RJ Lambrew, CT Ornato, JP Rydman, RJ Steele, P AF Zalenski, RJ Selker, HP Cannon, CP Farin, HM Gibler, WB Goldberg, RJ Lambrew, CT Ornato, JP Rydman, RJ Steele, P CA Natl Heart Attack Alert Program TI National Heart Attack Alert Program position paper: Chest pain centers and programs for the evaluation of acute cardiac ischemia SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; REDUCE PATIENT DELAY; LOW-RISK PATIENTS; SHORT-STAY UNIT; MEDIA CAMPAIGN; CLINICAL-TRIAL; PREDICTIVE INSTRUMENT; THROMBOLYTIC THERAPY; DIAGNOSTIC PROTOCOL; COST-EFFECTIVENESS AB The National Heart Attack Alert Program (NHAAP), which is coordinated by the National Heart, Lung, and Blood institute (NHLBI), promotes the early detection and optimal treatment of patients with acute myocardial infarction and other acute coronary ischemic syndromes. The NHAAP, having observed the development and growth of chest pain centers in emergency departments with special interest, created a task force to evaluate such centers and make recommendations pertaining to the management of patients with acute cardiac ischemia. This position paper offers recommendations to assist emergency physicians in EDs, including those with chest pain centers, in providing comprehensive care for patients with acute cardiac ischemia. C1 Wayne State Univ, Sch Med, Detroit, MI USA. RP Zalenski, RJ (reprint author), NHLBI, Natl Heart Attack Alert Program, NIH, Bldg 31,Room 4A16,31 Ctr Dr,MSC 2480, Bethesda, MD 20892 USA. NR 57 TC 37 Z9 38 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAY PY 2000 VL 35 IS 5 BP 462 EP 471 DI 10.1067/mem.2000.104027 PG 10 WC Emergency Medicine SC Emergency Medicine GA 310LT UT WOS:000086830200007 PM 10783408 ER PT J AU Johnson, NJ Backlund, E Sorlie, PD Loveless, CA AF Johnson, NJ Backlund, E Sorlie, PD Loveless, CA TI Marital status and mortality: The National Longitudinal Mortality Study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE marital status; mortality; longitudinal; cardiovascular; employment status ID DEATH-INDEX; CONJUGAL BEREAVEMENT; ALAMEDA COUNTY; HEART-DISEASE; SOCIAL-CLASS; MEN; RISK; MARRIAGE; ASCERTAINMENT; CANCER AB PURPOSE: To examine the effect of marital status (married, widowed, divorced/separated, and never-married) on mortality in a cohort of 281,460 men and women, ages 45 years and older, of black and white races, who were part of the National Longitudinal Mortality Study (NLMS). METHODS: Major findings are based on assessments of estimated relative risk (RR) from Cox proportional hazards models. Duration of bereavement for the widowed is also estimated using the Cox model. RESULTS: For persons aged 45-64, each of the non-married groups generally showed statistically significant increased risk compared to their married counterparts (RR for white males, 1.24-1,39; white females, 1.46-1.49; black males, 1.27-1.57; and black females, 1.10-1.36). Older age groups tended to, have smaller RRs than their younger counterparts. Elevated risk for nun-married females was comparable to that of non-married males. Fur cardiovascular disease mortality, widowed and never-married whits males ages 45-64 showed statistically significant increased RRs of 1.25 and 1.32, respectively, whereas each non-married group of white females showed statistically significant increased RRs from 1.50 ru 1.60. RRs for causes other than cardiovascular diseases or cancers were high (for white males ages 45-64: widowed, 1.85; divorced/separated, 2.15; and never married, 1.48). The importance of labor force status in determining the elevated risk of nun-married males compared to non-married females by race is shown. CONCLUSIONS: Each of the non-married categories show elevated RR of death compared to married persons, and these effects continue to be strong after adjustment for other sociocconomic factors. (C) 2000 Elsevier Science Inc. All rights reserved. C1 US Bur Census, Demog Stat Methods Div, Washington, DC 20233 USA. NHLBI, Epidemiol & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Johnson, NJ (reprint author), US Bur Census, Demog Stat Methods Div, Room 3725-3, Washington, DC 20233 USA. NR 79 TC 245 Z9 246 U1 4 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 2000 VL 10 IS 4 BP 224 EP 238 DI 10.1016/S1047-2797(99)00052-6 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 326KZ UT WOS:000087735800005 PM 10854957 ER PT J AU Wilson, RB Lynch, DR Farmer, JM Brooks, DG Fischbeck, KH AF Wilson, RB Lynch, DR Farmer, JM Brooks, DG Fischbeck, KH TI Increased serum transferrin receptor concentrations in Friedreich ataxia SO ANNALS OF NEUROLOGY LA English DT Article ID MITOCHONDRIAL IRON ACCUMULATION; FRATAXIN HOMOLOG; DEFICIENCY; GENE; FERRITIN AB Mitochondrial iron accumulation is thought to underlie the pathophysiology of Friedreich ataxia and may occur at the expense of cytosolic iron. Decreases in cytosolic iron induce expression of the transferrin receptor, some of which is released into the serum. Here, we demonstrate that serum transferrin receptor concentrations are increased in patients with Friedreich ataxia, which supports the hypothesis that it is a disease of abnormal intracellular iron distribution. C1 Univ Penn, Dept Pathol & Lab Med, Stellar Change Labs, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Wilson, RB (reprint author), Univ Penn, Dept Pathol & Lab Med, Stellar Change Labs, Sch Med, Room 509A,422 Curie Blvd, Philadelphia, PA 19104 USA. NR 20 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2000 VL 47 IS 5 BP 659 EP 661 DI 10.1002/1531-8249(200005)47:5<659::AID-ANA17>3.0.CO;2-T PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 308UJ UT WOS:000086731000017 PM 10805340 ER PT J AU Miron, A Schildkraut, JM Rimer, BK Winer, EP Skinner, CS Futreal, PA Culler, D Calingaert, B Clark, S Marcom, PK Iglehart, JD AF Miron, A Schildkraut, JM Rimer, BK Winer, EP Skinner, CS Futreal, PA Culler, D Calingaert, B Clark, S Marcom, PK Iglehart, JD TI Testing for hereditary breast and ovarian cancer in the southeastern United States SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 111th Annual Meeting of the Southern-Surgical-Association CY DEC 05-08, 1999 CL HOT SPRINGS, VIRGINIA SP SO Surg Assoc ID DECISION-MAKING; SUSCEPTIBILITY GENES; BRCA2 MUTATIONS; FAMILY HISTORY; RISK; CARRIERS; WOMEN; ATTITUDES AB Objectives To detail characterization of mutations and uncharacterized variants in the breast cancer susceptibility genes BRCA1 and BRCA2, as observed in a population of breast cancer patients from the southeastern United States, and to examine baseline characteristics of women referred for counseling and testing and provide a preliminary look at how counseling and testing affected intentions toward prophylactic surgery, Background Mutations in the BRCA1 and BRCA2 genes give rise to a dramatically increased risk of developing breast or ovarian cancer or both. There are many reports about special populations in which deleterious mutations are present ata high frequency. it is useful to study these genes in more heterogeneous populations, reflecting different geographic regions. Interest in preventive surgery for gene carriers is high in women and their surgeons. Methods Women were recruited through a prospective clinical trial of counseling and free genetic testing. BRCA1 and BRCA2 were screened for mutations using standard techniques, and results were given to participants. Baseline questionnaires determined interest in preventive surgery at the beginning of the study. Follow-up questionnaires for those who completed testing surveyed interest in prophylactic surgery after counseling and receiving test results, Results OC 213 women who completed counseling and testing, 44 (20.6%) had 29 separate mutations; there were II Jewish women carrying three founder mutations. Twenty-eight women (13.1%) had uncharacterized variants in BRCA1 or BRCA2; nine were not previously reported. Women overestimated their chances of possessing a deleterious gene mutation compared to a statistical estimate of carrier risk, A number of women changed their intentions toward preventive surgery after genetic counseling and testing, Conclusions Hereditary breast cancer due to mutations in BRCA1 and BRCA2 was a heterogeneous syndrome in the southeastern United States. Most mutations were seen just once, and uncharacterized variants were common and of uncertain clinical significance. in general, positive test results tended to reinforce intentions toward prophylactic surgery. in contrast, women not interested in surgery at the time of entry tended to remain reluctant after testing and counseling. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Family & Community Med, Durham, NC 27710 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Iglehart, JD (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. NR 32 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2000 VL 231 IS 5 BP 624 EP 632 DI 10.1097/00000658-200005000-00002 PG 9 WC Surgery SC Surgery GA 311CM UT WOS:000086867300002 PM 10767783 ER PT J AU Lamb, SE Guralnik, JM Buchner, DM Ferrucci, LM Hochberg, MC Simonsick, EM Fried, LP AF Lamb, SE Guralnik, JM Buchner, DM Ferrucci, LM Hochberg, MC Simonsick, EM Fried, LP CA Womens Hlth Aging Study TI Factors that modify the association between knee pain and mobility limitation in older women: the Women's Health and Aging Study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID GENERAL-POPULATION; DEPRESSIVE SYMPTOMS; CONTROLLED TRIAL; RISK-FACTORS; DISABILITY; OSTEOARTHRITIS; PREVALENCE; ARTHRITIS; EXERCISE; DETERMINANTS AB Objective-To investigate the influence of pain severity, knee extensor muscle weakness, obesity, depression, and activity on the association between recent knee pain and limitation of usual and fast paced walking, and ability to rise from a chair. Methods-A cross sectional analysis of 769 older women (mean age 77.8, range 65-101) with physical disability, but no severe cognitive impairment. Severity of knee pain in the past month was classified as none, moderate, or severe. Mobility was measured using timed performance tests. Results-The prevalence of recent knee pain was 53% (408/769). One third of the women with pain reported it to be severe. In general, knee pain was only significantly associated with limited mobility if severe. Obesity, activity and, to a lesser extent, depression intensified the effects of pain. Knee extensor weakness did not. Obesity was a distinctive risk factor in that it substantially increased the risk of mobility limitation, but only in women with pain. In women who had severe pain, activity (walking more than three city blocks in the past week) increased the risk of walking disability more than inactivity. Depression had a minor, but statistically significant effect on walking ability, but not the ability to rise hom a chair. Conclusion-In older women with recent knee pain, a high pain severity score, obesity, and activity are important factors that increase the risk of mobility limitation. C1 Coventry Univ, Sch Hlth & Social Sci, Coventry CV1 5FB, W Midlands, England. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA. Natl Res Inst, I Fracticini, Dept Geriatr, Florence, Italy. Johns Hopkins Med Inst, Sch Med, Dept Med & Epidemiol, Baltimore, MD 21205 USA. RP Lamb, SE (reprint author), Coventry Univ, Sch Hlth & Social Sci, Priory St, Coventry CV1 5FB, W Midlands, England. NR 39 TC 89 Z9 91 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAY PY 2000 VL 59 IS 5 BP 331 EP 337 DI 10.1136/ard.59.5.331 PG 7 WC Rheumatology SC Rheumatology GA 310RU UT WOS:000086841800003 PM 10784513 ER PT J AU Schrump, DS AF Schrump, DS TI Isolated lung perfusion for patients with unresectable metastases from sarcoma: A Phase I trial - Invited Commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 NCI, Surg Branch, Thorac Oncol Sect, Bethesda, MD 20892 USA. RP Schrump, DS (reprint author), NCI, Surg Branch, Thorac Oncol Sect, Bldg 10,Room 2B-07,10 Ctr Dr, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2000 VL 69 IS 5 BP 1549 EP 1549 DI 10.1016/S0003-4975(00)01169-3 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 324DD UT WOS:000087605800058 ER PT J AU Yamazaki, Y Tsuruga, M Gentsch, B Oka, S Kleinman, HK Mokotoff, M AF Yamazaki, Y Tsuruga, M Gentsch, B Oka, S Kleinman, HK Mokotoff, M TI Bioadhesive peptides as potential anticancer drug carriers: Activation via isopeptide deblocking by proteases SO ANTICANCER RESEARCH LA English DT Article DE laminin; peptide; protease; prodrug ID CELL; AMINOPEPTIDASE; CHAIN AB Background: Bioadhesive peptides are potentially useful as anticancer drug carriers, if the bioadhesivity becomes active only at the tumor site. We propose that this function can be achieved by the prodrug strategy using proteases in tumors. Materials and Methods: A laminin fragment peptide, Ac-AASIKVAVSADR-NH2 (5), and its derivatives, Ac-AASIK(L) VAVSADR-NH2 (6), Ac-AASIDpm(NH2)VAVSADR-NH2 (7) and Ac-AASIDpm(L)(NH2)VAVSADR-NH2 (8), were synthesized and tested for their bioadhesive activity with 6 cancer cell lines. Results: The strength of the binding was in the order of 5 much greater than 7 greater than or equal to 8 greater than or equal to 6 The attachment of mouse whole blood cells to peptide 6-coated surface was also weaker than to 5-coated surface. The Leu isopeptide linkage in 6 was enzymatically cleaved by the cells. Conclusion: The present results suggest that isopeptide 6, working as a prodrug form for the bioadhesive peptide 5, could serve as an anticancer drug carrier for tumor targeting. C1 Natl Inst Biosci & Human Technol, Agcy Ind Sci & Technol, Tsukuba, Ibaraki 3058566, Japan. Univ Pittsburgh, Sch Pharm, Pittsburgh, PA 15261 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Yamazaki, Y (reprint author), Natl Inst Biosci & Human Technol, Agcy Ind Sci & Technol, 1-1 Higashi, Tsukuba, Ibaraki 3058566, Japan. NR 10 TC 2 Z9 2 U1 2 U2 3 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 MAY-JUN PY 2000 VL 20 IS 3A BP 1381 EP 1384 PG 4 WC Oncology SC Oncology GA 352MK UT WOS:000089222300008 PM 10928047 ER PT J AU Jeong, KS Park, SJ Lee, CS Kim, TW Kim, SH Ryu, SY Williams, BH Veech, RL Lee, YS AF Jeong, KS Park, SJ Lee, CS Kim, TW Kim, SH Ryu, SY Williams, BH Veech, RL Lee, YS TI Effects of cyclocreatine in rat hepatocarcinogenesis model SO ANTICANCER RESEARCH LA English DT Article DE cyclocreatine; hepatocarcinogenesis; glutathione S-transferase placentral form (GST-P); diethylnitrosamine; apoptosis ID GLUTATHIONE S-TRANSFERASE; MEDIUM-TERM BIOASSAY; CREATINE-KINASE; PLACENTAL FORM; MULTIDRUG RESISTANCE; CANCER-CELLS; TUMOR-CELLS; LIVER; PRENEOPLASIA; CARCINOGENS AB Cyclocreatine (CCr), a substrate analogue of creatine kinase (CK: EC 2.7.3.2.), exhibits anti-tumor activity in vitro and in vivo. We examined the effects of CCr on the hepatocarcinogenesis of F344 rats caused by treatment with diethylnitrosamine (DEN), partial hepatectomy (PH) ol 2-acetylaminofluorene (2-AAF). The rats were given a single intraperitoneal injection of 200 mg of DEN per kg in 0.85% NaCl solution at four weeks of age. Two weeks later they were divided into two groups. One group was continuously fed a commercial powder diet containing 0.02% 2-AAF for 12 weeks and the other was continuously fed a commercial powder diet containing 2% CCr plus 0.02% 2-AAF for 12 weeks. A third group of rats as a cont, ol was given only a normal powder diet for 12 weeks. All the groups were subjected to a two-thirds partial hepatectomy (PH) at 3 weeks under avertin anesthesia. To elucidate the inhibitory effect of CCr on chemical induced hepatocarcinogenesis, we examined not only the distribution of glutathione-S-transferase placental form (GST-P) a marker used for tumorigenesis, but also the inhibition of the degree of apoptosis. The number (No./cm(2)) and area (mm(2)/cm(2)) of GST-P positive liver foci were significantly lower in the 2-AAF + CCr treated when compared to the group treated with 2-AAF only. Our data suggest that CCr inhibits the degrees of GST-P-positive cells and apoptosis and is active against hepatocarcinogenesis in mt models. This result points out the unique nature of an anticancer agent that inhibits progression of chemically induced hepatocarcinogenesis of rats. C1 Korea Canc Ctr Hosp, Lab Radiat Effect, Nowon Ku, Seoul 139706, South Korea. NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. Kyungpook Natl Univ, Coll Vet Med, Taegu 702701, South Korea. Chonnam Natl Univ, Coll Vet Med, Kwangju 500757, South Korea. Chungnam Natl Univ, Coll Vet Med, Taejon 305764, South Korea. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Lee, YS (reprint author), Korea Canc Ctr Hosp, Lab Radiat Effect, Nowon Ku, 215-4 Gongneung Dong, Seoul 139706, South Korea. NR 39 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 MAY-JUN PY 2000 VL 20 IS 3A BP 1627 EP 1633 PG 7 WC Oncology SC Oncology GA 352MK UT WOS:000089222300043 PM 10928082 ER PT J AU Munoz, FM Galasso, GJ Gwaltney, JM Hayden, FG Murphy, B Webster, R Wright, P Couch, RB AF Munoz, FM Galasso, GJ Gwaltney, JM Hayden, FG Murphy, B Webster, R Wright, P Couch, RB TI Current research on influenza and other respiratory viruses: II International Symposium SO ANTIVIRAL RESEARCH LA English DT Review C1 Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Macrae Grp, Rockville, MD USA. Univ Virginia, Sch Med, Charlottesville, VA 22903 USA. NIH, NIAID, Bethesda, MD USA. St Jude Children Hosp, Memphis, TN USA. Vanderbilt Univ, Nashville, TN USA. RP Munoz, FM (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, Room 221-D,1 Baylor Plaza, Houston, TX 77030 USA. NR 50 TC 29 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2000 VL 46 IS 2 BP 91 EP 124 DI 10.1016/S0166-3542(00)00092-9 PG 34 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 325FQ UT WOS:000087665900005 PM 10854663 ER PT J AU Haka, AS Levin, IW Lewis, EN AF Haka, AS Levin, IW Lewis, EN TI Uncooled barium strontium titanium focal plane array detection for mid-infrared Fourier transform spectroscopic imaging SO APPLIED SPECTROSCOPY LA English DT Article DE uncooled arrays; infrared microscopy; Fourier transform infrared spectroscopy; imaging; infrared arrays C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Lewis, EN (reprint author), Spectal Dimens Inc, 3403 Olandwood Court, Olney, MD 20832 USA. NR 8 TC 7 Z9 7 U1 0 U2 0 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD MAY PY 2000 VL 54 IS 5 BP 753 EP 755 DI 10.1366/0003702001950049 PG 3 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 323RE UT WOS:000087578100022 ER PT J AU Matt, D Xin, H Vortmeyer, AO Zhuang, ZP Burg, G Boni, R AF Matt, D Xin, H Vortmeyer, AO Zhuang, ZP Burg, G Boni, R TI Sporadic trichoepithelioma demonstrates deletions at 9q22.3 SO ARCHIVES OF DERMATOLOGY LA English DT Article ID BASAL-CELL CARCINOMA; GORLIN SYNDROME; GENE; HETEROZYGOSITY; CHROMOSOME-9; MUTATIONS AB Background: Trichoepithelioma (TE) is a benign cutaneous tumor that originates from hair follicles and occurs either in multiple or solitary lesions. Multiple TE is transmitted as an autosomal dominant trait, and a region at 9p21 is thought to be involved in the tumorigenesis. Solitary TE occurs more commonly than multiple TE and is not inherited. Histologically, TE tumors contain horn cysts and abortive hair papillae. A basal cell carcinoma appearance in some or all regions of a TE tumor can happen. In sporadic basal cell carcinoma, frequent deletions at 9q22.3 (Drosophila patched gene) have occurred. The objective of this study is to test whether loss of heterozygosity (LOH) on either 9p21 or on chromosome 9q22.3 could be detected in archival sporadic TE. Observations: We studied 29 randomly selected cases of sporadic TE by microdissection and polymerase chain reaction using paraffin-embedded, formalin-fixed tissue specimens on glass slides. Analysis was performed with the polymorphic markers IFNA and D9S171 (9p21) as well as D9S15, D9S303, D9S287, and D9S252 (9q22.3). Results: The LOH at 9q22.3 was identified in 14 (48%) of 29 cases with at least 1 marker, while LOH could not be demonstrated using the markers IFNA and D9S171 (9p21). Conclusions: The results show that the Drosophila patched gene LOH can be frequently identified in paraffin-embedded sporadic TE after routine processing and indicates a common gatekeeper mechanism for both TE and basal cell carcinoma. C1 Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Boni, R (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland. NR 16 TC 38 Z9 41 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 2000 VL 136 IS 5 BP 657 EP 660 DI 10.1001/archderm.136.5.657 PG 4 WC Dermatology SC Dermatology GA 313FJ UT WOS:000086989400010 PM 10815860 ER PT J AU Longnecker, MP Ryan, JJ Gladen, BC Schecter, AJ AF Longnecker, MP Ryan, JJ Gladen, BC Schecter, AJ TI Correlations among human plasma levels of dioxin-like compounds and polychlorinated biphenyls (PCBs) and implications for epidemiologic studies SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article ID HUMAN-MILK; POSTNATAL EXPOSURE; BLOOD-LEVELS; INFANTS; CONGENERS; FURANS; WOMEN; RISK AB In studies of the potential health effects of background-level exposure to organochlorine compounds (e.g., polychlorinated biphenyls, polychlorinated dibenzodioxins, and polychlorinated dibenzofurans), investigators have often measured either polychlorinated biphenyls or polychlorinated dibenzodioxins/polychlorinated dibenzofurans-but not both. We measured polychlorinated biphenyls (including specific non-, mono-, and di-ortho congeners) and specific polychlorinated dibenzodioxins/dibenzofurans among 63 Canadian blood donors. Levels of these compounds were, in general, fairly correlated. For example, Pearson's correlation coefficient between log total polychlorinated biphenyl and log total polychlorinated dibenzodioxins was .52. These results suggest that in epidemiologic studies of health effects of background-level exposures to these compounds, the quantitative dose-response relation observed for a given compound (or class of compounds acting through a similar mechanism) may easily be miscalibrated or confounded. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ Texas, Sch Publ Hlth, Dallas, TX 75230 USA. Hlth Canada, Hlth Protect Branch, Food Directorate, Ottawa, ON K1A 0L2, Canada. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, Box 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 27 TC 38 Z9 39 U1 0 U2 1 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD MAY-JUN PY 2000 VL 55 IS 3 BP 195 EP 200 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 335EU UT WOS:000088231300006 PM 10908103 ER PT J AU Chu, KC Tarone, RE Brawley, OW AF Chu, KC Tarone, RE Brawley, OW TI Racial differences in breast cancer mortality - In reply SO ARCHIVES OF FAMILY MEDICINE LA English DT Letter ID TRENDS; ENGLAND; RATES; WALES C1 NCI, Off Special Populat Res, Bethesda, MD 20892 USA. RP Chu, KC (reprint author), NCI, Off Special Populat Res, 900 Rockville Pike,Bldg EPS,Room 320, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1063-3987 J9 ARCH FAM MED JI Arch. Fam. Med. PD MAY PY 2000 VL 9 IS 5 BP 412 EP 413 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 312QN UT WOS:000086954100003 ER PT J AU Whitcup, SM Fortin, E Lindblad, AS Griffiths, P Metcalf, JA Robinson, MR Manischewitz, J Baird, B Perry, C Kidd, IM Vrabec, T Davey, RT Falloon, J Walker, RE Kovacs, JA Lane, HC Nussenblatt, RB Smith, J Masur, H Polis, MA AF Whitcup, SM Fortin, E Lindblad, AS Griffiths, P Metcalf, JA Robinson, MR Manischewitz, J Baird, B Perry, C Kidd, IM Vrabec, T Davey, RT Falloon, J Walker, RE Kovacs, JA Lane, HC Nussenblatt, RB Smith, J Masur, H Polis, MA TI Discontinuation of anticytomegalovirus therapy in patients with HIV infection and cytomegalovirus retinitis SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material C1 NEI, NIH, Bethesda, MD 20892 USA. RP Whitcup, SM (reprint author), NEI, NIH, 10-10S221,10 Ctr Dr,MSC 1863, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2000 VL 118 IS 5 BP 704 EP 704 PG 1 WC Ophthalmology SC Ophthalmology GA 313HJ UT WOS:000086994000013 ER PT J AU Whitcup, SM AF Whitcup, SM TI Cytomegalovirus retinitis in the era of highly active antiretroviral therapy SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material C1 NEI, NIH, Bethesda, MD 20892 USA. RP Whitcup, SM (reprint author), NEI, NIH, 10-10S221,10 Ctr Dr,MSC 1863, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2000 VL 118 IS 5 BP 705 EP 705 PG 1 WC Ophthalmology SC Ophthalmology GA 313HJ UT WOS:000086994000015 ER PT J AU Scheidt, PC Overpeck, MD Trifiletti, LB Cheng, T AF Scheidt, PC Overpeck, MD Trifiletti, LB Cheng, T TI Child and adolescent injury research in 1998 SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Injury-Control-Special-Interest-Group of the Ambulatory-Pediatrics-Association CY MAY 04, 1998 CL NEW ORLEANS, LOUISIANA SP Ambulatory Pediat Assoc, Injury Control Special Interest Grp ID GO AB Objective: To describe current research in child and adolescent injury prevention by pediatric and public health investigators for comparison with national recommendations and agendas. Data Sources: Abstracts submitted to the 1998 annual meetings of the Pediatric Academic Societies/Ambulatory Pediatrics Association and the American Public Health Association on injury or violence in children or adolescents. Study Selection: All abstracts of projects that addressed primarily injury or violence prevention involving children or adolescents. Data Extraction: For 123 abstracts, 2 coauthors extracted and classified age of the population, type of injury, study design, sizes of the sample and denominator, and type of outcome. Result: Adolescents were the most frequent (49%) age group included. The investigations were concerned most with injuries caused by violence (33%), followed by motor vehicle trauma (14%) and bums (7%). Descriptive surveillance (38%),surveys (32%), and case series (13%) comprised the overwhelming majority of methods used. The studies primarily sought to identify risk factors for injury (32%), describe the victims (20%), or measure knowledge and/or practice (26%). Nine studies (7%) sought to measure the effect of interventions in some way, and only 2 focused primarily on methodology development. Conclusions: Injury prevention research projects presented at the 1998 Pediatric Academic Societies and American Public Health Association meetings were proportionate to the frequencies of injury by age and by external cause in the United States. However, in comparison with recommendations for agendas of national injury prevention research, more research is needed to improve injury prevention methods and to evaluate interventions. C1 George Washington Univ, Childrens Natl Med Ctr, Sch Med & Hlth Sci, Washington, DC 20010 USA. George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Washington, DC 20010 USA. NICHHD, Bethesda, MD 20892 USA. RP Scheidt, PC (reprint author), George Washington Univ, Childrens Natl Med Ctr, Sch Med & Hlth Sci, 111 Michigan Ave NW, Washington, DC 20010 USA. RI McKenzie, Lara/C-5122-2012 NR 18 TC 3 Z9 4 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 MAY PY 2000 VL 154 IS 5 BP 442 EP 445 PG 4 WC Pediatrics SC Pediatrics GA 312MB UT WOS:000086946100004 PM 10807292 ER PT J AU Juo, SHH Han, ZH Smith, JD Colangelo, L Liu, K AF Juo, SHH Han, ZH Smith, JD Colangelo, L Liu, K TI Common polymorphism in promoter of microsomal triglyceride transfer protein gene influences cholesterol, ApoB, and triglyceride levels in young African American men - Results from the Coronary Artery Risk Development in Young Adults (CARDIA) Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE polymorphism; microsomal triglyceride transfer proteins; lipoproteins; apolipoproteins ID APOLIPOPROTEIN-E POLYMORPHISM; DENSITY-LIPOPROTEIN CHOLESTEROL; LONGITUDINAL DATA-ANALYSIS; B-CONTAINING LIPOPROTEINS; HEART-DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; SERUM-CHOLESTEROL; A-I; PLASMA; SECRETION AB The microsomal triglyceride transfer protein (MTP) plays a key role in the assembly of apolipoprotein B (apoB)-containing lipoproteins. We investigated the relation between lipid profiles and a common functional polymorphism (-493G/T) of the MTP gene in a large sample of young black men in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. We performed serial cross-sectional analyses on lipids of 586 black men in 5 exams over 10 years of follow-up. Total cholesterol, LDL cholesterol, and apoB levels were very similar between the GT and GG genotypes; therefore, the GT and GG genotypes were combined as 1 group when the 3 phenotypes were analyzed. The results from ANCOVA showed that the TT group (prevalence 7%) had higher levels of apoB-related lipids than did the GT+GG group: the difference in total cholesterol ranged from 2 (P=0.79) to 19 (P=0.002) mg/dL in exams 1 to 5; the difference in LDL cholesterol ranged from 10 (P=0.14) to 17 (P=0.003) mg/dL in exams 1 to 4, but in examination 5, the difference became negligible. The TT group had higher levels of apoB, measured in only 2 exams, by 6 (P=0.12) and 9 (P=0.03) mg/dL. The TT group had higher levels of triglycerides than did the TG or GG group by 3 to 34 (P=0.02 to approximate to 0.003) mg/dL in all 5 exams. HDL cholesterol and apolipoprotein A-I levels were similar among the 3 genotypes. Our serial cross-sectional analyses indicated that the TT genotype was associated with higher levels of total cholesterol, LDL cholesterol, triglycerides, and apoB in young black men, The broad effect of this polymorphism on several atherogenic traits suggests that the MTP gene could be influential in atherosclerosis. C1 Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. Rockefeller Univ, Biochem Genet & Metab Lab, New York, NY 10021 USA. NIH, Natl Human Genome Res Inst, Baltimore, MD USA. RP Liu, K (reprint author), Northwestern Univ, Sch Med, Dept Prevent Med, Suite 1102,680 N Lake Shore Dr, Chicago, IL 60611 USA. RI Juo, Suh-Hang/A-1765-2010; Juo, Suh-Hang/C-9545-2009 FU NHLBI NIH HHS [N01-HC-48048, N01-HC-48047, N01-HC-48049] NR 53 TC 38 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2000 VL 20 IS 5 BP 1316 EP 1322 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 314VF UT WOS:000087077700021 PM 10807748 ER PT J AU Dewanjee, MK Wu, SM Hsu, LC AF Dewanjee, MK Wu, SM Hsu, LC TI Effect of heparin reversal and fresh platelet transfusion on platelet emboli post-cardiopulmonary bypass in a pig model SO ASAIO JOURNAL LA English DT Article ID PROTAMINE; ANTITHROMBIN; THROMBIN; THROMBOGENICITY; COMPLEXES; SURGERY; SULFATE; RAT AB Heparin reversal by protamine and fresh platelet transfusion may decrease bleeding complications post-cardiopulmonary bypass (CPB) and may increase the level of organ trapped platelet emboli. Platelet emboli were quantified in two groups of 12 Yorkshire pigs (30-35 kg), where (111)indium labeled autologous platelets (INPLT: 850-1,200 mu Ci) were injected intravenously before and after CPB (BCPB, ACPB), and the platelet emboli level in intact organs and their samples (brain, heart, kidneys, lung, liver, and spleen) was quantified with an ion chamber and a gamma counter, respectively. All pigs were systemically heparinized (ACT > 400 sec). CPB was carried out at 2.5-3.5 L/min at 28 degrees C using a centrifugal pump, an oxygenator (OX:Bentley Univox 1.8 m(2)), an arterial filter (AF:0.25 m(2)), and a cardiotomy reservoir (CR: BMR 250) for 90 min. Heparin was reversed with an equivalent dose of protamine. The percent of INPLT dose (ID%, mean +/- SD) in organs of BCPB and ACPB pigs was calculated. The sequence of platelet emboli on a unit weight basis (ID%/g) had the following order: Spleen > Liver > Lung > Kidneys > Heart > Brain. The presence of significantly higher levels of emboli in brain, heart, and kidneys in the ACPB than the BCPB group suggest that platelet transfusion after heparin reversal with protamine may increase the risk of platelet emboli. However, it is an acceptable risk for patients having bleeding complications post-CPB. C1 Univ Illinois, Dept Vet Biosci, Div Physiol, Champaign, IL 61820 USA. Univ Illinois, Dept Vet Biosci, Div Nucl Med, Champaign, IL 61820 USA. Univ Illinois, Dept Vet Biosci, Div Bioengn, Champaign, IL 61820 USA. Bentely Labs, Irvine, CA USA. RP NIH, Ctr Sci Review, Bldg 5118,Rockledge Bldg 2,MSC 7854,6701 Rockledg, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL-47201] NR 40 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1058-2916 EI 1538-943X J9 ASAIO J JI Asaio J. PD MAY-JUN PY 2000 VL 46 IS 3 BP 313 EP 318 DI 10.1097/00002480-200005000-00014 PG 6 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 346RF UT WOS:000088884300014 PM 10826743 ER PT J AU Biswas, I Vijayvargia, R AF Biswas, I Vijayvargia, R TI Heteroduplex DNA and ATP induced conformational changes of a MutS mismatch repair protein from Thermos aquaticus SO BIOCHEMICAL JOURNAL LA English DT Article DE cross-linking; DNA binding; nucleotide cofactors; proteolysis; TaqMutS ID ESCHERICHIA-COLI; TRANSLOCATION MECHANISM; HMUTS-ALPHA; HELICASE-II; BASE PAIRS; BINDING; RECOGNITION; COMPLEX; GENE AB ATP hydrolysis by MutS homologues is required for the function of these proteins in mismatch repair. However, the function of ATP hydrolysis in the repair reaction is not very clear. We have examined the role of ATP hydrolysis in oligomerization of Thermus aquaticus (Taq) MutS protein in solution. Analytical gel filtration and cross-linking of MutS protein with disuccinimidyl suburate suggest that TaqMutS is a dimer in the presence of ATP. ATP binding and hydrolysis by TaqMutS reduces the heteroduplex-DNA binding by the protein. Using limited proteolysis we detected extensive conformational changes of the TaqMutS protein in the presence of ATP and heteroduplex DNA. Heteroduplex-DNA binding is necessary for the observed conformational changes since F39A mutant protein defective in DNA binding does not display ATP-induced conformational changes. The implications of the observed conformational changes in the MutS protein are discussed with respect to two different models proposed for the role of ATP hydrolysis by MutS in DNA mismatch repair. C1 Natl Ctr Cell Sci, Pune 411007, Maharashtra, India. NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Biswas, I (reprint author), Natl Ctr Cell Sci, Pune Univ Campus, Pune 411007, Maharashtra, India. NR 26 TC 23 Z9 23 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 2000 VL 347 BP 881 EP 886 DI 10.1042/0264-6021:3470881 PN 3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 316VA UT WOS:000087187700034 PM 10769195 ER PT J AU Deterding, LJ Kast, J Przybylski, M Tomer, KB AF Deterding, LJ Kast, J Przybylski, M Tomer, KB TI Molecular characterization of a tetramolecular complex between dsDNA and a DNA-binding leucine zipper peptide dimer by mass spectrometry SO BIOCONJUGATE CHEMISTRY LA English DT Article ID TRANSCRIPTIONAL ACTIVATOR PROTEIN; NONCOVALENT COMPLEXES; LIMITED PROTEOLYSIS; COILED COIL; LIQUID-CHROMATOGRAPHY; GENERAL CONTROL; DUPLEX DNA; YEAST GCN4; DOMAIN; JUN AB The characterization of sequence-specific noncovalent complexes of the GCN4 peptides and dsDNA using mass spectrometry is reported. The GCN4 peptides belong to a class of proteins which bind to sequence-specific dsDNA and are important in the regulation of gene transcription in yeast. These proteins contain a bZIP structural motif which consists of a basic DNA-binding domain and a leucine zipper dimerization domain. The protein dimers specifically bind double-stranded DNA containing the binding element 5'-ATGA(C/G)TCAT-3' to form a tetramolecular noncovalent complex. Using electrospray ionization, we report the detection of such a specific tetramolecular complex using mass spectrometry. Under conditions necessary for observation of the tetramolecular complex, no ions were detected far the GCN4 peptide dimer or the GCN4 monomer with dsDNA. These observations indicate that the specific interaction of the dsDNA with the protein dimer stabilizes the biologically significant noncovalent complex in the gas phase. Complexes were observed for various lengths of both blunt-ended and cohesive-ended double-stranded DNA containing the specific recognition sequence. The binding specificity of the complex was verified with the use of control DNA not containing the recognition sequence and control peptides not known to bind DNA specifically. Additionally, combining limited proteolysis of GCN4 peptide-DNA complexes with mass spectrometric determination of the products compared to identical experiments with noncomplexed peptides was used to probe interactions of specific amino acids with the DNA. The ability to observe these complexes by mass spectrometry. and to probe the specific interactions involved opens the door for utilizing this analytical technique to other structural biological problems including the study of transcription processes and determining the specific binding regions between dsDNA and proteins. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Konstanz, Fac Chem, D-78434 Constance, Germany. RP Deterding, LJ (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 62 TC 21 Z9 21 U1 0 U2 2 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 MAY-JUN PY 2000 VL 11 IS 3 BP 335 EP 344 DI 10.1021/bc990123c PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 318YX UT WOS:000087313200005 PM 10821649 ER PT J AU Vitiello, B Lederhendler, I AF Vitiello, B Lederhendler, I TI Research on eating disorders: Current status and future prospects SO BIOLOGICAL PSYCHIATRY LA English DT Review DE anorexia; bulimia; eating disorders; research ID GENE PROMOTER POLYMORPHISM; LATERAL HYPOTHALAMIC AREA; LONG-TERM FOLLOW; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; RISK-FACTORS; BODY-WEIGHT; PREPROHYPOCRETIN OREXIN; PSYCHIATRIC-DISORDERS; INDIVIDUAL THERAPY AB This report summarizes the main themes addressed at a workshop on research on eating disorders (EDs), which was hosted by the National Institute of Mental Health in December 1998. Both basic behavioral neuroscientists and clinical investigators met in an effort to integrate nl eas of research and foster collaborations. Considerable advances have been made in understanding the neuroendocrinological mechanisms that regulate appetite and food intake. These achievements are in sharp contrast with the limited progress in elucidating the pathogenesis of EDs and developing effective treatment and preventive interventions. Anorexia nervosa remains a highly morbid condition with the highest mortality of any other psychiatric disorder. Besides acute refeeding techniques, no specific interventions have been proven effective in changing the long-term course of anorexia nervosa. Efficacious treatments exist for bulimia nervosa, bur their underutilization calls for research on translating experimental findings into clinical practice. Closer interface between neuroscientists and clinical researchers is required for advancing our under-standing of ED pathogenesis and developing effective treatments. Recent studies are suggestive of a substantial genetic contribution to EDs that deserves further investigation. Finally, there is art urgent need to examine risk and protective factors for EDs, on which safe and effective prevention can be built. C1 NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, Room 7149,6001 Execut Blvd,MSC 9633, Bethesda, MD 20892 USA. NR 90 TC 30 Z9 31 U1 1 U2 5 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 MAY 1 PY 2000 VL 47 IS 9 BP 777 EP 786 DI 10.1016/S0006-3223(99)00319-4 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 312DW UT WOS:000086928800002 PM 10812036 ER PT J AU Kaye, WH Lilenfeld, LR Berrettini, WH Strober, M Devlin, B Klump, KL Goldman, D Bulik, CM Halmi, KA Fichter, MM Kaplan, A Woodside, DB Treasure, J Plotnicov, KH Polllice, C Rao, R McConaha, CW AF Kaye, WH Lilenfeld, LR Berrettini, WH Strober, M Devlin, B Klump, KL Goldman, D Bulik, CM Halmi, KA Fichter, MM Kaplan, A Woodside, DB Treasure, J Plotnicov, KH Polllice, C Rao, R McConaha, CW TI A search for susceptibility loci for anorexia nervosa: Methods and sample description SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anorexia nervosa; bulimia nervosa; eating disorders; genetics; linkage analysis; affected relative pairs ID GENETICALLY COMPLEX TRAITS; TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE; TERM WEIGHT RESTORATION; AFFECTED RELATIVE PAIRS; EATING DISORDER SCALE; BULIMIA-NERVOSA; LINKAGE STRATEGIES; SEROTONIN ACTIVITY; PROMOTER POLYMORPHISM; CONTROLLED FAMILY AB Background: Eating disorders have not traditionally been viewed as heritable illnesses; however, recent family and twin studies lend credence to the potential role of genetic transmission. The Price Foundation funded an international, multisite study to identify genetic factors contributing to the pathogenesis of anorexia nervosa (AN) by recruiting affective relative pairs. This article is an overview of study methods and the clinical characteristics of the sample. Methods: All probands met modified DSM-IV criteria for AN; all affected first, second, and third degree relatives met DSM-IV criteria for AN, bulimia nervosa (BN), or eating disorder not otherwise specified (NOS). Probands and affected relatives were assessed diagnostically with the Structured Interview for Anorexia and Bulimia. DNA was collected from probands, affected relatives and a subset of their biological parents. Results: Assessments were obtained from 196 probands and 237 affected relatives, over 98% of whom are of Caucasian ancestry. Overall, there were 229 relative pairs who were informative for linkage analysis. Of the proband-relative pairs, 63% were AN-AN, 20% were AN-BN, and 16% were AN-NOS. For family-based association analyses, DNA has been collected from both biological parents of 159 eating-disordered subjects. Few significant differences in demographic characteristics were found between proband and relative groups. Conclusions: The present study represents the first large-scale molecular genetic investigation of AN. Our successful recruitment of over 500 subjects, consisting of affected probands, affected relatives, and their biological parents, will provide the basis to investigate genetic transmission of eating disorders via a genome scan and assessment of candidate genes. Biol Psychiatry 2000;47:794-803 (C) 2000 Society of Biological Psychiatry. C1 Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Price Fdn Collaborat Grp Eating Disorders Module, Pittsburgh, PA 15213 USA. Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. Univ Penn, Sch Med, Dept Psychiat, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Sch Med, Neuropsychiat Inst & Hosp, Los Angeles, CA USA. NIAAA, NIH, Bethesda, MD USA. Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. Cornell Univ, New York Presbyterian Hosp Westchester, Weill Med Coll, White Plains, NY USA. Hosp Behav Med, Klin Roseneck, Munich, Germany. Toronto Hosp, Dept Psychiat, Toronto, ON, Canada. Maudsley & Bethlem Royal Hosp, Inst Psychiat, London, England. RP Kaye, WH (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Price Fdn Collaborat Grp Eating Disorders Module, 3811 OHara St E-724, Pittsburgh, PA 15213 USA. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Treasure, Janet/0000-0003-0871-4596 NR 75 TC 87 Z9 88 U1 1 U2 8 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 MAY 1 PY 2000 VL 47 IS 9 BP 794 EP 803 DI 10.1016/S0006-3223(99)00240-1 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 312DW UT WOS:000086928800004 PM 10812038 ER PT J AU George, DT Hibbeln, JR Ragan, PW Umhau, JC Phillips, MJ Doty, L Hommer, D Rawlings, RR AF George, DT Hibbeln, JR Ragan, PW Umhau, JC Phillips, MJ Doty, L Hommer, D Rawlings, RR TI Lactate-induced rage and panic in a select group of subjects who perpetrate acts of domestic violence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE domestic violence; lactate; rage; panic ID ALCOHOL; MEN; PROVOCATION; INFUSIONS; DISORDER; ANXIETY; ABUSERS; ATTACKS; BATTER AB Background: Perpetrators of domestic violence frequently report symptoms of autonomic arousal and a sense of fear and/or loss of control at the time of the violence. Since many of these symptoms are also associated with panic attacks, we hypothesized that perpetrators of domestic violence and patients with panic attacks may share similar exaggerated fear-related behaviors. To test this hypothesis, we employed the panicogenic agent sodium lactate to examine the response of perpetrators to anxiety/fear induced by a chemical agent. Methods: Using a double-blind, placebo-controlled design, we infused 0.5 mol/L sodium lactate or placebo over 20 min on separate days to a select group of subjects who perpetrate acts of domestic violence and two nonviolent comparison groups. We compared their behavioral, neuroendocrine, and physiologic responses. Results: Lactate administration elicited intense emotional responses in the perpetrators of domestic violence. Perpetrators evidenced more lactate-induced rage and panic and showed greater changes in speech, breathing, and motor activity than did nonviolent control subjects. There were no significant differences between the groups for any neuroendocrine or physiologic measure. Conclusions: These results are consistent with our hypothesis that some perpetrators of domestic violence have exaggerated fear-related behavioral responses. Biol Psychiatry 2000:47:804-812 (C) 2000 Society of Biological Psychiatry. C1 NIAAA, DICBR, Clin Studies Lab, Bethesda, MD 20892 USA. NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. Vanderbilt Med Sch, Dept Psychiat, Nashville, TN USA. RP George, DT (reprint author), NIAAA, DICBR, Clin Studies Lab, Bldg 10,Rm 6S-240,10 Ctr Dr MSC-1610, Bethesda, MD 20892 USA. NR 42 TC 20 Z9 22 U1 2 U2 7 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 MAY 1 PY 2000 VL 47 IS 9 BP 804 EP 812 DI 10.1016/S0006-3223(99)00300-5 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 312DW UT WOS:000086928800005 PM 10812039 ER PT J AU Ishibe, N Freedman, AN Michalek, AM Iacobuzio-Donahue, C Mettlin, CJ Petrelli, NJ Asirwatham, JE Hamilton, SR AF Ishibe, N Freedman, AN Michalek, AM Iacobuzio-Donahue, C Mettlin, CJ Petrelli, NJ Asirwatham, JE Hamilton, SR TI Expression of p27(Kip1) and bcl-2, cigarette smoking, and colorectal cancer risk SO BIOMARKERS LA English DT Article DE p27(Kip1); bcl-2; smoking; colorectal cancer ID KINASE INHIBITOR P27; LARGE-BOWEL-CANCER; ALCOHOL-CONSUMPTION; ADENOMATOUS POLYPS; DIGESTIVE-TRACT; TOBACCO SMOKING; RECTAL-CANCER; P53 MUTATIONS; CELL-DEATH; PROGNOSTIC-SIGNIFICANCE AB Although a positive association between cigarette smoking and colorectal adenoma development is consistently found, the association with colorectal cancer remains controversial. We evaluated the potential roles of p27(Kip1) and bcl-2 protein expressions in conjunction with cigarette smoking exposure and colorectal cancer risk in a hospital-based case-control study. A total of 163 colorectal cancer patients from Roswell Park Cancer Institute and Buffalo General Hospital and 326 healthy controls responded to a standardized questionnaire on colorectal cancer risk factors including detailed information on their history of cigarette smoking; 110 of the patients' tumours were available for immunohistochemical analysis of p27(Kip1) and bcl-2 protein overexpression. An avidin-biotin immunoperoxidase procedure was used to determine expression after incubation with mouse monoclonal p27(Kip1) and mouse monoclonal bcl-2 antibodies, respectively. A statistically significant trend for total pack-years of smoking was found when p27(Kip1) positive cases were compared with p27(Kip1) negative cases (trend test, p = 0.007). Although a weak inverse association was observed with smoking exposure among p27(Kip1) negative tumour cases in comparison to controls, a significant dose-response association was seen with p27(Kip1) positive tumours. The relative risk of developing a p27(Kip1) positive tumour was estimated to be 1.17 (95% CI 0.54-2.54) for those with less than 20 pack-years, 1.95 (95% CI 0.95-3.97) for those with 20-39 pack-years, and 2.25 (95% CI 1.14-4.45) for those with greater than 39 pack-years of smoking exposure (trend test, p = 0.009) when compared with controls. When cases with bcl-2 expression were compared with cases without bcl-2 expression, suggestion of a trend was also observed with pack-years smoked (trend test, p = 0.09). In our study of 110 patients with sporadic colorectal cancer and 326 controls, we observed differences in associations between cigarette smoking and expressions in p27(Kip1) and bcl-2. Our data suggest that bcl-2 overexpression (or a bcl-2 dependent pathway) is associated with cigarette smoking in the development of colorectal cancer, whereas a loss of p27(Kip1) expression is not. These associations indicate that there is aetiological heterogeneity in colorectal cancer development, and that they can indirectly allude to where these changes in protein expression occur in the adenoma-carcinoma sequence (i.e. early versus late events). C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20852 USA. NCI, Appl Res Program, Bethesda, MD 20852 USA. Roswell Pk Canc Inst, Dept Educ Affairs, Buffalo, NY 14263 USA. Johns Hopkins Med Inst, Div GI Liver Pathol, Baltimore, MD USA. Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. Univ Texas, MD Anderson Canc Ctr, Div Pathol & Lab Med, Houston, TX 77030 USA. Sisters Hosp, Buffalo, NY USA. RP Ishibe, N (reprint author), NCI, Genet Epidemiol Branch, 6120 Execut Blvd,MSC 7236, Bethesda, MD 20852 USA. NR 61 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD MAY-JUN PY 2000 VL 5 IS 3 BP 225 EP 234 DI 10.1080/135475000230389 PG 10 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 319FE UT WOS:000087330200007 PM 23889224 ER PT J AU Mekonnen, B Weiss, E Katz, E Ma, JY Ziffer, H Kyle, DE AF Mekonnen, B Weiss, E Katz, E Ma, JY Ziffer, H Kyle, DE TI Synthesis and antimalarial activities of base-catalyzed adducts of 11-azaartemisinin SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID N-SUBSTITUTED 11-AZAARTEMISININS; ARTEMISININ; DERIVATIVES AB A series of N-substituted 11-azaartemisinins were prepared in high yield employing base-catalyzed additions to an amide nitrogen of olefins and terminal acetylenes conjugated with electron withdrawing groups (EWGs). When the terminal acetylene was conjugated with carbomethoxy, N,N-dimethyl amide or carbonyl groups, the E-adducts resulted. A mixture of E- and Z-adducts were obtained when the EWG was a nitrile. In vitro antimalarial activities of each compound were determined against two drug-resistant strains of Plasmodium falciparum. Many of the compounds prepared were several times more active than artemisinin. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Parasitol, Washington, DC 20307 USA. RP Ziffer, H (reprint author), NIDDK, Chem Phys Lab, Room B1-31,Bldg 5, Bethesda, MD 20892 USA. NR 14 TC 26 Z9 27 U1 0 U2 2 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 MAY PY 2000 VL 8 IS 5 BP 1111 EP 1116 DI 10.1016/S0968-0896(00)00049-3 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 323DF UT WOS:000087549000024 PM 10882021 ER PT J AU Rao, TVS Haber, MT Sayer, JM Jerina, DM AF Rao, TVS Haber, MT Sayer, JM Jerina, DM TI Incorporation of 4-thiothymidine into DNA by the klenow fragment and HIV-1 reverse transcriptase SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID POLYMERASE-I KLENOW; NUCLEOTIDE ANALOG 2-AMINOPURINE; ESCHERICHIA-COLI; KINETIC MECHANISM; RESTRICTION-ENDONUCLEASE; REPLICATION FIDELITY; OLIGODEOXYNUCLEOTIDES; MISINCORPORATION; COMPLEXES; ECORV AB The 5'-triphosphate of 4-thiothymidine (4S-TTP) is an excellent substrate for the Klenow fragment of Escherichia coli DNA polymerase I and HIV-1 reverse transcriptase with values of k(cat)/K-m within a factor of similar to 3 of those for TTP. A large UV change (Delta epsilon = -9770 M-1 cm(-1) at 340 nm) associated with incorporation of 4S-TMP into nucleic acid duplexes makes possible a rapid, continuous spectrophotometric assay of the reaction progress. (C) 2000 Published by Elsevier Science Ltd. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Sayer, JM (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 28 TC 11 Z9 11 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 1 PY 2000 VL 10 IS 9 BP 907 EP 910 DI 10.1016/S0960-894X(00)00123-2 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 316GE UT WOS:000087158600014 PM 10853657 ER PT J AU Gao, Y Wu, L Luo, JH Guo, R Yang, D Zhang, ZY Burke, TR AF Gao, Y Wu, L Luo, JH Guo, R Yang, D Zhang, ZY Burke, TR TI Examination of novel non-phosphorus-containing phosphotyrosyl mimetics against protein-tyrosine phosphatase-1B and demonstration of differential affinities toward Grb2 SH2 domains SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID STRUCTURE-BASED DESIGN; SIGNAL-TRANSDUCTION; INHIBITORY PEPTIDES; POTENT INHIBITION; LIGANDS; BINDING; SPECIFICITY; DISCOVERY; MECHANISM AB Inhibitory potencies were compared of several mono- and dicarboxy-based pTyr mimetics in Grb2 SH2 domain versus PTP1B assays. Although in both systems pTyr residues provide critical binding elements, significant differences in the manner of recognition exist between the two. This is reflected in the current study, where marked variation in relative potencies was observed between the two systems. Of particular note was the poor potency of all monocarboxy-based pTyr mimetics against PTP1B when incorporated into a hexapeptide platform. The recently reported high PTP1B inhibitory potency of similar phenylphosphate mimicking moieties displayed in small molecule, non-peptide structures, raises questions on the limitations of using peptides as platforms for pTyr mimetics in the discovery of small molecule inhibitors. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bldg 37,Room 5C06, Bethesda, MD 20892 USA. RI Burke, Terrence/N-2601-2014 NR 27 TC 48 Z9 50 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 1 PY 2000 VL 10 IS 9 BP 923 EP 927 DI 10.1016/S0960-894X(00)00124-4 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 316GE UT WOS:000087158600018 PM 10853661 ER PT J AU Chizmadzhev, YA Kuzmin, PI Kumenko, DA Zimmerberg, J Cohen, FS AF Chizmadzhev, YA Kuzmin, PI Kumenko, DA Zimmerberg, J Cohen, FS TI Dynamics of fusion pores connecting membranes of different tensions SO BIOPHYSICAL JOURNAL LA English DT Article ID PHOSPHOLIPID-BILAYER MEMBRANES; MOUSE MAST-CELLS; EXOCYTOTIC FUSION; SECRETORY GRANULES; PLANAR MEMBRANE; LIPID FLOW; VESICLES; HEMAGGLUTININ; MATRIX; INTERMEDIATE AB The energetics underlying the expansion of fusion pores connecting biological or lipid bilayer membranes is elucidated. The energetics necessary to deform membranes as the pore enlarges, in some combination with the action of the fusion proteins, must determine pore growth. The dynamics of pore growth is considered for the case of two homogeneous fusing membranes under different tensions. It is rigorously shown that pore growth can be quantitatively described by treating the pore as a quasiparticle that moves in a medium with a viscosity determined by that of the membranes. Motion is subject to tension, bending, and viscous forces. Pore dynamics and lipid flow through the pore were calculated using Lagrange's equations, with dissipation caused by intra- and intermonolayer friction. These calculations show that the energy barrier that restrains pore enlargement depends only on the sum of the tensions; a difference in tension between the fusing membranes is irrelevant. in contrast, lipid flux through the fusion pore depends on the tension difference but is independent of the sum. Thus pore growth is not affected by tension-driven lipid flux from one membrane to the other. The calculations of the present study explain how increases in tension through osmotic swelling of vesicles cause enlargement of pores between the vesicles and planar bilayer membranes. In a similar fashion, swelling of secretory granules after fusion in biological systems could promote pore enlargement during exocytosis. The calculations also show that pore expansion can be caused by pore lengthening; lengthening may be facilitated by fusion proteins. C1 AN Frumkin Electrochem Inst, Moscow 117071, Russia. NICHHD, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. Rush Med Coll, Dept Physiol & Mol Biophys, Chicago, IL 60612 USA. RP Cohen, FS (reprint author), Rush Med Coll, Dept Physiol, 1750 W Harrison St, Chicago, IL 60612 USA. RI Wunder, Stephanie/B-5066-2012; Chizmadzhev, Yuri/L-1984-2013; Zdilla, Michael/B-4145-2011 FU FIC NIH HHS [R03 TW00715]; NIGMS NIH HHS [GM 27367] NR 61 TC 58 Z9 59 U1 1 U2 9 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 2000 VL 78 IS 5 BP 2241 EP 2256 PG 16 WC Biophysics SC Biophysics GA 311PF UT WOS:000086892500005 PM 10777723 ER PT J AU Brinton, LA Gammon, MD Coates, RJ Hoover, RN AF Brinton, LA Gammon, MD Coates, RJ Hoover, RN TI Tubal ligation and risk of breast cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; tubal ligation; epidemiology ID AGE 45 YEARS; OVARIAN-CANCER; STERILIZATION; HYSTERECTOMY; WOMEN AB Although it has been demonstrated in previous studies that tubal ligation can have widespread effects on ovarian function, including a decrease in the risk of subsequent ovarian cancer, few studies have evaluated effects on breast cancer risk. In a population-based case-control study of breast cancer among women 20-54 years of age conducted in three geographic areas, previous tubal ligations were reported by 25.3% of the 2173 cases and 25.8% of the 1990 controls. Initially it appeared that tubal ligations might impart a slight reduction in risk, particularly among women undergoing the procedure at young ages (< 25 years). However, women were more likely to have had the procedure if they were black, less educated, young when they bore their first child, or multiparous. After accounting for these factors, tubal ligations were unrelated to breast cancer risk (relative risk (RR) = 1.09, 95% confidence interval (CI) 0.9-1.3), with no variation in risk by age at, interval since. or calendar year of the procedure. The relationship of tubal ligations to risk did not vary according to the presence of a number of other risk factors, including menopausal status or screening history. Furthermore, effects of tubal ligation were similar for all stages at breast cancer diagnosis. Further studies would be worthwhile given the biologic plausibility of an association. However, future investigations should include information on type of procedure performed (since this may relate to biologic effects) as well as other breast cancer risk factors. (C) 2000 Cancer Research Campaign. C1 NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. RP Brinton, LA (reprint author), NCI, Environm Epidemiol Branch, Execut Plaza S,Rm 7068,6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 26 TC 10 Z9 10 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 2000 VL 82 IS 9 BP 1600 EP 1604 PG 5 WC Oncology SC Oncology GA 304JT UT WOS:000086480600017 PM 10789731 ER PT J AU Chan, MTY Nadareishvili, ZG Norris, JW AF Chan, MTY Nadareishvili, ZG Norris, JW CA Canadian Stroke Consortium TI Diagnostic strategies in young patients with ischemic stroke in Canada SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID ADULTS AB Background: A preliminary national survey of ischemic stroke in the young (15-45 years) undertaken by the Canadian Stroke Consortium indicated that in 44% of 356 patients, no cause was found. Objective: To determine the reason for this high incidence of diagnostic uncertainty in young patients with ischemic stroke. Methods: Neurologists in the ten Canadian stroke centers completed a detailed questionnaire for patients aged 15-45 years admitted to hospital between January 1993 and December 1997. Using a stepwise diagnostic algorithm incorporating clinical, neuroimaging, neurovascular and laboratory data, we divided patients into three groups: (1) those with established cause for the ischemic stroke, (2) those who remained unexplained despite adequate investigation, (3) those who remained unexplained but were, in our opinion, under-investigated. Results: In 197 patients (56%), an identified cause was established including cardioembolic sources (14%), extracranial arterial dissection (13%), lacunar infarcts (8%) atherosclerosis (6%). A miscellaneous group of 15%, included cerebral venous thrombosis, coagulopathies, vasculitis and others. In 159 patients (44%) with no apparent cause for their stroke, we considered only 81 (23%) adequately investigated, and 78 (21%) inadequately investigated. Conclusion: About one in five young patients was inadequately investigated by a stroke-oriented group of neurologists. The major problem appears to be restriction of investigations to neuroimaging alone (usually computerized cerebral tomography), without further tests such as cerebral angiography and cardiac imaging. C1 Univ Toronto, Sunnybrook & Womens Coll, Hlth Sci Ctr, Stroke Res Unit, Toronto, ON, Canada. RP Nadareishvili, ZG (reprint author), NINDS, Stroke Branch, NIH, 36 Convent Dr,Bldg 36,4A03, Bethesda, MD 20892 USA. RI Buchan, Alastair/B-9095-2009 OI Buchan, Alastair/0000-0002-2918-5200 NR 17 TC 27 Z9 31 U1 0 U2 0 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY, AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD MAY PY 2000 VL 27 IS 2 BP 120 EP 124 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 313DY UT WOS:000086986100006 PM 10830344 ER PT J AU Obrocea, GV Morris, ME AF Obrocea, GV Morris, ME TI Comparison of changes evoked by GABA (gamma-aminobutyric acid) and anoxia in [K+](o), [Cl-](o), and [Na+](o) in stratum pyramidale and stratum radiatum of the guinea pig hippocampus SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Review DE brain slices; ion-selective microelectrodes; stratum pyramidale; stratum radiatum; bicuculline methiodide; extracellular space shrinkage ID INHIBITORY POSTSYNAPTIC POTENTIALS; EXTRACELLULAR POTASSIUM ACTIVITY; STIMULUS-INDUCED CHANGES; CENTRAL NERVOUS-SYSTEM; RAT-BRAIN INVIVO; CEREBRAL-ISCHEMIA; AMINO-ACIDS; IN-VITRO; INTRACELLULAR CALCIUM; SYNAPTIC TRANSMISSION AB Ion-selective microelectrode recordings were made to assess a possible contribution of extracellular gamma-aminobutyric acid (GABA) accumulation to early responses evoked in the brain by anoxia and ischemia. Changes evoked by GABA or N-2 in [K+](o), [Cl-](o), [Na+](o), and [TMA(+)](o) were recorded in the cell body and dendritic regions of the stratum pyramidale (SP) and stratum radiatum (SR), respectively, of pyramidal neurons in CA1 of guinea pig hippocampal slices. Bath application of GABA (1-10 mM) for approximately 5 min evoked changes in [K+](o) and [Cl-](o) with respective EC50 levels of 3.8 and 4.1 mM in SP, and 4.7 and 5.6 mM in SR. In SP 5 mM GABA reversibly increased [K+](o) and [Cl-](o) and decreased [Na+](o); replacement of 95% O-2 -5% CO2 by 95% N-2 -5% CO2 for a similar period of time evoked changes which were for each ion in the same direction as those with GABA. In SR both GABA and N-2 caused increases in [K+](o) and decreases in [Cl-](o) and [Na+](o). The reduction of extracellular space, estimated from levels of [TMA(+)](o) during exposures to GABA and N-2, was 5-6% and insufficient to cause the observed changes in ion concentration. Ion changes induced by GABA and N-2 were reversibly attenuated by the GABA(A) receptor antagonist bicuculline methiodide (BMI, 100 mu M). GABA-evoked changes in [K+](o) in SP and SR and [Cl-](o) in SP were depressed by >=90%, and of [Cl-](o) in SR by 50%; N-2-evoked changes in [K+](o) in SP and SR were decreased by 70% and those of [Cl-](o) by 50%. BMI blocked delta [Na+](o) with both GABA and N-2 by 20-30%. It is concluded that during early anoxia: (i) accumulation of GABA and activation of GABA(A) receptors may contribute to the ion changes and play a significant role, and (ii) responses in the dendritic (SR) regions are greater than and (or) differ from those in the somal (SP) layers. A large component of the [K+](o) increase may involve a GABA-evoked Ca2+-activated g(k), secondary to [Ca2+](i) increase. A major part of [Cl-](o) changes may arise from GABA-induced g(Cl) and glial efflux, with strong stimulation of active outward transport and anion exchange at SP, and inward Na+/K+/2Cl(-) co-transport at SR. Na+ influx is attributable mainly to Na+-dependent transmitter uptake, with only a small amount related to GABA(A) receptor activation. Although the release and (or) accumulation of GABA during anoxia might be viewed as potentially protectant, the ultimate role may more likely be an important contribution to toxicity and delayed neuronal death. C1 Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada. NIMH, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Morris, ME (reprint author), Univ Ottawa, Dept Cellular & Mol Med, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada. NR 105 TC 3 Z9 3 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD MAY PY 2000 VL 78 IS 5 BP 378 EP 391 DI 10.1139/cjpp-78-5-378 PG 14 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 303VR UT WOS:000086445900004 PM 10841433 ER PT J AU Breslow, RA Graubard, BI Sinha, R Subar, AF AF Breslow, RA Graubard, BI Sinha, R Subar, AF TI Diet and lung cancer mortality: a 1987 National Health Interview Survey cohort study SO CANCER CAUSES & CONTROL LA English DT Article DE diet; lung cancer; mortality; National Health Interview Survey ID HETEROCYCLIC AMINE CONTENT; IOWA-WOMENS-HEALTH; NHANES-II SURVEY; ALCOHOL-CONSUMPTION; QUANTITATIVE DATA; NUTRIENT SOURCES; VARYING DEGREES; AMERICAN DIET; UNITED-STATES; RISK AB Objectives: To study the association between diet and lung cancer mortality in the United States. Methods: Records from 20,195 participants with usable dietary data in the 1987 National Health Interview Survey were linked to the National Death Index. Baseline diet was assessed with a 59-item food-frequency questionnaire. Food groups (fruits, vegetables, total meat/poultry/fish, red meats, processed meats, dairy products, breakfast cereals, other starches, added fats, and alcohol) were analyzed in cause-specific Cox proportional hazard regression models adjusted for age, gender and smoking. Results: There were 158 deaths from lung cancer (median follow-up 8.5 years). Frequencies of meat/poultry/fish intake (relative risk [RR] (highest compared to lowest quartile) = 2.0; 95% confidence interval [CI] 1.2-3.5, p for trend [p] < 0.027), and red meat intake (RR = 1.6; CI 1.0-2.6, p < 0.014), were positively and significantly associated with lung cancer mortality. Specifically, the red meats, including pork (RR = 1.6; CI 1.0-2.7, p < 0.028), and ground beef (RR = 2.0; CI 1.1-3.5, p < 0.096) were associated with increased risk, although for ground beef the trend was not significant. Dairy products (RR = 0.5; CI 0.3-0.8, p < 0.009) were inversely associated with lung cancer mortality. There was no statistically significant association between intake of fruits and vegetables and lung cancer mortality. Conclusions: In this nationally representative study, intake of red meats was positively associated with lung cancer mortality while intake of dairy products was inversely associated. While smoking is the major risk for lung cancer mortality, diet may have a contributory role. C1 Ctr Dis Control & Prevent, Natl Canc Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Epidemiol & Hlth Serv Res Branch, Atlanta, GA 30341 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Appl Res Branch, Bethesda, MD 20892 USA. RP Breslow, RA (reprint author), Ctr Dis Control & Prevent, Natl Canc Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Epidemiol & Hlth Serv Res Branch, 4770 Buford Highway,MS K-55, Atlanta, GA 30341 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 63 TC 55 Z9 55 U1 1 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2000 VL 11 IS 5 BP 419 EP 431 DI 10.1023/A:1008996208313 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 348PQ UT WOS:000088994300005 PM 10877335 ER PT J AU Rogan, WJ Ragan, NB Dinse, GE AF Rogan, WJ Ragan, NB Dinse, GE TI X-ray evidence of increased asbestos exposure in the US population from NHANES I and NHANES II, 1973-1978 SO CANCER CAUSES & CONTROL LA English DT Article DE asbestos-adverse effects; health surveys; NHANES I; NHANES II; occupational diseases; occupations-statistics and numerical data; pleural diseases; pneumoconiosis ID NUTRITION EXAMINATION SURVEY; 1ST NATIONAL-HEALTH; PLEURAL PLAQUES; ABNORMALITIES; PREVALENCE; MORTALITY; DISEASE; WORKERS AB Objectives: Jobs involving heavy asbestos exposure increase risk for lung cancer and mesothelioma substantially, and low-level exposures may carry some risk. At least one indicator of asbestos exposure, mesothelioma, has been increasing in the US for decades. We investigated the prevalence of another indicator, pleural thickening on x-ray, in a defined sample of the US population. Methods: Certified physicians read 1060 x-rays from the second National Health and Nutrition Examination Survey (1976-1980) for pleural changes consistent with pneumoconiosis, which are a reasonably specific indicator of asbestos exposure. Results: prevalence estimates, in NHANES II, in the age group 35-74 years, are 6.4% (+/-0.9%) among males, 1.7% (+/-0.6%) among females, and 3.9% (+/-0.6%) overall. These prevalences are approximately twice those estimated from NHANES I data (1971-1975). Conclusions: X-ray evidence of asbestos exposure was common in the late 1970s and increasing. The increase may be due to occupational asbestos exposure, but it is so large as to suggest some contribution from environmental, non-occupational asbestos exposure. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, POB 12233,RTP,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 29 TC 13 Z9 13 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2000 VL 11 IS 5 BP 441 EP 449 DI 10.1023/A:1008952426060 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 348PQ UT WOS:000088994300007 PM 10877337 ER PT J AU Butler, LM Potischman, NA Newman, B Millikan, RC Brogan, D Gammon, MD Swanson, CA Brinton, LA AF Butler, LM Potischman, NA Newman, B Millikan, RC Brogan, D Gammon, MD Swanson, CA Brinton, LA TI Menstrual risk factors and early-onset breast cancer SO CANCER CAUSES & CONTROL LA English DT Article DE breast neoplasm; menstruation; risk factors ID BODY-SIZE; REPRODUCTIVE FACTORS; OVULATORY CYCLES; EARLY MENARCHE; WOMEN; AGE; ESTROGENS; PROLIFERATION; PATTERNS; DISEASE AB Objectives: Epidemiologic studies provide evidence for increased breast cancer risk among women with prolonged exposure to endogenous estrogens and progesterone. Menstrual cycle characteristics, such as early menarche, rapid initiation of regular ovulatory cycles, short cycle length, and more days of flow, all potentially contribute to higher cumulative ovarian hormone exposure. Methods: We assessed the associations between these characteristics and breast cancer risk in a population-based, case-control study of 1505 controls and 1647 newly diagnosed cases, all younger than 45 years of age. Results: Compared to women with menarche at greater than or equal to 15 years, we observed some increase in risk for women with younger ages at menarche, although those with very early ages were not at particularly high risk [odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1-1.9 for menarche at age 12 and OR = 1.2, 95% CI = 0.9-1.7 for menarche at age less than or equal to 10]. Women who reported having regular menstrual cycles within 2 years of menarche were at increased breast cancer risk (OR = 1.7, 95% CI = 1.2-2.3), compared to those never having regular cycles. Stratification by current body mass index revealed slightly stronger associations with menstrual characteristics among thinner women (< 22.0 kg/m(2)) compared to heavier women (>28.8 kg/m(2)). Conclusions: These findings suggest that future studies should focus on clarifying how the interrelated effects of body size and menstrual factors, such as age at menarche and cycle regularity, contribute to breast cancer etiology. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. Queensland Univ Technol, Sch Publ Hlth, Brisbane, Qld 4001, Australia. Queensland Univ Technol, Ctr Publ Hlth Res, Brisbane, Qld 4001, Australia. Emory Univ, Dept Biostat, Atlanta, GA 30322 USA. NIH, Off Dietary Supplements, Rockville, MD USA. NCI, Environm Epidemiol Branch, Rockville, MD USA. RP Butler, LM (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, CB 7400, Chapel Hill, NC 27599 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 44 TC 27 Z9 27 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2000 VL 11 IS 5 BP 451 EP 458 DI 10.1023/A:1008956524669 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 348PQ UT WOS:000088994300008 PM 10877338 ER PT J AU Voeller, DM Grem, JL Pommier, Y Paull, K Allegra, CJ AF Voeller, DM Grem, JL Pommier, Y Paull, K Allegra, CJ TI Identification and proposed mechanism of action of thymidine kinase inhibition associated with cellular exposure to camptothecin analogs SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE thymidine kinase; camptothecin analogs; topoisomerase I; cross-inhibition; thymidylate synthase inhibitors ID DNA TOPOISOMERASE-I; THYMIDYLATE SYNTHASE; LEUKEMIA-CELLS; CYTOTOXICITY; RESISTANT; REPLITASE; COMPLEX; CEM/C2; DAMAGE; ENZYME AB Purpose: To investigate the effects of several camptothecin analogs including 9-aminocamptothecin (9-AC), SN38, topotecan, and irinotecan (CPT-11) on the enzymes involved in the pyrimidine salvage pathway including thymidylate synthase (TS). A COMPARE analysis using the NCI 60 cell line drug-screening panel suggested that there were similarities in the mechanisms of action of camptothecin analogs and TS inhibitors, Methods: TS enzymatic activity was measured by both an in situ tritium release assay using both the H630 colon cancer cell line and the CEM human leukemia cell line, and by a radiolabelled in vitro assay using partially purified human TS as the enzyme source. Thymidine kinase (TK) activity was measure by a radiolabelled in vitro assay using H630 colon cancer cell lysates as the enzyme source. Results: In vitro studies indicated that none of the analogs directly inhibited TS enzymatic activity; however, utilization of a coupled TS/TK in situ assay with radiolabelled deoxyuridine as the precursor revealed marked inhibition by the camptothecin analogs. 9-AC, SN38, and topotecan yielded IC50 values of 1.3, 1.6, and 1.1 mu M respectively. In contrast, there was no inhibition detected when deoxycytidine was used as the radiolabelled nucleoside precursor, suggesting that the drug effect was through inhibition of TK, rather than inhibition of TS. In vitro studies using cell lysates from H630 human colon cancer cells to measure TK activity showed no decrease in TK activity after 9-AC treatment. In addition, no changes were detected in the dATP and dTTP nucleotide pools, Permeabilizing the cell membranes with saponin did not abolish the inhibitory effect of the camptothecins indicating that altered cell transport was not responsible for the decreased activity in the in situ assay in intact cells. Conclusion: These studies suggest that there is inhibition of TK in intact cells associated with topoisomerase I inhibition by camptothecin analogs, and the inhibition of TK is the result of an indirect effect not related to feedback inhibition by changes in dTTP pools. C1 NCI, Med Branch, Bethesda Naval Hosp, Bethesda, MD 20089 USA. NCI, Med Branch, Div Clin Sci, Bethesda, MD 20889 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. RP Voeller, DM (reprint author), NCI, Med Branch, Bethesda Naval Hosp, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20089 USA. NR 29 TC 8 Z9 8 U1 1 U2 3 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 MAY PY 2000 VL 45 IS 5 BP 409 EP 416 DI 10.1007/s002800051010 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 307NU UT WOS:000086660100009 PM 10803925 ER PT J AU Marcus, PM Hayes, RB Vineis, P Garcia-Closas, M Caporaso, NE Autrup, H Branch, RA Brockmoller, J Ishizaki, T Karakaya, AE Ladero, JM Mommsen, S Okkels, H Romkes, M Roots, I Rothman, N AF Marcus, PM Hayes, RB Vineis, P Garcia-Closas, M Caporaso, NE Autrup, H Branch, RA Brockmoller, J Ishizaki, T Karakaya, AE Ladero, JM Mommsen, S Okkels, H Romkes, M Roots, I Rothman, N TI Cigarette smoking, N-acetyltransferase 2 acetylation status, and bladder cancer risk: A case-series meta-analysis of a gene-environment interaction SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CASE-ONLY DESIGNS; MOLECULAR EPIDEMIOLOGY; PHENOTYPE; GENOTYPE; SUSCEPTIBILITY; POLYMORPHISMS; NAT2; CARCINOGENESIS; POPULATION; EXPOSURE AB Tobacco use is an established cause of bladder cancer. The ability to detoxify aromatic amines, which are present in tobacco and are potent bladder carcinogens, is compromised in persons with the N-acetyltransferase 2 slow acetylation polymorphism. The relationship of cigarette smoking with bladder cancer risk therefore has been hypothesized to be stronger among slow acetylators, The few studies to formally explore such a possibility have produced inconsistent results, however. To assess this potential gene-environment interaction in as many bladder cancer studies as possible and to summarize results, we conducted a meta-analysis using data from 16 bladder cancer studies conducted in the general population (n = 1999 cases). Most had been conducted in European countries. Because control subjects were unavailable for a number of these studies, we used a case-series design, which can be used to assess multiplicative gene-environment interaction without inclusion of control subjects. A case-series interaction odds ratio (OR) >1.0 indicates that the relationship of cigarette smoking and bladder cancer risk is stronger among slow acetylators as compared with rapid acetylators, We observed an interaction between smoking and N-acetyltransferase 2 slow acetylation (OR, 1.3; 95% confidence interval, 1.0-1.6) that was somewhat stronger when analyses were restricted to studies conducted in Europe (OR, 1.5; confidence interval, 1.1-1.9), a pooling that included nearly 80% of the collected data. Using the predominantly male European study population and assuming a 2.5-fold elevation in bladder cancer risk from smoking, we estimated that the population attributable risk percent was 35% for slow acetylators who had ever smoked and 13% for rapid acetylators who had ever smoked. These results suggest that the relationship of smoking and bladder cancer is stronger among slow acetylators than among rapid acetylators. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Aarhus Univ, Dept Environm & Occupat Med, DK-8000 Aarhus, Denmark. Univ Pittsburgh, Ctr Clin Pharmacol, Pittsburgh, PA 15261 USA. Humboldt Univ, Dept Clin Pharmacol, Charite 74, D-10098 Berlin, Germany. Kumamoto Univ, Grad Sch Clin Pharm, Dept Pharmacol & Therapeut, Kumamoto 8620973, Japan. Gazi Univ, Dept Toxicol, TR-06100 Ankara, Turkey. Univ Complutense Madrid, Dept Med, Hosp Clin De San Carlos, Madrid 28040, Spain. Randers Hosp, Dept Surg, Urol Unit, DK-8900 Randers, Denmark. Univ Turin, Canc Epidemiol Unit, I-10126 Turin, Italy. RP Rothman, N (reprint author), NCI, Div Canc Epidemiol & Genet, Execut Plaza S,Room 8116,MSC 7240, Bethesda, MD 20892 USA. RI Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 NR 55 TC 117 Z9 119 U1 1 U2 6 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 MAY PY 2000 VL 9 IS 5 BP 461 EP 467 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 312WG UT WOS:000086966500002 PM 10815690 ER PT J AU Boone, CW Stoner, GD Bacus, JV Kagan, V Morse, MA Kelloff, GJ Bacus, JW AF Boone, CW Stoner, GD Bacus, JV Kagan, V Morse, MA Kelloff, GJ Bacus, JW TI Quantitative grading of rat esophageal carcinogenesis using computer-assisted image tile analysis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID N-NITROSOMETHYLBENZYLAMINE; INTRAEPITHELIAL NEOPLASIA; CANCER CHEMOPREVENTION AB Our objective was to grade, by computer-assisted quantitative image tile analysis, the intraepithelial neoplasia (also called dysplasia) that develops in esophagi of rats given N-nitrosomethybenzylamine (NMBA) for 5 weeks. To perform image tile analysis, the computer divides the video image of the neoplastic epithelium into a row of contiguous small rectangular images, or "tiles," 84 x 292 mu m in size, and quantitatively measures four selected tissue features within each image tile, The computer then calculates a tile grade for each image tile as the weighted sum of the four feature measurements, transformed into statistical Z-scores, the weights being determined by Fisher linear discriminant analysis of 300 tile grades of the neoplastic epithelium referenced to the mean tile grade (MTG) of 300 image tiles of normal epithelium. The two grading parameters, MTG and the percentage of tile grades exceeding the MTG of normal epithelium by >4 SD units (%TG>4SD), were validated as endpoints for screening chemopreventive agents in the rat NMBA-induced esophageal carcinogenesis model in two ways: (a) after NMBA treatment, %TG>4SD developed in parallel with tumor incidence and tumor multiplicity (number of papillomas/tumor-bearing rat); and (b) placing the chemopreventive phenethylisothiocyanate in the food of NMBA-treated rats produced parallel reductions in MTG, tumor incidence, and tumor multiplicity. Both MTG and %TG>4SD, measured by quantitative image tile analysis, are sensitive and objective continuous parametric response variables expressed to three significant figures, with wide dynamic range, that may be evaluated by t tests to compare tissue neoplastic changes before and after treatment with a chemopreventive agent. C1 Ohio State Univ, Sch Publ Hlth, Div Environm Hlth Sci, Columbus, OH 43210 USA. Bacus Labs, Lombard, IL 60148 USA. NCI, Chemoprevent Agent Dev Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Stoner, GD (reprint author), Ohio State Univ, Sch Publ Hlth, Div Environm Hlth Sci, CHRI 1148,300 W 10th Ave, Columbus, OH 43210 USA. NR 10 TC 19 Z9 20 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 MAY PY 2000 VL 9 IS 5 BP 495 EP 500 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 312WG UT WOS:000086966500006 PM 10815694 ER PT J AU Harty, LC Garcia-Closas, M Rothman, N Reid, YA Tucker, MA Hartge, P AF Harty, LC Garcia-Closas, M Rothman, N Reid, YA Tucker, MA Hartge, P TI Collection of buccal cell DNA using treated cards SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOMIC DNA; CYSTIC-FIBROSIS; ENZYMATIC AMPLIFICATION; PCR AMPLIFICATION; GUTHRIE CARDS; GENE; MUTATIONS; SAMPLES; BLOOD; RISK AB We devised a simple, noninvasive, cost-efficient technique for collecting buccal cell DNA for molecular epidemiology studies. Subjects (n = 52) brushed their oral mucosa and expectorated the fluid in their mouths, which was applied to "Guthrie" cards pretreated to retard bacterial growth and inhibit nuclease activity (IsoCode, Schleicher and Schuell, Keene, NH). The cards are well-suited for transport and storage because they dry quickly, need no processing, and are compact and lightweight. We stored the samples at room temperature for 5 days to mimic a field situation and then divided them into portions from which DNA was extracted either immediately or after storage for 9 months at room temperature, -20 degrees C, or -70 degrees C, The fresh samples had a median yield of 2.3 mu g of human DNA (range, 0.2-53.8 mu g), which was adequate for at least 550 PCR reactions. More than 90% of the samples were amplified in all three beta-globin gene fragment assays attempted. DNA extract frozen for 1 week at -20 degrees C also performed well. Stored samples had reduced DNA yields, which achieved statistical significance for room temperature and -70 degrees C, but not -20 degrees C, storage. However, because all of the stored samples tested were successfully amplified, the observed reduction may represent tighter DNA fixation to the card over time rather than loss of genetic material. We conclude that treated cards are an alternative to brushes! swabs and mouth rinses for the collection of buccal cell DNA and offer some advantages over these methods, particularly for large-scale or long-term studies involving stored samples and studies in which samples are collected off-site and transported. Future studies that enable direct comparisons of the various buccal cell collection methods are needed. C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. Amer Type Culture Collect, Manassas, VA 20110 USA. RP Tucker, MA (reprint author), NCI, Genet Epidemiol Branch, Execut Plaza S,7th Floor,6120 Execut Blvd,MSC 723, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015; Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 NR 28 TC 51 Z9 56 U1 1 U2 4 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 MAY PY 2000 VL 9 IS 5 BP 501 EP 506 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 312WG UT WOS:000086966500007 PM 10815695 ER PT J AU Hawk, E Breslow, RA Graubard, BI AF Hawk, E Breslow, RA Graubard, BI TI Male pattern baldness and clinical prostate cancer in the epidemiologic follow-up of the first National Health and Nutrition Examination Survey SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID STEROID 5-ALPHA-REDUCTASE; HEART-DISEASE; RISK-FACTORS; HUMAN SCALP; MEN; FINASTERIDE; ANDROGENS; EXPRESSION; FEATURES; ISOZYME AB Male pattern baldness (MPB) and prostate cancer are common in American males; however, MPB is clinically observable decades earlier. Aging, androgens, and heritability are risk factors for both conditions. We prospectively studied the association between MPB and clinical prostate cancer in a cohort representative of the United States male population. A total of 4,421 men 25-75 years old without a history of prostate cancer were examined for baldness in the Epidemiologic Follow-up Study of the first National Health and Nutrition Examination Survey. Participants were followed from baseline (1971-1974) through 1992, Incident cases of prostate cancer were identified by interviews, medical records, and death certificates. Age-standardized incidence rates and proportional hazards models were used to examine the association between MPB and clinical prostate cancer. Prostate cancer was diagnosed in 214 subjects over 17-21 years of follow-up. The age-standardized incidence of prostate cancer was greater among men with baldness at baseline (17.5 versus 12.5 per 10,000 person-years). The adjusted relative risk for prostate cancer among men with baldness was 1.50 (95% confidence interval, 1.12-2.00) and was similar regardless of the severity of baldness at baseline and was independent of other risk factors, including race and age. MPB seems to be a risk factor for clinical prostate cancer. C1 NCI, Div Canc Prevent, Gastrointestinal & Other Canc Res Grp, EPN,NIH, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Appl Res Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, NIH, Bethesda, MD 20892 USA. RP Hawk, E (reprint author), NCI, Div Canc Prevent, Gastrointestinal & Other Canc Res Grp, EPN,NIH, Suite 201,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 41 TC 44 Z9 45 U1 0 U2 1 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 MAY PY 2000 VL 9 IS 5 BP 523 EP 527 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 312WG UT WOS:000086966500011 PM 10815699 ER PT J AU Sausville, EA AF Sausville, EA TI Use of immunotoxins in the treatment of lymphoma SO CANCER JOURNAL LA English DT Editorial Material ID VASCULAR LEAK SYNDROME; B-CELL LYMPHOMA; PHASE-I; PSEUDOMONAS EXOTOXIN; CONTINUOUS-INFUSION; ENDOTHELIAL-CELLS C1 NCI, Dev Therapeut Program, Rockville, MD USA. RP Sausville, EA (reprint author), Execut Plaza N,Suite 843,6130 Execut Blvd, Rockville, MD 20852 USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAY-JUN PY 2000 VL 6 IS 3 BP 135 EP 138 PG 4 WC Oncology SC Oncology GA 343GV UT WOS:000088694100003 PM 10882327 ER PT J AU Longo, DL Duffey, PL Gribben, JG Jaffe, ES Curti, BD Gause, BL Janik, JE Braman, VM Esseltine, D Wilson, WH Kaufman, D Wittes, RE Nadler, LM Urba, WJ AF Longo, DL Duffey, PL Gribben, JG Jaffe, ES Curti, BD Gause, BL Janik, JE Braman, VM Esseltine, D Wilson, WH Kaufman, D Wittes, RE Nadler, LM Urba, WJ TI Combination chemotherapy followed by an immunotoxin (anti-B4-blocked ricin) in patients with indolent lymphoma: Results of a phase II study SO CANCER JOURNAL LA English DT Article ID NON-HODGKINS-LYMPHOMAS; TRIAL AB The purpose of this article was to evaluate the antitumor effects of a combination chemotherapy program based on ProMACE (prednisone, methotrexate, doxorubicin [Adriamycin], cyclophosphamide, etoposide) followed by a B cell-specific immunotoxin in the treatment of patients with advanced-stage indolent histology non-Hodgkin's lymphomas. We performed a prospective phase II clinical trial in a referral-based patient population. After confirmation of diagnosis and staging evaluation, 44 patients (10 small lymphocytic lymphoma, 27 follicular lymphoma, 7 mantle cell lymphoma; 30 without prior therapy, 14 previously treated) received six cycles of ProMACE-CytaBOM (cytarabine, bleomycin, vincristine [Oncovin], mechlorethamine) combination chemotherapy (with etoposide given orally daily for five days) followed by a 7-day continuous infusion of anti-B4-blocked ricin immunotoxin at 30 mu g/kg/day given every 14 days for up to six cycles. A complete response was achieved in 25 of 44 patients (57%), 21 from the chemotherapy alone, 3 converted from partial to complete response with the immunotoxin, and 1 patient became a complete responder after a surgical procedure to remove an enlarged spleen that was histologically negative for lymphoma. With a median follow-up of 5 years, 14 of 25 complete responders have relapsed (56%); median remission duration was 2 years, and overall survival was 61%. Forty-two percent of the complete responders have been in continuous remission for more than 4 years. The median number of courses of immunotoxin delivered was two usually because of the development of human anti-ricin antibodies. ProMACE- CytaBOM plus anti-B4-blocked ricin does not produce durable complete remissions in the majority of patients with indolent lymphoma. However, the remissions appear quite durable (> 4 years) in about 40% of the complete responders. C1 NCI, Frederick Canc Res & Dev Ctr, Biol Response Modifiers Program, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Div Clin Sci, Pathol Lab, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. ImmunoGen Inc, Cambridge, MA USA. RP Longo, DL (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 10 TC 27 Z9 28 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAY-JUN PY 2000 VL 6 IS 3 BP 146 EP 150 PG 5 WC Oncology SC Oncology GA 343GV UT WOS:000088694100005 PM 10882329 ER PT J AU Tikoo, A Shakri, R Connolly, L Hirokawa, Y Shishido, T Bowers, B Ye, LH Kohama, K Simpson, RJ Maruta, H AF Tikoo, A Shakri, R Connolly, L Hirokawa, Y Shishido, T Bowers, B Ye, LH Kohama, K Simpson, RJ Maruta, H TI Treatment of ras-induced cancers by the F-actin-bundling drug MKT-077 SO CANCER JOURNAL LA English DT Article DE ras; MKT-077; F-actin bundlers; F-actin cappers; tumor suppressors; HSC70; p53 ID BINDING PHOSPHOPROTEIN; PHYSARUM-POLYCEPHALUM; SUBUNIT-B; PROTEIN; PHOSPHORYLATION; TRANSFORMATION; CORTACTIN; VINCULIN; GAP AB A rhodacyanine dye called MKT-077 has shown a highly selective toxicity toward several distinct human malignant cell lines, including bladder carcinoma EJ, and has been subjected to clinical trials for cancer therapy. In the pancreatic carcinoma cell line CRL-1420, but not in normal African green monkey kidney cell line CV-1, it is selectively accumulated in mitochondria. However, both the specific oncogenes responsible for its selective toxicity toward cancer cells, and its target proteins in these cancer cells, still remain to be determined. This study was conducted using normal and ms-transformed NIH 3T3 fibroblasts to determine whether oncogenic ras mutants such as v-Ha-ras are responsible for the selective toxicity of MKT-077 and also to identify its targets, using its derivative called "compound 1" as a specific ligand. We have found that v-Ha-ras is responsible for the selective toxicity of MKT-077 in both in vitro and in vivo. Furthermore, we have identified and affinity purified at least two distinct proteins of 45 kD (p45) and 75 kD (p75), which bind MKT-077 in v-Ha-ras-transformed cells but not in parental normal cells. Microsequencing analysis has revealed that the p45 is a mixture of beta- and gamma-actin, whereas the p75 is HSC70, a constitutive member of the Hsp70 heat shack adenosine triphosphatase family, which inactivates the tumor suppressor p53. MKT-077 binds actin directly, bundles actin filaments by cross-linking, and blocks membrane ruffling. Like a few F-actin-bundling proteins such as HS1, alpha-actinin, and vinculin as well as F-actin cappers such as tensin and chaetoglobosin K (CK), the F-actin-bundling drug MKT-077 suppresses ras transformation by blocking membrane ruffling. These findings suggest that other selective F-actin-bundling/capping compounds are also potentially useful for the chemotherapy of ras-associated cancers. C1 Ludwig Inst Canc Res, Melbourne, Vic 3050, Australia. Fuji Photo Film Co Ltd, Ashigara Res Labs, Kanagawa, Japan. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Gunma Univ, Sch Med, Dept Pharmacol, Gunma, Japan. RP Maruta, H (reprint author), Ludwig Inst Canc Res, Melbourne, Vic 3050, Australia. NR 20 TC 19 Z9 19 U1 1 U2 3 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAY-JUN PY 2000 VL 6 IS 3 BP 162 EP 168 PG 7 WC Oncology SC Oncology GA 343GV UT WOS:000088694100008 PM 10882332 ER PT J AU Childs, RW AF Childs, RW TI Nonmyeloablative allogeneic peripheral blood stem-cell transplantation as immunotherapy for malignant diseases SO CANCER JOURNAL LA English DT Article; Proceedings Paper CT 2nd Oncology Frontiers Conference CY OCT 29-30, 1999 CL ST THOMAS, VIRGIN ISLANDS ID BONE-MARROW TRANSPLANTATION; TUMOR-INFILTRATING LYMPHOCYTES; CHRONIC MYELOGENOUS LEUKEMIA; GRAFT-VERSUS-LEUKEMIA; RECOMBINANT INTERLEUKIN-2; SPONTANEOUS REGRESSION; MYELOABLATIVE THERAPY; METASTATIC MELANOMA; ADVANCED CANCER; BREAST-CANCER C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Childs, RW (reprint author), NHLBI, NIH, Bldg 10,Room 7C-103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 40 TC 13 Z9 14 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAY-JUN PY 2000 VL 6 IS 3 BP 179 EP 187 PG 9 WC Oncology SC Oncology GA 343GV UT WOS:000088694100010 PM 10882334 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI Identification of cancer antigens: Impact on development of cancer immunotherapies SO CANCER JOURNAL LA English DT Article; Proceedings Paper CT 2nd Oncology Frontiers Conference CY OCT 29-30, 1999 CL ST THOMAS, VIRGIN ISLANDS ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; MELANOMA ANTIGEN; METASTATIC MELANOMA; PEPTIDE VACCINE; GENE; CELLS; TYROSINASE; EPITOPE; MART-1 C1 NCI, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, NIH, 900 Rockville Pike,Bldg 10,Room 2b42, Bethesda, MD 20892 USA. NR 37 TC 13 Z9 13 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAY PY 2000 VL 6 SU 3 BP S200 EP S207 PG 8 WC Oncology SC Oncology GA 343GX UT WOS:000088694300002 PM 10874489 ER PT J AU Zhuang, SM Wiseman, RW Soderkvist, P AF Zhuang, SM Wiseman, RW Soderkvist, P TI Mutation analysis of the pRb pathway in 2 ',3 '-dideoxycytidine- and 1,3-butadiene-induced mouse lymphomas SO CANCER LETTERS LA English DT Article DE Rb1; Cdk4; Cend1; pRb pathway; 2 ',3 '-dideoxycytidine; 1,3-butadiene ID CELL-CYCLE CONTROL; RETINOBLASTOMA PROTEIN; GENETIC ALTERATIONS; CDK INHIBITORS; CANCER; MELANOMA; CARCINOGENICITY; P15(INK4B); MICE; P53 AB The pRb pathway plays a key role in controlling the G1/S transition in cell cycle progression. Aberrations of various components of the pRh pathway, such as retinoblastoma protein and its upstream actors including cyclin D1, cyclin dependence kinase-4 and p16/p15 cyclin dependent kinase inhibitors, have been reported in a variety of human tumors. Furthermore, the alterations of retinoblastoma protein and its upstream components often occur in a reciprocal manner. Previously, we have reported frequent inactivation of the Cdkn2a/Cdkn2b loci encoding p16/p15 cyclin dependent kinase inhibitors in a subset of 2',3'-dideoxycytidine- and 1,3-butadiene-induced mouse lymphomas (S.