FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Reddy, DS Rogawski, MA AF Reddy, DS Rogawski, MA TI Chronic treatment with the neuroactive steroid ganaxolone in the rat induces anticonvulsant tolerance to diazepam but not to itself SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID AMINOBUTYRIC ACID(A) RECEPTOR; MAMMALIAN CORTICAL-NEURONS; DIFFERENT SEIZURE MODELS; GABA-A RECEPTOR; BENZODIAZEPINE RECEPTOR; WITHDRAWAL CHARACTERISTICS; ALLOSTERIC INTERACTIONS; ALPHA-4 SUBUNIT; MICE; NEUROSTEROIDS AB Ganaxolone (3 alpha -hydroxy-3 beta -methyl-5 alpha -pregnane-20-one), an orally active synthetic analog of the neuroactive steroid allopregnanolone, is a positive allosteric modulator of gamma -aminobutyric acid(A) receptors with anticonvulsant properties. We sought to determine whether tolerance occurs to the anticonvulsant activity of ganaxolone in the pentylenetetrazol seizure test and whether there is cross-tolerance with diazepam. Rats were treated with two daily injections of a 2 x ED50 dose of ganaxolone (7 mg/kg s.c.), diazepam (4 mg/kg i.p.), or vehicle for 3 or 7 days. On the day after the chronic treatment periods, the anticonvulsant potencies of ganaxolone and diazepam were determined. The ED50 values for ganaxolone after 3- and 7-day treatment with ganaxolone were not significantly different from that in naive rats (ED50 = 3.5 mg/kg). In contrast, in animals that were treated chronically with ganaxolone for 7 days, there was a significant reduction in the anticonvulsant potency of diazepam (ED50 = 4.0 versus 1.9 mg/kg for naive controls). Chronic treatment with diazepam was not associated with a reduction in the potency of ganaxolone, but there was a reduction in the potency of diazepam (ED50 = 3.7 mg/kg). Plasma ganaxolone determinations indicated that the pharmacokinetic properties of ganaxolone were unchanged after 7-day chronic ganaxolone treatment. The estimated equilibrium plasma concentrations of ganaxolone associated with threshold (750-950 ng/ml) and 50% seizure protection (1215-1295 ng/ml) were similar in naive and chronically treated rats. We conclude that there is no tolerance to the anticonvulsant activity of ganaxolone nor is there cross-tolerance to ganaxolone when tolerance develops to diazepam. However, there is cross-tolerance to diazepam with chronic ganaxolone treatment. C1 NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, 10 Ctr Dr,Room 5N-250 MSC 1408, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009; OI Rogawski, Michael/0000-0002-3296-8193; Reddy, Samba/0000-0003-2735-9550 NR 61 TC 88 Z9 91 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2000 VL 295 IS 3 BP 1241 EP 1248 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 374HD UT WOS:000165339000045 PM 11082461 ER PT J AU Ibrahim, S Peggins, J Knapton, A Licht, T Aszalos, A AF Ibrahim, S Peggins, J Knapton, A Licht, T Aszalos, A TI Influence of antipsychotic, antiemetic, and Ca2+ channel blocker drugs on the cellular accumulation of the anticancer drug daunorubicin: P-glycoprotein modulation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BLOOD-BRAIN-BARRIER; MULTIDRUG-RESISTANCE; EXPRESSION; PHARMACOKINETICS; PLASMA; CELLS; LINE; DOXORUBICIN; MONOLAYERS; INHIBITION AB We investigated the effect of antiemetic, antipsychotic, and Ca2+ blocker drugs on the function of P-glycoprotein (Pgp) in vitro and compared inhibitory concentrations with therapeutic blood levels. Human colon adenocarcinoma (Caco-2) and human blood-brain barrier endothelial cells were transfected or transduced to express Pgp, and the uptake of rhodamine123, calcein AM, or daunorubicin was measured by flow cytometry in the presence of the drugs. NIH3T3/MDR1 cells were used for reference testing. Results of the flow cytometric studies were supported by cell proliferation and monolayer permeability studies. Thirty-five drugs are included in this study, of which 13 modulate the function of Pgp at the therapeutic blood concentration and 8 at a concentration 2 to 4 times higher. Two drugs, which block the function of Pgp only partially at therapeutic blood concentrations, blocked the function of Pgp completely if used concomitantly. Based on these in vitro experiments, we conclude that administration of several drugs that modulate the function of Pgp simultaneously may adversely affect the natural function of this efflux pump and may cause drug-induced side effects in patients. C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. US FDA, Ctr Vet Med, Laurel, MD USA. US FDA, Div Appl Pharmacol Res, Laurel, MD USA. NCI, NIH, Bethesda, MD 20892 USA. RP Ibrahim, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, HFD-860,5600 Fishers Ln, Rockville, MD 20857 USA. NR 52 TC 25 Z9 25 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2000 VL 295 IS 3 BP 1276 EP 1283 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 374HD UT WOS:000165339000049 PM 11082465 ER PT J AU Cohen, LG AF Cohen, LG TI A window into the role of inhibitory and excitatory mechanisms of perception? SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. NR 5 TC 2 Z9 2 U1 3 U2 6 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 DEC 1 PY 2000 VL 529 IS 2 BP 283 EP 283 DI 10.1111/j.1469-7793.2000.00283.x PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 386YE UT WOS:000166092600001 PM 11101639 ER PT J AU Chung, V Horowitz, AM Canto, MT Siriphant, P AF Chung, V Horowitz, AM Canto, MT Siriphant, P TI Oral cancer educational materials for the general public: 1998 SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE oral cancer; educational materials; public ID UNITED-STATES; PREVENTION AB Objectives: Previous studies have shown that US adults are not well informed about oral cancers and only 15 percent ever have had an oral cancer examination. This study sought to determine the quantity and adequacy of educational materials designed to inform or educate US adults about risks for, and signs and symptoms of, oral cancer and the need for an oral cancer examination. Methods: Letters requesting copies of oral cancer educational materials produced by the organization or agency-leaflets, fact sheets, pamphlets, videos, posters--were sent to 172 national and state organizations or agencies. To determine the adequacy of the items, a previously developed, tested, and used form based on current science was adapted for this study. In addition, the SMOG index was used to determine readability for printed items. Results: Seventy-seven percent or 132 of the selected organizations responded to queries. A total of 59 it ems were received that focused on or included the topic of oral cancer. Twenty of these 59 items focused specifically on oral cancer; the balance, on other topics, but mentioned oral cancer. The readability ranged from sixth to 13th grade. Conclusions: This study demonstrates a dearth of educational materials about oral and pharyngeal cancers; most are written at too high a grade level for the general public. These findings may help to explain why the public is so uninformed about these neoplasms. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Coll Dent Med, Charleston, SC 29425 USA. Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. RP Horowitz, AM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. NR 20 TC 27 Z9 28 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 2000 VL 60 IS 1 BP 49 EP 52 DI 10.1111/j.1752-7325.2000.tb03292.x PG 4 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 295DT UT WOS:000085952000010 PM 10734617 ER PT J AU Chi-Fishman, G Sonies, BC AF Chi-Fishman, G Sonies, BC TI Motor strategy in rapid sequential swallowing: New insights SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE sequential swallowing; continuous drinking; deglutition; physiology; videofluoroscopy; surface electromyography ID COORDINATION; ACTIVATION AB This study examined the physiological properties and movement strategies of normal, rapid sequential swallowing during simultaneous videofluoroscopy (VFS) and submental surface electromyography (EMG). Ten subjects performed discrete (5 and 15 cc) and sequential (150 cc in tilted and upright head postures) swallowing tasks. Analyses included VFS event timing, movement/bolus passage characteristics, EMG amplitude waveforms, and peak and offset EMG amplitudes. Results revealed that sequential swallows were significantly shorter than discrete swallows in several VFS event durations, but significantly longer in pharynaeal transit and stage transition times. The hyolaryngeal system exhibited a cyclical "rise and partial fall" movement pattern during sequential swallows on VFS, corresponding to a repetitive "activation and partial deactivation" characteristic on EMG. Greater peak EMG amplitude for sequential than discrete swallows was found in 6/10 subjects. Pharyngeal bolus merging, preparatory laryngeal gestures, and penetration without aspiration were also observed in some subjects on VFS. Intersubject differences were significant in timing measures and EMG amplitude. Our Findings of individual variability and subject-specific strategies for task accommodation support the notion of built-in plasticity in the deglutitive motor complex. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Chi-Fishman, G (reprint author), NIH, Ctr Clin, Room 6S235,Bldg 10,SLP-RMD,900 Rockville Pike, Bethesda, MD 20892 USA. NR 28 TC 36 Z9 38 U1 0 U2 3 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD DEC PY 2000 VL 43 IS 6 BP 1481 EP 1492 PG 12 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 386MW UT WOS:000166067000014 PM 11193967 ER PT J AU Miyaguchi, K AF Miyaguchi, K TI Ultrastructure of the zonula adherens revealed by rapid-freeze deep-etching SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE cadherin; rapid-freeze deep-etching; retinal pigment epithelium; zonula adherens ID CELL-ADHESION MOLECULES; E-CADHERIN; VISUALIZATION; PROTEIN; DOMAIN AB The zonula adherens (ZA) in adult chicken retinal pigment epithelium was examined with cryo-electron microscopic methods. Deep-etching of the cross-fractured ZA showed globules in the intercellular space. These globules apparently correspond to the electron-dense structure seen in thin sections. Deep-etching of obliquely fractured ZA further revealed rod-like structures extending from the extracellular surface into the intercellular space. These rods (mean similar to9 nm thick, similar to 20 nm long) were straight and sometimes divided into two or three segments. The rods typically canted at similar to 60 degrees with respect to the plasma membrane, and they were often connected to the intercellular globules at their distal ends. When the rods are compared with the isolated cadherins reported previously, it is suggested that a combination of a rod and a globule may represent an extracellular part of cadherin. Membrane particles were observed on the P-face of the ZA plasma membrane, and their distribution density was approximately seven times that of the rods. The freeze-etching also revealed a characteristic particle complex on the ZA cytoplasmic surface, which may represent the cytosolic proteins linking cadherins to actin bundles, (C) 2000 Academic Press. C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Miyaguchi, K (reprint author), Osaka Univ, Grad Sch Med, Dept Neurol D4, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. NR 24 TC 42 Z9 42 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD DEC PY 2000 VL 132 IS 3 BP 169 EP 178 DI 10.1006/jsbi.2000.4244 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 410JQ UT WOS:000167437200001 PM 11243886 ER PT J AU Liu, XC Sun, ZX Uchiyama, M Li, Y Okawa, M AF Liu, XC Sun, ZX Uchiyama, M Li, Y Okawa, M TI Attaining nocturnal urinary control, nocturnal enuresis, and behavioral problems in Chinese children aged 6 through 16 years SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE nocturnal urinary control; anuresis; behavioral problems ID EMOTIONAL-PROBLEMS; AMERICAN-CHILDREN; TEACHER REPORTS; FOLLOW-UP; EPIDEMIOLOGY; ADOLESCENCE; PREVALENCE; CHILDHOOD AB Objective: To estimate the prevalence of nocturnal enuresis and to examine associations between nocturnal urinary control or enuresis and behavioral problems in Chinese children. Method: A community sample of 3,600 children aged 6 through 16 years was drawn from Shandong Province of China in 1997; 3,344 (93%) returned completed questionnaires. The Child Behavior Checklist and Teacher's Report Form were used to measure children's behavioral problems. Results: The proportion of children attaining nocturnal urinary control before age 2 was 7.7%; by age 3, this had increased to 53.1%, and by age 5 to 93%. The overall prevalence of nocturnal enuresis was 4.3%, with a significantly higher prevalence in boys than girls. There was no significant decrease in the prevalence of enuresis between 6 and 16 years of age. Multiple logistic regression analyses showed that attaining nocturnal urinary control after age 4 and current enuresis were significantly associated with an increased risk of behavioral, emotional, and academic problems. Conclusions: Chinese children attain nocturnal urinary control earlier than Western children. The prevalence of nocturnal enuresis is low but fairly stable in children between 6 and 16 years. The findings support the link between nocturnal enuresis and psychopathology in children and adolescents. C1 Shandong Med Univ, Dept Psychiat, Shandong, Peoples R China. NIMH, NCNP, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Med, Tokyo, Japan. RP Liu, XC (reprint author), NIEHS, Epidemiol Branch, Mail Drop A3-05,POB 12233,111 TW Alexander Dr,Roo, Res Triangle Pk, NC 27709 USA. NR 35 TC 44 Z9 48 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2000 VL 39 IS 12 BP 1557 EP 1564 DI 10.1097/00004583-200012000-00020 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 378GA UT WOS:000165575600018 PM 11128334 ER PT J AU Mohiddin, SA Begley, D Shih, J Fananapazir, L AF Mohiddin, SA Begley, D Shih, J Fananapazir, L TI Myocardial bridging does not predict sudden death in children with hypertrophic cardiomyopathy but is associated with more severe cardiac disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID DESCENDING CORONARY-ARTERY; BLOOD-FLOW VELOCITY; VASODILATOR RESERVE; ISCHEMIA; EXERCISE; ABNORMALITIES; OBSTRUCTION; ARREST AB OBJECTIVES We sought to examine the association between systolic compression of sections of epicardial coronary vessels (myocardial bridging) with myocardial perfusion abnormalities and clinical outcome in children with hypertrophic cardiomyopathy (HCM). BACKGROUND It has recently been suggested that myocardial bridging is an important cause of myocardial ischemia and sudden death in children with HCM. METHODS Angiograms from 57 children with HCM were reviewed for the presence of bridging (50% or more maximum systolic arterial compression). QT interval indices, echocardiographic and cardiac catheterization findings, treadmill exercise tests, exercise thallium scintigraphy, Holter monitoring and electrophysiologic study findings were compared in children with and without bridging. The findings were also related to the presence or absence of compression of septal branches of the left anterior descending artery (LAD). RESULTS Bridging was present in 23 (40%) of the children. Multiple coronary arteries were involved in four children. Bridging involved the LAD in 16 of 28 (57%) affected vessels. Myocardial perfusion abnormalities were present in 14 of 30 (47%) children without bridging and in 17 of 22 (94%) children with bridging, p = 0.002. However, bridging was associated with more severe septal hypertrophy (19 +/- 8 mm vs. 28 +/- 8 mm, p < 0.001), a higher septum:posterior wall thickness ratio (2.7 +/- 1.2 vs. 1.8 +/- 0.9, p < 0.001), and higher left ventricle (LV) outflow gradient (45 +/- 37 mm Hg vs. 16 +/- 28 mm Mg, p = 0.002). Compression of septal LAD branches was present in 37 (65%) of the children and was significantly associated with bridging, severity of LV hypertrophy and outflow obstruction. Multivariate analysis demonstrated that LV septal thickness and septal branch compression, and not bridging, were independent predictors of thallium perfusion abnormalities. There was a 90% power at 5% significance to detect an effect of bridging on thallium abnormalities at an odds ratio of 3. CONCLUSIONS Bridging was also not associated with significantly greater symptoms, increased QT and QTc intervals and QTc dispersion, ventricular tachycardia on Holter or induced at EP study, or a worse prognosis. Bridging and compression of septal branches of the LAD are common in HCM children and are related to magnitude of LV hypertrophy. Left ventricular hypertrophy and compression of intramyocardial branches of the epicardial coronary arteries may contribute to myocardial perfusion abnormalities. Our findings suggest that bridging does not result in myocardial ischemia and may not cause arrhythmias or sudden death in HCM children. (C) 2000 by the American College of Cardiology. C1 NHLBI, Cardiol Branch, Electrophysiol & Inherited Heart Dis Sect, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Fananapazir, L (reprint author), NHLBI, Cardiol Branch, Electrophysiol & Inherited Heart Dis Sect, Bldg 10,Room 7B-15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. NR 41 TC 54 Z9 60 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 2000 VL 36 IS 7 BP 2270 EP 2278 DI 10.1016/S0735-1097(00)00987-6 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 378TM UT WOS:000165600400038 PM 11127472 ER PT J AU Evans, CA Kleinman, DV AF Evans, CA Kleinman, DV TI The surgeon general's report on America's oral health: Opportunities for the dental profession SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB Background and Overview. The release this year of "Oral Health in America: A Report of the Surgeon General"-the first such report on this topic in U.S. history-gives national visibility to the scope and breadth of oral health and disease in America. The report emphasizes oral health's inextricable link to general health and well-being. Although the country has seen major improvements in oral health, some population groups have yet to benefit from these improvements. To address health disparities and improve quality of life for all Americans, the surgeon general's report calls for the development of a National Oral Health Plan. Conclusions. "Oral Health in America" identifies opportunities for the dental profession on behalf of the nation's overall health. The profession is uniquely positioned to ensure that all components of the National Oral Health Plan are addressed: changing perceptions to ensure that oral health is seen as integral to general health; removing barriers to care; enhancing health infrastructure; accelerating the transfer of science into practice; and continuing to participate in private/public partnerships. Clinical Implications. The report's findings highlight the importance of assessing patients' known risks of experiencing oral diseases and of educating patients about health-promoting behaviors. The integral role of oral health in general health, as described in the report, makes it imperative for health professionals to ensure appropriate referrals to practitioners in all areas of health care. C1 Los Angeles Cty Dept Hlth Serv, Los Angeles, CA 90012 USA. US Publ Hlth Serv, Bethesda, MD USA. Natl Inst Dental & Craniofacial Res, Bethesda, MD 20892 USA. RP Evans, CA (reprint author), Los Angeles Cty Dept Hlth Serv, Los Angeles, CA 90012 USA. NR 7 TC 50 Z9 50 U1 1 U2 7 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD DEC PY 2000 VL 131 IS 12 BP 1721 EP 1728 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 381KQ UT WOS:000165762300018 PM 11143736 ER PT J AU Van Duyn, MS Pivonka, E AF Van Duyn, MS Pivonka, E TI Overview of the health benefits of fruit and vegetable consumption for the dietetics professional: Selected literature SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID CORONARY HEART-DISEASE; SYMPTOMATIC DIVERTICULAR-DISEASE; DIETARY FIBER; CARDIOVASCULAR-DISEASE; RISK; MEN; PREVENTION; POPULATION; MORTALITY; ZUTPHEN AB Epidemiologic evidence of a protective role for fruits and vegetables in cancer prevention is substantial. The strength of this scientific base guides US national policymaking in diet and health issues and facilitates community and local programs that. address national dietary goals to increase fruit and vegetable consumption. Current scientific evidence also suggests a protective role for fruits and vegetables in prevention of coronary heart disease, and evidence is accumulating for a protective role in stroke. In addition, a new scientific base is emerging to support a protective role for fruits and vegetables in prevention of cataract formation, chronic obstructive pulmonary disease, diverticulosis, and possibly, hypertension. This article provides an overview of the health benefits associated with fruit and vegetable consumption for each of these conditions, including brief discussions of underlying protective mechanisms, identifies key scientific findings regarding the health benefits of fruit and vegetable consumption, and outlines applications of these findings for dietetics professionals. The evidence reviewed provides additional support for increased consumption of a wide variety of vegetables, in particular, dark-green leafy, cruciferous, and deep-yellow-orange ones, and a wide variety of fruits, in particular, citrus and deep-yellow-orange ones. Continued attention to increasing fruit and vegetable consumption is a practical and important way to optimize nutrition to reduce disease risk and maximize good health. C1 Produce Better Hlth Fdn, Wilmington, DE 19808 USA. NCI, Off Commun, Bethesda, MD 20892 USA. RP Pivonka, E (reprint author), Produce Better Hlth Fdn, 5301 Limestone Rd, Wilmington, DE 19808 USA. NR 51 TC 323 Z9 337 U1 9 U2 73 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD DEC PY 2000 VL 100 IS 12 BP 1511 EP 1521 DI 10.1016/S0002-8223(00)00420-X PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460MQ UT WOS:000170311700018 PM 11138444 ER PT J AU Leveille, SG Gray, S LaCroix, AZ Ferrucci, L Black, DJ Guralnik, JM AF Leveille, SG Gray, S LaCroix, AZ Ferrucci, L Black, DJ Guralnik, JM TI Physical inactivity and smoking increase risk for serious infections in older women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE infections; smoking; exercise; aged; women; hospitalization; cancer; lung disease ID DISEASE HOSPITALIZATIONS; UNITED-STATES; PNEUMONIA; HEALTH; EXERCISE; ADULTS; IMMUNOSENESCENCE; WALKING AB OBJECTIVE: This study examined health and behavioral risk factors for infections that required hospitalization in postmenopausal women who were enrollees of a large health maintenance organization (HMO). METHODS: Participants were 1365 generally healthy women aged 55 to 80 years who were followed for up to 6 years. Infection diagnoses listed first in the automated hospital discharge records were used to identify hospitalizations for which infections were the primary cause of admission. Potential risk factors for these serious infections were identified from baseline questionnaire information and automated HMO records from before baseline and during follow-up. Risks for infections associated with hospital admission were examined using multivariate logistic regression methods. RESULTS: Seventy-three women had a total of 90 hospital admissions in which infection was the primary discharge diagnosis. Behaviors that were independent predictors of infection were physical inactivity (adj, odds ratio = 4.08; 95% CI, 1.73-9.63) and smoking (adj. odds ratio = 2.64; 95% CI, 1.11-6.26). Incident cancer and lung disease were also associated with increased risk of infection. These associations were independent of age, body mass index, functional status, and other measures of health. CONCLUSIONS: Modifiable risk factors such as physical inactivity and smoking may place older women at risk for serious infections although the causal link is yet to be explained. Further research in this area may lead to new strategies aimed at reducing the serious burden of infections in the older population. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Natl Res Inst, Dept Geriatr, Florence, Italy. RP Leveille, SG (reprint author), Hebrew Rehabil Ctr Aged, Res & Training Inst, 1200 Ctr St, Boston, MA 02131 USA. FU NIA NIH HHS [K08AG00808-01] NR 35 TC 12 Z9 12 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2000 VL 48 IS 12 BP 1582 EP 1588 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 409EH UT WOS:000167371200006 PM 11129746 ER PT J AU Ferrucci, L Bandinelli, S Benvenuti, E Di Iorio, A Macchi, C Harris, TB Guralnik, JM AF Ferrucci, L Bandinelli, S Benvenuti, E Di Iorio, A Macchi, C Harris, TB Guralnik, JM CA InCHIANTI Grp TI Subsystems contributing to the decline in ability to walk: Bridging the gap between epidemiology and geriatric practice in the InCHIANTI study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE disability; Physical performance; walking; mobility; prevention; InCHIANTI; aging ID DISABLED OLDER WOMEN; LOWER-EXTREMITY FUNCTION; PHYSICAL-ACTIVITY; SUBSEQUENT DISABILITY; MAINTAINING MOBILITY; MUSCULAR STRENGTH; LEG EXTENSION; LOWER-LIMBS; GAIT SPEED; LATE-LIFE AB BACKGROUND: Older patients are often referred to geriatricians because of complaints of progressive difficulties in walking. The diagnostic and therapeutic approach to these patients is complex. Multiple physiologic subsystems may influence the ability to walk, and no standard criteria are currently available to establish whether these subsystems are functioning within the normal range. To address this lack of knowledge we conducted the InCHIANTI study. OBJECTIVE: To identify measures that clinicians can use to understand the causes of walking difficulties in older persons. DESIGN: A population-based study of persons living in the Chianti geographic area (Tuscany, Italy). PARTICIPANTS: 1453 persons (age-range 20-102 years; 91.6% of the eligible) selected from city registry of Greve in Chianti and Bagno a Ripoli (Tuscany, Italy), using a multistage sampling method. MEASUREMENTS: Factors that influence walking ability were classified into six main physiologic subsystems: central nervous system, perceptual system, peripheral nervous system, muscles, bone/joints, and energy production/delivery. Measures of the integrity and functioning of each of these proposed subsystems were identified and administered to all participants. CONCLUSIONS: Data collected in InCHIANTI will be used to identify the main risk factors that influence loss of the ability to walk in older persons, to define physiologic subsystems that are critical for walking, to select the brst measures of their integrity, and to establish critical ranges in these measures that are compatible with "normal" walking ability. The final goal is to translate epidemiological research into a geriatric clinical tool that makes possible more precise diagnosis and more effective treatment in patients with walking dysfunction. C1 INRA, Dept Geriatr, Lab Clin Epidemiol, I-50127 Florence, Italy. Univ G DAnnunzio, Dept Med & Imaging, Chieti, Italy. Fdn Don Gnocchi, Florence, Italy. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), INRA, Dept Geriatr, Lab Clin Epidemiol, Viale Michelangiolo 41, I-50127 Florence, Italy. FU NIMHD NIH HHS [263_MD_821336, 263_MD_9164_13] NR 77 TC 431 Z9 434 U1 2 U2 9 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2000 VL 48 IS 12 BP 1618 EP 1625 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 409EH UT WOS:000167371200012 PM 11129752 ER PT J AU Arend, LJ Smart, AM Briggs, JP AF Arend, LJ Smart, AM Briggs, JP TI Mouse beta(6) integrin sequence, pattern of expression, and role in kidney development SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CELL ATTACHMENT; SUBUNIT; FIBRONECTIN; DIFFERENTIATION; CLONING; MATRIX; ACTIN; CDNA AB Integrins mediate cell-cell and cell-extracellular matrix interactions and play key roles in development. beta (6) integrin expression has been demonstrated in human fetal kidney at a higher level than in the adult, making beta (6) integrin a marker of interest for the study of development of the nephron. The aims of this study were to determine the cDNA sequence for the mouse beta (6) integrin and to characterize beta (6) integrin expression in the developing mouse kidney. Two embryonic mouse kidney cDNA libraries were screened, and the coding region was sequenced. The mouse beta (6) nucleotide coding region sequence shows 82% nucleotide identity to the human sequence. The putative amino acid sequence has 89.5% identity to human beta (6) integrin and contains many conserved domains. By reverse transcription-PCR, beta (6) integrin mRNA expression is very low at 11 d of gestation in the mouse, increases dramatically by E14 and E17 (20-fold, normalized for increases in beta actin), and plateaus by 2 wk of age. beta (6) integrin expression is induced 15- to 20-fold after 5 d in metanephric explant culture. Reverse transcription-PCR of adult rat microdissected nephron segments demonstrates beta (6) integrin mRNA expression in proximal tubule, cortical thick ascending limb, distal nephron segments (inner and outer medullary collecting ducts), and macula densa-containing segments. Lectin-peroxidase and in situ colocalization studies demonstrated expression of beta (6) integrin mRNA in developing proximal tubules and thick ascending limb. Culture of mouse metanephric kidneys with antisense oligonucleotides to beta (6) integrin resulted in inhibition of ureteric bud branching and complete lack of mesenchyme condensation. These studies demonstrate a high homology between the human and mouse beta (6) integrin sequence, a different pattern of expression in the developing mouse kidney compared with the primate kidney, and abnormal metanephric development in culture in the absence of beta (6) integrin. These findings suggest an important role for beta (6) integrin in normal development of the mouse kidney. C1 Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Arend, LJ (reprint author), Univ Rochester, Med Ctr, Dept Pathol & Lab Med, 601 Elmwood Ave,Box 626, Rochester, NY 14642 USA. RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU NIDDK NIH HHS [K08-DK02515, NRSA-DK09325, R01-DK40042] NR 21 TC 11 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2000 VL 11 IS 12 BP 2297 EP 2305 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 378QT UT WOS:000165595600013 PM 11095652 ER PT J AU Dunson, DB Zhou, HB AF Dunson, DB Zhou, HB TI A Bayesian model for fecundability and sterility SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE demography; fertility; mixture model; probit model; reproductive epidemiology; time to pregnancy ID PROXIMATE DETERMINANTS; CIGARETTE-SMOKING; LONGITUDINAL DATA; MARKOV-CHAINS; FERTILITY; PREGNANCY; CONCEPTION; OVULATION; PROBABILITY; SURVIVAL AB There is increasing evidence that exposure to environmental toxins during key stages of development can disrupt the human reproductive system. Such effects have proven difficult to study due to the many behavioral and biological factors involved in human reproduction. We analyze data from a North Carolina fertility study to assess the effect of prenatal, childhood, and current cigarette smoking exposure on fecundability and sterility. We use a mixture model that adjusts for timing and frequency of intercourse and allows both fecundability and sterility to depend on multiple covariates. We account for dependency among menstrual cycles within individual couples using a mixture density for a latent cycle viability variable. The mixture consists of a normal distribution describing heterogeneity among fecund couples with a point mass at 0 for sterile couples. The resulting distribution is more biologically plausible than the standard beta density. A Markov chain Monte Carlo scheme is used for Bayesian estimation of the model. There is some evidence that spontaneous intrauterine mortality results in decreased fecundability in subsequent cycles. Both current cigarette smoking and prenatal exposure of the woman to her mother's cigarette smoking are shown to be associated with a decrease in the probability of menstrual cycle viability. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 42 TC 30 Z9 31 U1 1 U2 3 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2000 VL 95 IS 452 BP 1054 EP 1062 DI 10.2307/2669742 PG 9 WC Statistics & Probability SC Mathematics GA 376RJ UT WOS:000165470300004 ER PT J AU Follmann, DA AF Follmann, DA TI On the effect of treatment among would-be treatment compliers: An analysis of the Multiple Risk Factor Intervention Trial SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE clinical trial; compliance; mixture model; propensity score; pseudolikelihood ID CLINICAL-TRIALS; SMOKING CESSATION AB The Multiple Risk Factor Intervention Trial (MRFIT) was a major trial that examined the efficacy of a multifactor intervention on reducing coronary heart disease mortality. After a mean follow-up of 7 years, treatment was not significantly different from control, and extensive investigation was undertaken to explain the result. This article examines how the effect of treatment varies with compliance with treatment. The basic idea is that the binary characteristic "would comply with treatment" is balanced between groups by randomization, even though it is unobservable before randomization and only observed after randomization in the treatment group. Using baseline covariates, a prediction model for this observed characteristic is developed in the treatment group, and estimated probabilities of treatment compliance are calculated for all patients in both groups. The assumption that patients who would nut comply with treatment must have the same mean response in both groups is avoided. Two methods for examining how the effect of treatment depends on treatment compliance are described. Under the first approach, the predicted probabilities of treatment compliance are used to specify a treatment by covariate interaction. Under the second approach, a regression model is specified where the covariate "would comply with treatment" has an interaction with treatment. This produces a standard regression model in the treatment group and a mixture model with mixing over the unobserved binary covariate in the control group. The two methods are applied to MRFIT and the results compared. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Follmann, DA (reprint author), NHLBI, Off Biostat Res, Bldg 10, Bethesda, MD 20892 USA. NR 22 TC 29 Z9 29 U1 0 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2000 VL 95 IS 452 BP 1101 EP 1109 DI 10.2307/2669746 PG 9 WC Statistics & Probability SC Mathematics GA 376RJ UT WOS:000165470300008 ER PT J AU Nandram, B Sedransk, J Pickle, LW AF Nandram, B Sedransk, J Pickle, LW TI Bayesian analysis and mapping of mortality rates for chronic obstructive pulmonary disease SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE diagnostics for nonlinear Bayes models; disease mapping; hierarchical models; mortality modelling; Poisson distribution ID STATISTICS; VARIABILITY; REGRESSION; ASTHMA; MODELS AB This article summarizes our research on estimation of age-specific and age-adjusted mortality rates for chronic obstructive pulmonary disease (COPD) fur white males. Our objectives are more precise and informative displays (than previously available) of geographic variation of the age-specific mortality rates for COPD, and investigation of the relationships between the geographic variation in mortality rates and the corresponding variation in selected covariates. For a given age class, our estimates are displayed in a choropleth map of mean rates. We develop a variation map that identifies the geographical areas where inferences are reliable. Hers, the variation is measured by considering a set of maps produced using samples from the posterior distribution of the population mortality rates. Finally, we describe the spatial patterns in the age-specific maps and relate these to patterns in potential explanatory covariates such as smoking rate, annual rainfall, population density, elevation, and measures of air quality. C1 Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Case Western Reserve Univ, Dept Stat, Cleveland, OH 44106 USA. NCI, Div Canc Control & populat Sci, Bethesda, MD 20892 USA. RP Nandram, B (reprint author), Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. NR 35 TC 5 Z9 5 U1 2 U2 5 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2000 VL 95 IS 452 BP 1110 EP 1118 PG 9 WC Statistics & Probability SC Mathematics GA 376RJ UT WOS:000165470300009 ER PT J AU Liu, WH Medina, MA Thomann, W Piver, WT Jacobs, TL AF Liu, WH Medina, MA Thomann, W Piver, WT Jacobs, TL TI Optimization of intermittent pumping schedules for aquifer remediation using a genetic algorithm SO JOURNAL OF THE AMERICAN WATER RESOURCES ASSOCIATION LA English DT Article DE genetic algorithm; optimal pumping schedules; stochastic ground water; contaminant transport models ID COUPLED INVERSE PROBLEMS; GROUNDWATER REMEDIATION; PARAMETER-IDENTIFICATION; MANAGEMENT; UNCERTAINTY; TRANSPORT; DESIGN; SOLVE; FLOW AB Using a genetic algorithm (GA), optimal intermittent pumping schedules were established to simulate pump-and-treat remediation of a contaminated aquifer with known hydraulic limitations and a water miscible contaminant, located within the Duke Forest in Durham, North Carolina. The objectives of the optimization model were to minimize total costs, minimize health risks,and maximize the amount of contaminant removed from the aquifer. Stochastic ground water and contaminant transport models were required to provide estimates of contaminant concentrations at pumping wells. Optimization model simulations defined a tradeoff curve between the pumping cost and the amount of contaminant extracted from the aquifer. For this specific aquifer/miscible contaminant combination, the model simulations indicated that pump-and-treat remediation using intermittent pumping schedules for each pumping well produced significant reductions in predicted contaminant concentrations and associated health risks at a reasonable cost, after a remediation time of two years. C1 Geophex Ltd, Raleigh, NC 27603 USA. Duke Univ, Dept Civil & Environm Engn, Durham, NC 27708 USA. Med Ctr, Durham, NC 27710 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Sabre Inc, Southlake, TX 76092 USA. RP Liu, WH (reprint author), Geophex Ltd, 605 Mercury St, Raleigh, NC 27603 USA. NR 45 TC 13 Z9 13 U1 0 U2 1 PU AMER WATER RESOURCES ASSOC PI MIDDLEBURG PA 4 WEST FEDERAL ST, PO BOX 1626, MIDDLEBURG, VA 20118-1626 USA SN 1093-474X J9 J AM WATER RESOUR AS JI J. Am. Water Resour. Assoc. PD DEC PY 2000 VL 36 IS 6 BP 1335 EP 1348 DI 10.1111/j.1752-1688.2000.tb05730.x PG 14 WC Engineering, Environmental; Geosciences, Multidisciplinary; Water Resources SC Engineering; Geology; Water Resources GA 391LP UT WOS:000166357700010 ER PT J AU Moolchan, ET Berlin, I Robinson, ML Cadet, JL AF Moolchan, ET Berlin, I Robinson, ML Cadet, JL TI African-American teen smokers: Issues to consider for cessation treatment SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE adolescents; smoking cessation; ethnicity ID TOLERANCE QUESTIONNAIRE; SMOKING; BLACK; DEPENDENCE; COTININE AB Previous reports have indicated ethnic differences in both tobacco-related morbidity and treatment outcome for smoking cessation among adults. We assessed smoking-related characteristics in African-American and non-African American teenagers applying to a cessation trial. 115 teens (15.9 +/- 1.8 years, 68% females, 27% African-American) responded via telephone to media ads. Self-reported sociodemographic, medical and smoking-related data were obtained to determine pre-eligibility for a full intake screen prior to trial participation. Compared to non-African American, African American teen applicants were older (16.4 +/- 1.7 years versus 15.6 +/- 1.6, p = 0.015), had lower Fagerstrom Test for Nicotine Dependence (FTND) scores 15.3 -+/- 2.3 versus 6.1 +/- 1.8; p = 0.018, ANOVA controlling for age) and smoked fewer cigarettes on the weekend (27 +/- 16 versus 38 +/- 17, p = 0.001). African American teens reported similar duration of smoking (3.3 +/- 1.4 versus 3.1 +/- 1.5 years) and time elapsed between first cigarette ever smoked and daily smoking (0.7 +/- 0.9 versus 0.6 +/- 0.7 years). African American and non-African American teens had similar motivation to quit scores and frequency of reported health problems (e.g., asthma, psychiatric conditions). These data suggest that cessation treatment programs designed for African American youth should include lower Fagerstrom-defined levels, and possibly other criteria for tobacco dependence. These observations also highlight the importance of ethnocultural issues in treatment research programs. C1 NIH,NIDA, Intramural Res Program, Clin Pharmacol Therapeut Res Branch, Teen Tobacco Addict Treatment Res Clin, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), NIH,NIDA, Intramural Res Program, Clin Pharmacol Therapeut Res Branch, Teen Tobacco Addict Treatment Res Clin, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 28 TC 23 Z9 23 U1 2 U2 2 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD DEC PY 2000 VL 92 IS 12 BP 558 EP 562 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 444CJ UT WOS:000169380100015 PM 11202758 ER PT J AU McDermott, MM Criqui, MH Liu, K Guralnik, JM Greenland, P Martin, GJ Pearce, W AF McDermott, MM Criqui, MH Liu, K Guralnik, JM Greenland, P Martin, GJ Pearce, W TI Lower ankle/brachial index, as calculated by averaging the dorsalis pedis and posterior tibial arterial pressures, and association with leg functioning in peripheral arterial disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ANKLE-BRACHIAL INDEX; 6-MINUTE WALK; ARM INDEX; MORTALITY; PREDICTOR; WOMEN AB Objective: We compared three commonly used methods of ankle/brachial index (ABI) calculation to determine their relative association with objective measures of leg functioning in peripheral arterial disease. Method: The study design was cross-sectional; the setting was an academic medical center. The participants were 244 men and women, aged 55 years and older, with and without peripheral arterial disease, from a noninvasive vascular laboratory and a general medicine practice. The main outcome measures were walking velocity and endurance, measured with the 4-m walk and the 6-minute walk, respectively. Three methods of ABI calculation were assessed: using the highest arterial pressure within each leg (method #1), using the lowest pressure in each leg (method #2), and averaging the dorsalis pedis and posterior tibial pressures within each leg (method #3). for each method, we established the prevalence of peripheral arterial disease. We then used regression analyses to identify the ABI calculation method most closely associated with leg functioning. The ABI with the greatest statistical significance and largest regression coefficient was considered most closely associated with leg functioning. Results: Peripheral arterial disease prevalence ranged from 47% when method #1 was used to 59% when method #2 was used. When the right and left legs were compared, the leg with the lower ABI, as identified through use of method #3, was most associated with leg functioning. Within the leg with the lower ABI, method #3 was more closely associated with 6-minute walk distance (regression coefficient = 811.5 feet per 1 unit ABI; P < .001) and 4-m walking velocity (regression coefficient = 0.353 m/s per 1 unit ABI; P < .001) than method #1 or method #2. Conclusion: The lower ABI, determined by averaging the dorsalis pedis and posterior tibial arterial pressures in each leg, is most predictive of walking endurance and walking velocity in. peripheral arterial disease. C1 Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Div Vasc Surg, Dept Surg, Chicago, IL 60611 USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP McDermott, MM (reprint author), Northwestern Univ, Sch Med, Dept Med, 375 N St Clair,Suite 18-200, Chicago, IL 60611 USA. FU NCRR NIH HHS [RR 00048] NR 18 TC 159 Z9 164 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 2000 VL 32 IS 6 BP 1164 EP 1171 DI 10.1067/mva.2000.108640 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 382VE UT WOS:000165847400024 PM 11107089 ER PT J AU Imamichi, T Berg, SC Imamichi, H Lopez, JC Metcalf, JA Falloon, J Lane, HC AF Imamichi, T Berg, SC Imamichi, H Lopez, JC Metcalf, JA Falloon, J Lane, HC TI Relative replication fitness of a high-level 3 '-azido-3 '-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr -> Gly) at codon 69 SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; DYNAMICS IN-VIVO; COMBINATION THERAPY; DRUG-RESISTANCE; ANTIRETROVIRAL THERAPY; ZIDOVUDINE TREATMENT; NUCLEOSIDE ANALOGS; POL GENE; MUTATIONS; SENSITIVITY AB The combination of an amino acid deletion at codon 67 (Delta 67) and Thr-to-Gly change at codon 69 (T69G) in the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is associated with high-level resistance to multiple RT inhibitors. To determine the relative contributions of the Delta 67 and T69G mutations on viral fitness, we performed a series of studies of HIV replication using recombinant variants. A high-level 3 ' -azido-3 ' -deoxythymidine (AZT)-resistant variant containing Delta 67 plus T69G/K70R/L741/KI03N/T215F/ K219Q in RT replicated as efficiently as wild-type virus (Wt). In contrast, the construct without Delta 67 exhibited impaired replication (23% of growth of Wt). A competitive fitness study failed to reveal any differences in replication rates between the Delta 67+T69G/K70R/L741/KI03N/T215F/K219Q mutant and Wt. Evaluation of proviral DNA sequences over a 3-year period in a patient harboring the multiresistant HIV revealed that the T69G mutation emerged in the context of a D67NiK70R/T215F/K219Q mutant backbone prior to appearance of the Delta 67 deletion. To assess the impact of this stepwise accumulation of mutations on viral replication, a series of recombinant variants was constructed and analyzed for replication competence. The T69G mutation was found to confer 2 ' ,3 ' -dideoxyinosine resistance at the expense of fitness. Subsequently, the development of the Delta 67 deletion led to a virus with improved replication and high-level AZT resistance. C1 NCI, Frederick Canc Res & Dev Ctr, SAIF Frederick, Lab Mol Retrovirol,Clin Serv Program, Frederick, MD 21702 USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. Hosp Gen Gregorio Maranon, E-28007 Madrid, Spain. RP Imamichi, T (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIF Frederick, Lab Mol Retrovirol,Clin Serv Program, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 45 TC 60 Z9 61 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2000 VL 74 IS 23 BP 10958 EP 10964 DI 10.1128/JVI.74.23.10958-10964.2000 PG 7 WC Virology SC Virology GA 461LM UT WOS:000170365800011 PM 11069990 ER PT J AU Bukreyev, A Murphy, BR Collins, PL AF Bukreyev, A Murphy, BR Collins, PL TI Respiratory syncytial virus can tolerate an intergenic sequence of at least 160 nucleotides with little effect on transcription or replication in vitro and in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; ALTERED GROWTH-CHARACTERISTICS; STRAND RNA VIRUS; GENE JUNCTIONS; MESSENGER-RNA; FOREIGN GENE; L-PROTEIN; STABLE EXPRESSION; ELONGATION-FACTOR; COTTON RATS AB The intergenic sequences (IGS) between the first nine genes of human respiratory syncytial virus (RSV) vary in length from 1 to 56 nucleotides and lack apparent conserved sequence motifs. To investigate their influence on sequential transcription and viral growth, recombinant RSV strain A2, from which the SH gene had been deleted to facilitate manipulation, was further modified to contain an M-G IGS of 16, 30, 44, 58, 65, 72, 86, 100, 120, 140, or 160 nucleotides. All of the viruses were viable. For viruses with an M-G IGS of 100 nucleotides or more, plaque size decreased with increasing IGS length. In this same length range, increasing IGS length was associated with modest attenuation during single-step, but not multistep, growth in HEp-2 cells. Surprisingly, Northern blot analysis of the accumulation of six different mRNAs indicated that there was little or no change in transcription with increasing IGS length. Thus, the RSV polymerase apparently can readily cross IGS of various lengths, including unnaturally long ones, with little or no effect on the efficiency of termination and reinitiation. This finding supports the view that the IGS do not have much effect on sequential transcription and provides evidence from infectious virus that IGS length is not an important regulatory feature. To evaluate replication in vivo, BALB/c mice were infected intranasally with RSV containing an M-G IGS of 65, 140, or 160 nucleotides. Replication of the latter two viruses was decreased up to 5- and 25-fold in the upper and lower respiratory tracts, respectively, on day 3 following infection. However, the level of replication at both sites on days 4 and 5 was very similar to that of the virus with an IGS of 65 nucleotides. Thus, the modest attenuation in vivo associated with the longer IGS was additive to that conferred by deletion of the SH gene and might be useful to incrementally increase the level of attenuation of a live-attenuated vaccine virus. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 7,Room 100,7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. NR 39 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2000 VL 74 IS 23 BP 11017 EP 11026 DI 10.1128/JVI.74.23.11017-11026.2000 PG 10 WC Virology SC Virology GA 461LM UT WOS:000170365800018 PM 11069997 ER PT J AU Greengard, O Poltoratskaia, N Leikina, E Zimmerberg, J Moscona, A AF Greengard, O Poltoratskaia, N Leikina, E Zimmerberg, J Moscona, A TI The anti-influenza virus ahent 4-GU-DANA (Zanamivir) inhibits cell fusion mediated by human parainfluenza virus and influenza virus HA SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; MEMBRANE-FUSION; HEMAGGLUTININ-NEURAMINIDASE; SIALIC-ACID; IN-VITRO; TYPE-3; RECEPTOR; ASSAY; SENSITIVITY; HEMIFUSION AB 4-GU-DANA (zanamivir) (as well as DANA and 4-AM-DANA) was found to inhibit the neuraminidase activity of human parainfluenza virus type 3 (HPF3). The viral neuraminidase activity is attributable to hemagglutinin-neuraminidase (HN), an envelope protein essential for viral attachment and for fusion mediated by the other envelope protein, F. While there is no evidence that HN's neuraminidase activity is essential for receptor binding and syncytium formation, we found that 4-GU-DANA prevented hemadsorption and fusion of persistently infected cells with uninfected cells. In plaque assays, 4-GU-DANA reduced the number (but not the area) of plaques if present only during the adsorption period and reduced plaque area (but not number) if added only after the 90-min adsorption period. 4-GU-DANA also reduced the area of plaques formed by a neuraminidase-deficient variant, confirming that its interference with cell-cell fusion is unrelated to inhibition of neuraminidase activity. The order-of-magnitude lower 50% inhibitory concentrations of 4-GU-DANA (and also DANA and 4-AM-DANA) for plaque area reduction and for inhibition in the fusion assay than for reducing plaque number or blocking hemadsorption indicate the particular efficacy of these sialic acid analogs in interfering with cell-cell fusion. In cell lines expressing influenza virus hemagglutinin (RA) as the only viral protein, we found that 4-GU-DANA had no effect on hemadsorption but did inhibit HA2b-red blood cell fusion, as judged by both lipid mixing and content mixing. Thus, 4-GU-DANA can interfere with both influenza virus- and HPF3-mediated fusion. The results indicate that (i) in HPF3, 4-GU-DANA and its analogs have an affinity not only for the neuraminidase active site of HN but also for sites important for receptor binding and cell fusion and (ii) sialic acid-based inhibitors of influenza virus neuraminidase can also exert a direct, negative effect on the fusogenic function of the other envelope protein, HA. C1 CUNY Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Moscona, A (reprint author), CUNY Mt Sinai Sch Med, Dept Pediat, 1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIAID NIH HHS [R01 AI031971, AI 31971, R56 AI031971] NR 34 TC 47 Z9 48 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2000 VL 74 IS 23 BP 11108 EP 11114 DI 10.1128/JVI.74.23.11108-11114.2000 PG 7 WC Virology SC Virology GA 461LM UT WOS:000170365800027 PM 11070006 ER PT J AU Shuh, M Derse, D AF Shuh, M Derse, D TI Ternary complex factors and cofactors are essential for human T-cell leukemia virus type 1 tax transactivation of the serum response element SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; IMMEDIATE-EARLY GENES; HTLV-I TAX; ABERRANT INDUCTION; PROTEIN ELK-1; CARG BOXES; ACTIVATION; BINDING; DOMAIN; IKK AB The human T-cell leukemia virus type 1 Tax protein activates the expression of cellular immediate early genes controlled by the serum response element (SRE), which contains both the serum response factor (SRF) binding element (CArG box) and the ternary complex factor (TCF) binding element (Ets box). We show that TCF binding is necessary for Tax activation of the SRE and that Tax directly interacts with TCFs in vitro. In addition, Tax interactions with CREB binding protein (CBP) and p300- and CBP-associated factor were found to be essential for Tax activation of SRF-mediated transcription. C1 NCI, Basic Res Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Derse, D (reprint author), NCI, Basic Res Lab, Div Basic Sci, Frederick, MD 21702 USA. NR 26 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2000 VL 74 IS 23 BP 11394 EP 11397 DI 10.1128/JVI.74.23.11394-11397.2000 PG 4 WC Virology SC Virology GA 461LM UT WOS:000170365800061 PM 11070040 ER PT J AU Moore, SP Garfinkel, DJ AF Moore, SP Garfinkel, DJ TI Correct integration of model substrates by Ty1 integrase SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; YEAST RETROTRANSPOSON TY1; FULL-SITE INTEGRATION; IN-VITRO INTEGRATION; RETROVIRUS-LIKE DNA; CONCERTED INTEGRATION; VIRAL-DNA; SACCHAROMYCES-CEREVISIAE; NUCLEOCAPSID PROTEIN; CATALYTIC PROPERTIES AB The retrovirus-like mobile genetic element of Saccharomyces cerevisiae, Ty1, transposes to new genomic locations via the element-encoded integrase (IN). Here we report that purified recombinant IN catalyzed correct integration of a linear DNA into a supercoiled target plasmid. Ty1 virus-like particles (VLPs) integrated donor DNA more efficiently than IN. VLP and IN-mediated insertions occurred at random sites in the target. Mg2+ was preferred over Mn2+ for correct integration, and neither cation enhanced nonspecific nuclease activity of IN. Products consistent with correct integration events were also obtained by Southern analysis. Recombinant IN and VLPs utilized many, but not all, linear donor fragments containing non-Ty1 ends, including a U3 mutation which has been shown to be defective for transposition in vivo. Together, our results suggest that IN is sufficient for Ty1 integration in vitro and IN interacts with exogenous donors less stringently than with endogenous elements. C1 NCI, Frederick Canc Res & Dev Ctr, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA. RP Moore, SP (reprint author), NCI, Frederick Canc Res & Dev Ctr, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA. NR 39 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2000 VL 74 IS 24 BP 11522 EP 11530 DI 10.1128/JVI.74.24.11522-11530.2000 PG 9 WC Virology SC Virology GA 461LN UT WOS:000170365900012 PM 11090149 ER PT J AU Goldstein, S Ourmanov, I Brown, CR Beer, BE Elkins, WR Plishka, R Buckler-White, A Hirsch, VM AF Goldstein, S Ourmanov, I Brown, CR Beer, BE Elkins, WR Plishka, R Buckler-White, A Hirsch, VM TI Wide range of viral load in healthy African green monkeys naturally infected with simian immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS-MONKEYS; HIGHLY DIVERGENT; TANTALUS MONKEYS; IN-VIVO; SIV; MACAQUES; REPLICATION; DISEASE; DIVERSITY; SEQUENCE AB The distribution and levels of simian immunodeficiency virus (SIN) in tissues and plasma were assessed in naturally infected African green monkeys (AGM) of the vervet subspecies (Chlorocebus pygerythrus) by limiting-dilution coculture, quantitative PCR for viral DNA and RNA, and in situ hybridization for SIN expression in tissues. A wide range of SIV RNA levels in plasma was observed among these animals (< 1,000 to 800,000 copies per ml), and the levels appeared to be stable over long periods of time. The relative numbers of SIN-expressing cells in tissues of two monkeys correlated with the extent of plasma viremia. SIN expression was observed in lymphoid tissues and was not associated with immunopathology. Virus-expressing cells were observed in the lamina propria and lymphoid tissue of the gastrointestinal tract, as well as within alveolar macrophages in the lung tissue of one AGM. The range of plasma viremia in naturally infected AGM was greater than that reported in naturally infected sooty mangabeys. However, the degree of viremia in some AGM was similar to that observed during progression to AIDS in human immunodeficiency virus-infected individuals. Therefore, containment of viremia is an unlikely explanation for the lack of pathogenicity of SIVagm in its natural host species, AGM. C1 NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. NIAID, Infect Dis Lab, NIH, Rockville, MD 20852 USA. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, Twinbrook Facil,12441 Parklawn Dr, Rockville, MD 20852 USA. NR 48 TC 88 Z9 88 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2000 VL 74 IS 24 BP 11744 EP 11753 DI 10.1128/JVI.74.24.11744-11753.2000 PG 10 WC Virology SC Virology GA 461LN UT WOS:000170365900037 PM 11090174 ER PT J AU Gupta, K Ott, D Hope, TJ Siliciano, RF Boeke, JD AF Gupta, K Ott, D Hope, TJ Siliciano, RF Boeke, JD TI A human nuclear shuttling protein that interacts with human immunodeficiency virus type 1 matrix is packaged into virions SO JOURNAL OF VIROLOGY LA English DT Article ID EXPORT SIGNAL; HIV-1 MATRIX; NONDIVIDING CELLS; MACROPHAGE INFECTION; LOCALIZATION SIGNAL; CELLULAR PROTEINS; ENVELOPE PROTEIN; HUMAN HOMOLOG; GAG PROTEINS; IDENTIFICATION AB Active nuclear import of the human immunodeficiency virus type 1 (HIV-1) preintegration complex (PIG) is essential for the productive infection of nondividing cells. Nuclear import of the PIC is mediated by the HIV-1 matrix protein, which also plays several critical roles during viral entry and possibly during virion production facilitating the export of Pr55(Gag) and genomic RNA. Using a yeast two-hybrid screen, we identified a novel human virion-associated matrix-interacting protein (VAN) that is highly conserved in vertebrates and expressed in most human tissues. Its expression is upregulated upon activation of CD4(+) T cells. VAN is efficiently incorporated into HIV-1 virions and, like matrix, shuttles between the nucleus and cytoplasm. Furthermore, overexpression of VAN significantly inhibits HIV-1 replication in tissue culture. We propose that VAN regulates matrix nuclear localization and, by extension, both nuclear import of the PIC and export of Pr55(Gag) and viral genomic RNA during virion production. Our data suggest that this regulatory mechanism reflects a more global process for regulation of nucleocytoplasmic transport. C1 Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, Frederick, MD 21702 USA. Salk Inst Biol Studies, Infect Dis Lab, La Jolla, CA 92037 USA. RP Boeke, JD (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. FU NCI NIH HHS [N01CO56000]; NIAID NIH HHS [P01AI41215]; PHS HHS [A128108] NR 68 TC 45 Z9 47 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2000 VL 74 IS 24 BP 11811 EP 11824 DI 10.1128/JVI.74.24.11811-11824.2000 PG 14 WC Virology SC Virology GA 461LN UT WOS:000170365900044 PM 11090181 ER PT J AU Gorelick, RJ Benveniste, RE Lifson, JD Yovandich, JL Morton, WR Kuller, L Flynn, BM Fisher, BA Rossio, JL Piatak, M Bess, JW Henderson, LE Arthur, LO AF Gorelick, RJ Benveniste, RE Lifson, JD Yovandich, JL Morton, WR Kuller, L Flynn, BM Fisher, BA Rossio, JL Piatak, M Bess, JW Henderson, LE Arthur, LO TI Protection of Macaca nemestrina from disease following pathogenic simian immunodeficiency virus (SIV) challenge: Utilization of SIV nucleocapsid mutant DNA vaccines with and without an SIV protein boost SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; AFRICAN-GREEN MONKEYS; LONG-TERM PROTECTION; ZINC-FINGER MUTANTS; IMMUNE-RESPONSES; IN-VIVO; ATTENUATED SIV; MOLECULAR CHARACTERIZATION; ENVELOPE GLYCOPROTEIN; GENOMIC RNA AB Molecular clones were constructed that express nucleocapsid (NC) deletion mutant simian immunodeficiency viruses (SIVs) that are replication defective but capable of completing virtually all of the steps of a single viral infection cycle. These steps include production of particles that are viral RNA deficient yet contain a full complement of processed viral proteins. The mutant particles are ultrastructurally indistinguishable from wild-type virus. Similar to a live attenuated vaccine, this approach should allow immunological presentation of a full range of viral epitopes, without the safety risks of replicating virus. A total of 11 Macaca nemestrina macaques were inoculated with NC mutant SIV expressing DNA, intramuscularly (i.m.) in one study and i.m. and subcutaneously in another study. Six control animals received vector DNA lacking SIV sequences. Only modest and inconsistent humoral responses and no cellular immune responses were observed prior to challenge. Following intravenous challenge with 20 animal infectious doses of the pathogenic SIV(Mne) in a long-term study, all control animals became infected and three of four animals developed progressive SIV disease leading to death. All 11 NC mutant SIV DNA-immunized animals became infected following challenge but typically showed decreased initial peak plasma SIV RNA levels compared to those of control animals (P = 0.0007). In the long-term study, most of the immunized animals had low or undetectable postacute levels of plasma SIV RNA, and no CD4(+) T-cell depletion or clinical evidence of progressive disease, over more than 2 years of observation. Although a subset of immunized and control animals were boosted with SIV(Mne) proteins, no apparent protective benefit was observed. Immunization of macaques with DNA that codes for replication-defective but structurally complete virions appears to protect from or at least delay the onset of AIDS after infection with a pathogenic immunodeficiency virus. With further optimization, this may be a promising approach for vaccine development. C1 Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. Frederick Canc Res & Dev Ctr, Natl Canc Inst, Basic Res Lab, Frederick, MD 21702 USA. Univ Washington, Reg Primate Res Ctr, Seattle, WA 98195 USA. NCI, Anim Sci Branch, Bethesda, MD 20892 USA. RP Arthur, LO (reprint author), Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. RI Bess, Jr., Julian/B-5343-2012 FU NCI NIH HHS [N01CO56000]; NCRR NIH HHS [P51 RR000166]; NIAID NIH HHS [N01AI65302] NR 66 TC 29 Z9 34 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2000 VL 74 IS 24 BP 11935 EP 11949 DI 10.1128/JVI.74.24.11935-11949.2000 PG 15 WC Virology SC Virology GA 461LN UT WOS:000170365900057 PM 11090194 ER PT J AU Taaffe, DR Harris, TB Ferrucci, L Rowe, J Seeman, TE AF Taaffe, DR Harris, TB Ferrucci, L Rowe, J Seeman, TE TI Cross-sectional and prospective relationships of interleukin-6 and C-reactive protein with physical performance in elderly persons: MacArthur Studies of Successful Aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID ACUTE-PHASE PROTEINS; CARDIOVASCULAR-DISEASE; UNSTABLE ANGINA; OLDER PERSONS; PLASMA IL-6; CYTOKINES; RISK; INFLAMMATION; DISABILITY; OSTEOARTHRITIS AB Background. Chronic inflammation has been proposed as a biological mechanism underlying the decline in physical function that occurs with aging. The purpose of this investigation was to examine the cross-sectional and prospective relationships between markers of inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), with several measures of physical performance in older persons aged 70 to 79 years. Methods. Subjects were 880 high-functioning men and women participating in the MacArthur Study of Successful Aging (n = 1189), a subset of the Established Populations for Epidemiologic Studies of the Elderly (n = 4030). Plasma IL-6 and CRP levels were determined by enzyme linked immunosorbent assay and log transformed to normalize the distributions. Physical function measures included handgrip strength, signature time, chair stands (time to complete five repetitions), and 6-m walk time. Results. Women had lower (p <.05) IL-6 levels than men, but there was no significant difference between blacks and whites. IL-6 and CRP levels were higher (p <.05) in current smokers than in nonsmokers and in those with a greater body mass index (BMI). Hours per year undertaking moderate and strenuous physical activity were also related to inflammatory markers with higher (p <.001) IL-6 and CRP levels in less active individuals. After adjusting for age, sex, race, BMI, smoking status, use of nonsteroidal anti-inflammatory drugs, and prevalence of morbidity, those in the top two quartiles for walking speed had lower (p =.012) IL-6 levels than those in the bottom quartile. In addition, there was a trend (p =.038) for lower CRP levels in those with higher walking speed. CRP levels were also lower (p =.04) in individuals in the top quartile for grip strength. No significant differences were noted for chair stands or signature time performance. Repeat performance measures obtained on 405 subjects (67% of those eligible at baseline) obtained 7 years later had declined significantly (grip strength, 18%; signature time, 21%; walking speed, 31%; p <.001), except for the chair rise: however. baseline IL-6 and CRP were not associated with a change in performance. However, those who died or who were unable to undergo testing had higher baseline IL-6 and CRP levels (p <.01) and slower walking speed (p <.05). Conclusions. Although IL-6 has been shown to predict onset of disability in older persons and both IL-6 and CRP are associated with mortality risk, these markers of inflammation have only limited associations with physical performance, except for walking measures and grip strength at baseline, and do not predict change in performance 7 years later in a high-functioning subset of older adults. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. I Fraticini Natl Res Inst, Dept Geriatr, Florence, Italy. Mt Sinai Med Ctr, New York, NY 10029 USA. Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA USA. RP Taaffe, DR (reprint author), NIA, Epidemiol Demog & Biometry Program, Gateway Bldg,Room 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. NR 40 TC 214 Z9 218 U1 3 U2 17 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2000 VL 55 IS 12 BP M709 EP M715 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 390MH UT WOS:000166299600008 PM 11129392 ER PT J AU Lamb, ME Orbach, Y Sternberg, KJ Hershkowitz, I Horowitz, D AF Lamb, ME Orbach, Y Sternberg, KJ Hershkowitz, I Horowitz, D TI Accuracy of investigators' verbatim notes of their forensic interviews with alleged child abuse victims SO LAW AND HUMAN BEHAVIOR LA English DT Article ID EYEWITNESS MEMORY; SEXUAL-ABUSE; WITNESSES; QUESTION; SUGGESTIBILITY; COMPREHENSION; TESTIMONY; RESPONSES; RECALL AB Verbatim contemporaneous accounts of 20 investigative interviews were compared with audiotaped recordings thereof. More than half (57%) of the interviewers' utterance along with 25% of the incident-relevant details provided by the children were not reported in the "verbatim notes. The structure of the interviews was also represented inaccurately in these accounts. Fewer than half (44%) of the details provided by the children were attributed to the correct eliciting utterance type. Investigators systematically misattributed to the correct eliciting utterance type. Investigators systematically misattributed details to more open rather than more focused prompts. These results underscore the superiority of electronic recording when the content and structure of investigative interviews must be preserved. C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD 20892 USA. Univ Haifa, Sch Social Work, IL-31999 Haifa, Israel. Israeli Dept Labor & Social Affairs, Jerusalem, Israel. RP Lamb, ME (reprint author), NICHHD, Sect Social & Emot Dev, BSA Bldg,Room 331,9190 Rockville Pike, Bethesda, MD 20892 USA. EM Michael_Lamb@nih.gov NR 36 TC 38 Z9 38 U1 0 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-7307 J9 LAW HUMAN BEHAV JI Law Hum. Behav. PD DEC PY 2000 VL 24 IS 6 BP 699 EP 708 DI 10.1023/A:1005556404636 PG 10 WC Law; Psychology, Social SC Government & Law; Psychology GA 373XX UT WOS:000165316300006 PM 11105480 ER PT J AU Ginsberg, AM AF Ginsberg, AM TI Leprosy research-setting priorities and facilitating collaborations: a personal perspective SO LEPROSY REVIEW LA English DT Article; Proceedings Paper CT Workshop on Leprosy Research at the New Millennium CY JUN 26-28, 2000 CL PARIS, FRANCE SP Int Federat Anti Leprosy, Assoc Francaise Raoul Follereau, British Leprosy Relief Assoc, Sasakawa Mem Hlth Fdn ID PATHOGENESIS; GENOMICS AB In recent years, as the prevalence of leprosy has declined and the tuberculosis epidemic has gained increasing attention, leprosy research has generally taken a 'back seat' to research in tuberculosis and other emerging and re-emerging infections. This has resulted as much from perceived differences of scientific opportunities in these fields as from differences of the disease burden. At the United States National Institutes of Health (NIH), research priority setting is typically based on a number of factors. In the case of leprosy research, the technical difficulties associated with this scientific area have clearly lessened enthusiasm for and progress in this field. Today, however, we are confronted by the reality of not having sufficient scientific understanding to explain a stable or increasing number of leprosy cases detected annually in the face of a dramatically decreasing total number of identified cases. We also lack adequate tools for diagnosis and prevention. At the same time, new molecular and cellular approaches and knowledge of the complete sequence of the genome of Mycobacterium leprae render leprosy research significantly more tractable than ever before. The combination of these factors has led a number of groups, including the National Institute of Allergy and Infectious Diseases of the NIH, to review the current state of knowledge in leprosy research and draft recommendations for future leprosy research priorities. It is clear that many of the necessary and exciting research activities can best be addressed through collaborations among investigators, with control programmes, and among countries of high and low endemicity. C1 NIAID, DMID, RDB, NIH, Bethesda, MD 20892 USA. RP Ginsberg, AM (reprint author), NIAID, DMID, RDB, NIH, 6700-B Rockledge Dr,Room 3131, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU LEPRA PI COLCHESTER PA FAIRFAX HOUSE, CAUSTON ROAD, COLCHESTER CO1 1PU, ENGLAND SN 0305-7518 J9 LEPROSY REV JI Lepr. Rev. PD DEC PY 2000 VL 71 SU S BP S183 EP S187 PG 5 WC Dermatology; Infectious Diseases; Pathology; Tropical Medicine SC Dermatology; Infectious Diseases; Pathology; Tropical Medicine GA 401ZB UT WOS:000166958500059 PM 11201879 ER PT J AU van Brakel, WH Ji, BH Ginsberg, AM Brennan, PJ Lockwood, DNJ AF van Brakel, WH Ji, BH Ginsberg, AM Brennan, PJ Lockwood, DNJ TI Leprosy research-setting priorities and facilitating collaborations: a personal perspective - Discussion SO LEPROSY REVIEW LA English DT Editorial Material C1 TLM India, CNI Bhavan, New Delhi 110001, India. Fac Med Pitie Salpetriere, F-75634 Paris 13, France. NIAID, DMID, RDB, Bethesda, MD 20892 USA. Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA. Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, Clin Res Unit, London WC1E 7HT, England. RP van Brakel, WH (reprint author), TLM India, CNI Bhavan, 16 Pandit Pant Marg, New Delhi 110001, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LEPRA PI COLCHESTER PA FAIRFAX HOUSE, CAUSTON ROAD, COLCHESTER CO1 1PU, ENGLAND SN 0305-7518 J9 LEPROSY REV JI Lepr. Rev. PD DEC PY 2000 VL 71 SU S BP S187 EP S187 PG 1 WC Dermatology; Infectious Diseases; Pathology; Tropical Medicine SC Dermatology; Infectious Diseases; Pathology; Tropical Medicine GA 401ZB UT WOS:000166958500060 ER PT J AU Blagosklonny, MV AF Blagosklonny, MV TI The dilemma of apoptosis in myelodysplasia and leukemia: a new promise of therapeutic intervention? SO LEUKEMIA LA English DT Editorial Material ID LIVER C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Blagosklonny, MV (reprint author), NCI, Med Branch, NIH, Bldg 10,Room 12 N 226, Bethesda, MD 20892 USA. NR 14 TC 5 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 2000 VL 14 IS 12 BP 2017 EP 2018 DI 10.1038/sj.leu.2401979 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 388WX UT WOS:000166207000001 PM 11187888 ER PT J AU Handa, A Kashimura, T Yamamoto, A Murohashi, I Bessho, M Hirashima, K AF Handa, A Kashimura, T Yamamoto, A Murohashi, I Bessho, M Hirashima, K TI Granulocyte-colony stimulating factor induced intranuclear endonuclease in murine leukemia cell line SO LEUKEMIA RESEARCH LA English DT Article DE G-CSF; apoptosis; endonuclease; myeloid leukemia cells; c-myc; H-ras; p53; bcl-2; caspase3 ID MYC-INDUCED APOPTOSIS; SIZE DNA FRAGMENTATION; MYELOID-LEUKEMIA; C-MYC; DEATH; P53; BCL-2; SUSCEPTIBILITY; IDENTIFICATION; HEMATOPOIESIS AB We have reported that murine leukemia cell line (C2M-A5) induced apoptosis by G-CSF. To clarify the mechanism, mRNA expression of apoptosis-related genes was studied. It revealed transient over-expression of c-myc, H-ras and p53 and down-expression of bcl-2 These changes were known as triggers of endonuclease induction. After 96 h culture with G-CSF, apoptosis was occurred simultaneously with endonuclease (37 kd) activation. This endonuclease induced the digestion of double-strand DNA and might be associated with caspase3. Although G-CSF accelerates cell growth and prevents apoptosis in general, it is a contradictory effect. We concluded that G-CSF induced endogenous endonuclease activity in C2M-A5. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Saitama Med Sch, Dept Internal Med, Div Hematol & Infect Dis, Moroyama, Saitama 3500451, Japan. RP Handa, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7C 218,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 3 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD DEC PY 2000 VL 24 IS 12 BP 1033 EP 1039 DI 10.1016/S0145-2126(00)00074-6 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 374XW UT WOS:000165371000007 PM 11077117 ER PT J AU Baker, EJ Ichiki, AT Hodge, JW Sugantharaj, D Bamberger, EG Lozzio, CB AF Baker, EJ Ichiki, AT Hodge, JW Sugantharaj, D Bamberger, EG Lozzio, CB TI PMA-treated K-562 leukemia cells mediate a TH2-specific expansion of CD4+T cells in vitro SO LEUKEMIA RESEARCH LA English DT Article DE human CD4 cells; phorbol 12-myristate 13-acetate; K-562; Th1; Th2 ID T-CELLS; PHILADELPHIA CHROMOSOME; MYELOID-LEUKEMIA; CO-STIMULATION; EXPRESSION; ACTIVATION; LINE; DIFFERENTIATION; INTERLEUKIN-1; PROLIFERATION AB Highly enriched preparations of human CD3 + CD4 + T-lymphocytes were stimulated with mitogen or OKT3 to determine the capacity of K-562 cells to function as accessory cells. Phorbol 12-myristate 13-acetate (PMA)-treated K-562 cells were induced to differentiate along the megakaryocytic lineage and could supplant monocyte-accessory cell function. Intracytoplasmic analysis of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) established that IL-4, and not IFN-gamma, was preferentially produced by the activated lymphocytes. This polarized stimulation is compatible with a type 2 or humoral immune response of purified T cells co-cultured with differentiated K-562 cells in vitro, and may have implications in immunoregulation due to disease progression. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Tennessee, Med Ctr, Grad Sch Med, Dept Med Biol, Knoxville, TN 37920 USA. NCI, NIH, Bethesda, MD USA. RP Ichiki, AT (reprint author), Univ Tennessee, Med Ctr, Grad Sch Med, Dept Med Biol, 1924 Alcoa Highway, Knoxville, TN 37920 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 43 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD DEC PY 2000 VL 24 IS 12 BP 1049 EP 1057 DI 10.1016/S0145-2126(00)00082-5 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 374XW UT WOS:000165371000009 PM 11077119 ER PT J AU Lambert, G Sinal, CJ AF Lambert, G Sinal, CJ TI Nuclear receptors LXR and FXR control cholesterol and bile acid metabolism SO M S-MEDECINE SCIENCES LA French DT News Item C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Lambert, G (reprint author), NHLBI, Mol Dis Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD DEC PY 2000 VL 16 IS 12 BP 1456 EP 1458 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 383LZ UT WOS:000165885300029 ER PT J AU Kellman, P Sorger, JM Epstein, FH McVeigh, ER AF Kellman, P Sorger, JM Epstein, FH McVeigh, ER TI Low latency temporal filter design for real-time MRI using UNFOLD SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE interventional MR; UNFOLD; rapid imaging; real-time imaging; cardiac imaging AB To improve real-time control of interventional procedures such as guidance of catheters, monitoring of ablation therapy, or control of dosage during drug delivery, the image acquisition and reconstruction must be high speed and have low latency (small time delay) in processing. A number of different methods have been demonstrated which increase the speed of MR acquisition by decreasing the number of sequential phase-encodes. A design and implementation of the UNFOLD method which achieves the desired low latency with a recursive temporal filter is presented. The recursive filter design is characterized for this application and compared with more commonly used moving average filters. Experimental results demonstrate low-latency UNFOLD for two applications: 1) high-speed, realtime imaging of the heart to be used in conjunction with cardiac interventional procedures; and 2) the injection of drugs into muscle tissue with contrast enhancement, i.e., monitoring needle insertion and injection of a drug with contrast enhancement properties. Proof-of-concept was demonstrated by injecting a contrast agent. In both applications the UNFOLD technique was used to double the frame rate. (C) 2000 Wiley-Liss, Inc. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,MSC-1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL004608-08] NR 7 TC 11 Z9 11 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2000 VL 44 IS 6 BP 933 EP 939 DI 10.1002/1522-2594(200012)44:6<933::AID-MRM15>3.0.CO;2-I PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 377XN UT WOS:000165551700015 PM 11108631 ER PT J AU Fleischmajer, R Kuroda, K Utani, A MacDonald, ED Perlish, JS Arikawa-Hirasawa, E Sekiguchi, K Sanzen, N Timpl, R Yamada, Y AF Fleischmajer, R Kuroda, K Utani, A MacDonald, ED Perlish, JS Arikawa-Hirasawa, E Sekiguchi, K Sanzen, N Timpl, R Yamada, Y TI Differential expression of laminin alpha chains during proliferative and differentiation stages in a model for skin morphogenesis SO MATRIX BIOLOGY LA English DT Article DE skin; morphogenesis; laminin alpha chains ID HUMAN EPIDERMAL-KERATINOCYTES; BASEMENT-MEMBRANES; A-CHAIN; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; MUSCLE DEVELOPMENT; EPITHELIAL-CELLS; ALPHA-2-BETA-1 INTEGRINS; TERMINAL DIFFERENTIATION AB The purpose of this study was to determine the mRNA and protein expression of laminin oc chains at various stages of in vitro skin morphogenesis, Fibroblasts in mono-cultures express low levels of the mRNA of laminin alpha1,alpha2, alpha3 and alpha4 chains. When co-cultured with keratinocytes for 28 days, they expressed the mRNA for all these chains. Keratinocytes in monolayer expressed the laminin alpha3 chain mRNA and very low levels of the mRNA of the alpha1 and alpha2 chains, although, when recombined with fibroblasts they also expressed laminin alpha 1and alpha2 mRNA, but not the laminin alpha4 mRNA. Immunocytochemistry of cells in co-culture showed that laminin alpha1, alpha3 and alpha5 chains were expressed in the epidermis, while the laminin alpha2, beta1, and gamma1 chains were noted in the dermis and at the epidermo-dermal interface. The laminin alpha 1chain was first expressed during the proliferative stage (14-21 days) and the laminin alpha2 and alpha5 chains appeared later, during the differentiation stage (28-42 days). The above results suggest that epithelial-mesenchymal interactions are involved in the expression of laminin alpha chain mRNA during in vitro skin morphogenesis. In addition, there is distinct temporal and spatial expression of these chains during proliferative and differentiation stages, possibly reflecting different functions. (C) Elsevier Science B.V./International Society of Matrix Biology. All rights reserved. C1 CUNY Mt Sinai Sch Med, Dept Dermatol, New York, NY 10029 USA. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. Osaka Med Ctr Maternal & Child Hlth, Res Inst, Osaka 5941101, Japan. Max Planck Inst Biochem, D-82152 Martinsried, Germany. RP Fleischmajer, R (reprint author), CUNY Mt Sinai Sch Med, Dept Dermatol, Box 1047, New York, NY 10029 USA. EM rf@doc.mssm.edu FU NCRR NIH HHS [1 S10 RR0 9145-01] NR 69 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD DEC PY 2000 VL 19 IS 7 BP 637 EP 647 DI 10.1016/S0945-053X(00)00092-5 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 385YH UT WOS:000166032400009 PM 11102753 ER PT J AU Cesen-Cummings, K Walker, CL Davis, BJ AF Cesen-Cummings, K Walker, CL Davis, BJ TI Lessons from pregnancy and parturition: uterine leiomyomas result front discordant differentiation and dedifferentiation responses in smooth muscle cells SO MEDICAL HYPOTHESES LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR; RETINOID-X-RECEPTOR; MESSENGER-RIBONUCLEIC-ACID; SEX STEROID-RECEPTORS; MENSTRUAL-CYCLE; PROGESTERONE RECEPTORS; ESTROGEN-RECEPTOR; GENE-EXPRESSION; HORMONE AGONIST; PPAR-GAMMA AB Leiomyomas, benign smooth muscle tumors of the uterus, are the most common gynecological neoplasm in women. Studies with human tissues and primary cultures have revealed little about the development of leiomyomas, although several genes have been shown to be differentially expressed in leiomyomas compared to matched normal myometrium. We propose that uterine smooth muscle tumor cells mimic a differentiated myometrial cell of pregnancy, and are associated with a hypersensitivity to sex steroid hormones, preventing the cells from responding to normal apoptotic or dedifferentiation signals which would return the cells to a nongravid phenotype. Support of this hypothesis is derived from experimental studies in female Eker rats which develop uterine leiomyoma with many similarities to the human disease. Members of the steroid receptor superfamily as well as the binding partners and cc-regulators necessary for transactivation and gene transcription, may be involved in the altered pathway of cellular differentiation and regulation observed in uterine leiomyomas. (C) 2000 Harcourt Publishers Ltd. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Texas, MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX USA. RP Davis, BJ (reprint author), NIEHS, POB 12233,Mail Drop B3-06, Res Triangle Pk, NC 27709 USA. NR 68 TC 4 Z9 4 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD DEC PY 2000 VL 55 IS 6 BP 485 EP 490 DI 10.1054/mehy.2000.1098 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 381RL UT WOS:000165776900006 PM 11090295 ER PT J AU Peters, DC AF Peters, DC TI Fast contrast-enhanced imaging with projection reconstruction SO MEDICAL PHYSICS LA English DT Article C1 NIH, Bethesda, MD 20892 USA. RP Peters, DC (reprint author), NIH, 10 Ctr Dr,B1-D416, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2000 VL 27 IS 12 BP 2828 EP 2828 DI 10.1118/1.1328387 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 385KZ UT WOS:000166004600024 ER PT J AU Mudd, SH Jenden, DJ Capdevila, A Roch, M Levy, HL Wagner, C AF Mudd, SH Jenden, DJ Capdevila, A Roch, M Levy, HL Wagner, C TI Isolated hypermethioninemia: Measurements of S-adenosylmethionine and choline SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID METHIONINE ADENOSYLTRANSFERASE DEFICIENCY; PHOSPHATIDYLETHANOLAMINE N-METHYLTRANSFERASE; ISOLATED PERSISTENT HYPERMETHIONINEMIA; DOMINANT INHERITANCE; ARTERIOVENOUS DIFFERENCE; CEREBROSPINAL-FLUID; PLASMA CHOLINE; BRAIN CHOLINE; RAT; PATHWAY AB The concentrations of methionine and S-adenosylmethionine (AdoMet) in plasma and free choline and phospholipid-bound choline in both plasma and red blood cells from individuals with isolated hypermethioninemia have been measured. The only genetic abnormalities identified in these individuals have been inactivating mutations in MAT1A, the gene that encodes the subunit of the isozymes of methionine adenosyltransferase (MAT), MAT I, and MAT III, expressed only in adult liver. These measurements were performed to learn more about AdoMet metabolism and to test the working hypotheses that inadequate delivery of AdoMet, or of choline or a choline derivative, from liver to brain might be a cause of the neurologic disease often found in humans with the most severe tosses of MAT I/III activity. In striking contrast to the elevations of plasma AdoMet reported in control humans with hypermethioninemia resulting from methionine loading, plasma AdoMet levels were generally below the mean reference value in the MAT I/III-deficient hypermethioninemic patients. This is interpreted as a result of subnormal formation of AdoMet in river due to the deficient activity of MAT I/III and resultant lower-than-normal delivery of AdoMet from liver to plasma. A low plasma AdoMet concentration in the presence of an elevated methionine provides a useful diagnostic tool that pinpoints the cause of a case of hypermethioninemia as defective MAT I/III activity. Plasma-free choline concentrations were also generally somewhat below normal in the hypermethioninemic patients. However, neither plasma AdoMet nor plasma choline concentrations were strikingly lower in MAT I/III-deficient individuals with neurologic abnormalities than in those without. These results thus fail to provide support for the working hypotheses in question. Copyright (C) 2000 by W.B. Saunders Company. C1 NIMH, LMB, DIRP, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Dept Med & Mol Pharmacol, Los Angeles, CA USA. Vanderbilt Univ, Dept Biochem, Nashville, TN USA. Vanderbilt Univ, Clin Nutr Res Unit, Nashville, TN USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA. RP Mudd, SH (reprint author), NIMH, LMB, DIRP, Bldg 36,Room 1B-08,36 Convent Dr,MSC 4034, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK15289, DK54859] NR 63 TC 24 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2000 VL 49 IS 12 BP 1542 EP 1547 DI 10.1053/meta.2000.18521 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 381AQ UT WOS:000165740500006 PM 11145114 ER PT J AU Stoner, GL Jobes, DV Cobo, MF Agostini, HT Chima, SC Ryschkewisch, CF AF Stoner, GL Jobes, DV Cobo, MF Agostini, HT Chima, SC Ryschkewisch, CF TI JC virus as a marker of human migration to the Americas SO MICROBES AND INFECTION LA English DT Review DE JC virus; polyomavirus; Native Americans; African Americans; Hispanic Americans; phylogeny ID HUMAN POLYOMAVIRUS JC; COMPLETE GENOMES; NEW-WORLD; NATIVE-AMERICANS; MTDNA VARIATION; Y-CHROMOSOME; BK VIRUS; POPULATION; GENOTYPES; URINE AB JC virus is a ubiquitous human polyomavirus present in populations worldwide. Seven genotypes differing in DNA sequence by similar to1-3% characterize three Old World population groups (African, European and Asian) as well as Oceania. It is possible to follow Old World populations into the New World by the JC virus genotypes they carried. The first population to settle in the Americas, the Native Americans, brought with them type 2A from northeast Asia. European settlers arriving after Columbus carried primarily type 1 and type 4. Africans brought by the slave trade carried type 3 and type 6. (C) 2000 Editions scientifiques er medicales Elsevier SAS. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. ANLIS INEI, Dept Virus, Serv Biol Mol, RA-1281 Buenos Aires, DF, Argentina. Univ Freiburg, Dept Ophthalmol, D-79106 Freiburg, Germany. RP Stoner, GL (reprint author), NINDS, Neurotoxicol Sect, NIH, Bldg 36,Room 4A-27,MSC-4126,36 Convent Dr, Bethesda, MD 20892 USA. RI Chima, Sylvester Chidi/N-5564-2013 NR 45 TC 46 Z9 46 U1 0 U2 5 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD DEC PY 2000 VL 2 IS 15 BP 1905 EP 1911 DI 10.1016/S1286-4579(00)01339-3 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 397VY UT WOS:000166719500013 PM 11165934 ER PT J AU Bosetti, F Yu, GY Zucchi, R Ronca-Testoni, S Solaini, G AF Bosetti, F Yu, GY Zucchi, R Ronca-Testoni, S Solaini, G TI Myocardial ischemic preconditioning and mitochondrial F1F0-ATPase activity SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE ischemic preconditioning; myocardial ischemia; mitochondria; F1F0-ATPase; IF1 ID F1-ATPASE EPSILON-SUBUNIT; RETICULUM CA2+ CHANNELS; ADENOSINE-TRIPHOSPHATASE; ENERGY-METABOLISM; ATPASE INHIBITOR; CARDIAC-MUSCLE; RAT HEARTS; REPERFUSION; PROTEIN; BINDING AB A short period of ischemia followed by reperfusion (ischemic preconditioning) is known to trigger mechanisms that contribute to the prevention of ATP depletion. In ischemic conditions, most of the ATP hydrolysis can be attributed to mitochondrial F1F0-ATPase (ATP synthase). The purpose of the present study was to examine the effect of myocardial ischemic preconditioning on the kinetics of ATP hydrolysis by F1F0-ATPase. Preconditioning was accomplished by three 3-min periods of global ischemia separated by 3 min of reperfusion. Steady state ATP hydrolysis rates in both control and preconditioned mitochondria were not significantly different. This suggests that a large influence of the enzyme on the preconditioning mechanism may be excluded. However, the time required by the reaction to reach the steady state rate was increased in the preconditioned group before sustained ischemia, and it was even more enhanced in the first 5 min of reperfusion (101 +/- 3.0 sec in preconditioned vs. 83.4 +/- 4.4 sec in controls, p < 0.05). These results suggest that this transient increase in activation time may contribute to the cardioprotection by slowing the ATP depletion in the very critical early phase of post-ischemic reperfusion. C1 Scuola Super Sant Anna, Pisa, Italy. Univ Pisa, Sez Chim & Biochim Med, Dipartimento Sci Uomo & Ambiente, I-56100 Pisa, Italy. RP Bosetti, F (reprint author), NIA, Sect Brain Physiol & Metab, NIH Bldg 10,Room 6N202,9000 Rockville Pike, Bethesda, MD 20892 USA. OI ZUCCHI, RICCARDO/0000-0002-6450-3788; SOLAINI, GIANCARLO/0000-0001-7825-0446 NR 39 TC 26 Z9 28 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD DEC PY 2000 VL 215 IS 1-2 BP 31 EP 37 DI 10.1023/A:1026558922596 PG 7 WC Cell Biology SC Cell Biology GA 379KX UT WOS:000165642200004 PM 11204453 ER PT J AU Poizat, C Sartorelli, V Chung, G Kloner, RA Kedes, L AF Poizat, C Sartorelli, V Chung, G Kloner, RA Kedes, L TI Proteasome-mediated degradation of the coactivator p300 impairs cardiac transcription SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LARGE T-ANTIGEN; GENE-EXPRESSION; PROTEIN-DEGRADATION; ACTIVATION DOMAIN; PROGENITOR CELLS; FACTOR MYOD; MUSCLE; DIFFERENTIATION; DOXORUBICIN; CBP AB The transcription of tissue-specific genes is controlled by regulatory factors and cofactors and is suppressed in cardiac cells by the antineoplastic agent doxorubicin. Here we show that exposure of cultured cardiomyocytes to doxorubicin resulted in the rapid depletion of transcripts for MEF2C, dHAND, and NKX2.5, three pivotal regulators of cardiac gene expression. Delivery of exogenous p300, a coactivator of MEF2C and NKX2.5 in cardiomyocytes, restored cardiac transcription despite the presence of doxorubicin, Furthermore, p300 also restored the accumulation of transcripts for MEF2C itself, Importantly cardiocytes exposed to doxorubicin displayed reduced levels of p300 proteins. This was not due to alterations in the level of p300 transcripts; rather, and surprisingly, doxorubicin promoted selective degradation of p300 mediated by the 26S-proteasome machinery. Doxorubicin had no effect on the general level of ubiquitinated proteins or on the levels of beta -catenin, a protein known to be degraded by proteasome-mediated degradation. These results provide evidence for a new mechanism of transcriptional repression caused by doxorubicin in which the selective degradation of p300 results in reduced p300-dependent transcription, including production of MEF2C mRNA. C1 Univ So Calif, Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA USA. Good Samaritan Hosp, Inst Heart, Los Angeles, CA USA. Div Cardiol, Los Angeles, CA USA. NIAMSD, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kedes, L (reprint author), Univ So Calif, Sch Med, Inst Med Genet, 2250 Alcazar St, Los Angeles, CA 90033 USA. RI Kloner, Robert/B-2971-2012 NR 45 TC 82 Z9 84 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2000 VL 20 IS 23 BP 8643 EP 8654 DI 10.1128/MCB.20.23.8643-8654.2000 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 426UD UT WOS:000168366000002 PM 11073966 ER PT J AU Yoon, JH Love, DC Guhathakurta, A Hanover, JA Dhar, R AF Yoon, JH Love, DC Guhathakurta, A Hanover, JA Dhar, R TI Mex67p of Schizosaccharomyces pombe interacts with Rae1p in mediating mRNA export SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MESSENGER-RNA EXPORT; NUCLEAR-PORE COMPLEX; CONSTITUTIVE TRANSPORT ELEMENT; NUCLEOCYTOPLASMIC TRANSPORT; POLY(A)(+) RNA; FISSION YEAST; FUNCTIONALLY INTERACTS; HUMAN TAP; PROTEIN; BINDING AB We identified the Schizosaccharomyces pombe mex67 gene (spmex67) as a multicopy suppressor of rae1-167 nup184-1 synthetic lethality and the rae1-167 ts mutation, spMex67p, a 596-amino acid-long protein, has considerable sequence similarity to the Saccharomyces cerevisiae Mex67p (scMex67p) and human Tap. In contrast to seMEX67, spmex67 is essential for neither growth nor nuclear export of mRNA. However, an spmex67 null mutation (Delta mex67) is synthetically lethal with the rae1-167 mutation and accumulates poly(A)(+) RNA in the nucleus. We identified a central region (149 to 505 amino acids) within spMex67p that associates with a complex containing Rae1p that complements growth and mRNA export defects of the rae1-167 Delta mex67 synthetic lethality. This region is devoid of RNA-binding, N-terminal nuclear localization, and the C-terminal nuclear pore complex-targeting regions. The (149-505)-green fluorescent protein (GFP) fusion is found diffused throughout the cell. Overexpression of spMex67p inhibits growth and mRNA export and results in the redistribution of the diffused localization of the (149-505)-GFP fusion to the nucleus and the nuclear periphery. These results suggest that spMex67p competes for essential mRNA export factor(s). Finally we propose that the 149-505 region of spMex67p could act as an accessory factor in Rae1p-dependent transport and that spMex67p participates at various common steps with Rae1p export complexes in promoting the export of mRNA. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP NCI, Basic Res Lab, NIH, Bldg 41,Rm A222,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dharr@dce4l.nci.nih.gov NR 43 TC 50 Z9 51 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2000 VL 20 IS 23 BP 8767 EP 8782 DI 10.1128/MCB.20.23.8767-8782.2000 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 426UD UT WOS:000168366000014 PM 11073978 ER PT J AU Nie, ZQ Xue, WT Yang, DF Zhou, S Deroo, BJ Archer, TK Wang, WD AF Nie, ZQ Xue, WT Yang, DF Zhou, S Deroo, BJ Archer, TK Wang, WD TI A specificity and targeting subunit of a human SWI/SNF family-related chromatin-remodeling complex SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING PROTEINS; SWI-SNF COMPLEX; SACCHAROMYCES-CEREVISIAE; GLUCOCORTICOID RECEPTOR; TRANSCRIPTIONAL ACTIVATION; NUCLEAR RECEPTOR; DEAD RINGER; GLOBIN GENE; YEAST; DOMAIN AB The SWI/SNF family of chromatin-remodeling complexes facilitates gene activation by assisting transcription machinery to gain access to targets in chromatin. This family includes BAF (also called hSWI/SNF-A) and PBAF (hSWI/SNF-B) from humans and SWI/SNF and Rsc from Saccharomyces cerevisiae. However, the relationship between the human and yeast complexes is unclear because all human subunits published to date are similar to those of both yeast SWI/SNF and Rsc. Also, the two human complexes have many identical subunits, making it difficult to distinguish their structures or functions. Here we describe the cloning and characterization of BAF250, a subunit present in human BAF but not PBAF. BAF250 contains structural moths conserved in yeast SWI1 but not in any Rsc components, suggesting that BAF is related to SWI/SNF. BAF250 is also a homolog of the Drosophila melanogaster Osa protein, which has been shown to interact with a SWI/SNF-like complex in flies. BAF250 possesses at least two conserved domains that could be important for its function. First, it has an AT-rich DNA interaction-type DNA-binding domain, which can specifically bind a DNA sequence known to be recognized by a SWI/SNF family-related complex at the P-globin locus. Second, BAF250 stimulates glucocorticoid receptor-dependent transcriptional activation, and the stimulation is sharply reduced when the C-terminal region of BAF250 is deleted. This region of BAF250 is capable of interacting directly with the glucocorticoid receptor in vitro. Our data suggest that BAF250 confers specificity to the human BAF complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions. C1 NIA, Genet Lab, Baltimore, MD 21224 USA. Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Wang, WD (reprint author), NIA, Genet Lab, 333 Cassell Dr,TRIAD Ctr Room 4000, Baltimore, MD 21224 USA. NR 50 TC 181 Z9 188 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2000 VL 20 IS 23 BP 8879 EP 8888 DI 10.1128/MCB.20.23.8879-8888.2000 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 426UD UT WOS:000168366000024 PM 11073988 ER PT J AU Moriyama, H Edskes, HK Wickner, RB AF Moriyama, H Edskes, HK Wickner, RB TI [URE3] prion propagation in Saccharomyces cerevisiae: Requirement for chaperone Hsp104 and curing by overexpressed chaperone Ydj1p SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID YEAST SUP35 PROTEIN; IN-VITRO; PSI+ PRION; CYTOSOLIC HSP70; SHUTTLE VECTORS; SYSTEM; SCRAPIE; HSP40; GENE; DETERMINANT AB The [URE3] nonchromosomal genetic element is an infectious form (prion) of the Ure2 protein, apparently a self-propagating amyloidosis. We find that an insertion mutation or deletion of HSP104 results in inability to propagate the [URE3] prion. Our results indicate that Hsp104 is a common factor in the maintenance of two independent yeast prions. However, overproduction of Hsp104 does not affect the stability of [URE3], in contrast to what is found for the [PSI+] prion, which is known to be cured by either overproduction or deficiency of Hsp104. Like Hsp104, the Hsp40 class chaperone Ydj1p, with the Hsp70 class Ssa1p, can renature proteins. We find that overproduction of Ydj1p results in a gradual complete loss of [URE3]. The involvement of protein chaperones in the propagation of [URE3] indicates a role for protein conformation in inheritance. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr MSC0830, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov RI MORIYAMA, Hiromitsu/F-9256-2013 NR 60 TC 194 Z9 198 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2000 VL 20 IS 23 BP 8916 EP 8922 DI 10.1128/MCB.20.23.8916-8922.2000 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 426UD UT WOS:000168366000027 PM 11073991 ER PT J AU Hinnebusch, AG Dong, JS Garcia-Barrio, M Sattlegger, E Krishnamoorthy, T Qiu, HF Anderson, J AF Hinnebusch, AG Dong, JS Garcia-Barrio, M Sattlegger, E Krishnamoorthy, T Qiu, HF Anderson, J TI Translational control in by phosphorylation of initiation factor 2 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD, LEGR, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1 BP 1A EP 1A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900002 ER PT J AU Altan, N Roberts, TH Lippincott-Schwartz, J AF Altan, N Roberts, TH Lippincott-Schwartz, J TI Golgi fragmentation in prophase results from an alteration of constitutive membrane cycling pathways connecting the ER and Golgi complex. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Ward, Theresa/E-9650-2013 OI Ward, Theresa/0000-0002-9881-8649 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 9 BP 2A EP 2A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900010 ER PT J AU Wu, XFS Rao, K Copeland, NG Jenkins, NA Hammer, JA AF Wu, XFS Rao, K Copeland, NG Jenkins, NA Hammer, JA TI RAB27a and myosin Va cooperate to determine organeille distribution. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NHLBI, LCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 10 BP 2A EP 3A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900011 ER PT J AU Hager, GL McNally, JG Muller, WG Xiao, NQ Baumann, CT Fletcher, TM AF Hager, GL McNally, JG Muller, WG Xiao, NQ Baumann, CT Fletcher, TM TI The dynamic interaction of transcription factors with chromatin: Studies with living cells and reassembled templates SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 37 BP 8A EP 8A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900038 ER PT J AU Dundr, M Phair, R Misteli, T AF Dundr, M Phair, R Misteli, T TI Dynamics of proteins in the mammalian cell nucleus SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Bioinformat Serv, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 48 BP 10A EP 10A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900049 ER PT J AU Hollowell, GP Fan, JG Zelenka, PS Chepelinsky, AB AF Hollowell, GP Fan, JG Zelenka, PS Chepelinsky, AB TI Transcription factor AP-2 alpha gene expression in the lens SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 75 BP 15A EP 15A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900076 ER PT J AU Shimada, JN Cunnick, C Dvorak, JA AF Shimada, JN Cunnick, C Dvorak, JA TI Identification of nuclear pore complex proteins in Trypanosoma cruzi SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, LPD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 104 BP 20A EP 20A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900105 ER PT J AU Segura, M Craigie, R Wilson, KL AF Segura, M Craigie, R Wilson, KL TI Characterization of the nuclear function of Barrier-to-Autointegration Factor (BAF) through site-directed mutagenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 107 BP 21A EP 21A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900108 ER PT J AU Ewan, KB Wakefield, L Shyamala, WG Barcellos-Hoff, MH AF Ewan, KB Wakefield, L Shyamala, WG Barcellos-Hoff, MH TI The mammary phenotype of TGF-beta 1 null heterozygotes indicates that TGF-beta actively restrains ovarian steroid hormone-induced proliferation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 140 BP 27A EP 27A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900141 ER PT J AU Barsony, J Prufer, K Hegyi, K Schroder, C AF Barsony, J Prufer, K Hegyi, K Schroder, C TI Proteasomal degradation of retinoid X receptors blocks the anticancer effect of calcitriol in rat osteosarcoma cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 208 BP 40A EP 40A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900209 ER PT J AU Malinda, KM Wysocki, AB AF Malinda, KM Wysocki, AB TI Acute and chronic wound fluids stimulate cell migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCR, OIIB, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 245 BP 47A EP 47A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900246 ER PT J AU Park, GT Denning, MF Morasso, MI AF Park, GT Denning, MF Morasso, MI TI Phosphorylation of murine homeobox protein D1x3 by protein kinase C SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, LSB, NIH, Bethesda, MD 20892 USA. Loyola Univ, Med Ctr, Chicago, IL 60611 USA. NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 313 BP 60A EP 60A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900314 ER PT J AU Larsen, M Hoffman, MP Do, MH Yamada, KM AF Larsen, M Hoffman, MP Do, MH Yamada, KM TI Regulation of submandibular gland morphogenesis through inhibition of signal transduction pathways SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCR, CDBRB, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 320 BP 61A EP 61A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900321 ER PT J AU Joseph, D Ralston, E AF Joseph, D Ralston, E TI Synchronization of muscle cell differentiation by rapid reversal of the blockage induced by the p38 MAP kinase inhibitor SB202190. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, LN, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 339 BP 65A EP 65A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900340 ER PT J AU Liu, SH Leppla, SH AF Liu, SH Leppla, SH TI Anthrax toxin-resistant Chinese hamster ovary cell mutants obtained by retroviral insertional mutagenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 349 BP 67A EP 67A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900350 ER PT J AU Kim, SY Steinert, PM AF Kim, SY Steinert, PM TI Expression of transglutaminase 1 is highly increased in the cultured normal human myotubes with inflammatory cytokine treatment. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, LSB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 383 BP 73A EP 73A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900384 ER PT J AU Carroll, SL Herrera, AH Horowits, R AF Carroll, SL Herrera, AH Horowits, R TI Localization and functional role of N-RAP domains during myofibrillogenesis in cultured chick cardiomyocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 401 BP 77A EP 77A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900402 ER PT J AU Lo, CM Buxton, DB Adelstein, RS Dembo, M Wang, YL AF Lo, CM Buxton, DB Adelstein, RS Dembo, M Wang, YL TI Role of nonmuscle myosin II-B in the directional movement of mouse embryonic fibroblasts SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. NIH, NHLBI, Bethesda, MD 20892 USA. NIH, NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. Boston Univ, Boston, MA 02215 USA. RI Dembo, Micah/C-2755-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 462 BP 88A EP 89A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900463 ER PT J AU George, MD Smith, TM Akiyama, SK Olden, K Roberts, JD AF George, MD Smith, TM Akiyama, SK Olden, K Roberts, JD TI Modulation of cell spreading, focal adhesions, and the cytoskeleton in human breast carcinoma cells in response to arachidonic acid SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 524 BP 101A EP 101A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900526 ER PT J AU Marekov, LN Wu, KC Bryan, J Morasso, MI Parry, DA Steinert, PM AF Marekov, LN Wu, KC Bryan, J Morasso, MI Parry, DA Steinert, PM TI Residues in the 1A and 2A rod domain segments and the linker L2 are required for stabilizing the A11 molecular alignment mode in keratin intermediate filaments SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 534 BP 102A EP 103A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900536 ER PT J AU Steinert, PM Wang, H Jones, LN Marekov, LN Parry, DAD AF Steinert, PM Wang, H Jones, LN Marekov, LN Parry, DAD TI In vitro assembly and structure of trichocyte keratin intermediate filaments: Molecular modes of alignment change on oxidization SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Div Wool Technol, CSIRO, Belmont, Vic, Australia. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 533 BP 102A EP 102A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900535 ER PT J AU Hirayama, T Yahiro, K Wada, A Moss, J AF Hirayama, T Yahiro, K Wada, A Moss, J TI Protein tyrosine phosphatase activity of Helicobacter pylori VacA receptor, RPTP&beta, is not required for vacuolating activity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Nagasaki Univ, Inst Trop Med, Nagasaki 8528523, Japan. NIH, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 544 BP 104A EP 104A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900546 ER PT J AU Hohenstein, AC Roche, PA AF Hohenstein, AC Roche, PA TI SNAP-23 and SNAP-29 bind distinct syntaxins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, EIB, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 559 BP 107A EP 107A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900561 ER PT J AU Ablan, SD Puri, A Blumenthal, RL AF Ablan, SD Puri, A Blumenthal, RL TI Target membrane glycosphingolipids are involved in CD4-independent HIV-1 fusion SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Div Basic Sci, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 569 BP 109A EP 109A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900571 ER PT J AU Jones, CE Puri, A Blumenthal, RL AF Jones, CE Puri, A Blumenthal, RL TI Incorporation of exogenous lipids into CD4+cells: Effect on fusion and entry SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Maryland Baltimore Cty, Meyerhoff Scholarship Program, Baltimore, MD 21250 USA. NCI, Frederick Canc Res & Dev Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 570 BP 109A EP 109A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900572 ER PT J AU Kee, SH Steinert, PM AF Kee, SH Steinert, PM TI Disruption of microdubule induced cell-cell adhsion through activation of endogenous E-cadherin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 586 BP 112A EP 112A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900588 ER PT J AU Hiltbold, EM Anderson, HA Roche, PA AF Hiltbold, EM Anderson, HA Roche, PA TI Membrane lipid rafts facilitate class II-restricted antigen presentation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, DBS, EIB, NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 599 BP 115A EP 115A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900601 ER PT J AU Terskikh, AV Fradkov, A Zaraiskiy, A Kajava, AV Matz, M Kim, S Weissman, I Siebert, P AF Terskikh, AV Fradkov, A Zaraiskiy, A Kajava, AV Matz, M Kim, S Weissman, I Siebert, P TI "Fluorescent timer": Protein that changes color over time SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Stanford Univ, Med Ctr, Sch Med, Stanford, CA 94305 USA. Russian Acad Sci, Inst Bioorgan Chem, Moscow 117901, Russia. NIH, CIT, Ctr Mol Modeling, Bethesda, MD 20892 USA. Clontech Labs Inc, Palo Alto, CA USA. RI Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 648 BP 124A EP 124A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900650 ER PT J AU Bulte, JWM Douglas, T Strable, E van Gelderen, P Lewis, BK Frank, JA AF Bulte, JWM Douglas, T Strable, E van Gelderen, P Lewis, BK Frank, JA TI Cellular imaging: MR tracking of cell migration and pathfinding SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Temple Univ, Philadelphia, PA 19122 USA. RI Bulte, Jeff/A-3240-2008; Douglas, Trevor/F-2748-2011 OI Bulte, Jeff/0000-0003-1202-1610; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 652 BP 125A EP 125A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900654 ER PT J AU Maldonado, A Cawley, N Tam, W Loh, YP AF Maldonado, A Cawley, N Tam, W Loh, YP TI Identifying the essential residues in the sorting signal motif for targeting pro-opiomelanocortin to the regulated secretory pathway SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 712 BP 137A EP 137A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900715 ER PT J AU Caplan, S Hartnell, LM Naslavsky, N Patterson, GH Lodge, R Bonifacino, JS AF Caplan, S Hartnell, LM Naslavsky, N Patterson, GH Lodge, R Bonifacino, JS TI Induction of giant lysosomes by overexpression of human Vps39p/Vam6p SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, NICHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 719 BP 138A EP 139A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900722 ER PT J AU Naslavsky, N Donaldson, JG AF Naslavsky, N Donaldson, JG TI An alternative route to the lysosome via the ARF6-regulated endosomal compartment. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NLHBI, LCB, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 721 BP 139A EP 139A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900724 ER PT J AU Rafii, MS Creely, HM McKechnie, BA Ferri, RT Seo, NS Young, MF McQuillan, DJ Fallon, JR AF Rafii, MS Creely, HM McKechnie, BA Ferri, RT Seo, NS Young, MF McQuillan, DJ Fallon, JR TI Interactions of the proteoglycan Biglycan with the Dystrophin-Associated Protein Complex and its roles in muscular dystrophy and synaptogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Brown Univ, Dept Neurosci, Providence, RI 02912 USA. LifeCell Corp, Branchburg, NJ USA. Natl Inst Dental & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 757 BP 146A EP + PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900760 ER PT J AU Parent, CA Huang, YE Van Es, S Devreotes, PN AF Parent, CA Huang, YE Van Es, S Devreotes, PN TI Signaling responses involved in chemotaxis and phagocytosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Dept Cell Biol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 764 BP 147A EP 147A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900767 ER PT J AU Weiner, OD Servant, G Herzmark, P Balla, T Sedat, JW Bourne, HR AF Weiner, OD Servant, G Herzmark, P Balla, T Sedat, JW Bourne, HR TI Gradient amplification during eukaryotic chemotaxis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Bethesda, MD 20892 USA. RI Weiner, Orion/F-2576-2011 OI Weiner, Orion/0000-0002-1778-6543 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 765 BP 147A EP 148A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900768 ER PT J AU Pihan, GA Purohit, A Wallace, J Malhotra, R Jurczyk, A Liotta, L Doxsey, SJ AF Pihan, GA Purohit, A Wallace, J Malhotra, R Jurczyk, A Liotta, L Doxsey, SJ TI Evidence for a direct role for centrosome defects in human tumorigenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 775 BP 149A EP 149A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900778 ER PT J AU Griffis, ER Altan, N Lippincott-Schwartz, J Powers, MA AF Griffis, ER Altan, N Lippincott-Schwartz, J Powers, MA TI Nup98 is a dynamic component of the nuclear pore complex. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Atlanta, GA 30322 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 788 BP 152A EP 152A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900792 ER PT J AU Chung, MC Sukenick, S Kawamoto, S AF Chung, MC Sukenick, S Kawamoto, S TI Characterization of E-box binding factors involved in expression of the nonmuscle Myosin heavy chain II-A gene SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 821 BP 158A EP 158A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900825 ER PT J AU Tyska, MJ Huang, JD Skowron, J Mooseker, MS Jenkins, NA Copeland, NG AF Tyska, MJ Huang, JD Skowron, J Mooseker, MS Jenkins, NA Copeland, NG TI Mice null for brush border myosin I assemble brush borders and lack an overt phenotype SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT 06520 USA. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. NCI, Bethesda, MD 20892 USA. RI Huang, Jiandong/C-4277-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 849 BP 164A EP 164A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900853 ER PT J AU DeGiorgis, JA George, PF Schneider, EW Jones, KJ Reese, TS Bearer, EL AF DeGiorgis, JA George, PF Schneider, EW Jones, KJ Reese, TS Bearer, EL TI Analysis of myosin I, II and V expression in squid neuronal tissues: Implications for roles in transport. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Brown Univ, Dept Pathol, Providence, RI 02912 USA. NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 857 BP 165A EP 165A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900861 ER PT J AU Jones, KJ DeGiorgis, JA Reese, TS Bearer, EL AF Jones, KJ DeGiorgis, JA Reese, TS Bearer, EL TI Identification of a myosin I in squid axoplasm SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Brown Univ, Providence, RI 02912 USA. NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 855 BP 165A EP 165A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900859 ER PT J AU Verdier-Pinard, P Bai, R Yu, MJ Littlefield, BA Hamel, E AF Verdier-Pinard, P Bai, R Yu, MJ Littlefield, BA Hamel, E TI Interaction of ER-086526, a new synthetic halichondrin B analog, with tubulin. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Screening Technol Branch, Frederick, MD 21702 USA. NCI, Screening Technol Branch, DTP, DCTD, Frederick, MD 21702 USA. Eisai Res Inst, Andover, MA USA. NCI, Frederick, MD 21702 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 981 BP 188A EP 188A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900985 ER PT J AU Bai, R Covell, DG Kepler, JA Li, AQ Ewell, JB Pettit, GR Nguyen, NY Fisher, RJ Hamel, E AF Bai, R Covell, DG Kepler, JA Li, AQ Ewell, JB Pettit, GR Nguyen, NY Fisher, RJ Hamel, E TI Direct photoaffinity labeling of tubulin by [H-3]dolastatin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Screening Technol Branch, DTP, DCTD, Frederick, MD 21702 USA. NCI, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NCI, Prot Chem Lab, Frederick, MD 21702 USA. US FDA, Facil Biotechnol Resources, Rockville, MD 20857 USA. Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. NCI, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 986 BP 189A EP 189A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900990 ER PT J AU Ward, RD Watts, NR Miller, MW Sackett, DL AF Ward, RD Watts, NR Miller, MW Sackett, DL TI HIV-1 Rev binds to tubulin, forming bilayered ring polymers and destabilizing microtubules SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NINDS, Bethesda, MD 20892 USA. NIH, NIAMS, Bethesda, MD 20892 USA. Wright State Univ, Dayton, OH 45435 USA. NIH, NICHD, Lab Intgrat & Med Biophys, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1040 BP 199A EP 199A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901044 ER PT J AU Dhanvantari, S Loh, YP AF Dhanvantari, S Loh, YP TI A role for lipid rafts in receptor-mediated sorting to the regulated secretory pathway in endocrine cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RI Dhanvantari, Savita/B-5362-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1074 BP 206A EP 206A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901078 ER PT J AU Roberts, TH Hammond, AT Glick, BS Lippincott-Schwartz, J AF Roberts, TH Hammond, AT Glick, BS Lippincott-Schwartz, J TI In vivo dynamics of ERGIC-53 in the presence and absence of COPI and its implications for sorting in the early secretory pathway. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Univ Chicago, Chicago, IL 60637 USA. RI Ward, Theresa/E-9650-2013 OI Ward, Theresa/0000-0002-9881-8649 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1093 BP 209A EP 209A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901097 ER PT J AU Zhang, WY Kruth, HS Ishii, I AF Zhang, WY Kruth, HS Ishii, I TI Patocytosis, a cellular process by which monocyte-macrophages reverse LDL aggregation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, NIH, Sect Expt Atherosclerosis, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1128 BP 216A EP 216A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901132 ER PT J AU Nossal, R Jin, AJ AF Nossal, R Jin, AJ TI Rigidity of clathrin triskelia SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD, LIMB, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1131 BP 217A EP 217A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901135 ER PT J AU Colden-Stanfield, M Ford, BD AF Colden-Stanfield, M Ford, BD TI IRK1 and GIRK1 K+ channel expression in human THP-1 monocytes with clustered very late activation antigen-4 (VLA-4) integrins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Morehouse Sch Med, Dept Physiol, Atlanta, GA 30310 USA. NIMH, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1160 BP 222A EP 222A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901164 ER PT J AU Sigl, EM Zakalskiy, A Zisser, G Wendler, F Bergler, H Steven, A Hogenauer, G AF Sigl, EM Zakalskiy, A Zisser, G Wendler, F Bergler, H Steven, A Hogenauer, G TI Genetic approaches to identify the function of DRG1p in Saccharomyces cerevisiae SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Karl Franzens Univ Graz, IMBM, A-8010 Graz, Austria. NIAMS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1166 BP 223A EP 223A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901170 ER PT J AU Chin, MS Nagineni, CN Chesky, L Detrick, B Hooks, JJ AF Chin, MS Nagineni, CN Chesky, L Detrick, B Hooks, JJ TI Cyclooxygenase-2 is upregulated in human retinal pigment epithelial (HRPE) cells by cytokines. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1198 BP 229A EP 229A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901201 ER PT J AU Fields, KA Hackstadt, T AF Fields, KA Hackstadt, T TI Analysis of type III secretion in Chlamydia trachomatis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1241 BP 238A EP 238A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901244 ER PT J AU Traicoff, JL Callahan, R AF Traicoff, JL Callahan, R TI A novel Drosophila protein interacts with Drosophila elF3-p48/INT6 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, LTIB, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1254 BP 241A EP 241A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901257 ER PT J AU Cho, YJ Iwata, T Lunstrum, GP Horton, WA AF Cho, YJ Iwata, T Lunstrum, GP Horton, WA TI Activating mutations in Fgfr3 are responsible for decreased receptor degradation and altered intracellular localization SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1269 BP 244A EP 244A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901273 ER PT J AU Khan, NI Salomon, DS AF Khan, NI Salomon, DS TI Effect of growth factors and hormones on regulation of cripto expression in NTERA2 cells and mammary tumor cell lines. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, LTIB, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1277 BP 245A EP 246A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901281 ER PT J AU Chahdi, A Beaven, M AF Chahdi, A Beaven, M TI Localization of mastoparan-sensitive-PLD in the plasma membrane of mast cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1294 BP 249A EP 249A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901298 ER PT J AU Neary, CL Cho, YS Cho-Chung, YS AF Neary, CL Cho, YS Cho-Chung, YS TI Nuclear translocation of the regulatory subunit RII &similar to beta and the catalytic subunit C &similar to alpha of protein kinase A in apoptosis induced by protein kinase A RI &similar to alpha antisense in prostate cancer cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 LTIB, Bethesda, MD USA. NCI, CBS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1301 BP 250A EP 250A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901305 ER PT J AU Li, BS Pant, HC Kulkarni, AB AF Li, BS Pant, HC Kulkarni, AB TI Cyclin-dependent kinase-5 prevents neuronal apoptosis by negative regulation of c-Jun N-terminal kinase 3 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, Neurochem Lab, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NIDCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1321 BP 254A EP 254A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901325 ER PT J AU Lai, WC Wahl, L AF Lai, WC Wahl, L TI Differential regulation of lipopolysaccharide induced monocyte MMP-1 and MMP-9 by p38 and ERK1/2 MAP kinases SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1337 BP 257A EP 257A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901341 ER PT J AU Shi, YB Ishizuya-Oka, A Amano, T Damjanovski, S Li, Q Ueda, S AF Shi, YB Ishizuya-Oka, A Amano, T Damjanovski, S Li, Q Ueda, S TI Matrix metalloproteinase stromelysin-3 is critical for cell migration and apoptosis during intestinal metamorphosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, LME, Bethesda, MD 20892 USA. Dokkyo Univ, Sch Med, Mibu, Tochigi 32102, Japan. NICHD, Bethesda, MD 20892 USA. RI Damjanovski, Sashko/N-8728-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1352 BP 259A EP 260A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901356 ER PT J AU Hoffman, MP Larsen, M Ho, SH Lakhani, SH Kleinman, HK AF Hoffman, MP Larsen, M Ho, SH Lakhani, SH Kleinman, HK TI Gene expression profiles in developing mouse salivary glands. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NIDCR, CDBRB, Bethesda, MD 20892 USA. NIH, NIDCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1424 BP 273A EP 274A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901428 ER PT J AU Hirschberg, K Phair, RD Lippincott-Schwarz, J AF Hirschberg, K Phair, RD Lippincott-Schwarz, J TI Kinetic analysis of intra-Golgi trafficking SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, CBMB, NIH, Bethesda, MD 20892 USA. Bioinformat Serv, Rockville, MD 20854 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1461 BP 280A EP 281A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901465 ER PT J AU Lu, ZM Joseph, D Zaal, K Ralston, E AF Lu, ZM Joseph, D Zaal, K Ralston, E TI Fluorescence recovery after photobleaching (FRAP) demonstrates Golgi-to-ER recycling in muscle cells and fragmentation of the Golgi complex (GC) during differentiation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, LN, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1465 BP 281A EP 281A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901469 ER PT J AU Ralston, E Lu, ZM AF Ralston, E Lu, ZM TI Simultaneous observation of ER exit sites (ERES) and Golgi complex (GC) during nocodazole-induced CC dispersal in live cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, LN, Bethesda, MD USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1466 BP 281A EP 281A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901470 ER PT J AU Zavadil, J Bitzer, M Yang, YC Liang, D Massimi, A Piek, E Bottinger, EP AF Zavadil, J Bitzer, M Yang, YC Liang, D Massimi, A Piek, E Bottinger, EP TI Gene expression signatures of TGF-beta signaling in human keratinocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Albert Einstein Coll Med, Bronx, NY 10461 USA. NIH, NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1494 BP 287A EP 287A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901498 ER PT J AU Nagao, E Dvorak, JA AF Nagao, E Dvorak, JA TI Qualitative and quantitative analyses of parasite-induced knobs in Plasmodium falciparum-infected erythrocytes by atomic force microscopy. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1518 BP 291A EP 291A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901522 ER PT J AU Oka, T Tsuneyoshi, T AF Oka, T Tsuneyoshi, T TI The possible role of Gpx2 gene expression for cell survival during mammary gland involution. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1536 BP 295A EP 295A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901540 ER PT J AU de la Pena, MJ Wrathall, LS Nemani, D Sobel, ME AF de la Pena, MJ Wrathall, LS Nemani, D Sobel, ME TI Discovery of an additional small nucleolar RNA (snoRNA) encoded by the human RPSA gene SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1571 BP 302A EP 302A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901575 ER PT J AU Strunnikov, AV Aragon-Alcaide, L Freeman, L Kagansky, A AF Strunnikov, AV Aragon-Alcaide, L Freeman, L Kagansky, A TI Regulation of condensin function and targeting to chromatin in budding yeast. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, LME, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 20892 USA. RI Kagansky, Alexander/B-3137-2011 OI Kagansky, Alexander/0000-0002-6219-6892 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1580 BP 304A EP + PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901584 ER PT J AU Jang, SI Morasso, MI Steinert, PM AF Jang, SI Morasso, MI Steinert, PM TI Involvement of SP1, SP3, CREB and AP1 in regulation of the expression of human loricrin. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NIAMS, NIH, Skin Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1611 BP 310A EP 310A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901615 ER PT J AU Li, GQ Jang, SI Steinert, PM AF Li, GQ Jang, SI Steinert, PM TI The transcription regulation of mouse trichohyalin gene in cultured mouse hair follicle cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NIAMS, NIH, Skin Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1610 BP 310A EP 310A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901614 ER PT J AU Colarusso, P Spring, KR AF Colarusso, P Spring, KR TI Reticulated distribution of lipids in the apical membrane of MDCK cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1627 BP 313A EP 313A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901631 ER PT J AU Kenworthy, AK Nichols, BJ Bunnell, S Samelson, LE Kumar, M Zimmerberg, J Bekiranov, S Lippincott-Schwartz, J AF Kenworthy, AK Nichols, BJ Bunnell, S Samelson, LE Kumar, M Zimmerberg, J Bekiranov, S Lippincott-Schwartz, J TI Large-scale diffusion of lipid raft components in the plasma membrane: evidence that raft proteins are not associated in common, stable membrane domains SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NICHD, CBMB, Bethesda, MD 20892 USA. Rockefeller Univ, New York, NY 10021 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1639 BP 315A EP 315A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901643 ER PT J AU Sheets, ED Bunnell, S Samelson, L Jeromin, A Wiesner, A Holowka, D Baird, B AF Sheets, ED Bunnell, S Samelson, L Jeromin, A Wiesner, A Holowka, D Baird, B TI Real time spatial dynamics of IgE receptor-mediated signaling in mast cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Cornell Univ, Baker Lab, Ithaca, NY 14853 USA. NIH, Bethesda, MD 20892 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Cornell Univ, Ithaca, NY 14853 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1635 BP 315A EP 315A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901639 ER PT J AU Tokumasu, F Jin, AJ Dvorak, JA AF Tokumasu, F Jin, AJ Dvorak, JA TI Atomic force microscopy reveals lipid membrane structural transformations SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1643 BP 316A EP 316A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901647 ER PT J AU Kenworthy, AK Nichols, BJ Chiu, VK Philips, MR Lippincott-Schwartz, J AF Kenworthy, AK Nichols, BJ Chiu, VK Philips, MR Lippincott-Schwartz, J TI The dynamics of GFP-Ras in living cells provide evidence for NRas recycling between the cell surface and Golgi complex SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, CBMB, NIH, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1669 BP 321A EP 321A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901673 ER PT J AU Brown, FD Rozelle, A Yin, H Balla, T Donaldson, J AF Brown, FD Rozelle, A Yin, H Balla, T Donaldson, J TI Arf6 regulated membrane trafficking and the spatial control of PIP2 synthesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75235 USA. NICHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1691 BP 326A EP 326A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901695 ER PT J AU Gomez-Angelats, M Cidlowski, JA Carl, BD AF Gomez-Angelats, M Cidlowski, JA Carl, BD TI Fas receptor-induced apoptosis: modulatory effect of PKC on incipient stages of the cell death pathway in Jurkat T-cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1810 BP 349A EP 349A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901814 ER PT J AU McNeil, EL Basciano, PA Sellers, JR King-Smith, C AF McNeil, EL Basciano, PA Sellers, JR King-Smith, C TI Isolated pigment granules from teleost retinal pigment epithelial cells move along actin cables of the alga, Nitella axillaris SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 St Josephs Univ, Philadelphia, PA 19131 USA. NIH, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1841 BP 355A EP 355A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901845 ER PT J AU Yamashita, RA Sellers, JR Anderson, JB AF Yamashita, RA Sellers, JR Anderson, JB TI Identification and analysis of the myosin superfamily in Drosophila: A database approach SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1951 BP 376A EP 376A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901955 ER PT J AU Moreau, V Frischknecht, F Reckmann, I Vincentelli, R Rabut, G Stewart, D Ploubidou, A AF Moreau, V Frischknecht, F Reckmann, I Vincentelli, R Rabut, G Stewart, D Ploubidou, A TI A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 European Mol Biol Lab, Cell Biol Programme, D-69117 Heidelberg, Germany. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1971 BP 379A EP 380A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901975 ER PT J AU Jackson, TR Brown, FD Nie, ZZ Miura, K Foroni, L Sun, JL Hsu, VW Donaldson, JG Randazzo, PA Theibert, AB AF Jackson, TR Brown, FD Nie, ZZ Miura, K Foroni, L Sun, JL Hsu, VW Donaldson, JG Randazzo, PA Theibert, AB TI Centaurins: mediators of phospholipid and Arf signalling in the cell periphery SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Royal Free Hosp, Sch Med, Dept Haematol, London NW3 2PF, England. NHLBI, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 1994 BP 384A EP 384A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901998 ER PT J AU Boulanger, CA Smith, GH AF Boulanger, CA Smith, GH TI Reducing mammary cancer risk through premature stem cell senescence SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, LTIB, DBS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2089 BP 402A EP 403A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902093 ER PT J AU Messam, CA Hou, J Major, EO AF Messam, CA Hou, J Major, EO TI Molecular recognition of the human polyomavirus, JCV, distinguishes between human glial and neuronal progenitor cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, LMMN, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2128 BP 410A EP 410A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902132 ER PT J AU Yang, QF DePetrillo, PB AF Yang, QF DePetrillo, PB TI Calpain inhibitor and ritonavir block glutamate cytotoxicity in PC12 cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAAA, DICBR, LCS, UCBP,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2136 BP 411A EP 412A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902140 ER PT J AU Sans, NA Petralia, RS Wang, YX McCallum, J Wenthold, RJ AF Sans, NA Petralia, RS Wang, YX McCallum, J Wenthold, RJ TI SAP-97 is associated with intracellular and plasma membrane AMPA receptors SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2150 BP 414A EP 414A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902154 ER PT J AU Standley, S Roche, KW McCallum, J Sans, NA Wenthold, RJ AF Standley, S Roche, KW McCallum, J Sans, NA Wenthold, RJ TI PDZ-domain suppression of an ER retention signal in NMDAR1 splice variants. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2149 BP 414A EP 414A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902153 ER PT J AU Zhang, BJ Kusano, K Yamashita, M Field, R Iacangelo, A Young, WS Gainer, H AF Zhang, BJ Kusano, K Yamashita, M Field, R Iacangelo, A Young, WS Gainer, H TI Sorting and packaging of vasopressin- and Oxytocin-neurophysin-EGFP fusion proteins into Large Dense Core Vesicles and their secretion in vitro and in vivo. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, Neurochem Lab, Bethesda, MD 20892 USA. NIMH, Sect Neural Gene Express, Bethesda, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2156 BP 415A EP 415A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902160 ER PT J AU Snapp, EL Hendershot, LM Lippincott-Schwartz, J AF Snapp, EL Hendershot, LM Lippincott-Schwartz, J TI Mobility and retention of misfolded proteins in the endoplasmic reticulum of living cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, NIGMS, NIH, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2165 BP 417A EP 417A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902169 ER PT J AU Huizing, M Zhao, Y Sarangarajan, R Gahl, WA Boissy, RE AF Huizing, M Zhao, Y Sarangarajan, R Gahl, WA Boissy, RE TI Analysis of melanocyte dysfunction in Hermansky-Pudlak syndrome SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20851 USA. Univ Cincinnati, Dept Dermatol, Coll Med, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2179 BP 420A EP 420A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902183 ER PT J AU Hackstadt, T Swanson, JA AF Hackstadt, T Swanson, JA TI Probing the interior of the Chlamydia trachomatis inclusion SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2246 BP 432A EP 433A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902250 ER PT J AU Dyer, KD Rosenberg, HF AF Dyer, KD Rosenberg, HF TI Identification and characterization of a novel transcriptional enhancer element - Eosinophil Transcription Factor (EoTF). SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NIAID, Host Def Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2251 BP 433A EP 433A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902255 ER PT J AU Lee, FJS Lin, CY Huang, PH Liao, WL Cheng, HJ Huang, CF Kuo, JC Patton, W Massenburg, D Moss, J AF Lee, FJS Lin, CY Huang, PH Liao, WL Cheng, HJ Huang, CF Kuo, JC Patton, W Massenburg, D Moss, J TI ARL4, a developmentally regulated ARF-like protein, interacts with importin-alpha and is localized to nuclei and nucleoli SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Natl Taiwan Univ, Inst Mol Med, Taipei 100, Taiwan. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2303 BP 444A EP 444A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902307 ER PT J AU Ainsztein, AM Azuma, Y Dasso, MC AF Ainsztein, AM Azuma, Y Dasso, MC TI The SUMO-1 E1 subunit Uba2 functions in mitosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NICHD, LME, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2325 BP 448A EP 448A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902329 ER PT J AU Joe, YA Lee, Y Kim, HK Kim, YY Park, MH AF Joe, YA Lee, Y Kim, HK Kim, YY Park, MH TI Effects of N-1-guanyl-1,7-diaminoheptane, an inhibitor of deoxyhypusine synthase, on endothelial cell growth, differentiation and apoptosis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Catholic Univ Korea, Inst Canc Res, Seoul 137701, South Korea. NIDCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2362 BP 455A EP 455A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902366 ER PT J AU Zheng, B Peters, E Williams, C Ferraris, J Burg, M Schmieder, S AF Zheng, B Peters, E Williams, C Ferraris, J Burg, M Schmieder, S TI MIR16, a membrane glycerophosphodiester phosphodiesterase: Enzymatic activity, membrane topology and implications for membrane trafficking and signaling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2511 BP 485A EP 485A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902515 ER PT J AU Davey, PC Jones, TLZ AF Davey, PC Jones, TLZ TI Palmitate-dependent targeting RGS16 into membrane microdomains SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2522 BP 487A EP 487A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902526 ER PT J AU Young, ME Karpova, TS Moschenross, DM Wang, G Cooper, JA AF Young, ME Karpova, TS Moschenross, DM Wang, G Cooper, JA TI Novel cortical structure in Saccharomyces cerevisiae defined by integral plasma membrane protein Sur7p SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Washington Univ, Sch Med, St Louis, MO USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2535 BP 490A EP 490A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902539 ER PT J AU Kim, SJ Rahbar, R Mitra, D Salerno, J Snapp, EL Rutkowski, DT Lingappa, VR Hegde, RS AF Kim, SJ Rahbar, R Mitra, D Salerno, J Snapp, EL Rutkowski, DT Lingappa, VR Hegde, RS TI Regulation of secretory and membrane protein biogenesis by signal sequences SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. NICHD, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2558 BP 494A EP 494A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902562 ER PT J AU Vaidyanathan, V Roche, P AF Vaidyanathan, V Roche, P TI Structural features in SNAP-25 and SNAP-23 that regulate their interactions with Syntaxin and VAMP SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Natl Canc Inst, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2569 BP 496A EP 496A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902573 ER PT J AU Castle, AL Aviles-Hernandez, A Cushman, SW AF Castle, AL Aviles-Hernandez, A Cushman, SW TI The intracellular loop plays a role in both the turnover and subcellular trafficking of GLUT4 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2579 BP 498A EP 498A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902583 ER PT J AU Su, AW Shen, DW Chauhan, S Pastan, I Gottesman, MM AF Su, AW Shen, DW Chauhan, S Pastan, I Gottesman, MM TI Reduced cisplatin uptake seen in cisplatin-resistant cells reflects a generalized uptake defect: cross-resistance of cisplatin-resistant cells to Pseudomonas exotoxin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2623 BP 507A EP 507A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902627 ER PT J AU Patterson, G Lodge, R Bonifacino, J Lippincott-Schwartz, J AF Patterson, G Lodge, R Bonifacino, J Lippincott-Schwartz, J TI Lysosome-plasma membrane cycling dynamics of the lysosomal membrane protein, CD63. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NICHD, CBMB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2718 BP 525A EP 525A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902722 ER PT J AU Lewis, MK Adhikari, B Chen, V Bass, AH Wang, K AF Lewis, MK Adhikari, B Chen, V Bass, AH Wang, K TI Examination of the desmin lattice in single muscle fibers of fish sonic muscle SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NIAMS, Bethesda, MD 20892 USA. Cornell Univ, Ithaca, NY 14853 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2756 BP 532A EP 532A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902760 ER PT J AU Ahvazi, B Kim, HC Idler, WW Steinert, PM AF Ahvazi, B Kim, HC Idler, WW Steinert, PM TI Three-dimensional structures of human transglutaminase 3 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2776 BP 536A EP 537A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902780 ER PT J AU Buxton, DB Adelstein, RS AF Buxton, DB Adelstein, RS TI Threonine phosphorylation of nonmuscle myosin heavy chain by calcium/calmodulin-dependent protein kinase II in stimulated mast cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2798 BP 541A EP 541A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902802 ER PT J AU Conti, MA Du, YB Liu, CY Adelstein, RS AF Conti, MA Du, YB Liu, CY Adelstein, RS TI Ablation of nonmuscle myosin heavy chain II-A results in lethality at E7.5 in mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2800 BP 541A EP 541A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902804 ER PT J AU Ma, XF Kawamoto, S Du, YB Liu, CY Adelstein, RS AF Ma, XF Kawamoto, S Du, YB Liu, CY Adelstein, RS TI Neuronal-specific alternatively spliced isoforms of nonmuscle myosin heavy chain II-B SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD 20892 USA. NIH, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2801 BP 541A EP 541A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902805 ER PT J AU Takeda, K Yu, ZX Pato, MD Preston, YA Ferrans, VJ Adelstein, RS AF Takeda, K Yu, ZX Pato, MD Preston, YA Ferrans, VJ Adelstein, RS TI Hypertrophy and abnormal cytokinesis in cardiac myocytes of nonmuscle myosin heavy chain II-B (NMHC II-B)-ablated mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. Univ Saskatchewan, Saskatoon, SK S7N 0W0, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2799 BP 541A EP 541A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902803 ER PT J AU Wei, QZ Adelstein, RS AF Wei, QZ Adelstein, RS TI Analysis of the rod region responsible for filament formation in nonmuscle myosin II SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Mol Cardiol Lab, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2806 BP 542A EP 542A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902810 ER PT J AU Sellers, JR Chantler, PD AF Sellers, JR Chantler, PD TI TFP inhibits the actin-activated MgATPase and motility of both conventional and unconventional myosins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. Univ London Royal Vet Coll, London NW1 0TU, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2811 BP 543A EP 543A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902815 ER PT J AU Kalinin, A Idler, WW McPhie, P Marekov, LN Steinert, PM AF Kalinin, A Idler, WW McPhie, P Marekov, LN Steinert, PM TI Molecular parameters of envoplakin-periplakin copolymers SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NIAMS, Skin Biol Lab, Bethesda, MD 20892 USA. NIH, NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2841 BP 549A EP 549A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902845 ER PT J AU Warner, AK Pant, HC Sloboda, RD AF Warner, AK Pant, HC Sloboda, RD TI Mitotic apparatus phosphoprotein p62: Cell cycle and mass spectrometry analysis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Dartmouth Coll, Hanover, NH 03755 USA. NINDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 SU S MA 2946 BP 570A EP 570A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902950 ER PT J AU Haft, CR Sierra, MDL Bafford, R Lesniak, MA Barr, VA Taylor, SI AF Haft, CR Sierra, MDL Bafford, R Lesniak, MA Barr, VA Taylor, SI TI Human orthologs of yeast vacuolar protein sorting proteins Vps26, 29, and 35: Assembly into multimeric complexes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID INSULIN-RECEPTOR; GENE ENCODES; TRANSPORT; GOLGI; INTERNALIZATION; DEGRADATION; EXPRESSION; BIOGENESIS; RETRIEVAL; PATHWAYS AB Sorting nexin (SNX) 1 and SNX2 are mammalian orthologs of Vps5p, a yeast protein that is a subunit of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. We report the cloning and characterization of human orthologs of three additional components of the complex: Vps26p, Vps29p, and Vps35p. The close structural similarity between the yeast and human proteins suggests a similarity in function. We used both yeast two-hybrid assays and expression in mammalian cells to define the binding interactions among these proteins. The data suggest a model in which hVps35 serves as the core of a multimeric complex by binding directly to hVps26, hVps29, and SNX1. Deletional analyses of hVps35 demonstrate that amino acid residues 1-53 and 307-796 of hVps35 bind to the coiled coil-containing domain of SNX1. Ln contrast, hVps26 binds to amino acid residues 1-172 of hVps35, whereas hVps29 binds to amino acid residues 307-796 of hVps35. Furthermore, hVps35, hVps29, and hVps26 have been found in membrane-associated and cytosolic compartments. Gel filtration chromatography of COS7 cell cytosol showed that both recombinant and endogenous hVps35, hVps29, and hVps26 coelute as a large complex (similar to 220-440 kDa). In the absence of hVps35, neither hVps26 nor hVps29 is found in the large complex. These data provide the first insights into the binding interactions among subunits of a putative mammalian retromer complex. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Haft, CR (reprint author), NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NR 28 TC 165 Z9 173 U1 2 U2 6 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 IS 12 BP 4105 EP 4116 PG 12 WC Cell Biology SC Cell Biology GA 384PX UT WOS:000165955000005 PM 11102511 ER PT J AU Gasch, AP Spellman, PT Kao, CM Carmel-Harel, O Eisen, MB Storz, G Botstein, D Brown, PO AF Gasch, AP Spellman, PT Kao, CM Carmel-Harel, O Eisen, MB Storz, G Botstein, D Brown, PO TI Genomic expression programs in the response of yeast cells to environmental changes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID OXIDATIVE STRESS RESPONSES; SHOCK TRANSCRIPTION FACTOR; UNFOLDED PROTEIN RESPONSE; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; HEAT-SHOCK; ENDOPLASMIC-RETICULUM; OSMOTIC-STRESS; KINASE; PATHWAY AB We explored genomic expression patterns in the yeast Saccharomyces cerevisiae responding to diverse environmental transitions. DNA microarrays were used to measure changes in transcript levels over time for almost every yeast gene, as cells responded to temperature shocks, hydrogen peroxide, the superoxide-generating drug menadione, the sulfhydryl-oxidizing agent diamide, the disulfide-reducing agent dithiothreitol, hyper- and hypo-osmotic shock, amino acid starvation, nitrogen source depletion, and progression into stationary phase. A large set of genes (similar to 900) showed a similar drastic response to almost all of these environmental changes. Additional features of the genomic responses were specialized for specific conditions. Promoter analysis and subsequent characterization of the responses of mutant strains implicated the transcription factors Yap1p, as well as Msn2p and Msn4p, in mediating specific features of the transcriptional response, while the identification of novel sequence elements provided clues to novel regulators. Physiological themes in the genomic responses to specific environmental stresses provided insights into the effects of those stresses on the cell. C1 Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Lawrence Berkeley Natl Labs, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 94720 USA. Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA. RP Brown, PO (reprint author), Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. OI Eisen, Michael/0000-0002-7528-738X; Storz, Gisela/0000-0001-6698-1241 FU NHGRI NIH HHS [HG-00450, HG-00983] NR 57 TC 2777 Z9 2843 U1 22 U2 201 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 2000 VL 11 IS 12 BP 4241 EP 4257 PG 17 WC Cell Biology SC Cell Biology GA 384PX UT WOS:000165955000015 PM 11102521 ER PT J AU Grant, DJ Bell, DA AF Grant, DJ Bell, DA TI Bilirubin UDP-glucuronosyltransferase 1A1 gene polymorphisms: Susceptibility to oxidative damage and cancer? SO MOLECULAR CARCINOGENESIS LA English DT Article DE liver enzymes; bilirubin; antioxidants; DNA damage; carcinogenesis ID CORONARY-ARTERY DISEASE; GILBERTS-SYNDROME; SERUM BILIRUBIN; LIPID-PEROXIDATION; REACTIVE OXYGEN; NEONATAL HYPERBILIRUBINEMIA; SUPEROXIDE-DISMUTASE; ANTIOXIDANT ENZYMES; MISSENSE MUTATION; ACTIVE METABOLITE AB The UDP-glucuronosyltransferase 1A1 (UCT1A1) gene product catalyzes the glucuronidation of serum bilirubin as part of normal heme catabolism. Recently, TA repeat polymorphisms containing five, six, seven, and eight TA dinucleotides in a putative TATA box in the promoter region of the UGT1A1 gene have been described. TA repeat number modulates UGT1A1 transcriptional activity and the quantity of enzyme available to conjugate serum bilirubin. Serum bilirubin is a known antioxidant, and low serum bilirubin has been associated with increased risk for coronary artery disease and inhibition of reactive oxygen species (ROS)-induced damage to erythrocytes in vitro. We hypothesize that the UGT1A1 TA repeals or other functional polymorphisms resulting in lower serum bilirubin levels may be predictive of genetic susceptibility to oxidative damage and cancer. Exposure-related or endogenous production of ROS may impact the integrity of cellular macromolecules and infrastructure, lead to DNA base changes or chromosomal aberrations, and induce toxicity or apoptosis. ROS damage to lipoproteins may be a factor in formation of atherogenic plaques in coronary heart disease. Thus, cellular oxidative stress could contribute to tumorigenesis through mutagenic or epigenetic pathways, and higher serum bilirubin levels should inhibit this process. No definitive studies have been performed, but in a small prospective study of colon cancer, serum bilirubin levels were observed to be lower in these cases. Another study has suggested a link between UGT1A1 alleles, estrogen metabolism, and risk in breast cancer. Epidemiologic studies examining variation in ROS metabolism, ROS damage, bilirubin, and cancer risk will demonstrate the value of this hypothesis. Published 2000 Wiley-Liss, Inc.(dagger). C1 Natl Inst Environm Hlth Sci, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC 27709 USA. RP Bell, DA (reprint author), Natl Inst Environm Hlth Sci, Lab Computat Biol & Risk Assessment, C3-03,POB 12233, Res Triangle Pk, NC 27709 USA. NR 61 TC 19 Z9 20 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD DEC PY 2000 VL 29 IS 4 BP 198 EP 204 DI 10.1002/1098-2744(200012)29:4<198::AID-MC1001>3.0.CO;2-K PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 390DW UT WOS:000166281300002 PM 11170257 ER PT J AU Cannon, RE Graves, S Spalding, LW Trempus, CS Tennant, RW AF Cannon, RE Graves, S Spalding, LW Trempus, CS Tennant, RW TI Oral administration of dimethylvinyl chloride increases frequency of forestomach papillomas in Tg.AC mice SO MOLECULAR CARCINOGENESIS LA English DT Article DE transgenic; Tg.AC; ras; skin cancer; stomach cancer ID MOUSE SKIN; RAS; EXPRESSION AB This work was initiated to determine the potential for the Tg.AC mouse model to identify chemical carcinogens by an oral route of administration. Tg.AC v-Ha-ras transgenic mice were exposed to dimethyvinyl chloride (DMVC; 1-chloro-2-methylpropene), a structural analog of the human carcinogen vinyl chloride. In the National Toxicology Program 2-yr bioassay, DMVC induced tumors in the oral, nasal, and gastric epithelia of rats and mice, initial studies were performed in female Tg.AC mice to determine an appropriate oral dose of DMVC to evaluate the potential for stratified gastric or oral epi thelia of Tg.AC mice to serve as a target tissue for a transgene-dependent induced tumorigenic response. DMVC was administered to 13- to 14-wk-old Tg.AC mice by gavage at doses of 0, 50, 100, and 200 mg/kg five times a week for 20 wk. The forestomachs of DMVC-treated Tg.AC mice had an increasing number of papillomas, which were associated with an increase in the dose of DMVC. The average numbers of papillomas per mouse per dose were 2.4, 7.6, 14.1, and 12.6 for the 0, 50, 100, and 200-mg/kg dose groups, respectively. The optimum papillomagenic dose of 100 mg/kg DMVC was established and administered for 5, 10, and 15 wk to investigate the kinetics of papilloma induction in Tg.AC mice. The average numbers of papillomas per animal were 1.8, 8.8, and 19.0 at 5, 10, and 15 wk, respectively. Reverse transcription-polymerase chain reaction assays determined that the v-Ha-ras transgene was transcriptionally active in all tumor tissues but not in nontumor tissues. In si tu hybridization assays performed in conjunction with bromodeoxyuridine in vivo labeling localized the transgene-expressing cells of the forestomach papillomas to the proliferating cellular component of the tumors, as previously seen in skin papillomas of Tg.AC mice. The present results confirm that DMVC is tumorigenic and that oral routes of administration can be used to rapidly elicit a transgene-associated tumor response in the forestomach of Tg.AC mice. Published 2000 Wiley-Liss, Inc.(dagger). C1 Natl Inst Environm Hlth Sci, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. RP Cannon, RE (reprint author), Natl Inst Environm Hlth Sci, Lab Environm Carcinogenesis & Mutagenesis, POB 1223, Res Triangle Pk, NC 27709 USA. NR 15 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD DEC PY 2000 VL 29 IS 4 BP 229 EP 235 DI 10.1002/1098-2744(200012)29:4<229::AID-MC1005>3.0.CO;2-9 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 390DW UT WOS:000166281300006 PM 11170261 ER PT J AU Ortega, J Singh, SK Ishikawa, T Maurizi, MR Steven, AC AF Ortega, J Singh, SK Ishikawa, T Maurizi, MR Steven, AC TI Visualization of substrate binding and translocation by the ATP-dependent protease, ClpXP SO MOLECULAR CELL LA English DT Article ID ESCHERICHIA-COLI; CLPAP PROTEASE; CRYSTAL-STRUCTURE; 20S PROTEASOME; CHAPERONE; DEGRADATION; RECOGNITION; PROTEOLYSIS; RESOLUTION; SYMMETRY AB Binding and internalization of a protein substrate by E. coli ClpXP was investigated by electron microscopy. In sideviews of ATP gammaS-stabilized ClpXP complexes, a narrow axial channel was visible in ClpX, surrounded by protrusions on its distal surface. When substrate lambda O protein was added, extra density attached to this surface. Upon addition of ATP, this density disappeared as lambda O was degraded. When ATP was added to proteolytically inactive ClpXP-lambda O complexes, the extra density transferred to the center of ClpP and remained inside ClpP after separation from ClpX. We propose that substrates of ATP-dependent proteases bind to specific sites on the distal surface of the ATPase, and are subsequently unfolded and translocated into the internal chamber of the protease. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RI Ishikawa, Takashi/E-5023-2017 OI Ishikawa, Takashi/0000-0002-1976-7477 NR 35 TC 123 Z9 124 U1 2 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 2000 VL 6 IS 6 BP 1515 EP 1521 DI 10.1016/S1097-2765(00)00148-9 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 389LN UT WOS:000166239500023 PM 11163224 ER PT J AU Simone, NL Paweletz, CP Charboneau, L Petricoin, EF Liotta, LA AF Simone, NL Paweletz, CP Charboneau, L Petricoin, EF Liotta, LA TI Laser capture microdissection: Beyond functional genomics to proteomics SO MOLECULAR DIAGNOSIS LA English DT Article DE surface-enhanced laser desorption spectrometry; matrix-assisted laser desorption-ionization time-of-flight spectrometry; immunoassays; microdissection; proteomics ID PROSTATE-SPECIFIC ANTIGEN; BREAST CANCERS; GENE; RNA AB Proteomics will drive biology and medicine beyond genomics, and can have a profound impact on molecular diagnostics. The posttranslational modifications of cellular proteins that govern physiology and become deranged in disease cannot be accurately portrayed by gene expression alone. Consequently, new technology is being developed to discover, and quantitatively monitor, proteomic changes that are associated with disease etiology and progression. In the past, proteomic technologies were restricted to tumor cell lines or homogenized bulk tissue specimens. This source material may not accurately reflect molecular events taking place in the specific cells of the tissue itself. This article describes a completely new class of proteomic-based approaches aimed at the identification and investigation of protein markers in the actual histologically defined cell populations that an immersed in heterogeneous diseased tissue, it is envisioned that these investigations will eventually lead to novel diagnostic, prognostic, or therapeutic markers that can be applied to monitor therapeutic toxicity or efficacy. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Tissue Proteom Unit, Div Therapeut Prot, Washington, DC 20204 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 67 Z9 71 U1 0 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1084-8592 J9 MOL DIAGN JI Mol. Diagn. PD DEC PY 2000 VL 5 IS 4 BP 301 EP 307 DI 10.1054/modi.2000.19808a PG 7 WC Biotechnology & Applied Microbiology; Medical Laboratory Technology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Medical Laboratory Technology; Research & Experimental Medicine GA 389DA UT WOS:000166222300007 PM 11172494 ER PT J AU Tsigos, C Tsiotra, P Garibaldi, LR Stavridis, JC Chrousos, GP Raptis, SA AF Tsigos, C Tsiotra, P Garibaldi, LR Stavridis, JC Chrousos, GP Raptis, SA TI Mutations of the ACTH receptor gene in a new family with isolated glucocorticoid deficiency SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE ACTH receptor; ACTH resistance; adrenal insufficiency; glucocorticoid deficiency; G-protein-coupled receptors ID ADRENOCORTICOTROPIN RECEPTOR AB Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by primary adrenocortical insufficiency, without mineralocorticoid deficiency. Mutations of the ACTH receptor gene have been reported in several families with IGD. We have amplified and directly sequenced the entire intronless ACTH receptor gene in a new family with IGD. The proband was found to be compound heterozygote for two different point mutations, one in each allele: (a) a substitution (360C>G) which changed neutral serine at position 120 in the apolar third transmembrane domain of the receptor to a positively charged arginine (S120R), probably disrupting the ligand-binding site; and (b) a substitution (761A>G) changing tyrosine at position 254 to cysteine (Y254C) in the third extracellular loop of the receptor protein, that also likely disrupts its structure and interferes with ligand binding. Each of the two mutations in the proband has previously been described in a different family, S120R in compound heterozygosity with a stop codon (R201X) and Y254C in homozygote form. Thus, in the absence of in vitro functional studies, our findings confirm the pathogenetic role of the S120R and Y254C mutants in the development of resistance to ACTH. (C) 2000 Academic Press. C1 Hellen Natl Diabet Ctr, Athens 10675, Greece. Univ Athens, Lab Expt Physiol, Athens, Greece. Cardinal Glennon Childrens Hosp, Div Endocrinol, St Louis, MO 63104 USA. NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Univ Athens, Res Inst, Dept Internal Med 2, Athens, Greece. Univ Athens, Ctr Diabet, Athens, Greece. RP Tsigos, C (reprint author), Hellen Natl Diabet Ctr, 3 Ploutarchou St, Athens 10675, Greece. NR 20 TC 9 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD DEC PY 2000 VL 71 IS 4 BP 646 EP 650 DI 10.1006/mgme.2000.3090 PG 5 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 388FW UT WOS:000166167600015 PM 11136558 ER PT J AU Park, SS Ryu, CJ Kang, YJ Kashmiri, SVS Hong, HJ AF Park, SS Ryu, CJ Kang, YJ Kashmiri, SVS Hong, HJ TI Generation and characterization of a novel tetravalent bispecific antibody that binds to hepatitis B virus surface antigens SO MOLECULAR IMMUNOLOGY LA English DT Article DE antibody engineering; bispecific antibody; single-chain antibody; hepatitis B virus ID MONOCLONAL-ANTIBODY; ESCHERICHIA-COLI; FRAGMENTS; PROTEIN; HYBRIDOMAS; EXPRESSION; MOLECULE AB Hepatitis B virus (HBV) infection is a worldwide public health problem affecting about 350 million people. HBV envelope contains three surface antigens, called pre-S1, pre-S2 and S. For the prophylaxis of HBV infection, only an anti-S monoclonal antibody was tested for the protective efficacy against HBV infection, but it was shown to be incomplete. In addition, some immune escape mutants carrying mutations on the S antigen were reported. Therefore, a multivalent bispecific antibody rather than a single monoclonal antibody would be more beneficial for the prophylaxis of HBV infection. We have generated a novel tetravalent bispecific antibody with two binding sites for each of the S and pre-S2 antigens. Each of the antigen-binding sites was composed of a single-chain Fv (ScFv). The tetravalent antibody was generated by constructing a single gene encoding a single-chain protein. This protein consisted of an anti-S ScFv whose carboxyl end was tethered, through a 45 amino acid linker, to the amino terminus of anti-preS2 ScFv that in turn was joined to the hinge region of human yl constant region. The single-chain protein was expressed in Chinese hamster ovary cells and secreted in culture supernatant as a homodimeric molecule. The tetravalent bispecific antibody showed both anti-S and anti-pre-S2 binding activities. In addition, the binding affinity of the bispecific antiboy for HBV particles was greater than that of either parental antibody. The tetravalent bispecific antibody is a potentially useful reagent for the prevention and treatment of HBV infection. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Korea Res Inst Biosci & Biotechnol, Antibody Engn Res Lab, Taejon 305600, South Korea. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hong, HJ (reprint author), Korea Res Inst Biosci & Biotechnol, Antibody Engn Res Lab, POB 115, Taejon 305600, South Korea. NR 29 TC 13 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 2000 VL 37 IS 18 BP 1123 EP 1130 DI 10.1016/S0161-5890(01)00027-X PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 457RD UT WOS:000170149800004 PM 11451417 ER PT J AU Ginis, I Hallenbeck, JM Liu, J Spatz, M Jaiswal, R Shohami, E AF Ginis, I Hallenbeck, JM Liu, J Spatz, M Jaiswal, R Shohami, E TI Tumor necrosis factor and reactive oxygen species cooperative cytotoxicity is mediated via inhibition of NF-kappa B SO MOLECULAR MEDICINE LA English DT Article ID CLOSED-HEAD INJURY; DNA-BINDING ACTIVITY; FOCAL CEREBRAL-ISCHEMIA; TRAUMATIC BRAIN INJURY; CENTRAL-NERVOUS-SYSTEM; BETA-PEPTIDE TOXICITY; FACTOR-ALPHA; TNF-ALPHA; TRANSCRIPTION FACTOR; INDUCED APOPTOSIS AB Background: Tumor necrosis factor alpha (TNF alpha) plays a key role in pathogenesis of brain injury. However, TNF alpha exhibits no cytotoxicity in primary cultures of brain cells. This discrepancy suggests that other pathogenic stimuli that exist in the setting of brain injury precipitate TNF alpha cytotoxicity. The hypothesis was tested that reactive oxygen species (ROS), that are released early after brain injury, act synergistically with TNF alpha in causing cell death. Materials and Methods: Cultured human and rat brain capillary endothelial cells (RBEC), and cortical astrocytes were treated with TNF alpha alone or together with different doses of H2O2, and apoptotic cell death and DNA fragmentation were measured by means of 3'-OH-terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Hoechst fluorescence assay, respectively. The effect of H2O2 on TNF alpha -induced activation of nuclear factor kappa B (NF-kappaB) was measured by Western blots of cytoplasmic and nuclear extracts of RBEC using anti-inhibitor of NF-kappaB (I kappaB) and anti-p65 subunit of NF-kappaB antibodies. Nuclear translocation of NF-kappaB was investigated by immunofluorescent staining of RBEC with anti-p65 antibodies. Results: TNF alpha alone had no cytotoxic effect in brain endothelial cells and astrocytes at concentrations up to 100 ng/ml. Go-treatment with 5-10 muM of H2O2 caused a two-fold increase in the number of apoptotic cells 24 hr later. Similar doses (1-3 muM) of H2O2 initiated early DNA fragmentation. H2O2 inhibited TNF alpha -induced accumulation of p69 in the nucleus, although it had no effect on degradation of the I kappaB in cytoplasm. Immunostaining confirmed that H2O2 inhibited p65 transport to the nucleus. Conclusions: Reactive oxygen species could act synergistically with TNF alpha in causing cytotoxicity via inhibition of a cytoprotective branch of TNF alpha signaling pathways, which starts with NF-kappaB activation. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Sch Pharm, Dept Pharmacol, IL-91120 Jerusalem, Israel. NR 83 TC 37 Z9 37 U1 0 U2 2 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD DEC PY 2000 VL 6 IS 12 BP 1028 EP 1041 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 392MT UT WOS:000166415800004 PM 11474119 ER PT J AU Fields, KA Hackstadt, T AF Fields, KA Hackstadt, T TI Evidence for the secretion of Chlamydia trachomatis CopN by a type III secretion mechanism SO MOLECULAR MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; MESSENGER-RNA SIGNAL; YERSINIA YOP VIRULON; INFECTED-CELLS; INCLUSION MEMBRANE; PSEUDOMONAS-AERUGINOSA; EUKARYOTIC CELLS; ELEMENTARY BODY; EXOENZYME-S; IDENTIFICATION AB The medically significant, obligate intracellular pathogen Chlamydia trachomatis replicates within vacuoles termed inclusions. A developmental cycle is initiated after entry into a host cell and is manifested by the transformation of infectious elementary bodies (EBs) to larger, non-infectious reticulate bodies (RBs). Analysis of the C. trachomatis genome has revealed that chlamydiae possess genes that may encode a type III secretion apparatus. In other Gram-negative pathogens, the type III secretion mechanism is used to target virulence factors directly to the host cell cytoplasm and is essential for full virulence. To evaluate the possibility of a functional type III secretion mechanism in C. trachomatis, we initially focused on a locus containing genes encoding products with similarity to chaperones (Scc1), secretion pore components (Cds1 and Cds2) and secreted proteins (CopN) from other type III systems. Gene expression was tested by reverse transcriptase-polymerase chain reaction (RT-PCR) of total RNA extracted from infected HeLa cell monolayers at 2, 6, 12 and 20 h after infection and normalized for the number of C. trachomatis genomes present. Message was detected for Scc1 at all times, whereas message for all other tested genes was detected in significant amounts at 12 h and 20 h. Immunoblot analysis with Scc1- and CopN-specific antibodies revealed that CopN and Scc1 were present in EBs, RBs and whole-culture extracts harvested 20 h after infection. CopN is homologous to the secreted protein YopN of Yersinia sp., and analysis of monolayers 20 h after infection via indirect immunofluorescence showed specific labelling of inclusion membranes when probed with CopN-specific antibodies but not with Scc1-specific antibodies. His-tagged CopN and a chlamydial cytoplasmic control protein (NrdB) were expressed in Yersinia enterocolitica containing or lacking the virulence plasmid pYV. CopN, but not NrdB, was secreted by Y. enterocolitica in a Ca2+- and pYV-dependent fashion. These data indicate that components of the putative type III apparatus of C. trachomatis are expressed and that at least one of these products is secreted by chlamydiae to the inclusion membrane. The observation that CopN is also secreted by the Yersinia type III apparatus provides support for the notion that chlamydiae secrete proteins via a type III mechanism. C1 NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. RP NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. EM Ted_Hackstadt@NIH.GOV NR 67 TC 122 Z9 125 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 2000 VL 38 IS 5 BP 1048 EP 1060 DI 10.1046/j.1365-2958.2000.02212.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 395JD UT WOS:000166576500011 PM 11123678 ER PT J AU Ladenheim, B Krasnova, IN Deng, XL Oyler, JM Polettini, A Moran, TH Huestis, MA Cadet, JL AF Ladenheim, B Krasnova, IN Deng, XL Oyler, JM Polettini, A Moran, TH Huestis, MA Cadet, JL TI Methamphetamine-induced neurotoxicity is attenuated in transgenic mice with a null mutation for interleukin-6 SO MOLECULAR PHARMACOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; POSITRON-EMISSION-TOMOGRAPHY; RECEPTOR MESSENGER-RNA; ADULT-RAT BRAIN; PERIPHERAL BENZODIAZEPINE; SUBSTITUTED AMPHETAMINES; SUBSTANTIA-NIGRA; GENE-EXPRESSION; C-11 WIN-35,428; C57BL/6J MOUSE AB Increasing evidence implicates apoptosis as a major mechanism of cell death in methamphetamine (METH) neurotoxicity. The involvement of a neuroimmune component in apoptotic cell death after injury or chemical damage suggests that cytokines may play a role in METH effects. In the present study, we examined if the absence of IL-6 in knockout (IL-6-/-) mice could provide protection against METH-induced neurotoxicity. Administration of METH resulted in a significant reduction of [I-125] RTI-121-labeled dopamine transporters in the caudate-putamen (CPu) and cortex as well as depletion of dopamine in the CPu and frontal cortex of wild-type mice. However, these METH-induced effects were significantly attenuated in IL-6-/- animals. METH also caused a decrease in serotonin levels in the CPu and hippocampus of wild-type mice, but no reduction was observed in IL-6-/- animals. Moreover, METH induced decreases in [I-125]RTI-55-labeled serotonin transporters in the hippocampal CA3 region and in the substantia nigra-reticulata but increases in serotonin transporters in the CPu and cingulate cortex in wild-type animals, all of which were attenuated in IL-6-/- mice. Additionally, METH caused increased gliosis in the CPu and cortices of wild-type mice as measured by [H-3] PK-11195 binding; this gliotic response was almost completely inhibited in IL-6-/- animals. There was also significant protection against METH-induced DNA fragmentation, measured by the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeled (TUNEL) cells in the cortices. The protective effects against METH toxicity observed in the IL-6-/- mice were not caused by differences in temperature elevation or in METH accumulation in wild-type and mutant animals. Therefore, these observations support the proposition that IL-6 may play an important role in the neurotoxicity of METH. C1 NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NICHD NIH HHS [HD24605] NR 51 TC 81 Z9 85 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2000 VL 58 IS 6 BP 1247 EP 1256 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 377EA UT WOS:000165497900010 PM 11093760 ER PT J AU Miller, DS Nobmann, SN Gutmann, H Toeroek, M Drewe, J Fricker, G AF Miller, DS Nobmann, SN Gutmann, H Toeroek, M Drewe, J Fricker, G TI Xenobiotic transport across isolated brain microvessels studied by confocal microscopy SO MOLECULAR PHARMACOLOGY LA English DT Article ID RESISTANCE-ASSOCIATED PROTEIN; P-GLYCOPROTEIN; ENDOTHELIAL-CELLS; PROXIMAL TUBULES; BARRIER; EXPRESSION; DRUGS; LOCALIZATION; CAPILLARIES; PENETRATION AB To identify specific transporters that drive xenobiotics from central nervous system to blood, the accumulation of fluorescent drugs was studied in isolated capillaries from rat and pig brain using confocal microscopy and quantitative image analysis. Luminal accumulation of daunomycin and of fluorescent derivatives of cyclosporine A (CSA) and ivermectin was concentrative, specific, and energy-dependent (inhibition by NaCN). Transport was reduced by PSC 833, ivermectin, verapamil, CSA, and vanadate, but not by leukotriene C-4 (LTC4), indicating the involvement of P-glycoprotein. Luminal accumulation of the fluorescent organic anions sulforhodamine 101 and fluorescein methotrexate was also concentrative, specific, and energy-dependent. LTC4, chlorodinitrobenzene, and vanadate reduced transport of these compounds, but PSC 833 and verapamil did not, indicating the involvement of a multidrug resistance-associated protein (Mrp). Immunostaining localized P-glycoprotein and Mrp2 to the luminal surface of the capillary endothelium and quantitative polymerase chain reaction showed Mrp1 and Mrp2 expression. Finally, the HIV protease inhibitors saquinavir and ritonavir were potent inhibitors of transport mediated by both P-glycoprotein and Mrp. These results validate a new method for studying drug transport in isolated brain capillaries and implicate both P-glycoprotein and one or more members of the Mrp family in drug transport from central nervous system to blood. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Inst Pharmazeut Technol & Biopharm, Heidelberg, Germany. Univ Clin Kantonsspital & Childrens Hosp, Dept Res, Basel, Switzerland. Univ Clin Kantonsspital & Childrens Hosp, Dept Internal Med, Div Gastroenterol, Basel, Switzerland. Univ Clin Kantonsspital & Childrens Hosp, Dept Internal Med, Div Clin Pharmacol, Basel, Switzerland. RP Miller, DS (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 34 TC 208 Z9 210 U1 2 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2000 VL 58 IS 6 BP 1357 EP 1367 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 377EA UT WOS:000165497900024 PM 11093774 ER PT J AU Benya, RV Kusui, T Katsuno, T Tsuda, T Mantey, SA Battey, JF Jensen, RT AF Benya, RV Kusui, T Katsuno, T Tsuda, T Mantey, SA Battey, JF Jensen, RT TI Glycosylation of the gastrin-releasing peptide receptor and its effect on expression, G protein coupling, and receptor modulatory processes SO MOLECULAR PHARMACOLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; TUNICAMYCIN INCREASES DESENSITIZATION; N-LINKED GLYCOSYLATION; BOMBESIN RECEPTORS; HORMONE-BINDING; DOWN-REGULATION; ACETYLCHOLINE-RECEPTORS; CARBOHYDRATE MOIETY; LIGAND-BINDING; CELLS AB Many gastrointestinal G protein-coupled receptors are glycosylated; however, which potential glycosylation sites are actually glycosylated and their role in receptor transduction or receptor modulation (internalization, down-regulation, desensitization) is largely unknown. We used site-directed mutagenesis to address these issues with the gastrin-releasing peptide receptor (GRP-R). Each of the four potential glycosylation sites was mutated by converting the Asn (N) to Gln (Q). Transient expression in CHOP cells demonstrated that changing Asn(24) or Asn(191) inhibited GRP-R cell surface expression, whereas elimination of Asn(5) and Asn(20) had no effect. Using ligand crosslinking studies in stable mutants expressed in Balb 3T3 cells, all four potential extracellular sites were glycosylated with carbohydrate residues of approximately 13 kDa on Asn(5), 10 kDa on Asn(20), 5 kDa on Asn(24), and 9 kDa on Asn(191). Removal of three glycosylation sites (N5,20,24, Q mutant) did not alter receptor affinity or G protein coupling; therefore, it could be speculated that deglycosylation at Asn(191) might be responsible for the altered G protein coupling seen with complete enzymatic deglycosylation of the native receptor previously reported. Removal of any single glycosylation site did not interfere with GRP-R induced chronic desensitization or down-regulation. However, elimination of all three NH2-terminal sites (N5,20,24) markedly attenuated both processes, with no effect on acute homologous desensitization and with only a minimal alteration of GRP-R internalization, supporting the findings of other studies that suggest that chronic desensitization and down-regulation are functionally coupled, distinct from acute desensitization and distinct from internalization. These data show that separate and specific glycosylation sites are important for GRP-R trafficking to the cell surface, ligand binding, G protein coupling, chronic desensitization, and down-regulation. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Illinois, Sch Med, Dept Med, Chicago, IL USA. Natl Inst Deafness & Commun Disorders, NIH, Bethesda, MD USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10-9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK51168] NR 40 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2000 VL 58 IS 6 BP 1490 EP 1501 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 377EA UT WOS:000165497900039 PM 11093789 ER PT J AU Lin, ZC Wang, WF Uhl, GR AF Lin, ZC Wang, WF Uhl, GR TI Dopamine transporter tryptophan mutants highlight candidate dopamine- and cocaine-selective domains SO MOLECULAR PHARMACOLOGY LA English DT Article ID NOREPINEPHRINE TRANSPORTERS; STRUCTURAL DOMAINS; NUCLEUS-ACCUMBENS; INHIBITION; EXPRESSION; MECHANISM; SUBSTRATE; BINDING; RECOGNITION; MUTATIONS AB Cocaine blocks the normal role of the dopamine transporter (DAT) in terminating dopamine signaling and in restricting its spatial spread through molecular interactions that remain largely obscure. Cocaine analog structure-activity studies suggest roles for cationic and hydrophobic interactions between DAT, dopamine, cocaine, and the sodium and chloride ions whose gradients power uptake processes. Tryptophan residues lying in putative DAT transmembrane domains could contribute to both aromatic and cationic interactions between DAT and dopamine or cocaine. We thus produced mutant DATs with alanine substitutions for tryptophans lying in or near putative DAT transmembrane domains. We have focused analyses on mutations that exert selective influences on affinities for dopamine or the cocaine analog CFT [(-)-2-beta -carbomethoxy-3-beta-(4-fluorophenyl)tropane]. Substitutions W162A, W255A, and W310A reduced dopamine uptake affinities. 5W266A, 12W555A, and 12W561A each reduced dopamine superficial recognition affinities by more than 3-fold and all retained affinity for CFT. W406A, W496A and W523A each reduced CFT affinity, and W84A increased CFT affinity. None of these four mutations decreased dopamine uptake affinity. These data, current provisional DAT structural models, and results from parallel studies of other mutants identify candidate dopamine-selective DAT domains for transmembrane dopamine permeation and regions in which mutations selectively lower CFT affinities. Tryptophan residues may contribute more extensively to these selective domains than other previously studied DAT amino acids. These sites provide tempting targets for selective blockers of cocaine recognition by DAT. C1 NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. NR 37 TC 47 Z9 47 U1 2 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2000 VL 58 IS 6 BP 1581 EP 1592 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 377EA UT WOS:000165497900049 PM 11093799 ER PT J AU Larisch, S Yi, YS Lotan, R Kerner, H Eimerl, S Parks, WT Gottfried, Y Reffey, SB de Caestecker, MP Danielpour, D Book-Melamed, N Timberg, R Duckett, CS Lechleider, RJ Steller, H Orly, J Kim, SJ Roberts, AB AF Larisch, S Yi, YS Lotan, R Kerner, H Eimerl, S Parks, WT Gottfried, Y Reffey, SB de Caestecker, MP Danielpour, D Book-Melamed, N Timberg, R Duckett, CS Lechleider, RJ Steller, H Orly, J Kim, SJ Roberts, AB TI A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif SO NATURE CELL BIOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; PROGRAMMED CELL-DEATH; CYTOCHROME-C; EPITHELIAL-CELLS; MAMMALIAN SEPTIN; TGF-BETA; CYTOSKELETAL; DROSOPHILA; INDUCTION; GENE AB Here we describe a protein product of the human septin H5/PNUTL2/CDCrel2b gene, which we call ARTS (for apoptosis-related protein in the TGF-beta signalling pathway). ARTS is expressed in many cells and acts to enhance cell death induced by TGF-beta or, to a lesser extent, by other apoptotic agents. Unlike related septin gene products, ARTS is localized to mitochondria and translocates to the nucleus when apoptosis occurs. Mutation of the P-loop of ARTS abrogates its competence to activate caspase 3 and to induce apoptosis. Taken together, these observations expand the functional attributes of septins previously described as having roles in cytokinesis and cellular morphogenesis. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Rambam Med Ctr, Dept Pathol, Haifa, Israel. Hebrew Univ Jerusalem, Dept Biol Chem, Alexander Silberman Inst Life Sci, IL-91904 Jerusalem, Israel. Case Western Reserve Univ, Ctr Canc, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NR 41 TC 155 Z9 168 U1 0 U2 5 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD DEC PY 2000 VL 2 IS 12 BP 915 EP 921 PG 7 WC Cell Biology SC Cell Biology GA 382GK UT WOS:000165814500014 PM 11146656 ER PT J AU Pishvaee, B Costaguta, G Yeung, BG Ryazantsev, S Greener, T Greene, LE Eisenberg, E McCaffery, JM Payne, GS AF Pishvaee, B Costaguta, G Yeung, BG Ryazantsev, S Greener, T Greene, LE Eisenberg, E McCaffery, JM Payne, GS TI A yeast DNA J protein required for uncoating of clathrin-coated vesicles in vivo SO NATURE CELL BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; GENE DELETION; DOMAIN; AUXILIN; HSC70; ENDOCYTOSIS; RECRUITMENT; COMPARTMENT; CHAPERONE; APPENDAGE AB Clathrin-coated vesicles mediate diverse processes such as nutrient uptake, downregulation of hormone receptors, formation of synaptic vesicles, virus entry, and transport of biosynthetic proteins to lysosomes. Cycles of coat assembly and disassembly are integral features of clathrin-mediated vesicular transport (Fig. la). Coat assembly involves recruitment of clathrin triskelia, adaptor complexes and other factors that influence coat assembly, cargo sequestration, membrane invagination and scission(1-3) (Fig. 1a). Coat disassembly is thought to be essential for fusion of vesicles with target membranes and for recycling components of clathrin coats to the cytoplasm for further rounds of vesicle formation. In vitro, cytosolic heat-shock protein 70 (Hsp70) and the J-domain co-chaperone auxilin catalyse coat disassembly(4). However, a specific function of these factors in uncoating in vivo has not been demonstrated, leaving the physiological mechanism and significance of uncoating unclear. Here we report the identification and characterization of a Saccharomyces cerevisiae J-domain protein, Aux1. Inactivation of Aux1 results in accumulation of clathrin-coated vesicles, impaired cargo delivery, and an increased ratio of vesicle-associated to cytoplasmic clathrin. Our results demonstrate an in vivo uncoating function of a J domain cc-chaperone and establish the physiological significance of uncoating in transport mediated by clathrin-coated vesicles. C1 Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90024 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biol, Integrated Imaging Ctr, Baltimore, MD 21218 USA. RP Pishvaee, B (reprint author), Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90024 USA. FU NIGMS NIH HHS [R01 GM39040] NR 32 TC 72 Z9 76 U1 0 U2 7 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD DEC PY 2000 VL 2 IS 12 BP 958 EP 963 DI 10.1038/35046619 PG 6 WC Cell Biology SC Cell Biology GA 382GK UT WOS:000165814500021 PM 11146663 ER PT J AU Riazuddin, S Castelein, CM Ahmed, ZM Lalwani, AK Mastroianni, MA Naz, S Smith, TN Liburd, NA Friedman, TB Griffith, AJ Riazuddin, S Wilcox, ER AF Riazuddin, S Castelein, CM Ahmed, ZM Lalwani, AK Mastroianni, MA Naz, S Smith, TN Liburd, NA Friedman, TB Griffith, AJ Riazuddin, S Wilcox, ER TI Dominant modifier DFNM1 suppresses recessive deafness DFNB26 SO NATURE GENETICS LA English DT Article ID MITOCHONDRIAL TRNA(SER(UCN)) GENE; NON-SYNDROMIC DEAFNESS; HEARING IMPAIRMENT; SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS; MUTATION; FAMILY; EXISTENCE; FORM AB More than 50% of severe childhood deafness is genetically determined, approximately 70% of which occurs without other abnormalities and is thus termed nonsyndromic(1,2). So far, 30 nonsyndromic recessive deafness loci have been mapped and the defective genes at 6 loci, DFNB1, DFNB2, DFNB3, DFNB4, DFNB9 and DFNB21, have been identified, encoding connexin-26 (ref. 3), myosin VIIA (ref. 4), myosin XV (ref. 5), pendrin(6) otoferlin(7) and alpha -tectorin(8), respectively. Here we map a new recessive nonsyndromic deafness locus, DFNB26, to a 1.5-cM interval of chromosome 4q31 in a consanguineous Pakistani family. A maximum rod score of 8.10 at theta =0 was obtained with D4S1610 when only the 8 affected individuals in this family were included in the calculation. There are seven unaffected family members who are also homozygous for the DFNB26-linked haplotype and thus are non-penetrant. A dominant modifier, DFNM1. that suppresses deafness in the 7 nonpenetrant individuals was mapped to a 5.6-cM region on chromosome 1q24 with a rod score of 4.31 at theta =0 for D1S2815. C1 NIDCD, Genet Mol Lab, NIH, Rockville, MD 20852 USA. Punjab Univ, Ctr Excellence Mol Biol, Lahore, Pakistan. Univ Calif San Francisco, Dept Otolaryngol, Lab Mol Otol, San Francisco, CA 94143 USA. NIDCD, Neurootol Branch, NIH, Bethesda, MD USA. RP Wilcox, ER (reprint author), NIDCD, Genet Mol Lab, NIH, Rockville, MD 20852 USA. OI Naz, Sadaf/0000-0002-1912-0235 FU NIDCD NIH HHS [Z01DC00035] NR 31 TC 77 Z9 81 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2000 VL 26 IS 4 BP 431 EP 434 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 379YX UT WOS:000165671700014 PM 11101839 ER PT J AU Siegel, RM Chan, FKM Chun, HJ Lenardo, MJ AF Siegel, RM Chan, FKM Chun, HJ Lenardo, MJ TI The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity SO NATURE IMMUNOLOGY LA English DT Review ID DOMAIN-CONTAINING RECEPTOR; TUMOR-NECROSIS-FACTOR; MATURE T-LYMPHOCYTES; DEATH-DOMAIN; LYMPHOPROLIFERATIVE SYNDROME; MEDIATED APOPTOSIS; ANTIGEN RECEPTOR; TNF RECEPTOR; B-CELLS; MONOCLONAL-ANTIBODY AB Originally identified as a cell surface receptor that triggered the death of lymphocytes and tumor cells, it is now recognized that pas (also known as CD95 or Apo-I) has distinct functions in the life and death of different cell types in the immune system, pas signaling may also be involved in T cell costimulation and proliferation. Although pas deficiency in humans and mice predisposes them towards systemic autoimmunity, Fas-FasL interactions can also facilitate organ-specific immunopathology. Proximal signaling by pas and related receptors depends on subunit preassembly, which accounts for the dominant-negative effect of pathogenic receptor mutants and natural splice variants. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Siegel, Richard/C-7592-2009; Chun, Hyung/K-1859-2013; Chan, Francis/E-9647-2014; Chan, Francis K. L./F-4851-2010 OI Siegel, Richard/0000-0001-5953-9893; Chan, Francis/0000-0002-4803-8353; Chan, Francis K. L./0000-0001-7388-2436 NR 115 TC 292 Z9 296 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2000 VL 1 IS 6 BP 469 EP 474 DI 10.1038/82712 PG 6 WC Immunology SC Immunology GA 380VR UT WOS:000165724600009 PM 11101867 ER PT J AU Terabe, M Matsui, S Noben-Trauth, N Chen, HJ Watson, C Donaldson, DD Carbone, DP Paul, WE Berzofsky, JA AF Terabe, M Matsui, S Noben-Trauth, N Chen, HJ Watson, C Donaldson, DD Carbone, DP Paul, WE Berzofsky, JA TI NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway SO NATURE IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN-E PRODUCTION; RECEPTOR GAMMA-CHAIN; TOXIC LYMPHOCYTES-T; CLASS-I MOLECULES; INTERLEUKIN-4 RECEPTOR; DENDRITIC CELLS; TH2 CELLS; EXPRESSION; RESPONSES; COMPLEX AB Using a mouse model in which tumors show a growth-regression-recurrence pattern, we investigated the mechanisms for down-regulation of cytotoxic T lymphocyte-mediated tumor immunosurveillance. We found that interleukin 4 receptor (IL-4R) knockout and downstream signal transducer and activator of transcription 6 (STAT6) knockout, but not IL-4 knockout, mice resisted tumor recurrence, which implicated IL-13, the only other cytokine that uses the IL-4R-STAT6 pathway,We confirmed this by IL-13 inhibitor (sIL-13R alpha2-Fc) treatment. Loss of natural killer T eel Is (NKT cells) in CDI knockout mice resulted in decreased IL-13 production and resistance to recurrence, Thus, NKT cells and IL-13, possibly produced by NKT cells and signaling through the IL-4R-STAT6 pathway, are necessary for down-regulation of tumor immunosurveillance. IL-13 inhibitors may prove to be a useful tool in cancer immunotherapy. C1 NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Genet Inst, Andover, MA 01810 USA. Vanderbilt Univ, Sch Med, Vanderbilt Canc Ctr, Dept Med, Nashville, TN 37232 USA. RP Berzofsky, JA (reprint author), NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, Bethesda, MD 20892 USA. NR 50 TC 461 Z9 485 U1 4 U2 12 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2000 VL 1 IS 6 BP 515 EP 520 DI 10.1038/82771 PG 6 WC Immunology SC Immunology GA 380VR UT WOS:000165724600016 PM 11101874 ER PT J AU Liu, Z Murray, EA Richmond, BJ AF Liu, Z Murray, EA Richmond, BJ TI Learning motivational significance of visual cues for reward schedules requires rhinal cortex SO NATURE NEUROSCIENCE LA English DT Article ID MONKEYS MACACA-MULATTA; LONG-TERM-MEMORY; RHESUS-MONKEYS; PERIRHINAL CORTEX; PARAHIPPOCAMPAL CORTICES; OBJECT-DISCRIMINATION; STIMULUS ASSOCIATION; AMYGDALOID COMPLEX; TEMPORAL CORTEX; MACAQUE MONKEY AB The limbic system is necessary to associate stimuli with their motivational and emotional significance. The perirhinal cortex is directly connected to this system, and neurons in this region carry signals related to a monkey's progress through visually cued reward schedules. This task manipulates motivation by displaying different visual cues to indicate the amount of work remaining until reward delivery. We asked whether rhinal (that is, entorhinal and perirhinal) cortex is necessary to associate the visual cues with reward schedules. When faced with new visual cues in reward schedules, intact monkeys adjusted their motivation in the schedules, whereas monkeys with rhinal cortex removals failed to do so. Thus, the rhinal cortex is critical for forming associations between visual stimuli and their motivational significance. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. OI Murray, Elisabeth/0000-0003-1450-1642 NR 39 TC 61 Z9 61 U1 2 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2000 VL 3 IS 12 BP 1307 EP 1315 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 405UA UT WOS:000167177900017 PM 11100152 ER PT J AU van Turennout, M Ellmore, T Martin, A AF van Turennout, M Ellmore, T Martin, A TI Long-lasting cortical plasticity in the object naming system SO NATURE NEUROSCIENCE LA English DT Article ID EVENT-RELATED FMRI; PREFRONTAL CORTEX; MEMORY STORAGE; TERM-MEMORY; MECHANISMS; HUMANS; ACTIVATION; CIRCUITRY AB A single exposure to an object can produce long-lasting behavioral change. Here, using event-related functional magnetic resonance imaging (fMRI), we provide evidence for long-lasting changes in cortical activity associated with perceiving and naming objects. In posterior regions, we observed an immediate (30-second) and long-lasting (3-day) decrease in neural activity after brief (200-ms) exposure to nameable and nonsense objects. In addition, slower-developing decreases in left inferior frontal activity were observed concurrently with increases in left insula activity, only for nameable objects. These time-dependent cortical changes may reflect two distinct learning mechanisms: the formation of sparser, yet more object-form-specific, representations in posterior regions, and experience-induced reorganization of the brain circuitry underlying lexical retrieval in anterior regions. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP van Turennout, M (reprint author), Max Planck Inst Psycholinguist, Wundtlaan 1, NL-6525 XD Nijmegen, Netherlands. RI martin, alex/B-6176-2009; OI Ellmore, Timothy/0000-0001-6125-0044 NR 32 TC 165 Z9 167 U1 4 U2 13 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2000 VL 3 IS 12 BP 1329 EP 1334 DI 10.1038/81873 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 405UA UT WOS:000167177900020 PM 11100155 ER PT J AU Jansma, JM Ramsey, NF Coppola, R Kahn, RS AF Jansma, JM Ramsey, NF Coppola, R Kahn, RS TI Specific versus nonspecific brain activity in a parametric n-back task SO NEUROIMAGE LA English DT Article DE MRI; working memory; parametric design; n-back task; prefrontal cortex; parietal cortex; anterior cingulate ID SPATIAL WORKING-MEMORY; HUMAN PREFRONTAL CORTEX; FUNCTIONAL MRI; NEURAL SYSTEM; SCHIZOPHRENIA; ACTIVATION; DYSFUNCTION; DIFFICULTY; RETRIEVAL; DYNAMICS AB In this study functional magnetic resonance imaging (fMRI) was used to examine cerebral activity patterns in relation to increasing mental load of a working memory task. Aim of the experiment was to distinguish nonspecific task-related processes from specific workload processes analytically. Twelve healthy volunteers engaged in a spatial n-back task with four levels. FMRI data were acquired with the SD-PRESTO pulse sequence. Analysis entailed a two-step multiple regression algorithm, which was specifically designed to measure and separate load-sensitive and load-insensitive activity simultaneously, while preserving the original high spatial resolution of the fMRI signal. Load-sensitive and load-insensitive activity was found in both dorsolateral-prefrontal and parietal cortex, predominantly bilaterally, and in the anterior cingulate. As expected, the left primary sensorimotor cortex showed predominantly load-insensitive activity. Load-sensitive activity reflects specific working memory functions, such as temporary retention and manipulation of information, while load-insensitive activity reflects supportive functions, such as visual orientation, perception, encoding, and response selection and execution. Good performance was correlated with a large area of load-sensitive activity in anterior cingulate, and with a small area of load-insensitive activity in the right parietal cortex. The findings indicate that nonspecific and specific working memory processes colocalize and are represented in multiple frontal and parietal regions. Implication of this analytical strategy for application in research on psychiatric disorders is discussed. (C) 2000 Academic Press. C1 Univ Utrecht, Med Ctr, Dept Psychiat, NL-3508 GA Utrecht, Netherlands. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Jansma, JM (reprint author), Univ Utrecht, Med Ctr, Dept Psychiat, HP A01-126,POB 85500, NL-3508 GA Utrecht, Netherlands. NR 47 TC 131 Z9 136 U1 2 U2 18 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD DEC PY 2000 VL 12 IS 6 BP 688 EP 697 DI 10.1006/nimg.2000.0645 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 378BT UT WOS:000165562300008 PM 11112400 ER PT J AU Benazzouz, A Hallett, M AF Benazzouz, A Hallett, M TI Mechanism of action of deep brain stimulation SO NEUROLOGY LA English DT Article; Proceedings Paper CT Meeting on Deep Brain Stimulation for Parkinson's Disease and Tremor CY FEB, 1997 CL MIAMI, FLORIDA DE high-frequency stimulation; deep brain stimulation; action potentials; depolarization block ID HIGH-FREQUENCY STIMULATION; NIGRA PARS RETICULATA; SUBTHALAMIC NUCLEUS; PARKINSONS-DISEASE; ELECTRICAL-STIMULATION; ELECTROPHYSIOLOGICAL DATA; PALLIDAL STIMULATION; MOVEMENT-DISORDERS; SYMPTOMS; MONKEYS AB Initial observations in patients with tremor treated with deep brain stimulation (DBS) of the thalamus suggested that application of high-frequency stimulation (HFS) had a lesion-like effect. New clinical information from patients treated with DBS of the subthalamic nucleus (STN) and globus pallidus internus (GPi) suggested a more complex mechanism of action. Recent experiments in the rat have shown that HFS of the STN was accompanied by increased release of glutamate and dopamine in the substantia nigra and striatum, respectively. Observations made in the GPI of parkinsonian patients during surgery suggest that stimulation may excite GABA release in axons from afferent connections. Therefore, although depolarization block may remain a major mechanism of action, generation of action potentials and release of neurotransmitters may also be involved in the therapeutic effects of DBS in Parkinson's disease. C1 CHRU, INSERM, U318, Lab Neurobiol Preclin, F-88043 Grenoble 09, France. NINDS, Bethesda, MD 20892 USA. RP Benazzouz, A (reprint author), CHRU, INSERM, U318, Lab Neurobiol Preclin, Pavill B,BP 217, F-88043 Grenoble 09, France. RI Benazzouz, Abdelhamid/E-5050-2016 NR 32 TC 156 Z9 161 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 2000 VL 55 IS 12 SU 6 BP S13 EP S16 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 386TT UT WOS:000166078200004 PM 11188968 ER PT J AU Kok, CC Boyt, A Gaudieri, S Martins, R Askanas, V Dalakas, M Kiers, L Mastaglia, F Garlepp, M AF Kok, CC Boyt, A Gaudieri, S Martins, R Askanas, V Dalakas, M Kiers, L Mastaglia, F Garlepp, M TI Mitochondrial DNA variants in inclusion body myositis SO NEUROMUSCULAR DISORDERS LA English DT Article DE inclusion body myositis; Alzheimer's disease; mitochondrial DNA; phylogenetic analysis ID ALZHEIMERS-DISEASE; MYOPATHIES; DELETIONS; MUTATION; POLYMYOSITIS; MUSCLE; RISK AB Mitochondrial DNA variants have been shown to be associated with many diseases, Mutations at mitochondrial DNA nucleotide positions 3192, 3196, 3397 and 4336 have been described in association with late-onset Alzheimer's disease. The pathological similarities between inclusion body myositis and Alzheimer's disease prompted an analysis of the relationship between the reported mutations and sporadic inclusion body myositis. The 4336G variant was not significantly increased in patients with inclusion body myositis or Alzheimer's disease when compared to controls. None of the patients with inclusion body myositis carried mutations at nucleotide positions 3192, 3196 and 3397. A transition at nucleotide position 4580 was detected in some patients with inclusion body myositis and Alzheimer's disease but was not significantly higher in frequency when compared to controls. Phylogenetic analysis showed that the 4336G and 4580A variants clustered together in their respective group. A group of patients with inclusion body myositis also clustered together an a separate branch of the phylogenetic tree. Closer investigation of this group revealed a common polymorphism at nucleotide position 16311. The frequency of the 16311C variant was higher in inclusion body myositis than in Alzheimer's disease and controls, although when only caucasian patients were considered the increased frequency was not statistically significant. Further studies will be required to determine whether this variant plays a role in the pathogenesis of inclusion body myositis. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Curtin Univ Technol, Sch Pharm, Perth, WA 6845, Australia. Univ Western Australia, Queen Elizabeth II Med Ctr, Australian Neuromuscular Res Inst, Nedlands, WA, Australia. Hollywood Private Hosp, Univ Dept Surg, Nedlands, WA, Australia. Univ Western Australia, Ctr Mol Immunol & Instrumentat, Nedlands, WA 6009, Australia. Univ So Calif, Sch Med, Dept Neurol, Neuromuscular Ctr, Los Angeles, CA 90033 USA. NINDS, NIH, Bethesda, MD 20892 USA. Royal Melbourne Hosp, Dept Neurol, Melbourne, Vic, Australia. RP Garlepp, M (reprint author), Curtin Univ Technol, Sch Pharm, GPO Box U 1987, Perth, WA 6845, Australia. NR 34 TC 11 Z9 11 U1 0 U2 0 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 DEC PY 2000 VL 10 IS 8 BP 604 EP 611 DI 10.1016/S0960-8966(00)00144-9 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 374VK UT WOS:000165364900011 PM 11053689 ER PT J AU Sakai, R Henderson, JT O'Bryan, JP Elia, AJ Saxton, TM Pawson, T AF Sakai, R Henderson, JT O'Bryan, JP Elia, AJ Saxton, TM Pawson, T TI The mammalian ShcB and ShcC phosphotyrosine docking proteins function in the maturation of sensory and sympathetic neurons SO NEURON LA English DT Article ID NERVE GROWTH-FACTOR; SIGNAL-TRANSDUCTION PATHWAYS; MICE LACKING GDNF; ADAPTER PROTEIN; SRC HOMOLOGY-2; TRK RECEPTORS; SH2 DOMAIN; CUTANEOUS MECHANORECEPTORS; NEUROTROPHIC FACTOR; BINDING DOMAINS AB Shc proteins possess SH2 and PTB domains and serve a scaffolding function in signaling by a variety of receptor tyrosine kinases. There are three known mammalian She genes, of which ShcB and ShcC are primarily expressed in the nervous system. We have generated null mutations in ShcB and ShcC and have obtained mice lacking either ShcB or ShcC or both gene products. ShcB-deficient animals exhibit a loss of peptidergic and nonpeptidergic nociceptive sensory neurons, which is not enhanced by additional loss of ShcC. Mice lacking both ShcB and ShcC exhibit a significant loss of neurons within the superior cervical ganglia, which is not observed in either mutant alone. The results indicate that these She family members possess both unique and overlapping functions in regulating neural development and suggest physiological roles for ShcB/ShcC in TrkA signaling. C1 Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, Toronto, ON M5G 1X5, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5S 1A8, Canada. Amgen Inst, Toronto, ON M5G 2C1, Canada. Natl Canc Ctr, Res Inst, Div Virol, Chuo Ku, Tokyo 1040045, Japan. NIEHS, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Pawson, T (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, 600 Univ Ave, Toronto, ON M5G 1X5, Canada. RI Pawson, Tony/E-4578-2013 NR 65 TC 70 Z9 72 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC PY 2000 VL 28 IS 3 BP 819 EP 833 DI 10.1016/S0896-6273(00)00156-2 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 386JJ UT WOS:000166057500019 PM 11163269 ER PT J AU Standley, S Roche, KW McCallum, J Sans, N Wenthold, RJ AF Standley, S Roche, KW McCallum, J Sans, N Wenthold, RJ TI PDZ domain suppression of an ER retention signal in NMDA receptor NR1 splice variants SO NEURON LA English DT Article ID CELL-SURFACE EXPRESSION; ENDOPLASMIC-RETICULUM; SUBUNIT COMPOSITION; GLUTAMATE RECEPTORS; SECRETORY PATHWAY; MEMBRANE-PROTEINS; TERMINAL DOMAIN; RAT; AFFINITY; PHOSPHORYLATION AB The NMDA receptor NR1 subunit has four splice variants that differ in their C-terminal, cytoplasmic domain. We investigated the contribution of the C-terminal cassettes, CO, C1, C2, and C2', to trafficking of NR1 in heterologous cells and neurons. We identified an ER retention signal (RRR) in the C1 cassette of NR1, which is similar to the RXR motif in ATP-sensitive K+ channels (Zerangue et al., 1999). We found that surface expression of NR1-3, which contains C1, is due to a site on the C2' cassette, which includes the terminal 4 amino acid PDZ-interacting domain. This site suppresses ER retention of the C1 cassette and leads to surface expression. These findings suggest a role for PDZ proteins in facilitating the transition of receptors from an intracellular pool to the surface of the neuron. C1 Natl Inst Deafness & Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Standley, S (reprint author), Natl Inst Deafness & Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. OI Roche, Katherine/0000-0001-7282-6539 NR 64 TC 255 Z9 264 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC PY 2000 VL 28 IS 3 BP 887 EP 898 DI 10.1016/S0896-6273(00)00161-6 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 386JJ UT WOS:000166057500024 PM 11163274 ER PT J AU Wu, CWH Kaas, JH AF Wu, CWH Kaas, JH TI Spinal cord atrophy and reorganization of motoneuron connections following long-standing limb loss in primates SO NEURON LA English DT Article ID PRIMARY MOTOR CORTEX; NEURON-SPECIFIC EPITOPE; ISCHEMIC NERVE BLOCK; SELECTIVE REINNERVATION; MEDIAL GASTROCNEMIUS; GAMMA-MOTONEURONS; NEUROMUSCULAR-JUNCTION; HORSERADISH-PEROXIDASE; INTERCOSTAL MUSCLES; PARTIAL DENERVATION AB Primates with long-standing therapeutic amputations of a limb at a young age were used to investigate the possibility that deefferented motor nerves sprout to new muscle targets. Injections of anatomical tracers into the muscles proximal to the amputated stump labeled a larger extent of motoneurons than matched injections on the intact side or in normal animals, including motoneurons that would normally supply only the missing limb muscles. Although the total numbers of distal limb motoneurons remained normal, some distal limb motoneurons on the amputated side were smaller in size and simpler in form. These results suggest that deprived motoneurons survive and retain function by reinnervating new muscle targets. The sprouted motor efferents may account for some of the reorganization of primary motor cortex that follows long-standing amputation. C1 Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. NINDS, Human Cortic Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. EM jon.kaas@vanderbilt.edu FU NINDS NIH HHS [NS 16446] NR 73 TC 30 Z9 30 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD DEC PY 2000 VL 28 IS 3 BP 967 EP 978 DI 10.1016/S0896-6273(00)00167-7 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 386JJ UT WOS:000166057500030 PM 11163280 ER PT J AU Ishai, A Ungerleider, LG Haxby, JV AF Ishai, A Ungerleider, LG Haxby, JV TI Distributed neural systems for the generation of visual images SO NEURON LA English DT Article ID PRIMATE TEMPORAL CORTEX; MENTAL-IMAGERY; WORKING-MEMORY; AUTOMATED ALGORITHM; FUNCTIONAL-ANATOMY; NEURONAL CORRELATE; SUSTAINED ACTIVITY; FACE PERCEPTION; TERM-MEMORY; ATTENTION AB Visual perception of houses, faces, and chairs evoke differential responses in ventral temporal cortex. Using fMRI, we compared activations evoked by perception and imagery of these object categories. We found content-related activation during imagery in extrastriate cortex, but this activity was restricted to small subsets of the regions that showed category-related activation during perception. Within ventral temporal cortex, activation during imagery evoked stronger responses on the left whereas perception evoked stronger responses on the right. Additionally, visual imagery evoked activity in parietal and frontal cortex, but this activity was not content related. These results suggest that content-related activation during imagery in visual extrastriate cortex may be implemented by "top-down" mechanisms in parietal and frontal cortex that mediate the retrieval of face and object representations from long-term memory and their maintenance through visual imagery. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Ishai, A (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. NR 55 TC 343 Z9 346 U1 6 U2 27 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC PY 2000 VL 28 IS 3 BP 979 EP 990 DI 10.1016/S0896-6273(00)00168-9 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 386JJ UT WOS:000166057500031 PM 11163281 ER PT J AU Sokoloff, L AF Sokoloff, L TI Seymour Kety, 1915-2000 - In memoriam SO NEUROPSYCHOPHARMACOLOGY LA English DT Biographical-Item C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bldg 36, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2000 VL 23 IS 6 BP 717 EP 721 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 372ZY UT WOS:000165265000011 ER PT J AU Markovic-Plese, S AF Markovic-Plese, S TI Molecular mimicry in neurological diseases SO NEUROSCIENTIST LA English DT Article DE molecular mimicry; cross-reactivity; T cell receptor specificity ID MYELIN BASIC-PROTEIN; T-CELL RECEPTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; PEPTIDE COMBINATORIAL LIBRARIES; MULTIPLE-SCLEROSIS; TRANSGENIC MICE; ANTIGEN RECOGNITION; VIRAL-INFECTION; IDENTIFICATION; HOMOLOGY AB Several mechanisms have been implicated in the activation and expansion of myelin-specific T cells in multiple sclerosis, a presumed autoimmune disease of the central nervous system. In this article, we will review the mechanisms of molecular mimicry whereby myelin-specific T lymphocytes may be activated by foreign antigens. Recent studies from our laboratory have documented an unexpected flexibility of T cell receptor recognition and demonstrated that sequence homology is not a requirement for cross-recognition. Using synthetic combinatorial peptide libraries, it was possible to identify the entire spectrum of molecular mimics for T cell clones. This approach may prove useful for the development of antigen-specific therapies and vaccines. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD DEC PY 2000 VL 6 IS 6 BP 428 EP 432 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 375KD UT WOS:000165397400017 ER PT J AU Flynn, KM Ferguson, SA Delclos, KB Newbold, RR AF Flynn, KM Ferguson, SA Delclos, KB Newbold, RR TI Multigenerational exposure to dietary genistein has no severe effects on nursing behavior in rats SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 17th International Neurotoxicology Conference CY OCT 17-20, 1999 CL LITTLE ROCK, ARKANSAS SP Natl Ctr Environm Assessment, USEPA, Agcy Toxic Substances & Dis Registry, NICHHD, Natl Inst Environm Hlth Sci, Natl Ctr Environm Health/CDC, Neurotoxicol Div/NHEERL/US EPA DE phytoestrogen; endocrine disrupter; estrogen ID MATERNAL-BEHAVIOR; SHR RATS; PHYTOESTROGENS; ISOFLAVONES; DAIDZEIN; ONSET; CARE; BETA AB The phytoestrogen and principal isoflavone in soy, genistein, has adverse effects on reproductive physiology in rodents. Since physiology and behavior are both sensitive to perturbations by estrogens, genistein may produce behavioral alterations as well. This paper reports one aspect of a study in wh ich several adult rodent behaviors will be assessed following long term multigenerational dietary exposure to genistein. Since maternal care may affect offspring behaviors in adulthood, it is important to determine the potential for genistein to affect maternal behavior. Here, rats (FU generation) were fed soy-free diets containing 0, 5, 100, or 500 ppm genistein (approx. 0, 0.4, 8, and 40 mg/kg/day for an adult) beginning on postnatal day (PND) 42. Two generations of offspring (F1 and F2) were continued on these diets and all treatment groups of the F3 generation were returned to 0 ppm at weaning (PND 22). In the first 3 weeks after parturition (for each generation), darns were assessed on 6 occasions for the presence of the arched back posture with at least one pup nursing. Data were analyzed by 3 way repeated measures analysis of variance (ANOVA) with generation, treatment, and postnatal day as factors, and p<0.05 required for significance There were no significant interactions among treatment, generation, or day, and no overall effects of treatment or generation. As expected, there was a significant overall effect of day, with animals nursing less on later days (p<0.0001). As assessed here, these results suggest that lifelong and multigenerational exposure to dietary genistein has no severe effects on nursing behavior in rodents. (C) 2000 Inter Press Inc. 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. Natl Inst Environm Hlth Sci, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC USA. RP Flynn, KM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd,HFT-132, Jefferson, AR 72079 USA. NR 24 TC 19 Z9 20 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 2000 VL 21 IS 6 BP 997 EP 1001 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 405TQ UT WOS:000167177000009 PM 11233769 ER PT J AU Germanier, M Defais, M Bohr, VA Larminat, F AF Germanier, M Defais, M Bohr, VA Larminat, F TI Transcription-coupled repair is inducible in hamster cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; DNA-REPAIR; COCKAYNES-SYNDROME; DHFR GENE; XERODERMA-PIGMENTOSUM; SYNDROME FIBROBLASTS; PYRIMIDINE DIMERS; ULTRAVIOLET-LIGHT; MISMATCH REPAIR; NUCLEAR MATRIX AB In mammalian cells, the rate of nucleotide excision repair of UV dimers is heterogeneous throughout the genome, with repair occurring more rapidly in the transcribed strand of active genes than in the genome overall. This repair pathway is termed transcription-coupled repair (TCR) and is thought to permit the rapid resumption of RNA synthesis following UV irradiation. To evaluate the inducibility of the TCR process, we examined the repair of UV-induced cyclobutane pyrimidine dimers (CPDs) at the level of the gene following exposure of hamster cells to a sub-lethal UV fluence, 3 h prior to a higher dose. Repair was detected by a well-established technique allowing quantification of CPDs at the level of a specific strand by Southern blot hybridization. Here, we show that prior low-dose irradiation clearly enhanced the early rate of CPD removal in the transcribed strand of the active DHFR gene. Furthermore, the RNA synthesis recovery following UV exposure was stimulated by the priming UV dose. Thus, we provide evidence for an inducible TCR response to CPDs in hamster cells. This pathway is independent of the p53 activation, since the hamster cell line that we used expresses high levels of mutant p53 protein. C1 Inst Pharmacol & Biol Struct, CNRS, UMR 5089, F-31400 Toulouse, France. NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP Larminat, F (reprint author), Inst Pharmacol & Biol Struct, CNRS, UMR 5089, 205 Route Narbonne, F-31400 Toulouse, France. NR 34 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 1 PY 2000 VL 28 IS 23 BP 4674 EP 4678 DI 10.1093/nar/28.23.4674 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 381QL UT WOS:000165774400014 PM 11095677 ER PT J AU Brown, CD Higgins, M Donato, KA Rohde, FC Garrison, R Obarzanek, E Ernst, ND Horan, M AF Brown, CD Higgins, M Donato, KA Rohde, FC Garrison, R Obarzanek, E Ernst, ND Horan, M TI Body mass index and the prevalence of hypertension and dyslipidemia SO OBESITY RESEARCH LA English DT Article DE blood pressure; blood cholesterol; high density lipoprotein-cholesterol; overweight; obesity ID NUTRITION EXAMINATION SURVEYS; HIGH BLOOD CHOLESTEROL; UNITED-STATES ADULTS; NATIONAL-HEALTH; RISK FACTOR; CARDIOVASCULAR-DISEASE; MILD HYPERTENSION; SMOKING CESSATION; WEIGHT-REDUCTION; OVERWEIGHT MEN AB Objective: To describe and evaluate relationships between body mass index (BMI) and blood pressure, cholesterol, high-density lipoprotein-cholesterol (HDL-C), and hyper tension and dyslipidemia. Research Methods and Procedures: A national survey of adults in the United States that included measurement of height, weight, blood pressure, and lipids (National Health and Nutrition Examination Survey III 1988-1994). Crude age-adjusted, age-specific means and proportions, and multivariate odds ratios that quantify the association between hypertension or dyslipidemia and BMI, controlling for race/ethnicity, education, and smoking habits are presented. Results: More than one-half of the adult population is overweight (BMI of 25 to 29.9) or obese (BMI of greater than or equal to 30). The prevalence of high blood pressure and mean levels of systolic and diastolic blood pressure increased as BMI increased at ages younger than 60 years. The prevalence of high blood cholesterol and mean levels of cholesterol were higher at BMI levels over 25 rather than below 25 but did not increase consistently with increasing BMI above 25. Rates of low HDL-C increased and mean levels of HDL-C decreased as levels of BMI increased. The associations of BMI with high blood pressure and abnormal lipids were statistically significant after controlling for age, race or ethnicity, education, and smoking; odds ratios were highest at ages 20 to 39 but most trends were apparent at older ages. Within BMI categories, hypertension was more prevalent and HDL-C levels were higher in black than white or Mexican American men and women. Discussion: These data quantify the strong associations of BMI with hypertension and abnormal lipids. They are consistent with the national emphasis on prevention and control of overweight and obesity and indicate that blood pressure and cholesterol measurement and control are especially important for overweight and obese people. C1 NHLBI, Obes Educ Initiat, NIH, Bethesda, MD 20892 USA. CODA Res, Silver Spring, MD USA. Univ Michigan, Dept Epidemiol & Internal Med, Ann Arbor, MI 48109 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Jackson State Univ, Jackson Heart Study Coordinating Ctr, Jackson, MS USA. RP Donato, KA (reprint author), NHLBI, Obes Educ Initiat, NIH, Bldg 10,31 Ctr Dr MSC,2480, Bethesda, MD 20892 USA. NR 65 TC 356 Z9 379 U1 3 U2 23 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD DEC PY 2000 VL 8 IS 9 BP 605 EP 619 DI 10.1038/oby.2000.79 PG 15 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 400UQ UT WOS:000166890400001 PM 11225709 ER PT J AU Ivy, SP AF Ivy, SP TI NCI cooperative research and development agreements SO ONCOLOGY-NEW YORK LA English DT Article AB The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) currently sponsors more than 160 Investigational New, Drug applications (INDs) and is involved in approximately 1,600 active protocols. It is also currently involved in more than 50 collaborative agreements with pharmaceutical companies. These agreements consist of cooperative research and development agreements (CRADAs) and clinical trials agreements (CTAs). A CRADA is a detailed contract between the NCI and a pharmaceutical company for the clinical co-development of an investigational agent, and may include preclinical development that stipulates terms for a broader scope of research than that covered by a CTA. The CTEP/investigational Drag Branch is currently involved in a number of oxaliplatin (Eloxatin) protocols under the CRADA program. C1 NCI, Invest Drug Branch,Dev Chemotherapy Sect, Canc Therapy Evaluat Program, Div Canc Treatment Diag & Ctr, Rockville, MD 20852 USA. RP Ivy, SP (reprint author), NCI, Invest Drug Branch,Dev Chemotherapy Sect, Canc Therapy Evaluat Program, Div Canc Treatment Diag & Ctr, 6130 Execut Blvd,EPN 700, Rockville, MD 20852 USA. NR 0 TC 2 Z9 2 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 DEC PY 2000 VL 14 IS 12 SU 11 BP 27 EP 29 PG 3 WC Oncology SC Oncology GA 390DE UT WOS:000166279700004 PM 11204659 ER PT J AU Anand, R Bressler, SB Davis, MD Ferris, FL Klein, R Lindblad, AS Milton, RC Sperduto, RD AF Anand, R Bressler, SB Davis, MD Ferris, FL Klein, R Lindblad, AS Milton, RC Sperduto, RD CA Age Related Eye Dis Study Res Grp TI Risk factors associated with age-related macular degeneration - A case-control study in the Age-Related Eye Disease Study: Age-Related Eye Disease Study report number 3 SO OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; NUTRITION EXAMINATION SURVEY; BLUE-MOUNTAINS EYE; CIGARETTE-SMOKING; 5-YEAR INCIDENCE; NATIONAL-HEALTH; MACULOPATHY; POPULATION; SUNLIGHT; ABNORMALITIES AB Objective: To investigate possible risk factors for age-related macular degeneration (AMD) in participants in the Age-Related Eye Disease Study (AREDS). Design: Case-control study. Participants: Of the 4757 persons enrolled in AREDS, 4519 persons aged 60 to 80 years were included in this study. The lesions associated with AMD ranged from absent in both eyes to advanced in one eye. Main Outcome Measures: Stereoscopic color fundus photographs of the macula were used to place participants into one of five groups, based on the frequency and severity of lesions associated with AMD. Participants with fewer than 15 small drusen sewed as the control group. Results: Staged model building techniques were used to compare each of the four case groups with the control group. Increased age was a consistent finding of all four of the case groups compared with the control group, and all the following associations were age adjusted. Persons with either intermediate drusen, extensive smalt drusen, or the pigment abnormalities associated with AMD (group 2) were more likely to be female, more likely to have a history of arthritis, and less likely to have a history of angina. Persons with one or more large drusen or extensive intermediate drusen (group 3) were more likely to use hydrochlorothiazide diuretics and more likely to have arthritis. Hypertension, hyperopia, presence of lens opacities, and white race were also found more frequently in this group as well as in persons with neovascular AMD (group 5). Only persons in group 5 were more likely to have an increased body mass index, whereas persons with geographic atrophy (group 4) as well as those in groups 3 and 5 were more likely to have completed fewer years in school or to be smokers. Those with geographic atrophy were also more likely to use thyroid hormones and antacids. Conclusions: Our findings for smoking and hypertension, which have been noted in previous studies, suggest that two important public health recommendations, the avoidance of smoking and the prevention of hypertension, may reduce the risk of developing AMD. Other associations, such as those for hyperopia, lens opacities, less education, female gender, increased body mass index, and white race, which have been noted in other studies, are also seen in the AREDS population. The increased use of thyroid hormones and antacids in persons with geographic atrophy and the increased likelihood of arthritis or hydrochlorothiazide use in persons with one or more large drusen or extensive intermediate drusen have not been previously reported and need additional investigation. (C) 2000 by the American Academy of Ophthalmology. C1 EMMES Corp, AREDS Coordinating Ctr, Age Related Eye Dis Study Grp, Potomac, MD 20854 USA. Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. Univ Wisconsin, Dept Ophthalmol & Vis Sci, Fundus Photog Reading Ctr, Madison, WI USA. NEI, Div Biometry & Epidemiol, NIH, Bethesda, MD 20892 USA. RP Anand, R (reprint author), EMMES Corp, AREDS Coordinating Ctr, Age Related Eye Dis Study Grp, 11325 7 Locks Rd,Suite 214, Potomac, MD 20854 USA. NR 54 TC 398 Z9 402 U1 10 U2 36 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2000 VL 107 IS 12 BP 2224 EP 2232 PG 9 WC Ophthalmology SC Ophthalmology GA 378LY UT WOS:000165586900045 ER PT J AU Milam, AH Curcio, CA Cideciyan, AV Saxena, S John, SK Kruth, HS Malek, G Heckenlively, JR Weleber, RG Jacobson, SG AF Milam, AH Curcio, CA Cideciyan, AV Saxena, S John, SK Kruth, HS Malek, G Heckenlively, JR Weleber, RG Jacobson, SG TI Dominant late-onset retinal degeneration with regional variation of sub-retinal pigment epithelium deposits, retinal function, and photoreceptor degeneration SO OPHTHALMOLOGY LA English DT Article ID HUMAN ATHEROSCLEROTIC LESIONS; SORSBYS-FUNDUS-DYSTROPHY; BASAL LAMINAR DEPOSIT; AGE-RELATED-CHANGES; BRUCHS MEMBRANE; RETINITIS-PIGMENTOSA; MACULAR DEGENERATION; ELECTRON-MICROSCOPY; FIBROUS PLAQUES; LIPID DROPLETS AB Purpose: To clarify the pathogenesis of late-onset retinal degeneration (L-ORD), an autosomal dominant disorder characterized by thick deposits of lipid-rich material between the retinal pigment epithelium (RPE) and Bruch's membrane. Study Design: Comparative clinicopathologic case report and case series. Tissues: Eyes of an 82-year-old L-ORD eye donor and an age-matched control. Subjects: Five descendants of the eye donor and his affected sister. Methods: The eyes were processed for histopathologic examination, including electron microscopy and immunohistochemistry. Family members were examined clinically and with retinal function tests. Results: The L-ORD eye had sub-RPE deposits that were positive for lipid, including esterified and unesterified cholesterol. The deposits were thinnest in the macula, which retained the highest percentage of photoreceptors. In the periphery, RPE thinning and photoreceptor loss correlated with thickness of the sub-RPE deposits. The eye donor was asymptomatic until his late 50s, when he developed problems with adapting to darkness. At age 68, the eye donor had normal acuity but a midperipheral scotoma and subnormal electroretinograms (ERGs); Visual loss was progressive. The five descendants (at the time of examination ages 44-58) of the eye donor and his affected sister, who were at 50/50 risk of inheriting L-ORD, had normal ERGs, but four showed defects in dark adaptation. The dark adaptation abnormalities had a distribution similar to the thickness of the sub-RPE deposits in the eye donor, with slow kinetics in the midperiphery and normal kinetics centrally. Conclusions: The L-ORD donor eye differed from a previous case in the regional distribution of sub-RPE deposits and photoreceptors. In the next generation of this L-ORD family, the first expression of disease, abnormal dark adaptation, mirrored the regional distribution of the deposits in the donor eye. The fine structure and staining characteristics of the sub-RPE deposits in L-ORD resemble those in age-related macular degeneration and Sorsby fundus dystrophy. (C) 2000 by the American Academy of Ophthalmology. C1 Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. Univ Alabama, Dept Ophthalmol, Birmingham, AL 35294 USA. NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. Univ Alabama, Vis Sci Training Program, Birmingham, AL USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Oregon Hlth Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. RP Milam, AH (reprint author), Univ Penn, Scheie Eye Inst, 51 N 39th St, Philadelphia, PA 19104 USA. RI Cideciyan, Artur/A-1075-2007 OI Cideciyan, Artur/0000-0002-2018-0905 FU NEI NIH HHS [EY06109, EY05627] NR 44 TC 45 Z9 45 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2000 VL 107 IS 12 BP 2256 EP 2266 DI 10.1016/S0161-6420(00)00419-X PG 11 WC Ophthalmology SC Ophthalmology GA 378LY UT WOS:000165586900051 PM 11097607 ER PT J AU Weiss, EI Shaniztki, B Dotan, M Ganeshkumar, N Kolenbrander, PE Metzger, Z AF Weiss, EI Shaniztki, B Dotan, M Ganeshkumar, N Kolenbrander, PE Metzger, Z TI Attachment of Fusobacterium nucleatum PK1594 to mammalian cells and its coaggregation with periodontopathogenic bacteria are mediated by the same galactose-binding adhesin SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE coaggregation; attachment; oral bacteria; Fusobacterium nucleatum ID CAPNOCYTOPHAGA-OCHRACEA ATCC-33596; ORAL BACTERIA; POLYMORPHONUCLEAR LEUKOCYTES; PORPHYROMONAS-GINGIVALIS; ACTINOMYCES-NAESLUNDII; BACTEROIDES-GINGIVALIS; MONOCLONAL-ANTIBODIES; LECTIN; STRAINS; IDENTIFICATION AB It has been shown that Fusobacterium nucleatum PK1594 coaggregates with Prophyromonas gingivalis PK1924 through a galactose binding adhesin. In the present study, attachment of F. nucleatum PK1594 to a variety of mammalian cells was characterized. F. nucleatum PK1594 attached to all eukaryotic cells tested, including human buccal epithelial cells, gingival and periodontal ligament fibroblasts, HeLa cells and murine lymphocytes, macrophages, and polymorphonuclear leukocytes, These attachments were (i) inhibited by galactose, lactose and N-acetylgalactosamine and (ii) inhibited by monoclonal antibody specific for the galactose-binding adhesin of F. nucleatum PK1594. In addition, a coaggregation-defective mutant of F. nucleatum PK1594 (PK2172), which does not exhibit galactose binding activity, did not attach to the mammalian cells. Coaggregation of F. nucleatum PK1594 with P. gingivalis PK 1924 and Actinobacillus actinomycetemcomitans JP2, but not with other bacteria, showed a similar pattern with sugars, monoclonal antibody, and the adhesin-deficient mutant. The results suggest that the attachment of F. nucleatum PK1594 to mammalian cells and its coaggregation with periodontal pathogens are mediated by the same galactose-binding adhesin. C1 Tel Aviv Univ, Maurice & Gabriella Goldshleger Sch Dent Med, Dept Oral Biol, Sackler Fac Med, IL-69978 Tel Aviv, Israel. Forsyth Dent Ctr, Dept Mol Genet, Boston, MA 02115 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Weiss, EI (reprint author), Tel Aviv Univ, Maurice & Gabriella Goldshleger Sch Dent Med, Dept Oral Biol, Sackler Fac Med, IL-69978 Tel Aviv, Israel. FU NIDCR NIH HHS [DE-10969] NR 47 TC 41 Z9 46 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD DEC PY 2000 VL 15 IS 6 BP 371 EP 377 DI 10.1034/j.1399-302x.2000.150606.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 371ND UT WOS:000165184300006 PM 11154434 ER PT J AU DeNucci, DJ Chen, CC Sobiski, C Meehan, S AF DeNucci, DJ Chen, CC Sobiski, C Meehan, S TI The use of SPECT bone scans to evaluate patients with idiopathic jaw pain SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID ATYPICAL FACIAL-PAIN; EMISSION COMPUTED-TOMOGRAPHY; LOW-BACK-PAIN; ALVEOLAR OSTEONECROSIS; DIFFERENTIAL-DIAGNOSIS; ODONTALGIA; THROMBOPHILIA; NEURALGIA; HYPOFIBRINOLYSIS; PATHOPHYSIOLOGY AB Objective. The purpose of this study was to investigate the potential usefulness of single photon emission computed tomography (SPECT) bone scanning with technetium-99m methylene diphosphonate (Tc-99m MDP) in the diagnosis of idiopathic jaw pain. Unlike planar bone scanning, SPECT uses tomographic technology to provide 3-dimensional images, which are more useful in localizing small lesions. Study design, Twenty patients, each with a diagnosis of chronic idiopathic jaw pain, were compared after SPECT bone scanning with 20 age-matched and gender-matched normal controls. Uptake was identified and compared in sites with previously detected jaw pathoses and jaw pain. Results. Nineteen of 20 patients with jaw pain evaluated with SPECT had positive scans, in contrast with 12 of 20 control subjects (P < .04). Positive scans were correlated with painful sites in 15 of 20 patients, with the remaining 5 patients demonstrating no uptake in painful locations. Patients with jaw pain demonstrated 37 of 80 mouth quadrants with positive scans, in contrast with 21 of 80 mouth quadrants in the controls (P < .01). Nineteen of 24 painful mouth quadrants had uptake in the pain group. Of the 21 quadrants positive in the controls, 17 were correlated with previously detected jaw pathoses. The sensitivity and specificity for detecting painful sites were 0.79 and 0.68, respectively The sensitivity and specificity for detecting previously identified pathoses in the jaws of normal controls were 0.80 and 0.93, respectively. Conclusion. Patients with idiopathic jaw pain had a significantly greater frequency of positive SPECT bone scans when compared with normal controls. However, the sensitivity and specificity of SPECT bone scans in detecting painful sites were low. These findings suggest that SPECT bone scanning with Tc-99m MDP is not indicated as a routine imaging procedure for the detection of jaw pathoses, but may be considered as a potential research tool in the future study of chronic idiopathic jaw pain. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. NIDR, Clin Invest & Patient Care Branch, NIH, Bethesda, MD 20892 USA. RP DeNucci, DJ (reprint author), 10925 Citreon Ct, N Potomac, MD 20878 USA. NR 46 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, 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 DEC PY 2000 VL 90 IS 6 BP 750 EP 757 DI 10.1067/moe.2000.105906 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 384FV UT WOS:000165932900013 PM 11113822 ER PT J AU Fleisher, TA Ballow, M AF Fleisher, TA Ballow, M TI Primary immune deficiencies: Presentation, diagnosis, and management - Preface SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. SUNY Coll Buffalo, Childrens Hosp Buffalo, Dept Pediat,Sch Med & Biomed Sci, Div Allergy Immunol & Rheumatol, Buffalo, NY 14222 USA. RP NIH, Warren G Magnuson Clin Ctr, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0031-3955 EI 1557-8240 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD DEC PY 2000 VL 47 IS 6 BP XI EP XII DI 10.1016/S0031-3955(05)70266-2 PG 2 WC Pediatrics SC Pediatrics GA 381JX UT WOS:000165760500001 ER PT J AU Fleisher, TA Bleesing, JJH AF Fleisher, TA Bleesing, JJH TI Immune function SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID INNATE IMMUNITY; SYSTEM; INFLAMMATION; LYMPHOCYTES; COMPLEMENT; BIOLOGY; THERAPY; CELLS AB The immune system consists of two complementary response pathways: (1) the innate immune system and (2) the adaptive immune system. This tightly regulated and complex system provides host protection to a massive array of potentially damaging microorganisms. When immune function is deficient, the host has increased susceptibility to infections. There are multiple cells and a vast array of humoral mediators and cell receptors that are necessary for a normal immune response, and defects in a number of these are responsible for the immune disorders discussed in this issue. C1 NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. RP Fleisher, TA (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. NR 28 TC 8 Z9 9 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD DEC PY 2000 VL 47 IS 6 BP 1197 EP + DI 10.1016/S0031-3955(05)70267-4 PG 14 WC Pediatrics SC Pediatrics GA 381JX UT WOS:000165760500002 PM 11130992 ER PT J AU Uzel, G Holland, SM AF Uzel, G Holland, SM TI Th1 T-cell and monocyte defects SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID INTERFERON-GAMMA-RECEPTOR; CALMETTE-GUERIN INFECTION; AVIUM COMPLEX INFECTION; NECROSIS-FACTOR-ALPHA; MYCOBACTERIAL INFECTION; IFN-GAMMA; MONONUCLEAR PHAGOCYTES; TYROSINE PHOSPHORYLATION; DEFICIENCY; INTERLEUKIN-12 AB Mutations predisposing to infections with intracellular pathogens and affecting Th1 T-cells and monocytes have been identified in the past few years. In this article, the authors review the interaction of T cells and monocytes in the context of host defense against intracellular pathogens. Known genetic defects in these pathways are summarized. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Uzel, G (reprint author), NIAID, Host Def Lab, NIH, 10 Ctr Dr,11N103, Bethesda, MD 20892 USA. NR 51 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD DEC PY 2000 VL 47 IS 6 BP 1275 EP + DI 10.1016/S0031-3955(05)70271-6 PG 17 WC Pediatrics SC Pediatrics GA 381JX UT WOS:000165760500006 PM 11130996 ER PT J AU Bleesing, JJH Straus, SE Fleisher, TA AF Bleesing, JJH Straus, SE Fleisher, TA TI Autoimmune lymphoproliferative syndrome - A human disorder of abnormal lymphocyte survival SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; FAS APO-1/CD95 GENE; BONE-MARROW TRANSPLANTATION; CD95 FAS/APO-1 MUTATIONS; NEGATIVE T-CELLS; THROMBOCYTOPENIC PURPURA; CLINICAL MANIFESTATIONS; DEFECTIVE APOPTOSIS; POINT MUTATION; LPR MICE AB An important aspect of the immune system is the maintenance of a homeostatic balance between lymphocyte survival and death. This is regulated by apoptosis (programmed cell death). One pathway of this active process of cell suicide is mediated by the lymphocyte receptor Fas (CD95). Its importance in this homeostatic balance is underscored by the consequences of defective Pas-mediated apoptosis in patients with autoimmune lymphoproliferative syndrome (ALPS). Abnormal accumulation of lymphocytes results in lymphadenopathy, hepatosplenomegaly, and hypersplenism Failure of removal of potentially autoreactive lymphocytes is associated with the appearance of autoimmune manifestations. Finally, inappropriate survival of lymphocytes may lead to the development of malignancies. C1 NIAID, Dept Lab Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. RP Bleesing, JJH (reprint author), NIAID, Dept Lab Med, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 2C410, Bethesda, MD 20892 USA. NR 66 TC 47 Z9 49 U1 2 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD DEC PY 2000 VL 47 IS 6 BP 1291 EP + DI 10.1016/S0031-3955(05)70272-8 PG 21 WC Pediatrics SC Pediatrics GA 381JX UT WOS:000165760500007 PM 11130997 ER PT J AU Segal, BH Holland, SM AF Segal, BH Holland, SM TI Primary phagocytic disorders of childhood SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID CHRONIC GRANULOMATOUS-DISEASE; CHEDIAK-HIGASHI-SYNDROME; BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING-FACTOR; LEUKOCYTE ADHESION DEFICIENCY; SEVERE CONGENITAL NEUTROPENIA; RECOMBINANT INTERFERON-GAMMA; MEDIATED GENE-TRANSFER; PERIPHERAL-BLOOD PROGENITORS; RESPIRATORY-BURST OXIDASE AB Although immune deficiency diseases stemming from phagocytic disorders are rare, they are important to diagnose early in life. Infections in these disorders usually involve the skin and soft tissues by common pathogens. Early recognition and aggressive treatment of infections by incision and drainage, surgical debridement, and antibiotics are important. Newer therapies with cytokines, bone marrow transplantation, and gene therapy are promising strategies. C1 SUNY Buffalo, Roswell Pk Canc Inst, Div Infect Dis, Buffalo, NY 14263 USA. SUNY Buffalo, Roswell Pk Canc Inst, Div Rheumatol Allergy & Immunol, Buffalo, NY 14263 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Segal, BH (reprint author), SUNY Buffalo, Roswell Pk Canc Inst, Div Infect Dis, Elm & Carlton St, Buffalo, NY 14263 USA. NR 144 TC 31 Z9 32 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD DEC PY 2000 VL 47 IS 6 BP 1311 EP + DI 10.1016/S0031-3955(05)70273-X PG 29 WC Pediatrics SC Pediatrics GA 381JX UT WOS:000165760500008 PM 11130998 ER PT J AU Horwitz, ME AF Horwitz, ME TI Stem-cell transplantation for inherited immunodeficiency disorders SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; CHRONIC GRANULOMATOUS-DISEASE; HYPER-IGM SYNDROME; IN-UTERO TRANSPLANTATION; CHEDIAK-HIGASHI-SYNDROME; NUCLEOSIDE PHOSPHORYLASE-DEFICIENCY; LEUKOCYTE ADHESION DEFICIENCY; CARTILAGE-HAIR HYPOPLASIA; WISKOTT-ALDRICH SYNDROME AB For many congenital immunodeficiency disorders, stem-cell transplantation is curative. The decision to proceed with this potentially dangerous treatment depends on the severity of the underlying illness. This article discusses the mechanics of allogeneic stem-cell transplantation and the clinical experience to date in the treatment of immunodeficiency disorders. The recent advent of nonmyeloablative, stem-cell transplantation also is presented in the context of clinical trials examining the efficacy of this less-toxic approach to stem-cell replacement for immunodeficiency disorders. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Horwitz, ME (reprint author), NIAID, Host Def Lab, NIH, 10 Ctr Dr,Bldg 10,Room 11N117, Bethesda, MD 20892 USA. NR 92 TC 10 Z9 12 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD DEC PY 2000 VL 47 IS 6 BP 1371 EP + DI 10.1016/S0031-3955(05)70276-5 PG 18 WC Pediatrics SC Pediatrics GA 381JX UT WOS:000165760500011 PM 11131001 ER PT J AU Candotti, F AF Candotti, F TI The potential for therapy of immune disorders with gene therapy SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; CHRONIC GRANULOMATOUS-DISEASE; BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC STEM-CELLS; ADENOSINE-DEAMINASE DEFICIENCY; LEUKOCYTE ADHESION DEFICIENCY; PERIPHERAL-BLOOD PROGENITORS; RETROVIRUS PACKAGING CELLS; NONDIVIDING HUMAN-CELLS; CD34(+) CELLS AB Gene therapy often is considered the ultimate form of therapy, based on its potential for correcting genetic diseases at the molecular level as opposed to merely treating the symptoms of the defect. Primary disorders of immunity have played a major role in the development of gene therapy, with the first human experiment being performed on ADA-deficient patients in 1990 and the first clear clinical benefit of genetic correction being reported in X-Linked severe combined immunodeficiency patients in 2000. After a decade of clinical experimentation, the challenges and potential of gene therapy for immunodeficiencies are better defined and are discussed in this article together with a brief description of the techniques that commonly are used for corrective gene transfer. C1 NHGRI, Disorders Immun Sect, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Candotti, F (reprint author), NHGRI, Disorders Immun Sect, Clin Gene Therapy Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10C103, Bethesda, MD 20892 USA. NR 86 TC 7 Z9 7 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 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD DEC PY 2000 VL 47 IS 6 BP 1389 EP 1407 DI 10.1016/S0031-3955(05)70277-7 PG 19 WC Pediatrics SC Pediatrics GA 381JX UT WOS:000165760500012 PM 11131002 ER PT J AU Kearns, GL Abdel-Rahman, SM Blumer, JL Reed, MD James, LP Jacobs, RF Welshman, IR Jungbluth, GL Stalker, DJ AF Kearns, GL Abdel-Rahman, SM Blumer, JL Reed, MD James, LP Jacobs, RF Welshman, IR Jungbluth, GL Stalker, DJ CA Pediat Pharmacology Res Unit Netwo TI Single dose pharmacokinetics of linezolid in infants and children SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Infectious-Diseases-Society-of-America CY NOV 12-15, 1998 CL DENVER, COLORADO SP Infect Dis Soc Amer DE pharmacokinetics; linezolid; infants; children ID IN-VITRO ACTIVITIES; OXAZOLIDINONE ANTIBACTERIAL AGENTS; STAPHYLOCOCCUS-AUREUS; ANTIMICROBIAL AGENTS; STREPTOCOCCUS-PNEUMONIAE; RESISTANT ENTEROCOCCI; BACTERIAL-INFECTIONS; PENICILLIN-RESISTANT; U-100766; VANCOMYCIN AB Background. Linezolid is an oxazolidinone antibiotic with excellent in vitro activity against a number of Gram-positive organisms including antibiotic-resistant isolates. The safety and pharmacokinetics of intravenously administered linezolid were evaluated in children and adolescents to examine the potential for developmental dependence on its disposition characteristics. Methods. Fifty-eight children (3 months to 16 years old) participated in this study; 44 received a single 1.5-mg/kg dose and 14 received a single 10-mg/kg dose of linezolid administered by intravenous infusion. Repeated blood samples (n = 10 in children greater than or equal to 12 months; n = 8 in children 3 to 12 months) were obtained during 24 h after drug administration, and linezolid was quantitated from plasma by high performance liquid chromatography with mass spectrometry detection. Plasma concentration us, time data were evaluated with a model independent approach. Results. Linezolid was web-tolerated by all subjects. The disposition of linezolid appears to be age-dependent. A significant although weak correlation between age and total body clearance was observed. The mean (+/-SD) values for elimination half-life, total clearance and apparent volume of distribution were 3.0 +/- 1.1 h, 0.34 +/- 0.15 liter/h/kg and 0.73 +/- 0.18 liter/kg, respectively. Estimates of total body clearance and volume of distribution were significantly greater in children than historical values of adult data. As such maximum achievable linezolid plasma concentrations were slightly lower in children, and concentrations 12 h after a single 10-mg/kg dose were below the MTC,, for selected pathogens with in vitro susceptibility to the drug. Conclusion. Based on these data a linezolid dose of 10 mg/kg given two to three times daily would appear appropriate for use in pediatric therapeutic clinical trials of this agent. C1 Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. Pharmacia & Upjohn Inc, Kalamazoo, MI 49001 USA. Arkansas Childrens Hosp, Div Infect Dis, Little Rock, AR 72202 USA. Arkansas Childrens Hosp, Div Pediat Clin Pharmacol & Toxicol, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. Rainbow Babies & Childrens Hosp, Div Pediat Pharmacol & Crit Care Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. Childrens Mercy Hosp, Dept Pediat, Sect Pediat Clin Pharmacol & Expt Therapeut, Kansas City, MO 64108 USA. Univ Missouri, Dept Pharm Practice, Kansas City, MO 64110 USA. Univ Missouri, Dept Pharmacol, Kansas City, MO 64110 USA. Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA. RP Kearns, GL (reprint author), Childrens Mercy Hosp, Dept Pediat, Sect Pediat Clin Pharmacol & Expt Therapeut, 2401 Gillham Rd, Kansas City, MO 64108 USA. FU NICHD NIH HHS [1 U10 HD31313-06] NR 24 TC 49 Z9 54 U1 0 U2 2 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 DEC PY 2000 VL 19 IS 12 BP 1178 EP 1184 DI 10.1097/00006454-200012000-00012 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 382YH UT WOS:000165854600011 PM 11144380 ER PT J AU Robinson, MR Fine, HF Ross, ML Mont, EK Bryant-Greenwood, PK Hertle, RW Tisdale, JF Young, NS Zeichner, SL Van Waes, C Whitcup, SM Walsh, TJ AF Robinson, MR Fine, HF Ross, ML Mont, EK Bryant-Greenwood, PK Hertle, RW Tisdale, JF Young, NS Zeichner, SL Van Waes, C Whitcup, SM Walsh, TJ TI Sino-orbital-cerebral aspergillosis in immunocompromised pediatric patients SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE sinusitis; aspergillosis; case report; immunodeficiency; pediatric ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACQUIRED-IMMUNE-DEFICIENCY; CENTRAL-NERVOUS-SYSTEM; INVASIVE ASPERGILLOSIS; ANTIFUNGAL ACTIVITY; INFECTED CHILDREN; AMPHOTERICIN-B; AIDS; SINUSITIS; FUMIGATUS C1 Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Diabet & Digest Kidney Disorders, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. Natl Inst Diabet & Digest Kidney Disorders, Malignancy Branch, NIH, Bethesda, MD USA. Natl Inst Diabet & Digest Kidney Disorders, Pathol Lab, NIH, Bethesda, MD USA. NEI, NIH, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, NIH, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. NR 39 TC 11 Z9 13 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 DEC PY 2000 VL 19 IS 12 BP 1197 EP 1203 DI 10.1097/00006454-200012000-00017 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 382YH UT WOS:000165854600015 PM 11144384 ER PT J AU Heegaard, ED Hasle, K Skibsted, L Bock, J Brown, KE AF Heegaard, ED Hasle, K Skibsted, L Bock, J Brown, KE TI Congenital anemia caused by parvovirus B19 infection SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE congenital anemia; hydrops fetalis; parovirus B19 ID PREGNANT-WOMEN; FETAL HYDROPS; SERUM; MANAGEMENT; DNA; PCR C1 Univ State Hosp, Rigshosp, Dept Clin Microbiol, Copenhagen, Denmark. Univ State Hosp, Rigshosp, Dept Ultrasound, Copenhagen, Denmark. Univ State Hosp, Rigshosp, Dept Obstet, Copenhagen, Denmark. Skejby Hosp, Dept Pediat, Aarhus, Denmark. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Heegaard, ED (reprint author), Univ State Hosp, Rigshosp, Dept Clin Microbiol, Copenhagen, Denmark. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 15 TC 11 Z9 14 U1 0 U2 1 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 DEC PY 2000 VL 19 IS 12 BP 1216 EP 1218 DI 10.1097/00006454-200012000-00024 PG 3 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 382YH UT WOS:000165854600022 PM 11144391 ER PT J AU Jakowlew, SB Zakowicz, H Moody, TW AF Jakowlew, SB Zakowicz, H Moody, TW TI Retinoic acid down-regulates VPAC(1) receptors and TGF-beta 3 but upregulates TGF-beta 2 in lung cancer cells SO PEPTIDES LA English DT Article DE retinoic acid; VIP receptors; cAMP; transforming growth factor beta; lung cancer ID VASOACTIVE-INTESTINAL-PEPTIDE; CHICKEN-EMBRYO CHONDROCYTES; HUMAN NEUROBLASTOMA-CELLS; NEURO-BLASTOMA CELL; GROWTH-FACTOR; MOLECULAR-CLONING; MESSENGER-RNAS; TGF-BETA; DIFFERENTIAL EXPRESSION; FUNCTIONAL EXPRESSION AB The effects of retinoic acid (RA) on lung cancer cells were investigated. Both all-trans (t-RA) and 13-cis RA (c-RA) decreased specific I-125-VIP binding to NCI-H1299 cells in a time- and concentration-dependent manner. After 20 hr, 30 muM t-RA decreased specific I-125-VIP binding by 60%. By Scatchard analysis, the density of VIP binding sites but not the affinity was reduced by 42%. NCI-H1299 VPAC(1) receptor mRNA was reduced by 48%. VIP caused a 3-fold elevation in the NCI-H1299 cAMP, and the increase in cAMP caused by VIP was reduced by 38% if the NCI-H1299 cells were treated with t-RA. Using the MTT assay, 3 muM t-RA and 3 muM c-RA inhibited NCI-H 1299 proliferation by 60 and 23% respectively. Also, transforming growth factor (TGF)-beta2 increased after treatment of NCI-H1299 cells with t-RA whereas TGF-beta1 mRNA was unaffected and TGF-beta3 mRNA was decreased. These results suggest that RA may inhibit lung cancer growth by down-regulating VPAC(1) receptor and TGF-beta3 mRNA but up-regulating TGF-beta2 mRNA. (C) 2000 Published by Elsevier Science Inc. C1 NCI, Med Branch, Cell & Canc Biol Dept, Rockville, MD 20850 USA. RP Moody, TW (reprint author), NCI, Med Branch, Cell & Canc Biol Dept, Rockville, MD 20850 USA. NR 49 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 2000 VL 21 IS 12 BP 1831 EP 1837 DI 10.1016/S0196-9781(00)00344-2 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 394TA UT WOS:000166538300009 PM 11150643 ER PT J AU Boykins, RA Ardans, JA Wahl, LM Lal, RB Yamada, KM Dhawan, S AF Boykins, RA Ardans, JA Wahl, LM Lal, RB Yamada, KM Dhawan, S TI Immunization with a novel HIV-1-Tat multiple-peptide conjugate induces effective immune response in mice SO PEPTIDES LA English DT Article DE monocytes; macrophages; HIV-1-Tat; HIV; AIDS; pathogenesis; vaccine ID IMMUNODEFICIENCY-VIRUS TYPE-1; TAT PROTEIN; ENDOTHELIAL-CELLS; AIDS VACCINE; INFECTION; DOMAIN; PATHOGENESIS; MONOCYTES; IDENTIFICATION; CORECEPTORS AB We report here a novel, highly immunogenic synthetic, multiple-peptide conjugate comprising functional domains Tat(21-40) and Tat(53-68) from HIV-I group M plus Tat(9-20) from HIV-I group O of the HIV-Tat protein (HIV-1-Tat-MPC). Vaccination of mice with HIV-I-Tat-MPC induced an effective immune response to all three functional domains. The anti-HTV-1-Tat-MPC antibodies efficiently inhibited Tar-induced viral activation in monocytes infected with HIV(Ba-L) as well as with various clinical HIV-l isolates, and reduced Tat-mediated cytopathicity in infected cells by 60-75%. Our results indicate that anti-HIV-l-Tat-MPC antibodies inhibit viral pathogenesis, possibly by blocking functional determinants of Tar and disrupting autocrine and paracrine actions of secreted Tat protein. This epitope-specific, synthetic Tat construct may, therefore, provide a subunit AIDS vaccine candidate for inducing an effective immunoprophylaxis response to reduce progression of HIV infection. (C) 2000 Elsevier Science Inc. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Immunopathogenesis Sect, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Immunopathogenesis Lab, Atlanta, GA 30333 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Parasit Biol & Biochem, Bethesda, MD 20892 USA. RP Dhawan, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Immunopathogenesis Sect, Bethesda, MD 20892 USA. EM dhawan@cber.fda.gov OI Yamada, Kenneth/0000-0003-1512-6805 NR 38 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 2000 VL 21 IS 12 BP 1839 EP 1847 DI 10.1016/S0196-9781(00)00334-X PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 394TA UT WOS:000166538300010 PM 11150644 ER PT J AU Pio, R Martinez, A Elsasser, TH Cuttitta, F AF Pio, R Martinez, A Elsasser, TH Cuttitta, F TI Presence of immunoreactive adrenomedullin in human and bovine milk SO PEPTIDES LA English DT Article DE adrenomedullin; radioimmunoassay; human milk; bovine milk; intestine 407 ID HYPOTENSIVE PEPTIDE; HUMAN PLASMA; GROWTH-FACTOR; EXPRESSION; INCREASES; FLUID; SKIN; RAT AB We examined by radioimmunoassay the presence of immunoreactive adrenomedullin (ir-AM) ih human and bovine milk. Milk samples displaced I-125-AM from the AM-antiserum in parallel to the standard curve. RP-HPLC revealed. a main immunoreactive peak eluting as synthetic AM. Concentrations in human milk ranged between 140 and 404 pg/mL. In cow, the levels of AM were 73.5 +/- 3.8 pg/mL, Bovine milk products had AM levels similar to those found in fresh bovine milk. Human milk had growth promoting activity on the human intestinal cell line Int-307 that could be partially blocked with an anti-AM antibody: (C) 2000 Published by Elsevier Science Inc. C1 NCI, Dept Cell & Canc Biol, NIH, Bethesda, MD 20892 USA. USDA ARS, Growth Biol Lab, Beltsville, MD 20705 USA. RP Pio, R (reprint author), NCI, Dept Cell & Canc Biol, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Martinez, Alfredo/A-3077-2013; Pio, Ruben/F-5353-2017 OI Martinez, Alfredo/0000-0003-4882-4044; Pio, Ruben/0000-0002-6831-6111 NR 37 TC 20 Z9 21 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 2000 VL 21 IS 12 BP 1859 EP 1863 DI 10.1016/S0196-9781(00)00341-7 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 394TA UT WOS:000166538300012 PM 11150646 ER PT J AU Bekersky, I Boswell, GW Hiles, R Fielding, RM Buell, D Walsh, TJ AF Bekersky, I Boswell, GW Hiles, R Fielding, RM Buell, D Walsh, TJ TI Safety, toxicokinetics and tissue distribution of long-term intravenous liposomal amphotericin B (AmBisome (R)): A 91-day study in rats SO PHARMACEUTICAL RESEARCH LA English DT Article DE amphotericin B; liposomes; pharmacokinetics; toxicokinetics; tissue distribution; toxicity ID FUNGAL-INFECTIONS; COLLOIDAL DISPERSION; LIPID COMPLEX; FORMULATION; PHARMACOKINETICS; UNILAMELLAR; ELIMINATION; DELIVERY; TOXICITY; SYSTEM AB Purpose. Amphotericin B in small, unilamellar liposomes (AmBisome(R)) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures. the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated. Methods, Rats(174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg). dextrose. or empty liposomes for 91 days with a 30-day recovery. Safety (including clinical and microscopic pathology) and toxicokinetics in plasma and tissues were evaluated. Results. Chemical and histopathologic changes demonstrated that the kidneys and liver were the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate (urean nitrogen [BUN] less than or equal to 51 mg/ dl: creatinine: unchanged). Liposome-related changes (vacuolated macrophages and hypercholesterolemia) were also observed. Although plasma and tissue accumulation was nonlinear and progressive (clearance and volume decreased, half-life increased with dose and time), most toxic changes occurred early, stabilized by the end of dosing, and reversed during recovery. There were no delayed toxicities. Concentrations in liver and spleen greatly exceeded those in plasma: kidney and lung concentrations were similar to those in plasma. Elimination half-lives were 1-4 weeks in all tissues. Conclusions. Despite nonlinear accumulation. AmBisome revealed predictable hepatic and renal toxicities after 91 days. with no new or delayed effects after prolonged treatment at high doses that resulted in plasma levels >200 mug/ml and tissue levels >3000 mug/g. C1 Fujisawa Healthcare Inc, Deerfield, IL 60015 USA. Calvert Preclin Serv, Olyphant, PA USA. Amylin Pharmaceut Inc, San Diego, CA USA. Biol Serv, Boulder, CO USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Bekersky, I (reprint author), Fujisawa Healthcare Inc, Deerfield, IL 60015 USA. NR 30 TC 35 Z9 38 U1 1 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD DEC PY 2000 VL 17 IS 12 BP 1494 EP 1502 DI 10.1023/A:1007605024942 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 411BG UT WOS:000167477800008 PM 11303959 ER PT J AU Hu, WS Pathak, VK AF Hu, WS Pathak, VK TI Design of retroviral vectors and helper cells for gene therapy SO PHARMACOLOGICAL REVIEWS LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; SPLEEN NECROSIS VIRUS; LONG TERMINAL REPEAT; CIS-ACTING SEQUENCES; CAP-INDEPENDENT TRANSLATION; CHAIN VARIABLE FRAGMENT; NONDIVIDING HUMAN-CELLS; RIBOSOMAL ENTRY SITE; LEUKEMIA-VIRUS; HIGH-TITER AB During the past decade, gene therapy has been applied to the treatment of disease in hundreds of clinical trials. Various tools have been developed to deliver genes into human cells; among them, genetically engineered retroviruses are currently the most popular tool for gene delivery. Most of the systems contain vectors that are capable of accommodating genes of interest and helper cells that can provide the viral structural proteins and enzymes to allow for the generation of vector-containing infectious viral particles. Retroviridae is a family of retroviruses that differs in nucleotide and amino acid sequence, genome structure, pathogenicity, and host range. This diversity provides opportunities to use viruses with different biological characteristics to develop different therapeutic applications. Currently, a variety of retro-viruses that provide distinct advantages for gene delivery has been modified and used in clinical trials. In this review, the genome structures of oncoviruses, lentiviruses, and spumaviruses are reviewed and examples of vectors derived from these viruses are described. As with any delivery tool, the efficiency, the ability to target certain tissue or cell type, the expression of the gene of interest, and the safety of retroviral-based systems are important for successful application of gene therapy. Significant efforts have been dedicated to these areas of research in recent years. Various modifications have been made to retroviral-based vectors and helper cells to alter gene expression, target delivery, improve viral titers, and increase safety. The principles and design of these modifications are discussed in this review. C1 NCI, HIV Drug Resistance Program, FCRDC, Frederick, MD 21702 USA. W Virginia Univ, Sch Med, Dept Microbiol & Immunol, Morgantown, WV 26506 USA. W Virginia Univ, Sch Med, Dept Biochem, Morgantown, WV 26506 USA. W Virginia Univ, Sch Med, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, FCRDC, Bldg 535,Rm 336, Frederick, MD 21702 USA. EM whu@mail.ncifcrf.gov FU NCI NIH HHS [CA58875] NR 166 TC 57 Z9 64 U1 1 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 EI 1521-0081 J9 PHARMACOL REV JI Pharmacol. Rev. PD DEC PY 2000 VL 52 IS 4 BP 493 EP 511 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 379ED UT WOS:000165627200002 PM 11121508 ER PT J AU Elenkov, IJ Wilder, RL Chrousos, GP Vizi, ES AF Elenkov, IJ Wilder, RL Chrousos, GP Vizi, ES TI The sympathetic nerve - An integrative interface between two supersystems: The brain and the immune system SO PHARMACOLOGICAL REVIEWS LA English DT Review ID TUMOR-NECROSIS-FACTOR; BETA-ADRENERGIC-RECEPTOR; CORTICOTROPIN-RELEASING HORMONE; NITRIC-OXIDE PRODUCTION; PERIPHERAL-BLOOD LYMPHOCYTES; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; PITUITARY-ADRENAL AXIS; PROTEIN-KINASE-A; MESSENGER-RNA EXPRESSION; THYMIC EPITHELIAL-CELLS AB The brain and the immune system are the two major adaptive systems of the body. During an immune response the brain and the immune system "talk to each other" and this process is essential for maintaining homeostasis. Two major pathway systems are involved in this cross-talk: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). This overview focuses on the role of SNS in neuroimmune interactions, an area that has received much less attention than the role of HPA axis. Evidence accumulated over the last 20 years suggests that norepinephrine (NE) fulfills the criteria for neurotransmitter/neuromodulator in lymphoid organs. Thus, primary and secondary lymphoid organs receive extensive sympathetic/noradrenergic innervation. Under stimulation, NE is released from the sympathetic nerve terminals in these organs, and the target immune cells express adrenoreceptors. Through stimulation of these receptors, locally released NE, or circulating catecholamines such as epinephrine, affect lymphocyte traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid cells. Although there exists substantial sympathetic innervation in the bone marrow, and particularly in the thymus and mucosal tissues, our knowledge about the effect of the sympathetic neural input on hematopoiesis, thymocyte development, and mucosal immunity is extremely modest. In addition, recent evidence is discussed that NE and epinephrine, through stimulation of the beta (2)-adrenoreceptor-cAMP-protein kinase A pathway, inhibit the production of type 1/proinflammatory cytokines, such as interleukin (IL-12), tumor necrosis factor-alpha, and interferon-gamma by antigen-presenting cells and T helper (Th) 1 cells, whereas they stimulate the production of type 2/anti-inflammatory cytokines such as IL-10 and transforming growth factor-beta. Through this mechanism, systemically, endogenous catecholamines may cause a selective suppression of Th1 responses and cellular immunity, and a Th2 shift toward dominance of humoral immunity. On the other hand, in certain local responses, and under certain conditions, catecholamines may actually boost regional immune responses, through induction of IL-1, tumor necrosis factor-alpha, and primarily IL-8 production. Thus, the activation of SNS during an immune response might be aimed to localize the inflammatory response, through induction of neutrophil accumulation and stimulation of more specific humoral immune responses, although systemically it may suppress Th1 responses, and, thus protect the organism from the detrimental effects of proinflammatory cytokines and other products of activated macrophages. The above-mentioned immunomodulatory effects of catecholamines and the role of SNS are also discussed in the context of their clinical implication in certain infections, major injury and sepsis, autoimmunity, chronic pain and fatigue syndromes, and tumor growth. Finally, the pharmacological manipulation of the sympathetic-immune interface is reviewed with focus on new therapeutic strategies using selective alpha (2)- and beta (2)-adrenoreceptor agonists and antagonists and inhibitors of phosphodiesterase type IV in the treatment of experimental models of autoimmune diseases, fibromyalgia, and chronic fatigue syndrome. C1 Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, H-1450 Budapest, Hungary. NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat Endocrinol Sect, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, H-1085 Budapest, Hungary. RP Vizi, ES (reprint author), Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, POB 67, H-1450 Budapest, Hungary. EM esvizi@koki.hu NR 443 TC 1139 Z9 1208 U1 12 U2 149 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD DEC PY 2000 VL 52 IS 4 BP 595 EP 638 PG 44 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 379ED UT WOS:000165627200005 PM 11121511 ER PT J AU Morgan, GD Fox, BJ AF Morgan, GD Fox, BJ TI Promoting cessation of tobacco use SO PHYSICIAN AND SPORTSMEDICINE LA English DT Article C1 NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. Univ Wisconsin, Sch Med, Ctr Tobacco Res & Intervent, Madison, WI USA. RP Morgan, GD (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Rm 4034 MSC 7337, Rockville, MD 20852 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0091-3847 J9 PHYSICIAN SPORTSMED JI Physician Sportsmed. PD DEC PY 2000 VL 28 IS 12 BP 59 EP 60 PG 2 WC Primary Health Care; Orthopedics; Sport Sciences SC General & Internal Medicine; Orthopedics; Sport Sciences GA 381HZ UT WOS:000165757800005 PM 20086617 ER PT J AU Holmes, A Parmigiani, S Ferrari, PF Palanza, P Rodgers, RJ AF Holmes, A Parmigiani, S Ferrari, PF Palanza, P Rodgers, RJ TI Behavioral profile of wild mice in the elevated plus-maze test for anxiety SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE wild mice; elevated plus-maze; anxiety; escape; ethological methods ID CORTICOTROPIN-RELEASING-FACTOR; ANTIPREDATOR DEFENSIVE BEHAVIOR; ESCAPE-RELATED BEHAVIORS; RECEPTOR MUTANT MICE; ONE-TRIAL TOLERANCE; SWISS-WEBSTER MICE; TEST BATTERY; PHARMACOLOGICAL CHARACTERIZATION; ETHOPHARMACOLOGICAL ANALYSIS; ETHOLOGICAL ANALYSIS AB Systematic observations of the defensive behavior of wild rodents have greatly informed the experimental study of anxiety and its neural substrates in laboratory animals. However, as the former work has been almost exclusively carried out in rats, few data are available concerning the reactivity of wild mice to standardized tests of anxiety-related behavior. In the present experiments, we employed ethological measures to examine the behavioral responses of a wild-derived population of house mice (Mus musculus) in the elevated plus-maze. Ln direct comparisons with laboratory Swiss mice, male wild mice exhibited substantially elevated levels of exploratory activities and an overall "preference" for the open arms of the plus-maze. On re-exposure to the plus-maze, male wild mice showed further increases in open arm exploration, while Swiss mice showed a marked shift to the enclosed parts of the plus-maze. Tested over a single session, female wild mice also exhibited a profile of high open arm exploration, but showed levels of exploratory behaviors and locomotor activity similar to female Swiss counterparts. While exploratory patterns in wild mice show similarities to profiles seen in certain laboratory strains (e.g., BALB/c), wild mice displayed a number of additional behaviors that are unprecedented in plus-maze studies with laboratory mice. These included actual and attempted jumps from the maze, spontaneous freezing, and exploration of the upper ledges of the closed arms. Thus, while in conventional terms the behavior of wild mice was consistent with one of low anxiety-like behavior, the presence of these unique elements instead indicates a profile more accurately characterized by high reactivity and escape motivation. We discuss how the use of an ethological approach to measuring plus-maze behavior can support accurate interpretation of other exceptional profiles in this test, such as those possibly arising from phenotyping of transgenic and gene knockout mice. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bethesda, MD 20892 USA. Univ Parma, Dipartimento Biol Evolut & Funzionale, I-43100 Parma, Italy. Univ Parma, Ist Fisiol Umana, I-43100 Parma, Italy. Univ Leeds, Sch Psychol, Ethopharmacol Lab, Leeds LS2 9JT, W Yorkshire, England. RP Holmes, A (reprint author), NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bldg 10,Room 4D11, Bethesda, MD 20892 USA. EM aholmes@codon.nih.gov OI PARMIGIANI, STEFANO/0000-0002-6658-2029 NR 68 TC 65 Z9 70 U1 5 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD DEC PY 2000 VL 71 IS 5 BP 509 EP 516 DI 10.1016/S0031-9384(00)00373-5 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 387BT UT WOS:000166100800010 PM 11239669 ER PT J AU Hall, FS Huang, S Fong, GW Sundstrom, JM Pert, A AF Hall, FS Huang, S Fong, GW Sundstrom, JM Pert, A TI Differential basis of strain and rearing effects on open-field behavior in Fawn Hooded and Wistar rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE social isolation; strain; anxiety; novelty; open field; corticosterone ID SOCIAL-ISOLATION; RESPONSES; HYPERACTIVITY; EXPLORATION; ANXIETY; MODEL; CHLORDIAZEPOXIDE; RESOCIALIZATION; ENVIRONMENTS; HABITUATION AB Open-field behavior was examined under several conditions in isolation-reared, and socially reared, Fawn Hooded (FH) and Wistar rats. Lighting conditions (red or white light) and complexity (object or no object) were varied: Experiment 1, white light, no object; Experiment 2, red light, no object; Experiment 3, white light, object; Experiment 4, red light, object. ii-he plasma corticosterone (CORT) response to open-field exposure was examined two further experiments. Observation of differences in open-field behavior, resulting from strain or rearing condition, was dependent on both lighting condition and complexity. Differences in exploratory behavior exhibited by isolation-reared rats were best explained by changes in response to novelty, while those in FH, relative to Wistar, rats were primarily due to increased anxiety. Supporting these conclusions, FH rats had enhanced stimulated CORT levels, while isolation rearing was without effect. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIAAA, Clin Studies Lab, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Hall, FS (reprint author), NIDA, Mol Neurobiol Branch, IRP, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 NR 31 TC 48 Z9 48 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD DEC PY 2000 VL 71 IS 5 BP 525 EP 532 DI 10.1016/S0031-9384(00)00372-3 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 387BT UT WOS:000166100800012 PM 11239671 ER PT J AU Bianchi, SM Casper, LM AF Bianchi, SM Casper, LM TI American families SO POPULATION BULLETIN LA English DT Review ID AFTER-SCHOOL CARE; SINGLE-PARENT FAMILIES; UNITED-STATES; LIVING ARRANGEMENTS; MARITAL DISRUPTION; INCOME INEQUALITY; CHILDREN; MARRIAGE; COHABITATION; TRENDS C1 Univ Maryland, Ctr Populat Gender & Social Inequal, College Pk, MD 20742 USA. NICHHD, Demog & Behav Sci Branch, Bethesda, MD 20892 USA. RP Bianchi, SM (reprint author), Univ Maryland, Ctr Populat Gender & Social Inequal, College Pk, MD 20742 USA. RI Brower, Susan/C-7090-2009 NR 137 TC 18 Z9 18 U1 1 U2 5 PU POPULATION REFERENCE BUREAU INC PI WASHINGTON PA 1875 CONNECTICUT AVE, NW, STE 520, CIRCULATION DEPT, WASHINGTON, DC 20009-5728 USA SN 0032-468X J9 POPUL BULL JI Popul. Bull. PD DEC PY 2000 VL 55 IS 4 BP 3 EP 43 PG 41 WC Demography SC Demography GA 390MD UT WOS:000166299100001 ER PT J AU Wu, Z Aguilera, G Sandberg, K AF Wu, Z Aguilera, G Sandberg, K TI Adrenalectomy regulates corticotropin-releasing factor receptor expression by regulating mRNA binding proteins SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20057 USA. NICHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD DEC PY 2000 VL 225 IS 3 BP 234 EP 234 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 375NK UT WOS:000165406700020 ER PT J AU Oriji, GK AF Oriji, GK TI Adenosine induced direct negative inotropic effect is abolished during global ischemia: role of protein kinase C and prostacyclin SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID RAT-HEART; CORONARY FLOW; RABBIT HEART; GUINEA-PIG; PROTECTION; RECEPTORS; RELEASE; INJURY AB Adenosine acts as a cardioprotective agent by producing coronary vasodilation, decreasing heart rate and by antagonizing the cardiostimulatory effect of catecholamines; adenosine also exerts a direct negative inotropic effect. Myocardial ischemia is known to be associated with enhanced levels of adenosine, increased protein kinase C (PKC) activity and prostacyclin (PGI(2)) release. The present study was conducted to determine if myocardial ischemia alters the cardioprotective effect of adenosine by increasing PKC activity and PGI(2) release in the isolated rat heart perfused at 10 ml/min with Krebs-Henseleit buffer (KHB; 95% O-2+5% CO2). Adenosine (10 mmol/min) reduced myocardial contractility as indicated by a decrease in contractility (dp/dt(max)), heart rate (HR) and coronary perfusion pressure (PP). In hearts subjected to 30 min of ischemia (without perfusion) and then reperfused with KHB, adenosine failed to decrease dp/dt(max), HR or PP. however, during infusion of PKC inhibitor H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine hydrochloride) (H-7; 6 mmol/min), which commenced 10 min before ischemia and continued throughout reperfusion, adenosine produced a decrease in dp/dt(max), HR and PP, similar to that before ischemia. Infusion of the PKC activator phorbol 12;13-dibutyrate (PDBu; 2 nmol/min) but not an inactive analogue in non-ischemic hearts prevented the adenosine induced decrease in dp/dt(max). During infusion of H-7, PDBu failed to block the direct negative inotropic effect of adenosine in non-ischemic hearts. In addition, pretreatment with H-7 or indomethacin (cyclooxygenase inhibitor) significantly reduced the PGI(2) release following ischemia. This data suggest that PKC and PGI(2) regulate the direct negative inotropic effect of adenosine, which is abolished during ischemia. (C) 2000 Harcourt Publishers Ltd. C1 William Paterson State Coll, Coll Sci & Hlth, Dept Biol, Wayne, NJ 07470 USA. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. RP Oriji, GK (reprint author), William Paterson State Coll, Coll Sci & Hlth, Dept Biol, Wayne, NJ 07470 USA. NR 24 TC 1 Z9 1 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 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD DEC PY 2000 VL 63 IS 6 BP 343 EP 349 DI 10.1054/plef.2000.0225 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 392KA UT WOS:000166409200003 PM 11133171 ER PT J AU Trumbore, MW Berger, SL AF Trumbore, MW Berger, SL TI Prothymosin alpha is a nonspecific facilitator of nuclear processes: Studies of run-on transcription SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID RNA-POLYMERASE-II; IN-VIVO; HISTONE H1; PROTEIN; EXPRESSION; GENE; PHOSPHORYLATION; CDNA; ELONGATION-FACTOR-2; THYMOSIN-ALPHA-1 AB The effect of prothymosin a on transcriptional elongation has been examined. The addition of prothymosin a to COS-l and NIH3T3 cell nuclei engaged in run-on transcription stimulated RNA synthesis approximately two- to threefold in a dose-dependent manner. Polyglutamic acid or a random polypeptide composed of glutamic acid, alanine, and tyrosine, did not substitute for prothymosin a. Enhanced transcription occurred in the presence of high and low doses of actinomycin D and in the presence of cu-amanitin, but not in nuclear extracts. The stimulatory effect was dependent on a limiting concentration of one nucleoside triphosphate and was nearly abrogated by saturating levels of precursors. In the presence of Sarkosyl, which itself increases transcription, prothymosin a was almost ineffectual. The data are consistent with a model in which prothymosin a does not interact directly with polymerases but, instead, nonspecifically decreases the barriers to diffusion of charged molecules in electrostatically charged environments. C1 NCI, Sect Genes & Gene Prod, NIH, Bethesda, MD 20892 USA. RP Berger, SL (reprint author), NCI, Sect Genes & Gene Prod, NIH, Bldg 8,Room 311A, Bethesda, MD 20892 USA. NR 40 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD DEC PY 2000 VL 20 IS 3 BP 414 EP 420 DI 10.1006/prep.2000.1332 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 378XU UT WOS:000165611300009 PM 11087681 ER PT J AU Tzeng, SR Pai, MT Lung, FDT Wu, CW Roller, PP Lei, BF Wei, CJ Tu, SC Chen, SH Soong, WJ Cheng, JW AF Tzeng, SR Pai, MT Lung, FDT Wu, CW Roller, PP Lei, BF Wei, CJ Tu, SC Chen, SH Soong, WJ Cheng, JW TI Stability and peptide binding specificity of Btk SH2 domain: Molecular basis for X-linked agammaglobulinemia SO PROTEIN SCIENCE LA English DT Article DE Btk; CD; phosphopeptide binding; SH2 domain; SPR; XLA ID BRUTONS TYROSINE KINASE; PLECKSTRIN HOMOLOGY DOMAIN; BETA-GAMMA-SUBUNITS; PHOSPHOPEPTIDE BINDING; MUTATION ANALYSIS; POINT MUTATION; PI 3-KINASE; PH DOMAIN; PROTEIN; GENE AB X-linked agammaglobulinemia (XLA) is caused by mutations in the Bruton's tyrosine kinase (Btk). The absence of functional Btk leads to failure of B-cell development that incapacitates antibody production in XLA patients leading to recurrent bacterial infections. Btk SH? domain is essential for phospholipase C-gamma phosphorylation. and mutations in this domain were shown to cause XLA. Recently, the B-cell linker protein (BLNK) was found to interact with the SH2 domain of Btk, and this association is required for the activation of phospholipase C-gamma. However, the molecular basis for the interaction between the Btk SH2 domain and BLNK and the cause of XLA remain unclear. To understand the role of Btk in B-cell development, we have determined the stability and peptide binding affinity of the Btk SH2 domain. Our results indicate that both the structure and stability of Btk SH2 domain closely resemble with other SH2 domains, and it binds with phosphopeptides in the order pYEEI > pYDEP > pYMEM > pYLDL > pYIIP. We expressed the R288Q, R288W, L295P, R307G, R307T. Y334S, Y361C, L369F, and I370M mutants: of the Btk SH2 domain identified from XLA patients and measured their binding affinity with the phosphopeptides. Our studies revealed that mutation of R288 and R307 located in the phosphotyrosine binding site resulted in a more than 200-fold decrease in the peptide binding compared to L295, Y334, Y361, L369, and 1370 mutations in the pY + 3 hydrophobic binding pecker (similar to3- to 17-folds). Furthermore. mutation of the Tyr residue at the beta D5 position reverses the binding order of Btk SH2 domain to pYIIP > pYLDL > pYDEP > pYMEM > pYEEI. This altered binding behavior of mutant Btk SH2 domain likely leads to XLA. C1 Natl Tsing Hua Univ, Dept Life Sci, Div Struct Biol & Biomed Sci, Hsinchu 300, Taiwan. China Med Coll, Dept Nutr, Taichung 400, Taiwan. NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Vet Gen Hosp, Childrens Med Ctr, Dept Pediat, Taipei 112, Taiwan. RP Cheng, JW (reprint author), Natl Tsing Hua Univ, Dept Life Sci, Div Struct Biol & Biomed Sci, Hsinchu 300, Taiwan. NR 58 TC 22 Z9 23 U1 1 U2 1 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 DEC PY 2000 VL 9 IS 12 BP 2377 EP 2385 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 396YH UT WOS:000166665200011 PM 11206059 ER PT J AU Kumar, S Nussinov, R AF Kumar, S Nussinov, R TI Fluctuations between stabilizing and destabilizing electrostatic contributions of ion pairs in conformers of the c-Myc-Max leucine zipper SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE NMR; ensemble; coiled coil; energy landscape; solution ID HELICAL COILED-COILS; MOLECULAR-DYNAMICS SIMULATION; SALT BRIDGES STABILIZE; PROTEIN STRUCTURES; CRYSTAL-STRUCTURE; OLIGOMERIZATION-STATE; FOLDING FUNNELS; ALPHA-HELICES; NMR STRUCTURE; AMINO-ACIDS AB In solution proteins often exhibit backbone and side-chain flexibility. Yet electrostatic interactions in proteins are sensitive to motions. Hence, here we study the contribution of ion pairs toward protein stability in a range of conformers which sample the conformational space in solution. Specifically, we focus on the electrostatic contributions of ion pairs to the stability of each of the conformers in the NMR ensemble of the c-Myc-Max leucine zipper and to their average energy minimized structure. We compute the electrostatic contributions of inter- and intra-helical ion pairs and of an ion pair network. We find that the electrostatic contributions vary considerably among the 40 NMR conformers. Each ion pair, and the network, fluctuates between being stabilizing and being destabilizing. This fluctation reflects the variability in the location of the ion pairing residues and in the geometric orientation of these residues, both with respect to each other and with respect to other charged groups in the rest of the protein. Ion pair interactions in the c-Myc-Max leucine zipper in solution depend on the protein conformer which is analyzed. Hence, the overall stabilizing (or destabilizing) contribution of an ion pair is conformer population-dependent. This study indicates that free energy calculations performed using the continuum electrostatics methodology are sensitive to protein conformational details. Proteins 2000; 41:485-497. (C) 2000 Wiley-Liss, Inc. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr,Lab Expt & Computat, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr,Lab Expt & Computat, Bldg 469,Rm 151, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 53 TC 23 Z9 24 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 0887-3585 J9 PROTEINS JI Proteins PD DEC 1 PY 2000 VL 41 IS 4 BP 485 EP 497 DI 10.1002/1097-0134(20001201)41:4<485::AID-PROT60>3.0.CO;2-E PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 374VR UT WOS:000165365500006 PM 11056036 ER PT J AU Bergman, J France, CP Holtzman, SG Katz, JL Koek, W Stephens, DN AF Bergman, J France, CP Holtzman, SG Katz, JL Koek, W Stephens, DN TI Agonist efficacy, drug dependence, and medications development: preclinical evaluation of opioid, dopaminergic, and GABA(A)-ergic ligands SO PSYCHOPHARMACOLOGY LA English DT Review DE efficacy; receptor theory; spare receptor; receptor reserve; mu-opioid; dopamine D-1 agonist; GABA(A); benzodiazepine; abecarnil; irreversible antagonism; cocaine; transport inhibitor; antinociception; drug discrimination; antagonism; partial agonist; partial generalization; drug development; dependence ID BETA-CARBOLINE ABECARNIL; BENZODIAZEPINE RECEPTOR OCCUPANCY; DIFFERING INTRINSIC EFFICACIES; RATS DISCRIMINATING FENTANYL; SCHEDULE-CONTROLLED BEHAVIOR; ADENYLATE-CYCLASE ACTIVITY; PROTOTYPE OPIATE DRUGS; LONG-TERM TREATMENT; SQUIRREL-MONKEYS; RHESUS-MONKEYS AB Background: The general premise that receptor theory provides a useful framework for understanding the behavioral effects of psychoactive drugs has been a central tenet of behavioral pharmacology. Objectives. The purpose of this review is to reiterate this basic theme and, in particular, the proposition that current concepts of pharmacological efficacy can be effectively used to examine behavioral effects of drugs with abuse or dependence potential in a way that contributes to the discovery of drugs to treat drug dependence. Experimental data: The review begins by briefly introducing the concept of efficacy and follows with several illustrations of how our current understanding of efficacy can be used to address important research questions in drug discovery. In the first, the likelihood of developing novel opioid analgesics with reduced abuse potential is addressed by considering the different efficacy requirements for the discriminative-stimulus and antinociceptive effects of mu -opioids. From a pharmacologically different perspective within drug abuse research, the review continues with an exposition of efficacy-related differences in the behavioral effects of dopamine D-1 agonists and how such differences might be exploited in different medications strategies for treating cocaine dependence. The principles of pharmacological efficacy also have come to guide the development of novel GABA(A)-related antianxiety medications, and this is illustrated in a discussion of the utility of low-efficacy agonists in the treatment of benzodiazepine dependence. The second half of the paper provides counterpoint to the several examples of how principles of efficacy can be applied in drug discovery. The counterpoint includes, first, a critical evaluation of how the concept of efficacy has been applied in the development of monoamine transport inhibitors as anti-cocaine medications and, in particular, the difficulties this may pose for data analysis. The review ends with a discussion of efficacy-based analysis in drug discrimination research and illustrates some of the obstacles that may be encountered in pharmacologically classifying drugs on this basis. Conclusions: Ample evidence indicates that many receptor systems can be activated in a graded manner and that principles of efficacy can be judiciously applied to understand and exploit the behavioral effects of drugs that result from such graded activation. However, as cautioned in the last sections, the misapplication of pharmacological concepts in behavioral studies of drugs may obscure their behavioral pharmacology and potentially confound drug discovery. C1 Harvard Univ, McLean Hosp, Sch Med, ADARC, Belmont, MA 02178 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. NIDA, NIH, IRP, Baltimore, MD 21224 USA. Ctr Rech Pierre Fabre, F-81106 Castres, France. Univ Sussex, Brighton BN1 9QG, E Sussex, England. RP Bergman, J (reprint author), Harvard Univ, McLean Hosp, Sch Med, ADARC, 115 Mill St, Belmont, MA 02178 USA. RI Stephens, David/G-2384-2012 FU NIDA NIH HHS [DA 03774, DA 10566] NR 123 TC 33 Z9 33 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2000 VL 153 IS 1 BP 67 EP 84 DI 10.1007/s002130000567 PG 18 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 389CA UT WOS:000166220000006 PM 11255930 ER PT J AU Dixon, LB Tershakovec, AM McKenzie, J Shannon, B AF Dixon, Lori Beth Tershakovec, Andrew M. McKenzie, Jeannie Shannon, Barbara TI Diet quality of young children who received nutrition education promoting lower dietary fat SO PUBLIC HEALTH NUTRITION LA English DT Article DE Cardiovascular disease; Children; Dietary recommendations; Diet quality; Diet quality index; Intervention; Nutrition education AB Objective: To evaluate the impact of nutrition education promoting lower dietary fat on the overall diet quality in children using a multidimensional index that measures nutrient and food intakes in relation to US dietary recommendations. Design: Prospective cohort study with two intervention and two control groups. Children with elevated low density lipoprotein (LDL) cholesterol were randomized to one of two intervention groups or an at-risk control group. The intervention children received either the parent-child autotutorial (PCAT) programme, a 10-week home-based self-instruction nutrition education programme, or nutrition counselling from a registered dietitian. Children with non-elevated plasma cholesterol formed the not-atrisk control group. Dietary and blood data were collected at baseline and at 3 months. Setting: Paediatric practices in suburbs north of Philadelphia, PA. Subjects: Two hundred and twenty-seven 4-10-year-old children with elevated LDL cholesterol between the 80th and 98th percentiles, and 76 age-and gender-matched children with non-elevated plasma cholesterol, were studied. Results: Children who received PCAT or counselling significantly improved their overall diet quality (-0.6 and -0.4 change in diet quality index (DQI) scores) compared with at-risk control children. Children who received either form of nutrition education were more likely to meet the recommendations for three components of the DQI (total fat, saturated fat, sodium) (OR>1.7), but did not improve their intakes of three components of the DQI (vegetables and fruits, complex carbohydrates, calcium) at 3 months. Conclusions: Nutrition education promoting lower dietary fat improved children's overall diet quality. However, several dietary behaviours important for long-term health remained unchanged. C1 [Dixon, Lori Beth] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Tershakovec, Andrew M.] Childrens Hosp Philadelphia, Div Gastroenterol & Nutr, Philadelphia, PA 19104 USA. [McKenzie, Jeannie; Shannon, Barbara] Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. RP Dixon, LB (reprint author), NCI, Canc Prevent Div, Bethesda, MD 20892 USA. EM ld120i@nih.gov FU National Heart, Lung and Blood Institute, National Institutes of Health [HL43880-03]; Howard Heinz Endowment; National Dairy Promotion and Research Board in conjunction with the National Dairy Council FX The Children's Health Project was supported by grant HL43880-03 from the National Heart, Lung and Blood Institute, National Institutes of Health; a grant from the Howard Heinz Endowment; and a grant from the National Dairy Promotion and Research Board in conjunction with the National Dairy Council. Informed consent was obtained from the caretakers of all participants in accordance with the internal review board at the Children's Hospital of Philadelphia and the Office of Regulatory Compliance for the Protection of Human Subjects at the Pennsylvania State University. The authors greatly appreciate the insightful comments of Drs Christopher Gardner, Michaela Kiernan and Marilyn Winkleby on earlier drafts of the manuscript. NR 28 TC 10 Z9 10 U1 1 U2 3 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 DEC PY 2000 VL 3 IS 4 BP 411 EP 416 DI 10.1017/S1368980000000471 PG 6 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA V32YG UT WOS:000208985900005 PM 11135795 ER PT J AU Lubin, JH AF Lubin, JH TI A brief history of the American Statistical Association conference on radiation and health SO RADIATION RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2000 VL 154 IS 6 BP 715 EP 716 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 380MG UT WOS:000165705200015 ER PT J AU Kraemer, KH AF Kraemer, KH TI Predisposition, susceptibility and DNA repair in radiation-induced skin cancer SO RADIATION RESEARCH LA English DT Meeting Abstract ID XERODERMA-PIGMENTOSUM C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 6 TC 1 Z9 1 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2000 VL 154 IS 6 BP 724 EP 724 PG 1 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 380MG UT WOS:000165705200026 PM 11187013 ER PT J AU Gilbert, E AF Gilbert, E TI Discussion: Temporal effects in radiation Epidemiology - II SO RADIATION RESEARCH LA English DT Meeting Abstract ID IONIZING-RADIATION; CANCER MORTALITY; WORKERS C1 NCI, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2000 VL 154 IS 6 BP 734 