-M. Zhuang, A. Schippert, A. Haugen-Strano, R.W. Wiseman, P. Soderkvist, Inactivation of p16(INK4)-alpha ,p16(INK4a)-beta and p15(INK4b) genes in 2',3'-dideoxycytidine- and 1,3-butadiene-induced lymphomas, Oncogene 16 (1998) 803-808), indicating the involvement of pRb pathway in lymphomagenesis. To investigate whether alteration of other components in pRb pathway is an alternative mechanism underlying the development of these chemically induced lymphomas, we have examined the genetic status of Rb1, Ccnd1 and Cdk4 genes that encode retinoblastoma protein, cyclin D1 and cyclin dependence kinase-4, respectively. Gross alterations of the Rb1, Ccnd1, and Cdk4 genes were not detected by Southern analysis in any of the tumors examined. In addition, single-strand conformation analysis failed to reveal point mutations in the Cdk4 amino terminal domain that is important for its association with Cdkn2a gene products. These results indicate that the mechanisms underlying the development of 2',3'-dideoxycytidine- and 1,3-butadiene-induced lymphomas involve inactivation of p16/p15 cyclin-dependent kinase inhibitors but not genomic alterations of the Rb1, Ccnd1 and Cdk4 genes. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Linkoping Univ, Fac Hlth Sci, Dept Biomed & Surg, Div Cell Biol, S-58185 Linkoping, Sweden. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Zhuang, SM (reprint author), Linkoping Univ, Fac Hlth Sci, Dept Biomed & Surg, Div Cell Biol, S-58185 Linkoping, Sweden. NR 24 TC 1 Z9 2 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 1 PY 2000 VL 152 IS 2 BP 129 EP 134 DI 10.1016/S0304-3835(99)00447-4 PG 6 WC Oncology SC Oncology GA 396WT UT WOS:000166661300003 PM 10773403 ER PT J AU Hurwitz, AA Foster, BA Kwon, ED Truong, T Choi, EM Greenberg, NM Burg, MB Allison, JP AF Hurwitz, AA Foster, BA Kwon, ED Truong, T Choi, EM Greenberg, NM Burg, MB Allison, JP TI Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade SO CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; T-CELL RESPONSE; ANTITUMOR IMMUNITY; TUMOR-CELLS; DENDRITIC CELLS; GENE-TRANSFER; IN-VIVO; COSTIMULATION; VACCINATION; CD40 AB We have previously shown that antibodies to CTLA-4, an inhibitory receptor on T cells, can be effective at inducing regression of transplantable murine tumors. In this study, we demonstrate that an effective immune response against primary prostate tumors in transgenic (TRAMP) mice can be elicited using a strategy that combines CTLA-4 blockade and an irradiated tumor cell vaccine. Treatment of TRAMP mice at 14 Reeks of age resulted in a significant reduction in tumor incidence (15% versrus control, 75%), as assessed 2 months after treatment. Histopathological analysis revealed that treated mice had a lower tumor grade with significant accumulation of inflammatory cells in interductal spaces when treated with anti-CTLA-4 and a granulocyte-macrophage colony-stimulating factor-expressing vaccine, Vaccination of nontransgenic mice with this regimen resulted in marked prostatitis accompanied by destruction of epithelium, indicating that the immune response was, at feast in part, directed against normal prostate antigens, These findings demonstrate that this combinatorial treatment can elicit a potent antiprostate response and suggest potential of this approach for treatment of prostate cancer. C1 Univ Calif Berkeley, Canc Res Lab, Berkeley, CA 94720 USA. Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX USA. Loyola Univ, Sch Med, Dept Urol, Maywood, IL 60153 USA. Loyola Univ, Sch Med, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Allison, JP (reprint author), SUNY Upstate Med Univ, Dept Microbiol & Immunol, 766 Irving Ave, Syracuse, NY 13210 USA. NR 33 TC 279 Z9 298 U1 1 U2 11 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 MAY 1 PY 2000 VL 60 IS 9 BP 2444 EP 2448 PG 5 WC Oncology SC Oncology GA 311AM UT WOS:000086862100023 PM 10811122 ER PT J AU Sanchez-Prieto, R Rojas, JM Taya, Y Gutkind, JS AF Sanchez-Prieto, R Rojas, JM Taya, Y Gutkind, JS TI A role for the p38 mitogen-activated protein kinase pathway in the transcriptional activation of p53 on genotoxic stress by chemotherapeutic agents SO CANCER RESEARCH LA English DT Article ID DAMAGE-INDUCED PHOSPHORYLATION; SIGNAL-TRANSDUCTION PATHWAY; DNA-DAMAGE; ENHANCED PHOSPHORYLATION; IONIZING-RADIATION; GAMMA-RADIATION; GENE-EXPRESSION; WILD-TYPE; IN-VITRO; APOPTOSIS AB The tumor suppressor p53 plays a central role in sensing damaged DNA and orchestrating the consequent cellular responses. However, how DNA damage leads to the activation of p53 is still poorly understood. In this study, we have found that the p38 mitogen-activated protein kinase (MAPK) plays a key role in the activation of p53 by genotoxic stress when provoked by chemotherapeutic agents. Indeed, we found that blockade of p38 prevents stimulation of the transcriptional activity of p53 and that activation of the p38 pathway is sufficient to stimulate p53 function. Furthermore, we observed that p38 does not affect the accumulation of p53 in response to DNA damage or its nuclear localization. In contrast, we observed that p38 associates physically with p53, and we provide evidence that this MAPK phosphorylates the NH2-terminal transactivation domain of p5.7 in serine 33, thereby stimulating its functional activity. Moreover, inhibition of the p38 MAPK diminished the apoptotic fraction of cells exposed to chemotherapeutic agents and increased cell survival, thus suggesting a role for p38 activation in the apoptotic response to genotoxic stress when elicited by drugs used in cancer therapy. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Natl Canc Ctr, Res Inst, Tokyo 104, Japan. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 211, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; Sanchez-Prieto, Ricardo/B-6877-2008 OI Sanchez-Prieto, Ricardo/0000-0003-0882-9780 NR 55 TC 179 Z9 188 U1 1 U2 7 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 MAY 1 PY 2000 VL 60 IS 9 BP 2464 EP 2472 PG 9 WC Oncology SC Oncology GA 311AM UT WOS:000086862100026 PM 10811125 ER PT J AU Acs, P Beheshti, M Szallasi, Z Li, LW Yuspa, SH Blumberg, PM AF Acs, P Beheshti, M Szallasi, Z Li, LW Yuspa, SH Blumberg, PM TI Effect of a tyrosine 155 to phenylalanine mutation of protein kinase C delta on the proliferative and tumorigenic properties of NIH 3T3 fibroblasts SO CARCINOGENESIS LA English DT Article ID HIGH-AFFINITY RECEPTOR; PKC-DELTA; SIGNAL-TRANSDUCTION; RAT FIBROBLASTS; PHOSPHORYLATION; ACTIVATION; CELLS; EXPRESSION; GROWTH; EPSILON AB Tyrosine phosphorylation has emerged as an important mechanism in the regulation of enzyme function. In this paper, we describe a mutant of PKC delta altered at a single tyrosine residue which has the opposite effect compared with mild-type PKC delta on the growth characteristics of NIH 3T3 cells. Overexpression of wild-type PKC delta results in a decreased growth rate and a lower cell density at confluency. On the other hand, overexpression of PKC delta with a mutation from tyrosine to phenylalanine at position 155 results in a significantly higher rate of growth and a higher density at confluency compared with vector controls, Moreover, these cells are able to grow in soft agar and to form tumors in nude mice. In contrast to kinase negative PKC constructs, this mutant maintains in vitro kinase activity and shows a subcellular localization and a translocation pattern that are similar to those of the wild-type PKC delta, Whether the altered biological effect is due to the missing phosphorylation on tyrosine or the mutation from tyrosine to phenylalanine per se remains under investigation. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. RP Blumberg, PM (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NR 25 TC 29 Z9 30 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 MAY PY 2000 VL 21 IS 5 BP 887 EP 891 DI 10.1093/carcin/21.5.887 PG 5 WC Oncology SC Oncology GA 315WZ UT WOS:000087137100005 PM 10783308 ER PT J AU Chen, KH Srivastava, DK Singhal, RK Jacob, S Ahmed, AE Wilson, SH AF Chen, KH Srivastava, DK Singhal, RK Jacob, S Ahmed, AE Wilson, SH TI Modulation of base excision repair by low density lipoprotein, oxidized low density lipoprotein and antioxidants in mouse monocytes SO CARCINOGENESIS LA English DT Article ID DNA-POLYMERASE-BETA; HERITABLE HYPERLIPIDEMIC RABBIT; SMOOTH-MUSCLE CELLS; OXIDATIVE MODIFICATION; UP-REGULATION; VITAMIN-C; ATHEROSCLEROSIS; DAMAGE; 8-HYDROXYGUANINE; MACROPHAGES AB In the present study, we found that oxidized low density lipoprotein, but not low density lipoprotein, down-regulated base excision repair activity in extracts of mouse monocyte cell line PU5-1.8. An enzyme required in this pathway, DNA polymerase beta, was also down-regulated, In contrast, treatment of monocytes with a combination of ascorbate and alpha-tocopherol up-regulated base excision repair activity and expression of DNA polymerase beta, Go-treatment of monocytes with antioxidants plus oxidized low density lipoprotein prevented down-regulation by oxidized low density lipoprotein. Oxidative DNA damage, as measured by 8-hydroxyguanine accumulation in genomic DNA, was found in cells treated with oxidized tow density lipoprotein; 8-hydroxyguannine was not found in the cells treated with lon density lipoprotein, antioxidants or oxidized low density lipoprotein plus antioxidants, These results establish a linkage between the DNA base excision repair pathway, oxidative DNA damage and oxidized low density lipoprotein treatment in mouse monocytes, Since oxidized low density lipoprotein is implicated in chronic disease conditions such as atherogenesis, these findings facilitate understanding of genetic toxicology mechanisms related to human health and disease. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77555 USA. New York Hosp, Cornell Med Ctr, Dept Pediat, New York, NY 10021 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [ES06492] NR 50 TC 23 Z9 23 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 MAY PY 2000 VL 21 IS 5 BP 1017 EP 1022 DI 10.1093/carcin/21.5.1017 PG 6 WC Oncology SC Oncology GA 315WZ UT WOS:000087137100024 PM 10783327 ER PT J AU Bialkowska, A Bialkowski, K Gerschenson, M Diwan, BA Jones, AB Olivero, OA Poirier, MC Anderson, LM Kasprzak, S Sipowicz, MA AF Bialkowska, A Bialkowski, K Gerschenson, M Diwan, BA Jones, AB Olivero, OA Poirier, MC Anderson, LM Kasprzak, S Sipowicz, MA TI Oxidative DNA damage in fetal tissues after transplacental exposure to 3 '-azido-3 '-deoxythymidine (AZT) SO CARCINOGENESIS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE; ZIDOVUDINE TREATMENT; MITOCHONDRIAL-DNA; RISK-FACTORS; MOUSE-LIVER; IN-UTERO; MICE; TRANSMISSION; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE AB The nucleoside analogue 3'-azido-3'-deoxythymidine (AZT) has been used successfully to reduce the incidence of transplacental and perinatal transmission of the HIV virus. However, prolonged treatment with high doses of AZT is utilized in this therapy, and AZT has been found to be a perinatal carcinogen in mice, Any possible perinatal carcinogenic side effects in the human can best be managed if the mechanism is understood. AZT targets mitochondria and might cause increased intracellular production of reactive oxygen species (ROS), We tested whether transplacental AZT may cause oxidative damage in nuclear DNA of fetal tissues. CD-1 Swiss pregnant mice were treated with the transplacental carcinogenesis regimen (25 mg/day AZT, for gestation days 12-18) and tissues collected on the day of birth. Significant increases in 8-oxo-2'-deoxyguanosine (8-oxo-dG) were found in the livers, a target tissue for transplacental carcinogenesis, and in the kidneys. A nonsignificant increase occurred in brain, with no change in lung. Tissues were also obtained from fetal patas monkeys (Erythrocebus patas), whose mothers had received 10 mg AZT/day during the last half of gestation. Although limited numbers of samples were available, possible increases in 8-oxo-dG were noted, relative to controls, for placenta and for fetal lung and brain (P = 0.055 for treatment-related increases in these tissues). These results suggest that an increase in reactive oxygen species could contribute to the mechanism of transplacental carcinogenesis by AZT in mice, and that this may also occur in primates. C1 NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick Inc, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Sch Med Sci, Dept Clin Biochem, Bydgoszcz, Poland. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP Anderson, LM (reprint author), NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RI Bialkowski, Karol/E-2328-2014; Bialkowska, Aneta/G-9280-2014 FU NCI NIH HHS [N01-CO-56000] NR 29 TC 59 Z9 61 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2000 VL 21 IS 5 BP 1059 EP 1062 DI 10.1093/carcin/21.5.1059 PG 4 WC Oncology SC Oncology GA 315WZ UT WOS:000087137100030 PM 10783333 ER PT J AU Shin, Y Daly, JW Choi, OH AF Shin, Y Daly, JW Choi, OH TI Diverse effects of sphingosine on calcium mobilization and influx in differentiated HL-60 cells SO CELL CALCIUM LA English DT Article ID PROTEIN-KINASE-C; PHOSPHOLIPASE C-CA2+ SYSTEM; INTRACELLULAR CA2+ STORES; COUPLED RECEPTOR EDG-1; HUMAN NEUTROPHILS; LEUKEMIA-CELLS; RBL-2H3 CELLS; INOSITOL TRISPHOSPHATE; DIFFUSIBLE MESSENGER; BINDING PROTEINS AB Sphingosine induces a biphasic increase in cytosolic-free Ca2+ ([Ca2+](i)) with an initial peak followed by a sustained increase in HL-60 cells differentiated into neutrophil-like cells. The initial peak is not affected by the presence of ethylene glycol bis (beta-aminoethyl ether) N, N, N', N-tetraacetic acid (EGTA) in the buffer and appears to be dependent on conversion of sphingosine to sphingosine -1-phosphate (S1P) by sphingosine kinase, since it is blocked by the presence of N, N-dimethylsphingosine (DMS), which, like sphingosine, causes a sustained increase itself. The sustained increase that is elicited by sphingosine or DMS is abolished by the presence of EGTA in the buffer. The sustained sphingosine-induced Ca2+ influx does not appear due to Ca2+ influx through store-operated Ca2+ (SOC) channels, since the influx is not inhibited by SKF 96365, nor is it augmented by loperamide. In addition, sphingosine and DMS attenuate the Ca2+ influx through SOC channels that occurs after depletion of intracellular stores by ATP or thapsigargin. Both the initial peak and the sustained increase in [Ca2+](i) elicited by sphingosine can be blocked by phorbol 12-myristate 13-acetate (PMA)-elicited activation of protein kinase C. Thus, in HL-60 cells sphingosine causes a mobilization of Ca2+ from intracellular Ca2+ stores, which requires conversion to S1P, while both sphingosine and DMS elicit a Ca2+ influx through an undefined Ca2+ channel and cause a blockade of SOC channels. (C) Harcourt Publishers Ltd 2000. C1 Natl Inst Diabet & Digest Disorder Kidney, Bioorgan Chem Lab, NIH, Bethesda, MD USA. RP Choi, OH (reprint author), Meharry Med Coll, Dept Biochem, Basic Sci Bldg,Room 2126,1005 DB Todd Blvd, Nashville, TN 37208 USA. FU NCRR NIH HHS [RR03032] NR 61 TC 16 Z9 18 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD MAY PY 2000 VL 27 IS 5 BP 269 EP 280 DI 10.1054/ceca.2000.0118 PG 12 WC Cell Biology SC Cell Biology GA 334UH UT WOS:000088203700003 PM 10859593 ER PT J AU Takeda, K Yu, ZX Qian, S Chin, TK Adelstein, RS Ferrans, VJ AF Takeda, K Yu, ZX Qian, S Chin, TK Adelstein, RS Ferrans, VJ TI Nonmuscle myosin II localizes to the Z-lines and intercalated discs of cardiac muscle and to the Z-lines of skeletal muscle SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE nonmuscle myosin II-A and II-B; indirect immunofluorescence; confocal microscopy; cardiac development; human; mice ID HEAVY-CHAIN EXPRESSION; SMOOTH-MUSCLE; DIFFERENTIAL LOCALIZATION; IN-VITRO; MYOFIBRILLOGENESIS; CELLS; CARDIOMYOCYTES; ISOFORMS; CLONING; KINASE AB To understand the role of nonmuscle myosin II in cardiac and skeletal muscle, we used a number of polyclonal antibodies, three detecting nonmuscle myosin heavy chain II-B (NMHC II-B) and two detecting NMHC II-A, to examine the localization of these two proteins in fresh-frozen, acetone-fixed sections of normal human and mouse hearts and human skeletal muscles. Results were similar in both species and were confirmed by examination of fresh-frozen sections of human hearts subjected to no fixation or to treatment with either 4% p-formaldehyde or 50% glycerol. NMHC II-B was diffusely distributed in the cytoplasm of cardiac myocytes during development, but after birth it was localized to the Z-lines and intercalated discs. Dual labeling showed almost complete colocalization of NMHC II-B with alpha-actinin. Whereas endothelial cells, smooth muscle cells and fibroblasts showed strong immunoreactivity for NMHC II-A and NMHC II-B, cardiac myocytes only showed reactivity for the latter. The Z-lines of human skeletal muscle cells, in contrast to those of cardiac myocytes, gave positive reactions for both NMHC II-A and NMHC II-B. The presence of a motor protein in the Z-lines and intercalated discs raises the possibility that these structures may play a more dynamic role in the contraction/relaxation mechanism of cardiac and skeletal muscle than has been previously suspected. (C) 2000 Wiley-Liss, Inc. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. E Tennessee State Univ, James H Quillen Coll Med, Johnson City, TN 37614 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Room 8N202,10 Ctr Dr,MSC 1762, Bethesda, MD 20892 USA. OI Adelstein, Robert/0000-0002-8683-2144 NR 22 TC 56 Z9 58 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD MAY PY 2000 VL 46 IS 1 BP 59 EP 68 DI 10.1002/(SICI)1097-0169(200005)46:1<59::AID-CM6>3.0.CO;2-Q PG 10 WC Cell Biology SC Cell Biology GA 321LD UT WOS:000087456200006 PM 10842333 ER PT J AU Resnick, SM Goldszal, AF Davatzikos, C Golski, S Kraut, MA Metter, EJ Bryan, RN Zonderman, AB AF Resnick, SM Goldszal, AF Davatzikos, C Golski, S Kraut, MA Metter, EJ Bryan, RN Zonderman, AB TI One-year age changes in MRI brain volumes in older adults SO CEREBRAL CORTEX LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 06-12, 1997 CL WAIKOLOA, HAWAII SP Amer Coll Neuropsychopharmacol ID VISUAL-RETENTION TEST; HUMAN CEREBRAL-CORTEX; WHITE-MATTER CHANGES; ALZHEIMERS-DISEASE; SEX-DIFFERENCES; TEMPORAL-LOBE; CARDIOVASCULAR HEALTH; LONGITUDINAL CT; AGING BRAIN; GRAY-MATTER AB Longitudinal studies indicate that declines in cognition and memory accelerate after age 70 years. The neuroanatomic and neurophysiologic underpinnings of cognitive change are unclear, as there is little information on longitudinal brain changes. We are conducting a longitudinal neuroimaging study of nondemented older participants in the Baltimore Longitudinal Study of Aging. This report focuses on age and sex differences in brain structure measured by magnetic resonance imaging during the first two annual evaluations. Cross sectional results from 116 participants aged 59-85 years reveal significantly larger ventricular volumes and smaller gray and white matter volumes in older compared with younger participants and in men compared with women. Regional brain volumes show that the effects of age and sex are not uniform across brain regions. Age differences are greatest for the parietal region. Sex differences tend to be larger for frontal and temporal than parietal and occipital regions. Longitudinal analysis demonstrates an increase of 1526 mm(3) in ventricular volume over 1 year, but no detectable change in total or regional brain volumes. Definition of the pattern and rate of longitudinal brain changes will facilitate the detection of pathological brain changes, which may be predictors of dementia. C1 NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. RP Resnick, SM (reprint author), NIA, Lab Personal & Cognit, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Bryan, R. Nick/P-1661-2014; OI Zonderman, Alan B/0000-0002-6523-4778 NR 44 TC 324 Z9 328 U1 1 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAY PY 2000 VL 10 IS 5 BP 464 EP 472 DI 10.1093/cercor/10.5.464 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 310AG UT WOS:000086802700003 PM 10847596 ER PT J AU Boroojerdi, B Bushara, KO Corwell, B Immisch, I Battaglia, F Muellbacher, W Cohen, LG AF Boroojerdi, B Bushara, KO Corwell, B Immisch, I Battaglia, F Muellbacher, W Cohen, LG TI Enhanced excitability of the human visual cortex induced by short-term light deprivation SO CEREBRAL CORTEX LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; CHARLES-BONNET-SYNDROME; OCCIPITAL CORTEX; DARK-ADAPTATION; STRIATE CORTEX; BLIND HUMANS; PLASTICITY; BRAIN; HALLUCINATIONS; MONKEYS AB Long term deprivation of visual input for several days or weeks leads to marked changes in the excitability and function of the occipital cortex. The time course of these changes is poorly understood. In this study, we addressed the question whether a short period of light deprivation (minutes to a few hours) can elicit such changes in humans. Noninvasive transcranial magnetic stimulation (TMS) of the human occipital cortex can evoke the perception of flashes or spots of light (phosphenes). To assess changes in visual cortex excitability following light deprivation, we measured the minimum intensity of stimulation required to elicit phosphenes (phosphene threshold) and the number of phosphenes elicited by different TMS stimulus intensities (stimulus-response curves). A reduced phosphene threshold was detected 45 min after the onset of light deprivation and persisted for the entire deprivation period (180 min). Following re-exposure to light, phosphene thresholds returned to predeprivation values over 120 min. Stimulus-response curves were significantly enhanced in association with this intervention. In a second experiment, we studied the effects of light deprivation on functional magnetic resonance imaging (fMRI) signals elicited by photic stimulation. fMRI results showed increased visual cortex activation after 60 min of light deprivation that persisted following 30 min of re-exposure to light. Our results demonstrated a substantial increase in visual cortex excitability. These changes may underlie behavioral gains reported in humans and animals associated with light deprivation. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bldg 10,Room 5N 234,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 42 TC 141 Z9 143 U1 3 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAY PY 2000 VL 10 IS 5 BP 529 EP 534 DI 10.1093/cercor/10.5.529 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 310AG UT WOS:000086802700009 PM 10847602 ER PT J AU Rouhani, F Paone, G Smith, NK Krein, P Barnes, P Brantly, ML AF Rouhani, F Paone, G Smith, NK Krein, P Barnes, P Brantly, ML TI Lung neutrophil burden correlates with increased proinflammatory cytokines and decreased lung function in individuals with alpha(1)-antitrypsin deficiency SO CHEST LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Univ Coll Med, Gainesville, FL USA. NR 0 TC 21 Z9 23 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2000 VL 117 IS 5 SU 1 BP 250S EP 251S DI 10.1378/chest.117.5_suppl_1.250S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 316PY UT WOS:000087178200021 ER PT J AU Martin, LD Norford, D Voynow, J Adler, KB AF Martin, LD Norford, D Voynow, J Adler, KB TI Response of human airway epithelium in vitro to inflammatory mediators - Dependence on the state of cellular differentiation SO CHEST LA English DT Meeting Abstract C1 N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Durham, NC USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2000 VL 117 IS 5 SU 1 BP 267S EP 267S DI 10.1378/chest.117.5_suppl_1.267S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 316PY UT WOS:000087178200028 ER PT J AU Hurd, SS AF Hurd, SS TI International efforts directed at attacking the problem of COPD SO CHEST LA English DT Article; Proceedings Paper CT Workshop on COPD - Working Towards a Greater Understanding CY JUN, 1999 CL ASPEN, COLORADO DE COPD; diagnosis; Global Initiative for Obstructive Lung Disease; worldwide prevalence AB COPD is the only leading cause of death that is increasing in prevalence worldwide. The lack of international standardization in the diagnosis of COPD means that intercountry comparisons are difficult. This review highlights the Global Initiative for Obstructive Lung Disease, a program aimed at focusing attention on the importance of COPD as a global health problem, and designing and implementing consistent international strategies for effective prevention, diagnosis, and treatment. C1 NHLBI, Div Lung Dis, Bethesda, MD USA. RP Hurd, SS (reprint author), POB 34262, Bethesda, MD 20827 USA. NR 2 TC 27 Z9 27 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2000 VL 117 IS 5 SU 2 BP 336S EP 338S DI 10.1378/chest.117.5_suppl_2.336S PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 316PZ UT WOS:000087178300004 PM 10843973 ER PT J AU Earle, CC Venditti, LN Neumann, PJ Gelber, RD Weinstein, MC Potosky, AL Weeks, JC AF Earle, CC Venditti, LN Neumann, PJ Gelber, RD Weinstein, MC Potosky, AL Weeks, JC TI Who gets chemotherapy for metastatic lung cancer? SO CHEST LA English DT Article DE chemotherapy; non-small cell lung cancer; practice patterns ID MULTICENTER RANDOMIZED TRIAL; NEGATIVE BREAST-CANCER; 2 RURAL STATES; PROSTATE-CANCER; SOCIOECONOMIC-STATUS; TREATMENT PATTERNS; OLDER WOMEN; CARE; RACE; MANAGEMENT AB Study objectives: To determine the prevalence and factors associated with chemotherapy use in elderly patients presenting with advanced lung cancer. Design: A retrospective cohort study using administrative data. Setting and patients: We analyzed the medical bills for the 6,308 Medicare patients > 65 years old with diagnosed stage IV non-small cell lung cancer (NSCLC) in the 11 SEER (survival, epidemiology, and end results) regions between 1991 and 1993, The main outcome measure, chemotherapy administration, was identified by the relevant medical billing codes, Patient sociodemographic and disease characteristics were obtained from the SEER database and census data. Results: Almost 22% of patients received chemotherapy at some time for their metastatic NSCLC. As expected, younger patients and those with fewer comorbid conditions were more likely to receive chemotherapy. However, several nonmedical factors, such as nonblack race, higher socioeconomic status, treatment in a teaching hospital, and living in the Seattle/Puget Sound or Los Angeles SEER regions, also significantly increased a patient's likelihood of receiving chemotherapy, Conclusion: Compared to previous reports, the prevalence of chemotherapy use for advanced NSCLC appears to be increasing, However, despite uniform health insurance coverage, there is wide variation in the utilization of palliative chemotherapy among Medicare patients, and nonmedical factors are strong predictors of whether a patient receives chemotherapy. While it is impossible to know the appropriate rate of usage, nonmedical factors should only influence a patient's likelihood of receiving treatment if they reflect patient treatment preference. Research to further clarify the costs, benefits, and patient preferences for chemotherapy in this patient population is warranted in order to minimize the effect of nonmedical biases on management decisions. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Program Econ Evaluat Med Technol, Boston, MA 02115 USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. RP Earle, CC (reprint author), Dana Farber Canc Ctr, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 72663] NR 60 TC 175 Z9 177 U1 2 U2 6 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2000 VL 117 IS 5 BP 1239 EP 1246 DI 10.1378/chest.117.5.1239 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 315DL UT WOS:000087097300008 PM 10807806 ER PT J AU Leslie, LK Landsverk, J Horton, MB Ganger, W Newton, RR AF Leslie, LK Landsverk, J Horton, MB Ganger, W Newton, RR TI The heterogeneity of children and their experiences in kinship care SO CHILD WELFARE LA English DT Article ID FOSTER-CARE; NEW-YORK; ILLINOIS AB Increasingly, children in need of out-of-home care are being placed in kinship care, yet few studies have followed their placement histories longitudinally to determine if these children constitute a homogeneous group or heterogeneous subgroups. This study of 484 children in kinship care in San Diego County, California, indicates that children in kinship care have markedly different sociodemographic and maltreatment histories, as well as heterogeneous placement experiences. C1 Childrens Hosp San Diego, Child & Family Res Grp, San Diego, CA 92123 USA. Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. NIMH, Ctr Res Child & Adolescent Mental Hlth Serv, San Diego, CA USA. Childrens Hosp San Diego, Ctr Child Protect, San Diego, CA 92123 USA. San Diego State Univ, Sch Social Work, San Diego, CA 92182 USA. Childrens Hosp San Diego, Community Programs, San Diego, CA 92123 USA. Childrens Hosp San Diego, Ctr Healthier Communities, San Diego, CA 92123 USA. Calif State Univ Fullerton, Dept Sociol, Fullerton, CA 92634 USA. RP Leslie, LK (reprint author), Childrens Hosp San Diego, Child & Family Res Grp, 3020 Childrens Way,MC 5033, San Diego, CA 92123 USA. FU NIMH NIH HHS [K08 MH064816, R01 MH059672] NR 27 TC 24 Z9 24 U1 0 U2 0 PU CHILD WELFARE LEAGUE AMER, INC PI WASHINGTON PA 440 FIRST ST, NW, THIRD FLOOR, WASHINGTON, DC 20001-2085 USA SN 0009-4021 J9 CHILD WELFARE JI Child Welf. PD MAY-JUN PY 2000 VL 79 IS 3 BP 315 EP 334 PG 20 WC Family Studies; Social Work SC Family Studies; Social Work GA 554YR UT WOS:000175765200004 PM 10813086 ER PT J AU Schnizlein-Bick, CT Spritzler, J Wilkening, CL Nicholson, JKA O'Gorman, MRG AF Schnizlein-Bick, CT Spritzler, J Wilkening, CL Nicholson, JKA O'Gorman, MRG CA Site Investigators NIAID DAIDS New Technologies Evalu TI Evaluation of TruCount absolute-count tubes for determining CD4 and CD8 cell numbers in human immunodeficiency virus-positive adults SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID FLOW-CYTOMETRY; PERIPHERAL-BLOOD; HEMATOLOGY; INFECTION; LYMPHOCYTES AB A single-platform technology that uses an internal bead standard and three-color flow cytometry to determine CD4 and CD8 absolute counts was evaluated for reproducibility and agreement. Values obtained using TruCount absolute-count tubes were compared to those obtained using a two-color predicate methodology. Sixty specimens from human immunodeficiency virus type 1-infected donors were shipped to five laboratories, Each site also analyzed replicates of 14 human immunodeficiency virus type 1-infected local specimens at 6 h and again at 24 h, The interlaboratory variability was significantly less with TruCount (median difference in percent coefficient of variation [%CV] between the two methods was -8% and-3% for CD4 and CD8, respectively) than with the predicate method. Intralaboratory variability was smaller, with a median difference in %CV of -1% for both CD4 and CD8 with 6-h samples and -2% and -3% for CD4 and CD8, respectively, with 24-h samples. Use of TruCount for shipped samples resulted in a median CD4 count change of 7 cells (50th estimated percentile) when all laboratories and CD4 strata were combined. For on-site samples, the median CD4 count change was 10 CD4 cells for 6-h samples and 2 CD4 cells for 24-h samples, Individual site biases occurred in both directions and cancelled each other when the data were combined for all laboratories, Thus, the combined data showed a smaller change in median CD4 count than what may have occurred at an individual site. In summary, the use of TruCount decreased both the inter- and intralaboratory variability in determining absolute CD4 and CD8 counts. C1 Indiana Univ, Sch Med, Dept Med Infect Dis, Indianapolis, IN 46202 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02146 USA. Ctr Dis Control, Natl Ctr Infect Dis, Div HIV AIDS, Atlanta, GA 30333 USA. Northwestern Univ, Childrens Mem Hosp, Sch Med, Chicago, IL 60614 USA. Northwestern Univ, Dept Pediat, Sch Med, Chicago, IL 60614 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Childrens Hosp Philadelphia, Philadelphia, PA USA. Hlth Canada, LCDC, Bur HIV AIDS & STD, Ottawa, ON K1A 0L2, Canada. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ N Carolina, Chapel Hill, NC 27515 USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. RP Schnizlein-Bick, CT (reprint author), Indiana Univ, Sch Med, Dept Med Infect Dis, 1001 W 10th St,Room OPW 430, Indianapolis, IN 46202 USA. FU NIAID NIH HHS [N0-AI-45175] NR 17 TC 85 Z9 88 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAY PY 2000 VL 7 IS 3 BP 336 EP 343 DI 10.1128/CDLI.7.3.336-343.2000 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 311FB UT WOS:000086873100003 PM 10799443 ER PT J AU Reimann, KA O'Gorman, MRG Spritzler, J Wilkening, CL Sabath, DE Helm, K Campbell, DE AF Reimann, KA O'Gorman, MRG Spritzler, J Wilkening, CL Sabath, DE Helm, K Campbell, DE CA NIAID DAIDS New Technologies Evalu TI Multisite comparison of CD4 and CD8 T-lymphocyte counting by single- versus multiple-platform methodologies: evaluation of Beckman Coulter flow-count fluorospheres and the tetraONE system SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERIPHERAL-BLOOD; CYTOMETRY; AIDS; ANTICOAGULANT; QUANTITATION; ENUMERATION; HEMATOLOGY; DISEASE AB New analytic methods that permit absolute CD4 and CD8 T-cell determinations to be performed entirely on the flow cytometer have the potential for improving assay precision and accuracy, In a multisite trial, we compared two different single-platform assay methods with a predicate two color assay in which the absolute lymphocyte count was derived by conventional hematology, A two-color method employing lymphocyte light scatter gating and Beckman Coulter Flow-Count fluorospheres for absolute counting produced within-laboratory precision equivalent to that of the two-color predicate method, as measured by coefficient of variation of replicate measurements. The fully automated Beckman Coulter tetraONE System four-color assay employing CD45 lymphocyte gating, automated analysis, and absolute counting by fluorospheres resulted in a small but significant improvement in the within-laboratory precision of CD4 and CD8 cell counts and percentages suggesting that the CD45 lymphocyte gating and automated analysis might have contributed to the improved performance. Both the two-color method employing Flow-Count fluorospheres and the four-color tetraONE System provided significant and substantial improvements in between-laboratory precision of absolute counts, In some laboratories, absolute counts obtained by the single-platform methods showed small but consistent differences relative to the predicate method. Comparison of each laboratory's absolute counts with the five laboratory median value suggested that these differences resulted from a bias in the absolute lymphocyte count obtained from the hematology instrument in some laboratories. These results demonstrate the potential for single-platform assay methods to improve within-laboratory and between-laboratory precision of CD4 and CDS T-cell determinations compared with conventional assay methods. C1 Harvard Univ, Sch Med, Beth Israel Deaconess med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA. Univ Washington, Seattle, WA 98195 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Hlth Canada, Bur HIV AIDS & STD, Ottawa, ON K1A 0L2, Canada. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ N Carolina, Chapel Hill, NC USA. Indiana Univ, Indianapolis, IN 46204 USA. NIAID, DAIDA, NIH, Bethesda, MD 20892 USA. RP Reimann, KA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess med Ctr, Div Viral Pathogenesis, RE-113,POB 15732, Boston, MA 02215 USA. FU NIAID NIH HHS [N0-AI-45175] NR 19 TC 66 Z9 70 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAY PY 2000 VL 7 IS 3 BP 344 EP 351 DI 10.1128/CDLI.7.3.344-351.2000 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 311FB UT WOS:000086873100004 PM 10799444 ER PT J AU Sanada, H Asico, LD Shigetomi, S Tanaka, K Niimura, S Watanabe, H Goldstein, DS Felder, RA AF Sanada, H Asico, LD Shigetomi, S Tanaka, K Niimura, S Watanabe, H Goldstein, DS Felder, RA TI The effect of docarpamine, a dopamine pro-drug, on blood pressure and catecholamine levels in spontaneously hypertensive rats SO CLINICAL AND EXPERIMENTAL HYPERTENSION LA English DT Article; Proceedings Paper CT 35th Annual Scientific Meeting of the Society-for-the-Spontaneously-Hypertensive-Rat (SHR) CY AUG 26-27, 1999 CL SAPPORO, JAPAN SP masaru Minami, Dept Pharmacol, Fac Pharmaceut Sci, Univ Hokkaido, Hlth Sci, Hokkaido, Japan DE dopamine pro-drug; vasopressin; alpha-adrenergic receptor ID ANESTHETIZED RATS; PRODRUG TA-870; VASOPRESSIN; RECEPTOR; STIMULATION; FENOLDOPAM; RELEASE; ACTIVATION; MECHANISMS; QUINPIROLE AB We studied the effects of bolus intravenous injection of the dopamine prodrug, docarpamine (200 mu g/kg), on mean arterial pressure (MAP) and heart rate (HR) in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). In WKY rats (n=18), MAP and HR increased 5 min after docarpamine and then returned to baseline levels within 15 min. In contrast, in SHRs (n=15), MAP and HR gradually increased, reaching a nadir 20 min after injection. Five min after docarpamine, plasma dopamine and 3,4-dihydroxy phenyl acetic (DOPAC) levels increased in both WKY rats (n=5) and SHRs (n=5). The docarpamine-induced changes in MAP and HR in both rat strains (n=5/strain) were blocked by the DI-like antagonist, SCH23390. alpha-Adrenergic (n=4) and vasopressin V-1 (n=3) receptor blockade also abrogated the effects of docarparmine in WKY rats. We conclude that docarpamine differentially affects MAP and HR in WKY and SHRs. In SHRs, the depressor and bradycardiac effects of docarpamine are mediated by D-1-like receptors. In WKY rats, the pressor and tachycardiac responses are caused by an interaction among D-1-like, alpha-adrenergic, and V-1 receptors. C1 Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22903 USA. Fukushima Med Univ, Dept Med 3, Fukushima, Japan. Georgetown Univ, Med Ctr, Dept Med 3, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. NINDS, Clin Neurochem Sect, Clin Neurosci Branch, Bethesda, MD 20892 USA. RP Sanada, H (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22903 USA. FU NHLBI NIH HHS [HL23081]; NIDDK NIH HHS [DK49361, DK44756] NR 36 TC 7 Z9 8 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1064-1963 J9 CLIN EXP HYPERTENS JI Clin. Exp. Hypertens. PD MAY PY 2000 VL 22 IS 4 BP 419 EP 429 DI 10.1081/CEH-100100081 PG 11 WC Pharmacology & Pharmacy; Peripheral Vascular Disease SC Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA 326QF UT WOS:000087745700002 PM 10830753 ER PT J AU Giannakakou, P Fojo, T AF Giannakakou, P Fojo, T TI Discodermolide: Just another microtubule-stabilizing agent? No! A lesson in synergy SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID COMBINATION CHEMOTHERAPY; CELL-DEATH; TAXOL; DYNAMICS; PACLITAXEL; PHOSPHORYLATION; BINDING; CANCER C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NCI, Med Branch, Div Clin Sci, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 22 Z9 24 U1 0 U2 0 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 MAY PY 2000 VL 6 IS 5 BP 1613 EP 1615 PG 3 WC Oncology SC Oncology GA 312LY UT WOS:000086945800003 PM 10815877 ER PT J AU Eder, JP Kantoff, PW Roper, K Xu, GX Bubley, GJ Boyden, J Gritz, L Mazzara, G Oh, WK Arlen, P Tsang, KY Panicali, D Schlom, J Kufe, DW AF Eder, JP Kantoff, PW Roper, K Xu, GX Bubley, GJ Boyden, J Gritz, L Mazzara, G Oh, WK Arlen, P Tsang, KY Panicali, D Schlom, J Kufe, DW TI A phase I trial of a recombinant vaccinia virus expressing prostate-specific antigen in advanced prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; CARCINOEMBRYONIC ANTIGEN; CELL-LINE; MELANOMA; PEPTIDE; PSA; RESTRICTION; GENERATION; PROTEINS; GENES AB A recombinant vaccinia virus encoding human prostate-specific antigen (rV-PSA) was administered as three consecutive monthly doses to 33 men with rising PSA levels after radical prostatectomy, radiation therapy, both, or metastatic. disease at presentation. Dose levels were 2.65 x 10(6), 2.65 x 10(7), and 2.65 x 10(8) plaque forming units. Ten patients who received the highest dose also received 250 mu g/m(2) granulocyte-macrophage colony-stimulating factor (GM-CSF) as an immunostimulatory adjunct. No patient experienced any virus-related effects beyond grade I cutaneous toxicity. Pustule formation and/or erythema occurred after the first dose in all 27 men who received greater than or equal to 2.65 x 10(7) plaque forming units. GM-CSF administration was associated with fevers and myalgias of grade 2 or lower in 9 of 10 patients. PSA levels in 14 of 33 men treated with rV-PSA with or without GM-CSF were stable for at least 6 months after primary immunization. Nine patients remained stable for 11-25 months; six of these remain progression free with stable PSA levels. Immunological studies demonstrated a specific T-cell response to PSA-3, a 9-mer peptide derived from PSA. rV-PSA is safe and can elicit clinical and immune responses, and certain patients remain without evidence of clinical progression for up to 21 months or longer. C1 Brigham & Womens Hosp, Dept Med, Div Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Dept Med,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA 02115 USA. NCI, NIH, Bethesda, MD 20892 USA. Ther Biol Corp, Cambridge, MA 02142 USA. RP Eder, JP (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 1B34, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU NCI NIH HHS [UO-CA62490] NR 30 TC 211 Z9 216 U1 2 U2 8 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 MAY PY 2000 VL 6 IS 5 BP 1632 EP 1638 PG 7 WC Oncology SC Oncology GA 312LY UT WOS:000086945800006 PM 10815880 ER PT J AU Pai-Scherf, LH Carrasquillo, JA Paik, C Gansow, O Whatley, M Pearson, D Webber, K Hamilton, M Allegra, C Brechbiel, M Willingham, MC Pastan, I AF Pai-Scherf, LH Carrasquillo, JA Paik, C Gansow, O Whatley, M Pearson, D Webber, K Hamilton, M Allegra, C Brechbiel, M Willingham, MC Pastan, I TI Imaging and phase I study of In-111- and Y-90-labeled anti-Lewis(Y) monoclonal antibody B3 SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LYMPHOMA; COLORECTAL-CANCER; ANTI-CD20 ANTIBODY; BREAST-CANCER; RADIOIMMUNOTHERAPY; Y-90; BIODISTRIBUTION; DOSIMETRY; CARCINOMA; THERAPY AB B3 is a murine monoclonal antibody (mAb) that recognizes a Lewis(Y) carbohydrate antigen present on the surface of many carcinomas. An imaging and Phase I trial was performed to study the ability of In-111-mAb B3 to image known metastasis and determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), kinetics, and biodistribution of Y-90-mAb B3, Patients (n = 26) with advanced epithelial tumors that express the Lewis' antigen were entered. All patients received 5 mCi of In-111-mAb B3 for imaging. Y-90-mAb B3 doses were escalated from 5 to 25 mCi in 5-mCi increments. In-111-mAb BS and Y-90-mAb B3 were coadministered over a 1-h infusion. Definite tumor imaging was observed in 20 of 26 patients. Sites imaged included lung, liver, bone, and soft tissues. The MTD of Y-90-mAb B3 was determined to be 20 mCi, The DLTs were neutropenia and thrombocytopenia, Tumor doses ranged from 7.7 to 65.1 rad/mCi. In-111- and Y-90-mAb B3 serum pharmacokinetics (n = 23) were found to be similar, The amount of B3 administered (5, 10, and 50 mg) did not alter the pharmatokinetics, Bone marrow biopsies (n = 23) showed 0.0038 +/- 0.0016% of injected dose/gram for In-111-mAb B3 compared to 0.0046 +/- 0.0017% of injected dose/gram for Y-90-mAb B3 (P = 0.009). When given to patients with carcinomas that express the Lewis' antigen, In-111-mAb B3 demonstrated good tumor localization. The MTD of Y-90-mAb B3 is 20 mCi, with myelosuppression as the DLT. Higher doses of radioactivity need to be delivered to achieve an antitumor effect. Humanized mAb B3 is being developed for evaluation in radioimmunotherapy. A clinical trial to explore the use of higher doses of Y-90-mAb B3 with autologous stem cell support is planned. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. Wake Forest Univ, Dept Pathol, Winston Salem, NC 27157 USA. NCI, Dept Nucl Med, Warren G Magnuson Clin Canc Ctr, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Chem Sect, ROB, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 55 TC 29 Z9 29 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 MAY PY 2000 VL 6 IS 5 BP 1720 EP 1730 PG 11 WC Oncology SC Oncology GA 312LY UT WOS:000086945800016 PM 10815890 ER PT J AU Tamm, I Kornblau, SM Segall, H Krajewski, S Welsh, K Kitada, S Scudiero, DA Tudor, G Qui, YH Monks, A Andreeff, M Reed, JC AF Tamm, I Kornblau, SM Segall, H Krajewski, S Welsh, K Kitada, S Scudiero, DA Tudor, G Qui, YH Monks, A Andreeff, M Reed, JC TI Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias SO CLINICAL CANCER RESEARCH LA English DT Article ID APOPTOSIS INHIBITORY PROTEIN; ACUTE MYELOGENOUS LEUKEMIA; PROGRAMMED CELL-DEATH; BACULOVIRAL-INHIBITOR; CASPASES; SURVIVIN; PROTEASES; REPEAT; MOTIF AB Expression of several inhibitor of apoptosis proteins (IAPs) was investigated in the National Cancer Institute panel of 60 human tumor cell lines, and the expression and prognostic significance of one of these, XIAP, was evaluated in 78 previously untreated patients with acute myelogenous leukemia (AML). XIAP and cIAP1 were expressed in most cancer Lines analyzed, with substantial variability in their relative levels, In contrast, NAIP mRNA was not detectable, and cIAP2 was found at the mRNA and protein levels in only 34 (56%) and 5 (8%) of the 60 tumor cell lines analyzed, respectively. Interestingly, XIAP, cIAP1, and cIAP2 mRNA levels did not correlate with protein levels in the tumor lines, indicating posttranscriptional regulation of expression High levels of XIAP protein in tumor cell lines were unexpectedly correlated with sensitivity to some anticancer drugs, particularly cytarabine and other nucleosides, whereas higher level; of cIAP1 protein levels were associated with resistance to several anticancer drugs. The relevance of XIAP to in vivo responses to cytarabine was explored in AML, making correlations with patient outcome (n = 78), Patients with lower levels of XIAP protein had significantly longer survival (median, 133 versus 52.5 weeks; P = 0.05) and a tendency toward longer remission duration (median, 87 versus 52.5 weeks; P = 0.13) than those with higher levels of XIAP. Altogether, these findings show that IAPs are widely but differentially expressed in human cancers and leukemias and suggest that higher XIAP protein levels may have adverse prognostic significance for patients with AML. C1 Burnham Inst, La Jolla, CA 92037 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NIH, Frederick Canc Res & Dev Ctr, Dev Therapeut Program, Frederick, MD USA. RP Reed, JC (reprint author), Burnham Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. FU NCI NIH HHS [5P01CA69381-04, CA-55164-08]; NIA NIH HHS [AG 15402] NR 38 TC 455 Z9 502 U1 1 U2 21 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 MAY PY 2000 VL 6 IS 5 BP 1796 EP 1803 PG 8 WC Oncology SC Oncology GA 312LY UT WOS:000086945800026 PM 10815900 ER PT J AU Tanner, MM Grenman, S Koul, A Johannsson, O Meltzer, P Pejovic, T Borg, A Isola, JJ AF Tanner, MM Grenman, S Koul, A Johannsson, O Meltzer, P Pejovic, T Borg, A Isola, JJ TI Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN BREAST-CANCER; COMPARATIVE GENOMIC HYBRIDIZATION; TYROSINE-PHOSPHATASE PTP1B; DNA FLOW-CYTOMETRY; GENETIC CHANGES; PROGESTERONE; CARCINOMAS; ESTROGEN; OVERREPRESENTATION; OVEREXPRESSION AB DNA amplification at chromosomal region 20q12-q13, which is common in breast cancer, has recently been described also in ovarian tumors. We studied the amplification of the recently identified candidate oncogenes in this region in 24 sporadic, 3 familial and 4 hereditary ovarian carcinomas, and in 8 ovarian cancer cell lines. High-level amplification of at least one of the five nonsyntenic regions at 20q12-q13.2 was found in 13 sporadic (54%) and in all four hereditary tumors. Typically, two or more distinct amplicons (separated by nonamplified DNA) were found coamplified in various combinations. The regions defined by the AIB1 and PTPN1 genes (at 20q12 and 20q13.1, respectively) were amplified in 25% and 29% of the sporadic tumors, also without simultaneous coamplification of other regions. Amplification of AIB1 (a steroid receptor coactivator gene) was associated with estrogen receptor positivity in sporadic ovarian carcinomas (P = 0.01) and showed a tendency to correlate with poor survival of patients. Of the genes amplified in breast cancer, the BTAK gene was amplified in 21%, the MYBL2 gene in 17%, and the ZNF217 gene in 12.5% of the sporadic tumors. The high frequency of gene amplification at 20q12-q13.2 suggests that the genes amplified therein may play a central role in the pathogenesis of sporadic and hereditary ovarian carcinoma. C1 Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. Univ Hosp, FIN-33101 Tampere, Finland. Univ Lund, Dept Oncol, Jubileum Inst, S-22185 Lund, Sweden. Univ Turku, Dept Biochem Med, FIN-20520 Turku, Finland. Turku Univ, Cent Hosp, Dept Obstet & Gynecol, FIN-20520 Turku, Finland. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06520 USA. RP Tanner, MM (reprint author), Univ Tampere, Inst Med Technol, Canc Genet Lab, POB 607, FIN-33101 Tampere, Finland. NR 27 TC 244 Z9 254 U1 1 U2 5 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 MAY PY 2000 VL 6 IS 5 BP 1833 EP 1839 PG 7 WC Oncology SC Oncology GA 312LY UT WOS:000086945800031 PM 10815905 ER PT J AU McShane, LM Aamodt, R Cordon-Cardo, C Cote, R Faraggi, D Fradet, Y Grossman, HB Peng, A Taube, SE Waldman, FM AF McShane, LM Aamodt, R Cordon-Cardo, C Cote, R Faraggi, D Fradet, Y Grossman, HB Peng, A Taube, SE Waldman, FM CA Natl Canc Inst Bladder Tumor Marke TI Reproducibility of p53 immunohistochemistry in bladder tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID NUCLEAR OVEREXPRESSION; DISEASE PROGRESSION; CANCER; MUTATIONS; EXPRESSION; CARCINOMA; PROTEIN; GENE; ACCUMULATION AB The National Cancer Institute Bladder Tumor Marker Network conducted a study to evaluate the reproducibility of immunohistochemistry for measuring p53 expression in bladder tumors, Fifty paraffin blocks (10 from each of the five network institutions) were chosen at random from among high-grade invasive primary bladder tumors. Two sections from each block were sent to each laboratory for staining and scoring, and then all sections were randomly redistributed among the laboratories for a second scoring. Intra- and interlaboratory reproducibility was assessed with regard to both staining and scoring, For overall assessments of p53 positivity, the results demonstrated that intralaboratory reproducibility was quite good. Concordance across the five participating laboratories was high for specimens exhibiting no or minimal nuclear immunostaining of tumor cells or high percentages of tumor cells with nuclear immunoreactivities. However, there was a reduced level of concordance on specimens with percentages of stained tumor cells in an intermediate range. The discordancies mere due mainly to staining differences in one of the five laboratories and scoring differences in another laboratory. These results indicate that some caution must be used in comparing results across studies from different groups. Standardization of staining protocols and selection of a uniform threshold for binary interpretation of results may improve assay reproducibility between laboratories. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ So Calif, Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Univ Haifa, IL-31905 Haifa, Israel. Univ Laval, Quebec City, PQ G1R 2J6, Canada. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Emmes Corp, Potomac, MD 20854 USA. RP McShane, LM (reprint author), NCI, Biometr Res Branch, Room 739,Execut Plaza N,MSC 7434,6130 Execut Blvd, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA47538, CA47526, CA70903] NR 25 TC 67 Z9 68 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 MAY PY 2000 VL 6 IS 5 BP 1854 EP 1864 PG 11 WC Oncology SC Oncology GA 312LY UT WOS:000086945800034 PM 10815908 ER PT J AU Wu, YY Delgado, RM Sunderland, T Csako, G AF Wu, YY Delgado, RM Sunderland, T Csako, G TI Semiautomated PCR-single-strand conformation polymorphism method for detection of a novel sequence polymorphism (Ile1000Val) in human alpha(2)-macroglobulin SO CLINICAL CHEMISTRY LA English DT Article ID ONSET ALZHEIMERS-DISEASE; ALPHA-2-MACROGLOBULIN A2M GENE; RECEPTOR-RELATED PROTEIN; BETA-AMYLOID PEPTIDE; DELETION POLYMORPHISM; FIBRIL FORMATION; ASSOCIATION; CLONING C1 NIMH, Dept Clin Pathol, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIMH, Geriatr Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Csako, G (reprint author), NIMH, Dept Clin Pathol, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Rm 2C-407, Bethesda, MD 20892 USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 2000 VL 46 IS 5 BP 715 EP 718 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 313QL UT WOS:000087010300020 PM 10794757 ER PT J AU Rabkin, CS AF Rabkin, CS TI Editorial response: The need for investigations of prophylactic regimens to prevent AIDS-associated non-Hodgkin's lymphoma SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; EPSTEIN-BARR-VIRUS; ANTIRETROVIRAL THERAPY; KAPOSIS-SARCOMA; INFECTION; COHORT; DNA C1 NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RP Rabkin, CS (reprint author), NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. NR 18 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 2000 VL 30 IS 5 BP 762 EP 763 DI 10.1086/313780 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 323GN UT WOS:000087557900007 PM 10816145 ER PT J AU Winterer, G Ziller, M Dorn, H Frick, K Mulert, C Wuebben, Y Herrmann, WM Coppola, R AF Winterer, G Ziller, M Dorn, H Frick, K Mulert, C Wuebben, Y Herrmann, WM Coppola, R TI Schizophrenia: reduced signal-to-noise ratio and impaired phase-locking during information processing SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE event-related potential; signal-to-noise ratio; phase locking; coherence; stochastic resonance; attention; schizophrenia ID EVENT-RELATED POTENTIALS; SINGLE TRIAL ANALYSIS; STOCHASTIC RESONANCE; EVOKED-RESPONSE; STIMULUS-INTENSITY; P300; DEPRESSION; COMPONENT; OSCILLATIONS; MECHANISMS AB Objective: This study was performed in order to clarify the mechanisms which underlie the reduced signal-to-noise of event-related potentials in schizophrenic patients. Specifically, we wanted to find out, whether it is reduced activation and/or synchronization (phase-locking) in specific frequency bands of the ongoing EEG which is related to the decreased signal amplitude and signal-to-noise ratio in schizophrenics. Methods: We investigated 41 unmedicated schizophrenics (10 of them drug-naive) and compared them with healthy control subjects (n = 233) as well as unmedicated subjects with schizotypal personality (n = 21), who were considered to be high-risk subjects for schizophrenia, and unmedicated depressive patients (n = 71). We measured event-related activity during an acoustical choice reaction paradigm and calculated the signal-to-noise ratio, signal power and noise for a time interval of 50-200 ms after stimulus presentation. Signal-to-noise ratio was calculated from the power of the averaged trials (signal power) divided by the mean power of the single trials minus the power of the average (noise power). Also, we performed a frequency analysis of the pre- and poststimulus EEG based on a factor analytical approach. Group comparisons were performed with ANCOVA. Results: As expected, a decreased signal-to-noise ratio of evoked activity was found in the schizophrenic and a non-significant trend in the schizotypal subjects and the depressive patients. We were able to show that the observed decrease is due to a reduced signal power and an increase of absolute noise power. Frequency analysis of the evoked activity revealed that normals, schizophrenics schizotypal subjects and depressive patients increased theta/delta activity between pre- and poststimulus interval to a similar extend. However, this theta/delta-augmentation does not correlate with signal power in schizophrenics. Also, normals and depressive subjects augment coherence between both temporal lobes during information processing, which is not found in schizophrenics and schizotypal subjects. In contrast, these two groups augment frontal lobe coherence, which goes along with an increase of noise. Conclusions: Reduced stimulus-induced phase-locking and bitemporal coherence of cortically evoked activity but not a failure to activate the cortex may be responsible for the observed low signal-to-noise ratio during information processing in schizophrenics. Accordingly, schizophrenics increase noise after stimulus presentation instead of building up a signal. This is discussed in the framework of the theory of stochastic resonance. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Free Univ Berlin, Dept Psychiat, Lab Clin Psychophysiol, D-1000 Berlin, Germany. RP Winterer, G (reprint author), NIMH, Clin Brain Disorders Branch, 10 Ctr Dr,Room 4S235,MSC 1379, Bethesda, MD 20892 USA. RI Mulert, Christoph/F-2576-2012 NR 50 TC 118 Z9 119 U1 1 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD MAY PY 2000 VL 111 IS 5 BP 837 EP 849 DI 10.1016/S1388-2457(99)00322-3 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 321BF UT WOS:000087434500012 PM 10802455 ER PT J AU Roby, CA Anderson, GD Kantor, E Dryer, DA Burstein, AH AF Roby, CA Anderson, GD Kantor, E Dryer, DA Burstein, AH TI St John's Wort: Effect on CYP3A4 activity SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID URINARY 6-BETA-HYDROXYCORTISOL; ENZYME-INDUCTION; HERBAL REMEDIES; HYPERICUM-PERFORATUM; GENETIC VARIANT; IN-VIVO; EXCRETION; METABOLISM; CAUCASIANS; INDICATOR AB Background: St John's Wort is a widely used herbal product. Information regarding its potential for drug interactions is required for responsible treatment of patients using St John's Wort. CYP3A4 is a metabolic enzyme implicated in most clinically significant drug-drug interactions. Objective: To determine the in vivo effect of reagent-grade St John's Wort extract on CYP3A4 activity through evaluation of urinary 6-beta-hydroxycortisol/cortisol ratios. Methods: Thirteen subjects ranging in age from 18 to 25 years participated in this unblinded, multiple-dose, single-treatment before-after trial conducted in a university-based pharmacokinetics and biopharmaceutics laboratory. Each subject ingested a 300-mg tablet of reagent-grade St John's Wort extract standardized to 0.3% hypericin three times a day for 14 days. Baseline and posttreatment CYP3A4 activity was assessed with the urinary 6-beta-hydroxycortisol/cortisol ratio after a 24-hour urine collection. Results: The mean +/- SD urinary 6-beta-hydroxycortisol/cortisol ratio significantly increased (P =.003) from a baseline value of 7.1 +/- 4.5 to 13 +/- 4.9. The mean +/- SD percentage increase was 114% +/- 95%, with a range from -25% to 259%. All but one subject had an increase in the ratio. Conclusions: Treatment with St John's Wort for 14 days resulted in significant increases in the urinary 6-beta-hydroxycortisol/cortisol ratio. This finding suggests that St John's Wort is an inducer of CYP3A4. C1 NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. St Agnes Hosp, Dept Pharm, Baltimore, MD USA. Univ Washington, Dept Pharm, Seattle, WA 98195 USA. Univ Maryland, Student & Employee Hlth Serv, Baltimore, MD 21201 USA. Univ Maryland, Dept Pharm Practice & Sci, Pharmacokinet & Biopharmaceut Lab, Baltimore, MD 21201 USA. RP Burstein, AH (reprint author), NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bldg 10,Room 1N257, Bethesda, MD 20892 USA. NR 39 TC 218 Z9 225 U1 0 U2 5 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 MAY PY 2000 VL 67 IS 5 BP 451 EP 457 DI 10.1067/mcp.2000.106793 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 315MD UT WOS:000087116800002 PM 10824623 ER PT J AU Wharton, CM Grafman, J Flitman, SS Hansen, EK Brauner, J Marks, A Honda, M AF Wharton, CM Grafman, J Flitman, SS Hansen, EK Brauner, J Marks, A Honda, M TI Toward neuroanatomical models of analogy: A positron emission tomography study of analogical mapping SO COGNITIVE PSYCHOLOGY LA English DT Article; Proceedings Paper CT Analogy 98 Workshop CY JUL, 1998 CL NEW BULGARIAN UNIV, SOFIA, BULGARIA SP New Bulgarian Univ HO NEW BULGARIAN UNIV DE reasoning; analogy; analogical mapping; neuroimaging; PET ID CEREBRAL BLOOD-FLOW; DORSOMEDIAL FRONTAL-CORTEX; WORKING-MEMORY; PREFRONTAL CORTEX; HEMISPHERIC-SPECIALIZATION; FUNCTIONAL-ANATOMY; COGNITIVE ACTIVITY; COMPREHENSION; BRAIN; PERFORMANCE AB Several brain regions associated with analogical mapping were identified using O-15-positron emission tomography with 12 normal, high intelligence adults. Each trial presented during scanning consisted of a source picture of colored geometric shapes, a brief delay, and a target picture of colored geometric shapes. Analogous pictures did not share similar geometric shapes but did share the same system of abstract visuospatial relations. Participants judged whether each source-target pairing was analogous (analogy condition) or identical (literal condition). The results of the analogy-literal comparison showed activation in the dorsomedial frontal cortex and in the left hemisphere; the inferior, middle, and medial frontal cortices; the parietal cortex; and the superior occipital cortex. Based on these results as well as evidence from relevant cognitive neuroscience studies of reasoning and of executive working memory, we hypothesize that analogical mapping is mediated by the left prefrontal and inferior parietal cortices. (C) 2000 Academic Press. C1 NINDS, Max Planck Inst Cognit Neurosci, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Max Planck Inst Cognit Neurosci, NIH, Bldg 10,Room 5C205, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 88 TC 62 Z9 66 U1 4 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0010-0285 J9 COGNITIVE PSYCHOL JI Cogn. Psychol. PD MAY PY 2000 VL 40 IS 3 BP 173 EP 197 DI 10.1006/cogp.1999.0726 PG 25 WC Psychology; Psychology, Experimental SC Psychology GA 312FU UT WOS:000086933200001 PM 10790322 ER PT J AU Ackerman, MJ Banvard, RA AF Ackerman, MJ Banvard, RA TI Imaging outcomes from the National Library of Medicine's Visible Human Project (R) SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Editorial Material C1 Natl Lib Med, Off High Performance Comp & Commun, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Ackerman, MJ (reprint author), Natl Lib Med, Off High Performance Comp & Commun, Lister Hill Natl Ctr Biomed Commun, MS-42,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 0 TC 13 Z9 14 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD MAY-JUN PY 2000 VL 24 IS 3 BP 125 EP 126 DI 10.1016/S0895-6111(00)00012-4 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 326LD UT WOS:000087736200001 PM 10838006 ER PT J AU Perdue, KA Shaw, RE Mage, RG AF Perdue, KA Shaw, RE Mage, RG TI Declawing of neonatal rabbits destined for use in Animal Biosafety Level 4 containment studies SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID PAIN; ANESTHESIA; ANALGESIA; STRESS AB To protect personnel and protective outerwear from damage by scratching; rabbits to be housed in an Animal Biosafety Level 4(ABSL4) facility are declawed routinely. The objective of the study presented here was to establish a procedure for declawing all four feet of neonatal rabbits in preparation for use in ABSL4 studies, Combining procedures conducted in private veterinary practice to remove dewclaws of canine pups with those used to declaw cats, we declawed rabbit kits at 3 to 8 days of age. Declawing neonates was believed to be advantageous because they are non-ambulatory, have soft, cartilaginous digits, and do not have extensive hair growth. These features resulted in decreased surgical preparation and surgery time, minimal bleeding, and minimal aftercare. The optimal age for declawing a litter was 6 or 7 days. Declawing of neonatal rabbits is relatively simple and efficient to perform and offers advantages over declawing of older animals. By using the method described, rabbits can be introduced into ABSL4 facilities by 12 weeks of age with confidence that nail regrowth will not occur. C1 NIAID, NIH, Bethesda, MD 20892 USA. Spring Valley Labs, Woodbine, MD USA. RP Perdue, KA (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 13 TC 0 Z9 0 U1 0 U2 7 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD MAY PY 2000 VL 39 IS 3 BP 13 EP 18 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 317VT UT WOS:000087248200004 PM 11178319 ER PT J AU Velarde, CA Short, BL Rivera, O Seale, W Howard, R Kolobow, T Rais-Bahrami, K AF Velarde, CA Short, BL Rivera, O Seale, W Howard, R Kolobow, T Rais-Bahrami, K TI A comparison of intratracheal pulmonary ventilation to conventional ventilation in a surfactant deficient animal model SO CRITICAL CARE MEDICINE LA English DT Article DE intratracheal pulmonary ventilation; surfactant deficiency ID TRACHEAL GAS INSUFFLATION; ITPV AB Objective: To compare intratracheal pulmonary ventilation (ITPV) with conventional ventilation in a rabbit model of surfactant deficiency. Design: A prospective randomized animal study. Setting: The Children's National Medical Center Research Animal Facility in Washington, DC. Subjects: Adult male New Zealand white rabbits (n = 20), weighing 1.4-4.2 kg. Interventions: After anesthesia and catheter placement, rabbits were tracheotomized, paralyzed, and placed on the conventional ventilator. We determined pulmonary functions at baseline. We washed surfactant out of the lungs by using serial bronchoalveolar lavages. Pulmonary function studies were determined after completion of the bronchoalveolar lavages and were used as an indication of severity of lung injury. Animals were randomized into two groups: We placed ten animals on ITPV, using the ITPV reverse thruster catheter designed by Kolobow and a prototype ITPV ventilator designed at Children's National Medical Center; we placed ten animals on conventional ventilation using the Sechrist iv-100 ventilator. Arterial blood gases were drawn every 15 mins, and the ventilator settings were adjusted to the minimal level that would maintain arterial blood gases in the following ranges: pH 7.35-7.45, PaCO2 30-40 torr (3.99-5.33 kPa), PaO2 50-70 torr (6.66-9.33 kPa), Animals were ventilated with the randomized ventilation techniques for 4 hrs. Measurements and Main Results: Peak inspiratory pressure, mean airway pressure, and positive end-expiratory pressure were measured at the distal end of the endotracheal tube. We recorded these variables plus respiratory rate at baseline and every 30 mins for a total of 4 hrs of ventilation. Lung compliance did not differ between groups at the postlavage study period (ITPV, 0.56 +/- 0.13 mL/cm H2O/kg; conventional 0.49 +/- 0.15 mL/cm H2O/kg). At the end of the 4 hr study period, peak inspiratory pressure (ITPV, 26.2 +/- 4.6 cm H2O; conventional, 32.4 +/- 5.04 cm H2O, p = .007) and positive end-expiratory pressure (ITPV, 3.9 +/- 1.96 cm H2O; conventional, 6.3 +/- 1.42 cm H2O, p = .005) were lower in the ITPV ventilation group. Peak inspiratory pressure was significantly lower in the ITPV group by 2 hrs into the study. Conclusion: In this model of surfactant deficiency lung injury, ventilation and oxygenation were achieved at significantly lower ventilator settings using ITPV compared with conventional ventilation. Long-term studies are needed to determine whether this reduction in ventilation is maintained, and if so, if lung injury is reduced. C1 Childrens Natl Med Ctr, Dept Neonatol, Washington, DC 20010 USA. George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Div Neonatol, Washington, DC 20052 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rais-Bahrami, K (reprint author), Childrens Natl Med Ctr, Dept Neonatol, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 15 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2000 VL 28 IS 5 BP 1455 EP 1458 DI 10.1097/00003246-200005000-00033 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 316LE UT WOS:000087167800033 PM 10834695 ER PT J AU Danis, M AF Danis, M TI Deciding whether to withdraw life-support in critically ill children: Insightful data on hard choices SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE pediatric; palliative care; intensive care unit; life-sustaining treatment C1 NIH, Bethesda, MD 20892 USA. RP Danis, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 2 Z9 2 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2000 VL 28 IS 5 BP 1685 EP 1686 DI 10.1097/00003246-200005000-00091 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 316LE UT WOS:000087167800091 PM 10834753 ER PT J AU Casper, LM Cohen, PN AF Casper, LM Cohen, PN TI How does POSSLQ measure up? Historical estimates of cohabitation SO DEMOGRAPHY LA English DT Article; Proceedings Paper CT Annual Meeting of the Population-Association-of-America CY MAR, 1999 CL NEW YORK, NEW YORK SP Populat Assoc Amer ID UNITED-STATES; MARRIAGE; TRANSITION; RATES AB We use March Current Population Survey (CPS) data from 1977 to 1997 to produce a new historical series of indirect cohabitation prevalence estimates. We compare our new estimates with those produced by the traditional method and evaluate the new estimates. We then compare the indirect estimates with the new direct estimates to investigate whether biases exist in the indirect estimates. Our findings indicate that the traditional indirect method of estimating cohabitation prevalence underestimates cohabiters in different subpopulations, especially among those with children. We also find that the new indirect measure produces relatively unbiased estimates of cohabitors' characteristics. C1 NICHHD, Fertil & Family Stat Branch, US Census Bur, Bethesda, MD 20892 USA. NICHHD, Demog & Behav Sci Branch, Populat Res Ctr, Bethesda, MD 20892 USA. Univ Calif Irvine, Populat Div, US Census Bur, Irvine, CA USA. Univ Calif Irvine, Dept Sociol, Irvine, CA USA. RP Casper, LM (reprint author), NICHHD, Fertil & Family Stat Branch, US Census Bur, 6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA. RI Cohen, Philip/H-2269-2016 OI Cohen, Philip/0000-0003-2839-3144 NR 23 TC 65 Z9 66 U1 1 U2 4 PU POPULATION ASSN AMER PI WASHINGTON PA 1722 N ST NW, WASHINGTON, DC 20036 USA SN 0070-3370 J9 DEMOGRAPHY JI Demography PD MAY PY 2000 VL 37 IS 2 BP 237 EP 245 DI 10.2307/2648125 PG 9 WC Demography SC Demography GA 315XZ UT WOS:000087139400009 PM 10836181 ER PT J AU Faloon, P Arentson, E Kazarov, A Deng, CX Porcher, C Orkin, S Choi, K AF Faloon, P Arentson, E Kazarov, A Deng, CX Porcher, C Orkin, S Choi, K TI Basic fibroblast growth factor positively regulates hematopoietic development SO DEVELOPMENT LA English DT Article DE hemangioblast; hematopoiesis; vasculogenesis; bFGF; BL-CFC; Flk1; scl ID EMBRYONIC STEM-CELLS; BONE MORPHOGENETIC PROTEIN-4; IN-VITRO DIFFERENTIATION; SCL GENE; DEFINITIVE HEMATOPOIESIS; MESODERM INDUCTION; ENDOTHELIAL-CELLS; COMMON PRECURSOR; REQUIRES FGF; YOLK-SAC AB Recently identified BLast Colony Forming Cells (BL-CFCs) from in vitro differentiated embryonic stem (ES) cells represent the common progenitor of hematopoietic and endothelial cells, the hemangioblast. Access to this initial cell population committed to the hematopoietic lineage provides a unique opportunity to characterize hematopoietic commitment events. Here, we show that BL-CFC expresses the receptor tyrosine kinase, Flk1, and thus we took advantage of the BL-CFC assay, as well as fluorescent activated cell sorter (FACS) analysis for Flk1(+) cells to determine quantitatively if mesoderm-inducing factors promote hematopoietic lineage development. Moreover, we have analyzed ES lines carrying targeted mutations for fibroblast growth factor receptor-1 (fgfr1), a receptor for basic fibroblast growth factor (bFGF), as well as scl, a transcription factor, for their potential to generate BL-CFCs and Flk1(+) cells, to further define events leading to hemangioblast development. Our data suggest that bFGF-mediated signaling is critical for the proliferation of the hemangioblast and that cells expressing both Flk1 and SCL may represent the hemangioblast. C1 Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. NIDDKD, Sect Mammalian Genet, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Div Hematol & Oncol, Boston, MA USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Choi, K (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. RI Porcher, Catherine/D-7026-2016; deng, chuxia/N-6713-2016 FU NHLBI NIH HHS [R29HL55337] NR 44 TC 167 Z9 186 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 2000 VL 127 IS 9 BP 1931 EP 1941 PG 11 WC Developmental Biology SC Developmental Biology GA 317WJ UT WOS:000087249700015 PM 10751181 ER PT J AU Corsi, AK Kostas, SA Fire, A Krause, M AF Corsi, AK Kostas, SA Fire, A Krause, M TI Caenorhabditis elegans Twist plays an essential role in non-striated muscle development SO DEVELOPMENT LA English DT Article DE CeTwist; C. elegans; mesoderm; hlh-8; enteric muscles; sex muscles; bHLH ID LOOP-HELIX PROTEIN; C-ELEGANS; MESSENGER-RNA; BHLH PROTEIN; DORSOVENTRAL PATTERN; MOUSE EMBRYOGENESIS; DROSOPHILA EMBRYOS; ZYGOTIC GENE; EXPRESSION; NEMATODE AB The basic helix-loop-helix (bHLH) transcription factor Twist plays a role in mesodermal development in both invertebrates and vertebrates. In an effort to understand the role of the unique Caenorhabditis elegans Twist homolog, hlh-8, we analyzed mesodermal development in animals with a deletion in the hlh-8 locus. This deletion was predicted to represent a null allele because the HLH domain is missing and the reading frame for the protein is disrupted. Animals lacking CeTwist function were constipated and egg-laying defective. Both of these defects were rescued in transgenic mutant animals expressing wild-type hlh-8. Observing a series of mesoderm-specific markers allowed us to characterize the loss of hlh-8 function more thoroughly. Our results demonstrate that CeTwist performs an essential role in the proper development of a subset of mesodermal tissues in C, elegans, We found that CeTwist was required for the formation of three out of the four non-striated enteric muscles born in the embryo. In contrast, CeTwist was not required for the formation of the embryonically derived striated muscles. Most of the post-embryonic mesoderm develops from a single lineage. CeTwist was necessary for appropriate patterning in this lineage and was required for expression of two downstream target genes, but was not required for the expression of myosin, a marker of differentiation. Our results suggest that mesodermal patterning by Twist is an evolutionarily conserved function. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Carnegie Inst Washington, Dept Embryol, Baltimore, MD 21210 USA. Johns Hopkins Univ, Biol Grad Program, Baltimore, MD 21218 USA. RP Krause, M (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. OI Krause, Michael/0000-0001-6127-3940 FU NIGMS NIH HHS [T32GM07231, R01 GM037706, R01GM37706] NR 63 TC 48 Z9 58 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 2000 VL 127 IS 10 BP 2041 EP 2051 PG 11 WC Developmental Biology SC Developmental Biology GA 324TB UT WOS:000087636500005 PM 10769229 ER PT J AU Jeffery, WR Strickler, AG Guiney, S Heyser, DG Tomarev, SI AF Jeffery, WR Strickler, AG Guiney, S Heyser, DG Tomarev, SI TI Prox 1 in eye degeneration and sensory organ compensation during development and evolution of the cavefish Astyanax SO DEVELOPMENT GENES AND EVOLUTION LA English DT Article DE Prox 1; cavefish; eye development; sensory organ compensation; taste buds ID CENTRAL-NERVOUS-SYSTEM; HOMEOBOX GENE PROX-1; CRYSTALLIN GENES; DEVELOPING LENS; EXPRESSION; PAX-6; MOUSE; PROSPERO; DROSOPHILA; FASCIATUS AB We have investigated expression of the homeobox gene Prox 1 during eye degeneration and sensory organ compensation in cavefish embryos. The teleost Astyanax mexicans consists of sighted surface-dwelling forms (surface fish) and several populations of blind cave-dwelling forms (cavefish), which have evolved independently. Eye formation is initiated during cavefish development, but the lens vesicle undergoes apoptosis, and the eye subsequently attests and degenerates. The requirement of Prox 1 for lens fiber differentiation and gamma-crystallin expression in the mouse suggests that changes in the expression of this gene could be involved in cavefish eye degeneration, Surface fish and cavefish embryos stained with a Prox 1 antibody showed Prox 1 expression in the lens, neuroretina, myotomes, heart, hindbrain, and gut, as reported in other vertebrates. We found that Prox 1 expression is not altered during cavefish lens development. Prox 1 protein was detected in the lens vesicle as soon as it formed and persisted until the time of lens degeneration in each cavefish population. The cavefish lens vesicle was also shown to express a gamma-crystallin gene, suggesting that Prox 1 is functional in cavefish lens development. In addition to the tissues described above, Prox 1 is expressed in developing taste buds and neuromasts in cavefish, which are enhanced to compensate for blindness. It is concluded that the Prox 1 gene is not involved in lens degeneration, but that expansion of the Prox 1 expression domain occurs during taste bud and neuromast development in cavefish. C1 Univ Maryland, Dept Biol, College Pk, MD 20742 USA. Penn State Univ, Dept Biol, University Pk, PA 16802 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Jeffery, WR (reprint author), Univ Maryland, Dept Biol, College Pk, MD 20742 USA. NR 32 TC 63 Z9 67 U1 4 U2 16 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0949-944X J9 DEV GENES EVOL JI Dev. Genes Evol. PD MAY PY 2000 VL 210 IS 5 BP 223 EP 230 DI 10.1007/s004270050308 PG 8 WC Cell Biology; Evolutionary Biology; Developmental Biology SC Cell Biology; Evolutionary Biology; Developmental Biology GA 314UK UT WOS:000087075800001 PM 11180826 ER PT J AU Bosse, A Stoykova, A Nieselt-Struwe, K Chowdhury, K Copeland, NG Jenkins, NA Gruss, P AF Bosse, A Stoykova, A Nieselt-Struwe, K Chowdhury, K Copeland, NG Jenkins, NA Gruss, P TI Identification of a novel mouse iroquois homeobox gene, Irx5, and chromosomal localisation of all members of the mouse iroquois gene family SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Iroquois; prepattern gene; homeobox; mouse; Xenopus; chick; human; neurogenesis; otic vesicle; branchial cleft; heart; limb; scerotome ID HELIX TRANSCRIPTION FACTORS; NEURAL CREST CELLS; NERVOUS-SYSTEM; DROSOPHILA-MELANOGASTER; XENOPUS HOMOLOG; EXPRESSION; ACHAETE; SCUTE; NEUROGENESIS; PATTERN AB The Drosophila genes of the Iroquois-Complex encode homeodomain containing transcription factors that positively regulate the activity of certain proneural Achaete/Scute-C (AS-C) genes during the formation of external sensory organs (J. L. Gomez-Skarmeta and J, Modolell, EMBO J 17:181-190, 1996), Previously, we have identified three highly-related genes of the mouse Iroquois gene family that exert specific expression patterns in the central nervous system (A. Bosse et al,, Mech Dev 69:169-181, 1997), In the present paper, we report the identification of a novel member of the Iroquois gene family, Irx5, that shows a restricted spatio/temporal expression during early mouse embryogenesis, distinct from the expression of Irx1-3. An extensive sequence analysis of 20 Iroquois-like genes from seven organisms reveals a high conservation of the homeodomain, Phylogenetic tree reconstruction showed a clustering of the members of the Iroquois gene family into groups of orthologous genes, Together, with the data obtained from the chromosomal mapping analysis, the results indicate that these genes have appeared in vertebrates during evolution as a result of gene duplication. (C) 2000 Wiley-Liss, Inc. C1 Max Planck Inst Biophys Chem, Dept Mol Cell Biol, D-37077 Gottingen, Germany. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD USA. RP Gruss, P (reprint author), Max Planck Inst Biophys Chem, Dept Mol Cell Biol, Fassberg, D-37077 Gottingen, Germany. NR 59 TC 44 Z9 45 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAY PY 2000 VL 218 IS 1 BP 160 EP 174 DI 10.1002/(SICI)1097-0177(200005)218:1<160::AID-DVDY14>3.0.CO;2-2 PG 15 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 309WJ UT WOS:000086792000014 PM 10822268 ER PT J AU Ahnert, L Rickert, H Lamb, ME AF Ahnert, L Rickert, H Lamb, ME TI Shared caregiving: Comparisons between home and child-care settings SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID FAMILY DEVELOPMENT PROJECT; INFANT-MOTHER ATTACHMENT; PENNSYLVANIA INFANT; MATERNAL EMPLOYMENT; PROFESSIONAL CAREGIVERS; QUALITY; WORK; SOCIALIZATION; EXPERIENCE; PATTERNS AB The experiences of 84 German toddlers (12-24 months old) who were either enrolled or not enrolled in child care were described with observational checklists from the time they woke up until they went to bed. The total amount of care experienced over the course of a weekday by 35 pairs of toddlers (1 member of each pair in child care, 1 member not) did not differ according to whether the toddlers spent time in child care. Although the child-care toddlers received lower levels of care from care providers in the centers, their mothers engaged them in more social interactions during nonworking hours than did the mothers of home-only toddlers, which suggests that families using child care provided different patterns of care than families not using child care. Child-care toddlers experienced high levels of emotional support at home, although they experienced less prompt responses to their distress signals. Mothers' ages were unrelated to the amounts of time toddlers spent with them, but older mothers initiated more proximity. C1 Interdisciplinary Ctr Appl Res Socializat, D-13125 Berlin, Germany. NICHHD, Bethesda, MD 20892 USA. RP Ahnert, L (reprint author), Interdisciplinary Ctr Appl Res Socializat, Tichauer Str 46, D-13125 Berlin, Germany. NR 53 TC 18 Z9 18 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD MAY PY 2000 VL 36 IS 3 BP 339 EP 351 DI 10.1037//0012-1649.36.3.339 PG 13 WC Psychology, Developmental SC Psychology GA 312EA UT WOS:000086929200005 PM 10830978 ER PT J AU Stoffers, DA Kieffer, TJ Hussain, MA Drucker, DJ Bonner-Weir, S Habener, JF Egan, JM AF Stoffers, DA Kieffer, TJ Hussain, MA Drucker, DJ Bonner-Weir, S Habener, JF Egan, JM TI Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas SO DIABETES LA English DT Article ID TYPE-2 DIABETES-MELLITUS; FACTOR-I IPF-1; TRANSCRIPTION FACTOR; BETA-CELLS; GENE-TRANSCRIPTION; GLUCOSE-TOLERANCE; MICE; REGENERATION; RECEPTOR; PDX-1 AB Diabetes is caused by a failure of the pancreas to produce insulin in amounts sufficient to meet the body's needs. A hallmark of diabetes is an absolute (type 1) or relative (type 2) reduction in the mass of pancreatic beta-cells that produce insulin, Mature beta-cells have a lifespan of similar to 48-56 days (rat) and are replaced by the replication of preexisting beta-cells and by the differentiation and proliferation of new beta-cells (neogenesis) derived from the pancreatic ducts. Here, we show that the insulinotropic hormone glucagon-like peptide (GLP)-1, which is produced by the intestine, enhances the pancreatic expression of the homeodomain transcription factor IDX-1 that is critical for pancreas development and the transcriptional regulation of the insulin gene. Concomitantly, GLP-1 administered to diabetic mice stimulates insulin secretion and effectively lowers their blood sugar levels. GLP-1 also enhances beta-cell neogenesis and islet size. Thus, in addition to stimulating insulin secretion, GLP-1 stimulates the expression of the transcription factor IDX-1 while stimulating beta-cell neogenesis and may thereby be an effective treatment for diabetes. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Howard Hughes Med Inst, Boston, MA 02114 USA. Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Boston, MA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Natl Inst Aging, Clin Invest Lab, Diabet Sect, Baltimore, MD USA. Toronto Gen Hosp, Dept Med, Toronto, ON M5G 1L7, Canada. Univ Alberta, Dept Med, Heritage Med Res Ctr, Edmonton, AB, Canada. Univ Alberta, Dept Physiol, Heritage Med Res Ctr, Edmonton, AB, Canada. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Howard Hughes Med Inst, 55 Fruit St,WEL320, Boston, MA 02114 USA. RI Stoffers, Doris/H-6157-2012; Drucker, Daniel/A-4092-2010 FU NIDDK NIH HHS [DK30457, DK30834, DK44523] NR 45 TC 417 Z9 451 U1 3 U2 17 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2000 VL 49 IS 5 BP 741 EP 748 DI 10.2337/diabetes.49.5.741 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 313EP UT WOS:000086987600011 PM 10905482 ER PT J AU Gautier, JF Chen, KW Salbe, AD Bandy, D Pratley, RE Heiman, M Ravussin, E Reiman, EM Tataranni, PA AF Gautier, JF Chen, KW Salbe, AD Bandy, D Pratley, RE Heiman, M Ravussin, E Reiman, EM Tataranni, PA TI Differential brain responses to satiation in obese and lean men SO DIABETES LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; FOOD-INTAKE; DIETARY-FAT; HUMANS; CORTEX; DISTENSION; SATIETY; HUNGER AB Knowledge of how the brain contributes to the regulation of food intake in humans is limited. We used positron emission tomography and measures of regional cerebral blood flow (rCBF) (a marker of neuronal activity) to describe the functional anatomy of satiation (i.e., the response to a liquid meal) in the context of extreme hunger (36-h fast) in 11 obese (BMI greater than or equal to 35 kg/m(2), age 27 +/- 5 years, weight 115 +/- 11 kg, 38 +/- 7% body fat; mean +/- SD) and 11 lean (BMI less than or equal to 25 kg/m(2), age 35 +/- 8 years, weight 73 +/- 9 kg, 19 +/- 6% body fat) men. As in lean men, satiation in obese men produced significant increases in rCBF in the vicinity of the ventromedial and dorsolateral prefrontal cortex and significant decreases in rCBF in the vicinity of the limbic/paralimbic areas (i.e., hippocampal formation, temporal pole), striatum (i.e., caudate, putamen), precuneus, and cerebellum. However, rCBF increases in the prefrontal cortex were significantly greater in obese men than in lean men (P < 0.005). rCBF decreases in limbic/paralimbic areas, temporal and occipital cortex, and cerebellum were also significantly greater in obese men then in lean men (P < 0.005), whereas rCBF decreases in the hypothalamus and thalamus were attenuated in obese men compared with lean men (P < 0.05). This study raises the possibility that the brain responses to a meal in the prefrontal areas (which may be involved in the inhibition of inappropriate response tendencies) and limbic/paralimbic areas (commonly associated with the regulation of emotion) may be different in obese and lean men. Additional studies are required to investigate how these differential responses are related to the pathophysiology of obesity. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Good Samaritan Reg Med Ctr, Positron Emiss Tomog Ctr, Phoenix, AZ USA. Univ Arizona, Dept Psychiat, Tucson, AZ USA. Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. RP Tataranni, PA (reprint author), NIDDK, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 NR 42 TC 167 Z9 170 U1 2 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2000 VL 49 IS 5 BP 838 EP 846 DI 10.2337/diabetes.49.5.838 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 313EP UT WOS:000086987600024 PM 10905495 ER PT J AU Hsueh, WC Wagner, MJ Mitchell, BD St Jean, PL Aburomia, R Knowler, WC Pollin, T Burns, DK Sakul, H Bell, CJ Ehm, MG Shuldiner, AR Michelsen, BK AF Hsueh, WC Wagner, MJ Mitchell, BD St Jean, PL Aburomia, R Knowler, WC Pollin, T Burns, DK Sakul, H Bell, CJ Ehm, MG Shuldiner, AR Michelsen, BK TI Diabetes in the Old Order Amish - Characterization and heritability analysis of the Amish Family Diabetes Study SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; BODY-MASS INDEX; CARDIOVASCULAR RISK-FACTORS; GENOME-WIDE SEARCH; MOLECULAR-GENETICS; AMERICAN FAMILIES; PHYSICAL-ACTIVITY; FAT DISTRIBUTION; PLASMA LEPTIN; PIMA-INDIANS AB OBJECTIVE - The Old Order Amish (OOA) are a genetically well-defined closed Caucasian founder population. The Amish Family Diabetes Study was initiated to identify susceptibility genes for type 2 diabetes. This article describes the genetic epidemiology of type 2 diabetes and related traits in this unique population. RESEARCH DESIGN AND METHODS- The study cohort comprised Amish probands with diabetes who were diagnosed between 35 and 65 years of age and their extended adult family members. We recruited 953 adults who represented 45 multigenerational families. Phenotypic characterization included anthropometry, blood pressure, diabetes status, lipid profile, and leptin levels. RESULTS - The mean age of study participants was 46 years, and the mean BMI was 26.9 kg/m(2). Subjects with type 2 diabetes were older, more obese, and had higher insulin levels. The prevalence of diabetes in the OOA was approximately half that of the Caucasian individuals who participated in the Third National Health and Nutrition Examination Survey (95% CI 0.23-0.84). The prevalence of diabetes in the siblings of the diabetic probands was 26.5% compared with a prevalence of 7.0% in spouses (lambda(s) = 3.28, 95% CI 1.58-6.80). The heritability of diabetes-related quantitative traits was substantial (13-70% for obesity-related traits, 10-42% for glucose levels, and 11-24% for insulin levels during the oral glucose tolerance test; P = 0.01 to <0.0001). CONCLUSIONS - Type 2 diabetes in the Amish has similar phenotypic features to that of the overall Caucasian population, although the prevalence in the Amish community is lower than that of the Caucasian population. There is significant familial clustering of type 2 diabetes and related traits. This unique family collection will be an excellent resource for investigating the genetic underpinnings of type 2 diabetes. C1 Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. Axys Pharmaceut, La Jolla, CA USA. Glaxo Wellcome, Res Triangle Pk, NC USA. Hagedorn Res Inst, Gentofte, Denmark. NIDDKD, NIH, Phoenix, AZ USA. RP Shuldiner, AR (reprint author), Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, 725 W Lombard St,Room S-422, Baltimore, MD 21201 USA. OI Mitchell, Braxton/0000-0003-4920-4744 NR 47 TC 112 Z9 114 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2000 VL 23 IS 5 BP 595 EP 601 DI 10.2337/diacare.23.5.595 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 313WN UT WOS:000087022800008 PM 10834415 ER PT J AU Fetsch, PA Cowan, KH Weng, DE Freifield, A Filie, AC Abati, A AF Fetsch, PA Cowan, KH Weng, DE Freifield, A Filie, AC Abati, A TI Detection of circulating tumor cells and micrometastases in stage II, III, and IV breast cancer patients utilizing cytology and immunocytochemistry SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE circulating tumor cells; micrometastases; immunocytochemistry; cytokeratin ID POLYMERASE CHAIN-REACTION; BONE-MARROW MICROMETASTASES; HIGH-DOSE CHEMOTHERAPY; PERIPHERAL-BLOOD; PROGNOSTIC-SIGNIFICANCE; MICRO-METASTESES; CARCINOMA-CELLS; FOLLOW-UP; RT-PCR; IMMUNOHISTOCHEMISTRY AB Evaluation for circulating tumor cells and bone marrow micrometastases has generated considerable interest due to a potential association with disease recurrrence and poor prognosis. In this study, we examined bone marrow and apheresis samples from Stage II, III, and IV patients (n 120) enrolled in various clinical breast cancer trials at the National Institutes of Health/National Cancer Institute. For each patient sample, two Diff-Quik-stained cytospins were reviewed for morphology, and approximately 1 10(6) cells were analyzed for the expression of cytokeratins using an avidin-biotin immunoperoxidase method. Keratin-positive malignant cells appearing as single cells or in small clusters were detected in bone marrow samples from Stage IV patients only (9/68, 13%) and detected in apheresis samples from both Stage III and IV patients (13/245, 5%). These findings indicate that the combination of cytomorphology with immunocytochemistry can be utilized Sor the investigation of circulating tumor cells and bone marrow micrometastases, and that positive results appear to correlate with high tumor stage/burden. Diagn. Cytopathol. 2000; 22:323-328. Published 2000 Wiley-Liss, Inc. C1 NCI, Cytopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NCI, Cytopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2A19,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. NR 34 TC 24 Z9 25 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD MAY PY 2000 VL 22 IS 5 BP 323 EP 328 DI 10.1002/(SICI)1097-0339(200005)22:5<323::AID-DC13>3.0.CO;2-L PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 307NJ UT WOS:000086659100013 PM 10790242 ER PT J AU Fedorko, DP Williams, EC Nelson, NA Mazyck, TD Hanson, KL Cartwright, CP AF Fedorko, DP Williams, EC Nelson, NA Mazyck, TD Hanson, KL Cartwright, CP TI Performance of Para-Pak (TM) Ultra ECOFIX (TM) compared with ParaPak (TM) Ultra formalin/mercuric chloride-based polyvinyl alcohol for concentration and permanent stained smears of stool parasites SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE fecal preservative; stool specimens; intestinal parasites; protozoa; helminths ID INTESTINAL PROTOZOAN MORPHOLOGY; SULFATE AB ECOFIX(TM) is a mercury and formalin-free fecal preservative that can be used for concentration of stool specimens and preparation of permanently-stained slides. In this study, the standard two-vial ParaPak(TM) Ultra system was compared with ECOFIX(TM) Ultra for the detection of intestinal parasites. A total of 261 specimens in 92 sets (77 with 3 specimens, 15 with 2 specimens) were collected in ECOFIX(TM), formalin, and low viscosity polyvinyl alcohol (LV-PVA). Concentrations were performed from ECOFIX(TM) using Hemo-De and saline and from formalin using ethyl acetate and formalin. To prepare permanently-stained smears, ECOSTAIN(TM) (a modification of Wheatley's trichrome stain) was used on ECOFIX(TM) material and Wheatley's trichrome stain was used on specimens preserved in PVA. A total of 157 protozoa and helminths were detected; 132 (84.1%) were recovered in formalin/PVA and 129 (82.2%) in ECOFIX(TM). fn permanently-stained smears, 139 protozoa were observed, 116 (83.5%) in PVA-preserved material and 117 (84.2%) in ECOFIX(TM). Fecal concentration yielded 111 parasites (103 protozoa and 8 helminths), of which 98 (88.3%) were detected in formalin-fixed stool and 48 (43.2%) in ECOFIX(TM). Significantly fewer ECOFIX(TM)-preserved concentrates were positive for Blastocystis hominis (35 versus 15, p-value <0.001) and Endolimax nana (19 versus 2, p-value <0.001). In conclusion, use of the ECOFIX(TM) Ultra collection device in combination with ECOSTAIN(TM) resulted in largely comparable recovery of enteric parasites to the conventional two-vial ParaPak(TM) Ultra system when both sedimentation-concentration and permanently stained smears were performed, and 2-3 specimens per patient were evaluated. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIH, Warren Grant Magnuson Clin Ctr, Microbiol Serv, Dept Clin Pathol, Bethesda, MD 20892 USA. Hennepin Cty Med Ctr, Clin Microbiol Lab, Minneapolis, MN 55415 USA. RP Fedorko, DP (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Microbiol Serv, Dept Clin Pathol, Bldg 10,Room 2C385,10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. NR 11 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD MAY PY 2000 VL 37 IS 1 BP 37 EP 39 DI 10.1016/S0732-8893(00)00121-8 PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 348UV UT WOS:000089005600007 PM 10794938 ER PT J AU Marques, AR Straus, SE AF Marques, AR Straus, SE TI Herpes simplex type 2 infections - An update SO DM DISEASE-A-MONTH LA English DT Review ID RECURRENT GENITAL HERPES; PLACEBO-CONTROLLED TRIAL; HUMAN-IMMUNODEFICIENCY-VIRUS; DOUBLE-BLIND TRIAL; T-CELL SUBSETS; ORAL ACYCLOVIR; GLYCOPROTEIN-D; LYMPHOCYTE-T; GUINEA-PIGS; PHARMACOKINETIC PROPERTIES C1 NIAID, Clin Studies Unit, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Marques, AR (reprint author), NIAID, Clin Studies Unit, Clin Invest Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 141 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 0011-5029 J9 DM-DIS MON JI DM-Dis.-a-Mon. PD MAY PY 2000 VL 46 IS 5 BP 328 EP 359 PG 32 WC Medicine, General & Internal SC General & Internal Medicine GA 317WD UT WOS:000087249200001 ER PT J AU Yang, X McGraw, RA Su, X Katakam, P Grosse, WM Li, OW Ferguson, DC AF Yang, X McGraw, RA Su, X Katakam, P Grosse, WM Li, OW Ferguson, DC TI Canine thyrotropin beta-subunit gene: cloning and expression in Escherichia coli, generation of monoclonal antibodies, and transient expression in the Chinese hamster ovary cells SO DOMESTIC ANIMAL ENDOCRINOLOGY LA English DT Article ID THYROID-STIMULATING HORMONE; GLYCOPROTEIN HORMONES; SERUM; HYPOTHYROIDISM; DOGS; DIAGNOSIS; SEQUENCE; PROTEINS; ASSAY AB The gene encoding the mature beta subunit of canine thyroid stimulating hormone (cTSH beta) was cloned, sequenced and expressed in Escherichia coli and in Chinese hamster ovary (CHO) cells, and monoclonal antibodies against the recombinant cTSH beta purified from E. coli were generated. The gene fragment that encodes mature TSH beta was cloned from the canine genomic DNA by direct polymerase chain reaction (PCR) using primers that were designed based on the consensus sequences from other species. The resulting 891 basepairs (bp) of genomic DNA consisted of two coding exons of the canine TSH beta gene and an intron of 450 bp. The two exons, which encode the mature cTSH beta subunit, was joined together by an overlap PCR and was expressed in E. coli as 6xHis-tagged protein. The purified recombinant cTSH beta with a molecular weight of about 15 kDa was recognized by the polyclonal antibodies prepared against the native canine TSH in Western blot. Monoclonal antibodies were raised against the purified cTSH beta and subsequently characterized. For transient expression in CHO cells; that are permanently transfected with the bovine common alpha gene, a 60-oligonucleotide signal peptide coding sequence was added to the 5' end of the cTSH beta gene before it was cloned into the mammalian expression vector pRSV and used to transfect CHO cells. The medium from these transfected cells, presumably containing the bovine ct and canine TSH beta in heterodimeric confirmation, exhibited TSH bioactivity as indicated by the stimulation of cAMP production in the cultured FRTL-5 thyrocytes. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Georgia, Coll Vet Med, Dept Physiol & Pharmacol, Athens, GA 30602 USA. Univ Georgia, Coll Pharm, Dept Pharmacol & Toxicol, Athens, GA 30602 USA. NIAID, Bethesda, MD 20892 USA. RP Yang, X (reprint author), NIEHS, F2-06,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 41 TC 5 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 0739-7240 J9 DOMEST ANIM ENDOCRIN JI Domest. Anim. Endocrinol. PD MAY PY 2000 VL 18 IS 4 BP 363 EP 378 DI 10.1016/S0739-7240(00)00056-4 PG 16 WC Agriculture, Dairy & Animal Science; Endocrinology & Metabolism SC Agriculture; Endocrinology & Metabolism GA 330DF UT WOS:000087947000002 PM 10869856 ER PT J AU Yang, X McGraw, RA Ferguson, DC AF Yang, X McGraw, RA Ferguson, DC TI CDNA cloning of canine common alpha gene and its co-expression with canine thyrotropin beta gene in baculovirus expression system SO DOMESTIC ANIMAL ENDOCRINOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; PITUITARY GLYCOPROTEIN HORMONES; THYROID-STIMULATING HORMONE; NUCLEOTIDE-SEQUENCE; MOUSE THYROTROPIN; SUBUNIT; SERUM; HYPOTHYROIDISM; DOGS; IMMUNOASSAY AB The common alpha gene of the canine glycoprotein hormones was cloned, sequenced and co-expressed with the canine thyrotropin beta (TSH beta) gene in the baculovirus expression system, and a bioactive recombinant canine TSH was purified. The canine common alpha gene was cloned from the total RNA extracted from the canine pituitary gland by the reverse transcription polymerase chain reaction (RT-PCR) using primers that were designed based on the consensus sequences from other species. The resulting 476 bp PCR product is consisted of the full coding sequence for the 96 amino acid mature alpha subunit, and a sequence encoding a 24 amino acid signal peptide. Homology analysis with other species revealed that the canine common alpha subunit potentially contains five disulfide bonds and two oligosaccharide chains N-linked to Asn residues located at positions 56 and 82. For expression in the baculovirus expression system, the common alpha gene was cloned downstream of the p10 promoter of the pAcUW51 transfer vector, and the previously cloned canine TSH beta gene was inserted under the polyhedrin promoter of the same vector. The recombinant virus containing both alpha and beta genes was generated and propagated before being used to transfect the Sf9 insect cells for expression. The medium from the Sf9 cultures, presumably containing canine TSH alpha and beta in native heterodimer confirmation, exhibited TSH bioactivity as indicated in the cAMP stimulation assay in FRTL-5 cells. The expressed recombinant protein was purified from the culture medium with an affinity column that was coupled with IgG purified from the polyclonal antibodies generated against the partially purified native canine TSH. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Georgia, Coll Vet Med, Dept Physiol & Pharmacol, Athens, GA 30602 USA. RP Yang, X (reprint author), NIEHS, 111 Alexander Dr,F2-06, Res Triangle Pk, NC 27709 USA. NR 44 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0739-7240 J9 DOMEST ANIM ENDOCRIN JI Domest. Anim. Endocrinol. PD MAY PY 2000 VL 18 IS 4 BP 379 EP 393 DI 10.1016/S0739-7240(00)00057-6 PG 15 WC Agriculture, Dairy & Animal Science; Endocrinology & Metabolism SC Agriculture; Endocrinology & Metabolism GA 330DF UT WOS:000087947000003 PM 10869857 ER PT J AU Baumann, MH Rothman, RB Ali, SF AF Baumann, MH Rothman, RB Ali, SF TI Comparative neurobiological effects of ibogaine and MK-801 in rats SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE ibogaine; MK-801; dopamine; corticosterone; prolactin; addiction ID NMDA RECEPTOR COMPLEX; ANTI-ADDICTIVE DRUG; RADIOLIGAND-BINDING; IN-VIVO; MORPHINE; DOPAMINE; COCAINE; MECHANISMS; METABOLITE; ANTAGONIST AB Ibogaine is a plant-derived alkaloid with putative 'anti-addictive' properties. Although ibogaine binds to multiple targets in the brain, recent evidence suggests the drug acts as an N-methyl-D-aspartate (NMDA) antagonist similar to MK-801. The purpose of the present study was to compare neurochemical and neuroendocrine effects of ibogaine and MK-801 in vivo. Male rats received either i.p. saline, ibogaine (10 and 100 mg/kg), or MK-801 (0.1 and 1 mg/kg). Groups of rats (N = 6-8/group) were decapitated 30 or 60 min after injection. Brains were harvested for analysis of dopamine (DA) and its metabolites, while trunk blood was collected for analysis of plasma corticosterone and prolactin. Ibogaine produced marked dose-dependent reductions in tissue DA with concurrent increases in the metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This profile of ibogaine-induced effects on DA metabolism was consistently observed in the cortex, striatum: olfactory tubercle, and hypothalamus. MK-801, on the other hand, did not reduce DA levels in any brain region but did cause modest region-specific elevations in DA metabolites. Ibogaine and MK-801 caused comparable elevations in circulating corticosterone, but only ibogaine increased prolactin. The present findings show that the effects of ibogaine on DA neurotransmission and neuroendocrine secretion are not fully mimicked by MK-801. Thus, the wide spectrum of in vivo actions of ibogaine can probably not be explained simply on the basis of antagonism at NMDA receptors. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 NIDA, Intramural Res Program, Medicat Discovery Res Branch, NIH, Baltimore, MD 21224 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Baumann, MH (reprint author), NIDA, Intramural Res Program, Medicat Discovery Res Branch, NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 41 TC 7 Z9 7 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY 1 PY 2000 VL 59 IS 2 BP 143 EP 151 DI 10.1016/S0376-8716(99)00113-1 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 308KH UT WOS:000086709700004 PM 10891627 ER PT J AU Negrao, AB Licinio, J AF Negrao, AB Licinio, J TI Obesity: on the eve of a major conceptual revolution SO DRUG DISCOVERY TODAY LA English DT Editorial Material ID QUANTITATIVE TRAIT LOCUS; LEPTIN DEFICIENCY; ADIPOSE-TISSUE; GENE; INSULIN; EXPRESSION; RESISTANCE; WEIGHT; REGION C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Gonda Goldschmied Neurosci & Genet Res Ctr 3357A, Los Angeles, CA 90095 USA. RP Negrao, AB (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, Bldg 10,Room 2D46,10 Ctr Dr, Bethesda, MD 20892 USA. RI Negrao, Andre Brooking/C-9526-2014; Licinio, Julio/L-4244-2013 OI Negrao, Andre Brooking/0000-0002-8133-6723; Licinio, Julio/0000-0001-6905-5884 NR 14 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD MAY PY 2000 VL 5 IS 5 BP 177 EP 179 DI 10.1016/S1359-6446(00)01478-1 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 309EH UT WOS:000086755000004 ER PT J AU Heath, EI Grochow, LB AF Heath, EI Grochow, LB TI Clinical potential of matrix metalloprotease inhibitors in cancer therapy SO DRUGS LA English DT Article ID ABDOMINAL AORTIC-ANEURYSM; GELATINASE-B; PHASE-I; EXPRESSION; CARCINOMA; COLLAGENASE; METASTASIS; BATIMASTAT; INVASION; MICE AB Matrix metalloproteases (MMP) are a family of enzymes that contribute to the degradation of the extracellular matrix. The destruction of the extracellular matrix eventually leads to tumour invasion, metastasis and angiogenesis. Realising this mechanism of action, there is tremendous potential for inhibitors of MMP in cancer therapy. Extensive preclinical data have shown that administration of matrix metalloprotease inhibitors (MMPI) to different animal models results in a reduction in primary tumour growth as well as in the number and size of metastatic lesions. Based on promising preclinical studies, synthetic MMPI have been developed and taken into clinical trials. These include marimastat, BAY-129566, CGS-27023A, prinomastat (AG-3340), EMS-275291 and metastat (COL-3). These drugs are all in different stages of clinical development, ranging from phase I to III. In general, musculoskeletal problems, such as joint stiffness and pain in hands, arms and shoulders seem to affect most patients in varying degrees, depending on the dose and type of compound administered. In addition to single agent therapy, several MMPI have entered trials of combination therapy. The objective of combining chemotherapy with an MMPI is to potentiate tumour cytotoxicity as well as to reduce the size and number of metastatic lesions. Several compounds have entered phase III combination therapy trials, but it is still too early to report any data. There is ongoing research in correlating biological endpoints, such as levels of MMP and markers of angiogenesis with clinical response. As the field of MMP and their inhibitors continues to mature, its role in cancer therapeutics will be better defined. C1 Johns Hopkins Oncol Ctr, Div Med Oncol, Baltimore, MD 21231 USA. NCI, Rockville, MD USA. RP Heath, EI (reprint author), Johns Hopkins Oncol Ctr, Div Med Oncol, Bunting Blaustein Canc Res Bldg,1650 Orleans St, Baltimore, MD 21231 USA. NR 61 TC 78 Z9 83 U1 1 U2 11 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PD MAY PY 2000 VL 59 IS 5 BP 1043 EP 1055 DI 10.2165/00003495-200059050-00002 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 322YZ UT WOS:000087538400002 PM 10852638 ER PT J AU Gianazza, E Sirtori, CR Castiglioni, S Eberini, I Chrambach, A Rondanini, A Vecchio, G AF Gianazza, E Sirtori, CR Castiglioni, S Eberini, I Chrambach, A Rondanini, A Vecchio, G TI Interactions between carbonic anhydrase and its inhibitors revealed by gel electrophoresis and circular dichroism SO ELECTROPHORESIS LA English DT Article DE carbonic anhydrase; sulfonamide inhibitors; denaturant gradient gel electrophoresis; urea; sodium dodecyl sulfate; circular dichroism; complex dissociation; protein unfolding ID MOLTEN GLOBULE STATE; GRADIENT ELECTROPHORESIS; POLYACRYLAMIDE GELS; PROTEINS; DENATURATION; ACETAZOLAMIDE; ASSOCIATION; COMPLEXES; SPECTRUM; MOBILITY AB Structural properties, and especially the differential stability, of complexes between carbonic anhydrase (CA) and three sulfonamide inhibitors, acetazolamide, dorzolamide and methazolamide, were investigated by spectroscopic and electrophoretic techniques. These included denaturant gradient gel electrophoresis either across a urea or a steady-state transverse sodium dodecyl sulfate (SDS) gradient. Acetazolamide, the smallest and most hydrophilic of the sulfonamides, forms the most stable complex in the presence of urea, whereas dorzolamide, with a bulky and hydrophobic structure, is most stable against the effects of SDS. At pH 7.4, complexes with dorzolamide show minimal changes in mobility across the SDS gradient, as if unaffected by the detergent, both in the presence and in the absence of excess ligand in the gel. When bound to both acetazolamide and methazolamide, on the other hand, CA displays an increase in mobility above 0.05% SDS, lower in the presence than in the absence of excess ligand. The finding of a distinct pattern for the unliganded enzyme, however, suggests the complexes can still retain the ligand, although binding of the surfactant changes their charge density. Under saturating conditions and in the presence of SDS, the surface charge of all complexes is much lower than for unliganded, denatured CA. Circular dichroism (CD) spectra clearly indicate that the increase in secondary structure and the decrease in tertiary structure brought about in CA by the presence of low concentrations of SDS are largely prevented by complexing with the inhibitors. These observations point out peculiar properties of each CA inhibitor, of potential value in the definition of their biological activities and also in the potential development of novel antagonist molecules. C1 Univ Milan, Ist Sci Farmacol, I-20133 Milan, Italy. NIH, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. CNR, Ist Biocatalisi & Riconoscimento, I-20133 Milan, Italy. RP Gianazza, E (reprint author), Univ Milan, Ist Sci Farmacol, Via Balzaretti 9, I-20133 Milan, Italy. RI Sirtori, Cesare/F-4658-2012 NR 44 TC 4 Z9 4 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAY PY 2000 VL 21 IS 8 BP 1435 EP 1445 DI 10.1002/(SICI)1522-2683(20000501)21:8<1435::AID-ELPS1435>3.0.CO;2-E PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 315YL UT WOS:000087140500001 PM 10832870 ER PT J AU Kramer, PR Krishnamurthy, R Mitchell, PJ Wray, S AF Kramer, PR Krishnamurthy, R Mitchell, PJ Wray, S TI Transcription factor activator protein-2 is required for continued luteinizing hormone-releasing hormone expression in the forebrain of developing mice SO ENDOCRINOLOGY LA English DT Article ID GAMMA-AMINOBUTYRIC-ACID; EMBRYONIC OLFACTORY PLACODE; ANTERIOR HYPOTHALAMIC AREA; EXPLANT CULTURES EXHIBIT; CENTRAL-NERVOUS-SYSTEM; GNRH GENE-EXPRESSION; FACTOR AP-2; MESSENGER-RNA; LHRH NEURONS; RECEPTOR GENE AB LHRH is the neuropeptide responsible for reproductive function. Prenatally, LHRH expression begins when neurons are in the olfactory pit and continues as these cells migrate into the brain. Thus, LHRH neurons maintain neuropeptide expression through very distinct environments. The regulatory interactions that control onset and continued expression of the LHRH phenotype are unknown. To begin to address this question primary LHRH neurons were removed from nasal explants at different ages. A complementary DNA (cDNA) subtraction screen was performed comparing a 3.5-days in vitro LHRH neuron [approximately embryonic day 15 (E15) in vivo] to two 10.5-days in vitro LHRH neurons (approximately postnatal day 1 in vivo). The transcription factor activator protein-2 (AP-2 alpha) was differentially expressed and was present in the developmentally younger LHRH neuron. In vivo analysis revealed that LHRH neurons expressed AP-2 as they migrated across the cribriform plate and into the forebrain beginning on E13.5, but that coexpression of LHRH and AP-2 was no longer detected in postnatal day 1 animals. This suggested a regulatory role for AP-2 in LHRH neurons. Analysis of animals lacking AP-2 alpha revealed a dramatic decrease in forebrain LHRH neurons between E13.5 and E14.5, correlating with normal onset of AP-2 expression in LHRH neurons as they entered the central nervous system. Nasal cells robustly expressing LHRH were still present on E14.5. The continued presence of forebrain LHRH cells is proposed based on a second marker, galanin, and lack of increased apoptotic/necrotic cells in this region. A decrease in LHRH messenger RNA in forebrain neurons indicates regulation of LHRH occurred at the transcriptional or posttranscriptional level in mutant animals. These results indicate a developmentally restricted involvement of the transcription factor AP-2 in LHRH expression once the LHRH neurons have migrated into the forebrain, but before establishment of an adult-like distribution. C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16302 USA. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bldg 36,Room 5A-25, Bethesda, MD 20895 USA. EM swray@codon.nih.gov OI Kramer, Phillip/0000-0003-0117-542X; wray, susan/0000-0001-7670-3915 NR 74 TC 41 Z9 41 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 MAY PY 2000 VL 141 IS 5 BP 1823 EP 1838 DI 10.1210/en.141.5.1823 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WL UT WOS:000088386000030 PM 10803593 ER PT J AU Evans-Storms, RB Cidlowski, JA AF Evans-Storms, RB Cidlowski, JA TI Delineation of an antiapoptotic action of glucocorticoids in hepatoma cells: The role of nuclear factor-kappa B SO ENDOCRINOLOGY LA English DT Article ID LIVER-REGENERATION; PREVENTS APOPTOSIS; HUMAN NEUTROPHILS; ARACHIDONIC-ACID; THYROID-HORMONE; HTC CELLS; BCL-X; DEXAMETHASONE; ACTIVATION; INHIBITION AB Glucocorticoids are primarily recognized for their profound antiinflammatory actions and their ability to induce lymphocyte apoptosis. We report here that, in contrast to their effect on cells of the immune system, glucocorticoids suppress serum deprivation induced apoptosis of rat hepatoma (HTC) cells. Suppression of apoptosis in these cells occurs at physiological concentrations of glucocorticoid and is abrogated by the glucocorticoid antagonist RU486. Although HTC cells also express receptors for progesterone, estrogen, and thyroid hormone, ligands for these receptors fail to rescue these cells from programmed cell death. Because the sensitivity of cells to apoptotic stimuli is often regulated by the ratio of antiapoptotic to proapoptotic Bcl-2 family members, we analyzed the influence of glucocorticoids and induction of apoptosis by serum starvation on the expression of these proteins. Bcl-2, Bcl-x(L), Bad, Bak, and Bar levels were not altered by either treatment. Mitochondrial function has recently been implicated as a critical early regulator of apoptosis in many cells including hepatocytes. Dexamethasone treatment blocked a decrease in this potential (Delta psi(m)) during serum deprivation induced apoptosis in HTC cells, indicating an action of this hormone upstream of mitochondria. We also show that the induction of apoptosis in HTC cells is associated with a decrease in nuclear factor (NF)-kappa B. Treatment with dexamethasone effectively blocked the loss of nuclear NF-kappa B, suggesting that this hormone acts to suppress apoptosis of HTC cells via regulation of this nuclear transcription factor. This hypothesis was confirmed by transfection experiments that show that expression of a superrepressor of NF-kappa B inhibits the ability of dexamethasone to rescue HTC cells from apoptosis induced by serum deprivation. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), POB 12233,MD E2-02, Res Triangle Pk, NC 27709 USA. EM Cidlowski@niehs.nih.gov NR 66 TC 75 Z9 76 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 MAY PY 2000 VL 141 IS 5 BP 1854 EP 1862 DI 10.1210/en.141.5.1854 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WL UT WOS:000088386000033 PM 10803596 ER PT J AU Mage, DT Alavanja, MCR Sandler, DP McDonnell, CJ Kross, B Rowland, A Blair, A AF Mage, DT Alavanja, MCR Sandler, DP McDonnell, CJ Kross, B Rowland, A Blair, A TI A model for predicting the frequency of high pesticide exposure events in the agricultural health study SO ENVIRONMENTAL RESEARCH LA English DT Article DE pesticides; pesticide poisoning; accidental exposures; farmers; exposure assessment ID COHORT; INJURY AB The frequency of self-reported high pesticide exposure events (HPEE) has been recorded in the NCI/EPA/NIEHS Agricultural Health Study (AHS). Fourteen percent (14%) of the enrolled applicators responding reported "an incident or experience while using any pesticide which caused an unusually high exposure." These data show, as expected, that the probability of a report of an HPEE increases with the cumulative number of days of pesticide application reported by the applicator. We have developed a three-parameter model that predicts the risk odds ratio (OR) of an HPEE as a function of the number of days that pesticides are applied. These events are costly in terms of resulting health-care visits, lost time from work, and potential risk for cancer and other chronic diseases. We propose that failure to carefully follow all the pesticide manufacturer's label requirements, inexperience, and random events (i.e., breaking hose) are the three factors responsible for the events observed. Special precautions for new or infrequent users of pesticides are indicated. (C) 2000 Academic Press. C1 US EPA, Natl Ctr Environm Assessment, Res Triangle Pk, NC 27711 USA. NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. NIEHS, Res Triangle Pk, NC 27709 USA. SRA Technol Inc, Falls Church, VA USA. Univ Iowa, Iowa City, IA USA. RP Mage, DT (reprint author), US EPA, Natl Ctr Environm Assessment, MD-52, Res Triangle Pk, NC 27711 USA. OI Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [N01-CP-33048, N01-CP-33047, N01-CP-21905] NR 10 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD MAY PY 2000 VL 83 IS 1 BP 67 EP 71 DI 10.1006/enrs.1999.4032 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 313PG UT WOS:000087007600007 PM 10845783 ER PT J AU Longnecker, MP Gladen, BC Patterson, DG Rogan, WJ AF Longnecker, MP Gladen, BC Patterson, DG Rogan, WJ TI Polychlorinated biphenyl (PCB) exposure in relation to thyroid hormone levels in neonates SO EPIDEMIOLOGY LA English DT Article DE thyroid hormones; polychlorinated biphenyls; perinatology; maternal exposures ID HUMAN-MILK; POSTNATAL EXPOSURE; HUMAN HEALTH; INFANTS; DIOXINS; DDE; AROCLOR-1254; CONGENERS; THYROXINE; SYSTEM AB Polychlorinated biphenyls (PCBs) are industrially produced environmentally persistent compounds. In developed countries all humans have detectable levels in blood and other tissues. PCBs alter thyroid hormone metabolism in animal experiments, and human data suggest background-level exposure may have similar effects in neonates. We evaluated this possible effect among 160 North Carolina children whose in utero PCB exposure was estimated on the basis of the mother's PCB levels in milk and blood, in 1978-1982 (estimated median PCB level in milk at birth, 1.8 mg/kg lipid). Their umbilical cord sera were thawed in 1998 and assayed for total thyroxine, free thyroxine, and thyroid stimulating hormone. We found that PCB exposure was not strongly related to any of the thyroid measures. For example, for a one unit change in milk PCB concentration (mg/kg lipid), the associated multivariate-adjusted increase in thyroid stimulating hormone level was 7% (95% confidence limits (CL) = -6, 21), Despite the possibility of sample degradation, these data suggest that within the range of background-level exposure in the United States, in utero PCB exposure is only slightly related to serum concentration of total thyroxine, free thyroxine, and thyroid stimulating hormone at birth. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Ctr Dis Control, Div Environm Hlth Lab Sci, Atlanta, GA 30333 USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012; OI Rogan, Walter/0000-0002-9302-0160; Longnecker, Matthew/0000-0001-6073-5322 NR 35 TC 67 Z9 67 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2000 VL 11 IS 3 BP 249 EP 254 DI 10.1097/00001648-200005000-00004 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 306KV UT WOS:000086596600004 PM 10784239 ER PT J AU Pinsky, PF AF Pinsky, PF TI Does hereditary nonpolyposis colorectal cancer explain the observed excess risk of colorectal cancer associated with family history? SO EPIDEMIOLOGY LA English DT Article DE adenomatous polyps; colorectal cancer; family history; hereditary nonpolyposis colorectal cancer; relative risk ID ADENOMATOUS POLYPS; COLON-CANCER; POPULATION; FREQUENCY; TUMORS AB Several studies have found an increased risk of colorectal cancer associated with a family history of colorectal cancer. Some studies, although not all, have also suggested that family history of colorectal cancer may be a risk factor for adenomatous polyps. Hereditary nonpolyposis colorectal cancer is a known genetic syndrome predisposing to colorectal cancer. The hypothesis of this paper is that the preponderance of the genetic or familial risk for colorectal cancer in the United States is mediated by hereditary nonpolyposis colorectal cancer. To test this hypothesis, I have incorporated what is known about hereditary nonpolyposis colorectal cancer into a genetic model that generates probabilities of family clustering of colo-rectal cancer. Using this model, which assumes that all familial risk for colorectal cancer is due to hereditary nonpolyposis colorectal cancer, the expected relative risks for colorectal cancer (and adenomas) associated with given types of family histories were calculated. The relative risks predicted by the model fairly closely matched the results found in the literature, especially those reported from a large cohort study. As observed in several studies, the model predicts that relative risks decrease sharply with age. In contrast to the elevated risk for colorectal cancer, the model predicts no elevated risk for adenomas associated with family history of colorectal cancer. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Div Canc Prevent, 6130 Execut Blvd,EPN 330, Bethesda, MD 20892 USA. NR 28 TC 5 Z9 5 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2000 VL 11 IS 3 BP 297 EP 303 DI 10.1097/00001648-200005000-00012 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 306KV UT WOS:000086596600012 PM 10784247 ER PT J AU Svanberg, E Ohlsson, C Kimball, SR Lundholm, K AF Svanberg, E Ohlsson, C Kimball, SR Lundholm, K TI rhIGF-I/IGFBP-3 complex, but not free rhIGF-I, supports muscle protein biosynthesis in rats during semistarvation SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE 4E-binding protein 1; eucaryotic initiation factor 4E; messenger RNA; nutrition; protein synthesis ID GROWTH-FACTOR-I; MESSENGER-RNA LEVELS; FACTOR-BINDING PROTEIN-3; IGF-I; SOLUTION HYBRIDIZATION; NUTRITIONAL REGULATION; PERIPHERAL-TISSUES; SKELETAL-MUSCLE; GENE-EXPRESSION; WHOLE-BODY AB Background The aim of this study was to evaluate the effect of insulin like growth factor-I (rhIGF-I) in complex with binding protein 3 (IGFBP 3) compared to the effect of free IGF-I on muscle protein biosynthesis in undernourished animals. Methods Three groups of female Sprague-Dawley rats (200 g) were initially semi-starved for 3 days and then treated with saline (controls), rhIGF-I (1 mu g g(-1)) or equimolar amounts of rhIGF-I/rhIGFBP-3 complex (5 mu g g(-1)) i.v. twice daily for 3 days during continuous semistarvation. Protein metabolism in hind limb skeletal muscle was studied by incorporation of L-[C-14-U]phenylalanine into proteins, western blot determination of translation initiation factors involved in the binding of the 40S ribosomal subunit to mRNA, and quantification of mRNA content for IGF-I, IGF-IR and GH-R. Plasma measurements of insulin, IGF-I and amino acids were also performed. Results rhIGF-I/rhIGFBP-3, but not rhIGF-I alone, stimulated protein synthesis by 177 +/- 26% (P less than or equal to 0.05) in semi-starved rats. This stimulation was associated with dissociation of the 4E-BP1.eIF-4E complex, implicating increased binding of the 40S ribosomal subunit to mRNA, and hence increased initiation of protein synthesis in these animals. Muscle content of IGF-I mRNA was reduced in semi-starved animals, whereas IGF-I receptor mRNA was unaltered despite food restriction. Plasma concentration of IGF-I was 20% (P less than or equal to 0.05) higher in rhIGF-I/rhIGFBP-3 treated animals as compared to rats treated with saline or free IGF-I. Plasma concentrations of amino acids were increased in rhIGF-I/rhIGFBP-3 treated animals (P less than or equal to 0.05 vs. semi-starved controls). Conclusion rhIGF-I/rhIGFBP-3 (SomatoKine) was a significant stimulator of muscle protein synthesis in chronically semi-starved animals whereas IGF-I alone failed to increase protein synthesis during the same experimental conditions. This stimulation was because of increased initiation of translation, likely induced by more physiologic concentrations/kinetics of plasma IGF-I and amino acids following rhIGF-I/rhIGFBP-3 treatment, compared to IGF-I in its free form. C1 Gothenburg Univ, Sahlgrens Univ Hosp, Dept Surg, S-41345 Gothenburg, Sweden. Gothenburg Univ, Sahlgrens Univ Hosp, Dept Internal Med, S-41345 Gothenburg, Sweden. NIDDK, NIH, Bethesda, MD USA. Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA USA. RP Svanberg, E (reprint author), Gothenburg Univ, Sahlgrens Univ Hosp, Dept Surg, S-41345 Gothenburg, Sweden. NR 46 TC 24 Z9 26 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD MAY PY 2000 VL 30 IS 5 BP 438 EP 446 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 317CM UT WOS:000087208100010 PM 10809904 ER PT J AU Pope, SH Fibach, E Sun, J Chin, K Rodgers, GP AF Pope, SH Fibach, E Sun, J Chin, K Rodgers, GP TI Two-phase liquid culture system models normal human adult erythropoiesis at the molecular level SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE erythropoiesis; gene expression; globins; transcription factors ID TRANSCRIPTION FACTOR GATA-1; BETA-GLOBIN GENE; LOCUS-CONTROL REGION; ERYTHROID DEVELOPMENT; HEMATOPOIETIC-CELLS; RECEPTOR GENE; ALPHA-GLOBIN; SP1; DIFFERENTIATION; EXPRESSION AB We have studied the patterns of expression of various genes during maturation of normal human adult erythroid precursors cultured in a two-phase liquid culture method. In the first phase, peripheral blood mononuclear cells are cultured for one week in the presence of a combination of growth factors, but not erythropoietin (Epo). In Phase II, Epo is included in the medium. Cell samples were taken throughout phase II, and expression of globins, transcription factors, and cytokine receptors was assayed by RT-PCR and quantified by phosphor imaging. We have divided phase II into stages: early (days 0-5), intermediate (days 6-10) and late (days 11-15) and measured maximum expression of each gene. During early phase II, gamma-globin, Sp1, and GATA-2 mRNAs were expressed at their highest levels. As the cells matured during the intermediate period, GATA-2 levels remained high, and then declined, while the transcription factors GATA-1, EKLF, NF-E2, and the Epo receptor (EpoR) reached maximum expression. In late phase II, beta-globin increased and reached its maximum level of expression. This erythroid culture system appears to recapitulate normal adult erythropoiesis at the molecular level, and thus may be a suitable model to examine the molecular basis of severe congenital or acquired disorders of erythropoiesis. C1 NIDDK, Mol & Clin Branch, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Dept Hematol, IL-91120 Jerusalem, Israel. RP Rodgers, GP (reprint author), NIDDK, Mol & Clin Branch, NIH, 10-9N119,10 Ctr Dr MSC 1822, Bethesda, MD 20892 USA. NR 49 TC 60 Z9 61 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD MAY PY 2000 VL 64 IS 5 BP 292 EP 303 DI 10.1034/j.1600-0609.2000.90032.x PG 12 WC Hematology SC Hematology GA 315XQ UT WOS:000087138600002 PM 10863975 ER PT J AU Ben-Sasson, SZ Makedonski, K Hu-Li, J Paul, WE AF Ben-Sasson, SZ Makedonski, K Hu-Li, J Paul, WE TI Survival and cytokine polarization of naive CD4(+) T cells in vitro is largely dependent on exogenous cytokines SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE naive T cell; IL-4; IL-6; Th1; Th2 polarization ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; LINKING FC-RECEPTORS; IN-VIVO; INTERLEUKIN-4 PRODUCTION; SECRETE INTERLEUKIN-4; IL-6-DEFICIENT MICE; GAMMA PRODUCTION; INNATE IMMUNITY; IFN-GAMMA; TH2 CELLS AB Naive CD4(+) T cells differ from memory cells by their heightened expression of the disialoceramide recognized by antibody 3G11.3G11(bright) cells respond well to immobilized anti-CD3/anti-CD28 and to their cognate antigens but produce little or no IFN-gamma or IL-4 "acutely" and undergo cell death even in the presence of IL-2. They can be rescued by IL-4, IL-6 or IL-12. IL-6 is particularly notable since it is neutral in regard to Th1/Th2 priming, allowing an assessment of the role of endogenous IL-4 in priming for IL-4 production. Naive TCR-transgenic BALB/c scid T cells cultured with an ovalbumin peptide and IL-4(-/-) antigen-presenting cells in the presence of IL-6 showed a modest degree of priming for IL-4 production if both IFN-gamma and IL-12 were neutralized. This priming is far less than that observed if IL-4 is added to the priming culture. These results indicate that IL-4 production as a result of TCR engagement is sufficient for only a minor component of the polarization observed when unseparated BALB/c CD4 T cell populations are primed or when IL-4 is intentionally added to the priming culture. C1 NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, IL-91010 Jerusalem, Israel. RP Paul, WE (reprint author), NIAID, NIH, Immunol Lab, Bldg 10,Rm 11N311,10 Ctr Dr MSC 1892,L1, Bethesda, MD 20892 USA. NR 46 TC 31 Z9 31 U1 0 U2 0 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 MAY PY 2000 VL 30 IS 5 BP 1308 EP 1317 DI 10.1002/(SICI)1521-4141(200005)30:5<1308::AID-IMMU1308>3.0.CO;2-I PG 10 WC Immunology SC Immunology GA 317VM UT WOS:000087247700007 PM 10820376 ER PT J AU Wu, CY Gadina, M Wang, KN O'Shea, J Seder, RA AF Wu, CY Gadina, M Wang, KN O'Shea, J Seder, RA TI Cytokine regulation of IL-12 receptor beta 2 expression: differential effects on human T and NK cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cytokine; IFN; IL-12 receptor; NK cell; T cell ID INTERFERON-GAMMA PRODUCTION; TH2 CELLS; GENE-EXPRESSION; INTERLEUKIN-12 RESPONSIVENESS; SELECTIVE EXPRESSION; VIRAL-INFECTION; IN-VITRO; ACTIVATION; ALPHA; INHIBITION AB The biological activities of IL-12 are mediated through a specific, high-affinity receptor composed of IL-12 receptor(R)beta 1 and IL-12R beta 2 subunits that exist primarily on T and NK cells. Remarkably, the expression of IL-12R beta 2 on CD4(+) T cells in mouse and humans appears to be differentially regulated by IFN-gamma and IFN-alpha, respectively. Using an antibody specific for the human IL-12R beta 2 subunit, the effect of IFN-gamma, IFN-alpha, IL-12 and IL-2 on the regulation of IL-12R expression and IL-12 responsiveness of human T and NK cells was assessed. The presence of IFN-alpha or IFN-gamma in cultures enhanced IL-12R beta 2 expression of CD4(+) and CD8(+) T cells. The enhancing effect of IFN-alpha and IFN-gamma was independent of endogenous IL-12. Furthermore, the dearest effects of IFN-alpha and IFN-gamma on IL-12R beta 2 expression on T cells were seen by abrograting the inhibition induced by the presence of IL-4 in cultures. In contrast to T cells, IFN-alpha and IFN-gamma had little effect on regulating IL-12R beta 2 expression on human NK cells. Taken together, these data show that there is differential regulation of IL-12R beta 2 expression by IFN-alpha and IFN-gamma on human T and NK cells. C1 NIAID, LCI, NIH, Clin Immunol Sect, Bethesda, MD 20892 USA. NIAMSD, Arthritis & Theumatism Branch, Lymphocyte Cell Biol, NIH, Bethesda, MD 20892 USA. NIAID, Lab Clin Invest, Med Virol Sect, NIH, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIAID, LCI, NIH, Clin Immunol Sect, 10 Ctr Dr,Room 10-11C215, Bethesda, MD 20892 USA. NR 22 TC 44 Z9 50 U1 0 U2 0 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 MAY PY 2000 VL 30 IS 5 BP 1364 EP 1374 DI 10.1002/(SICI)1521-4141(200005)30:5<1364::AID-IMMU1364>3.0.CO;2-U PG 11 WC Immunology SC Immunology GA 317VM UT WOS:000087247700014 PM 10820383 ER PT J AU Auerbach, JM Eiden, MV McKay, RDG AF Auerbach, JM Eiden, MV McKay, RDG TI Transplanted CNS stem cells form functional synapses in vivo SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE CNS stem cells; electrophysiology; hippocampus; rat; synapse formation; transplantation ID CENTRAL-NERVOUS-SYSTEM; TRANSPORTER CURRENTS; GLUTAMATE RELEASE; PROGENITOR CELLS; DIFFERENTIATION; PRECURSORS; NEURONS; FOREBRAIN; BRAIN; NEUROGENESIS AB An understanding of developmental mechanisms and new cell therapies can be achieved by transplantation into the nervous system. Multipotential stem cells have been isolated from the foetal and adult central nervous system (CNS). Immortalized and primary precursor cells integrate into the developing brain generating both neurons and glia as defined by immunological and morphological criteria. Here we show for the first time that in vitro-expanded CNS precursors, upon transplantation into the brains of rats, form electrically active and functionally connected neurons. These neurons exhibit spontaneous and evoked postsynaptic events and respond to focal glutamate application. Donor cells were grafted into the foetal hippocampus, and the amplitude and frequency of spontaneous synaptic events were monitored in the grafted cells in area CA1 for the first month of postnatal life. The formation of synapses onto grafted neurons indicates that grafted CNS stem cells can be used to study synaptic development in vivo and has important implications for clinical cell replacement therapies. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP McKay, RDG (reprint author), NINDS, Mol Biol Lab, NIH, 36 Convent Dr, Bldg 36 Room 5A29 MCS 4157, Bethesda, MD 20892 USA. NR 38 TC 77 Z9 88 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2000 VL 12 IS 5 BP 1696 EP 1704 DI 10.1046/j.1460-9568.2000.00067.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 313YK UT WOS:000087027200018 PM 10792447 ER PT J AU Highfield, D Clements, A Shalev, U McDonald, R Featherstone, R Stewart, J Shaham, Y AF Highfield, D Clements, A Shalev, U McDonald, R Featherstone, R Stewart, J Shaham, Y TI Involvement of the medial septum in stress-induced relapse to heroin seeking in rats SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE disinhibition; drug self-administration; extinction; reinstatement; relapse; stress; septum; tetrodotoxin ID CORTICOTROPIN-RELEASING-FACTOR; FUNCTIONAL ABLATION; DRUG; TETRODOTOXIN; BEHAVIOR; SENSITIZATION; LOCALIZATION; ACQUISITION; CONNECTIONS; EXTINCTION AB Intermittent footshock stress has been shown to reinstate extinguished drug-taking behaviour in rats, but the brain areas involved in this effect are to a large degree unknown. Here we studied the role of the septum in stress-induced reinstatement of heroin seeking. Rats were trained to self-administer heroin for 9-10 days (three 3-h sessions per day, 0.1 mg/kg per infusion). Following training, extinction sessions were given for 8-13 days by substituting saline for heroin, and then tests for reinstatement of heroin seeking were carried out. Reversible inactivation of the medial septum with tetrodotoxin (TTX; 1-5 ng, infused 25-40 min before the test sessions) reliably reinstated heroin seeking, mimicking the effect of 15 min of intermittent footshock. This effect of TTX was not observed after infusions made 1.5 mm dorsally into the lateral septum. In other experiments, it was found that infusions of a low, subthreshold dose of TTX (0.5 ng) into the medial septum, when combined with 2 min of footshock that in itself was ineffective, reinstated heroin seeking. Furthermore, electrical stimulation (400 mu A pulses, 100 mu s duration, 100 Hz frequency) of the medial septum during exposure to 10 min of intermittent footshock attenuated footshock-induced reinstatement of heroin seeking. These data suggest a role for the medial septum in stress-induced relapse to drug seeking. The septum is thought to be involved in neuronal processes underlying behavioural inhibition, thus we speculate that stressors provoke relapse by interfering with these processes. C1 NIA, IRP, Behav Neurosci Branch, Baltimore, MD 21224 USA. Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. Concordia Univ, Dept Psychol, CSBN, Montreal, PQ H3G 1M8, Canada. RP Shaham, Y (reprint author), NIA, IRP, Behav Neurosci Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI featherstone, robert/F-8255-2011; shaham, yavin/G-1306-2014 NR 54 TC 30 Z9 33 U1 3 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2000 VL 12 IS 5 BP 1705 EP 1713 DI 10.1046/j.1460-9568.2000.00037.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 313YK UT WOS:000087027200019 PM 10792448 ER PT J AU Zalla, T Koechlin, E Pietrini, P Basso, G Aquino, P Sirigu, A Grafman, J AF Zalla, T Koechlin, E Pietrini, P Basso, G Aquino, P Sirigu, A Grafman, J TI Differential amygdala responses to winning and losing: a functional magnetic resonance imaging study in humans SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE brain; competition; emotion; motivation; punishment; reward ID UNILATERAL TEMPORAL LOBECTOMY; FACIAL EXPRESSIONS; PREFRONTAL CORTEX; BASAL GANGLIA; VENTRAL STRIATUM; NEURAL RESPONSES; DOPAMINE NEURONS; REWARD; MEMORY; ACTIVATION AB The amygdala has been shown to respond to many distinct types of affective stimuli, including reward and punishment feedback in animals. In humans, winning and losing situations can be considered as reward and punishment experiences, respectively. In this study, we used functional magnetic resonance imaging (fMRI) to measure regional brain activity when human subjects were given feedback on their performance during a simple response time task in a fictitious competitive tournament. Lexical stimuli were used to convey positive 'win' or negative 'lose' feedback. The frequency of positive and negative trials was parametrically varied by the experimenters independently from the subjects' actual performance and unbeknownst to them. The results showed that the parametric increase of winning was associated with left amygdala activation whereas the parametric increase of losing was associated with right amygdala activation. These findings provide functional evidence that the human amygdala differentially responds to changes in magnitude of positive or negative reinforcement conveyed by lexical stimuli. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Univ Pisa, Dept Human & Environm Sci, I-56100 Pisa, Italy. Inst Cognit Sci, F-69675 Bron, France. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RI Basso, Gianpaolo/A-9208-2012; Koechlin, Etienne/E-5061-2016; OI Basso, Gianpaolo/0000-0002-6245-9402; Grafman, Jordan H./0000-0001-8645-4457 NR 68 TC 105 Z9 108 U1 7 U2 11 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2000 VL 12 IS 5 BP 1764 EP 1770 DI 10.1046/j.1460-9568.2000.00064.x PG 7 WC Neurosciences SC Neurosciences & Neurology GA 313YK UT WOS:000087027200024 PM 10792453 ER PT J AU Kiyatkin, EA Rebec, GV AF Kiyatkin, EA Rebec, GV TI Dopamine-independent action of cocaine on striatal and accumbal neurons SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE addictive behaviour; cocaine reward; dopamine uptake; local anaesthesia; rats; sodium channels ID TRANSPORTER KNOCKOUT MICE; RAT NUCLEUS-ACCUMBENS; FREELY MOVING RATS; IN-VIVO; REINFORCING PROPERTIES; LOCAL-ANESTHETICS; UNRESTRAINED RATS; INHIBITION; GLUTAMATE; RECEPTORS AB Increasing evidence suggests that dopamine (DA) mechanisms alone cannot fully explain the psychoemotional and behavioural effects of cocaine, including its ability to induce drug-taking behaviour. Although it is known that cocaine, after intravenous administration or smoking, may reach brain levels high enough to inhibit Na+ transport, the role of this action remains unclear. To examine the contribution of local anaesthetic and DA mechanisms to changes in striatal and accumbal neuronal activity induced by cocaine, single-unit recording was combined with iontophoresis in awake, unrestrained rats. Most spontaneously active and glutamate-stimulated neurons were highly sensitive to brief cocaine applications (0-40 nA); cocaine-induced inhibitions occurred at small ejection currents (0-5 nA), were dose-dependent, highly stable during repeated applications and strongly dependent on basal activity rates. These neuronal responses remained almost unchanged after systemic administration of either a selective D1 antagonist (SCH-23390, 0.2 mg/kg) or a combination of SCH-23390 (1 mg/kg) and eticlopride (1 mg/kg), a D2 antagonist. Whereas SCH-23390 alone had a weak attenuating effect, no effect and even a slight enhancement of responses to cocaine occurred in fast-firing glutamate (GLU)-stimulated units after the combined blockade of D1 and D2 receptors. Responses to cocaine were mimicked by iontophoretic procaine (0-40 nA), a short-acting local anaesthetic with minimal effect on DA uptake. Procaine-induced inhibitions occurred at the same low currents, had a similar time-course, and were also strongly dependent on basal discharge rate. Our data support the existence of a DA-independent mechanism for the action of cocaine involving a direct interaction with Na+ channels. Although further studies are required to clarify this mechanism and its interaction with other pharmacological and behavioural variables, a direct interaction with Na+ channels may contribute to changes in neuronal activity induced by self-injected cocaine, thereby playing a role in mediating the psychoemotional and behavioural effects of this drug. C1 Indiana Univ, Dept Psychol, Program Neural Sci, Bloomington, IN 47405 USA. RP Kiyatkin, EA (reprint author), NIDA, IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA02451, DA00335] NR 49 TC 27 Z9 27 U1 2 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2000 VL 12 IS 5 BP 1789 EP 1800 DI 10.1046/j.1460-9568.2000.00066.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 313YK UT WOS:000087027200027 PM 10792456 ER PT J AU Eisenhofer, G Pacak, K Goldstein, DS Chen, C Shulkin, B AF Eisenhofer, G Pacak, K Goldstein, DS Chen, C Shulkin, B TI I-123-MIBG scintigraphy of catecholamine systems: impediments to applications in clinical medicine SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Letter ID MIBG SCINTIGRAPHY C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. RP Eisenhofer, G (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NR 6 TC 13 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD MAY PY 2000 VL 27 IS 5 BP 611 EP 612 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 314GW UT WOS:000087048900022 PM 10853820 ER PT J AU Kallasmaa, T Allik, J Realo, A McCrae, RR AF Kallasmaa, T Allik, J Realo, A McCrae, RR TI The Estonian version of the NEO-PI-R: An examination of universal and culture-specific aspects of the five-factor model SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article ID PERSONALITY-INVENTORY; 5-FACTOR MODEL; SELF-CONSCIOUSNESS; SCALES AB In this article, we examine universal and culture-specific aspects of the Five-Factor Model measured with the Revised NEO Personality Inventory. First, our purpose was to rest the replicability of the original (North American) factor structure in the Estonian-speaking population. The translation was administered to 711 Estonian men and women aged 18 to 82, When the 30 facet scales were factored, parallel analysis suggested that Jive components should be retained. In the interpersonal plane defined by Extraversion and Agreeableness factors, Estonian facets formed a semicircular array that resembled the American pattern at a distance of about 21 degrees. After these axes were aligned by Procrustes rotation, all five factor congruences exceeded 0.96, providing further evidence that the underlying five-factor structure of the personality instrument is replicable in languages and cultures which differ substantially from those in which it was originally identified Second we tested the hypothesis that the orientation of varimax axes in the interpersonal plane is associated with the culture's degree of individualism-collectivism. We calculated the angular degree of difference between E and A factors in the American sample and in 21 other available samples, correlated it with individualism ratings, and found mixed support for the hypothesis, suggesting that continued research on this issue is merited Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Univ Tartu, Dept Psychol, EE-50410 Tartu, Estonia. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Kallasmaa, T (reprint author), Univ Tartu, Dept Psychol, Tiigi 78, EE-50410 Tartu, Estonia. RI Allik, Juri/D-5609-2009; Realo, Anu/M-9524-2016 OI Allik, Juri/0000-0002-8358-4747; NR 46 TC 57 Z9 57 U1 0 U2 13 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD MAY-JUN PY 2000 VL 14 IS 3 BP 265 EP 278 DI 10.1002/1099-0984(200005/06)14:3<265::AID-PER376>3.0.CO;2-B PG 14 WC Psychology, Social SC Psychology GA 327NL UT WOS:000087799900005 ER PT J AU Lomnitski, L Nyska, A Shohami, E Chen, Y Michaelson, DM AF Lomnitski, L Nyska, A Shohami, E Chen, Y Michaelson, DM TI Increased levels of intracellular iron in the brains of ApoE-deficient mice with closed head injury SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE apolipoprotein E; head injury, iron, intracellular; brain, intracellular iron; oxidation-stress ID CENTRAL-NERVOUS-SYSTEM; APOLIPOPROTEIN-E; DISEASE; EXPRESSION; METABOLISM; RADICALS; MODEL AB Previous studies have revealed that apolipoprotein E (apoE)-deficient mice have distinct memory deficits and neurochemical derangements and are oxidatively stressed prior to and following closed head injury. The objective of this study was to evaluate the possibility that the enhanced susceptibility of apoE-deficient mice to closed head injury is related to impairments in their antioxidative iron-chelating mechanisms. ApoE-deficient and control mice were subjected to closed had injury, after which the extent of brain-damage and the level of iron-containing cells were assessed. Examination of the brain-damaged areas in the injured mice revealed that, by Day 3 post injury, animals of both groups were maximally and similarly affected. While the size of the damaged area of the injured control mice diminished significantly by Day 7, however recovery was not observed in injured apoE-deficient mice up to at least 14 days post-injury. Histopathologically, the decrease in the damaged areas in the control mice was interpreted as related to decreased edema. Numbers of iron-containing cells at Days 3 and 7 after injury were greater in the brains of control mice than in the apoE-deficient mice. Whereas the number of iron-containing cells in injured control mice decreased at days 9 and 14-post injury, that of the injured apoE-deficient mice plateaued by Day 9 at a level more than two-fold higher than the maximal level seen for controls. The size of the damaged areas and the number of iron-containing cells were correlated (P < 0.03) for both mouse groups at days 9 and 14 after injury. The data suggest that the increased susceptibility of apoE-deficient mice to closed head injury may be due, at least in part, to impaired iron scavenging and sustained oxidative stress. C1 Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. NIEHS, Res Triangle Pk, NC 27709 USA. Hebrew Univ Jerusalem, Dept Pharmacol, Jerusalem, Israel. RP Michaelson, DM (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. NR 35 TC 10 Z9 13 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD MAY PY 2000 VL 52 IS 2 BP 177 EP 183 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 319KY UT WOS:000087341100014 PM 10965994 ER PT J AU Quaia, C Pare, M Wurtz, RH Optican, LM AF Quaia, C Pare, M Wurtz, RH Optican, LM TI Extent of compensation for variations in monkey saccadic eye movements SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE saccades; accuracy; curvature; compensation; monkey ID STEM OMNIPAUSE NEURONS; SUPERIOR COLLICULUS; REVERSIBLE INACTIVATION; MODEL; TRANSFORMATION; CEREBELLUM; VELOCITY AB We investigated and quantified the ability of the primate saccadic system to generate accurate eye movements in spite of naturally occurring variations in saccadic speed and trajectory. We show that the amplitude of a series of saccades directed to the same target is positively correlated to their peak speed, i.e., the faster the saccade, the bigger its amplitude. We demonstrate that this result cannot be simply accounted for by the main sequence, and that on average the saccadic system is able to compensate for only 61% of the variability in speed. Deviations from the average trajectory are also only partially compensated: the underlying mechanism, which tends to bring the eyes back toward the desired trajectory, underperforms for small movements and overperforms for large movements. We also demonstrate that the performance of this compensatory mechanism, and the metrics of saccades in general, do not depend on the presence of visual information during the movement. By showing that deviations From the desired behavior are corrected during the saccade, our results further support the hypothesis that the innervation signal that generates saccadic eye movements is not pre-programmed but rather is dynamically adjusted during the movement. However, the compensation For deviations from the desired behavior is only partial, and the underlying mechanisms have yet to be completely understood. Although none of the current models of the saccadic system can account for our results, some of them, if appropriately modified, probably could. C1 NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Optican, LM (reprint author), NEI, Sensorimotor Res Lab, Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. EM loptican@nih.gov NR 38 TC 30 Z9 30 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 2000 VL 132 IS 1 BP 39 EP 51 DI 10.1007/s002219900324 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 313AZ UT WOS:000086977300004 PM 10836634 ER PT J AU Kamishohara, M Kenney, S Domergue, R Vistica, DT Sausville, EA AF Kamishohara, M Kenney, S Domergue, R Vistica, DT Sausville, EA TI Selective accumulation of the endoplasmic reticulum-Golgi intermediate compartment induced by the antitumor drug KRN5500 SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Golgi apparatus; endoplasmic reticulum; antitumor drugs; KRN5500; drug resistance ID FLUORESCENT CERAMIDE ANALOG; BREFELDIN-A; FORMIMINOTRANSFERASE-CYCLODEAMINASE; SECRETORY PATHWAY; MONOCLONAL-ANTIBODY; LEGUMINOUS LECTINS; RECYCLING PATHWAY; MEMBRANE-PROTEIN; 58-KDA PROTEIN; CIS-GOLGI AB KRN5500 is a semisynthetic spicamycin analogue consisting of a seven-carbon amino sugar linked to a C-14 unsaturated fatty acid through glycine and to the amino group of adenine, The drug inhibits cell growth potently and has antitumor activity in in vivo models. The mechanism of the antiproliferative effect of KRN5500 remains to be elucidated, We have found that acute exposure of drug-sensitive HT-29 colon adenocarcinoma cells to the drug results initially in swelling of the Golgi apparatus. Continuous exposure to the drug resulted in the emergence of a resistant population of cells characterized by numerous intracellular vacuoles, These KRN5500-resistant tumor cells exhibited increased staining with the Golgi stain NBD C-6-ceramide and the ER-Golgi fluorescent dye BODIPY-brefeldin A, which, unlike the parental drug-sensitive cells, was dispersed throughout the cytoplasm, Marker enzymes associated with the ER (glucose 6-phosphatase) and cis-Golgi (GalNAc transferase) were elevated >2-fold and nearly 4-fold, respectively, in drug-resistant cell lines while the trans-Golgi marker enzyme, galactosyltransferase, was not, The additional findings that the KRN5500-resistant cells have a >2-fold elevation in ERGIC-S3, a cis-Golgi marker protein of the ER Golgi intermediate compartment (ERGIC), as well as increased 58K, a 58-kDa microtubule-binding protein with formiminotransferase cyclodeaminase activity, and tubulin indicate that the cellular secretory pathway is a primary determinant of sensitivity to KRN5500, as resistance to this agent corresponds with accumulation of several components relatable to ER and cis-Golgi function. Further support for this conclusion is provided by studies which demonstrate that KRN5500 alters the distribution of newly synthesized carcinoembryonic antigen within the secretory pathway, including arrest of this N-glycosylated protein in the Golgi of LS-174T colon carcinoma cells. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Vistica, DT (reprint author), NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 53 TC 6 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 1 PY 2000 VL 256 IS 2 BP 468 EP 479 DI 10.1006/excr.2000.4851 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 311MR UT WOS:000086888500013 PM 10772819 ER PT J AU Hsi, LC Baek, SJ Eling, TE AF Hsi, LC Baek, SJ Eling, TE TI Lack of cyclooxygenase-2 activity in HT-29 human colorectal carcinoma cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLON-CANCER CELLS; SULINDAC SULFIDE; EPITHELIAL-CELLS; EXPRESSION; APOPTOSIS; PROSTAGLANDINS; SYNTHASE-2; APC; DIFFERENTIATION AB Induction of cyclooxygenase-2 (COX-2) is an early event in the sequence of polyp formation to colon carcinogenesis, COX-2 is at elevated levels in human colorectal cancers and in tumors and polyps of mouse models of colorectal cancer, Mutation of the adenomatous polyposis coli (APC) gene is the initial event leading to colorectal cancer, Colorectal cells in culture which express mutant APC are often used to examine the association of COX-2 expression and apoptosis, The expression of full-length APC in HT-29 cells, a human colorectal carcinoma cell line which normally expresses truncated APC and highly expresses COX-2, inhibits cell growth through increased apoptosis and results in a down-regulation of COX-2 protein, In this report, we examine whether down-regulation of COX-2 is directly linked to the increase in apoptosis observed in these HT-29-APC cells, We present evidence that COX-2 and apoptosis are not linked since COX-2, although expressed, is catalytically inactive. Interestingly, the COX-2 cloned from HT-29 cells is catalytically active when transfected into HCT-116 cells, a colorectal cell line which normally does not express COX-2, but is not active in the HT-29 cell line itself. C1 NIEHS, Eicosanoid Biochem Sect, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Eling, TE (reprint author), NIEHS, Eicosanoid Biochem Sect, Mol Carcinogenesis Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 37 TC 44 Z9 44 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 1 PY 2000 VL 256 IS 2 BP 563 EP 570 DI 10.1006/excr.2000.4863 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 311MR UT WOS:000086888500022 PM 10772828 ER PT J AU Saxena, RK Adler, WH AF Saxena, RK Adler, WH TI In vitro erythrocidal activity of activated spleen cells from young and old mice SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE erythrocytes; aging; Fas; cytotoxicity; phagocytosis ID TUMOR-NECROSIS-FACTOR; AGE-RELATED-CHANGES; T-CELLS; LYMPHOKINE PRODUCTION; PHAGOCYTOSIS AB We have recently reported that activated mouse spleen mononuclear cells (MNCs) efficiently lyse autologous erythrocytes in vitro (Saxena and Chandrasekhar, 2000). In the present study, we have investigated erythrocyte-depleting ability (EDA) of spleen MNCs from young and old mice. Time kinetics of survival of erythrocytes in mitogen-activated spleen cell cultures indicated that the erythrocyte depletion was significantly faster in young spleen cell cultures than in the old. Poorer EDA of old MNCs was in spite of the fact that the susceptibility to lysis actually increased in erythrocytes from old mice. Erythrocytes opsonized by a hamster anti mouse Fas monoclonal antibody, were destroyed with a much greater efficiency by young MNCs, whereas the corresponding effect of opsonization was only moderate for old MNCs. Depletion of macrophages from MNC preparations by plastic adherence as well as carbonyl-iron and magnet treatment had a marginal if any effect on EDA of young and old mouse MNCs, indicating that a lower lymphocyte-associated erythrocidal activity as one of the factors responsible for overall lower EDA associated with spleen derived MNCs of old mice. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India. NIA, Immunol Sect, GRC, NIH, Baltimore, MD 21224 USA. RP Saxena, RK (reprint author), Jawaharlal Nehru Univ, Sch Life Sci, New Delhi 110067, India. NR 22 TC 1 Z9 2 U1 0 U2 0 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 MAY PY 2000 VL 35 IS 3 BP 409 EP 416 DI 10.1016/S0531-5565(00)00091-7 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 322XV UT WOS:000087535400013 PM 10832060 ER PT J AU Charlab, R Rowton, ED Ribeiro, JMC AF Charlab, R Rowton, ED Ribeiro, JMC TI The salivary adenosine deaminase from the sand fly Lutzomyia longipalpis SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Lutzomyia longipalpis; Phlebotomine sand flies; blood-feeding insects; salivary glands; adenosine deaminase (EC 3.5.4.4); adenosine; inosine ID PURIFICATION; EXPRESSION; IDENTIFICATION; VASODILATORS; ARTHROPODS; RECEPTORS; MAXADILAN; BINDING; CLONING; PEPTIDE AB In the process of sequencing a subtracted cDNA library from the salivary glands of the sand fly Lutzomyia longipalpis, we identified a cDNA with similarities to gene products of the adenosine deaminase family. Prompted by this cDNA finding, we detected adenosine deaminase activity at levels of 1 U/mg protein in salivary gland homogenates. The activity was significantly reduced following a blood meal indicating its apparent secretory fate. The native enzyme has a K-m of similar to 10 mu M, an isoelectric pH between 4.5 and 5.5, and an apparent molecular weight of 52 kDa by size exclusion chromatography. The possible role of this enzyme, which converts adenosine to inosine, in the feeding physiology of L. longipalpis is discussed. C1 NIAID, Parasit Dis Lab, Sect Med Entomol, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Entomol, Washington, DC 20307 USA. RP Charlab, R (reprint author), NIAID, Parasit Dis Lab, Sect Med Entomol, NIH, Bldg 4,Room 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. RI Rowton, Edgar/A-4474-2012; Rowton, Edgar/A-1975-2011; OI Rowton, Edgar/0000-0002-1979-1485; Ribeiro, Jose/0000-0002-9107-0818 NR 35 TC 49 Z9 50 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAY PY 2000 VL 95 IS 1 BP 45 EP 53 DI 10.1006/expr.2000.4503 PG 9 WC Parasitology SC Parasitology GA 327XA UT WOS:000087818700006 PM 10864517 ER PT J AU Georgiev, VS AF Georgiev, VS TI Necatoriasis: treatment and developmental therapeutics SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE albendazole; Ancylostoma duodenale; cutaneous larva migrans; drug resistance; iron-deficiency anaemia; ivermectin; mebendazole; Necator americanus; necatoriasis ID CUTANEOUS LARVA-MIGRANS; MEMBRANE GLYCOPROTEIN-IIB; HUMAN HOOKWORM INFECTIONS; PAPUA-NEW-GUINEA; AMERICANUS INFECTION; TRICHURIS-TRICHIURA; IRON-DEFICIENCY; INTESTINAL HELMINTHIASIS; ANCYLOSTOMA-CEYLANICUM; PLATELET ACTIVATION AB Two hookworm parasites, Necator americanus and Ancylostoma duodenale, infect approximately one billion people worldwide. These hookworms are one of the leading causes of iron-deficiency anaemia especially in children, resulting directly from intestinal capillary blood loss following the feeding activities of fourth-stage (L-4) larva and adult worms. If ignored, human hookworm infections caa retard growth and the intellectual development of children. Another clinical manifestation often associated with hookworm infections is cutaneous larva migrans (CLM). It is a well recognised, usually self-limiting condition caused by the infectious larvae of nematodes, especially Ancylostoma spp. CLM is characterised by skin eruption and represents a clinical description rather than a definitive diagnosis. Of the hookworm parasites, the dog and cat worm A. braziliense and A. caninum are the most common nematodes causing CLM, although many other species have also been implicated. The major subject of this review article will be discussion of the evolution of therapies and treatment of human necatoriasis and the development of experimental infections with N. americanus. Difference in the clinical efficacy of mebendazole and albendazole will be discussed along with drug resistance of N. americanus. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Georgiev, VS (reprint author), NIAID, NIH, 7600-B Rockledge Dr,Room 2102, Bethesda, MD 20892 USA. NR 151 TC 5 Z9 6 U1 1 U2 5 PU ASHLEY PUBL LTD PI LONDON PA 1ST FL, THE LIBRARY, 1 SHEPHERDS HILL HIGHGATE, LONDON N6 5QJ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD MAY PY 2000 VL 9 IS 5 BP 1065 EP 1078 DI 10.1517/13543784.9.5.1065 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 344VR UT WOS:000088780600009 PM 11060728 ER PT J AU Macaluso, M Demand, M Artz, L Fleenor, M Robey, L Kelaghan, J Cabral, R Hook, EW AF Macaluso, M Demand, M Artz, L Fleenor, M Robey, L Kelaghan, J Cabral, R Hook, EW TI Female condom use among women at high risk of sexually transmitted disease SO FAMILY PLANNING PERSPECTIVES LA English DT Article ID SEX WORKERS; PREVENTION; ACCEPTABILITY; HIV AB Context: Whereas the female condom has been evaluated in many hypothetical acceptability or short-term use studies, there is little information about its suitability for the prevention of sexually transmitted diseases (STDs) or HIV over extended periods of time. Methodology: As part of a six-month prospective follow-up study of 1,159 STD clinic patients, clients were interviewed during their initial visit, exposed to a behavioral intervention promoting condoms, given a physical examination and provided with instructions on completing a sexual diary Potential predictors of trying the female condom were evaluated using logistic regression, and three condom-use groups (exclusive users of female condoms, exclusive users of male condoms and users of both types of condoms) were compared using multinomial regression. Results: Among 895 women who reported having engaged in vaginal intercourse during the study period, one-half had sex with only one partner, while one-quarter each had two partners or three or more partners. A total of 731 women reported using the female condom at least once during the follow-up period-85% during the first month of follow-up. Multiple logistic regression analyses indicated that employed women and those with a regular sexual partner at baseline were significantly more likely to try the female condom. By the end of the follow-up period, 8% of participants had used the female condom exclusively, 15% had used the male condom exclusively, 73% had used both types of condom and 3% had used no condoms. Twenty percent of women who tried the female condom used it only once and 13% used it twice, while 20% used 5-9 female condoms and 32% used 10 or more. Consistent condom users (N = 309) were predominantly users of both types of condom (75%), and were less often exclusive users of the male condom (78%) or the female condom (7%). According to a multivariate analysis, women who used the female condom exclusively or who mixed condom types were more likely to be black, were more likely to be employed and were more likely to have a regular partner than were users of the male condom. Conclusions: Women at risk of STDs find the female condom acceptable and will try it, and some use it consistently Mixing use of female condoms and male condoms may facilitate consistent condom use. The female condom may improve an individual's options for risk reduction and help reduce the spread of STDs. C1 Univ Alabama, Sch Publ Hlth, Dept Epidemiol & Int Hlth, Birmingham, AL 35294 USA. Jefferson Cty Dept Hlth, Birmingham, AL USA. Madison Cty Hlth Dept, Huntsville, AL USA. NICHHD, Ctr Populat Res, Bethesda, MD 20892 USA. NCI, Community Oncol & Prevent Trials Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. CDC, Ctr Dis Control & Prevent, Natl Ctr Chron Dis Control & Prevent, Div Reprod Hlth,Womens Hlth & Fertil Branch, Atlanta, GA 30333 USA. Univ Alabama, Sch Med, Dept Med, Birmingham, AL USA. Jefferson Cty Dept Hlth, Birmingham, AL USA. RP Macaluso, M (reprint author), Univ Alabama, Sch Publ Hlth, Dept Epidemiol & Int Hlth, Birmingham, AL 35294 USA. RI Macaluso, Maurizio/J-2076-2015 OI Macaluso, Maurizio/0000-0002-2977-9690 FU NICHD NIH HHS [N01-HD-1-3135]; PHS HHS [U48/CCU409679-02, SIP 10] NR 25 TC 44 Z9 44 U1 0 U2 2 PU ALAN GUTTMACHER INST PI NEW YORK PA 120 WALL STREET, NEW YORK, NY 10005 USA SN 0014-7354 J9 FAM PLANN PERSPECT JI Fam. Plann. Perspect. PD MAY-JUN PY 2000 VL 32 IS 3 BP 138 EP 144 DI 10.2307/2648163 PG 7 WC Demography; Family Studies SC Demography; Family Studies GA 327YF UT WOS:000087821500006 PM 10894260 ER PT J AU Pedersen, WA Luo, H Kruman, I Kasarskis, E Mattson, MP AF Pedersen, WA Luo, H Kruman, I Kasarskis, E Mattson, MP TI The prostate apoptosis response-4 protein participates in motor neuron degeneration in amyotrophic lateral sclerosis SO FASEB JOURNAL LA English DT Article DE NSC-19; oxidative stress; spinal cord; superoxide dismutase; transgenic mice ID LIPID-PEROXIDATION PRODUCT; AMYLOID BETA-PEPTIDE; TRANSGENIC MOUSE MODEL; SUPEROXIDE-DISMUTASE MUTATION; METHYL-D-ASPARTATE; OXIDATIVE STRESS; SPINAL-CORD; GLUTAMATE TRANSPORTER; FAMILIAL ALS; MITOCHONDRIAL DYSFUNCTION AB Prostate apoptosis response-4 (Par-4), a protein containing a leucine zipper domain within a death domain, is up-regulated in prostate cancer cells and hippocampal neurons induced to undergo apoptosis, Here, we report higher Par-4 levels in lumbar spinal cord samples from patients with amyotrophic lateral sclerosis (ALS) than in lumbar spinal cord samples from neurologically normal patients, We also compared the levels of Par-4 in lumbar spinal cord samples from wild-type and transgenic mice expressing the human Cu/Zn-superoxide dismutase gene with a familial ALS mutation. Relative to control samples, higher Par-4 levels were observed in lumbar spinal cord samples prepared from the transgenic mice at a time when they had hind-limb paralysis, Immunohistochemical analyses of human and mouse lumbar spinal cord sections revealed that Par-4 is localized to motor neurons in the ventral horn region. In culture studies, exposure of primary mouse spinal cord motor neurons or NSC-19 motor neuron cells to oxidative insults resulted in a rapid and large increase in Par-4 levels that preceded apoptosis, Pretreatment of the motor neuron cells with a Par-4 antisense oligonucleotide prevented oxidative stress-induced apoptosis and reversed oxidative stress-induced mitochondrial dysfunction that preceded apoptosis, Collectively, these data suggest a role for Par-4 in models of motor neuron injury relevant to ALS. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, GRC 4F01,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 FU NIA NIH HHS [AG14554]; NINDS NIH HHS [NS35253] NR 69 TC 56 Z9 62 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2000 VL 14 IS 7 BP 913 EP 924 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 309CG UT WOS:000086749500009 PM 10783145 ER PT J AU Iida, R Saito, K Yamada, K Basile, AS Sekikawa, K Takemura, M Fujii, H Wada, H Seishima, M Nabeshima, T AF Iida, R Saito, K Yamada, K Basile, AS Sekikawa, K Takemura, M Fujii, H Wada, H Seishima, M Nabeshima, T TI Suppression of neurocognitive damage in LP-BM5-infected mice with a targeted deletion of the TNF-alpha gene SO FASEB JOURNAL LA English DT Article DE animal model; AIDS; TNF-alpha-(-/-) mice; dementia; learning; behavior ID TUMOR-NECROSIS-FACTOR; CENTRAL-NERVOUS-SYSTEM; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; RETROVIRUS-INDUCED IMMUNODEFICIENCY; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PERIPHERAL BENZODIAZEPINE RECEPTORS; MURINE MODEL; LEUKEMIA-VIRUS; DEFICIENT MICE; MESSENGER-RNA AB Brain levels of TNF-alpha increase in many including HIV-1 infection and may contribute to neurodegenerative processes. The paucity of agents that can selectively and potently block TNF-alpha processing or its receptors has led us to investigate the role of TNF-alpha in chronic neurodegeneration associated with retroviral infection using mice with targeted deletions of the TNF-alpha gene, Infection of wild-type C57BL/6 mice with the LP-BM5 murine leukemia retrovirus mixture leads to the development of a severe immunodeficiency as well as cognitive deficits and neuronal damage. TNF-alpha-(-/-) mice infected with LP-BM5 developed a systemic immunopathology indistinguishable in severity from that observed in contemporaneously infected wild-type mice. In contrast, the performance of infected TNF-alpha-(-/-) mice in the Y-maze and Morris water maze was not different from that of uninfected TNF-alpha-(-/-) mice. The extent of glial activation in the striatum, as indicated by the increase in density of peripheral benzodiazepine receptors, was equivalent in both groups of LP-BM5-infected mice. However, the decrease in striatal MAP-2 expression, a marker of neurodegeneration observed in infected wild-type mice, was not found in infected TNF-alpha-(-/-) mice. While the loss of TNF-alpha appeared to have no effect on the course or severity of the central or peripheral immunopathology resulting from LP-BM5 infection, the behavioral and biochemical manifestations were substantially curtailed in the TNF-alpha-(-/-) mice. These findings directly support a role for TNF-ai in the neurodegenerative processes associated with viral infections such as HIV-1. C1 Gifu Univ, Sch Med, Dept Lab Med, Gifu 5008705, Japan. Nagoya Univ, Grad Sch Med, Dept Neuropsychopharmacol & Hosp Pharm, Nagoya, Aichi 4668560, Japan. JBC Inc, Gifu Res Lab, Gifu 5030628, Japan. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Natl Inst Anim Hlth, Dept Immunol, Tsukuba, Ibaraki 3050856, Japan. RP Gifu Univ, Sch Med, Dept Lab Med, Gifu 5008705, Japan. EM saito@cc.gifu-u.ac.jp; tnabeshi@.med.nagoya-u.ac.jp RI Yamada, Kiyofumi/I-7487-2014 OI Yamada, Kiyofumi/0000-0002-5280-5180 NR 50 TC 22 Z9 22 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD MAY PY 2000 VL 14 IS 7 BP 1023 EP 1031 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 309CG UT WOS:000086749500022 PM 10783158 ER PT J AU Hsu, TC Young, MR Cmarik, J Colburn, NH AF Hsu, TC Young, MR Cmarik, J Colburn, NH TI Activator protein 1 (AP-1)- and nuclear factor kappa B (NF-kappa B)-dependent transcriptional events in carcinogenesis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE AP-1; NF-kappa B; JB6 cells; tumor promotion; free radical ID TUMOR-NECROSIS-FACTOR; MOUSE EPIDERMAL-CELLS; MANGANESE-SUPEROXIDE-DISMUTASE; DNA-BINDING ACTIVITY; INDUCED NEOPLASTIC TRANSFORMATION; PROMOTER-INDUCED TRANSFORMATION; SIGNAL-TRANSDUCTION PATHWAYS; SENSITIVE JB6 CELLS; BREAST-CANCER CELLS; KINASE-C SUBSTRATE AB Generation of reactive oxygen species (ROS) during metabolic conversion of molecular oxygen imposes a constant threat to aerobic organisms. Other than the cytotoxic effects, many ROS and oxidants are also potent tumor promoters linking oxidative stress to carcinogenesis. Clonal variants of mouse epidermal JB6 cells originally identified for their differential susceptibility to tumor promoters also show differential reduction-oxidation (redox) responses providing a unique model to study oxidative events in tumor promotion. AP-1 and NF-kappa B, inducible by tumor promoters or oxidative stimuli, show differential protein levels or activation in response to tumor promoters in JB6 cells. We further demonstrated that AP-1 and NF-kappa B are both required for maintaining the transformed phenotypes where inhibition of either activity suppresses transformation response in JB6 cells as well as human keratinocytes and transgenic mouse. NF-kappa B proteins or extracellular signal-regulated kinase (ERK) but not AP-1 proteins are shown to be sufficient for conversion from transformation-resistant to transformation-susceptible phenotype. Insofar as oxidative events regulate AP-1 and NF-kappa B transactivation, these oxidative events can be important molecular targets for cancer prevention. (C) 2000 Elsevier Science Inc. C1 NCI, Gene Regulat Sect, FCRDC, Basic Res Lab, Frederick, MD 21702 USA. SAIC Frederick, IRSP, Frederick, MD USA. RP Colburn, NH (reprint author), NCI, Gene Regulat Sect, FCRDC, Basic Res Lab, Bldg 560,Room 21-89, Frederick, MD 21702 USA. NR 168 TC 202 Z9 214 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY 1 PY 2000 VL 28 IS 9 BP 1338 EP 1348 DI 10.1016/S0891-5849(00)00220-3 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 340KG UT WOS:000088531200004 PM 10924853 ER PT J AU Shackelford, RE Kaufmann, WK Paules, RS AF Shackelford, RE Kaufmann, WK Paules, RS TI Oxidative stress and cell cycle checkpoint function SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE reactive oxygen species; oxidative stress; DNA damage; cell cycle; checkpoints; free radicals ID MATURATION-PROMOTING FACTOR; TUMOR-SUPPRESSOR GENE; CHINESE-HAMSTER OVARY; INDUCED DNA-DAMAGE; ATAXIA-TELANGIECTASIA FIBROBLASTS; P53-DEPENDENT G(1) ARREST; OXYGEN FREE-RADICALS; INDUCED G2 ARREST; B-TYPE CYCLINS; MAMMALIAN-CELLS AB Oxidative stress and the damage that results from it have been implicated in a wide number of disease processes including atherosclerosis, autoimmune disorders, neuronal degeneration, and cancer. Reactive oxygen species (ROS) are ubiquitous and occur naturally in all aerobic species, coming from both exogenous and endogenous sources. ROS are quite reactive and readily damage biological molecules, including DNA. While the damaging effects of ROS on DNA have been intensively studied, the effects of oxidative damage on cell cycle checkpoint function have not. Here will we review several biologically important ROS and their sources, the cell cycle, checkpoints, and current knowledge about the effects of ROS on initiating checkpoint responses. (C) 2000 Elsevier Science Inc. C1 NIEHS, Growth Control & Canc Grp, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Paules, RS (reprint author), NIEHS, Growth Control & Canc Grp, Mail Drop F1-05,POB 12233, Res Triangle Pk, NC 27709 USA. FU NCI NIH HHS [CA42765, CA81343, P01 CA042765] NR 275 TC 333 Z9 346 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY 1 PY 2000 VL 28 IS 9 BP 1387 EP 1404 DI 10.1016/S0891-5849(00)00224-0 PG 18 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 340KG UT WOS:000088531200009 PM 10924858 ER PT J AU Harland, M Holland, EA Ghiorzo, P Mantelli, M Bianchi-Scarra, G Goldstein, AM Tucker, MA Ponder, BAJ Mann, GJ Bishop, DT Bishop, JN AF Harland, M Holland, EA Ghiorzo, P Mantelli, M Bianchi-Scarra, G Goldstein, AM Tucker, MA Ponder, BAJ Mann, GJ Bishop, DT Bishop, JN TI Mutation screening of the CDKN2A promoter in melanoma families SO GENES CHROMOSOMES & CANCER LA English DT Article ID TUMOR-SUPPRESSOR GENE; CANCER CELL-LINES; GERMLINE MUTATIONS; MALIGNANT-MELANOMA; LINKAGE ANALYSIS; DNA METHYLATION; PRONE FAMILIES; CYCLE ARREST; P16; P16(INK4A) AB Germline mutations of CDKN2A, at 9p21, are responsible for predisposition to melanoma in some families. However, evidence of linkage to 9p21 has been demonstrated in a significant proportion of kindreds with no detectable mutations in CDKN2A. It is possible that mutations in noncoding regions may be responsible for predisposition to melanoma in these families. We have analyzed approximately 1 kb of the CDKN2A promoter upstream of the start codon in an attempt to identify causal mutations in 107 melanoma families. Four sequence variants were detected. Two of these (A-191G and A-493T) did not segregate with disease and were present in a control population at a comparable frequency, indicating that they are unlikely to predispose to melanoma. The A-493T variant appeared to be in linkage disequilibrium with the previously described CDKN2A polymorphism Ala 148Thr. The variant G-735A was detected in the control population, but segregation of this variant with melanoma within families could not be discounted. The fourth variant (G-34T), located in the 5' UTR, creates an aberrant initiation codon. This variant appeared to segregate with melanoma and was not detected in a control population. G-34T has recently been identified in a subset of Canadian melanoma families and was concluded to be associated with predisposition to melanoma. The creation of an aberrant initiation site in the 5' UTR may have an important role in carcinogenesis in a small percentage of families; however, mutations in the CDKN2A promoter appear to have a limited role in predisposition to melanoma, Genes Chromosomes Cancer 28:45-57, 2000. (C) 2000 Wiley-Liss, Inc. C1 St James Univ Hosp, Imperial Canc Res Fund, Canc Med Res Unit, Leeds LS9 7TF, W Yorkshire, England. St James Univ Hosp, Imperial Canc Res Fund, Genet Epidemiol Lab, Leeds LS9 7TF, W Yorkshire, England. Univ Sydney, Westmead Hosp, Westmead Inst Canc Res, Sydney, NSW 2006, Australia. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Addenbrookes Hosp, CRC, Human Canc Genet Grp, Cambridge, England. RP Bishop, JN (reprint author), St James Univ Hosp, Imperial Canc Res Fund, Canc Med Res Unit, Beckett St, Leeds LS9 7TF, W Yorkshire, England. RI Mann, Graham/G-4758-2014; Bianchi Scarra, Giovanna/G-8933-2014; Tucker, Margaret/B-4297-2015; OI Mann, Graham/0000-0003-1301-405X; Bianchi Scarra, Giovanna/0000-0002-6127-1192; Bishop, Tim/0000-0002-8752-8785 NR 48 TC 56 Z9 58 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 2000 VL 28 IS 1 BP 45 EP 57 DI 10.1002/(SICI)1098-2264(200005)28:1<45::AID-GCC6>3.0.CO;2-F PG 13 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 298BV UT WOS:000086120200006 PM 10738302 ER PT J AU Debelenko, LV Swalwell, JI Kelley, MJ Brambilla, E Manickam, P Baibakov, G Agarwal, SK Spiegel, AM Marx, SJ Chandrasekharappa, SC Collins, FS Travis, WD Emmert-Buck, MR AF Debelenko, LV Swalwell, JI Kelley, MJ Brambilla, E Manickam, P Baibakov, G Agarwal, SK Spiegel, AM Marx, SJ Chandrasekharappa, SC Collins, FS Travis, WD Emmert-Buck, MR TI MENI gene mutation analysis of high-grade neuroendocrine lung carcinoma SO GENES CHROMOSOMES & CANCER LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-1; COMPARATIVE GENOMIC HYBRIDIZATION; GERMLINE MUTATIONS; TUMORS; P53; IDENTIFICATION; HETEROZYGOSITY; CRITERIA; REGION; LOCUS AB Neuroendocrine tumors of the lung consist of a spectrum of neoplasms, including typical carcinoids, atypical carcinoids, large-cell neuroendocrine carcinomas (LCNEC), and small-cell lung carcinomas (SCLC). We previously reported frequent inactivation of the gene responsible for multiple endocrine neoplasia type I (MENI) in both typical and atypical carcinoid tumors. In the present study, we extend the analysis of human NE lung tumors to include 9 primary SCLCs, 36 SCLC cell lines, and 13 primary LCNECs for MENI gene inactivation. In SCLC, loss of heterozygosity (LOH) at the MENI gene on chromosome band 11q13 was detected in one primary tumor and two cell lines. The coding sequence and splice junctions of the MENI gene were screened for mutations in all 44 tumors and cell lines, and no mutations were detected. Northern blot analysis of 13 SCLC cell lines showed the MENI transcript to be present and of normal size. In LCNECs, a somatic frameshift in the MENI gene (1226delC) was found in one of 13 tumors, representing the first mutation observed outside the spectrum of neoplasms associated with MENI. Interestingly, neither a deletion nor a mutation was detected in the other allele, and wild-type mRNA sequence was expressed in the tumor, suggesting that the MENI gene was not inactivated by a conventional two-hit mechanism. The data support the hypothesis chat SCLC and lung carcinoids develop via distinct molecular pathways; however, further investigation is necessary to determine the significance of the MENI gene mutation observed in a single case of LCNEC. Genes Chromosomes Cancer 28:58-65, 2000. Published 2000 Wiley-Liss, Inc. C1 NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Dept Med, Div Med Oncol & Transplantat, Durham, NC USA. Ctr Hosp Reg Univ Grenoble, Grp Rech Canc Bronch, Pathol Cellulaire Lab, Grenoble, France. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, NIH, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Brambilla, Elisabeth/L-8796-2013; Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 37 TC 40 Z9 40 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 2000 VL 28 IS 1 BP 58 EP 65 DI 10.1002/(SICI)1098-2264(200005)28:1<58::AID-GCC7>3.0.CO;2-2 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 298BV UT WOS:000086120200007 PM 10738303 ER PT J AU Cheng, Y Stanbridge, EJ Kong, H Bengtsson, U Lerman, MI Lung, ML AF Cheng, Y Stanbridge, EJ Kong, H Bengtsson, U Lerman, MI Lung, ML TI A functional investigation of tumor suppressor gene activities in a nasopharyngeal carcinoma cell line HONEI using a monochromosome transfer approach SO GENES CHROMOSOMES & CANCER LA English DT Article ID EPSTEIN-BARR-VIRUS; P53 GENE; CHROMOSOME TRANSFER; POINT MUTATION; BREAST-CANCER; BAND 11Q13; P16 GENE; HETEROZYGOSITY; DELETION; EXPRESSION AB Monochromosome transfers of selected chromosomes into a nasopharyngeal carcinoma (NPC) cell line were performed to determine if tumor suppressing activity for NPC mapped to chromosomes 9, 11, and 17. Current information from cytogenetic and molecular allelotyping studies indicate that these chromosomes may harbor potential tumor suppressor genes vital to NPC. The present results shaw the importance of CDKN2A on chromosome 9 in NPC development. There was no functional suppression of tumor development in nude mice with microcell hybrids harboring the newly transferred chromosome 9 containing an interstitial deletion at 9p21, whereas transfection of CDKN2A into the NPC HONEI cells resulted in obvious growth suppression. Whereas intact chromosome 17 transfers into HONEI cells showed no functional suppression of tumor formation, chromosome 11 was able to do so. Molecular analysis of chromosome 11 tumor segregants indicated that at least two tumor suppressive regions mapping to 11q13 and 11q22-23 may be critical for the development of NPC. Genes Chromosomes Cancer 28:82-41, 2000. (C) 2000 Wiley-Liss, Inc. C1 Hong Kong Univ Sci & Technol, Dept Biol, Kowloon, Hong Kong, Peoples R China. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. NCI, Frederick, MD 21701 USA. RP Lung, ML (reprint author), Hong Kong Univ Sci & Technol, Dept Biol, Clear Water Bay, Kowloon, Hong Kong, Peoples R China. RI Cheng, Yue/E-9853-2010 OI Cheng, Yue/0000-0002-2472-1879 FU NCI NIH HHS [CA19401] NR 49 TC 33 Z9 36 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 2000 VL 28 IS 1 BP 82 EP 91 DI 10.1002/(SICI)1098-2264(200005)28:1<82::AID-GCC10>3.0.CO;2-8 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 298BV UT WOS:000086120200010 PM 10738306 ER PT J AU Simon, R Desper, R Papadimitriou, CH Peng, A Alberts, DS Taetle, R Trent, JM Schaffer, AA AF Simon, R Desper, R Papadimitriou, CH Peng, A Alberts, DS Taetle, R Trent, JM Schaffer, AA TI Chromosome abnormalities in ovarian adenocarcinoma: III. Using breakpoint data to infer and test mathematical models for oncogenesis SO GENES CHROMOSOMES & CANCER LA English DT Article ID CANCER-CELLS; CARCINOMA AB Cancer geneticists seek to identify genetic changes in tumor cells and to relate the genetic changes to tumor development. Because single changes can disrupt the cell cycle and promote other genetic changes, it is extremely hard to distinguish cause from effect. in this article we illustrate how 7 techniques from statistics, theoretical computer science, and phylogenetics can be used to infer and test possible models of tumor progression from single genome-wide descriptions of aberrations in a large sample of tumors. Specifically, we propose 4 tree models for tumor progression inferred from the large ovarian cancer data set described in the first 2 articles in this series. The models are derived from 2 different methods to select the non-random genetic aberrations and 2 different methods to infer the trees, given a set of events. Various aspects of the tree models are tested and extended by 5 methods: overall tests of independence, likelihood ratio tests, principal components analysis, directed acyclic graph modeling, and Bayesian survival analysis. Ail our methods lead to strikingly consistent conclusions about chromosomal breakpoints in ovarian adenocarcinoma, including(1) the non-random breakpoints in ovarian adenocarcinoma do not occur independently; (2) breakpoints in regions 1p3 and 11p1 are important early events and distinguish a class of tumors associated with poor prognosis; and (3) breakpoints in 1p1, 3p1, and 1q2 distinguish a class of ovarian tumors, and the breaks at 1p1 and 3p1 are associated with poor prognosis. Genes Chromosomes Cancer 28:106-120, 2000. (C) 2000 Wiley-Liss, Inc. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. Deutsch Krebsforschungszentrum, Abt Theoret Bioinformat, D-6900 Heidelberg, Germany. Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. Emmes Corp, Potomac, MD USA. Univ Arizona, Dept Med, Tucson, AZ USA. Univ Arizona, Dept Pathol, Tucson, AZ USA. Arizona Canc Ctr, Tucson, AZ USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. RP Schaffer, AA (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bldg 38A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA. RI Schaffer, Alejandro/F-2902-2012 FU NCI NIH HHS [CA23074, CA41183]; NIEHS NIH HHS [ES-95-32] NR 30 TC 44 Z9 45 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 2000 VL 28 IS 1 BP 106 EP 120 DI 10.1002/(SICI)1098-2264(200005)28:1<106::AID-GCC13>3.0.CO;2-S PG 15 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 298BV UT WOS:000086120200013 PM 10738309 ER PT J AU Plisov, SY Ivanov, SV Yoshino, K Dove, LF Plisova, TM Higinbotham, KG Karavanova, I Lerman, M Perantoni, AO AF Plisov, SY Ivanov, SV Yoshino, K Dove, LF Plisova, TM Higinbotham, KG Karavanova, I Lerman, M Perantoni, AO TI Mesenchymal-epithelial transition in the developing metanephric kidney: Gene expression study by differential display SO GENESIS LA English DT Article DE kidney development; differential display; in situ hybridization; gene expression; epithelial cell differentiation ID BETA-CATENIN; ADHESION MOLECULES; RENAL DEVELOPMENT; INDUCTIVE TISSUE; URETERAL BUD; CYCLIN D1; TGF-BETA; MICE; CALRETICULIN; MORPHOGENESIS AB The developing metanephric kidney is a convenient model to study molecular events associated with epithelial cell differentiation. To determine the genes involved in the defining event of this process, namely, the conversion of metanephric mesenchyme to the epithelium of the nephron, we applied differential display (DD) techniques. Explants of rat metanephric mesenchymes were induced to condense ex vivo with fibroblast growth factor 2 (FGF2) or to form tubules with FGF2 and conditioned medium (CM) from a cell line (RUB1) of ureteric bud, the renal inductive tissue. Three time points (6, 24, and 72 h) were chosen to track the dynamics of gene expression during morphogenesis. Seventy-two up- or down-regulated mRNAs were identified, including 36 novel sequences and those of cell cycle regulatory proteins (TGF-beta 2, Cyclin D1, p57Kip2), transcription factors (beta-catenin, Sox11, DP1), signaling proteins (SH3-domain binding protein, G-protein-coupled receptor, Ser-Thr protein kinase), cell adhesion molecules (syndecan-4, integrin-beta 1), and also gene33, H19, SM20, IGFBP5, MAMA receptor, lectin, keratin, beta-tubulin, calreticulin, GRP78, ERp72, MnSoD, thioredoxin, and others. Some have previously been associated with kidney development and serve as good controls for expected changes, while most have not been linked with kidney epithelial cell differentiation. Using thin sections of embryonic kidney and labeled antisense RNA probes. we applied RNA hybridization to confirm the results of DD and related the expression of these genes to specific cell lineages of the developing kidney. These results provide a window into the events that mediate this critical differentiation process and suggest that a limited number of interrelated events direct the epithelial conversion of metanephric mesenchyme, genesis 27: 22-31, 2000, Published 2000 Wiley-Liss, Inc. C1 NCI, Human Genet Sect, Intramural Res Support Program, SAIC Frederick,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NICHHD, Dev Neurobiol Lab, Bethesda, MD 20892 USA. RP Plisov, SY (reprint author), NCI, Human Genet Sect, Intramural Res Support Program, SAIC Frederick,Frederick Canc Res & Dev Ctr, Bldg 538,Room 205E, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 44 TC 30 Z9 30 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 1526-954X J9 GENESIS JI Genesis PD MAY PY 2000 VL 27 IS 1 BP 22 EP 31 DI 10.1002/1526-968X(200005)27:1<22::AID-GENE40>3.0.CO;2-V PG 10 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 358KH UT WOS:000089556900004 PM 10862152 ER PT J AU Musser, JM Amin, A Ramaswamy, S AF Musser, JM Amin, A Ramaswamy, S TI Negligible genetic diversity of Mycobacterium tuberculosis host immune system protein targets: Evidence of limited selective pressure SO GENETICS LA English DT Article ID 45/47-KILODALTON ANTIGEN COMPLEX; HEPARIN-BINDING HEMAGGLUTININ; HEAT-SHOCK PROTEINS; T-CELL RESPONSES; EXTRACELLULAR PROTEINS; PULMONARY TUBERCULOSIS; MOLECULAR CHARACTERIZATION; ESCHERICHIA-COLI; CULTURE FILTRATE; PHYLOGENETIC ANALYSIS AB A common theme in medical microbiology is that the amount of amino acid sequence variation in proteins that are targets of the host immune system greatly exceeds that found in metabolic enzymes or other housekeeping proteins. Twenty-four Mycobacterium tuberculosis genes coding for targets of the host immune system were sequenced in 16 strains representing the breadth of genomic diversity in the species. Of the 24 genes, 19 were invariant and only six polymorphic nucleotide sires were identified in the 5 genes that did have variation. The results document the highly unusual circumstance that prominent M. tuberculosis antigenic proteins have negligible structural variation worldwide. The data are best explained by a combination of three factors: (i) evolutionarily recent global dissemination in humans, (ii) lengthy intracellular quiescence, and (iii) active replication in relatively few fully immunocompetent hosts. The very low level of amino acid diversity in antigenic proteins may be cause for optimism in the difficult fight to control global tuberculosis. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Baylor Coll Med, Dept Pathol, Inst Study Human Bacterial Pathogenesis, Houston, TX 77030 USA. RP Musser, JM (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM jmusser@niaid.nih.gov FU NIAID NIH HHS [AI-37004, AI-41168]; NIDA NIH HHS [DA-09238] NR 86 TC 99 Z9 101 U1 0 U2 3 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 2000 VL 155 IS 1 BP 7 EP 16 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 311DH UT WOS:000086869200002 PM 10790380 ER PT J AU Hallsson, JH Favor, J Hodgkinson, C Glaser, T Lamoreux, ML Magnusdottir, R Gunnarsson, GJ Sweet, HO Copeland, NG Jenkins, NA Steingrimsson, E AF Hallsson, JH Favor, J Hodgkinson, C Glaser, T Lamoreux, ML Magnusdottir, R Gunnarsson, GJ Sweet, HO Copeland, NG Jenkins, NA Steingrimsson, E TI Genomic, transcriptional and mutational analysis of the mouse microphthalmia locus SO GENETICS LA English DT Article ID WAARDENBURG-SYNDROME; MESSENGER-RNA; DNA-BINDING; MITF GENE; REGULATOR; ISOFORM; PROTEIN; DOMAIN; FAMILY; MAX AB Mouse microphthalmia transcription factor (Mitf) mutations affect the development of four cell types: melanocytes, mast cells, osteoclasts, and pigmented epithelial cells of the eye. The mutations are phenotypically diverse and can be arranged in an allelic series. In humans, MITF mutations cause Waardenburg syndrome type 2A (WS2A) and Tietz syndrome, autosomal dominant disorders resulting in deafness and hypopigmentation. Mitf mice thus represent an important model system for the study of human disease. Here we report the complete exon/intron structure of the mouse Mitf gene and show it to be similar to the human gene. We also found that the mouse gene is transcriptionally complex and is capable of generating at least 13 different Mitf isoforms. Some of these isoforms are missing important functional domains of the protein, suggesting that they might play an inhibitory role in Mitf function and signal transduction. In addition, we determined the molecular basis for six microphthalmia mutations. Two of the mutations are reported for the first time here (Mitf(mi-enu198) and Mitf(mi-x39)), while the others (Mitf(mi-ws), Mitf(mi-bws), Mitf(mi-ew), and Mitf(mi-di)) have been described but the molecular basis for the mutation nor determined. When analyzed in terms of the genomic and transcriptional data presented here, it is apparent that these mutations result from RNA processing or transcriptional defects. Interestingly, three of the mutations (Mitf(mi-x39), Mitf(mi-bws), and Mitf(mi-ws)) produce proteins that are missing important functional domains of the protein identified in in vitro studies, further confirming a biological role for these domains in the whole animal. C1 Univ Iceland, Sch Med, Dept Biochem & Mol Biol, IS-101 Reykjavik, Iceland. GSF, Inst Mammalian Genet, D-85764 Neuherberg, Germany. Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. Texas A&M Univ, Coll Vet Med, Dept Vet Pathobiol, College Stn, TX 77843 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Steingrimsson, E (reprint author), Univ Iceland, Sch Med, Dept Biochem & Mol Biol, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland. EM eirikurs@hi.is FU NEI NIH HHS [EY-10223] NR 40 TC 84 Z9 85 U1 0 U2 2 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 2000 VL 155 IS 1 BP 291 EP 300 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 311DH UT WOS:000086869200025 PM 10790403 ER PT J AU Biesecker, LG AF Biesecker, LG TI To the editor SO GENETICS IN MEDICINE LA English DT Letter C1 NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 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 MAY-JUN PY 2000 VL 2 IS 3 BP 203 EP 203 DI 10.1097/00125817-200005000-00008 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 409PV UT WOS:000167392800008 PM 11256667 ER PT J AU Thomas, JW Summers, TJ Lee-Lin, SQ Maduro, VVB Idol, JR Mastrian, SD Ryan, JF Jamison, DC Green, ED AF Thomas, JW Summers, TJ Lee-Lin, SQ Maduro, VVB Idol, JR Mastrian, SD Ryan, JF Jamison, DC Green, ED TI Comparative genome mapping in the sequence-based era: Early experience with human chromosome 7 SO GENOME RESEARCH LA English DT Article ID GENETIC-MAP; MOUSE; RESOLUTION; CALUMENIN; PROJECT; CLONES; DNA AB The success of the ongoing Human Genome Project has resulted in accelerated plans for completing the human genome sequence and the earlier-than-anticipated initiation of efforts to sequence the mouse genome. As a complement to these efforts, we are utilizing the available human sequence to refine human-mouse comparative maps and to assemble sequence-ready mouse physical maps. Here we describe how rile First glimpses of genomic sequence from human chromosome 7 are directly facilitating these activities. Specifically, we are actively enhancing the available human-mouse comparative map by analyzing human chromosome 7 sequence For the presence of orthologs of mapped mouse genes. Such orthologs can then be precisely positioned relative to mapped human STSs and other genes. The chromosome 7 sequence generated to date has allowed us to more than double the number of genes that can be placed on the comparative map. The latter effort reveals that human chromosome 7 is represented by at least 20 orthologous segments of DNA in the mouse genome. A second component of our program involves systematically analyzing the evolving human chromosome 7 sequence for the presence of matching mouse genes and expresses-sequence tags (ESTs). Mouse-specific hybridization probes are designed from such sequences and used to screen a mouse bacterial artificial chromosome (BAC) library, with the resulting data used to assemble BAC contigs based on probe-content data. Nascent contigs are then expanded using probes derived from newly generated BAG-end sequences. This approach produces BAG-based sequence-ready maps that are known to contain a gene(s) and are homologous to segments of the human genome for which sequence is already available. Our ongoing efforts have thus far resulted in the isolation and mapping of >3,800 mouse BACs, which have been assembled into >100 contigs. These contigs include >250 genes and represent similar to 40% of the mouse genome that is homologous to human chromosome 7. Together, these approaches illustrate how the availability of,of genomic sequence directly Facilitates studies in comparative genomics and genome evolution. C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM egreen@nhgri.nih.gov NR 35 TC 22 Z9 23 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD MAY PY 2000 VL 10 IS 5 BP 624 EP 633 DI 10.1101/gr.10.5.624 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 314UZ UT WOS:000087077100004 PM 10810084 ER PT J AU Murphy, WJ Sun, S Chen, ZQ Yuhki, N Hirschmann, D Menotti-Raymond, M O'Brien, SJ AF Murphy, WJ Sun, S Chen, ZQ Yuhki, N Hirschmann, D Menotti-Raymond, M O'Brien, SJ TI A radiation hybrid map of the cat genome: Implications for comparative mapping SO GENOME RESEARCH LA English DT Article ID IN-SITU HYBRIDIZATION; ANCHOR TAGGED SEQUENCES; GENETIC-LINKAGE MAP; ZOO-FISH ANALYSIS; DOMESTIC CAT; CHAIN GENE; PERSIAN CATS; MOUSE GENOME; ANIMAL-MODEL; FELIS-CATUS AB Ordered gene maps of mammalian species are becoming increasingly valued in assigning gene variants to function in human and animal models, as well as recapitulating the natural history of genome organization. To extend this power to the domestic cat, a radiation hybrid (RH) map of the cat was constructed integrating 424 Type I-coding genes with 176 microsatellite markers, providing cover age over all 20 feline chromosomes. Alignment of parallel RH maps of human and cat reveal 100 conserved segments ordered (CSOs) between the species, nearly three times the number observed with reciprocal chromosome painting analyses. The observed number is equivalent to theoretical predictions of the number of conserved segments to be found between cat and human, implying that 300-400 Type I gene markers is sufficient to reveal nearly all conserved segments for species that exhibit the most frequently observed "slow" tate of genome reorganization. The cat-human RH map comparisons provide a new genomic tool for comparative gene mapping in the cat and related Felidae, and provide confirmation that the cat genome organization is remarkably conserved compared with human. These data demonstrate that order ed RH-based gene maps provide the most precise assessment of comparing genomes, short of contig construction or full-sequence determination. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. George Mason Univ, Grad Program Biol, Fairfax, VA 22030 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. RP Murphy, WJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. NR 54 TC 100 Z9 100 U1 0 U2 6 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAY PY 2000 VL 10 IS 5 BP 691 EP 702 DI 10.1101/gr.10.5.691 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 314UZ UT WOS:000087077100012 PM 10810092 ER PT J AU Kalehua, AN Taub, D Baskar, PV Hengemihle, J Munoz, J Trambadia, M Speer, DL De Simoni, MG Ingram, DK AF Kalehua, AN Taub, D Baskar, PV Hengemihle, J Munoz, J Trambadia, M Speer, DL De Simoni, MG Ingram, DK TI Aged mice exhibit greater mortality concomitant to increased brain and plasma TNF-alpha levels following intracerebroventricular injection of lipopolysaccharide SO GERONTOLOGY LA English DT Article DE aging; neuroinflammation; glia; endotoxin; cytokine; interleukins ID TUMOR-NECROSIS-FACTOR; AMEBOID MICROGLIAL CELLS; CENTRAL-NERVOUS-SYSTEM; CLASS-II ANTIGEN; RAT-BRAIN; INTRAPERITONEAL INJECTIONS; ALZHEIMERS-DISEASE; INFLAMMATORY RESPONSE; CYTOKINE PRODUCTION; SOLUBLE RECEPTORS AB Background: Age-related defects in the development of peripheral inflammatory responses have been observed in rodents and humans. Objective: We examined the effects of age on a centrally injected endotoxin-induced cytokine production and cellular activation in mice. Methods: Male C57BL/6J (B6) mice, C3H/HeN mice, and C3H/HeJ mice received an intracerebroventricular injection of lipopolysaccharide (LPS) and were sacrificed at various times (2, 4, 8 h) thereafter. ELISA for IL-1 beta, IL-6, IL-12, and TNF-alpha were conducted on forebrain tissue homogenates as well as plasma samples, and lectin staining to detect activated microglia was prepared for selected brain slices. Results: Intracerebroventricular injection of LPS in B6 mice produced an age-associated increase in mortality which was paralleled with a significant increase in brain and plasma levels of TNF-alpha. Anti-TNF-alpha-and IL-6-immunoreactive cells possessed macrophage-like morphologies and were observed along the LPS injection tract and scattered throughout the hilus of the dorsal hippocampus and cerebral cortices. This LPS-mediated response was found to be specific in that the LPS-hyporesponsive mouse strain (C3H/HeJ) failed to demonstrate significant brain or plasma levels of TNF-alpha after LPS administration compared to C3H/HeN mice. Conclusion: These results suggest that the age-related increases in TNF-alpha production and mortality following the intracerebroventricular administration of LPS may be due to an increased endotoxin hypersensitivity of brain microglia/macrophages within aged animals. Copyright (C) 2000 S. Karger AG, Basel. C1 NIA, Mol Physiol & Genet Sect, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, Immunol Lab, Clin Immunol Sect, NIH, Baltimore, MD 21224 USA. NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. Mario Negri Inst, Dept Neurosci, Milan, Italy. RP Ingram, DK (reprint author), NIA, Mol Physiol & Genet Sect, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 53 TC 35 Z9 36 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PD MAY-JUN PY 2000 VL 46 IS 3 BP 115 EP 128 DI 10.1159/000022146 PG 14 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 307GU UT WOS:000086645700001 PM 10754368 ER PT J AU Thoits, PA Hohmann, AA Harvey, MR Fletcher, B AF Thoits, PA Hohmann, AA Harvey, MR Fletcher, B TI Similar-other support for men undergoing coronary artery bypass surgery SO HEALTH PSYCHOLOGY LA English DT Article DE social support; intervention; physical health; depression; psychological distress; bypass surgery ID LONG-TERM RECOVERY; SOCIAL SUPPORT; HEART-DISEASE; BUFFERING HYPOTHESIS; STRESS; HEALTH; INTERVENTION; PERCEPTIONS; AFFILIATION; ADJUSTMENT AB This field experiment examined effects of a support intervention on the physical and mental health of coronary artery bypass graft (CABG) surgery patients. Control participants (N = 90) received usual hospital care; experimental participants (N = 100) also received visits from a "similar other" while in the hospital. Similar others were Veterans Administration veterans who had CABG surgery previously and were trained in simple supportive techniques. Outcomes were assessed prior to surgery and at 1,6, and 12 months afterwards. Unexpectedly, the intervention generally had no effects on participants' well-being. Further analysis showed that participants who talked often with fellow cardiac patients in the hospital ("de facto similar others") experienced improvements in their physical and emotional well-being over time. C1 Vanderbilt Univ, Dept Sociol, Nashville, TN 37235 USA. NIMH, Bethesda, MD 20892 USA. RP Thoits, PA (reprint author), Vanderbilt Univ, Dept Sociol, Box 1811-B, Nashville, TN 37235 USA. EM thoits@vanderbilt.edu NR 58 TC 27 Z9 28 U1 1 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAY PY 2000 VL 19 IS 3 BP 264 EP 273 DI 10.1037//0278-6133.19.3.264 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 322BM UT WOS:000087490400007 PM 10868771 ER PT J AU Lanford, PJ Platt, C Popper, AN AF Lanford, PJ Platt, C Popper, AN TI Structure and function in the saccule of the goldfish (Carassius auratus): a model of diversity in the non-amniote ear SO HEARING RESEARCH LA English DT Article DE hair cell; saccule; cellular variation; review ID POST-SYNAPTIC POTENTIALS; AUDITORY-NERVE FIBERS; SENSORY HAIR-CELLS; INNER-EAR; SYNAPSES; ORGAN; FISH; ZEBRAFISH; AFFERENT; NOTCH AB The vertebrate inner ear is comprised of a remarkable diversity of cell types, including several types of sensory hair cells. In amniotes (reptiles, birds, and mammals), the morphological and physiological characteristics that distinguish these cell types have been well documented, while cellular variation in the ears of non-amniotes (all other vertebrate groups) has remained underrecognized. Since non-amniotes have become increasingly popular models for developmental and genetic research, a more comprehensive understanding of structure and function in the inner ears of these species is warranted. This paper first reviews the large body of data describing the morphology and physiology of hair cells and afferent neurons in the inner ear of the goldfish (Carassius auratus). In particular, we examine the structure of the goldfish saccule, an endorgan that has been the subject of numerous investigations on audition. New data on the structural variation of synaptic bodies in saccular hair cells are also presented, and the functional implications of these data are discussed. Finally, we conclude that hair cell structure varies along the length of the goldfish saccule in a manner consistent with known physiological characteristics of the endorgan. The saccule provides an excellent model for investigating structure-function relationships in the vertebrate inner ear, Bs well as the development of auditory and vestibular sensory epithelia. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Maryland, Dept Biol, College Pk, MD 20742 USA. RP Lanford, PJ (reprint author), Natl Inst Deafness & Other Commun Disorders, 5 Res Ct, Rockville, MD 20850 USA. FU NIDCD NIH HHS [5T32DC00046-02] NR 68 TC 30 Z9 31 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 2000 VL 143 IS 1-2 BP 1 EP 13 DI 10.1016/S0378-5955(00)00015-0 PG 13 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 309AK UT WOS:000086744900001 PM 10771179 ER PT J AU Connelly, B Gunzerath, L Knebel, A AF Connelly, B Gunzerath, L Knebel, A TI A pilot study exploring mood state and dyspnea in mechanically ventilated patients SO HEART & LUNG LA English DT Article ID VISUAL ANALOG SCALE AB OBJECTIVE: The objective of this study was to explore preweaning mood state and dyspnea, in mechanically ventilated patients. METHODS: Before ventilatory weaning, 21 critically ill patients completed the short profile of mood states (higher scores equal greater disturbance), and a 10 cm dyspnea visual analogue scale (none to extremely severe). Weaning outcome at 24 hours was recorded. RESULTS: The mean +/- SD total mood disturbance (possible range, 0 to 16) and subscale scores (possible range, 0 to 4) were as follows: total, 6.10 +/- 4.06; tension, 1.07 +/- 0.64; depression, 1.16 +/- 0.93; anger, 1.05 +/- 0.82; vigor, 1.04 +/- 0.84; fatigue, 1.96 +/- 0.90; and confusion, 1.27 +/- 0.91. Mean dyspnea was 3.22 +/- 2.26 cm. Dyspnea intensify correlated negatively with vigor (r = -0.38, P <.10). Lower preweaning vigor tended to differentiate successful from unsuccessful weaning (Mann-Whitney U = 22.0; P=.07). CONCLUSION: Patients who weaned successfully experienced greater mood disturbance. Moderate mood disturbance may be a necessary stimulus for successful weaning. C1 Northwestern Univ, Evanston, IL USA. RP Knebel, A (reprint author), NIH, Ctr Clin, Dept Nursing, Bldg 10,Room 2C206,10 Ctr Dr MSC 1506, Bethesda, MD 20892 USA. NR 22 TC 14 Z9 14 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD MAY-JUN PY 2000 VL 29 IS 3 BP 173 EP 179 DI 10.1067/mhl.2000.105689 PG 7 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 319FK UT WOS:000087330700003 PM 10819799 ER PT J AU Peterson, TC Hodgson, P Fernandez-Salguero, P Neumeister, M Gonzalez, FJ AF Peterson, TC Hodgson, P Fernandez-Salguero, P Neumeister, M Gonzalez, FJ TI Hepatic fibrosis and cytochrome P450: experimental models of fibrosis compared to AHR knockout mice SO HEPATOLOGY RESEARCH LA English DT Article DE Ahr -/-; fibrosis; collagen; bile duct ligation; animal models of fibrosis ID HYDROCARBON HYDROXYLASE-ACTIVITY; GROWTH-FACTOR-BETA; LIVER-DISEASE; RAT; PENTOXIFYLLINE; OXIDATION; APOPTOSIS; RECEPTOR; COLLAGEN; PROTEIN AB Hepatic fibrosis is characterized by abnormal collagen deposition resulting fi om increased collagen synthesis and decreased collagen degradation. Cytochrome P450 mediates major drug metabolizing enzyme activity in the liver and this activity is reduced in hepatic fibrosis. In this study we assess cytochrome P450 and CYP 1A mRNA in livers of animals that have been induced to hepatic fibrosis using the heterologous serum induced model of fibrosis in rats compared to controls. Fibrosis was confirmed by assessing the collagen in liver sections as quantified by Sirius red/Fast green staining, a quantitative measure of fibrosis as well as by visualization of the hepatic fibrosis. Collagen levels in the liver sections of heterologous serum induced fibrotic rats was increased by 33% compared to controls and a typical fibrotic pattern was seen. Messenger RNA was prepared from heterologous serum induced fibrotic rats and compared to controls. CYP 1A2 was assessed using a specific probe and the CYP 1A2 level was significantly reduced in the heterologous serum induced fibrotic rats compared to controls. These results further suggest that cytochrome P450 is reduced in the presence of hepatic fibrosis. Thus, in three well established experimental models of hepatic fibrosis which had clearly developed hepatic fibrosis (as shown by Sirius red/Fast green staining), cytochrome P450 mediated enzyme activity, or specifically. CYP 1A messenger RNA is decreased. We then investigated a transgenic mouse, deficient in the arylhydrocarbon hydroxylase receptor (AHR), which has undetectable levels of CYP 1A messenger RNA. We quantitated the collagen in liver sections obtained from AHR knockout mice compared to controls, as an indication of the presence of hepatic fibrosis. Collagen concentration was significantly increased by 53% (P < 0.0005) in sections from Ahr- / - (knockout) mice compared to wild-type controls. Collagen in livers of the Ahr + / - heterozygous mice was nor different from wild-type controls. The increase in collagen concentration in liver sections is an indication of fibrosis in Ahr - / - mice. Collagen protein deposition was also elevated in liver sections from bile duct ligated rats (by 44%) compared to sham operated controls, was elevated in liver sections from heterologous serum induced fibrosis in rats (33%) compared to controls, and was elevated in liver sections from yellow phosphorous induced hepatic fibrosis (74%) compared to vehicle treated controls. In conclusion, these results indicate that cytochrome P450 and specific subtypes of P450, the CYP 1A subgroup, are significantly reduced in three experimental models of hepatic fibrosis when there is evidence of increased collagen deposition in the livers. These results also indicate that mice that are deficient in CYP 1A have elevated levels of hepatic collagen protein, an indication of hepatic fibrosis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Dalhousie Univ, Dept Med, Halifax, NS B3H 4H7, Canada. Dalhousie Univ, Dept Pharmacol, Halifax, NS B3H 4H7, Canada. NCI, Lab Metab, NIH, Bethesda, MD USA. RP Peterson, TC (reprint author), Dalhousie Univ, Dept Med, Tupper Med Bldg,Rm 11 C1, Halifax, NS B3H 4H7, Canada. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 29 TC 22 Z9 26 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1386-6346 J9 HEPATOL RES JI Hepatol. Res. PD MAY PY 2000 VL 17 IS 2 BP 112 EP 125 DI 10.1016/S1386-6346(99)00068-6 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 296AT UT WOS:000086001400003 ER PT J AU Burger, IM Wilfond, BS AF Burger, IM Wilfond, BS TI Limitations of informed consent for in utero gene transfer research: Implications for investigators and institutional review boards SO HUMAN GENE THERAPY LA English DT Article ID STEM-CELL TRANSPLANTATION; LONG-TERM EXPRESSION; PHASE-I TRIALS; CYSTIC-FIBROSIS; CLINICAL-TRIALS; THERAPY; FETAL; SHEEP; INUTERO; CHEMOTHERAPY AB Only 10 years after the first human gene transfer protocols were approved for adults and children, researchers have begun to consider gene transfer on the fetus. While preliminary animal research is ongoing, the enthusiasm and pace of research in this area suggest that human protocols for irt utero gene transfer research may be seriously considered in the foreseeable future. Federal guidelines for fetal research rely on minimizing risk and informed consent to protect the "rights and welfare" of both the fetus and pregnant woman. However, in utero gene transfer research poses special challenges to informed consent. This research represents an innovative approach for very ill subjects and takes place in the prenatal setting. These features may converge to undermine the expectant parents' comprehension of, and voluntariness for participation in, research. In this case, informed consent may not be able to bear the weight of adequately protecting the fetus from undue research risks. To compensate for this limitation, and using the regulations for pediatric research as a guide, a greater emphasis should be placed on the benefit/harm assessment rather than informed consent. Selecting diseases/patients where good alternative treatments exist may maximize informed consent, yet this may be a trade-off that exposes the fetus to greater relative risks. On the other hand, selecting diseases/patients without good alternative treatments to prolong life may convey an overestimation of the potential benefits of these interventions, and although care should be taken to strive to improve understanding of these limitations, misunderstanding may persist. However, selecting diseases/patients with no good alternatives might make serious risks more tolerable, and this should take precedence over informed consent. The limitations of informed consent brought into focus by the special features of in utero gene transfer research may be relevant to a broader range of innovative investigations. C1 Natl Human Genome Res Inst, Med Genet Branch, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wilfond, BS (reprint author), Natl Human Genome Res Inst, Dept Clin Bioeth, Bldg 10,Room 1C2118,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 51 TC 3 Z9 3 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 MAY 1 PY 2000 VL 11 IS 7 BP 1057 EP 1063 DI 10.1089/10430340050015365 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 310PA UT WOS:000086835500008 PM 10811234 ER PT J AU Shevchenko, YO Compton, JG Toro, JR DiGiovanna, JJ Bale, SJ AF Shevchenko, YO Compton, JG Toro, JR DiGiovanna, JJ Bale, SJ TI Splice-site mutation in TGM1 in congenital recessive ichthyosis in American families: molecular, genetic, genealogic, and clinical studies SO HUMAN GENETICS LA English DT Article ID LAMELLAR ICHTHYOSIS; KERATINOCYTE TRANSGLUTAMINASE; EXPRESSION; FEATURES; LOCUS AB Lamellar ichthyosis (LI, OMIM no. 242300) is a severe autosomal recessive genodermatosis with an estimated prevalence of 1:200,000. LI represents one end of the spectrum of congenital recessive ichthyosis (CRI). Mutations in the gene for transglutaminase-1 (TGM1) are responsible for many cases of LI and occur throughout the coding sequence of the gene. Our analyses of patients with CRI revealed a common TGM1 mutation involving loss of the intron 5 splice acceptor site leading to alternative splicing of the message. We found families in which the splice acceptor site mutation was homozygous, and families where the patients were compound heterozygotes for the splice acceptor site mutation and another TGM1 mutation. A mutation at this same site occurs in the majority of Norwegian patients as a founder effect. In our ethnically diverse patient population, none of whom have known Norwegian ancestry, haplotype analysis of the TGM1 chromosomal region also suggested the existence of a founder effect. Comparison of the common haplotype in our data with the Norwegian data showed that 2/7 of our splice acceptor site mutation chromosomes had the full reported Norwegian haplotype, and the remaining five chromosomes exhibited recombination at the most distal marker studied. History, family origins, and haplotype analysis suggested that the mutation originally arose on a German background and was introduced into Norway around 800-1000 AD. We also found a limited correlation between genotype and phenotype in our study, with the four homozygous patients having less severe disease than many of the heterozygotes, and no patient with a splice acceptor site mutation having erythroderma or a congenital ichthyosiform erythroderma phenotype. C1 NIAMSD, Genet Studies Sect, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP Bale, SJ (reprint author), NIAMSD, Genet Studies Sect, Skin Biol Lab, NIH, Bldg 6,Room 429,6 Ctr Dr,MSC 2757, Bethesda, MD 20892 USA. NR 17 TC 25 Z9 25 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 MAY PY 2000 VL 106 IS 5 BP 492 EP 499 DI 10.1007/s004390000284 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 331CR UT WOS:000088000200004 PM 10914678 ER PT J AU Ren, ZX Li, AR Shastry, BS Padma, T Ayyagari, R Scott, MH Parks, MM Kaiser-Kupfer, MI Hejtmancik, JF AF Ren, ZX Li, AR Shastry, BS Padma, T Ayyagari, R Scott, MH Parks, MM Kaiser-Kupfer, MI Hejtmancik, JF TI A 5-base insertion in the gamma C-crystallin gene is associated with autosomal dominant variable zonular pulverulent cataract SO HUMAN GENETICS LA English DT Article ID CONGENITAL CATARACT; EYE LENS; HETEROGENEITY; SUPERFAMILY; BLINDNESS; PROTEINS; CLEARER AB A seven-generation family with 30 members affected by highly variable autosomal dominant zonular pulverulent cataracts has been previously described. We have localized the cataracts to a 19-cM interval on chromosome 2q33-q35 including the gamma-crystallin gene cluster. Maximum rod scores are 4.56 (theta=0.02) with D2S157, 3.66 (theta=0.12) with D2572, and 3.57 (theta=0.052) with CRYG. Sequencing and allele-specific oligonucleotide analysis of the pseudo gamma E-crystallin promoter region from individuals in the pedigree suggest that activation of the gamma E-crystallin pseudo gene is unlikely to cause the cataracts in the family. In addition, base changes in the TATA box but not the Spl-binding site have been found in unaffected controls and can be excluded as a sole cause of cataracts. In order to investigate the underlying genetic mechanism of cataracts in this family further, exons of the highly expressed gamma C- and gamma D-crystallin genes have been sequenced. The gamma D-crystallin gene shows no abnormalities, but a 5-bp duplication within exon 2 of the gamma C-crystallin gene has been found in one allele of each affected family member and is absent from both unaffected family members and unaffected controls. This mutation disrupts the reading frame of the gamma C-crystallin coding sequence and is pre-dieted to result in the synthesis of an unstable gamma C-crystallin with 38 amino acids of the first "Greek key" motif followed by 52 random amino acids. This finding suggests that the appropriate association of mutant beta gamma-crystallins into oligomers is not necessary to cause cataracts and may give us new insights into the genetic mechanism of cataract formation. C1 NEI, NIH, Bethesda, MD 20892 USA. Oakland Univ, Eye Res Inst, Rochester, MI 48309 USA. Osmania Univ, Dept Genet, Hyderabad 500007, Andhra Pradesh, India. Univ Michigan, Dept Ophthalmol, Ann Arbor, MI 48109 USA. RP Hejtmancik, JF (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 30 TC 82 Z9 89 U1 0 U2 2 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 MAY PY 2000 VL 106 IS 5 BP 531 EP 537 DI 10.1007/s004390050021 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 331CR UT WOS:000088000200009 PM 10914683 ER PT J AU Shugart, YY Hemminki, K Vaittinen, P Kingman, A Dong, CH AF Shugart, YY Hemminki, K Vaittinen, P Kingman, A Dong, CH TI A genetic study of Hodgkin's lymphoma: an estimate of heritability and anticipation based on the familial cancer database in Sweden SO HUMAN GENETICS LA English DT Article ID DISEASE AB Hodgkin's lymphoma (HL) is a heterogeneous hemopoietic malignancy Previous studies have implicated a genetic etiology responsible fur familial HL. We have estimated the heritability of HL and tested the hypothesis of genetic anticipation by using a high quality cancer database of the Swedish population. Heritability was estimated by employing a threshold-liability model. To test the hypothesis of anticipation, the usual T-test procedure was used to test whether there was a difference in cancer age-of-onset between parents and children who were affected with HL, A randomization test was carried out to test the validity of the P-values. Additional analyses were performed after stratifying the data based on birth cohorts. This data set revealed that there was a difference between the age-of-onset of parents and of off-spring who were affected with HL. We also estimated the heritability of HL in the Swedish population to be approximately 28.4%. Both findings provide further evidence for a genetic basis for HL. C1 Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD 21224 USA. Karolinska Inst, Dept Biosci, Huddinge, Sweden. Natl Board Hlth & Welf, Ctr Epidemiol, Stockholm, Sweden. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. RP Shugart, YY (reprint author), Johns Hopkins Univ, Ctr Inherited Dis Res, 333 Cassell Dr,Suite 2000, Baltimore, MD 21224 USA. FU NCI NIH HHS [CA85135-01] NR 16 TC 39 Z9 40 U1 0 U2 2 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 MAY PY 2000 VL 106 IS 5 BP 553 EP 556 DI 10.1007/s004390050024 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 331CR UT WOS:000088000200012 PM 10914686 ER PT J AU Fend, F Quintanilla-Martinez, L Raffeld, M AF Fend, F Quintanilla-Martinez, L Raffeld, M TI Composite lymphoma SO HUMAN PATHOLOGY LA English DT Letter C1 Tech Univ Munich, Dept Pathol, D-8000 Munich, Germany. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Fend, F (reprint author), Tech Univ Munich, Dept Pathol, D-8000 Munich, Germany. NR 2 TC 1 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2000 VL 31 IS 5 BP 626 EP 627 DI 10.1016/S0046-8177(00)80046-5 PG 2 WC Pathology SC Pathology GA 313TE UT WOS:000087014700016 PM 10836305 ER PT J AU Stratton, P Hartog, B Hajizadeh, N Piquion, J Sutherland, D Merino, M Lee, YJ Nieman, LK AF Stratton, P Hartog, B Hajizadeh, N Piquion, J Sutherland, D Merino, M Lee, YJ Nieman, LK TI A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women SO HUMAN REPRODUCTION LA English DT Article DE antiprogestin; CDB-2914; endometrium; follicle ID MIDCYCLE GONADOTROPIN SURGE; ESTROGEN-RECEPTOR; MENSTRUAL-CYCLE; PROGESTERONE; RU-486; RU486; MATURATION; OVULATION; PHASE; MIFEPRISTONE AB Previous studies in women have shown that the antiprogestin mifepristone delays or inhibits folliculogenesis. The purpose of this study was to explore whether a new analogue, CDB-2914, has similar effects on folliculogenesis, ovulation, or on subsequent luteal phase endometrial maturation. Forty-four normally cycling, healthy women recorded urine LH and vaginal bleeding during pre-treatment, treatment, and post-treatment cycles. At a lead follicle diameter of 14-16 mm, a single oral dose (10, 50, 100 mg) of CDB-2914 or placebo was given, and daily ultrasound, oestradiol and progesterone were obtained until follicular collapse; an endometrial biopsy was obtained 5-7 days later. Single doses of CDB-2914 were well tolerated. Mid-follicular CDB-2914 suppressed lead follicle growth, causing a dose-dependent delay in folliculogenesis and suppression of plasma oestradiol. At higher doses, a new lead follicle was often recruited. Although luteinized unruptured follicles were observed at the 100 mg dose, all women had follicular collapse. There was a significant delay in endometrial maturation after CDB-2914 at all doses. The treatment cycle was lengthened by 1-2 weeks in 30% at 100, 27% at 50 and 9% at 10 mg. CDB-2914 altered ovarian and endometrial physiology without major effects on menstrual cyclicity and may have therapeutic utility. C1 NICHHD, Pediat & Reprod Dev Endocrinol Branch, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Washington, DC 20037 USA. NICHHD, Div Epidemiol Stat & Prevent, Bethesda, MD 20892 USA. NCI, Dept Nursing, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. RP Stratton, P (reprint author), NICHHD, Pediat & Reprod Dev Endocrinol Branch, Bldg 10,Room 9D42,10 Ctr Dr,MSC 1583, Bethesda, MD 20892 USA. OI hajizadeh, negin/0000-0002-6404-1018 FU NICHD NIH HHS [N01-HD-1-3137] NR 30 TC 57 Z9 58 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD MAY PY 2000 VL 15 IS 5 BP 1092 EP 1099 DI 10.1093/humrep/15.5.1092 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 310TP UT WOS:000086843700023 PM 10783359 ER PT J AU Larner, JM Reel, JR Blye, RP AF Larner, JM Reel, JR Blye, RP TI Circulating concentrations of the antiprogestins CDB-2914 and mifepristone in the female rhesus monkey following various routes of administration SO HUMAN REPRODUCTION LA English DT Article; Proceedings Paper CT 10th International Congress of Endocrinology CY JUN 12-15, 1996 CL SAN FRANCISCO, CALIFORNIA DE antiprogestin; bioavailability; contraception; protein binding; rhesus monkey ID CLINICAL PHARMACOKINETICS; RECEPTOR-BINDING; RU-486; METABOLITES; PROTEINS; HUMANS; SINGLE; RATS AB The overall aim of these studies was to investigate the oral and i.m. bioavailability of CDB-2914 in intact female rhesus monkeys, and to compare the serum concentrations of CDB-2914 with that of mifepristone following oral administration. In the first study, a 50 mg bolus of CDB-2914 per monkey was administered intravenously, orally or intramuscularly. The area under the serum concentration-time curve for 72 h (AUC(0-72)) following i.v. injection was 18 320 +/- 2718 ng/ml.h, and that for oral administration was 10 464 +/- 3248 ng/ml.h. Thus, the oral bioavailability of CDB-2914 equivalents was 56%. The AUC(0-168) (h) following i.m. injection was 11 226 +/- 1130 ng/ml.h. Therefore, the i.m. bioavailability of CDB-2914 equivalents was 62%. In the second study, the serum concentrations of CDB-2914 and mifepristone equivalents were compared following an oral bolus dose in two different formulations. When administered at 5 mg/kg in aqueous suspending vehicle (ASV), the mean peak serum concentration (C-max) of CDB-2914 equivalents (192 +/- 64 ng/ml) occurred at 5 +/- 1 h, whereas the C-max of mifepristone equivalents (82 +/- 25 ng/ml) occurred at 3 +/- 1 h. Following administration in gelatin capsules (35 mg/monkey), the C-max of CDB-2914 equivalents (129 +/- 24 ng/ml) occurred at 5 +/- 1 h, while the C-max of mifepristone equivalents (31 +/- 8 ng/ml) occurred at 3 +/- 1 h. The serum concentration (AUC(0-120) h) Of CDB-2914 equivalents was 4.7- or 5.3-fold greater than that of mifepristone equivalents when administered orally in ASV or gelatin capsules respectively. The serum protein binding characteristics of CDB-2914 were also studied. CDB-2914 bound to human alpha(1)-acid glycoprotein (AAG), but not with as high an affinity as mifepristone, In contrast, neither CDB-2914 nor mifepristone bound with high affinity to AAG, corticosteroid binding globulin or sex hormone binding globulin in monkey serum. Collectively, these results indicated that CDB-2914 was more efficiently absorbed than mifepristone following oral administration to female rhesus monkeys. C1 BIOQUAL Inc, Rockville, MD 20850 USA. NICHHD, Contracept & Reprod Hlth Branch, Bethesda, MD 20892 USA. RP Reel, JR (reprint author), BIOQUAL Inc, Rockville, MD 20850 USA. FU NICHD NIH HHS [N01-HD-1-3130, N01-HD-6-3259] NR 28 TC 18 Z9 18 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD MAY PY 2000 VL 15 IS 5 BP 1100 EP 1106 DI 10.1093/humrep/15.5.1100 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 310TP UT WOS:000086843700024 PM 10783360 ER PT J AU Izzo, JL Levy, D Black, HR AF Izzo, JL Levy, D Black, HR TI Importance of systolic blood pressure in older Americans SO HYPERTENSION LA English DT Editorial Material DE clinical advisory statement; hypertension, detection and control; elderly; blood pressure ID CORONARY HEART-DISEASE; RANDOMIZED TRIAL; PULSE PRESSURE; RENAL-DISEASE; HYPERTENSION; RISK; PROGRESSION; PREVALENCE; POPULATION; FRAMINGHAM C1 SUNY Buffalo, Dept Med, Div Clin Pharm, Buffalo, NY 14209 USA. NHLBI, Natl High Blood Pressure Educ Program, Bethesda, MD 20892 USA. RP Izzo, JL (reprint author), SUNY Buffalo, Dept Med, Div Clin Pharm, 3 Gates Circle, Buffalo, NY 14209 USA. NR 25 TC 217 Z9 226 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2000 VL 35 IS 5 BP 1021 EP 1024 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 317MD UT WOS:000087228400002 PM 10818056 ER PT J AU Saitoh, S Arudchandran, R Manetz, TS Zhang, WG Sommers, CL Love, PE Rivera, J Samelson, LE AF Saitoh, S Arudchandran, R Manetz, TS Zhang, WG Sommers, CL Love, PE Rivera, J Samelson, LE TI LAT is essential for Fc epsilon RI-mediated mast cell activation SO IMMUNITY LA English DT Article ID AFFINITY IGE RECEPTOR; VAV PROTOONCOGENE PRODUCT; BASOPHILIC LEUKEMIA-CELLS; PROTEIN-TYROSINE KINASE; GRB2 ADAPTER PROTEIN; T-CELLS; PHOSPHOLIPASE C-GAMMA-1; SIGNAL TRANSDUCTION; ALLERGIC MEDIATORS; MOLECULAR-CLONING AB The linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement of T cells. LAT is also expressed in platelets, NK, and mast cells. Although LAT-deficient mice contain normal numbers of mast cells, we found that LAT-deficient mice were resistant to IgE-mediated passive systemic anaphylaxis. LAT-deficient bone marrow-derived mast cells (BMMC) showed normal growth and development. Whereas tyrosine phosphorylation of Fc epsilon RI, Syk, and Vav was intact in LAT-deficient BMMCs following Fc epsilon RI engagement, tyrosine phosphorylation of SLP-76, PLC-gamma 1, and PLC-gamma 2 and calcium mobilization were dramatically reduced. LAT-deficient BMMCs also exhibited profound defects in activation of MAPK, degranulation, and cytokine production after Fc epsilon RI cross-linking. These results show that LAT plays a critical role in Fc epsilon RI-mediated signaling in mast cells. C1 NCI, Cellular & Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NIAMSD, Sect Chem Immunol, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Div Basic Sci, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 53 TC 272 Z9 273 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2000 VL 12 IS 5 BP 525 EP 535 DI 10.1016/S1074-7613(00)80204-6 PG 11 WC Immunology SC Immunology GA 319RT UT WOS:000087356400008 PM 10843385 ER PT J AU Caplan, S Dell'Angelica, EC Gahl, WA Bonifacino, JS AF Caplan, S Dell'Angelica, EC Gahl, WA Bonifacino, JS TI Trafficking of major histocompatibility complex class II molecules in human B-lymphoblasts deficient in the AP-3 adaptor complex SO IMMUNOLOGY LETTERS LA English DT Article DE Hermansky-Pudlak syndrome; lysosomes; antigen-processing; invariant chain; dileucine-based signals ID INVARIANT CHAIN CONTAINS; CYTOPLASMIC TAIL; SORTING SIGNALS; INTRACELLULAR-TRANSPORT; LYSOSOMAL COMPARTMENTS; MONOCLONAL-ANTIBODIES; TARGETING SIGNALS; BETA-CHAIN; EXPRESSION; DISTINCT AB The major histocompatibility complex class II subunits (MHC-II) alpha and beta assemble with the invariant chain (Ii) in the endoplasmic reticulum and are transported to endosomal-lysosomal organelles known as MHC class II compartments (MIICs). Although it has been shown that two dileucine-based signals in the cytosolic tail of Ii, as well as a dileucine-based signal in the tail of the beta chain mediate sorting to MIICs, the molecular mechanisms by which alpha beta Ii complexes are sorted have yet to be resolved fully. The AP-3 adaptor complex stands oat as a particularly good candidate for mediating this targeting because: (i) it has a proven role in the trafficking of membrane proteins to lysosome-related organelles; and (ii) it has the ability to interact with dileucine-based signals in vitro. To investigate the potential role of AP-3 in transport of MHC-II to MIICs. we have examined MHC-II trafficking in human B-lymphoblast lines from patients with Hermansky-Pudlak syndrome type 2 (HPS-2), which are deficient in the AP-3 complex. Pulse-chase analyses revealed no significant alteration in the kinetics of synthesis and degradation of either MHC-II subunits or Ii. Moreover, we observed neither impairment of the formation of compact SDS-resistant alpha beta dimers, nor delay in the appearance of a conformational epitope indicative of a mature, Ii-free alpha beta dimer. Finally, we demonstrated that in HPS-2 patients' cells, there was no delay in the expression of the alpha beta dimers on the cell surface. Thus, AP-3 does not seem to be essential for normal trafficking of MHC-II. These findings have important implications for HPS-2 patients, because they suggest that the recurrent bacterial infections suffered by these patients are not likely due to impaired antigen processing and presentation by MHC-II. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldt 18T Room 101,18 Lib Dr MSC 5430, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 29 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD MAY 1 PY 2000 VL 72 IS 2 BP 113 EP 117 DI 10.1016/S0165-2478(00)00176-0 PG 5 WC Immunology SC Immunology GA 323EJ UT WOS:000087551600007 PM 10841946 ER PT J AU Murphy, WJ Longo, DL AF Murphy, WJ Longo, DL TI Growth hormone as an immunomodulating therapeutic agent SO IMMUNOLOGY TODAY LA English DT Article ID BONE-MARROW TRANSPLANTATION; T-CELL DEVELOPMENT; RECONSTITUTION AB When the immune system is under stress it can be stimulated by growth hormone. At a recent meeting*, scientists and clinicians discussed the potential for human growth hormone to act as an immunomodulator in T-cell deficiency states such as after cancer treatment, after bone marrow transplantation and during antiretroviral therapy in AIDS. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NIA, Baltimore, MD 21224 USA. RP Murphy, WJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NR 8 TC 39 Z9 45 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 MAY PY 2000 VL 21 IS 5 BP 211 EP 213 DI 10.1016/S0167-5699(00)01594-2 PG 3 WC Immunology SC Immunology GA 311QC UT WOS:000086894700004 PM 10877541 ER PT J AU Caplan, S Baniyash, M AF Caplan, S Baniyash, M TI Searching for significance in TCR-cytoskeleton interactions SO IMMUNOLOGY TODAY LA English DT Article ID T-CELL RECEPTOR; ANTIGEN-RECEPTOR; ZETA-CHAIN; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; ANCHORED PROTEINS; MEMBRANE DOMAINS; ACTIVATION MOTIF; B-CELLS; REORGANIZATION AB Two T-cell receptor (TCR) populations are expressed on T cells; one is linked to the cytoskeleton via its zeta chain. These cytoskeleton-linked receptors (30-40% of the total number of TCRs) might be important in TCR-mediated signaling and/or concurrent events. Here, differences between the two populations are summarized, and new data are examined to speculate on the functional significance of cytoskeleton-linked TCRs. C1 Inst Chil Hlth & Human Dev, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel. RP Caplan, S (reprint author), Inst Chil Hlth & Human Dev, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 48 TC 25 Z9 25 U1 0 U2 1 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 MAY PY 2000 VL 21 IS 5 BP 223 EP 228 DI 10.1016/S0167-5699(00)01604-2 PG 6 WC Immunology SC Immunology GA 311QC UT WOS:000086894700007 PM 10782053 ER PT J AU Parra, M Hui, G Johnson, AH Berzofsky, JA Roberts, T Quakyi, IA Taylor, DW AF Parra, M Hui, G Johnson, AH Berzofsky, JA Roberts, T Quakyi, IA Taylor, DW TI Characterization of conserved T- and B-cell epitopes in Plasmodium falciparum major merozoite surface protein 1 SO INFECTION AND IMMUNITY LA English DT Article ID CARBOXYL-TERMINAL FRAGMENT; MONOCLONAL-ANTIBODY; PARASITE GROWTH; AOTUS MONKEYS; MALARIA; RECOMBINANT; GP195; RECOGNITION; IMMUNITY; ANTIGENS AB Vaccines for P. falciparum will need to contain both T- and B-cell epitopes. Conserved epitopes are the most desirable, but they are often poorly immunogenic. The major merozoite surface protein 1 (MSP-1) is currently a leading vaccine candidate antigen. In this study, six peptides from conserved or partly conserved regions of MSP-1 were evaluated for immunogenicity in B10 congenic mice. Following immunization with the peptides, murine T cells were tested for the ability to proliferate in vitro and antibody responses to MSP-1 were evaluated in vivo. The results showed that one highly conserved sequence (MSP-1#1, VTHESYQELVKKLEALEDAV; located at amino acid positions 20 to 39) and one partly conserved sequence (MSP-1#23, GLFHKEKMIL NEEEITTKGA; located at positions 44 to 63) contained both T- and B-cell epitopes. Immunization of mice with these peptides resulted in T-cell proliferation and enhanced production of antibody to MSP-1 upon exposure to merozoites. MSP-1#1 stimulated T-cell responses in three of the six strains of mice evaluated, whereas MSP-1#23 was immunogenic in only one strain. Immunization with the other four peptides resulted in T-cell responses to the peptides, but none of the resulting peptide-specific T cells recognized native MSP-1. These results demonstrate that two sequences located in the N terminus of MSP-1 can induce T- and B-cell responses following immunization in a murine model. Clearly, these sequences merit further consideration for inclusion in a vaccine for malaria. C1 Georgetown Univ, Dept Biol, Washington, DC 20057 USA. Georgetown Univ, Dept Pediat, Washington, DC 20057 USA. John A Burns Sch Med, Dept Trop Med & Med Microbiol, Honolulu, HI 96816 USA. NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Parra, M (reprint author), Georgetown Univ, Dept Biol, Reiss Sci Bldg,Rm 406,37th & O St NW, Washington, DC 20057 USA. FU NIAID NIH HHS [R21-AI37943, N01-AI45242] NR 26 TC 18 Z9 18 U1 0 U2 0 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 MAY PY 2000 VL 68 IS 5 BP 2685 EP 2691 DI 10.1128/IAI.68.5.2685-2691.2000 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 305ZX UT WOS:000086572600039 PM 10768960 ER PT J AU Collazo, CM Miller, C Yap, G Hieny, S Caspar, P Schwartz, RH Sher, A AF Collazo, CM Miller, C Yap, G Hieny, S Caspar, P Schwartz, RH Sher, A TI Host resistance and immune deviation in pigeon cytochrome c T-cell receptor transgenic mice infected with Toxoplasma gondii SO INFECTION AND IMMUNITY LA English DT Article ID IFN-GAMMA; MONOCLONAL-ANTIBODY; INTERLEUKIN-12; PARASITE; CYTOKINE; LYMPHOCYTES; INTERFERON; RESPONSES; CLONES; CD4(+) AB Resistance to Toxoplasma gondii has been shown to be mediated by gamma interferon (IFN-gamma) produced by NK, CD4(+), and CD8(+) T cells. While studies of SCID mice have implicated NK cells as the source of the cytokine in acute infection, several lines of evidence suggest that IFN-gamma production by CD4(+) T lymphocytes also plays an important role in controlling early parasite growth. To evaluate whether this function is due to nonspecific as opposed to T-cell receptor (TCR)-dependent stimulation by the parasite, we have examined the resistance to T. gondii infection of pigeon cytochrome c transgenic (PCC-Tg) Rag-2(-/-) mice in which all CD4(+) T lymphocytes are unreactive with the protozoan. When inoculated with the ME49 strain, PCC-Tg animals exhibited only temporary control of acute infection and succumbed by day 17. Intracellular cytokine staining by flow cytometry revealed that, in contrast to infected nontransgenic controls, infected PCC-Tg animals failed to develop IFN-gamma-producing CD4(+) T cells. Moreover, the CD4(+) lymphocytes from these mice showed no evidence of activation as judged by lack of upregulated expression of CD44 or CD69, Nevertheless, when acutely infected transgenic mice were primed by PCC injection, the lymphokine responses measured after in vitro antigen restimulation displayed a strong Th1 bias which was shown to be dependent on endogenous interleukin 12 (IL-12), The above findings argue that, while T. gondii-induced IL-12 cannot trigger IFN-gamma production by CD4(+) T cells in the absence of TCR ligation, the pathogen is able to nonspecifically promote Th1 responses against nonparasite antigens, an effect that may explain the immunostimulatory properties of T. gondii infection. C1 NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Collazo, CM (reprint author), NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr, Bethesda, MD 20892 USA. NR 26 TC 5 Z9 5 U1 0 U2 1 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 MAY PY 2000 VL 68 IS 5 BP 2713 EP 2719 DI 10.1128/IAI.68.5.2713-2719.2000 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 305ZX UT WOS:000086572600043 PM 10768964 ER PT J AU Freidag, BL Melton, GB Collins, F Klinman, DM Cheever, A Stobie, L Suen, W Seder, RA AF Freidag, BL Melton, GB Collins, F Klinman, DM Cheever, A Stobie, L Suen, W Seder, RA TI CpG oligodeoxynucleotides and interleukin-12 improve the efficacy of Mycobacterium bovis BCG vaccination in mice challenged with M-tuberculosis SO INFECTION AND IMMUNITY LA English DT Article ID DNA VACCINE; IMMUNE-RESPONSES; INTERFERON-GAMMA; CUTTING EDGE; IMMUNOGENICITY; IL-12; LEISHMANIASIS; PROTECTION; RESISTANCE; ANTIGEN-85 AB Mycobacterium bovis bacillus Calmette-Guerin (BCG) is the only vaccine approved for prevention of tuberculosis. It has been postulated that serial passage of BCG over the years may have resulted in attenuation of its effectiveness. Because interleukin-12 (IL-12) and oligodeoxynucleotides (ODN) containing cytidine phosphate guanosine (CpG) motifs have been shown to enhance Th1 responses in vivo, they were chosen as adjuvants to increase the effectiveness of BCG vaccination. in this report, mice were vaccinated with BCG with or without IL-12 or CpG ODN and then challenged 6 weeks later via the aerosol route with the Erdman strain of M. tuberculosis. Mice vaccinated with BCG alone showed a 1- to 2-log reduction in bacterial load compared with control mice that did not receive any vaccination prior to M.. tuberculosis challenge. Moreover, the bacterial loads of mice vaccinated with BCG plus IL-12 or CpG ODN were a Further two- to fivefold lower than those of mice vaccinated with BCG alone. As an immune correlate, the antigen-specific production IFN-gamma and mRNA expression in spleen cells prior to challenge were evaluated. Mice vaccinated with BCG plus IL-12 or CpG ODN showed enhanced production of IFN-gamma compared with mice vaccinated with BCG done. Finally, granulomas in BCG-vaccinated mice were smaller and more lymphocyte rich than those in unvaccinated mice; however, the addition of IL-12 or CpG ODN to BCG vaccination did not alter granuloma formation or result in added pulmonary damage. These observations support a role for immune adjuvants given with BCG vaccination to enhance its biologic efficacy. C1 NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mycobacteria, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD USA. RP Seder, RA (reprint author), NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, 10 Ctr Dr,Room 10-11C215, Bethesda, MD 20892 USA. NR 23 TC 89 Z9 97 U1 0 U2 0 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 MAY PY 2000 VL 68 IS 5 BP 2948 EP 2953 DI 10.1128/IAI.68.5.2948-2953.2000 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 305ZX UT WOS:000086572600072 PM 10768993 ER PT J AU Vukovic, P Hogarth, PM Barnes, N Kaslow, DC Good, MF AF Vukovic, P Hogarth, PM Barnes, N Kaslow, DC Good, MF TI Immunoglobulin G3 antibodies specific for the 19-kilodalton carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein 1 transfer protection to mice deficient in Fc-gamma RI receptors SO INFECTION AND IMMUNITY LA English DT Article ID RECOMBINANT PROTEIN; IMMUNE-RESPONSE; IN-VIVO; MALARIA; IMMUNIZATION; VACCINE; IGG AB Merozoite surface protein 1 (MSP-1(19)) is a leading malaria vaccine candidate. Specific antibodies contribute to immunity; binding to macrophages is believed to represent the main action of malaria antibodies. We show that an MSP-1(19)-specific immunoglobulin G3 (IgG3) monoclonal antibody can passively transfer protection to mice deficient in the alpha chain of Fc-gamma RI whose macrophages cannot bind IgG3. C1 Queensland Inst Med Res, Cooperat Res Ctr Vaccine Technol, Brisbane, Qld 4029, Australia. Univ Queensland, Australian Ctr Int & Trop Hlth & Nutr, Brisbane, Qld 4029, Australia. Austin Res Inst, Heidelberg, Vic 3084, Australia. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Good, MF (reprint author), Queensland Inst Med Res, PO Royal Brisbane Hosp, Brisbane, Qld 4029, Australia. NR 19 TC 26 Z9 26 U1 0 U2 0 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 MAY PY 2000 VL 68 IS 5 BP 3019 EP 3022 DI 10.1128/IAI.68.5.3019-3022.2000 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 305ZX UT WOS:000086572600086 PM 10769007 ER PT J AU Fahey, BJ Henderson, DK Coe, L Koziol, D Schmitt, J Crawford, A Holland, SM von Reyn, CF AF Fahey, BJ Henderson, DK Coe, L Koziol, D Schmitt, J Crawford, A Holland, SM von Reyn, CF TI Tuberculin skin testing in the era of multidrug resistant tuberculosis SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Letter ID COMPLEX C1 Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Fahey, BJ (reprint author), Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAY PY 2000 VL 21 IS 5 BP 302 EP 303 DI 10.1086/503223 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 314AC UT WOS:000087031100003 PM 10823557 ER PT J AU Kumari, P Levy, CS McHenry, KS Fedorko, D Lucey, DR AF Kumari, P Levy, CS McHenry, KS Fedorko, D Lucey, DR TI C-amycolatum: A novel cause of breast abscess SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Article ID CORYNEBACTERIUM-AMYCOLATUM; INFECTION; XEROSIS; SEPSIS C1 Washington Hosp Ctr, Infect Dis Serv, Washington, DC 20010 USA. Washington Hosp Ctr, Microbiol Serv, Washington, DC 20010 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Clin Pathol, Microbiol Serv, Bethesda, MD 20892 USA. RP Levy, CS (reprint author), Washington Hosp Ctr, Infect Dis Serv, Room 2A-56,110 Irving St NW, Washington, DC 20010 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD MAY PY 2000 VL 9 IS 4 BP 179 EP 181 DI 10.1097/00019048-200009040-00009 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 309FD UT WOS:000086756900009 ER PT J AU Tani, K Murphy, WJ Chertov, O Salcedo, R Koh, CY Utsunomiya, I Funakoshi, S Asai, O Herrmann, SH Wang, JM Kwak, LW Oppenheim, JJ AF Tani, K Murphy, WJ Chertov, O Salcedo, R Koh, CY Utsunomiya, I Funakoshi, S Asai, O Herrmann, SH Wang, JM Kwak, LW Oppenheim, JJ TI Defensins act as potent adjuvants that promote cellular and humoral immune responses in mice to a lymphoma idiotype and carrier antigens SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE antibody formation; cytokine; IFN-gamma; IL-4; tumor antigen ID DELAYED-TYPE HYPERSENSITIVITY; RED-BLOOD-CELLS; IFN-GAMMA; T-CELLS; MONOCLONAL-ANTIBODY; PEPTIDE DEFENSINS; IN-VIVO; ANTIMICROBIAL PEPTIDES; ANTIBIOTIC PROTEINS; SELECTIVE DEPLETION AB Defensins released by neutrophils are able to kill a broad spectrum of microbes. They also induce leukocyte migration in vitro and elicit inflammatory leukocyte responses at s.c, injection sites in mice, In vitro experiments showed that human defensins enhanced concanavalin A-stimulated murine spleen cell proliferation and IFN-gamma production, This led us to examine the effects of human defensins on specific immune responses in vivo. BALB/c mice were immunized with 50 mu g of keyhole limpet hemocyanin (KLH) adsorbed to aluminum hydroxide and administered with defensins in aqueous solution. Intraperitoneal administration of defensins significantly increased the production of KLH-specific IgG1, IgG2a and IgG2b antibodies 14 days after immunization. In vitro splenic KLH-specific proliferative responses were higher in mice treated with KLH and defensins than in those treated with KLH alone, Increased IFN-gamma and, to a lesser extent, IL-4 production were also detected in the supernatants of ex vivo KLH-activated spleen cells from mice treated with defensins, Finally, defensins significantly enhanced the antibody response to a syngeneic tumor antigen, lymphoma Ig idiotype and also augmented resistance to tumor challenge. These results indicate that defensins act as potent immune adjuvants by inducing the production of lymphokines, which promote T cell-dependent cellular immunity and antigen-specific Ig production. Thus, defensins appear to function as neutrophil-derived signals that promote adaptive immune responses. C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Dept Expt Transplantat & Immunol, Med Branch, Frederick, MD 21702 USA. Genet Inst, Cambridge, MA 02140 USA. RP Oppenheim, JJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RI Koh, Crystal/D-9986-2013 NR 50 TC 136 Z9 151 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 2000 VL 12 IS 5 BP 691 EP 700 DI 10.1093/intimm/12.5.691 PG 10 WC Immunology SC Immunology GA 315TM UT WOS:000087129100012 PM 10784615 ER PT J AU Catalano, MG Pfeffer, U Raineri, M Ferro, P Curto, A Capuzzi, P Corno, F Berta, L Fortunati, N AF Catalano, MG Pfeffer, U Raineri, M Ferro, P Curto, A Capuzzi, P Corno, F Berta, L Fortunati, N TI Altered expression of androgen-receptor isoforms in human colon-cancer tissues SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID STEROID-HORMONE RECEPTORS; COLORECTAL-CANCER; RISK AB Many groups have examined of androgen the effects on normal and neoplastic colon tissues, but no clear picture has hitherto emerged, In particular, the presence and the function of the androgen receptor (AR) has only partially been investigated in the past. The present study reports analysis of expression of the AR gene as messenger RNA and as protein in surgical samples of neoplastic colon mucosa and of corresponding healthy surrounding tissue. Specific binding for DHT, demonstrating the presence of AR, was observed in almost all the samples (2 samples out of 12 were negative), No significant difference was observed between healthy and neoplastic mucosa, or between male and female patients. A further characterization of AR was performed with Western blot, using 2 different primary antibodies. Both AR isoforms, AR-B and AR-A, were detected in healthy mucosa, while only AR-A, resolving at 87 kDa, was observed in neoplastic mucosa, RT-PCR analysis revealed the transcript for AR in both healthy and neoplastic mucosa in 10 samples; no message was detectable in 2 samples (negative also for binding); 2 additional samples presented AR mRNA only in healthy colon mucosa, 2 others only in neoplastic mucosa. In addition, a variant AR messenger RNA, probabily derived from alternative splicing, was observed. We found that AR is expressed both in healthy and in neoplastic colon mucosa, either as mRNA or as protein. Neoplastic colon tissue shows a characteristic loss of expression of the AR-B isoform, while AR-A expression is maintained. These findings underscore the possible role of androgen and its receptor in colon carcinogenesis. Int. J, Cancer 86:325-330, 2000, (C) 2000 Wiley-Liss, Inc. C1 Azienda Osped S Giovanni Battista, UOADU Med Gen 2, Lab Endocrinol, I-10126 Turin, Italy. Univ Turin, I-10126 Turin, Italy. Natl Canc Inst, CBA, IST, Mol Biol Lab, Genoa, Italy. Azienda Osped San Giovanni Battista, UOADU Gen Surg 1, Turin, Italy. RP Fortunati, N (reprint author), II UOADU Med Gen, Lab Endocrinol, Via Genova 3, I-10126 Turin, Italy. RI Catalano, Maria Graziella/J-4320-2016; Fortunati, Nicoletta/K-3081-2016; Pfeffer, Ulrich/J-7064-2016 OI Catalano, Maria Graziella/0000-0002-1170-8245; Fortunati, Nicoletta/0000-0001-8069-9621; Pfeffer, Ulrich/0000-0003-0872-4671 NR 21 TC 24 Z9 25 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2000 VL 86 IS 3 BP 325 EP 330 DI 10.1002/(SICI)1097-0215(20000501)86:3<325::AID-IJC4>3.0.CO;2-G PG 6 WC Oncology SC Oncology GA 301MZ UT WOS:000086315100004 PM 10760818 ER PT J AU Thomas, GR Chen, Z Enamorado, I Bancroft, C Van Waes, C AF Thomas, GR Chen, Z Enamorado, I Bancroft, C Van Waes, C TI IL-12-and IL-2-induced tumor regression in a new murine model of oral squamous-cell carcinoma is promoted by expression of the CD80 co-stimulatory molecule and interferon-gamma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ESTABLISHED TUMORS; GENE-THERAPY; INTERLEUKIN-12; CANCER; HEAD; NECK; APOPTOSIS; IMMUNITY; B7.1 AB Therapy with IL-12 or IL-2 induces tumor regression in only a few patients with head-and-neck squamous cell carcinoma (SCC), and the factors promoting responsiveness have not been well defined. In this study, we examined whether combined IL-12 and IL-2 therapy can induce tumor regression in a new murine model of oral SCC and determined if the anti-tumor response is promoted by expression of the immune co-stimulatory molecule CD80 and cytokine IFN-gamma, In CD80-positive or -negative subclones of a BALB/c oral SCC line in syngeneic mice, we showed that systemic rIL-12 alone was comparable in effectiveness to combined therapy with IL-12 and peri-tumoral rIL-2, inducing complete regression of the CD80(+) line B7E1 1-4scid. However, therapy with these cytokines had no effect on growth of the CD80(-) subclone B7E3-4scid and did not induce complete regression of the CD80(+) subclone B7E1 1-4scid in congenic BALB/c IFN-gamma knockout mice, indicating that expression of the CD80 co stimulatory molecule and IFN-gamma contributes to tumor regression, In cytokine-treated mice that rejected the CD80(+) SCC line, an increase in infiltrating CD4(+) lymphocytes and apoptotic bodies within the tumor specimens was observed, and resistance to rechallenge with the same tumor was detected in 50% of recipients, consistent with an immune response, Our results provide evidence that regression of oral head-and-neck SCC may be induced by therapy with systemic IL-12 and that expression of the CD80 co stimulatory molecule by SCC and IFN-gamma by the host promote IL-12 induced regression of SCC. Published 2000 Wiley-Liss, Inc(dagger). C1 NIDCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. RP Van Waes, C (reprint author), NIDCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bldg 10,Room 5D-55,10 Ctr Dr, Bethesda, MD 20892 USA. FU NIDCD NIH HHS [Z01DC00016] NR 21 TC 23 Z9 24 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2000 VL 86 IS 3 BP 368 EP 374 DI 10.1002/(SICI)1097-0215(20000501)86:3<368::AID-IJC11>3.0.CO;2-1 PG 7 WC Oncology SC Oncology GA 301MZ UT WOS:000086315100011 PM 10760825 ER PT J AU Albert, MR AF Albert, MR TI Dermatology related advertisements from the 1920s and 1930s SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Albert, MR (reprint author), NIH, Dermatol Branch, Bldg 10,Room 22N260,10 Ctr Dr, Bethesda, MD 20892 USA. NR 53 TC 2 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD MAY PY 2000 VL 39 IS 5 BP 389 EP 395 DI 10.1046/j.1365-4362.2000.00817.x PG 7 WC Dermatology SC Dermatology GA 319JY UT WOS:000087338800017 PM 10849135 ER PT J AU Walder, K Hanson, RL Kobes, S Knowler, WC Ravussin, E AF Walder, K Hanson, RL Kobes, S Knowler, WC Ravussin, E TI An autosomal genomic scan for loci linked to plasma leptin concentration in Pima Indians SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE genetics; leptin; linkage analysis; obesity ID ASSESSING GENETIC-LINKAGE; QUANTITATIVE-TRAIT LOCI; SERUM LEPTIN; INSULIN-RESISTANCE; DIABETES-MELLITUS; SIB-PAIR; ALPHA GENE; TNF-ALPHA; OBESITY; WEIGHT AB OBJECTIVE: To identify chromosomal regions linked to plasma leptin concentrations. DESIGN: Autosomal genome-wide scan, including 516 microsatellite markers. Sib-pair (Haseman-Elston) and variance components methods were used to assess genetic linkage. SUBJECTS: 770 Pima Indians comprising 239 nuclear families (for a total of 1199 sibling-pairs). MEASUREMENTS: Plasma leptin concentrations and body mass index (BMI), adjusted for age and sex. RESULTS: The strongest evidence for linkage with plasma leptin concentration was on chromosome 6p logarithm of odds (LOD) = 2.1 by variance components analysis. There was no evidence for linkage to BMI in this region. Additional regions with marginal evidence for linkage to plasma leptin concentration (LOD greater than or equal to 1.0) were detected on chromosomes 3, 11, 13, 15 and 16. CONCLUSIONS: The results suggest that a locus on chromosome 6p influences plasma leptin concentrations. Replication studies are needed to exclude the possibility that linkage has been falsely detected. C1 NIDDKD, Diabet & Arthritis Epidemiol Sect, NIH, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA. RP Hanson, RL (reprint author), NIDDKD, Diabet & Arthritis Epidemiol Sect, NIH, Phoenix Epidemiol & Clin Res Branch, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NCRR NIH HHS [1 P41 RR03655] NR 37 TC 29 Z9 29 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 2000 VL 24 IS 5 BP 559 EP 565 DI 10.1038/sj.ijo.0801197 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 315UG UT WOS:000087130900006 PM 10849576 ER PT J AU Jenkinson, CP Cray, K Walder, K Herzog, H Hanson, R Ravussin, E AF Jenkinson, CP Cray, K Walder, K Herzog, H Hanson, R Ravussin, E TI Novel polymorphisms in the neuropeptide-Y Y5 receptor associated with obesity in Pima Indians SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE NPY; NPY5R; obesity; association; feeding; polymorphisms ID FOOD-INTAKE; FEEDING-BEHAVIOR; MICE LACKING; GENE; WEIGHT; MAGNITUDE; LEPTIN; LOCI AB OBJECTIVE: To investigate whether the neuropeptide Y receptor 5 gene (NPY5R) is associated with obesity in humans. DESIGN: The NPY5R gene was screened for polymorphisms by direct sequencing in two groups of Pima Indians, selected for extremes of body mass index (BMI). Genotype frequencies were analyzed for association with BMI extreme. SUBJECTS: Full-heritage Pima Indians, non-diabetic and not first degree relatives. Obese group: 19 M/24 F, BMI = 49 +/- 7 kg/m(2) (mean +/- s.d.) age = 24 +/- 2 y, lean group: 16 M/16 F, BMI = 23 +/- 2 kg/m(2), age = 27 +/- 3 y. MEASUREMENTS: Initially, the entire gene (proximal promoter, exon 1A, coding sequence, 5' and 3' UTRs) was sequenced in a subset of 20 individuals. No variants were found in the coding sequence, however three novel single nucleotide polymorphisms were detected in the non-coding regions: (1) a C-->T transition located within the promoter 28 bp upstream of the exon 1A transcription start site; (2) a T-->C transition 94 bp downstream of the stop codon; and (3) a G-->A transition 432 bp downstream of the stop codon. The polymorphisms were then screened in all 75 subjects. RESULTS: The polymorphisms had mean heterozygosities of 0.34-0.50 and were in strong linkage disequilibrium (P < 0.001). Genotype frequencies differed significantly in lean and obese Pimas for P2 (P = 0.04) and for a triple haplotype (P = 0.02, Bonferroni corrected). CONCLUSION: Considering the importance of this gene in regulation of body weight, the association of these polymorphisms with extremes of BMI in Pima Indians indicates that NPY5R, or a locus nearby, may contribute to susceptibility to obesity in this population. C1 NIDDK, CDNS, NIH, Phoenix, AZ 85014 USA. Garvan Inst, Sydney, NSW, Australia. RP Jenkinson, CP (reprint author), NIDDK, CDNS, NIH, Bldg 1,Lab 8,1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NIDDK NIH HHS [R01 DK079195] NR 30 TC 30 Z9 30 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAY PY 2000 VL 24 IS 5 BP 580 EP 584 DI 10.1038/sj.ijo.0801200 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 315UG UT WOS:000087130900009 PM 10849579 ER PT J AU Jiang, XX Lim, LY Daly, JW Li, AH Jacobson, KA Roberge, M AF Jiang, XX Lim, LY Daly, JW Li, AH Jacobson, KA Roberge, M TI Structure-activity relationships for G2 checkpoint inhibition by caffeine analogs SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE caffeine; cell cycle checkpoint; DNA damage; radiosensitization; structure-activity ID CELL-CYCLE CHECKPOINTS; INDUCED MITOTIC DELAY; HUMAN-TUMOR-CELLS; ADENOSINE RECEPTORS; P34(CDC2) KINASE; P53 FUNCTION; G(2) DELAY; DNA-DAMAGE; RADIOSENSITIZATION; METHYLXANTHINES AB Caffeine inhibits the G2 checkpoint activated by DNA damage and enhances the toxicity of DNA-damaging agents towards p53-defective cancer cells. The relationship between structure and G2 checkpoint inhibition was determined for 56 caffeine analogs. Replacement of the methyl group at position 3 or 7 resulted in loss of activity, while replacement at position 1 by ethyl or propyl increased activity slightly. 8-Substituted caffeines retained activity, but were relatively insoluble. The structure-activity profile did not resemble those for other known pharmacological activities of caffeine. The active analogs also potentiated the killing of p53-defective cells by ionizing radiation, but none was as effective as caffeine. C1 Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Roberge, M (reprint author), Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 39 TC 16 Z9 16 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 MAY PY 2000 VL 16 IS 5 BP 971 EP 978 PG 8 WC Oncology SC Oncology GA 305ZB UT WOS:000086570700013 PM 10762633 ER PT J AU Angulo, AF Reijgers, R Brugman, J Kroesen, I Hekkens, FEN Carle, P Bove, JM Tully, JG Hill, AC Schouls, LM Schot, CS Roholl, PJM Polak-Vogelzang, AA AF Angulo, AF Reijgers, R Brugman, J Kroesen, I Hekkens, FEN Carle, P Bove, JM Tully, JG Hill, AC Schouls, LM Schot, CS Roholl, PJM Polak-Vogelzang, AA TI Acholeplasma vituli sp nov., from bovine serum and cell cultures SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article DE Acholeplasma vituli sp nov.; taxonomy; description ID MYCOPLASMAS; IDENTIFICATION; SPIROPLASMA; REQUIREMENT; MOLLICUTES; GROWTH AB Organisms isolated from commercial foetal bovine serum and from cell culture lines containing such serum supplements were found to consist of non-helical, non-motile, pleomorphic coccoid forms. One strain (FC 097-2(T)) cultivated directly from foetal bovine serum was selected for characterization. In ultrastructural examination, individual round cells lacked cell wall structures and cells varied in sire, with a mean diameter of about 700 nm. However, variable numbers of cells were filterable through membranes of 300 nm. Optimum growth occurred between 30 and 37 degrees C. The organism fermented glucose, fructose and mannose, but did not hydrolyse arginine. The strain was insensitive to 500 U penicillin ml(-1) and was capable of growing in the absence of serum or cholesterol. The organism was serologically distinct from all 13 currently described species in the genus Acholeplasma and from other sterol-requiring species in the genus Mycoplasma, using growth inhibition, immunoperoxidase and immunofluorescence tests. Strain FC 097-2(T) was found to have a DNA G+C composition between 37.6+/-1 mol% and 38.3+/-1 mol%. The genome size was determined to be 2095 kbp. The 16S rDNA sequence of strain FC 097-2(T) was compared to 16S rDNA sequences of other mollicutes in nucleotide databases. No deposited sequence was found to be identical; the closest relatives were several members of the genus Acholeplasma. On the basis of these findings and other similarities to acholeplasmas in morphology and growth, the! absence of a sterol requirement for growth, and similar genomic characteristics, the organism was assigned to the genus Acholeplasma. Strain FC 097-2(T) is designated the type strain (ATCC 700667(T)) of a new species, Acholeplasma vituli. C1 Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. INRA, Biol Cellulaire & Mol Lab, F-33883 Villenave Dornon, France. Univ Bordeaux 2, F-33883 Villenave Dornon, France. NIAID, Mycoplasma Sect, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. MRC, Toxicol Unit, Carshalton SM5 4EF, Surrey, England. RP Angulo, AF (reprint author), Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. EM a.angulo@rivm.nl NR 42 TC 6 Z9 6 U1 1 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 EI 1466-5034 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD MAY PY 2000 VL 50 BP 1125 EP 1131 PN 3 PG 7 WC Microbiology SC Microbiology GA 316PK UT WOS:000087176500022 PM 10843054 ER PT J AU Monks, A Harris, ED Vaigro-Wolff, A Hose, CD Connelly, JW Sausville, EA AF Monks, A Harris, ED Vaigro-Wolff, A Hose, CD Connelly, JW Sausville, EA TI UCN-01 enhances the in vitro toxicity of clinical agents in human tumor cell lines SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE UCN-01; combination; synergy ID PROTEIN-KINASE-C; SELECTIVE INHIBITOR; 7-HYDROXYSTAUROSPORINE UCN-01; CDC25C PHOSPHATASE; ANTITUMOR-ACTIVITY; CARCINOMA-CELLS; G(2) ARREST; CYTOTOXICITY; CISPLATIN; GROWTH AB UCN-01 is undergoing Phase I evaluation and is a candidate for combination strategies in the clinic. UCN-01 has been shown to have a variety of effects on cellular targets and the cell cycle. It has also been reported to sensitize cells to several clinical drugs in vitro, possibly in a manner related to p53 status. Thus, combinations of UCN-01 with a series of clinical agents in variety of cell lines have been investigated in vitro. Certain cell lines demonstrated synergistic interactions with combinations of UCN-01 (20-150 nM) and thiotepa, mitomycin C, cisplatin, melphalan, topotecan, gemcitabine, fludarabine or 5-fluorouracil. In contrast, UCN-01 combinations with the antimitotic agents, paclitaxel and vincristine, or topoisomerase II inhibitors, adriamycin and etoposide, did not result in synergy, only in additive toxicity. Cells with non-functional p53 were significantly more susceptible to the supra-additive effects of certain DNA-damaging agents and UCN-01 combinations, than cells expressing functional p53 activity. In contrast, there was no significant relationship between p53 status and susceptibility to synergy between antimetabolites and UCN-01. The mechanism behind the observed synergy appeared unrelated to effects on protein kinase C or abrogation of the cell cycle in G2. Moreover, increased apoptosis did not fully explain the supradditive response. These data indicate that UCN-01 sensitizes a variety of cell lines to certain DNA-damaging agents (frequently covalent DNA-binding drugs) and antimetabolites in vitro, but the mechanism underlying this interaction remains undefined. C1 NCI, SAIC Frederick, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, DCTD, Rockville, MD USA. RP Monks, A (reprint author), NCI, SAIC Frederick, POB B,Bldg 432, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 29 TC 62 Z9 62 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD MAY PY 2000 VL 18 IS 2 BP 95 EP 107 DI 10.1023/A:1006313611677 PG 13 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 306WZ UT WOS:000086622800001 PM 10857990 ER PT J AU Schmidt, NB Storey, J Greenberg, BD Santiago, HT Li, Q Murphy, DL AF Schmidt, NB Storey, J Greenberg, BD Santiago, HT Li, Q Murphy, DL TI Evaluating gene x psychological risk factor effects in the pathogenesis of anxiety: A new model approach SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN TRANSPORTER GENE; PANIC DISORDER; PROMOTER POLYMORPHISM; ENVIRONMENTAL-FACTORS; CO2 CHALLENGE; RAT-BRAIN; SENSITIVITY; ATTACKS; HYPERVENTILATION AB The present study evaluated the singular and interactive effects of a functional polymorphism (variation) in the serotonin transporter (5-HTT) gene and a psychological trait (anxiety sensitivity [AS], i.e., fear of arousal symptoms) in predicting subjective and physiological responses to a 35% carbon dioxide (CO2) challenge in a community sample (N = 72). Genotypes were divided into 2 groups in accord with prior research. Findings were partially supportive of the hypothesized risk model. These indicated that the Group L genotype (homozygous for the l allele), compared with the Group S genotype (homozygous fur the s allele plus heterozygous individuals), predicted greater fearful response to the biological challenge. There was also an AS X Genotype interaction predicting heart rate variability (HRV) in response to the CO2, suggesting that high AS plus Group L status predicts decreased HRV. C1 Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Schmidt, NB (reprint author), Ohio State Univ, Dept Psychol, 245 Townshend Hall, Columbus, OH 43210 USA. NR 90 TC 47 Z9 47 U1 8 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2000 VL 109 IS 2 BP 308 EP 320 DI 10.1037//0021-843X.109.2.308 PG 13 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 328ZA UT WOS:000087880600015 PM 10895569 ER PT J AU Cooper, ER Charurat, M Burns, DN Blattner, W Hoff, R AF Cooper, ER Charurat, M Burns, DN Blattner, W Hoff, R CA Women Infants Transmission Study G TI Trends in antiretroviral therapy and mother-infant transmission of HIV SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretroviral therapy; vertical transmission; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; REDUCTION; PREGNANCY; TYPE-1 AB Trends in the vertical transmission rate of HIV and evolving antiretroviral usage between 1990 and 1998 within the Women and Infants Transmission Study were evaluated. A decline in mother-infant transmission was temporally associated with advances in therapy, especially when regimens including a protease inhibitor were included in the analysis. C1 Boston Univ, Med Ctr, Pediat AIDS Program, Sch Med,Dept Pediat, Boston, MA 02118 USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. RP Cooper, ER (reprint author), Boston Univ, Med Ctr, Pediat AIDS Program, Sch Med,Dept Pediat, 774 Albany St,5th Floor, Boston, MA 02118 USA. NR 6 TC 43 Z9 44 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAY 1 PY 2000 VL 24 IS 1 BP 45 EP 47 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 326KJ UT WOS:000087734400006 PM 10877494 ER PT J AU Harlow, SD Schuman, P Cohen, M Ohmit, SE Cu-Uvin, S Lin, XH Anastos, K Burns, D Greenblatt, R Minkoff, H Muderspach, L Rompalo, A Warren, D Young, MA Klein, RS AF Harlow, SD Schuman, P Cohen, M Ohmit, SE Cu-Uvin, S Lin, XH Anastos, K Burns, D Greenblatt, R Minkoff, H Muderspach, L Rompalo, A Warren, D Young, MA Klein, RS TI Effect of HIV infection on menstrual cycle length SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; menstruation; menstruation disorders; amenorrhea ID HUMAN-IMMUNODEFICIENCY-VIRUS; WOMEN; EPIDEMIOLOGY; DISEASE AB HIV serostatus and menstrual function were examined using prospectively collected menstrual data from 802 HIV-seropositive and 273 HIV-seronegative women, ages 20 to 44, enrolled in two cohort studies of HIV infection in North American women. The associations between HIV serostatus and the probabilities of having a cycle lasting >40 days (n = 541 cycles), >90 days (n = 67 cycles), <18 days (n = 315 cycles) and mean length and variability of 18 to 30 day cycles (n = 3634) were assessed. After adjustment for demographic characteristics, body mass index, and substance use, seropositivity increased the odds of having a very short cycle (<18 days, odds ratio [OR], 1.45; 95% confidence interval [CI], 1.00-2.11) and a very long cycle (>90 days, OR, 1.32; 95% CI, 0.68-2.58) slightly, although the latter CIs include one. Seropositivity did nor increase the odds of having a moderately long cycle (>40 days, OR, 1.14) or affect mean cycle length or variability (beta, 0.30 +/- 0.20: between-woman standard deviation [SD]. 2.2 days [HIV-seronegative] and 1.9 days [HIV-seropositive]: within-woman SD, 3.5 days for both). Although seropositivity may slightly increase the probability of very short cycles, HIV serostatus has little overall effect on amenorrhea, menstrual cycle length, or variability. Among HIV-seropositive women, higher viral loads and lower CD4(+) counts were associated with increased cycle variability and polymenorrhea. C1 Univ Michigan, Ann Arbor, MI 48109 USA. Wayne State Univ, Detroit, MI USA. Cook Cty Hosp, Chicago, IL 60612 USA. Brown Univ, Providence, RI 02912 USA. Catholic Med Ctr Brooklyn, Jamaica, NY USA. Catholic Med Ctr Queens, Jamaica, NY USA. Natl Inst Child Hlth & Dev, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. SUNY, Brooklyn, NY USA. Univ So Calif, Los Angeles, CA USA. Johns Hopkins Univ, Baltimore, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Georgetown Univ, Washington, DC USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Harlow, SD (reprint author), Dept Epidemiol, 109 Observ St, Ann Arbor, MI 48109 USA. FU NIAID NIH HHS [U01-AI-31834, U01-AI-34994, U01-AI-35004] NR 25 TC 54 Z9 56 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAY 1 PY 2000 VL 24 IS 1 BP 68 EP 75 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 326KJ UT WOS:000087734400010 PM 10877498 ER PT J AU Hartos, JL Eitel, P Haynie, DL Simons-Morton, BG AF Hartos, JL Eitel, P Haynie, DL Simons-Morton, BG TI Can I take the car? Relations among parenting practices and adolescent problem-driving practices SO JOURNAL OF ADOLESCENT RESEARCH LA English DT Article ID YOUNG DRIVERS; SUBSTANCE USE; RISK-TAKING; LONGITUDINAL EXAMINATION; RECKLESS BEHAVIOR; ACCIDENT RISK; PERSONALITY; DRINKING; SCHOOL; INVOLVEMENT AB The goal of this study was to examine relations among problem-driving practices and parenting practices. Three hundred adolescents licensed 2 years or less were interviewed about driving behaviors, parenting practices, and orientations toward deviance Factors significantly related to risky driving behaviors, traffic violations, and motor vehicle crashes included lower levels of parental monitoring and control and lenient parental restrictions on driving (i.e., friends as passengers and driving curfews). Parental monitoring was among the subset of variables most useful in predicting risky driving behaviors. Violations were 4 times more likely with lenient restrictions related to frequency of friends as passengers and 2 times more likely with low parental control. Crashes were 7 rimes more likely with lenient restrictions related to frequency of friends as passengers. Overall, the findings suggest that adolescent problem driving is related to parenting practices. C1 NICHHD, Bethesda, MD USA. Menninger Fdn, Topeka, KS USA. RP Hartos, JL (reprint author), NICHHD, Bethesda, MD USA. OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 NR 47 TC 88 Z9 88 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0743-5584 J9 J ADOLESCENT RES JI J. Adolesc. Res. PD MAY PY 2000 VL 15 IS 3 BP 352 EP 367 DI 10.1177/0743558400153003 PG 16 WC Psychology, Developmental SC Psychology GA 310XH UT WOS:000086854500003 ER PT J AU Leonard, WJ Lin, JX AF Leonard, WJ Lin, JX TI Cytokine receptor signaling pathways SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE cytokine; cytokine receptor; IL-2; STAT proteins; Jak kinases; XSCID ID SEVERE COMBINED IMMUNODEFICIENCY; HUMAN INTERLEUKIN-2 RECEPTOR; DEFECTIVE LYMPHOID DEVELOPMENT; PROTEIN-TYROSINE-PHOSPHATASE; MICE LACKING JAK3; T-CELL LINE; IL-2 RECEPTOR; GAMMA-CHAIN; BETA-CHAIN; PHOSPHATIDYLINOSITOL 3-KINASE AB Cytokines represent a diverse group of molecules that transmit intercellular signals. These signals may either be autocrine (where the same cell both produces the cytokine and responds to it) or paracrine (where the cytokine is made by one cell and acts on another). Both these situations can occur simultaneously. Cytokines use multiple signaling pathways. This review will focus on signaling by type I cytokines and in particular on signaling by the IL-2 family of cytokines, as an illustrative example. The major signaling pathway that mill be discussed is the Jak-STAT pathway, although other pathways will also be reviewd. The Jak-STAT pathway is a very rapid cytosol-to-nuclear signaling pathway that underscores how quickly extra-cellular signals ran be transmitted to the nucleus. Aspects related to cytokine redundancy, pleiotropy, and specificity will be discussed. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7N252, Bethesda, MD 20892 USA. NR 112 TC 94 Z9 106 U1 3 U2 9 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2000 VL 105 IS 5 BP 877 EP 888 DI 10.1067/mai.2000.106899 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA 316TW UT WOS:000087185000003 PM 10808165 ER PT J AU Sousa, AR Lane, SJ Cidlowski, JA Staynov, DZ Lee, TH AF Sousa, AR Lane, SJ Cidlowski, JA Staynov, DZ Lee, TH TI Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor beta-isoform SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE glucocorticoid receptor alpha and beta; glucocorticoid-resistant asthma ID BRONCHIAL-ASTHMA; HORMONE; TRANSCRIPTION; PREDNISOLONE; MODULATION AB Background: Glucocorticoid-resistant bronchial asthma is characterized by failure of corticosteroids to suppress key asthma-relevant, cell-mediated inflammatory responses in the airways. Objective: The mechanism of this phenomenon is not clear but may involve aberrant expression of the beta-isoform of the glucocorticoid receptor. Methods: We have measured expression of the alpha- and beta-glucocorticoid receptor isoforms in tuberculin-driven cutaneous cell-mediated inflammatory lesions in people with asthma who are glucocorticoid sensitive and resistant after 9 days of therapy with oral prednisolone (40 mg/day) or matching placebo in a random order, crossover design, Results: After placebo therapy, the mean numbers of cells expressing glucocorticoid receptor alpha immunoreactivity in the lesions evoked in glucocorticoid-sensitive and -resistant patients with asthma were statistically equivalent. The numbers of cells expressing glucocorticoid receptor beta were significantly elevated in the patients who were glucocorticoid resistant, resulting in an 8-fold higher ratio of expression of glucocorticoid receptor alpha/glucocorticoid receptor beta in the patients who were glucocorticoid sensitive. Glucocorticoid receptor alpha/glucocorticoid receptors beta were colocalized to the same cells. Oral prednisolone therapy was associated with a significant decrease in the numbers of cells expressing glucocorticoid receptor alpha but not glucocorticoid receptor beta in the subjects who were glucocorticoid sensitive. No significant change was found in the numbers of cells expressing glucocorticoid receptor alpha and glucocorticoid receptor beta in the patients who were glucocorticoid resistant. Prednisolone therapy reduced the ratio of glucocorticoid receptor alpha/glucocorticoid receptor beta expression for the patients who were glucocorticoid sensitive to a level seen in the patients who were glucocorticoid resistant before therapy. Conclusion: Because glucocorticoid receptor beta inhibits alpha-glucocorticoid receptor-mediated transactivation of target genes, the increased expression of glucocorticoid receptor beta in inflammatory cells might be a critical mechanism for conferring glucocorticoid resistance. C1 Guys Hosp, Univ London Kings Coll, Dept Resp Med & Allergy, London SE1 9RT, England. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Lee, TH (reprint author), Guys Hosp, Univ London Kings Coll, Dept Resp Med & Allergy, 5th Floor Thomas Guy House, London SE1 9RT, England. NR 20 TC 164 Z9 175 U1 1 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2000 VL 105 IS 5 BP 943 EP 950 DI 10.1067/mai.2000.106486 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 316TW UT WOS:000087185000013 PM 10808175 ER PT J AU Sayeed, S Reaves, L Radnedge, L Austin, S AF Sayeed, S Reaves, L Radnedge, L Austin, S TI The stability region of the large virulence plasmid of Shigella flexneri encodes an efficient postsegregational killing system SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; CLONING VECTORS; PARTITION SITE; CELL-DEATH; P1; DNA AB The large virulence plasmid pMYSH6000 of Shigella flexneri contains a determinant that is highly effective in stabilizing otherwise unstable plasmids in Escherichia coli. Expression of two small contiguous genes, mvpA and mvpT (formerly termed STBORF1 and STBORF2), was shown to be sufficient for stability. Mutations in mvpT abolished plasmid stability, and plasm ids expressing only mvpT kilted the cells unless mvpA was supplied from a separate plasmid or from the host chromosome. When replication of a plasmid earning the minimal mvp region was blocked, growth of the culture stopped after a short lag and virtually all of the surviving cells retained the plasmid. Thus, the mvp system stabilizes by a highly efficient postsegregational killing (PSK) mechanism, with mvpT encoding a cell toxin and mvpA encoding an antidote. The regions that surround the mvp genes in their original context have an inhibitory effect that attenuates plasmid stabilization and PSK. The region encompassing the mvp genes also appears to contain an additional element that can aid propagation of a pSC101-based plasmid under conditions where replication initiation is marginal. However, this appears to be a relatively nonspecific effect of DNA insertion into the plasmid vector. C1 NCI, Frederick Canc Res & Dev Ctr, Gene Regulat & Chromosome Biol Lab, ABL Basic Res Program, Frederick, MD 21702 USA. RP Austin, S (reprint author), NCI, Frederick Canc Res & Dev Ctr, Gene Regulat & Chromosome Biol Lab, ABL Basic Res Program, Frederick, MD 21702 USA. NR 20 TC 31 Z9 33 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2000 VL 182 IS 9 BP 2416 EP 2421 DI 10.1128/JB.182.9.2416-2421.2000 PG 6 WC Microbiology SC Microbiology GA 304RZ UT WOS:000086499100009 PM 10762240 ER PT J AU Bono, JL Elias, AF Kupko, J Stevenson, B Tilly, K Rosa, P AF Bono, JL Elias, AF Kupko, J Stevenson, B Tilly, K Rosa, P TI Efficient targeted mutagenesis in Borrelia burgdorferi SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; CIRCULAR PLASMID; MOTILITY OPERON; GENE; EXPRESSION; AGENT; DNA; TRANSFORMATION; REPLICATION; SEQUENCE AB Genetic studies in Borrelia burgdorferi have been hindered by the lack of a nonborrelial selectable marker. Currently, the only selectable marker is gyrB(r), a mutated form of the chromosomal gyrB gene that encodes the B subunit of DNA gyrase and confers resistance to the antibiotic coumermycin A(1). The utility of the coumermycin-resistant gyrB(r) gene for targeted gene disruption is limited by a high frequency of recombination with the endogenous gyrB gene. A kanamycin resistance gene (kan) was introduced into B, burgdorferi, and its use as a selectable marker was explored in an effort to improve the genetic manipulation of this pathogen. B. burgdorferi transformants with the kan gene expressed from its native promoter were susceptible to kanamycin, In striking contrast, transformants with the kan gene expressed from either the B. burgdorferi flaB or flgB promoter mere resistant to high levels of kanamycin. The kanamycin resistance marker allows efficient direct selection of mutants in B. burgdorferi and hence is a significant improvement in the ability to construct isogenic mutant strains in this pathogen. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Bono, JL (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 36 TC 147 Z9 152 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2000 VL 182 IS 9 BP 2445 EP 2452 DI 10.1128/JB.182.9.2445-2452.2000 PG 8 WC Microbiology SC Microbiology GA 304RZ UT WOS:000086499100013 PM 10762244 ER EF