EP 735 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 380MG UT WOS:000165705200038 ER PT J AU Ron, E AF Ron, E TI Protraction effects in radiation studies: Epidemiology SO RADIATION RESEARCH LA English DT Meeting Abstract C1 NCI, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2000 VL 154 IS 6 BP 737 EP 738 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 380MG UT WOS:000165705200041 PM 11187024 ER PT J AU Lubin, J Tucker, M AF Lubin, J Tucker, M TI Major cancer susceptibility genes and radiation: What do we know? SO RADIATION RESEARCH LA English DT Meeting Abstract ID BASAL-CELL CARCINOMA; RETINOBLASTOMA; MUTATIONS; RISK C1 NCI, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 NR 14 TC 0 Z9 0 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 2000 VL 154 IS 6 BP 740 EP 741 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 380MG UT WOS:000165705200044 ER PT J AU Tan, W Zolotukhin, AS Bear, J Patenaude, DJ Felber, BK AF Tan, W Zolotukhin, AS Bear, J Patenaude, DJ Felber, BK TI The mRNA export in Caenorhabditis elegans is mediated by Ce-NXF-1, an ortholog of human TAP/NXF and Saccharomyces cerevisiae Mex67p SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE import; nuclear rim; nucleocytoplasmic transport; nucleoporin; RNA binding; RNA interference; shuttling protein ID IMMUNODEFICIENCY-VIRUS TYPE-1; MESSENGER-RNA EXPORT; CONSTITUTIVE TRANSPORT ELEMENT; DOUBLE-STRANDED-RNA; NUCLEAR EXPORT; HUMAN TAP; NUCLEOCYTOPLASMIC TRANSPORT; GENETIC INTERFERENCE; REV; PROTEIN AB Human TAP and Saccharomyces cerevisiae Mex67p belong to a family of proteins that mediate mRNA export. Computer searches identified previously two Caenorhabditis elegans genes, C15H11.3 and C15H11.6, that encode putative homologs of hTAP and Mex67p (Segref et al., EMBO J, 1997, 16:3256-3271). Using RNA interference experiments in C. elegans, we found that functional knockout of C15H11.3 resulted in nuclear accumulation of poly(A)-containing RNAs and was lethal for both embryos and adult nematodes. No embryonic or progeny abnormality was observed in functional knockout of C15H11.6. Taken together, these data established that the C15H11.3 gene product is an ortholog of hTAP and Mex67p; thus, it was named Ce-NXF-1. Ce-NXF-1 binds RNA directly and is a nucleocytoplasmic shuttle protein accumulating in the nucleoplasm and at the nuclear rim. The rim association is mediated via unique signals present in the C-terminal portion of all TAP/NXF and Mex67p proteins. This region was shown to interact with the PC-repeat domains of nucleoporins Nup98, Nup153, and Nup214, indicating that the rim association occurs through components of the nuclear pore complex. In summary, Ce-NXF-1 belongs together with hTAP and Mex67p to a family of proteins that participate in mRNA export and can provide a direct molecular link between mRNAs and components of the nuclear pore complex. Therefore, despite differences in mRNA metabolism between these species, they utilize a conserved mRNA transport mechanism. C1 NCI, Basic Res Lab, Human Retrovirus Pathogenesis Sect, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Felber, BK (reprint author), NCI, Basic Res Lab, Human Retrovirus Pathogenesis Sect, Frederick Canc Res & Dev Ctr, Bldg 535,Room 110, Frederick, MD 21702 USA. NR 40 TC 82 Z9 87 U1 1 U2 5 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 DEC PY 2000 VL 6 IS 12 BP 1762 EP 1772 DI 10.1017/S1355838200000832 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 384BF UT WOS:000165918600011 PM 11142376 ER PT J AU Sheard, MA Sharrow, SO Takahama, Y AF Sheard, MA Sharrow, SO Takahama, Y TI Synchronous deletion of Mtv-superantigen-reactive thymocytes in the CD3(medium/high) CD4(+)CD8(+) subset SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; MAMMARY-TUMOR VIRUS; NEGATIVE SELECTION; TRANSGENIC MICE; POSITIVE SELECTION; ANTIGEN RECEPTOR; CLONAL DELETION; I-E; EXPRESSION; THYMUS AB Multiple model systems have demonstrated that negatively selected thymocytes can be deleted during the immature CD4(+)CD8(+) CD3(low) stage after high affinity interaction of T-cell receptors (TCRs) with antigen:major histocompatibility complex (MHC) complexes. Superantigens (SAGs) derived from endogenous mammary tumour viruses (Mtv) induce negative selection of Mtv-SAG-reactive thymocytes regardless of which peptide antigen is presented by MHC molecules. In this study, the timing of deletion of multiple subsets of Mtv-SAG-reactive CD4(+)CD8(+) thymocytes was investigated by a 4 colour flow cytometry in SJL x CBA/J cross-bred mice. Deletion of V beta3(+), V beta5(+), V beta 11(+), and V beta 17(+) Mtv-SAG-reactive thymocytes was found to occur synchronously in the most mature CD3(medium) and early CD3(high) subsets of CD4(+)CD8(+) thymocytes, in contrast with reports showing that the deletion of Mtv-SAG-reactive thymocytes can occur at different stages in particular model systems. C1 Masaryk Mem Canc Inst, Flow Cytometry Lab, Dept Cellular & Mol Oncol, Brno 65653, Czech Republic. NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. Univ Tokushima, Inst Genome Res, Dept Expt Immunol, Tokushima 770, Japan. RP Sheard, MA (reprint author), Masaryk Mem Canc Inst, Flow Cytometry Lab, Dept Cellular & Mol Oncol, Zluty Kopec 7, Brno 65653, Czech Republic. RI Takahama, Yousuke/A-5863-2010 NR 31 TC 3 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 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD DEC PY 2000 VL 52 IS 6 BP 550 EP 554 DI 10.1046/j.1365-3083.2000.00814.x PG 5 WC Immunology SC Immunology GA 383YD UT WOS:000165911500005 PM 11119259 ER PT J AU Mezey, E Chandross, KJ Harta, G Maki, RA McKercher, SR AF Mezey, E Chandross, KJ Harta, G Maki, RA McKercher, SR TI Turning blood into brain: Cells bearing neuronal antigens generated in vivo from bone marrow SO SCIENCE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELLS; ADULT MAMMALIAN FOREBRAIN; IN-VIVO; RAT; DIFFERENTIATE; ASTROCYTES; MICE; NEUN; IDENTIFICATION AB Bone marrow stern cells give rise to a variety of hematopoietic Lineages and repopulate the blood throughout adult Life. We show that, in a strain of mice incapable of developing colts of the myeloid and Lymphoid lineages,transplanted adult bone marrow cells migrated into the brain and differentiated into cells that expressed neuron-specific antigens. These findings raise the possibility that bone marrow-derived cells may provide an alternative source of neurons in patients with neurodegenerative diseases or central nervous system injury. C1 NINDS, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. NINDS, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. Burnham Inst, La Jolla, CA 92037 USA. Neurocrine Biosci, San Diego, CA 92121 USA. RP Mezey, E (reprint author), NINDS, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI30656] NR 43 TC 1317 Z9 1497 U1 5 U2 35 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 DEC 1 PY 2000 VL 290 IS 5497 BP 1779 EP 1782 DI 10.1126/science.290.5497.1779 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 379FY UT WOS:000165632400047 PM 11099419 ER PT J AU Hasegawa, RP Blitz, AM Geller, NL Goldberg, ME AF Hasegawa, RP Blitz, AM Geller, NL Goldberg, ME TI Neurons in monkey prefrontal cortex that track past or predict future performance SO SCIENCE LA English DT Article ID DELAYED-RESPONSE TASK; WORKING-MEMORY; SINGLE NEURONS; DOPAMINE; PRIMATE; LESIONS; FIELDS AB Although frontal cortex is thought to be important in controlling behavior across Long periods of time, most studies of this area concentrate on neuronal responses instantaneously relevant to the current task. In order to investigate the relationship of frontal activity to behavior over Longer time periods, we trained rhesus monkeys on a difficult oculomotor task. Their performance fluctuated during the day, and the activity of prefrontal neurons, even measured while the monkeys waited for the targets to appear at the beginning of each set of trials, correlated with performance in a probabilistic rather than a determinist manner: neurons reflected past or predicted future performance, much more than they reflected current performance. We suggest that this activity is related to processes such as arousal or motivation that set the tone for behavior rather than controlling it on a millisecond basis, and could result from ascending pathways that utilize slow, second-messenger synaptic processes. C1 NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Neurol, Washington, DC 20007 USA. RP Hasegawa, RP (reprint author), NEI, Sensorimotor Res Lab, Bldg 10, Bethesda, MD 20892 USA. NR 19 TC 47 Z9 48 U1 1 U2 1 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 DEC 1 PY 2000 VL 290 IS 5497 BP 1786 EP 1789 DI 10.1126/science.290.5497.1786 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 379FY UT WOS:000165632400049 PM 11099421 ER PT J AU Wilson, WH AF Wilson, WH TI Chemotherapy sensitization by rituximab: Experimental and clinical evidence SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT 2nd Annual Oncology Consensus Conference on Recent Advances and New Therapeutic Directions for Hematologic Malignacies CY JAN 12-16, 2000 CL NW UNIV MED SCH, KAILUA-KONA, HAWAII HO NW UNIV MED SCH ID ANTI-CD20 MONOCLONAL-ANTIBODY; B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; CYCLE PROGRESSION; APOPTOSIS; COMBINATION; SENSITIVITY; GLUTATHIONE C1 NCI, Div Clin Sci, Med Branch, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Div Clin Sci, Med Branch, Bldg 10,Room 12N-226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 44 TC 30 Z9 31 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2000 VL 27 IS 6 SU 12 BP 30 EP 36 PG 7 WC Oncology SC Oncology GA 401ZD UT WOS:000166958700006 PM 11225998 ER PT J AU Cantor, D AF Cantor, D TI RSI and the experts: The construction of medical knowledge SO SOCIAL HISTORY OF MEDICINE LA English DT Book Review C1 NIH, Bethesda, MD 20892 USA. RP Cantor, D (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0951-631X J9 SOC HIST MED JI Soc. Hist. Med. PD DEC PY 2000 VL 13 IS 3 BP 581 EP 582 PG 2 WC History; History & Philosophy Of Science SC History; History & Philosophy of Science GA 386JM UT WOS:000166057800033 ER PT J AU Park, BS AF Park, BS TI The contexts of simultaneous discovery: Slater, Pauling, and the origins of hybridisation SO STUDIES IN HISTORY AND PHILOSOPHY OF MODERN PHYSICS LA English DT Article ID CHEMISTRY C1 NIH, Hist Off, Bethesda, MD 20892 USA. RP Park, BS (reprint author), NIH, Hist Off, Bldg 31 Room 2B09, Bethesda, MD 20892 USA. NR 38 TC 10 Z9 10 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1355-2198 J9 STUD HIST PHILOS M P JI Stud. Hist. Philos. Mod. Phys. PD DEC PY 2000 VL 31B IS 4 BP 451 EP 474 DI 10.1016/S1355-2198(00)00027-7 PG 24 WC History & Philosophy Of Science; Physics, Multidisciplinary SC History & Philosophy of Science; Physics GA 372PT UT WOS:000165243000003 ER PT J AU Libutti, SK Choyke, PL Alexander, HR Glenn, G Bartlett, DL Zbar, B Lubensky, I McKee, SA Maher, ER Linehan, WM Walther, MM AF Libutti, SK Choyke, PL Alexander, HR Glenn, G Bartlett, DL Zbar, B Lubensky, I McKee, SA Maher, ER Linehan, WM Walther, MM TI Clinical and genetic analysis of patients with pancreatic neuroendocrine tumors associated with von Hippel-Lindau disease SO SURGERY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the American-Association-of-Endocrine-Surgeons CY MAY 22-25, 2000 CL LONDON, ENGLAND SP Amer Assoc Endocrine Surgeons ID ISLET CELL TUMORS; SUPPRESSOR GENE; PREVALENCE; LESIONS AB Background. Patients with von Hippel-Lindau disease (VHL) may develop pancreatic neuroendocrine tumors (PNETs), which can behave in a malignant fashion. We prospectively evaluated size criteria for resection of lesions and the role of genotype/phenotype analysis of germline VHL mutations in predicting clinical course. Methods. From December 1988 through December 1999 we screened 389 patients with VHL. The diagnosis of PNET was made by pathologic analysis of tissues or by radiographic appearance. Germline mutations were determined by quantitative Southern blotting, fluorescence in situ hybridization and complete gene sequencing. Results. Forty-four patients with PNETs have been identified; 25 have undergone surgical resection, 5 had metastatic disease, and 14 are being monitored. No patient who has undergone resection based on turner size criteria has developed metastases. Patients with PNETs were mom likely to have missense mutations (58%), and 4 of 5 patients (80%) with metastatic disease had mutations nz exon 3 compared with 18 of 39 (46%) patients without metastatic disease. Conclusions. Imaging-for detection and surgical resection based on size criteria have resulted in the successful management of VHL patients with PNETs. Analysis of germline mutations may help identify patients at risk for PNET and which patients may benefit from surgical intervention. C1 NCI, Surg Branch, Surg Metab Sect, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, Surg Metab Sect, Bldg 10,Room 2B07,10 Ctr Dr, Bethesda, MD 20892 USA. RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 19 TC 52 Z9 52 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2000 VL 128 IS 6 BP 1022 EP 1027 DI 10.1067/msy.2000.110239 PG 6 WC Surgery SC Surgery GA 381RC UT WOS:000165776000038 PM 11114638 ER PT J AU Feingold, DL Alexander, HR Chen, CC Libutti, SK Shawker, TH Simonds, WF Marx, SJ Skarulis, MC Doppman, JL Schrump, DS Bartlett, DL AF Feingold, DL Alexander, HR Chen, CC Libutti, SK Shawker, TH Simonds, WF Marx, SJ Skarulis, MC Doppman, JL Schrump, DS Bartlett, DL TI Ultrasound and sestamibi scan as the only preoperative imaging tests in reoperation for parathyroid adenomas SO SURGERY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the American-Association-of-Endocrine-Surgeons CY MAY 22-25, 2000 CL LONDON, ENGLAND SP Amer Assoc Endocrine Surgeons ID PRIMARY HYPERPARATHYROIDISM; LOCALIZATION; PERSISTENT; SURGERY AB Background. In an effort to determine an efficient algorithm for the evaluation of patients with parathyroid adenomas in the reoperative setting; we explored the combination of using ultrasound scans (US) and sestamibi scintigraphy as the only preoperative imaging tests. Methods. We analyzed the outcomes of 62 consecutive patients who were treated between January 1995 and May 1999 and who were referred for persistent primary hyperparathyroidism after initial surgical exploration, at which time no abnormal parathyroid glands had been found. Although all patients underwent US, computed tomography scan, magnetic resonance imaging, and sestamibi scan, we analyzed the success of localization and reoperation using only the results of US and sestamibi scan. Results, Sixty-one patients (98%) underwent curative reoperations. The sensitivity, positive predictive value, and accuracy for US were 90%, 86%, and 84%, respectively; the corresponding values for sestamibi imaging were 78%, 94%, and 74%, respectively. In 58 of 62 cases (94%) preoperative US and/or sestamibi scan accurately identified the adenoma. In 3 patients for whom combined US and sestamibi scan were inaccurate, 1 adenoma was found by intraoperative US in the strap muscle; 1 adenoma was found by blind cervical thymectomy, and 1 adenoma was found by planned sternotomy that was based on computed tomography findings. Conclusions. This study supports an algorithm of obtaining US and sestamibi scan as the initial and perhaps only preoperative localization tests for patients with primary hyperparathyroidism after failed operation, at which time no abnormal glands had been found. C1 NCI, Surg Branch, Thorac Oncol Sect, NIH, Bethesda, MD 20892 USA. NCI, Surg Metab Sect, NIH, Bethesda, MD 20892 USA. NIDDKD, Dept Nucl Med, NIH, Bethesda, MD 20892 USA. NIDDKD, Dept Diagnost Radiol, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Bartlett, DL (reprint author), NCI, Surg Branch, Thorac Oncol Sect, NIH, Bldg 10,9000 Rockville Pike,Room 2B16, Bethesda, MD 20892 USA. NR 10 TC 51 Z9 52 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2000 VL 128 IS 6 BP 1103 EP 1109 DI 10.1067/msy.2000.109963 PG 7 WC Surgery SC Surgery GA 381RC UT WOS:000165776000059 PM 11114649 ER PT J AU Spivak, CE Beglan, CL AF Spivak, CE Beglan, CL TI Kinetics of recovery from opioids at wild-type and mutant mu opioid receptors expressed in Xenopus oocytes SO SYNAPSE LA English DT Article DE G protein-coupled receptor; GIRK1; voltage clamp; steric model ID SITE-DIRECTED MUTAGENESIS; LIGAND-BINDING; TRANSMEMBRANE DOMAIN; SIGNAL-TRANSDUCTION; ADENOSINE RECEPTOR; ANTAGONIST BINDING; OPIATE RECEPTOR; CLONING; AGONIST; ACTIVATION AB To investigate a previous observation that classical antagonists behave as agonists at mutant H297N and H297Q mu opioid receptors, we compared the kinetics of recovery from opioids at wild-type and mutant mu receptors expressed in voltage-clamped Xenopus oocytes. The cDNA for the potassium channel GIRK1 was coinjected into the oocytes with that of the mu receptors to transduce agonist binding into a coupled electrophysiological response. The kinetics of recovery were estimated by brief test pulses of the agonist normorphine given at a frequency of 0.67 or 1 per min. After treatment with a variety of agonists, the receptors recovered from desensitization at rates that depended on the agonist, but there was little difference between mutant and wild-type receptors. Antagonists, however, induced agonist-like currents and demonstrated faster recovery at the mutant receptors. These results suggest that His-297 may comprise part of an antagonist subsite. This conclusion, when coupled with the steric theory that intrinsic activity depends on independent binary equilibration of a drug between agonist and antagonist subsites, could unify the paired observations that antagonists become agonists and recover faster at the mutant than at the wild-type receptors. Published 2000 Wiley-Liss, Inc.dagger C1 Natl Inst Drug Abuse, Intramural Res Program, Cellular Neurobiol Branch, Baltimore, MD 21224 USA. RP Spivak, CE (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Cellular Neurobiol Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 40 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD DEC 1 PY 2000 VL 38 IS 3 BP 254 EP 260 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 366FD UT WOS:000089993400004 PM 11020228 ER PT J AU Hirshberg, B Veldhuis, JD Sarlis, NJ AF Hirshberg, B Veldhuis, JD Sarlis, NJ TI Diurnal thyrotropin secretion in short-term profound primary hypothyroidism: Does it ever persist? SO THYROID LA English DT Article; Proceedings Paper CT 11th International Congress of Endocrinology (ICE 2000) CY 2000 CL SYDNEY, AUSTRALIA ID SERUM THYROTROPIN; PLASMA THYROTROPIN; PULSATILE THYROTROPIN; THYROID-DISORDERS; SLEEP-DEPRIVATION; TSH RELEASE; NORMAL MEN; LONG-TERM; PROLACTIN; HORMONE AB Circulating serum thyrotropin (TSH) levels in euthyroid humans show a definite circadian variation, which is maintained in both mild hyperthyroidism and mild hypothyroidism. Yet conflicting data exist with regard to whether this variation persists in at least some patients with severe primary hypothyroidism. We, therefore, studied the diurnal variation in serum TSH in 10 patients (age range 20 to 84 years) with a history of thyroid failure due to prior total thyroidectomy and radioiodine (RAI) ablative treatment performed for thyroid cancer after short-term discontinuation of thyroid hormone (TH) therapy. Serum TSH was measured hourly for a 24-hour period. All data were normalized by converting the TSH values to a percentage (%), designating the 11:00 hour value as 100% (baseline). The average serum TSH levels were markedly elevated in all patients. There was no statistically significant difference between the TSH % values at any time during the 24-hour period when compared with baseline. Further, cosine regression analysis showed absence of rhythmicity in TSH % values over time; notably, no patient showed a variation in TSH % values greater than or equal to 15% of baseline. In conclusion, diurnal rhythmicity in serum TSH levels was abolished in a uniform cohort of patients with short-term severe primary hypothyroidism. We speculate that the complete lack of peripheral negative feedback input to the hypothalamus or pituitary or both may override the central rhythm-sustaining influences on TSH secretion. C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Div Intramural Res, Bethesda, MD 20892 USA. Univ Virginia, Hlth Syst, Div Endocrinol & Metab, Charlottesville, VA USA. RP Sarlis, NJ (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bldg 10,Room 8D12C,10 Ctr Dr,MSC 1758, Bethesda, MD 20892 USA. NR 54 TC 5 Z9 5 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD DEC PY 2000 VL 10 IS 12 BP 1101 EP 1106 DI 10.1089/thy.2000.10.1101 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 392NN UT WOS:000166417700012 PM 11201856 ER PT J AU Chhabra, SK Anderson, LM Perella, C Desai, D Amin, S Kyrtopoulos, SA Souliotis, VL AF Chhabra, SK Anderson, LM Perella, C Desai, D Amin, S Kyrtopoulos, SA Souliotis, VL TI Coexposure to ethanol with N-nitrosodimethylamine or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone during lactation of rats: Marked increase in O-6-methylguanine-DNA adducts in maternal mammary gland and in suckling lung and kidney SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE nitrosamine; alcohol; O-6-methylguanine; rat; mammary; lactation; N-nitrosodimethylamine (NDMA); 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; (NNK); lung; kidney ID FOOD-DERIVED CARCINOGEN; BREAST-MILK; POLYCHLORINATED-BIPHENYLS; ALCOHOL-CONSUMPTION; TRANSGENIC MICE; LIVER-TUMORS; DNA ALKYLTRANSFERASE; THYMIC LYMPHOMAS; PATAS MONKEYS; MUTAGEN PHIP AB Use of alcoholic beverages increases risk of cancer at several target sites, including the breast. Of several possible mechanisms for this effect, competitive inhibition by ethanol of hepatic clearance of nitrosamines, resulting in increased dose delivery to posthepatic tissues; gives the quantitatively most pronounced enhancement. We investigated whether this effect would pertain to the mammary gland, and to ethanol and nitrosamines delivered translactationally to sucklings Ethanol (1.6 g/kg) was administered by gavage to nursing Sprague-Dawley rats 10 min before 5 mg/kg N-nitrosodimethylamine (NDMA) or 50 mg/kg 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); treatment was on postnatal days 1, 7, or 14. Tissues taken 4 h later for analysis of O-6-methylguanine in DNA were liver, blood, and mammary glands from the mothers, and liver, lung, kidney, and blood from the sucklings. Ethanol cotreatment resulted in a marked, Ill-fold increase in O-6-methylguanine adducts from NDMA in mammary gland, as well as smaller but significant increases in this tissue from NNK and in maternal blood cells from both chemicals; adducts in maternal liver decreased slightly. In the sucklings, ethanol cotreatment also lowered adducts in liver after NDMA or NNK treatment. After NDMA, adducts were also defected in suckling lung and kidney and were increased five- to 10-fold after ethanol coexposure. Adducts from either chemical, with or without ethanol, decreased markedly in all suckling tissues with development from postnatal day 1 to day 14. Thus ethanol coexposure with nitrosamines increases O-6-methylguanine DNA adducts in mammary gland and strongly influences adduct formation in suckling tissues after translactational delivery. (C) 2000 Academic Press. C1 SAIC Frederick Inc, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Ft Detrick, MD 21702 USA. Amer Hlth Fdn, Valhalla, NY 10595 USA. Natl Hellen Res Fdn, Inst Biol Res & Biotechnol, GR-11635 Athens, Greece. RP Anderson, LM (reprint author), SAIC Frederick Inc, Frederick Canc Res & Dev Ctr, Bldg 538, Ft Detrick, MD 21702 USA. NR 70 TC 12 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 1 PY 2000 VL 169 IS 2 BP 191 EP 200 DI 10.1006/taap.2000.9068 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 383RZ UT WOS:000165897800009 PM 11097872 ER PT J AU McEntyre, J AF McEntyre, J TI This round's on TiBS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP McEntyre, J (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,Rm 8S806,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2000 VL 25 IS 12 BP 581 EP 581 DI 10.1016/S0968-0004(00)01724-2 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 394GN UT WOS:000166515800002 ER PT J AU Maizel, JV AF Maizel, JV TI SDS polyacrylamide gel electrophoresis SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Maizel, JV (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. NR 15 TC 10 Z9 10 U1 3 U2 17 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 DEC PY 2000 VL 25 IS 12 BP 590 EP 592 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 394GN UT WOS:000166515800008 PM 11116183 ER PT J AU Baumeister, W Steven, AC AF Baumeister, W Steven, AC TI Macromolecular electron microscopy in the era of structural genomics SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID LARGE RIBOSOMAL-SUBUNIT; X-RAY CRYSTALLOGRAPHY; CRYOELECTRON MICROSCOPY; ANGSTROM RESOLUTION; 3-DIMENSIONAL STRUCTURE; 8-ANGSTROM RESOLUTION; PURPLE MEMBRANE; WATER CHANNEL; ATOMIC MODEL; VIRUS AB Macromolecular machines carry out many cellular functions. Cryo-electron microscopy (cryo-EM) is emerging as a powerful method for studying the structure, assembly and dynamics of such macromolecules, and their interactions with substrates. With resolutions still improving, 'single-particle' analyses are already depicting secondary structure. Moreover, cryo-EM can be combined in several ways with X-ray diffraction to enhance the resolution of cryo-EM and the applicability of crystallography. Electron tomography holds promise for visualizing machines at work inside cells. C1 Max Planck Inst Biochem, Dept Mol Struct Biol, D-82152 Martinsried, Germany. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Baumeister, W (reprint author), Max Planck Inst Biochem, Dept Mol Struct Biol, Klopferspitz 18A, D-82152 Martinsried, Germany. NR 62 TC 112 Z9 114 U1 1 U2 10 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 DEC PY 2000 VL 25 IS 12 BP 624 EP 631 DI 10.1016/S0968-0004(00)01720-5 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 394GN UT WOS:000166515800015 PM 11116190 ER PT J AU Reitman, ML Arioglu, E Gavrilova, O Taylor, SI AF Reitman, ML Arioglu, E Gavrilova, O Taylor, SI TI Lipoatrophy revisited SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID CONGENITAL GENERALIZED LIPODYSTROPHY; HIV PROTEASE INHIBITORS; ADIPOSE-TISSUE; DIABETES-MELLITUS; INSULIN-RESISTANCE; JUVENILE DERMATOMYOSITIS; GENE; MICE; LEPTIN; OBESITY AB The lipoatrophy syndromes are a heterogeneous group of syndromes characterized by a paucity of adipose tissue. Severe lipoatrophy is associated with insulin-resistant diabetes mellitus (DM). The loss of adipose tissue can have a genetic, immune, or infectious/drug-associated etiology. Causative mutations have been identified in patients for one form of partial lipoatrophy - Dunnigan-type familial partial lipodystrophy. Experiments using lipoatrophic mice demonstrate that the diabetes results from the lack of fat and that leptin deficiency is a contributing factor Thiazolidinedione therapy improves metabolic control in lipoatrophic patients; the efficacy of leptin treatment is currently being investigated. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Reitman, ML (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 10,Room 8N-250,10 Ctr Dr, Bethesda, MD 20892 USA. RI Reitman, Marc/B-4448-2013; OI Reitman, Marc/0000-0002-0426-9475; Oral, Elif/0000-0002-9171-1144 NR 62 TC 138 Z9 144 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD DEC PY 2000 VL 11 IS 10 BP 410 EP 416 DI 10.1016/S1043-2760(00)00309-X PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 383AY UT WOS:000165860600004 PM 11091118 ER PT J AU Hottiger, MO Nabel, GJ AF Hottiger, MO Nabel, GJ TI Viral replication and the coactivators p300 and CBP SO TRENDS IN MICROBIOLOGY LA English DT Review ID LARGE-T-ANTIGEN; HUMAN-PAPILLOMAVIRUS TYPE-16; ADENOVIRAL ONCOPROTEIN E1A; NUCLEAR-PROTEIN CBP; NF-KAPPA-B; HISTONE ACETYLTRANSFERASE; HIV-1 TAT; TRANSCRIPTIONAL ACTIVATION; DEPENDENT KINASES; CELL-CYCLE AB Productive viral infection requires coordinate regulation of viral and cellular gene expression. Viruses of different classes have evolved different mechanisms to conform to, adapt to and exploit programs of cellular gene expression. Many viral gene products influence and respond to cellular signals that control differentiation and proliferation Transcriptional coactivators are central to the regulation of the expression of genes controlling these events, p300 and CBP are closely related coactivators that regulate the transcription of specific genes, modify chromatin structure and influence cell cycle progression. In this review, the different molecular interactions of proteins encoded by DNA tumor viruses and lentiviruses with these transcriptional coactivators and related cellular proteins are summarized. C1 Univ Zurich, Inst Vet Biochem, CH-8057 Zurich, Switzerland. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Hottiger, MO (reprint author), Univ Zurich, Inst Vet Biochem, Winterthurerstr 190, CH-8057 Zurich, Switzerland. RI Hottiger, Michael/J-7747-2013 OI Hottiger, Michael/0000-0002-7323-2270 NR 40 TC 31 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD DEC PY 2000 VL 8 IS 12 BP 560 EP 565 DI 10.1016/S0966-842X(00)01874-6 PG 6 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 392RH UT WOS:000166425100017 PM 11115752 ER PT J AU Fields, RD Stevens, B AF Fields, RD Stevens, B TI ATP: an extracellular signaling molecule between neurons and glia SO TRENDS IN NEUROSCIENCES LA English DT Review ID TRANSMEMBRANE CONDUCTANCE REGULATOR; INCREASES INTRACELLULAR CALCIUM; FROG NEUROMUSCULAR-JUNCTION; MYELINATING SCHWANN-CELLS; DEVELOPING NERVOUS-SYSTEM; CYCLIC-AMP ACCUMULATION; MOUSE MICROGLIAL CELLS; EXCITATORY AMINO-ACIDS; ROOT GANGLION NEURONS; PROTEIN-KINASE-C AB Recent studies on Schwann cells at the neuromuscular junction and non-synaptic regions of premyelinated axons indicate that extracellular ATP can act as an activity-dependent signaling molecule in communication between neurons and glia. Several mechanisms have been observed for the regulated release of ATP from synaptic and non-synaptic regions, and a diverse family of receptors for extracellular ATP has been characterized. the findings suggest functional consequences of neuron-glial communication beyond homeostasis of the extracellular environment surrounding neurons, including regulating synaptic strength, gene expression, mitotic rate, and differentiation of glia according to impulse activity in neural circuits. C1 NICHD, Neurocytol & Physiol Unit, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Biol, Neurosci & Cognit Sci Program, College Pk, MD 20892 USA. RP Fields, RD (reprint author), NICHD, Neurocytol & Physiol Unit, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A38,49 Convent Dr, Bethesda, MD 20892 USA. NR 93 TC 228 Z9 238 U1 2 U2 12 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD DEC PY 2000 VL 23 IS 12 BP 625 EP 633 DI 10.1016/S0166-2236(00)01674-X PG 9 WC Neurosciences SC Neurosciences & Neurology GA 382CW UT WOS:000165801700011 PM 11137153 ER PT J AU Rovner, E Propert, KJ Brensinger, C Wein, AJ Foy, M Kirkemo, A Landis, JR Kusek, JW Nyberg, LM AF Rovner, E Propert, KJ Brensinger, C Wein, AJ Foy, M Kirkemo, A Landis, JR Kusek, JW Nyberg, LM CA Interstitial Cystitis Data Base St TI Treatments used in women with interstitial cystitis: The Interstitial Cystitis Data Base (ICDB) study experience SO UROLOGY LA English DT Article ID DIAGNOSIS; EPIDEMIOLOGY AB Objectives. To evaluate the frequency and types of treatments reported at baseline in women who entered the Interstitial Cystitis Data Base (ICDB) cohort study. Methods. From 1993 to 1997, 581 women were enrolled and followed in the ICDB. All treatments reported at study entry, including those prescribed for interstitial cystitis (IC) and concomitant medications, were reviewed. The number and types of treatments were evaluated with respect to baseline factors such as prior diagnosis of IC and symptom severity. Results. One hundred five (18%) women were receiving no therapy at baseline. Single-mode therapy was reported by 195 (34%) women, and a combination of two treatments was reported by 119 (21%) women. Three or more treatments were reported in 162 (28%) women, A total of 183 different types of therapies were recorded. The five most commonly used therapies for IC symptoms were cystoscopy and hydrodistention, amitriptyline, phenazopyridine, special diet, and intravesical heparin. Because most patients entered the ICDB before the approval of oral pentosan polysulfate sodium (PPS), only 6% of women reported oral PPS use at baseline. There were statistically significant associations between the number and types of treatments and clinical center, a prior diagnosis of IC, and symptom severity. Conclusions. The diversity of IC therapies underscores the lack of understanding about the treatment of this syndrome. Further research in IC is essential to develop and to evaluate rational therapies and treatment algorithms. These algorithms should be "evidence based" and should be revised as the underlying etiology and pathophysiology of IC is delineated. UROLOGY 56: 940-945, 2000. (C) 2000, Elsevier Science Inc. C1 Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Metropolitan Urol Specialists PA, St Paul, MN USA. NIDDKD, Bethesda, MD 20892 USA. RP Propert, KJ (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Blockley Hall,6th Floor,423 Guardian Dr, Philadelphia, PA 19104 USA. RI Landis, J. Richard/A-9330-2010 FU NIDDK NIH HHS [U01-DK-54127, UO1-DK-45013, UO1-DK-45021] NR 22 TC 73 Z9 75 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD DEC PY 2000 VL 56 IS 6 BP 940 EP 945 DI 10.1016/S0090-4295(00)00845-1 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 383QQ UT WOS:000165894200012 PM 11113737 ER PT J AU Walther, MM Rehak, NN Venzon, D Myers, CE Linehan, WM Figg, WD AF Walther, MM Rehak, NN Venzon, D Myers, CE Linehan, WM Figg, WD TI Suramin administration is associated with a decrease in serum calcium levels SO WORLD JOURNAL OF UROLOGY LA English DT Article ID INDEPENDENT PROSTATE-CANCER; BONE-RESORPTION; HYDROCORTISONE; WITHDRAWAL; DRUG AB Suramin has been shown to have an effect on bone resorption in in vitro models. It is not clear if a similar effect is seen in patients treated with suramin. The clinical effect of suramin treatment on total serum calcium was examined in two groups of patients with hormone-refractory prostate cancer. In all, 28 patients in group 1 were examined within 2 weeks before and 2 weeks after suramin treatment and 72 patients in group 2 were examined within 2 weeks before, during, and after treatment with suramin. In addition. calcium controls spiked with suramin were run in three different commercially available assays for evaluation of the effect of suramin dose on calcium determination. Group 1 patients showed a decrease in serum calcium after treatment with suramin. The mean uncorrected serum calcium level was 2.29 +/- 0.025 mmol/l before treatment and 2.09 +/- 0.025 mmol/l after treatment (P < 0.0001, paired Wilcox-on test). The mean serum calcium value corrected for albumin was 2.33 +/- 0.02 mmol/l before treatment and 2.24 +/- 0.02 mmol/l after treatment (P = 0.0022, paired Wilcoxon test). Group 2 patients also displayed a decrease in serum calcium after treatment with suramin. The mean baseline value was 2.23 mmol/l (median 2.26 mmol/l, range 1.2-2.54 mmol/l). The mean level of serum calcium corrected for albumin as determined at the end of treatment was 2.14 mmol/l (median 2.16 mmol/1, range 0.98-2.46 mmol/l). In all, 48 patients for whom pre- and posttreatment values were available for analysis displayed a median calcium decrease of 0.09 mmol/l (P = 0.0005, Wilcoxon signed-rank test for the null hypothesis of no change). For 68 patients in group 2, data on serial serum calcium measurements during treatment were available for analysis. A projected median decrease in serum calcium of 0.06 mmol/l (range -0.43 to 0.72 mmol/l) over an 8-week interval of suramin therapy was found. Overall, 47 of the 68 slopes were negative (P = 0.0022, Wilcoxon signed-rank test). Nine patients were treated with suramin for less than 6 weeks. These patients' calcium levels were significantly higher than those of 50 patients treated for longer periods (median value 2.24 versus 2.16 mmol/l, P = 0.035, Wilcoxon rank-sum test). No correlation was found between suramin dose and calcium level using the Kodak Ektachem, Hitachi 914, or Synchron Clinical System CX3 method. In conclusion, suramin treatment was consistently associated with decreases in serum calcium in two groups of patients with hormone-refractory cancer. Suramin placed in calcium controls did not affect calcium determination using three commercially available methods. C1 NCI, Urol Oncol Branch, DCS, NIH, Bethesda, MD 20892 USA. NIH, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NIH, Div Canc Treatment, Bethesda, MD 20892 USA. NCI, Ctr Clin, NIH, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Dept Med, Div Hematol Oncol, Charlottesville, VA 22908 USA. RP Walther, MM (reprint author), NCI, Urol Oncol Branch, DCS, NIH, Bldg 10,Room 2B-43,10 Ctr Dr,MSC 1501, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008; Figg Sr, William/M-2411-2016 NR 13 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD DEC PY 2000 VL 18 IS 6 BP 388 EP 391 DI 10.1007/s003459900095 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 392MB UT WOS:000166413900003 PM 11204256 ER PT J AU Cho, YS Lee, YN Cho-Chung, YS AF Cho, YS Lee, YN Cho-Chung, YS TI Biochemical characterization of extracellular cAMP-dependent protein kinase as a tumor marker SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE cAMP; protein kinase A; cancer; extracellular protein kinase A; serum tumor marker ID CYCLIC-AMP; REGULATORY SUBUNIT; ECTOPROTEIN KINASE; MESSENGER-RNA; CELLS; DIFFERENTIATION; PHOSPHORYLATION; EXPRESSION; PEPTIDE; SURFACE AB In a recent report (Cho ct al., Proc. Natl. Acad. Sci. USA 97, 835-840, 2000), we showed that cancer cells of various cell types secrete cAMP-dependent protein kinase (PKA) into the conditioned medium and that in the serum of cancer patients this extracellular PICA (ECPKA) is upregulated 10-fold as compared with normal serum. Here, we characterized the enzymatic properties of ECPKA that is present in the conditioned medium of PC3M prostate cancer cells and in the serum of cancer patients, and we compared ECPKA with PICA found in the cell extracts of PC3M cells. ECPKA present in the conditioned medium and human serum was not activated by cAMP addition, but intracellular PHA activity was totally dependent on the addition of cAMP. This indicates that the ECPKA is present in active, free C subunit form, whereas intracellular PICA is present in inactive holoenzyme form. ECPKA activity increased in a substrate concentration- and time-dependent manner, as did intracellular PICA Both ECPKA and intracellular PICA activities were specifically inhibited by the PICA inhibitor protein, PHI. However, ECPKA activity was more temperature-sensitive than intracellular PKA; after two cycles of freezing/thawing, only 20% of initial ECPKA activity was detected compared with over 40% of intracellular PICA activity. Western blot analysis revealed the presence of a 40 kDa C-alpha subunit of PICA in both conditioned medium and in the serum of cancer patients. These results suggest that ECPKA, out of the context of cAMP regulation, may function as a growth factor promoting cell growth and transformation; thus, it may serve as a tumor biomarker. C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 26 TC 19 Z9 20 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 NOV 30 PY 2000 VL 278 IS 3 BP 679 EP 684 DI 10.1006/bbrc.2000.3853 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 380KW UT WOS:000165701900029 PM 11095968 ER PT J AU DePetrillo, PB Yang, QF Rackoff, J SanMiguel, A Karimullah, K AF DePetrillo, PB Yang, QF Rackoff, J SanMiguel, A Karimullah, K TI Surface fractal computation and its application to immunofluorescent histochemical studies of calpain and calpastatin in PC12 cells SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE fractal; calpain; calpastatin; actin; alcohol; ethyl ID NEURITE OUTGROWTH; DIMENSION; MEMBRANE AB The purpose of this report is to present a method which can be used to parameterize patterns of immunofluorescent staining in cultured neural cells. The algorithm is based on the observation that the variance in pixel intensity of the image is a power function of the magnitude of the area in immunofluorescently stained PC12 cells. This property is used to derive the fractal dimension (D) of the region of interest (ROI), and corresponds to the complexity of the pixel intensity associated with the ROI, which is analogous to a fractal surface. We show that the measure is useful in characterizing immunofluorescent staining patterns, and apply this measure to study the effects of ethanol exposure on mu -calpain and calpasratin-associated immunoreactivity. Exposure of PC12 cells to ethanol (80 mM) x 48 h resulted in alterations in immunofluorescent signal (Control vs ethanol) associated with actin, calpastatin and mu -calpain: 2289 +/- 166 vs 1709 +/- 69, P < 0.01; 1681 +/- 38 vs 2224 +/- 95, P < 0.001; 1823 +/- 39 vs 2841 +/- 68, P < 0.0001 respectively, magnitudes being pixel intensity units on a scale of 0-4095. D-values for the three proteins in the same order were: 2.32 +/- 0.01 vs 2.31 +/- 0.03, NS; 2.31 +/- 0.01 vs 2.32 +/- 0.01, NS; 2.16 +/- 0.03 vs 2.24 +/- 0.02, P < 0.01, with a possible D-value range of 2-3. (C) 2000 Published by Elsevier Science B.V. C1 NIAAA, Unit Clin & Biochem Pharmacol, Clin Studies Lab, Div Intramural Clin & Biochem Res,NIH, Bethesda, MD 20892 USA. RP DePetrillo, PB (reprint author), NIAAA, Unit Clin & Biochem Pharmacol, Clin Studies Lab, Div Intramural Clin & Biochem Res,NIH, Bldg 10,Room 3C-103,10 Ctr Dr MSC 1256, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD NOV 30 PY 2000 VL 103 IS 2 BP 191 EP 197 DI 10.1016/S0165-0270(00)00317-4 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 377KF UT WOS:000165512200008 PM 11084212 ER PT J AU Hager, GL Lim, CS Elbi, C Baumann, CT AF Hager, GL Lim, CS Elbi, C Baumann, CT TI Trafficking of nuclear receptors in living cells SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 113th Nobel Symposium on Estrogens and Women's Health: Benefit or Threat CY JUN 29-JUL 01, 1999 CL KARLSKRONA, SWEDEN SP Nobel Fdn DE steroid receptor; estrogen receptor ID GREEN-FLUORESCENT PROTEIN; HUMAN PROGESTERONE-RECEPTOR; THYROID-HORMONE RECEPTORS; GLUCOCORTICOID RECEPTOR; ESTROGEN-RECEPTOR; A-FORM; LOCALIZATION; VISUALIZATION; CHIMERA; TRANSCRIPTION AB Most of the steroid receptor family, with the exception of the estrogen receptor. are classically viewed as 'translocating receptors'. That is, they move from an exclusively, or principally, cytoplasmic distribution in the absence of hormone to a predominately nuclear localization in hormone stimulated cells. The estrogen receptor and the nuclear receptor family are found exclusively in the nucleus, both in hormone stimulated and hormone free cells. This behavior has now been studied with GFP-fusions in living cells, and has in general been confirmed. However, there are important exceptions, and new findings, particularly with regard to sub-nuclear localization. We propose that the intracellular distribution of both receptor classes is dependent not only on subcellular localization signals directly encoded in the receptors, but also on the nature and composition of the large, macromolecular complexes formed by each receptor. Furthermore, we find that most members of the receptor superfamily Form focal accumulations within the nucleus in response to ligand, and suggest that these structures may participate in the biological life cycle of the receptors. Finally, we propose that receptor movement in the nucleus is highly dynamic, with the receptors undergoing constant exchange between genomic regulatory elements, multi-protein complexes with other transcription factor partners, and subnuclear structures that are as yet poorly defined. Published by Elsevier Science Ltd. C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602,41 Lib Dr, Bethesda, MD 20892 USA. NR 33 TC 93 Z9 95 U1 3 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD NOV 30 PY 2000 VL 74 IS 5 BP 249 EP 254 DI 10.1016/S0960-0760(00)00100-X PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 387JW UT WOS:000166120300003 PM 11162932 ER PT J AU Couse, JF Hewitt, SC Korach, KS AF Couse, JF Hewitt, SC Korach, KS TI Receptor null mice reveal contrasting roles for estrogen receptor alpha and beta in reproductive tissues SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 113th Nobel Symposium on Estrogens and Women's Health: Benefit or Threat CY JUN 29-JUL 01, 1999 CL KARLSKRONA, SWEDEN SP Nobel Fdn DE estrogen receptor; estrogen insensitivity; uterus; ovary; testis; mammary gland ID FOLLICLE-STIMULATING-HORMONE; MOUSE LACTOFERRIN GENE; MESSENGER-RNA EXPRESSION; RAT GRANULOSA-CELLS; PROGESTERONE-RECEPTOR; TARGETED DISRUPTION; LUTEINIZING-HORMONE; OVARIAN FOLLICLES; KNOCKOUT MOUSE; ER-BETA C1 NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH, MD B3-02,POB 12233, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 83 TC 89 Z9 93 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD NOV 30 PY 2000 VL 74 IS 5 BP 287 EP 296 DI 10.1016/S0960-0760(00)00105-9 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 387JW UT WOS:000166120300008 PM 11162937 ER PT J AU Sullivan, NJ Sanchez, A Rollin, PE Yang, ZY Nabel, GJ AF Sullivan, NJ Sanchez, A Rollin, PE Yang, ZY Nabel, GJ TI Development of a preventive vaccine for Ebola virus infection in primates SO NATURE LA English DT Article ID T-CELL INDUCTION; PROTECTIVE EFFICACY; IMMUNE-RESPONSES; RECOMBINANT; IMMUNIZATION; ADENOVIRUS; PROTEIN; MALARIA; IMMUNOGENICITY; THERAPY AB Outbreaks of haemorrhagic fever caused by the Ebola virus are associated with high mortality rates that are a distinguishing feature of this human pathogen. The highest lethality is associated with the Zaire subtype, one of four strains identified to date(1,2). Its rapid progression allows little opportunity to develop natural immunity, and there is currently no effective anti-viral therapy. Therefore, vaccination offers a promising intervention to prevent infection and limit spread. Here we describe a highly effective vaccine strategy for Ebola virus infection in non-human primates. A combination of DNA immunization and boosting with adenoviral vectors that encode viral proteins generated cellular and humoral immunity in cynomolgus macaques. Challenge with a lethal dose of the highly pathogenic, wild-type, 1976 Mayinga strain of Ebola Zaire virus resulted in uniform infection in controls, who progressed to a moribund state and death in less than one week. In contrast, all vaccinated animals were asymptomatic for more than six months, with no detectable virus after the initial challenge. These findings demonstrate that it is possible to develop a preventive vaccine against Ebola virus infection in primates. C1 NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Special Pathogens Branch, Atlanta, GA 30333 USA. RP Nabel, GJ (reprint author), NIH, Vaccine Res Ctr, 40 Convent Dr,MSC-3005, Bethesda, MD 20892 USA. NR 29 TC 447 Z9 471 U1 30 U2 393 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 30 PY 2000 VL 408 IS 6812 BP 605 EP 609 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 377WE UT WOS:000165548600123 PM 11117750 ER PT J AU Lipsky, PE van der Heijde, DMFM St Clair, EW Furst, DE Breedveld, FC Kalden, JR Smolen, JS Weisman, M Emery, P Feldmann, M Harriman, GR Maini, RN AF Lipsky, PE van der Heijde, DMFM St Clair, EW Furst, DE Breedveld, FC Kalden, JR Smolen, JS Weisman, M Emery, P Feldmann, M Harriman, GR Maini, RN CA Anti-Tumor Necrosis Factor Trial TI Infliximab and methotrexate in the treatment of rheumatoid arthritis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NECROSIS-FACTOR-ALPHA; CHIMERIC MONOCLONAL-ANTIBODY; RADIOGRAPHIC PROGRESSION; RADIOLOGICAL PROGRESSION; FUSION PROTEIN; DOUBLE-BLIND; DISEASE; EFFICACY; PLACEBO; TRIAL AB Background: Neutralization of tumor necrosis factor alpha (TNF-alpha) for three to six months reduces the symptoms and signs of rheumatoid arthritis. However, the capacity of this approach to effect a more sustained benefit and its effect on joint damage are not known. Methods: We treated 428 patients who had active rheumatoid arthritis despite methotrexate therapy with placebo or infliximab, a chimeric monoclonal antibody against TNF-alpha, in intravenous doses of 3 or 10 mg per kilogram of body weight every 4 or 8 weeks in combination with oral methotrexate for 54 weeks. We assessed clinical responses with use of the criteria of the American College of Rheumatology, the quality of life with a health-status questionnaire, and the effect on joint damage radiographically. Results: The combination of infliximab and methotrexate was well tolerated and resulted in a sustained reduction in the symptoms and signs of rheumatoid arthritis that was significantly greater than the reduction associated with methotrexate therapy alone (clinical response, 51.8 percent vs. 17.0 percent; P<0.001). The quality of life was also significantly better with infliximab plus methotrexate than with methotrexate alone. Radiographic evidence of joint damage increased in the group given methotrexate, but not in the groups given infliximab and methotrexate (mean change in radiographic score, 7.0 vs. 0.6; P<0.001). Radiographic evidence of progression of joint damage was absent in infliximab-treated patients whether or not they had a clinical response. Conclusions: In patients with persistently active rheumatoid arthritis despite methotrexate therapy, repeated doses of infliximab in combination with methotrexate provided clinical benefit and halted the progression of joint damage. (N Engl J Med 2000;343:1594-602.) (C) 2000, Massachusetts Medical Society. C1 Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Hosp Maastricht, Maastricht, Netherlands. Duke Univ, Med Ctr, Durham, NC USA. Virginia Mason Res Ctr, Seattle, WA 98101 USA. Leiden Univ, Leiden, Netherlands. Inst Clin Immunol, Erlangen, Germany. Univ Vienna, Vienna, Austria. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Leeds, Res Sch Med, Leeds, W Yorkshire, England. Kennedy Inst Rheumatol, London, England. Charing Cross Hosp, Imperial Coll, Sch Med, London, England. Centocor Inc, Malvern, PA 19355 USA. RP Lipsky, PE (reprint author), NIAMSD, NIH, 9000 Rockville Pike,Bldg 10,Rm 9N228, Bethesda, MD 20892 USA. NR 38 TC 2140 Z9 2230 U1 10 U2 112 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 30 PY 2000 VL 343 IS 22 BP 1594 EP 1602 DI 10.1056/NEJM200011303432202 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 377JT UT WOS:000165511000002 PM 11096166 ER PT J AU De Luca, A Arra, C D'Antonio, A Casamassimi, A Losito, S Ferraro, P Ciardiello, F Salomon, DS Normanno, N AF De Luca, A Arra, C D'Antonio, A Casamassimi, A Losito, S Ferraro, P Ciardiello, F Salomon, DS Normanno, N TI Simultaneous blockade of different EGF-like growth factors results in efficient growth inhibition of human colon carcinoma xenografts SO ONCOGENE LA English DT Article DE TGF alpha; amphiregulin; cripto; colon carcinoma; antisense ID MAMMARY EPITHELIAL-CELLS; PROTEIN-KINASE-A; FACTOR-ALPHA; IMMUNOHISTOCHEMICAL DETECTION; ANTISENSE OLIGONUCLEOTIDES; ANTITUMOR-ACTIVITY; COLORECTAL TUMORS; FACTOR FAMILY; CANCER CELLS; AMPHIREGULIN AB A majority of human colon carcinomas coexpress the epidermal growth factor (ECF)-related peptides transforming growth factor alpha (TGF alpha), amphiregulin (AR) and CRIPTO-1 (CR). We have synthesized novel, antisense mixed backbone oligonucleotides (AS MBOs) directed against TGF alpha. AR and CR, We screened the EGF-related (AS MBOs) for their ability to inhibit the anchorage independent growth of GEO human colon carcinoma cells. Tbe MBOs that showed a high in vitro efficacy were then used for in vitro experiments. TGF alpha, AR and CR AS MBOs were able to inhibit the growth of CEO tumor xenografts in nude mice in a dose-dependent manner. Furthermore, the AS MBOs were able to specifically inhibit the expression of the target mRNAs and proteins in the tumor xenografts. A more significant tumor growth inhibition was observed when mice were treated with a combination of the three AS MBOs as compared to treatment with a single AS MBO, Finally, tumors from mice treated with TGF alpha, AR and CR AS MBOs showed a significant reduction of microvessel count, as compared with tumors from untreated mice or from mire treated with a single AS MBO, These data suggest that combinations of AS oligonucleotides directed against different growth factors might represent a novel, experimental therapy approach of colon carcinomas. C1 ITN Fdn Pascale, Novel Therapeut Approaches Sect Oncol Sperimental, I-80131 Naples, Italy. ITN Fdn Pascale, Anim Fac, I-80131 Naples, Italy. Anat Pathol ULSS 3, I-36061 Bassano Del Grappa, VI, Italy. ITN Fdn, Anat Patol, I-80131 Naples, Italy. Univ Naples Federico II, Dip Endocrinol & Oncol Mol & Clin, Cattedra Oncol Med, I-80131 Naples, Italy. NCI, LTIB, Tumor Growth Factor Sect, NIH, Bethesda, MD 20892 USA. RP Normanno, N (reprint author), ITN Fdn Pascale, Novel Therapeut Approaches Sect Oncol Sperimental, I-80131 Naples, Italy. RI De Luca, Antonella/J-8737-2016; OI De Luca, Antonella/0000-0001-5762-447X; Ciardiello, Fortunato/0000-0002-3369-4841; Arra, Claudio/0000-0003-3162-2091; Normanno, Nicola/0000-0002-7158-2605 NR 37 TC 47 Z9 48 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 30 PY 2000 VL 19 IS 51 BP 5863 EP 5871 DI 10.1038/sj.onc.1203979 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 378CA UT WOS:000165563100005 PM 11127817 ER PT J AU Zarich, N Oliva, JL Jorge, R Santos, E Rojas, JM AF Zarich, N Oliva, JL Jorge, R Santos, E Rojas, JM TI The isoform-specific stretch of hSos1 defines a new Grb2-binding domain SO ONCOGENE LA English DT Article DE hSos1; isoforms; Grb2; SH3 domains ID NUCLEOTIDE EXCHANGE FACTOR; RECEPTOR TYROSINE KINASES; ACTIVATED PROTEIN-KINASE; SRC HOMOLOGY-3 DOMAINS; RAS SIGNALING PATHWAY; SH3 DOMAINS; FACTOR SON; SH3-LIGAND INTERACTIONS; STRUCTURAL BASIS; ADAPTER PROTEIN AB hSos1 isoform II, defined by the presence of a 15 amino acid stretch in its carboxy-terminal region, exhibits higher Grb2 affinity than hSos1 isoform I. In this study, we investigated the cause for this difference and observed that, in addition to the four currently accepted Grb2-binding motifs, a number of additional, putative SH3-minimal binding sites (SH3-MBS) could be identified. The isoform II-specific 15 amino acid stretch contained one of them, Indeed, me demonstrated by site-directed mutagenesis that these SH3-MBS were responsible for the Grb2 interaction, and we found that C-terminal fragments of the two hSos1 isoforms (lacking the four cannonical Grb2-binding motifs, but containing the SH3-minimal binding sites) were able to bind Grb2, with the isoform II fragment showing higher Grb2 affinity than the corresponding isoform I fragment. Furthermore, we provide evidence that C-terminal truncated mutants of either hSos1 isoform, containing only the SH3-minimal binding sites, were able to originate in vivo stable complexes with Grb2, Although, Grb2-binding remains higher in both full-length isoforms, compared to the C-terminal truncated mutants, these mutants were also able to activate Ras, supporting a potential role of this C-terminal region as negative modulator of Sos1 activity. These findings document the existence of a new, functional, SH3-minimal binding site located in the specific stretch of hSos1 isoform II which may be responsible for the increased Grb2 affinity of this isoform in comparison to isoform I, and for the physiological properties differences between both isoforms, Moreover, these SH3-minimal binding sites may be sufficient to attain stable and functional hSos1-Grb2 complexes. C1 Inst Salud Carlos III, Ctr Nacl Biol Fundamental, Unidad Biol Celular, Madrid 28220, Spain. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rojas, JM (reprint author), Inst Salud Carlos III, Ctr Nacl Biol Fundamental, Unidad Biol Celular, Madrid 28220, Spain. NR 57 TC 14 Z9 15 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 30 PY 2000 VL 19 IS 51 BP 5872 EP 5883 DI 10.1038/sj.onc.1203955 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 378CA UT WOS:000165563100006 PM 11127818 ER PT J AU Moon, HR Ford, H Marquez, VE AF Moon, HR Ford, H Marquez, VE TI A remarkably simple chemicoenzymatic approach to structurally complex bicyclo[3.1.0]hexane carbocyclic nucleosides SO ORGANIC LETTERS LA English DT Article ID REVERSE-TRANSCRIPTASE; DUPLEX STABILITY; SUGAR RING; ANALOGS; THYMIDINE; OLIGONUCLEOTIDES; DEAMINASE AB [GRAPHICS] Intramolecular cyclopropanation of a carbene engendered from the corresponding diazo beta -ketoester produced the desired bicyclo[3.1.0]hexane pseudosugar. Purine nucleosides obtained via Mitsunobu coupling were resolved with adenosine deaminase. The requisite beta -ketoester was assembled in one step from ethyl acetoacetate and acrolein. C1 NCI, Frederick Canc Res & Dev Ctr, Med Chem Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Marquez, VE (reprint author), NCI, Frederick Canc Res & Dev Ctr, Med Chem Lab, Div Basic Sci, Frederick, MD 21702 USA. NR 25 TC 31 Z9 31 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD NOV 30 PY 2000 VL 2 IS 24 BP 3793 EP 3796 DI 10.1021/ol000238s PG 4 WC Chemistry, Organic SC Chemistry GA 378ZL UT WOS:000165616300010 PM 11101421 ER PT J AU Torrey, EF Rawlings, R Yolken, RH AF Torrey, EF Rawlings, R Yolken, RH TI The antecedents of psychoses: a case-control study of selected risk factors SO SCHIZOPHRENIA RESEARCH LA English DT Article DE bipolar disorder; feline; pet; psychoses; schizoaffective disorder; schizophrenia ID HUMAN-IMMUNODEFICIENCY-VIRUS; BIPOLAR DISORDER; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; BREAST-MILK; CITY BIRTH; HTLV-I; SCHIZOPHRENIA; PETS; COMPLICATIONS AB Winter birth, urban birth and/or childhood residence, and perinatal complications have each been identified as environmental risk factors for the later development of schizophrenia, schizoaffective disorder, and bipolar disorder. A preliminary case-control study also identified cat exposure in childhood as a possible risk factor. To assess selected environmental events, including childhood exposure to pets, as possible risk factors for these diseases, a case-control telephone survey was carried out by the University of Maryland Survey Research Center for 264 mothers of cases and 528 mothers of matched controls. The cases were randomly selected mothers who were members of the National Alliance for the Mentally ill, and whose children had been diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder. The controls were mothers randomly selected from the same telephone exchanges. For five of the 19 major variables, there were statistically significant differences between cases and controls: fever during pregnancy, complications during delivery, city or suburban residence at birth, cat ownership between birth and age 13, and breast-feeding. In a multivariate logistic regression including these five variables, each variable made a significant contribution. The finding of perinatal complications, urban/suburban residence at birth, and cat ownership in childhood as risk factors for the later development of psychoses confirmed previous studies. Previous research on breast-feeding as a risk factor has yielded contradictory results. Additional research is needed to ascertain how such environmental risk factors interact with genetic risk factors. Understanding these could lead to better treatments and possible prevention strategies. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Stanley Fdn Res Programs, Bethesda, MD 20814 USA. NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Stanley Div Dev Neurovirol, Med Ctr, Baltimore, MD 21287 USA. RP Torrey, EF (reprint author), Stanley Fdn Res Programs, 5430 Grosvenor Lane,Suite 200, Bethesda, MD 20814 USA. EM millerj@stanleyresearch.org NR 38 TC 55 Z9 55 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV 30 PY 2000 VL 46 IS 1 BP 17 EP 23 PG 7 WC Psychiatry SC Psychiatry GA 383PU UT WOS:000165892000002 ER PT J AU Panzer, A Hamel, E Joubert, AM Bianchi, PC Seegers, JC AF Panzer, A Hamel, E Joubert, AM Bianchi, PC Seegers, JC TI Ukrain (TM) a semisynthetic Chelidonium majus alkaloid derivative, acts by inhibition of tubulin polymerization in normal and malignant cell lines SO CANCER LETTERS LA English DT Article DE Ukrain; chelidonium; alkaloid; chelidonine; tubulin polymerization ID CANCER-PATIENTS; BREAST-CANCER; ENHANCEMENT; SEPARATION; INVITRO; GROWTH; AGENT AB Ukrain (TM) has been described as a semisynthetic Chelidonium majus alkaloid derivative, which exhibits selective toxicity towards malignant cells only. Its mechanism of action has hitherto been uncertain, We found that Ukrain (TM) inhibits tubulin polymerization, leading to impaired microtubule dynamics. This results in activation of the spindle checkpoint and thus a metaphase block. The effects of Ukrainn (TM) on the growth, cell cycle progression and morphology of two normal, two transformed and two malignant cell lines did not differ. We could thus find no evidence for the selective cytotoxicity previously reported for Ukrain (TM). (C) 2000 Elsevier Science ireland Ltd. All rights reserved. C1 Univ Pretoria, Dept Physiol, ZA-0001 Pretoria, South Africa. NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Screening Technol Branch, Frederick, MD 21702 USA. Univ Witwatersrand, Dept Surg, Flow Cytometry Unit, ZA-2050 Wits, South Africa. RP Joubert, AM (reprint author), Univ Pretoria, Dept Physiol, POB 2034, ZA-0001 Pretoria, South Africa. RI Joubert, Anna/F-8706-2010 NR 31 TC 15 Z9 15 U1 0 U2 3 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 NOV 28 PY 2000 VL 160 IS 2 BP 149 EP 157 DI 10.1016/S0304-3835(00)00578-4 PG 9 WC Oncology SC Oncology GA 428AV UT WOS:000168439700004 PM 11053644 ER PT J AU Huster, D Dietrich, U Gutberlet, T Gawrisch, K Arnold, K AF Huster, D Dietrich, U Gutberlet, T Gawrisch, K Arnold, K TI Lipid matrix properties in cationic membranes interacting with anionic polyelectrolytes: A solid-state NMR approach SO LANGMUIR LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; DEXTRAN SULFATE; BILAYER-MEMBRANES; H-2 NMR; PHOSPHOLIPID-BILAYERS; BIOLOGICAL-MEMBRANES; ELECTROSTATIC FORCES; HYDROCARBON CHAINS; LIPOSOME COMPLEXES; SURFACES AB A combined solid-state NMR and small-angle X-ray scattering approach was employed to investigate morphology and lateral packing properties of mixed zwitterionic and cationic lipid membranes in the presence of an anionic polyelectrolyte. Binary mixtures of zwitterionic DMPC and cationic DODAP form stable lipid bilayers over a wide range of mixing ratios. Addition of negatively charged dextran sulfate (DS) leads to the formation of densely packed lipid bilayer stacks with the polyelectrolyte sandwiched between opposing lipid surfaces. Bridging of polyelectrolyte strands between bilayer surfaces provides attractive forces to overcompensate electrostatic and hydration repulsion, resulting in close approach of apposing membranes. The equilibrium surface distance is controlled by a balance of electrostatic, hydration, bridging, and entropic forces. Lipid molecules in the mixed membranes remain homogeneously distributed in both the absence and presence of DS. DS binds exclusively to cationic DODAP. As a result of DS binding, lipid chain order is equally increased throughout the lipid bilayer. Therefore, a partial penetration of the polyelectrolyte into the hydrophobic core of the membrane is unlikely. Increased order parameters correspond to a reduction of lateral lipid packing density equivalent to an average reduction of area per molecule of 2.9 Angstrom (2). We suggest that this area reduction is the result of membrane surface dehydration induced by the polyelectrolyte that creates attractive forces between bilayers. C1 Univ Leipzig, Inst Med Phys & Biophys, D-04103 Leipzig, Germany. NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. Univ Leipzig, Inst Expt Phys, D-04103 Leipzig, Germany. RP Arnold, K (reprint author), Univ Leipzig, Inst Med Phys & Biophys, Liebigstr 27, D-04103 Leipzig, Germany. RI Gutberlet, Thomas/D-5613-2014 OI Gutberlet, Thomas/0000-0002-6194-2259 NR 54 TC 11 Z9 11 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD NOV 28 PY 2000 VL 16 IS 24 BP 9225 EP 9232 DI 10.1021/la000620d PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 376VR UT WOS:000165477900024 ER PT J AU Rapin, I Lindenbaum, Y Dickson, DW Kraemer, KH Robbins, JH AF Rapin, I Lindenbaum, Y Dickson, DW Kraemer, KH Robbins, JH TI Cockayne syndrome and xeroderma pigmentosum - DNA repair disorders with overlaps and paradoxes SO NEUROLOGY LA English DT Review ID COMPLEMENTATION GROUP-G; EXCISION-REPAIR; NEUROPATHOLOGICAL FINDINGS; NEUROLOGICAL DISEASE; TRANSCRIPTION GENE; SYNDROME COMPLEX; TISSUE-CULTURE; TRICHOTHIODYSTROPHY; NEURODEGENERATION; MUTATIONS AB Objectives: To review genetic variants of Cockayne syndrome (CS) and xeroderma pigmentosum (XP), autosomal recessive disorders of DNA repair that affect the nervous system, and to illustrate them by the first case of xeroderma pigmentosum-Cockayne syndrome (XP-CS) complex to undergo neuropathologic examination. Methods: Published reports of clinical, pathologic, and molecular studies of CS, XP neurologic disease, and the XP-CS complex were reviewed, and a ninth case of XP-CS is summarized. Results: CS is a multisystem disorder that causes both profound growth failure of the soma and brain and progressive cachexia, retinal, cochlear, and neurologic degeneration, with a leukodystrophy and demyelinating neuropathy without an increase in cancer. XP presents as extreme photosensitivity of the skin and eyes with a 1000-fold increased frequency of cutaneous basal and squamous cell carcinomas and melanomas and a small increase in nervous system neoplasms. Some 20% of patients with XP incur progressive degeneration of previously normally developed neurons resulting in cortical, basal ganglia, cerebellar, and spinal atrophy, cochlear degeneration, and a mixed distal axonal neuropathy. Cultured cells from patients with CS or XP are hypersensitive to killing by ultraviolet (UV) radiation. Both CS and most XP cells have defective DNA nucleotide excision repair of actively transcribing genes; in addition, XP cells have defective repair of the global genome. There are two complementation groups in CS and seven in XP. Patients with the XP-CS complex fall into three XP complementation groups. Despite their XP genotype, six of nine individuals with the XP-CS complex, including the boy we followed up to his death at age 6, had the typical clinically and pathologically severe CS phenotype. Cultured skin and blood cells had extreme sensitivity to killing by UV radiation, DNA repair was severely deficient, post-UV unscheduled DNA synthesis was reduced to less than 5%, and post-UV plasmid mutation frequency was increased. Conclusions: The paradoxical lack of parallelism of phenotype to genotype is unexplained in these disorders. Perhaps diverse mutations responsible for UV sensitivity and deficient DNA repair may also produce profound failure of brain and somatic growth, progressive cachexia and premature aging, and tissue-selective neurologic deterioration by their roles in regulation of transcription and repair of endogenous oxidative DNA damage. C1 Albert Einstein Coll Med, Rose F Kennedy Ctr Res Mental Retardat & Human Dev, Saul R Korey Dept Neurol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Rose F Kennedy Ctr Res Mental Retardat & Human Dev, Dept Pediat, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Pathol, Div Neuropathol, Bronx, NY 10461 USA. Ohio State Univ, Coll Med, Dept Neurol, Columbus, OH 43210 USA. Mayo Clin Jacksonville, Dept Pathol, Jacksonville, FL 32224 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Rapin, I (reprint author), Albert Einstein Coll Med, Rose F Kennedy Ctr Res Mental Retardat & Human Dev, Saul R Korey Dept Neurol, Room 807,1410 Pelham Pkwy S, Bronx, NY 10461 USA. OI Dickson, Dennis W/0000-0001-7189-7917 FU Intramural NIH HHS [Z01 BC004517-31]; NIA NIH HHS [P01 AG003949] NR 49 TC 140 Z9 143 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 NOV 28 PY 2000 VL 55 IS 10 BP 1442 EP 1449 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 376DR UT WOS:000165443400004 PM 11185579 ER PT J AU Dalakas, MC Fujii, M Li, M McElroy, B AF Dalakas, MC Fujii, M Li, M McElroy, B TI The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome SO NEUROLOGY LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; INTRAVENOUS IMMUNOGLOBULIN; GABAERGIC NEURONS; AUTOANTIBODIES; ASSOCIATIONS; SUPRATYPES AB Objective: To evaluate the clinical spectrum of anti-GAD-positive patients with stiff-person syndrome (SPS) and provide reproducible means of assessing stiffness. Background: SPS can be difficult to diagnose. Delineation of the clinical spectrum in a well defined population will increase diagnostic sensitivity. Methods: In 20 anti-GAD-positive patients with SPS (six men, 14 women), screened among 38 referred patients, the authors assessed symptoms and signs, degree of disability, associated conditions, and immunogenetic markers. Degree of bending, distribution of stiff areas, timed activities, and magnitude of heightened sensitivity were examined monthly for 4 months in five patients. Results: Average age at symptom onset was 41.2 years. Time to diagnosis was delayed from 1 to 18 years (mean 6.2). Stiffness with superimposed episodic spasms and co-contractures of the abdominal and thoracic paraspinal muscles were characteristic. All had stiff gait and palpable stiffness in the paraspinal muscles. Stiffness was asymmetric or prominent in one leg in 15 patients (stiff-leg syndrome) and involved facial muscles in 13. In one patient spasms lasted for days (status spasticus). Twelve patients needed a cane and seven a walker due to truncal stiffness and frequent falls (average three to four per month). Distribution of stiffness and degree of heightened sensitivity were two reproducible indices of stiffness and spasms. Autoimmune diseases or autoantibodies were noted in 80% and an association of with DR beta1 0301 allele in 70%. Conclusions: SPS is 1) frequently misdiagnosed due to multifaceted presentations and asymmetric signs, 2) disabling if untreated, and 3) associated with other autoimmune conditions. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. NR 29 TC 121 Z9 123 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 28 PY 2000 VL 55 IS 10 BP 1531 EP 1535 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 376DR UT WOS:000165443400018 PM 11094109 ER PT J AU Slavotinek, AM Biesecker, LG AF Slavotinek, AM Biesecker, LG TI Phenotypic overlap of McKusick-Kaufman syndrome with Bardet-Biedl syndrome: A literature review SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Review DE McMusick-Kaufman syndrome; Bardet-Biedl syndrome; hydrometrocolpos; polydactyly ID CONGENITAL HEART-DISEASE; VAGINAL ATRESIA; GENETIC-HETEROGENEITY; ABDOMINAL DISTENSION; SYNDROME LOCUS; HYDROMETROCOLPOS; DIAGNOSIS; MANIFESTATIONS; HYDROCOLPOS; ASSOCIATION AB Hydrometrocolpos (HMC) and post-axial polydactyly (PAP) are common to both McKusick-Kaufman syndrome (MKS) and Bardet-Biedl syndrome (BBS). We review reported cases of MKS and BBS presenting with HMC and PAP early in life to determine if there are clinical features that allow discrimination between the two syndromes as the primary features of retinitis pigmentosa, obesity, learning disability in BBS are age-dependent. We did not find any phenotypic features that allowed reliable differentiation between the two syndromes in the neonatal period. However, uterine, ovarian, and fallopian tube anomalies are more common in BBS patients, and it may be that these clinical features prove to be useful discriminating features. We conclude that sporadic female infants with HMC and PAP cannot be diagnosed with MKS until at least age 5 years and that monitoring for the complications of BBS should be performed in these patients. Arm. J. Med. Genet. 95:208-215, 2000. Published 2000 Wiley-Liss, Inc.(dagger) C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Slavotinek, AM (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 81 TC 47 Z9 49 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 27 PY 2000 VL 95 IS 3 BP 208 EP 215 DI 10.1002/1096-8628(20001127)95:3<208::AID-AJMG5>3.0.CO;2-J PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 368KA UT WOS:000090115100005 PM 11102925 ER PT J AU Lacbawan, F Tifft, CJ Luban, NLC Schmandt, SM Guerrera, M Weinstein, S Pennybacker, M Wong, LJC AF Lacbawan, F Tifft, CJ Luban, NLC Schmandt, SM Guerrera, M Weinstein, S Pennybacker, M Wong, LJC TI Clinical heterogeneity in mitochondrial DNA deletion disorders: A diagnostic challenge of Pearson syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE mitochondrial disease; mitochodrial DNA deletion; Pearson syndrome; mtDNA heteroplasmy; mtDNA mutation ID KEARNS-SAYRE-SYNDROME; MARROW-PANCREAS-SYNDROME; MUTATIONS AB The clinical presentation of mitochondrial DNA (mtDNA) disorders is quite diverse. Very often, the initial symptoms do not fit a specific disease, and diagnosis is difficult to make, We describe a patient who presented with macrocytic anemia. Extensive biochemical and clinical work-up failed to provide an etiology for the macrocytic anemia. The patient over the course of 6 years developed gait problems, exercise intolerance, episodic vomiting, short stature, dermatological problems, and recurrent infection. At age 8 years she had encephalopathy with ataxia and dysphagia, The presence of elevated lactate, bilateral basal ganglia calcification, and ragged red fibers led to mtDNA mutational analysis, A novel 4.4-kb deletion from nucleotide position 10,560 to nucleotide position 14,980 was identified in muscle biopsy. The same heteroplasmic mtDNA deletion was present in blood, buccal cells, and hair follicles, but not in mother's blood, consistent with sporadic mutation in the patient. This case emphasizes the importance of considering mtDNA disorder in patients with multisystemic symptoms that cannot be explained by a specific diagnosis. Am. J, Med. Genet. 95:266-268, 2000. 2000 Wiley-Liss, Inc. C1 Georgetown Univ, Med Ctr, Inst Mol & Human Genet, Washington, DC 20007 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. RP Wong, LJC (reprint author), Georgetown Univ, Med Ctr, Inst Mol & Human Genet, Washington, DC 20007 USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 17 TC 30 Z9 31 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 27 PY 2000 VL 95 IS 3 BP 266 EP 268 DI 10.1002/1096-8628(20001127)95:3<266::AID-AJMG13>3.0.CO;2-0 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 368KA UT WOS:000090115100013 PM 11102933 ER PT J AU Ng, D Stratakis, CA AF Ng, D Stratakis, CA TI Premature adrenal cortical dysfunction in mandibuloacral dysplasia: A progeroid-like syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter ID SERUM CONCENTRATIONS; DEHYDROEPIANDROSTERONE; WOMEN; MEN; AGE; REPLACEMENT; STEROIDS; SULFATE C1 NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Unit Genet & Endocrinol, DEB, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. NR 15 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 27 PY 2000 VL 95 IS 3 BP 293 EP 295 DI 10.1002/1096-8628(20001127)95:3<293::AID-AJMG23>3.0.CO;2-5 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 368KA UT WOS:000090115100023 PM 11102943 ER PT J AU Loria, CM Ingram, DD Feldman, JJ Wright, JD Madans, JH AF Loria, CM Ingram, DD Feldman, JJ Wright, JD Madans, JH TI Serum folate and cardiovascular disease mortality among US men and women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; TOTAL HOMOCYSTEINE; PLASMA HOMOCYSTEINE; RISK; VITAMIN-B12; COBALAMIN; COHORT AB Background: Folate has been linked to cardiovascular disease (CVD) through its role in homocysteine metabolism. Objective: To assess the relationship between serum folate and CVD mortality. Design: In this prospective study, serum folate concentrations were measured on a subset of adults during the Second National Health and Nutrition Examination Survey (1976-1980) and vital status ascertained after 12 to 16 years. Setting and Patients: A national probability sample consisting of 689 adults who were 30 to 75 years of age and did not have a history of CVD at baseline. Main Outcome Measure: Vital status was determined by searching national databases that contained information about US decedents. Results: The associations between serum folate and CVD and all-cause mortality differed by diabetes status (P=.04 and P=.03, respectively). Participants without diabetes in the lowest compared with the highest serum folate tertile had more than twice the risk of CVD mortality after adjustment for age and sex (relative risk [RR], 2.64; 95% confidence interval [CI], 1.15-6.09). This increased risk for participants in the lowest tertile was attenuated after adjustment for CVD risk factors (RR, 2.28; 95% CI, 0.96-5.40). Serum folate tertiles were not significantly associated with total mortality, although the age- and sex-adjusted risk was increased for participants in the lowest compared with highest tertile (RR, 1.74; 95% CI, 0.96-3.15). Risk estimates for participants with diabetes were unstable because of the small sample size (n=52). Conclusion: These data suggest that low serum folate concentrations are associated with an increased risk of CVD mortality among adults who do not have diabetes. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Loria, CM (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 3701 Rockledge Dr,Room 8150, Bethesda, MD 20892 USA. NR 33 TC 53 Z9 53 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 27 PY 2000 VL 160 IS 21 BP 3258 EP 3262 DI 10.1001/archinte.160.21.3258 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 376KL UT WOS:000165456700012 PM 11088087 ER PT J AU Huang, SX Flanders, KC Roberts, AB AF Huang, SX Flanders, KC Roberts, AB TI Characterization of the mouse Smad1 gene and its expression pattern in adult mouse tissues SO GENE LA English DT Article DE bone morphogenetic proteins; exon-intron boundaries; genomic sequence; signal transduction; Smad proteins ID GROWTH-FACTOR-BETA; PROSTATE-CANCER CELLS; TGF-BETA; SIGNAL-TRANSDUCTION; TARGETED DISRUPTION; ACTIVATION; ACTIVIN; LACKING; RECEPTORS; SEQUENCE AB Smad1 belongs to a family of receptor-activated proteins which mediate signals from TGF-beta superfamily ligands, including TGF-beta and BMPs. Although much is known about the biochemistry of Smad1 signal transduction, the role of Smad1 in vivo is still unclear. Here we present the first description of the genomic structure of the mouse Smad1 gene and the characterization of its expression pattern in adult mouse tissues by immunohistochemistry. The Smad1 gene contains 7 exons and spans >42 kb of genomic DNA. Its coding region is contained within 6 exons and all introns, except intron 1, follow the GT/AG rule. Immunohistochemical analysis shows that Smad1 is widely expressed in adult mouse tissues, with a varying degree of nuclear localization in different cell types, suggesting a regulated function for this protein. This study assigns all of the exon-intron boundaries of the mouse Smad1 gene and provides the basis for assessing the functional significance of this gene using targeted gene manipulation in the mouse. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, 41 Lib Dr, Bethesda, MD 20892 USA. NR 32 TC 25 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 27 PY 2000 VL 258 IS 1-2 BP 43 EP 53 DI 10.1016/S0378-1119(00)00396-6 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 383RW UT WOS:000165897500005 PM 11111041 ER PT J AU Hu, P Deng, FM Liang, FX Hu, CM Auerbach, AB Shapiro, E Wu, XR Kachar, B Sun, TT AF Hu, P Deng, FM Liang, FX Hu, CM Auerbach, AB Shapiro, E Wu, XR Kachar, B Sun, TT TI Ablation of uroplakin III gene results in small urothelial plaques, urothelial leakage, and vesicoureteral reflux SO JOURNAL OF CELL BIOLOGY LA English DT Article DE urothelium; permeability; knockout mice; vesicoureteral reflux; hydronephrosis ID MAMMALIAN URINARY-BLADDER; ASYMMETRIC UNIT MEMBRANE; CONGENITAL-ANOMALIES; PLASMA-MEMBRANE; CELL-SURFACE; DIFFERENTIATION; EPITHELIUM; PROTEINS; HYDRONEPHROSIS; ASSOCIATION AB Urothelium synthesizes a group of integral membrane proteins called uroplakins, which form two-dimensional crystals (urothelial plaques) covering >90% of the apical urothelial surface. We show that the ablation of the mouse uroplakin III (UPIII) gene leads to overexpression, defective glycosylation, and abnormal targeting of uroplakin Ib, the presumed partner of UPIII. The UPIII-depleted urothelium features small plaques, becomes leaky, and has enlarged ureteral orifices resulting in the back flow of urine, hydronephrosis, and altered renal function indicators. Thus, UPIII is an integral subunit of the urothelial plaque and contributes to the permeability barrier function of the urothelium, and UPIII deficiency can lead to global anomalies in the urinary tract. The ablation of a single urothelial-specific gene can therefore cause primary vesicoureteral reflux (VUR). a hereditary disease affecting similar to1% Of pregnancies and representing a leading cause of renal failure in infants. The fact that VUR caused by UPIII deletion seems distinct from that caused by the deletion of angiotensin receptor II gene suggests the existence of VUR subtypes. Mutations in multiple gene, including some that are urothelial specific, may therefore cause different subtypes of primary reflux. Studies of VUR in animal models caused by well-defined genetic defects should lead to improved molecular classification, prenatal diagnosis, and therapy of this important hereditary problem. C1 NYU, Sch Med,Kaplan Comprehens Canc Ctr, Ronald O Perelman Dept Dermatol, Epithelial Biol Unit, New York, NY 10016 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, Dept Pharmacol, New York, NY 10016 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, Skirball Inst Biomol Med, New York, NY 10016 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, Dept Urol, New York, NY 10016 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, Dept Microbiol, New York, NY 10016 USA. Vet Adm Med Ctr, New York, NY 10010 USA. Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. RP Sun, TT (reprint author), NYU, Sch Med,Kaplan Comprehens Canc Ctr, Ronald O Perelman Dept Dermatol, Epithelial Biol Unit, 550 1st Ave, New York, NY 10016 USA. FU NIDDK NIH HHS [DK57269, R01 DK057269, R01 DK039753, P01 DK052206, DK39753, DK52206] NR 58 TC 156 Z9 159 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 NOV 27 PY 2000 VL 151 IS 5 BP 961 EP 971 DI 10.1083/jcb.151.5.961 PG 11 WC Cell Biology SC Cell Biology GA 378MN UT WOS:000165588300006 PM 11085999 ER PT J AU Shumake, J Poremba, A Edwards, E Gonzalez-Lima, F AF Shumake, J Poremba, A Edwards, E Gonzalez-Lima, F TI Congenital helpless rats as a genetic model for cortex metabolism in depression SO NEUROREPORT LA English DT Article DE brain mapping; cingulate; congenital learned helplessness; cytochrome oxidase; depression; genetic model; metabolism; prefrontal ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; PREFRONTAL CORTEX; UNIPOLAR DEPRESSION; GLUCOSE-METABOLISM; MAJOR DEPRESSION; ABNORMALITIES; MELANCHOLIA; PROJECTIONS; DISORDERS AB The validity of congenital helplessness as a genetic rat model for human depression was investigated in cortical regions of the rat brain thought to be analogous to those showing abnormalities in human neuroimaging studies. Cortex metabolism was analyzed using quantitative cytochrome oxidase histochemistry. Congenital helpless rats showed changes in frontal and cingulate regions comparable to those that have demonstrated metabolic differences in human depression. Significant metabolic decreases were found in dorsal frontal, medial orbital, and anterior cingulate, whereas a significant increase was found in infraradiata (subgenual) cingulate. The direction of these changes were the same as those seen in human studies. These findings support the validity of congenital helplessness as a model for human depression. NeuroReport 11:3793-3798 (C) 2000 Lippincott Williams & Wilkins. C1 Univ Texas, Dept Psychol, Austin, TX 78712 USA. Univ Texas, Inst Neurosci, Austin, TX 78712 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. RP Gonzalez-Lima, F (reprint author), Univ Texas, Dept Psychol, Mezes Hall 330, Austin, TX 78712 USA. FU NINDS NIH HHS [R01 NS37755] NR 25 TC 42 Z9 43 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 27 PY 2000 VL 11 IS 17 BP 3793 EP 3798 DI 10.1097/00001756-200011270-00040 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 378DM UT WOS:000165569800035 PM 11117493 ER PT J AU Waldvogel, D van Gelderen, P Immisch, I Pfeiffer, C Hallett, M AF Waldvogel, D van Gelderen, P Immisch, I Pfeiffer, C Hallett, M TI The variability of serial fMRI data: Correlation between a visual and a motor task SO NEUROREPORT LA English DT Article DE fMRI; reproducibility; variability ID CEREBRAL BLOOD-FLOW; FUNCTIONAL MRI; DIRECTED ATTENTION; MENSTRUAL-CYCLE; BOLD-CONTRAST; CORTEX; BRAIN; REPRODUCIBILITY; DEPENDENCE; ACTIVATION AB We investigated whether the intersession variability of serial fMRI studies correlates between two activation modalities, i.e. a standardized visual and a standardized motor task. Six volunteers were scanned in at least weekly intervals. The number of pixels activated as well as the activation amplitude varied widely. The maximal difference of the number of pixels activated was 1150%, of the activation amplitude 250%. In three volunteers, the variability was highly correlated between the two tasks. Three other volunteers showed one outlier each. We conclude that the intersession variability is due to global factors affecting the whole brain, but that due to unpredictable outliers, using a standardized task to normalize the data of interest is of limited value. NeuroReport 11:3843-3847 (C) 2000 Lippincott Williams & Wilkins. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NINDS, In Vivo NMR Res Ctr, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. NR 25 TC 38 Z9 39 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 27 PY 2000 VL 11 IS 17 BP 3843 EP 3847 DI 10.1097/00001756-200011270-00048 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 378DM UT WOS:000165569800043 PM 11117501 ER PT J AU Domachowske, JB Bonville, CA Gao, JL Murphy, PM Easton, AJ Rosenberg, HF AF Domachowske, JB Bonville, CA Gao, JL Murphy, PM Easton, AJ Rosenberg, HF TI MIP-1 alpha is produced but it does not control pulmonary inflammation in response to respiratory syncytial virus infection in mice SO CELLULAR IMMUNOLOGY LA English DT Article DE antiviral; inflammation; chemokines; eosinophils ID AIRWAY EPITHELIAL-CELLS; PNEUMONIA VIRUS; FUNCTIONAL EXPRESSION; MESSENGER-RNA; RANTES; RECEPTOR; GENE; EOSINOPHILS; SECRETIONS; MIP-1-BETA AB The intent of this study was to compare the cellular and biochemical inflammatory responses of mice infected with the paramyxovirus pathogens respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM), Although RSV is not a natural pathogen of mice, it has been used extensively in mouse models of the human disease, as a limited respiratory infection can be established via intranasal inoculation of virus at high titer. In earlier work, we found that acute infection with the natural rodent pathogen, PVM, elicited a rapid and sustained pulmonary inflammatory response (peak, 1.7 x 10(6) leukocytes/ml BAL fluid) that was dependent on both local production of MIP-1 alpha and signaling via its receptor, CCR1. We find here that MIP-1 alpha is also produced in response to RSV, although relatively few leukocytes (<200 ml BAL fluid) are recruited to the lungs in response. Further experiments with CCR1-deficient mice confirm the finding that although MIP-1 is produced in response to RSV infection, leukocytes do not respond via this pathway. Among the explanations for these findings, we propose that there are other, as yet to be identified proinflammatory mediators elicited in response to PVM (but not in response to RSV) that serve to prime the leukocytes in vivo, thus enabling them to respond to MIP-1 alpha signaling via CCR1, Furthermore, the differences in disease pathogenesis seen in response to each of these pneumovirus infections in mice raise questions regarding the extent to which primary RSV infection in mice can be used as a model of primary RSV infection in humans. (C) 2000 Academic Press. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England. SUNY Upstate Med Ctr, Dept Pediat, Syracuse, NY 13210 USA. RP Rosenberg, HF (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N104,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 33 TC 29 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV 25 PY 2000 VL 206 IS 1 BP 1 EP 6 DI 10.1006/cimm.2000.1730 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 395RQ UT WOS:000166595400001 PM 11161432 ER PT J AU Chen, YQ Zhou, YQ Angeloni, D Kurtz, AL Qiang, XZ Wang, MH AF Chen, YQ Zhou, YQ Angeloni, D Kurtz, AL Qiang, XZ Wang, MH TI Overexpression and activation of the RON receptor tyrosine kinase in a panel of human colorectal carcinoma cell lines SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE RON receptor tyrosine kinase; constitutive activation; colon cancer; motile-invasive phenotype ID MACROPHAGE-STIMULATING PROTEIN; HEPATOCYTE GROWTH-FACTOR; MET PROTOONCOGENE PRODUCT; FACTOR SCATTER FACTOR; EPITHELIAL-CELLS; C-MET; GENE; MUTATIONS; IDENTIFICATION; DOMAIN AB RON is a receptor tyrosine kinase belonging to the MET proto-oncogene family. The purposes of this study are to determine the expression and activation of RON in a panel of human colon carcinoma cell lines. Western blotting showed that RON is barely detectable in normal and SV-40-transformed colon epithelial cells, but highly expressed and constitutively activated in several colon carcinoma cell lines including Colo201, HT-29, HCT116, and SW837. Moreover, a novel RON variant with a molecular mass of 160 kDa (RON Delta 160) was identified from HT-29 cells. The cDNA encoding RON Delta 160 has an in-frame deletion of 109 amino acids in the extracellular domain of the RON beta chain, which is caused by splicing out of two exons in the RON mRNA. No mutations were found in the kinase domain of the RON gene in five carcinoma cell lines screened. By expressing RON in colon epithelial cells, we found that BON activation increases cell motile-invasive activities and protects cells against apoptotic death. These data suggest that RON expression and activation are deregulated in colon carcinoma cell lines. By abnormal activation of RON, this receptor and its variant may regulate motile-invasive phenotypes of certain colon carcinoma cells in vivo. (C) 2000 Academic Press. C1 HCHSC, Sch Med, Denver Hlth Med Ctr, Dept Med, Denver, CO 80204 USA. Zhejiang Univ, Affiliated Teaching Hosp 1, Sch Med, Div Neurosurg, Hangzhou, Peoples R China. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. RP Wang, MH (reprint author), HCHSC, Sch Med, Denver Hlth Med Ctr, Dept Med, 777 Bannock St,Mail Box 4000, Denver, CO 80204 USA. FU NIAID NIH HHS [R01 AI43516] NR 44 TC 70 Z9 76 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 NOV 25 PY 2000 VL 261 IS 1 BP 229 EP 238 DI 10.1006/excr.2000.5012 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 379BZ UT WOS:000165622200025 PM 11082293 ER PT J AU Patton, JT Spencer, E AF Patton, JT Spencer, E TI Genome replication and packaging of segmented double-stranded RNA viruses SO VIROLOGY LA English DT Review ID ROTAVIRUS MESSENGER-RNA; CONSERVED TERMINAL SEQUENCES; IN-VITRO REPLICATION; BLUETONGUE VIRUS; BACTERIOPHAGE PHI-6; REOVIRUS GENOME; SHELL PROTEIN; MINUS; PARTICLES; TRANSCRIPTION C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Santiago Chile, Fac Quim & Biol, Dept Ciencias Biol, Virol Lab, Santiago, Chile. 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 85 TC 91 Z9 98 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 NOV 25 PY 2000 VL 277 IS 2 BP 217 EP 225 DI 10.1006/viro.2000.0645 PG 9 WC Virology SC Virology GA 379EQ UT WOS:000165628300001 PM 11080470 ER PT J AU Smith, MS Foresman, L Lopez, GJ Tsay, J Wodarz, D Lifson, JD Page, A Wang, CY Li, Z Adany, I Buch, S Bischofberger, N Narayan, O AF Smith, MS Foresman, L Lopez, GJ Tsay, J Wodarz, D Lifson, JD Page, A Wang, CY Li, Z Adany, I Buch, S Bischofberger, N Narayan, O TI Lasting effects of transient postinoculation tenofovir [9-R-(2-phosphonomethoxypropyl)adenine] treatment on SHIVKU2 infection of rhesus macaques SO VIROLOGY LA English DT Article DE AIDS; PMPA; SHIVKU2; macaque; viral dynamics ID SIMIAN IMMUNODEFICIENCY VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; SIV INFECTION; 9-<2-(PHOSPHONOMETHOXY)PROPYL>ADENINE PMPA; PERIPHERAL-BLOOD; LYMPH-NODES; VIRAL LOAD; HIV-1; REPLICATION; PREVENTION AB SHIVKU2 replicates to high levels in inoculated macaques and reproducibly causes an acute depletion of CD4(+) T cells. We evaluated the ability of treatment with the antiretroviral drug 9-R-(2-phosphonomethoxypropyl)adenine (PMPA; tenofovir), begun 7 days postinoculation, to inhibit viral replication and associated pathogenesis. Highly productive infection (plasma viral RNA > 10(6) copy eq/mL) was present and CD4 depletion had started when treatment was initiated. PMPA treatment was associated with a rapid decline in plasma viral RNA to undetectable levels, with parallel decreases in the infectivity of plasma and infectious cells in PBMCs and CSF and stabilization of CD4(+)T-cell levels. Viral dynamics parameters were calculated for the initial phase of exponential viral replication and the treatment-related decline in plasma viremia. Following cessation of treatment after 12 weeks, plasma viral RNA was detectable intermittently at low levels, and spliced viral transcripts were detected in lymph nodes. Although treatment was begun after viral dissemination, high viremia, and CD4 decreases had occurred, following withdrawal of PMPA, CD4(+) T-cell counts normalized and stabilized in the normal range, despite persistent low-level infection. No PMPA-resistance mutations were detected. These results validate the similar viral replicative dynamics of SHIVKU2 and HIV and SIV, and also underscore the potential for long-term modulation of viral replication patterns and clinical course by perturbation of primary infection. (C) 2000 Academic Press. C1 Univ Kansas, Med Ctr, Marion Merrell Dow Lab Viral Pathogenesis, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Lab Anim Resources, Kansas City, KS 66160 USA. Inst Adv Study, Program Theoret Biol, Princeton, NJ 08540 USA. NCI, AIDS Vaccine Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Gilead Sci Inc, Foster City, CA 94404 USA. RP Smith, MS (reprint author), Univ Kansas, Med Ctr, Marion Merrell Dow Lab Viral Pathogenesis, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. OI Buch, Shilpa/0000-0002-3103-6685 FU NCRR NIH HHS [RR06753]; NIAID NIH HHS [AI38492]; NINDS NIH HHS [NS32203] NR 38 TC 25 Z9 25 U1 1 U2 1 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 NOV 25 PY 2000 VL 277 IS 2 BP 306 EP 315 DI 10.1006/viro.2000.0609 PG 10 WC Virology SC Virology GA 379EQ UT WOS:000165628300009 PM 11080478 ER PT J AU Allander, T Forns, X Emerson, SU Purcell, RH Bukh, J AF Allander, T Forns, X Emerson, SU Purcell, RH Bukh, J TI Hepatitis C virus envelope protein E2 binds to CD81 of tamarins SO VIROLOGY LA English DT Article ID GLYCOPROTEIN; CELLS; FLAVIVIRIDAE; INFECTION; RECEPTOR; ANTIBODY; AGENT AB Since recombinant envelope glycoprotein E2 of hepatitis C virus (HCV) binds to CD81 on human and chimpanzee cells, it has been suggested that CD81 may be a receptor for HCV. Humans and chimpanzees are the only species known to be susceptible to HCV infection. E2 has been reported not to bind to CD81 of the African green monkey, mouse, or rat, suggesting that binding of HCV to CD81 is species specific and may determine susceptibility to infection with HCV. We investigated the interaction between E2 of HCV and CD81 of tamarins, a group of small New World monkeys frequently used for the study of human viruses. Tamarins are not susceptible to HCV infection. Nonetheless, we found that three different forms of HCV 52 (intracellular, secreted, and cell surface-displayed) bound more efficiently to recombinant tamarin CD81 than to human CD81, as determined by ELISA and immunofluorescence. The affinity of the interaction was approximately 10-fold higher for tamarin than for human CD81. Binding of E2 to CD81 on cultured or primary tamarin cells was demonstrated by flow cytometry. In contrast to previous reports, there was also a low-affinity interaction between 52 and African green monkey CD81. Thus, the HCV 52 interaction with CD81 is not limited to humans and chimpanzees and does not predict susceptibility to HCV infection. C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Bukh, J (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bldg 7,Room 201,7 Ctr Dr,MSC 0740, Bethesda, MD 20892 USA. FU NCI NIH HHS [CO-56000] NR 24 TC 34 Z9 35 U1 1 U2 1 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 NOV 25 PY 2000 VL 277 IS 2 BP 358 EP 367 DI 10.1006/viro.2000.0617 PG 10 WC Virology SC Virology GA 379EQ UT WOS:000165628300014 PM 11080483 ER PT J AU Yu, ZG Xu, FY Huse, LM Morisseau, C Draper, AJ Newman, JW Parker, C Graham, L Engler, MM Hammock, BD Zeldin, DC Kroetz, DL AF Yu, ZG Xu, FY Huse, LM Morisseau, C Draper, AJ Newman, JW Parker, C Graham, L Engler, MM Hammock, BD Zeldin, DC Kroetz, DL TI Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids SO CIRCULATION RESEARCH LA English DT Article DE epoxyeicosatrienoic acids dihydroxyeicosatrienoic acids; cytochrome P450; soluble epoxide hydrolase; hypertension ID SPONTANEOUSLY HYPERTENSIVE RATS; ARACHIDONIC-ACID; CYTOCHROME-P450 METABOLITES; KIDNEY; EPOXYGENASE; PURIFICATION AB The cytochrome P450-derived epoxyeicosatrienoic acids (EETs) have potent effects on renal vascular reactivity and tubular sodium and water transport; however, the role of these eicosanoids in the pathogenesis of hypertension is controversial. The current study examined the hydrolysis of the EETs to the corresponding dihydroxyeicosatrienoic acids (DHETs) as a mechanism for regulation of EET activity and blood pressure. EET hydrolysis was increased 5- to 54-fold in renal cortical S9 fractions from the spontaneously hypertensive rat (SHR) relative to the normotensive Wistar-Kyoto (WKY) rat. This increase was most significant for the 14,15-EET regioisomer, and there was a clear preference for hydrolysis of 14,15-EET over the 8,9- and 11,12-EETs. Increased EET hydrolysis was consistent with increased expression of soluble epoxide hydrolase (sEH) in the SHR renal microsomes and cytosol relative to the WKY samples. The urinary excretion of 14,15-DHET was 2.6-fold higher in the SHR than in the WKY rat, confirming increased EET hydrolysis in the SHR in vivo. Blood pressure was decreased 22+/-4 mm Hg (P<0.01) 6 hours after treatment of SHRs with the selective sEH inhibitor N,N'-dicyclohexylurea; this treatment had no effect on blood pressure in the WKY rat. These studies identify sEH as a novel therapeutic target for control of blood pressure. The identification of a potent and selective inhibitor of EET hydrolysis will be invaluable in separating the vascular effects of the EET and DHET eicosanoids. C1 Univ Calif San Francisco, Dept Biopharmaceut Sci, Sch Pharm, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol Nursing, Sch Nursing, San Francisco, CA 94143 USA. Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Kroetz, DL (reprint author), Univ Calif San Francisco, Dept Biopharmaceut Sci, Sch Pharm, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [R29 HL53994]; NIEHS NIH HHS [F32 ES05808, R01 ES02710] NR 29 TC 300 Z9 305 U1 1 U2 20 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 NOV 24 PY 2000 VL 87 IS 11 BP 992 EP 998 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 378WA UT WOS:000165607100009 PM 11090543 ER PT J AU Speir, E Yu, ZX Takeda, K Ferrans, VJ Cannon, RO AF Speir, E Yu, ZX Takeda, K Ferrans, VJ Cannon, RO TI Competition for p300 regulates transcription by estrogen receptors and nuclear factor-kappa B in human coronary smooth muscle cells SO CIRCULATION RESEARCH LA English DT Article DE estrogen receptors alpha/beta; intercellular adhesion molecule-1; nuclear factor-kappa B; transcriptional coactivator p300; vascular smooth muscle cells ID CYTOMEGALOVIRUS; COACTIVATOR; EXPRESSION; ARTERY; GENE AB Previous studies suggest that estrogen may prevent expression of cell adhesion molecules implicated in vascular inflammation associated with atherosclerosis. We demonstrate the interaction and reciprocal interference of estrogen receptors (ERs) with p65, the nuclear factor-kappaB component, in smooth muscle cells that express ER alpha and ER beta after exposure to 17 beta -estradiol for 48 to 72 hours. ER and p65 do not associate directly, as shown by lack of coprecipitation, but instead compete for limiting amounts of p300, a close relative of the CREB-binding protein. Overexpressed p300 significantly reduced the inhibitory effect of ER on p65-dependent transcription as well as the inhibitory effect of p65 on ER-dependent transcription. These actions were ligand-dependent. The expression of both ER and nuclear factor-kappaB-dependent reporter genes was partially rescued from ER/p65 mutual inhibition by transient transfection of smooth muscle cells with a p300 expression vector. These actions of 17 beta -estradiol may play an important role in the cytokine-induced expression of immune and inflammatory genes implicated in atherogenesis. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Speir, E (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B15,10 Ctr Dr, Bethesda, MD 20892 USA. NR 21 TC 70 Z9 73 U1 0 U2 0 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 NOV 24 PY 2000 VL 87 IS 11 BP 1006 EP 1011 PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 378WA UT WOS:000165607100011 PM 11090545 ER PT J AU Koch, CA Wolkersdoerfer, G AF Koch, CA Wolkersdoerfer, G TI Hyperlipoproteinemia in HIV patients with antiretroviral therapy: Which risk is greater - Pancreatitis or coronary heart disease? SO DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT LA German DT Article ID PROTEASE INHIBITORS C1 NICHD, NIH, Bethesda, MD 20892 USA. RP Koch, CA (reprint author), NICHD, NIH, Bldg 10,Rm 9D42, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008 OI Koch, Christian/0000-0003-3127-5739 NR 7 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0012-0472 J9 DEUT MED WOCHENSCHR JI Dtsch. Med. Wochenschr. PD NOV 24 PY 2000 VL 125 IS 47 BP 1450 EP 1450 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 376GG UT WOS:000165449400007 PM 11130125 ER PT J AU Fukuhara, S Chikumi, H Gutkind, JS AF Fukuhara, S Chikumi, H Gutkind, JS TI Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho SO FEBS LETTERS LA English DT Article DE Rho; G protein; Ras; signal transduction; G protein-coupled receptor ID DBL ONCOGENE PRODUCT; CELLULAR-TRANSFORMATION; SIGNAL-TRANSDUCTION; ACTIN CYTOSKELETON; ALPHA-SUBUNIT; P115 RHOGEF; G-ALPHA(12); GTPASES; DOMAIN; GASTRULATION AB A putative guanine nucleotide exchange factor (GEF), termed leukemia-associated RhoGEF (LARG), was recently identified upon fusion to the coding sequence of the MLL gene in acute myeloid leukemia. Although the function of LARG is still unknown, it exhibits a number of structural domains suggestive of a role in signal transduction, including a PDZ domain, a LH/ RGS domain, and a Dbl homology/pleckstrin homology domain. Here, we show that LARG can activate Rho in vivo. Furthermore, we present evidence that LARG is an integral component of a novel biochemical route whereby G protein-coupled receptors (GPCRs) and heterotrimeric G proteins of the Gait family stimulate Rho-dependent signaling pathways. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 9000 Rockville Pike,Bldg 30,Room 211, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 27 TC 174 Z9 177 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 24 PY 2000 VL 485 IS 2-3 BP 183 EP 188 DI 10.1016/S0014-5793(00)02224-9 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 379NJ UT WOS:000165648800017 PM 11094164 ER PT J AU Singh, BB Liu, XB Ambudkar, IS AF Singh, BB Liu, XB Ambudkar, IS TI Expression of truncated transient receptor potential protein 1 alpha (Trp1 alpha) - Evidence that the Trp1 C terminus modulates store-operated Ca2+ entry SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CAPACITATIVE CALCIUM-ENTRY; HTRP3 CHANNELS; CELLS; ACTIVATION AB Transient receptor potential protein 1 (Trp1) has been proposed as a component of the store-operated Ca2+ entry (SOCE) channel. However, the exact mechanism by which Trp1 is regulated by store depletion is not known. Here, we examined the role of the Trpl C-terminal domain in SOCE by expressing hTrp1 alpha lacking amino acids 664-793 (Delta Trp1 alpha) or full-length hTrp1 alpha in the HSG (human submandibular gland) cell line. Both carbachol (CCh) and thapsigargin (Tg) activated sustained Ca2+ influx in control (nontransfected), Delta Trp1 alpha-, and Trp1 alpha -expressing cells. Sustained [Ca2+](i), following stimulation with either Tg or CCh in Delta Trp1 alpha -expressing cells, was about 1.5-2-fold higher than in Trp1 alpha -expressing cells and 4-fold higher than in control cells. Importantly, (i) basal Ca2+ influx and (ii) Tg- or CCh-stimulated internal Ca2+ release were similar in all the cells. A similar increase in Tg-stimulated Ca2+ influx was seen in cells expressing Delta 2Tr1 alpha, lacking the C-terminal domain amino acid 649-793, which includes the EWKFAR sequence. Further, both inositol 1,4,5-trisphosphate receptor-3 and caveolin-1 were immunoprecipitated with Delta Trp1 alpha and Trp1 alpha. In aggregate, these data suggest that (i) the EWKFAR sequence does not contribute significantly to the Trp1-associated increase in SOCE, and (ii) the Trpl C-terminal region, amino acids 664-793, is involved in the modulation of SOCE. C1 NIDCR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), NIDCR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Rm 1N-113, Bethesda, MD 20892 USA. OI Singh, Brij/0000-0003-0535-5997 NR 22 TC 29 Z9 29 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 NOV 24 PY 2000 VL 275 IS 47 BP 36483 EP 36486 DI 10.1074/jbc.C000529200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378GY UT WOS:000165577700002 PM 10980191 ER PT J AU Clark, AB Valle, F Drotschmann, K Gary, RK Kunkel, TA AF Clark, AB Valle, F Drotschmann, K Gary, RK Kunkel, TA TI Functional interaction of proliferating cell nuclear antigen with MSH2-MSH6 and MSH2-MSH3 complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-POLYMERASE-DELTA; BASE EXCISION-REPAIR; MISMATCH REPAIR; SACCHAROMYCES-CEREVISIAE; PCNA BINDING; REPLICATION; IDENTIFICATION; MUTATIONS; P21(WAF1); INHIBITOR AB Eukaryotic DNA mismatch repair requires the concerted action of several proteins, including proliferating cell nuclear antigen (PCNA) and heterodimers of MSH2 complexed with either MSH3 or MSH6. Here we report that MSH3 and MSH6, but not MSH2, contain N-terminal sequence moths characteristic of proteins that bind to PCNA. MSH3 and MSH6 peptides containing these motifs bound PCNA, as did the intact Msh2-Msh6 complex. This binding was strongly reduced when alanine was substituted for conserved residues in the moth. Yeast strains containing alanine substitutions in the PCNA binding motif of Msh6 or Msh3 had elevated mutation rates, indicating that these interactions are important for genome stability. When human MSH3 or MSH6 peptides containing the PCNA binding motif were added to a human cell extract, mismatch repair activity was inhibited at a step preceding DNA resynthesis. Thus, MSH3 and MSH6 interactions with PCNA may facilitate early steps in DNA mismatch repair and may also be important for other roles of these eukaryotic MutS homologs. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ Nevada, Dept Chem, Las Vegas, NV 89154 USA. Univ Nevada, UNLV Canc Inst, Las Vegas, NV 89154 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RI Gary, Ronald/A-8650-2008 OI Gary, Ronald/0000-0001-5079-1953 NR 30 TC 158 Z9 164 U1 0 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 NOV 24 PY 2000 VL 275 IS 47 BP 36498 EP 36501 DI 10.1074/jbc.C000513200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378GY UT WOS:000165577700006 PM 11005803 ER PT J AU Perugini, MA Schuck, P Howlett, GJ AF Perugini, MA Schuck, P Howlett, GJ TI Self-association of human apolipoprotein E3 and E4 in the presence and absence of phospholipid SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SODIUM DODECYL-SULFATE; LOW-DENSITY LIPOPROTEINS; RECEPTOR-BINDING DOMAIN; AMINO-ACID-SEQUENCE; E ISOFORMS; ALZHEIMERS-DISEASE; AQUEOUS-SOLUTIONS; NMR-SPECTROSCOPY; LAMM EQUATION; SEDIMENTATION AB Human apolipoprotein E (apoE) exists as three main isoforms, differing by single amino acid substitutions, with the apoE4 isoform strongly linked to the incidence of late onset Alzheimer's disease. We have expressed and purified apoE3 and apoE4 from Escherichia coli and compared their hydrodynamic properties by gel permeation liquid chromatography, capillary electrophoresis, circular dichroism, and sedimentation methods. Sedimentation velocity experiments, employing a new method for determining the size distribution of polydisperse macromolecules in solution (Schuck, P. (2000) Biophys. J. 78, 1606-1619), provide direct evidence for the heterogeneous solution structures of apoE3 and apoE4. In a lipid-free environment, apoE3 and apoE4 exist as a slow equilibrium mixture of monomer, tetramer, octamer, and a small proportion of higher oligomers. Both sedimentation velocity and equilibrium experiments indicate that apoE4 has a greater propensity to self-associate. We also demonstrate that apoE3 and apoE4 oligomers dissociate significantly in the presence of dihexanoylphosphatidylcholine micelles (20 mM) and to a lesser extent at submicellar concentrations (4 mM). The ct-helical content for both isoforms was almost identical (50%) in the presence and absence of dihexanoylphosphatidylcholine. These results reveal that apoE oligomers undergo phospholipid-induced dissociation to folded monomers, suggesting the monomeric form prevails on the lipoprotein surface in vivo. C1 Univ Melbourne, Russel Grimwade Sch Biochem & Mol biol, Parkville, Vic 3052, Australia. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Howlett, GJ (reprint author), Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia. EM g.howlett@biochemistry.unimelb.edu.au OI Schuck, Peter/0000-0002-8859-6966; Perugini, Matthew/0000-0001-8052-5584 NR 40 TC 81 Z9 81 U1 2 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 24 PY 2000 VL 275 IS 47 BP 36758 EP 36765 DI 10.1074/jbc.M005565200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378GY UT WOS:000165577700045 PM 10970893 ER PT J AU Andley, UP Song, Z Wawrousek, EF Fleming, TP Bassnett, S AF Andley, UP Song, Z Wawrousek, EF Fleming, TP Bassnett, S TI Differential protective activity of alpha A- and alpha B-crystallin in lens epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK-PROTEIN; CHAPERONE-LIKE ACTIVITY; MOLECULAR CHAPERONE; HUMAN HSP27; TNF-ALPHA; EXPRESSION; STRESS; APOPTOSIS; GENE; RESISTANCE AB alphaA- and alphaB-crystallins are molecular chaperones expressed at low levels in lens epithelial cells, and their expression increases dramatically during differentiation to lens fibers. However, the functions of alphaA- and alphaB-crystallins in lens epithelial cells have not been studied in detail. In this study, the relative ability of alphaA- and alphaB-crystallin, in protecting lens epithelial cells from apoptotic cell death was determined, The introduction of alphaA-crystallin in the transformed human lens epithelial (HLE) B-3 lens epithelial cell line (which expresses low endogenous levels of alphaB-crystallin) led to a nearly complete protection of cell death induced by staurosporine, Fas monoclonal antibody, or the cytokine tumor necrosis factor cu. To further study the relative protective activities of alphaA- and alphaB-crystallins, we created a cell line derived from alphaA-/-alphaB-/- double knockout mouse lens epithelia by infecting primary cells with Ad12-SV40 hybrid virus. The transformed cell line alpha AYBKO1 derived from alphaA/alphaB double knockout cells was transfected with alphaA- or alphaB-crystallin cDNA contained in pCIneo mammalian expression vector. Cells expressing different amounts of either alphaA-crystallin or alphaB-crystallin were isolated. The ability of alphaA- or aB-crystallin to confer protection from apoptotic cell death was determined by annexin labeling and flow cytometry of staurosporine- or UVA- treated cells. The results indicate that the anti-apoptotic activity of alphaA-crystallin was two to threefold higher than that of alphaB-crystallin, Our work suggests that comparing the in vitro annexin labeling of lens epithelial cells is an effective way to measure the protective activity of alphaA- and alphaB-crystallin. Since the expression of alphaA-crystallin is largely restricted to the lens, its greater protective effect against apoptosis suggests that it may play a significant role in protecting lens epithelial cells from stress. C1 Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Andley, UP (reprint author), Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, 660 S Euclid Ave,Campus Box 8096, St Louis, MO 63110 USA. RI Wawrousek, Eric/A-4547-2008 FU NEI NIH HHS [EY09852, R01-EY05681, EY02687] NR 37 TC 114 Z9 122 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 NOV 24 PY 2000 VL 275 IS 47 BP 36823 EP 36831 DI 10.1074/jbc.M004233200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378GY UT WOS:000165577700055 PM 10967101 ER PT J AU Chou, CL Yip, KP Michea, L Kador, K Ferraris, JD Wade, JB Knepper, MA AF Chou, CL Yip, KP Michea, L Kador, K Ferraris, JD Wade, JB Knepper, MA TI Regulation of aquaporin-2 trafficking by vasopressin in the renal collecting duct - Roles of ryanodine-sensitive Ca2+ stores and calmodulin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PANCREATIC BETA-CELLS; WATER PERMEABILITY; INTRACELLULAR CA2+; RAT; ACTIVATION; RECEPTOR; CALCIUM; EXPRESSION; CHANNELS; HORMONE AB In the renal collecting duct, vasopressin increases osmotic water permeability (P-f) by triggering trafficking of aquaporin-2 vesicles to the apical plasma membrane. We investigated the role of vasopressin-induced intracellular Ca2+ mobilization in this process. In isolated inner medullary collecting ducts (IMCDs), vasopressin (0.1 nM) and 8-(4-chlorophenylthio)-cAMP (0.1 mM) elicited marked increases in [Ca2+](i) (fluo-4), Vasopressin-induced Ca2+ mobilization was completely blocked by preloading with the Ca2+ chelator BAPTA, In parallel experiments, BAPTA completely blocked the vasopressin-induced increase in P-f without affecting adenosine 3',5'-cyclic monophosphate (cAMP) production. Previously, we demonstrated the lack of activation of the phosphoinositide-signaIing pathway by vasopressin in IMCD, suggesting an inositol 1,4,5-trisphosphate-independent mechanism of Ca2+ release. Evidence for expression of the type I ryanodine receptor (RyR1) in IMCD was obtained by immunofluorescence, immunoblotting, and reverse transcription-polymerase chain reaction, Ryanodine (100 muM), a ryanodine receptor antagonist, blocked the arginine vasopressin-mediated increase in P-f and blocked vasopressin-stimulated redistribution of aquaporin-2 to the plasma membrane domain in primary cultures of IMCD cells, as assessed by immunofluorescence immunocytochemistry. Calmodulin inhibitors (W7 and trifluoperazine) blocked the P-f response to vasopressin and the vasopressin-stimulated redistribution of aquaporin-2. The results suggest that Ca2+ release from ryanodine-sensitive stores plays an essential role in vasopressin-mediated aquaporin-2 trafficking via a calmodulin-dependent mechanism. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Univ S Florida, Coll Med, Dept Physiol & Biophys, Tampa, FL 33612 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,MSC 1603,Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. RI Yip, Kay-Pong/H-4639-2012 OI Yip, Kay-Pong/0000-0003-4364-6701 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 41 TC 129 Z9 133 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 NOV 24 PY 2000 VL 275 IS 47 BP 36839 EP 36846 DI 10.1074/jbc.M005552200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378GY UT WOS:000165577700057 PM 10973964 ER PT J AU Yang, Q Manicone, A Coursen, JD Linke, SP Nagashima, M Forgues, M Wang, XW AF Yang, Q Manicone, A Coursen, JD Linke, SP Nagashima, M Forgues, M Wang, XW TI Identification of a functional domain in a GADD45-mediated G(2)/M checkpoint SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID P53-REGULATED PROTEIN GADD45; CELL-CYCLE CHECKPOINTS; DNA-DAMAGING AGENTS; GROWTH ARREST; RAN/TC4 GTPASE; P53; INDUCTION; MITOSIS; YEAST; GENES AB Cell cycle checkpoints are essential for the maintenance of genomic stability in response to DNA damage. We demonstrated recently that GADD45, a DNA damage-inducible protein, activates a G(2)/M checkpoint induced by either UV radiation or alkylating agents. GADD45 can interact in vivo with the G(2) cell cycle-specific kinase, Cdc2, proliferating cell nuclear antigen (PCNA), and the cell cycle kinase inhibitor p21(waf1). The ability of GADD45 to induce a G2/M arrest may be caused in part by the inhibition of Cdc2 kinase activity. Here, we report the identification of a region of GADD45 that is involved in this G(2)/M checkpoint. Mutants of GADD45 that lacked either the first 35 or the last 80 residues still retained an ability to induce G(2)/M arrest. A mutant with a deletion of the central region (residues 50-76), which is conserved in the family members GADD45 beta and GADD45 gamma, lacked such activity. This mutant also lacked an ability to bind to Cdc2, PCNA, and p21(waf1) in vivo. Consistently, either GADD45 beta or GADD45 gamma bind to Cdc2 in vivo. However, unlike GADD45, neither GADD45 beta nor GADD45 gamma inhibited the Cdc2 kinase or induced G2/M arrest. The unique effect of GADD45 may be caused by the presence of a region containing DEDDDR residues. Alanine substitutions in the region abolished GADD45 induction of a G(2)/M arrest and its inactivation of the Cdc2 kinase but not its binding to Cdc2, PCNA, or p21(waf1). Therefore, the binding of GADD45 to Cdc2 was insufficient to induce a G2/M arrest, and additional activity contributed by the DEDDDR residues may be necessary to regulate the G(2)/M checkpoint. C1 NCI, Human Carcinogenesis Lab, DBS, NIH, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, DBS, NIH, 37 Convent Dr,MSC 4255,Bldg 37,Rm 2C08, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009 NR 35 TC 61 Z9 61 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 NOV 24 PY 2000 VL 275 IS 47 BP 36892 EP 36898 DI 10.1074/jbc.M005319200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378GY UT WOS:000165577700064 PM 10973963 ER PT J AU Brunet, A Samaan, A Deshaies, F Kindt, TJ Thibodeau, J AF Brunet, A Samaan, A Deshaies, F Kindt, TJ Thibodeau, J TI Functional characterization of a lysosomal sorting motif in the cytoplasmic tail of HLA-DO beta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLASS-II MOLECULES; INVARIANT CHAIN EXPRESSION; INTRACELLULAR-TRANSPORT; MICE LACKING; DR MOLECULES; HISTOCOMPATIBILITY ANTIGENS; CELL-SURFACE; MONOCLONAL-ANTIBODIES; ENDOCYTIC PATHWAY; TARGETING SIGNALS AB HLA-DO is an intracellular non-classical class II major histocompatibility complex molecule expressed in the endocytic pathway of B lymphocytes, which regulates the loading of antigenic peptides onto classical class II molecules such as HLA-DR. The activity of HLA-DO is mediated through its interaction with the peptide editor HLA-DM. Here, our results demonstrate that although HLA-DO is absolutely dependent on its association with DM: to egress the endoplasmic reticulum, the cytoplasmic portion of its beta chain encodes a functional lysosomal sorting signal, By confocal microscopy and flow cytometry analysis, we show that reporter transmembrane molecules fused to the cytoplasmic tail of HLA-DO beta accumulated in Lamp-1(+) vesicles of transfected HeLa cells. Mutagenesis of a leucine-leucine motif abrogated lysosomal accumulation and resulted in cell surface redistribution of reporter molecules. Finally, we show that mutation of the di-leucine sequence in DO beta did not alter its lysosomal sorting when associated with DM molecules. Taken together, these results demonstrate that lysosomal expression of the DO-DM complex is mediated primarily by the tyrosine-based motif of HLA-DM and suggest that the DO beta -encoded motif is involved in the fine-tuning of the intracellular sorting. C1 Univ Montreal, Dept Microbiol & Immunol, Lab Immunol Mol, Montreal, PQ H3C 3J7, Canada. NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA. RP Thibodeau, J (reprint author), Univ Montreal, Dept Microbiol & Immunol, Lab Immunol Mol, CP 6128,Succ Ctr Ville, Montreal, PQ H3C 3J7, Canada. NR 81 TC 25 Z9 26 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 NOV 24 PY 2000 VL 275 IS 47 BP 37062 EP 37071 DI 10.1074/jbc.M005112200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378GY UT WOS:000165577700085 PM 10964920 ER PT J AU Marcu, MG Chadli, A Bouhouche, I Catelli, M Neckers, LM AF Marcu, MG Chadli, A Bouhouche, I Catelli, M Neckers, LM TI The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HSP90 MOLECULAR CHAPERONE; CELL-FREE SYSTEM; PROGESTERONE-RECEPTOR; DNA GYRASE; IN-VITRO; GELDANAMYCIN; KINASE; SITE; HETEROCOMPLEX; CONFORMATION AB Heat shock protein 90 (Hsp90), one of the most abundant chaperones in eukaryotes, participates in folding and stabilization of signal-transducing molecules including steroid hormone receptors and protein kinases, The amino terminus of Hsp90 contains a non-conventional nucleotide-binding site, related to the ATP-binding motif of bacterial DNA gyrase. The anti-tumor agents geldanamycin and radicicol bind specifically at this site and induce destabilization of Hsp90-dependent client proteins. We recently demonstrated that the gyrase inhibitor novobiocin also interacts with Hsp90, altering the affinity of the chaperone for geldanamycin and radicicol and causing in vitro and in vivo depletion of key regulatory Hsp90-dependent kinases including v-Src, Raf-l, and p185(ExbB2). In the present study we used deletion/mutation analysis to identify the site of interaction of novobiocin with Hsp90, and we demonstrate that the novobiocin-binding site resides in the carboxyl terminus of the chaperone. Surprisingly, this motif also recognizes ATP, and ATP and novobiocin efficiently compete with each other for binding to this region of Hsp90. Novobiocin interferes with association of the cochaperones Hsc70 and p23 with Hsp90. These results identify a second site on Hsp90 where the binding of small molecule inhibitors can significantly impact the function of this chaperone, and they support the hypothesis that both amino- and carboxyl-terminal domains of Hsp90 interact to modulate chaperone activity. C1 NCI, Dept Cell & Canc Biol, Med Branch, NIH, Rockville, MD 20850 USA. Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. CNRS, UPR Cochin Port Royal, F-75014 Paris, France. RP Neckers, LM (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, NIH, Rockville, MD 20850 USA. NR 37 TC 321 Z9 335 U1 3 U2 12 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 NOV 24 PY 2000 VL 275 IS 47 BP 37181 EP 37186 DI 10.1074/jbc.M003701200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378GY UT WOS:000165577700099 PM 10945979 ER PT J AU Li, YL Li, HM Martin, R Mariuzza, RA AF Li, YL Li, HM Martin, R Mariuzza, RA TI Structural basis for the binding of an immunodominant peptide from myelin basic protein in different registers by two HLA-DR2 proteins SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE multiple sclerosis; myelin basic protein; MHC class II; HLA-DR2; X-ray crystallography ID CLASS-II MOLECULES; MULTIPLE-SCLEROSIS PATIENTS; MHC CLASS-II; T-CELL RESPONSE; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; ANTIGENIC PEPTIDE; ESCHERICHIA-COLI; FINE SPECIFICITY; HIGH-AFFINITY AB Susceptibility to multiple sclerosis (MS) is associated with certain MHC class II haplotypes, in particular HLA-DR2. Two DR beta chains, DRB1*1501 and DRB5*0101, are co-expressed in the HLA-DR2 haplotype, resulting in the formation of two functional cell surface heterodimers, HLA-DR2a (DRA*0101, DRB5*0101) and HLA-DR2b (DRA*0101, DRB1*1501). Both isotypes can present an immunodominant peptide of myelin basic protein (MBP 84-102) to MBP-specific T cells from MS patients. We have determined the crystal structure of HLA-DR2a complexed with MBP 86-105 to 1.9 Angstrom resolution. A comparison of this structure with that of HLA-DR2b complexed with MBP 85-99, reported previously, reveals that the peptide register is shifted by three residues, such that the MBP peptide is bound in strikingly different conformations by the two MHC molecules. This shift in binding register is attributable to a large P1 pocket in DR2a, which accommodates Phe92, in conjunction with a relatively shallow P4 pocket, which is occupied by Ile95. In DR2b, by contrast, the small P1 pocket accommodates Val89, while the deep P4 pocket is filled by Phe92. Ln both complexes, however, the C-terminal half of the peptide is positioned higher in the binding groove than in other MHC class II/peptide structures. As a result of the register shift, different side-chains of the MBP peptide are displayed for interaction with T cell receptors in the DR2a and DR2b complexes. These results demonstrate that MHC molecules can impose different alignments and conformations on the same bound peptide as a consequence of topological differences in their peptide-binding sites, thereby creating distinct T cell epitopes. (C) 2000 Academic Press. C1 Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Mariuzza, RA (reprint author), Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, 9600 Guidelsky Dr, Rockville, MD 20850 USA. OI Li, Hongmin/0000-0002-8684-5308 FU NIAID NIH HHS [AI36900] NR 45 TC 83 Z9 87 U1 0 U2 2 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 NOV 24 PY 2000 VL 304 IS 2 BP 177 EP 188 DI 10.1006/jmbi.2000.4198 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 379YE UT WOS:000165670100005 PM 11080454 ER PT J AU Gharehbaghi, K Szekeres, T Yalowitz, JA Fritzer-Szekeres, M Pommier, YG Jayaram, HN AF Gharehbaghi, K Szekeres, T Yalowitz, JA Fritzer-Szekeres, M Pommier, YG Jayaram, HN TI Sensitizing human colon carcinoma HT-29 cells to cisplatin by cyclopentenylcytosine, in vitro and in vivo SO LIFE SCIENCES LA English DT Article DE cyclopentenylcytosine; cisplatin, synergy; antitumor activity; human colon carcinoma HT-29 ID DEPENDENT SYNERGISM; CYTOSINE; TRIPHOSPHATE; LINE; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; CYTOTOXICITY; INHIBITION; ANTITUMOR; ANALOGS; PHASE AB Cyclopentenylcytosine (CPEC) is cytotoxic to HT-29 cells in vitro and in vivo. Treatment with CPEC resulted in sensitizing HT-29 cells to cisplatin (CDDP), as evidenced by synergistic cytotoxicity. CPEC exhibits potent cytotoxicity to HT-29 cells in vitro, 2 and 24 h exposure providing an LC50 of 2.4 and 0.46 muM, respectively. Exposure of HT-29 cells to CDDP for 2 h resulted in an LC50 of 26 muM. Treatment of HT-29 cells with 1.0 or 1.25 muM CPEC and then incubating with CDDP showed synergistic cytotoxicity. Lesser synergy at very high concentrations of CPEC was demonstrated when HT-29 cells were first exposed to CDDP and then incubated with CPEC. Combination index calculations showed synergistic cytotoxicity in HT-29 cells when CPEC was combined with CDDP. Synergistic antitumor activity was demonstrable in vivo in mice transplanted with HT-29 tumor when treated with a combination of CPEC and CDDP without undue toxicity, since no excessive loss in mouse body weight or overt pathology was observed. CPEC had no influence on the total DNA adduct formation and CDDP did not affect the intracellular levels of CPEC or its metabolites, suggesting that enhanced CDDP cytotoxicity resulted from a step subsequent to excision of platinum-cross-linked DNA. These studies support a new approach for augmenting cytotoxic effect of CPEC with CDDP in treating human colon carcinoma. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. Krankenanstalt Rudolfstiftung, A-1030 Vienna, Austria. Univ Vienna, Sch Med, ClinInst Med & Chem Lab Diagnost, A-1090 Vienna, Austria. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Jayaram, HN (reprint author), Indiana Univ, Sch Med, Dept Biochem & Mol Biol, 635 Barnhill Dr,MS 4051, Indianapolis, IN 46202 USA. NR 28 TC 12 Z9 12 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD NOV 24 PY 2000 VL 68 IS 1 BP 1 EP 11 DI 10.1016/S0024-3205(00)00914-0 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 379DA UT WOS:000165624600001 PM 11132239 ER PT J AU Terskikh, A Fradkov, A Ermakova, G Zaraisky, A Tan, P Kajava, AV Zhao, XN Lukyanov, S Matz, M Kim, S Weissman, I Siebert, P AF Terskikh, A Fradkov, A Ermakova, G Zaraisky, A Tan, P Kajava, AV Zhao, XN Lukyanov, S Matz, M Kim, S Weissman, I Siebert, P TI "Fluorescent timer": Protein that changes color with time SO SCIENCE LA English DT Article ID GENE; MUTANTS; XANF-1 AB We generated a mutant of the red fluorescent protein drFP583. The mutant (E5) changes its fluorescence from green to red over time. The rate of color conversion is independent of protein concentration and therefore can be used to trace time-dependent expression. We used in vivo labeling with E5 to measure expression from the heat shock-dependent promoter in Caenorhabditis elegans and from the Otx-2 promoter in developing Xenopus embryos. Thus, E5 is a "fluorescent timer" that can be used to monitor both activation and downregulation of target promoters on the whole-organism scale. C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. Russian Acad Sci, Inst Bioorgan Chem, Moscow 117871, Russia. NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA. Clontech Labs, Palo Alto, CA 94303 USA. RP Terskikh, A (reprint author), Stanford Univ, Sch Med, Stanford, CA 94305 USA. RI Lukyanov, Sergey/F-9140-2014; Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 FU FIC NIH HHS [1 RO3 TW01362-01] NR 16 TC 228 Z9 241 U1 7 U2 30 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 NOV 24 PY 2000 VL 290 IS 5496 BP 1585 EP 1588 DI 10.1126/science.290.5496.1585 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376EX UT WOS:000165446200053 PM 11090358 ER PT J AU Williams, BO Barish, GD Klymkowsky, MW Varmus, HE AF Williams, BO Barish, GD Klymkowsky, MW Varmus, HE TI A comparative evaluation of beta-catenin and plakoglobin signaling activity SO ONCOGENE LA English DT Article DE beta-catenin; plakoglobin; Wnt; LEF/TCF ID F-BOX PROTEIN; GLYCOGEN-SYNTHASE KINASE-3; TRANSCRIPTION FACTOR LEF-1; TUMOR-SUPPRESSOR PROTEIN; XENOPUS EMBRYOS; AXIS FORMATION; HEPATOCELLULAR CARCINOMAS; FUNCTIONAL INTERACTION; NUCLEAR-LOCALIZATION; NEGATIVE REGULATOR AB Vertebrates have two Armadillo-like proteins, beta -catenin and plakoglobin. Mutant forms of beta -catenin with oncogenic activity are found in many human tumors, but plakoglobin mutations are not commonly found, In fact, plakoglobin has been proposed to suppress tumorigenesis, To assess differences between beta -catenin and plakoglobin, we compared several of their biochemical properties, After transient transfection of 293T cells with an expression vector encoding either of the two proteins, soluble wild type beta -catenin does not significantly accumulate, whereas soluble wild type plakoglobin is readily detected. As anticipated, beta -catenin is stabilized by the oncogenic mutation S37A; however, the analogous mutation in plakoglobin (S28A) does not alter its half-life. S37A-beta -catenin activates a TCF/LEF-dependent reporter 20-fold more potently than wild type beta -catenin, and similar to5-fold more potently than wild type or S28A plakoglobin. These differences may be attributable to an enhanced affinity of S37A beta -catenin for LEF1 and TCF4, as observed here by immunoprecipitation assays. We show that the carboxyl-terminal domain is largely responsible for the difference in signaling and that the Armadillo repeats account for the remainder of the difference, The relatively weak signaling by plakoglobin and the failure of the S28A mutation to enhance its stability, may explain why plakoglobin mutations are infrequent in malignancies. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Colorado, Boulder, CO 80309 USA. RP Williams, BO (reprint author), Van Andel Res Inst, 333 Bostwick NE, Grand Rapids, MI 49503 USA. RI Williams, Bart/A-3539-2013 OI Williams, Bart/0000-0002-5261-5301 FU NIGMS NIH HHS [GM54001] NR 87 TC 45 Z9 45 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 NOV 23 PY 2000 VL 19 IS 50 BP 5720 EP 5728 DI 10.1038/sj.onc.1203921 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 376VP UT WOS:000165477700003 PM 11126358 ER PT J AU Guo, TL McCay, JA Brown, RD Musgrove, DL Germolec, DR Butterworth, L Munson, AE White, KL AF Guo, TL McCay, JA Brown, RD Musgrove, DL Germolec, DR Butterworth, L Munson, AE White, KL TI Carbon tetrachloride is immunosuppressive and decreases host resistance to Listeria monocytogenes and Streptococcus pneumoniae in female B6C3F1 mice SO TOXICOLOGY LA English DT Article DE carbon tetrachloride; female B6C3F1 mice; hist resistance; mononuclear phagocyte system; antibody forming cell response ID DELAYED-TYPE HYPERSENSITIVITY; NATURAL-KILLER-CELLS; MURINE LISTERIOSIS; SECONDARY INFECTION; IMMUNE-RESPONSES; INTERFERON-GAMMA; LIVER-CIRRHOSIS; NUDE MICE; RATS; METABOLISM AB Carbon tetrachloride (CCl4) is an environmental contaminant that has been detected in ambient air, seawater, surface-water and snow. The immunotoxic potential of CCl4 was evaluated in female B6C3F1 mice. The animals were administered with CCl4 daily for 14 days at doses of 50, 100, 500 or 1000 mg/kg body weight by gavage with corn oil as a vehicle. Exposure to CCl4 resulted in an increase of liver weight but not the body weight and the weights of brain, spleen, lungs, thymus and kidneys. Exposure to CCl4 produced minimal effect on differential hematological parameters: however, it produced a significant increase in serum glutamic-pyruvic transaminase (SGPT) levels in all dose groups while other serum chemistries showed sporadic increases, primarily at the dose level of 1000 mg/kg. Exposure to CCl4 produced a decreased humoral immune response, the IgM antibody forming cell (AFC) response to sheep red blood cells (sRBC) was suppressed with the maximal decrease (45%) observed at the dose level of 1000 mg/kg. The IgM serum titer to sRBC was also reduced with a maximal decrease (54%) observed at the dose level of 500 mg/kg. Although exposure to CCl4 had no effects on the mixed leukocyte response (MLR), cytotoxic T lymphocyte activity and natural killer (NK) cell activity, a decrease in both the absolute number and the percentage of CD4(+) CD8(-) at the dose level of 500 mg/kg was observed. The functional activity of the mononuclear phagocyte system was compromised as reflected by a decrease in the vascular clearance of Cr-15-sRBC and a decrease in the uptake of Cr-51-sRBC by the liver. Finally, in the two host resistance models evaluated, exposure to CCl4 decreased host resistance to both Streptococcus pneumoniae and Listeria monocytogenes with greater susceptibility to the latter. Overall, these studies demonstrate that CCl4 was immunosuppressive in female B6C3F1 mice. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980613, Richmond, VA 23298 USA. FU NIEHS NIH HHS [ES55094] NR 48 TC 7 Z9 10 U1 0 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 NOV 23 PY 2000 VL 154 IS 1-3 BP 85 EP 101 DI 10.1016/S0300-483X(00)00327-9 PG 17 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 381UY UT WOS:000165782900009 PM 11118673 ER PT J AU Vousden, KH AF Vousden, KH TI p53: Death star SO CELL LA English DT Review ID P53-MEDIATED APOPTOSIS C1 NCI, Regulat Cell Growth Lab, Frederick, MD 21702 USA. RP Vousden, KH (reprint author), NCI, Regulat Cell Growth Lab, Frederick, MD 21702 USA. EM vousden@ncifcrf.gov NR 19 TC 624 Z9 643 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 22 PY 2000 VL 103 IS 5 BP 691 EP 694 DI 10.1016/S0092-8674(00)00171-9 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 375ZJ UT WOS:000165433100001 PM 11114324 ER PT J AU Roll-Mecak, A Cao, C Dever, TE Burley, SK AF Roll-Mecak, A Cao, C Dever, TE Burley, SK TI X-ray structures of the universal translation initiation factor IF2/elF5B: Conformational changes on GDP and GTP binding SO CELL LA English DT Article ID ELONGATION-FACTOR TU; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; FACTOR IF2; FACTOR-II; EF-TU; RNA; DIFFRACTION; RESOLUTION; HYDROLYSIS AB X-ray structures of the universal translation initiation factor IF2/eIF5B have been determined in three stales: free enzyme, inactive IF2/eIF5B.GDP, and active IF2/eIF5B.GTP. The "chalice-shaped" enzyme is a GTPase that facilitates ribosomal subunit joining and Met-tRNA(i) binding to ribosomes in all three kingdoms of life. The conserved core of IF2/eIF5B consists of an N-terminal G domain (I) plus an EF-Tu-type beta barrel (II), followed by a novel alpha/beta/alpha -sandwich (III) connected via an alpha helix to a second EF-Tu-type beta barrel (IV). Structural comparisons reveal a molecular lever, which amplifies a modest conformational change in the Switch 2 region of the G domain induced by Mg2+/GTP binding over a distance of 90 Angstrom from the G domain active center to domain IV. Mechanisms of GTPase function and ribosome binding are discussed. C1 Rockefeller Univ, Lab Mol Biophys, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. RP Burley, SK (reprint author), Rockefeller Univ, Lab Mol Biophys, 1230 York Ave, New York, NY 10021 USA. EM burley@rockvax.rockefeller.edu FU NIGMS NIH HHS [GM61262] NR 39 TC 163 Z9 165 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 22 PY 2000 VL 103 IS 5 BP 781 EP 792 DI 10.1016/S0092-8674(00)00181-1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 375ZJ UT WOS:000165433100010 PM 11114334 ER PT J AU Biggar, RJ Frisch, M AF Biggar, RJ Frisch, M TI Estimating the risk of cancer in children with AIDS - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Statens Serum Inst, Danish Epidemiol Sci Ctr, DK-2300 Copenhagen, Denmark. RP Biggar, RJ (reprint author), NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 NR 0 TC 5 Z9 5 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 NOV 22 PY 2000 VL 284 IS 20 BP 2593 EP 2594 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 373NU UT WOS:000165296200021 PM 11086360 ER PT J AU Podgornik, R Hansen, PL Parsegian, VA AF Podgornik, R Hansen, PL Parsegian, VA TI Elastic moduli renormalization in self-interacting stretchable polyelectrolytes SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID ELECTROSTATIC PERSISTENCE LENGTH; TENSION; CHAINS AB We study the effect of intersegment interactions on the effective bending and stretching moduli of a semiflexible polymer chain with a finite stretching modulus. For an interaction potential of a screened Debye-Huckel type, renormalization of the stretching modulus is derived on the same level of approximation as the celebrated Odijk-Skolnick-Fixman result for the bending modulus. The presence of mesoscopic intersegment interaction potentials couples the bending and stretching moduli in a manner different from that predicted by the macroscopic elasticity theory. We thus advocate a fundamental change in the perspective regarding the dependence of elastic moduli of a flexible polyelectrolyte on the ionic conditions: stretchability. The theory presented here and its consequences compare favorably with recent experiments on DNA bending and stretching at not too low salt conditions. [S0021-9606(00)50244-X]. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Univ Ljubljana, Fac Math & Phys, Dept Phys, SI-1000 Ljubljana, Slovenia. Jozef Stefan Inst, Dept Theoret Phys, SI-1000 Ljubljana, Slovenia. RP Podgornik, R (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 17 TC 58 Z9 58 U1 0 U2 5 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD NOV 22 PY 2000 VL 113 IS 20 BP 9343 EP 9350 DI 10.1063/1.1319380 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 372CQ UT WOS:000165217000053 ER PT J AU Xie, D Gulnik, S Erickson, JW AF Xie, D Gulnik, S Erickson, JW TI Dissection of binding energy with native and ligand-bound protein stabilities: Determining the affinity of ultratight-binding inhibitors of HIV-1 protease and its drug-resistance mutants SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DIFFERENTIAL SCANNING CALORIMETRY; DENATURATION C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Struct Biochem Program, Frederick, MD 21702 USA. RP Xie, D (reprint author), Tibotec Inc, 1330 Piccard Dr, Rockville, MD 20850 USA. NR 17 TC 12 Z9 12 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 22 PY 2000 VL 122 IS 46 BP 11533 EP 11534 DI 10.1021/ja003230m PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 378TL UT WOS:000165600300041 ER PT J AU Wang, L Menting, JGT Black, CG Stowers, A Kaslow, DC Hoffman, SL Coppel, RL AF Wang, L Menting, JGT Black, CG Stowers, A Kaslow, DC Hoffman, SL Coppel, RL TI Differences in epitope recognition, isotype and titer of antisera to Plasmodium falciparum merozoite surface protein 4 raised by different modes of DNA or protein immunization SO VACCINE LA English DT Article DE MSP4; DNA vaccination; antibody response ID CYTOTOXIC T-LYMPHOCYTES; FACTOR-LIKE DOMAIN; CIRCUMSPOROZOITE PROTEIN; ANTIBODY-RESPONSES; HUMAN MALARIA; MICE; VACCINATION; VACCINES; PLASMID; ANTIGEN AB Plasmodium falciparum merozoite surface protein 4 (MSP4) is being developed as a component of a subunit vaccine against asexual stages of malaria. Three DNA constructs were produced that induced expression of MSP4 either in the cytoplasm of transfected cells or secreted from cells under the control of the human tissue plasminogen activator (TPA) signal or the native P. falciparum MSP4 signal. Only the construct containing the TPA signal induced detectable antibodies in mice, although gene expression was demonstrated in all constructs and MSP4 was shown to be secreted using either signal by in vitro transient transfection of COS cells. Two recombinant MSP4 proteins that encoded the same sequence as the plasmid DNA were produced in E. coli (EcMSP4-His) and S. cerevisiae (yMSP4-His) and used to raise antibodies in mice. Comparison of the antibodies elicited by these various antigen formulations showed differences in titer, isotype and epitope recognition. The titer of antibodies induced by DNA:vaccination was lower than that induced by yMSP4-His, which in turn was lower than that induced by EcMSP3-His. The isotype profiles of the antibodies were also different, the plasmid DNA induced predominantly IgG, responses whereas the two proteins induced predominantly IgG(1) responses. The antibodies induced by DNA and yMSP4-His recognized predominantly the C-terminal epidermal growth factor (EGF)-like domain of the protein, whereas EcMSP3-His induced antibodies recognizing all domains of the protein equally. The antibodies induced by DNA vaccination were directed almost extensively to conformational epitopes so that reactivity with native MSP4 was abolished after disulfide bonds in the protein were disrupted. Antibodies induced by recombinant proteins recognized linear epitopes as well and reactivity to native MSP4 was preserved after reduction and alkylation of parasite proteins. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia. NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD 20852 USA. USN, Med Res Inst, Malaria PRogram, Rockville, MD 20852 USA. RP Coppel, RL (reprint author), Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia. RI Coppel, Ross/A-6626-2008; Black, Casilda/B-1519-2008 OI Coppel, Ross/0000-0002-4476-9124; Black, Casilda/0000-0002-0424-4593 FU NIDDK NIH HHS [DK32094] NR 43 TC 17 Z9 17 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 NOV 22 PY 2000 VL 19 IS 7-8 BP 816 EP 824 DI 10.1016/S0264-410X(00)00245-0 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 380PA UT WOS:000165709200017 PM 11115704 ER PT J AU Volk, DE Rice, JS Luxon, BA Yeh, HJC Liang, C Xie, G Sayer, JM Jerina, DM Gorenstein, DG AF Volk, DE Rice, JS Luxon, BA Yeh, HJC Liang, C Xie, G Sayer, JM Jerina, DM Gorenstein, DG TI NMR evidence for syn-anti interconversion of a trans opened (10R)-dA adduct of benzo[a]pyrene (7S,8R)-diol (9R,10S)-epoxide in a DNA duplex SO BIOCHEMISTRY LA English DT Article ID DEOXYADENOSINE N-6-AMINO GROUP; RAS CODON-61 SEQUENCE; DG MISMATCH OPPOSITE; DOSE-DEPENDENT DIFFERENCES; NONANUCLEOTIDE DUPLEX; SOLUTION CONFORMATION; OPTICAL ENANTIOMERS; ROTATING-FRAME; DIOL EPOXIDE; INTERCALATION AB 2D NMR has been used to examine the structure and dynamics of a 12-mer DNA duplex, d(T(1)A(2)G(3)T(4)C(5)A(6)A(7)*G(8)G(9)G(10)C(11)A(12))-d(T(13)G(14)C(15)C(16)C(17)T(18)T(19)G(20)A(21)C(22)T(23)A(24)) containing a 10R adduct at dA*(7), that corresponds to trans addition of the N-6-amino group of dA(7) to (-)-(7S,8R,9R,10S)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(-)-(S,R,R,S)-BP DE-2]. This DNA duplex contains the base sequence for the major dA mutational hot spot in the HPRT gene when Chinese hamster V79 cells are given low doses of the highly carcinogenic (+)-(R,S,S,R)-BP DE-2 enantiomer. NOE data indicate that the hydrocarbon is intercalated on the 5'-side of the modified base as has been seen previously for other oligonucleotides containing BP DE-2 (10R)-dA adducts. 2D chemical exchange-only experiments indicate dynamic behavior near the intercalation site especially at the 10R adducted dA, such that this base interconverts between the normal anti conformation and a less populated syn conformation. Ab initio molecular orbital chemical shift calculations of nucleotide and dinucleotide fragments in the syn and anti conformations support these conclusions. Although this DNA duplex containing a 10R dA adduct exhibits conformational flexibility as described, it is nevertheless more conformationally stable than the corresponding 10S adducted duplex corresponding to trans opening of the carcinogenic isomer (+)-(R,S,S,R)-BP DE-2, which was too dynamic to permit NMR structure determination. UV and imino proton NMR spectral observations indicated pronounced differences between these two diastereomeric 12-mer duplexes, consistent with conformational disorder at the adduct site and/or an equilibrium with a nonintercalated orientation of the hydrocarbon in the duplex containing the 10S adduct. The existence of conformational flexibility around adducts may be related to the occurrence of multiple mutagenic outcomes resulting from a single DE adduct. C1 Univ Texas, Med Branch, Sealy Ctr Struct Biol, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Gorenstein, DG (reprint author), Univ Texas, Med Branch, Sealy Ctr Struct Biol, Galveston, TX 77555 USA. RI Luxon, Bruce/C-9140-2012; OI Volk, David/0000-0002-4372-6915 FU NCI NIH HHS [1CO6CA59098]; NIEHS NIH HHS [ES06839, 1P30 ES06676] NR 43 TC 46 Z9 46 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 NOV 21 PY 2000 VL 39 IS 46 BP 14040 EP 14053 DI 10.1021/bi001669l PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 374QK UT WOS:000165355700005 PM 11087351 ER PT J AU Blaszczyk, J Van Coillie, E Proost, P Van Damme, J Opdenakker, G Bujacz, GD Wang, JM Ji, XH AF Blaszczyk, J Van Coillie, E Proost, P Van Damme, J Opdenakker, G Bujacz, GD Wang, JM Ji, XH TI Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors SO BIOCHEMISTRY LA English DT Article ID 3-DIMENSIONAL STRUCTURE; CHEMOATTRACTANT PROTEIN-3; BIOLOGICAL-ACTIVITIES; NMR ASSIGNMENTS; RESOLUTION; INTERLEUKIN-8; INFLAMMATION; RANTES; RIBONUCLEASE; SPECTROSCOPY AB Monocyte chemotactic protein 2 (MCP-2) is a CC chemokine that utilizes multiple cellular receptors to attract and activate human leukocytes. MCP-2 is a potent inhibitor of HIV-1 by virtue of its high-affinity binding to the receptor CCR5, one of the major coreceptors for HIV-1. Although a few structures of CC chemokines have been reported, none of these was determined with the N-terminal pyroglutamic acid residue (pGlu1) and a complete C-terminus. pGlu1 is essential for the chemotactic activity of MCP-2. Recombinant MCP-2 has Gln1 at the N terminus, 12-15% of which cyclizes automatically and forms pGlu1. The chemotactic activity of such MCP-2 mixture, which contains 12-15% pGlu1-form and 85-88% Gln1-form protein, is similar to 10 times lower when compared with that of fully cyclized MCP-2 preparation. Therefore, this chemokine is practically inactive without pGlu1. We have determined the complete crystal structure of MCP-2 that contains both pGlu1 and an intact C-terminus. With the existence of pGlu1, the conformation of the N-terminus allows two additional interactions between the two subunits of MCP-2 dimer: a hydrogen bond between pGlu1 and Asn17 and a salt bridge between Asp3 and Arg18. Consequently, both pGlu1 are anchored and buried, and thereby, both N-terminal regions are protected against protease degradation. We have also observed not previously reported extended helical nature of the C terminal region, which covers residues 58-74. C1 NCI, Program Struct Biol, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Katholieke Univ Leuven, Lab Mol Immunol, Rega Inst Med Res, B-3000 Louvain, Belgium. Lodz Tech Univ, Inst Tech Biochem, PL-90924 Lodz, Poland. RP Ji, XH (reprint author), NCI, Program Struct Biol, Frederick, MD 21702 USA. RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 NR 38 TC 33 Z9 34 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 NOV 21 PY 2000 VL 39 IS 46 BP 14075 EP 14081 DI 10.1021/bi0009340 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 374QK UT WOS:000165355700008 PM 11087354 ER PT J AU Pinsky, PF AF Pinsky, PF TI A multi-stage model of adenoma development SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article ID HYPERPLASTIC POLYPS; COLORECTAL-CANCER; COLON CANCER; CARCINOGENESIS; RISK; NEOPLASIA; GENETICS AB The overwhelming proportion of colorectal carcinomas are believed to originate as adenomatous polyps (adenomas), and the identification and removal of adenomas is an important component of colorectal cancer prevention efforts. Mathematical modeling of adenomas can increase our understanding of the natural history and biology of adenomas and colorectal cancer and can help in the effort to devise optimal prevention and screening strategies. Here we adapt the multi-stage model of carcinogenesis to the problem of the development and growth of adenomas. We show that, using plausible values for the biological parameters, the model can fit various aspects of adenoma data including adenoma prevalence by age, the size distribution of adenomas, clustering of adenomas within individuals and the correlation between distal and proximal adenomas. Explaining the clustering of adenomas within individuals, as well as other findings, requires heterogeneity in risk in the population; we show how such heterogeneity can be related to the distribution of biological parameters in the population. The model can also be adapted to account for adenoma development in two major syndromes related to colorectal cancer, familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. (C) 2000 Academic Press. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 31 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD NOV 21 PY 2000 VL 207 IS 2 BP 129 EP 143 DI 10.1006/jtbi.2000.2148 PG 15 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 374ZZ UT WOS:000165376200001 PM 11034825 ER PT J AU Dumbacher, JP Spande, TF Daly, JW AF Dumbacher, JP Spande, TF Daly, JW TI Batrachotoxin alkaloids from passerine birds: A second toxic bird genus (Ifrita kowaldi) from New Guinea SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POISON FROGS DENDROBATIDAE; CHEMICAL DEFENSE; HOMOBATRACHOTOXIN AB Batrachotoxins, including many congeners not previously described, were detected, and relative amounts were measured by using HPLC-mass spectrometry, in five species of New Guinean birds of the genus Pitohui as well as a species of a second toxic bird genus, Ifrita kowaldi. The alkaloids, identified in feathers and skin, were hatrachotoxinin-A cis-crotonate (1), an allylically rearranged 16-acetate (2), which can form from 1 by sigmatropic rearrangement under basic conditions, batrachotoxinin-A and an isomer (3 and 3a, respectively), batrachotoxin (4), batrachotoxinin-A 3'-hydroxypentanoate (5), homobatrachotoxin (6), and mono- and dihydroxylated derivatives of homobatrachotoxin, The highest levels of batrachotoxins were generally present in the contour feathers of belly, breast, or legs in Pitohui dichrous, Pitohui kirhocephalus, and Ifrita kowaldi, Lesser amounts are found in head, back, tail, and wing feathers. Batrachotoxin (4) and homobatrachotoxin (6) were found only in feathers and not in skin. The levels of batrachotoxins varied widely for different populations of Pitohui and Ifrita, a result compatible with the hypothesis that these birds are sequestering toxins from a dietary source. C1 Smithsonian Inst, Natl Zool Pk, Genet Mol Lab, Washington, DC 20008 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Dumbacher, JP (reprint author), Smithsonian Inst, Natl Zool Pk, Genet Mol Lab, 3001 Connecticut Ave NW, Washington, DC 20008 USA. NR 21 TC 70 Z9 74 U1 2 U2 20 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 NOV 21 PY 2000 VL 97 IS 24 BP 12970 EP 12975 DI 10.1073/pnas.200346897 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376UZ UT WOS:000165476300016 PM 11035772 ER PT J AU Xue, YT Canman, JC Lee, CS Nie, ZQ Yang, DF Moreno, GT Young, MK Salmon, ED Wang, WD AF Xue, YT Canman, JC Lee, CS Nie, ZQ Yang, DF Moreno, GT Young, MK Salmon, ED Wang, WD TI The human SWI/SNF-B chromatin-remodeling complex is related to yeast Rsc and localizes at kinetochores of mitotic chromosomes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SWI-SNF COMPLEX; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL REGULATION; MULTISUBUNIT COMPLEX; CYTOPLASMIC DYNEIN; GENE-PRODUCTS; HUMAN HOMOLOG; NUCLEOSOME; PROTEINS; BINDING AB The SWI/SNF family of chromatin-remodeling complexes facilitates gene expression by helping transcription factors gain access to their targets in chromatin. SWI/SNF and Rsc are distinctive members of this family from yeast. They have similar protein components and catalytic activities but differ in biological function. Rsc is required for cell cycle progression through mitosis, whereas SWI/ SNF is not, Human complexes of this family have also been identified, which have often been considered related to yeast SWI/SNF. However, all human subunits identified to date are equally similar to components of both SWI/SNF and Rsc, leaving open the possibility that some or all of the human complexes are rather related to Rsc, Here, we present evidence that the previously identified human SWI/SNF-B complex is indeed of the Rsc type. It contains six components conserved in both Rsc and SWI/SNF. Importantly, it has a unique subunit, BAF180, that harbors a distinctive set of structural motifs characteristic of three components of Rsc, Of the two mammalian ATPases known to be related to those in the yeast complexes, human SWI/SNF-B contains only the homolog that functions like Rsc during cell growth. Immunofluorescence studies with a BAF180 antibody revealed that SWI/ SNF-B localizes at the kinetochores of chromosomes during mitosis, Our data suggest that SWI/SNF-B and Rsc represent a novel subfamily of chromatin-remodeling complexes conserved from yeast to human, and could participate in cell division at kinetochores of mitotic chromosomes. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. City Hope Natl Med Ctr, Beckman Inst, Div Immunol, Duarte, CA 91010 USA. RP Wang, WD (reprint author), NIA, Genet Lab, NIH, 333 Cassell Dr,TRIAD Ctr Room 4000, Baltimore, MD 21224 USA. RI Canman, Julie/A-3875-2016 OI Canman, Julie/0000-0001-8135-2072 FU FDA HHS [GENBANK/A197569] NR 51 TC 160 Z9 166 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 NOV 21 PY 2000 VL 97 IS 24 BP 13015 EP 13020 DI 10.1073/pnas.240208597 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376UZ UT WOS:000165476300024 PM 11078522 ER PT J AU Antzutkin, ON Balbach, JJ Leapman, RD Rizzo, NW Reed, J Tycko, R AF Antzutkin, ON Balbach, JJ Leapman, RD Rizzo, NW Reed, J Tycko, R TI Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of beta-sheets in Alzheimer's beta-amyloid fibrils SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SYNCHROTRON X-RAY; IN-VITRO; DISEASE; PROTEIN; PEPTIDE; EXCITATION; MODEL; CORE; FIBRILLOGENESIS; PROTOFILAMENTS AB Senile plaques associated with Alzheimer's disease contain deposits of fibrils formed by 39- to 43-residue beta -amyloid peptides with possible neurotoxic effects. X-ray diffraction measurements on oriented fibril bundles have indicated an extended beta -sheet structure for Alzheimer's beta -amyloid fibrils and other amyloid fibrils, but the supramolecular organization of the beta -sheets and other structural details are not well established because of the intrinsically noncrystalline, insoluble nature of amyloid fibrils, Here we report solid-state NMR measurements, using a multiple quantum (MQ)C-13 NMR technique, that probe the beta -sheet organization in fibrils formed by the full-length, 40-residue beta -amyloid peptide (A beta (1-40)) Although an antiparallel beta -sheet organization often is assumed and is invoked in recent structural models for full-length beta -amyloid fibrils, the MQNMR data indicate an in-register, parallel organization. This work provides site-specific, atomic-level structural constraints on full-length beta -amyloid fibrils and applies MQNMR to a significant problem in structural biology. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Lulea Univ Technol, Div Inorgan Chem, S-97187 Lulea, Sweden. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. RI Reed, Jennifer/E-5137-2011 NR 43 TC 289 Z9 292 U1 0 U2 28 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 NOV 21 PY 2000 VL 97 IS 24 BP 13045 EP 13050 DI 10.1073/pnas.230315097 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376UZ UT WOS:000165476300029 PM 11069287 ER PT J AU Schubert, U Ott, DE Chertova, EN Welker, R Tessmer, U Princiotta, MF Bennink, JR Krausslich, HG Yewdell, JW AF Schubert, U Ott, DE Chertova, EN Welker, R Tessmer, U Princiotta, MF Bennink, JR Krausslich, HG Yewdell, JW TI Proteasome inhibition interferes with Gag polyprotein processing, release, and maturation of HIV-1 and HIV-2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN; UBIQUITIN; VPU; CELLS; DEGRADATION; SUBUNIT; P6(GAG); CD4 AB Retrovirus assembly and maturation involve folding and transport of viral proteins to the virus assembly site followed by subsequent proteolytic cleavage of the Gag polyprotein within the nascent virion. We report that inhibiting proteasomes severely decreases the budding, maturation, and infectivity of HIV. Although processing of the Env glycoproteins is not changed, proteasome inhibitors inhibit processing of tag polyprotein by the viral protease without affecting the activity of the HIV-1 viral protease itself, as demonstrated by in vitro processing of HIV-1 tag polyprotein Pr55. Furthermore, this effect occurs independently of the virus release function of the HIV-1 accessory protein Vpu and is not limited to HIV-1, as proteasome inhibitors also reduce virus release and tag processing of HIV-2. Electron microscopy analysis revealed ultrastructural changes in budding virions similar to mutants in the late assembly domain of p6(gag), a C-terminal domain of Pr55 required for efficient virus maturation and release. Proteasome inhibition reduced the level of free ubiquitin in HIV-1-infected cells and prevented monoubiquitination of p6(gag). Consistent with this, viruses with mutations in PR or p6(gag) were resistant to detrimental effects mediated by proteasome inhibitors. These results indicate the requirement for an active proteasome/ubiquitin system in release and maturation of infectious HIV particles and provide a potential pharmaceutical strategy for interfering with retrovirus replication. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Heinrich Pette Inst Expt Virol & Immunol, D-20251 Hamburg, Germany. RP Schubert, U (reprint author), NIAID, Viral Dis Lab, NIH, Room 209,Bldg 4,4 Ctr Dr,MSC 0440, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 FU NCI NIH HHS [N01-CO-56000] NR 25 TC 225 Z9 233 U1 0 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 NOV 21 PY 2000 VL 97 IS 24 BP 13057 EP 13062 DI 10.1073/pnas.97.24.13057 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376UZ UT WOS:000165476300031 PM 11087859 ER PT J AU Sachs, LM Shi, YB AF Sachs, LM Shi, YB TI Targeted chromatin binding and histone acetylation in vivo by thyroid hormone receptor during amphibian development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID XENOPUS-LAEVIS; TRANSCRIPTIONAL REPRESSION; GENE-EXPRESSION; BETA GENE; METAMORPHOSIS; DEACETYLASE; ACTIVATION; COMPLEX; COREPRESSOR; NUCLEOSOME AB Amphibian metamorphosis is marked by dramatic, thyroid hormone (TH)-induced changes involving gene regulation by TH receptor (TR). It has been postulated that TR-mediated gene regulation involves chromatin remodeling. In the absence of ligand, TR can repress gene expression by recruiting a histone deacetylase complex, whereas liganded Tn recruits a histone acetylase complex for gene activation. Earlier studies have led us to propose a dual function model for TR during development. In premetamorphic tadpoles, unliganded Tn represses transcription involving histone deacetylation. During metamorphosis, endogenous TH allows TR to activate gene expression through histone acetylation. Here using chromatin immunoprecipitation assay, we directly demonstrate TR binding to TH response genes constitutively in vivo in premetamorphic tadpoles. We further show that TH treatment leads to histone deacetylase release from TH response gene promoters. Interestingly, in whole animals, changes in histone acetylation show little correlation with the expression of TH response genes. On the other hand, in the intestine and tail, where TH response genes are known to be up-regulated more dramatically by TH than in most other organs, we demonstrate that TH treatment induces gene activation and histone H4 acetylation, These data argue for a role of histone acetylation in transcriptional regulation by TRs during amphibian development in some tissues, whereas in others changes in histone acetylation levels may play no or only a minor role, supporting the existence of important alternative mechanisms in gene regulation by TR. C1 NICHHD, Unit Mol Morphogenesis, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHHD, Unit Mol Morphogenesis, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. NR 42 TC 81 Z9 82 U1 0 U2 7 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 NOV 21 PY 2000 VL 97 IS 24 BP 13138 EP 13143 DI 10.1073/pnas.260141297 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376UZ UT WOS:000165476300045 PM 11078533 ER PT J AU Kaneshige, M Kaneshige, K Zhu, X Dace, A Garrett, L Carter, TA Kazlauskaite, R Pankratz, DG Wynshaw-Boris, A Refetoff, S Weintraub, B Willingham, MC Barlow, C Cheng, S AF Kaneshige, M Kaneshige, K Zhu, X Dace, A Garrett, L Carter, TA Kazlauskaite, R Pankratz, DG Wynshaw-Boris, A Refetoff, S Weintraub, B Willingham, MC Barlow, C Cheng, S TI Mice with a targeted mutation in the thyroid hormone beta receptor gene exhibit impaired growth and resistance to thyroid hormone SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LIGAND-BINDING DOMAIN; TRANSGENIC MICE; GENERALIZED RESISTANCE; WEIGHT-REDUCTION; DEFICIENT MICE; TR-BETA; PITUITARY; COACTIVATORS; THYROTROPIN; EXPRESSION AB Patients with mutations in the thyroid hormone receptor beta (TR beta) gene manifest resistance to thyroid hormone (RTH), resulting in a constellation of variable phenotypic abnormalities. To understand the molecular basis underlying the action of mutant TR beta in vivo, we generated mice with a targeted mutation in the TR beta gene (TR beta PV; PV, mutant thyroid hormone receptor kindred PV) by using homologous recombination and the Cre/loxP system. Mice expressing a single PV allele showed the typical abnormalities of thyroid function found in heterozygous humans with RTH, Homozygous PV mice exhibit severe dysfunction of the pituitary-thyroid axis, impaired weight gains, and abnormal bone development. This phenotype is distinct from that seen in mice with a null mutation in the TR beta gene. Importantly, we identified abnormal expression patterns of several genes in tissues of TR beta PV mice, demonstrating the interference of the mutant TR with the gene regulatory functions of the wild-type Tn in vivo. These results show that the actions of mutant and wild-type TR beta in vivo are distinct. This model allows further study of the molecular action of mutant TR in vivo, which could lead to better treatment for RTH patients. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. Inst Human Virol, Mol Endocrinol Lab, Baltimore, MD 21201 USA. Univ Chicago, Dept Med & Pediat, Chicago, IL 60637 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. RP Cheng, S (reprint author), Bldg 37,Room 2D24,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [R37 DK015070, DK15070, R01 DK015070] NR 28 TC 184 Z9 189 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 NOV 21 PY 2000 VL 97 IS 24 BP 13209 EP 13214 DI 10.1073/pnas.230285997 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376UZ UT WOS:000165476300058 PM 11069286 ER PT J AU Sabatino, DE Seidel, NE Aviles-Mendoza, GJ Cline, AP Anderson, SM Gallagher, PG Bodine, DM AF Sabatino, DE Seidel, NE Aviles-Mendoza, GJ Cline, AP Anderson, SM Gallagher, PG Bodine, DM TI Long-term expression of gamma-globin mRNA in mouse erythrocytes from retrovirus vectors containing the human gamma-globin gene fused to the ankyrin-1 promoter SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEMATOPOIETIC STEM-CELLS; LOCUS-CONTROL REGION; TRANSGENIC MICE; THERAPY; HEMOGLOBINOPATHIES; SITE-2; SAFE AB Gene therapy for patients with hemoglobin disorders has been hampered by the inability of retrovirus vectors to transfer globin genes and their cis-acting regulatory sequences into hematopoietic stem cells without rearrangement. In addition, the expression from intact globin gene vectors has been variable in red blood cells due to position effects and retrovirus silencing. We hypothesized that by substituting the globin gene promoter for the promoter of another gene expressed in red blood cells, we could generate stable retrovirus vectors that would express globin at sufficient levels to treat hemoglobinopathies. Recently, we have shown that the human ankyrin (Ank) gene promoter directs position-independent, copy number-dependent expression of a linked gamma -globin gene in transgenic mice. We inserted the Ank/(A)gamma -globin gene into retrovirus vectors that could transfer one or two copies of the Ank/(A)gamma -globin gene to target cells. Both vectors were stable, transferring only intact proviral sequences into primary mouse hematopoietic stem cells. Expression of Ank/(A)gamma -globin mRNA in mature red blood cells was 3% (single copy) and 8% (double copy) of the level of mouse alpha -globin mRNA, We conclude that these novel retrovirus vectors may be valuable for treating a variety of red cell disorders by gene replacement therapy including severe beta -thalassemia if the level of expression can be further increased. C1 NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Grad Program Genet, Washington, DC 20052 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. RP Bodine, DM (reprint author), NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NR 38 TC 40 Z9 39 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 NOV 21 PY 2000 VL 97 IS 24 BP 13294 EP 13299 DI 10.1073/pnas.230453097 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376UZ UT WOS:000165476300072 PM 11069298 ER PT J AU Zimonjic, DB Pollock, JL Westervelt, P Popescu, NC Ley, TJ AF Zimonjic, DB Pollock, JL Westervelt, P Popescu, NC Ley, TJ TI Acquired, nonrandom chromosomal abnormalities associated with the development of acute promyelocytic leukemia in transgenic mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; PML-RAR-ALPHA; COMMONLY DELETED SEGMENT; MYELOPROLIFERATIVE DISORDERS; MYELOID-LEUKEMIA; P53 GENE; EXPRESSION; REARRANGEMENTS; DELETIONS; 20Q AB We previously generated a transgenic mouse model for acute promyelocytic leukemia (APL) by expressing the promyelocytic leukemia (PML)-retinoic acid receptor (RAR alpha) cDNA in early myeloid cells. This fusion protein causes a myeloproliferative disease in 100% of animals, but only 15-20% of the animals develop acute leukemia after a long latency period (6-13 months). PML-RAR alpha is therefore necessary, but not sufficient, for APL development. The coexpression of a reciprocal form of the fusion, RAR alpha -PML, increased the likelihood of APL development (55-60%), but did not shorten latency. Together, these results suggested that additional genetic events are required for the development of APL. We therefore evaluated the splenic tumor cells from 18 transgenic mice with APL for evidence of secondary genetic events, by using spectral karyotyping analysis. Interstitial or terminal deletions of the distal region of one copy of chromosome 2 [del(2)] were found in 1/5 tumors expressing PML-RAR alpha, but in 11/13 tumors expressing both PML-RAR alpha and RAR alpha -PML (P < 0.05). Leukemic cells that contained a deletion on chromosome 2 often contained additional chromosomal gains (especially of 15), chromosomal losses (especially of 11 or X/Y), or were tetraploid (P 0.001). These changes did not commonly occur in nontransgenic littermates, nor in aged transgenic mice that did not develop APL. These results suggest that expression of RAR alpha -PML increases the likelihood of chromosome 2 deletions in APL cells. Deletion 2 appears to predispose APL cells to further chromosomal instability, which may lead to the acquisition of additional changes that provide an advantage to the transformed cells. C1 Washington Univ, Sch Med, Dept Med,Div Oncol, Sect Stem Cell Biol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet,Div Oncol, Sect Stem Cell Biol, St Louis, MO 63110 USA. NCI, Mol Cytogenet Sect, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Ley, TJ (reprint author), Washington Univ, Sch Med, Dept Med,Div Oncol, Sect Stem Cell Biol, 660 S Euclid Ave,Campus Box 8007, St Louis, MO 63110 USA. FU NCI NIH HHS [CA49712]; NHLBI NIH HHS [K08 HL003991, KO8 HL03991, T32 HL007088, T32 HL07088] NR 44 TC 90 Z9 91 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 NOV 21 PY 2000 VL 97 IS 24 BP 13306 EP 13311 DI 10.1073/pnas.97.24.13306 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376UZ UT WOS:000165476300074 PM 11087871 ER PT J AU Forns, X Thimme, R Govindarajan, S Emerson, SU Purcell, RH Chisari, FV Bukh, J AF Forns, X Thimme, R Govindarajan, S Emerson, SU Purcell, RH Chisari, FV Bukh, J TI Hepatitis C virus lacking the hypervariable region 1 of the second envelope protein is infectious and causes acute resolving or persistent infection in chimpanzees SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-LYMPHOCYTE RESPONSE; IMMUNE-RESPONSE; CDNA CLONE; ANTIBODY-RESPONSE; HYPERIMMUNE SERUM; VIRAL CLEARANCE; IN-VIVO; VARIANTS; GLYCOPROTEIN; BINDING AB Persistent infection with hepatitis C virus (HCV) is among the leading causes of chronic liver disease. Previous studies suggested that genetic variation in hypervariable region 1 (HVR1) of the second envelope protein, possibly in response to host immune pressure, influences the outcome of HCV infection. In the present study, a chimpanzee transfected intrahepatically with RNA transcripts of an infectious HCV clone (pCV-H77C) from which HVR1 was deleted became infected; the Delta HVR1 virus was subsequently transmitted to a second chimpanzee, Infection with Delta HVR1 virus resulted in persistent infection in the former chimpanzee and in acute resolving infection in the latter chimpanzee. Both chimpanzees developed hepatitis. The Delta HVR1 virus initially replicated to low titers, but virus titer increased significantly after mutations appeared in the viral genome, Thus, wild-type HCV without HVR1 was apparently attenuated, suggesting a functional role of HVR1, However, our data indicate that HVR1 is not essential for the viability of HCV, the resolution of infection, or the progression to chronicity. C1 NIAID, Hepatitis Sect, NIH, Bethesda, MD 20892 USA. NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol & Expt Med, Div Expt Pathol, La Jolla, CA 92037 USA. Univ So Calif, Rancho Los Amigos Med Ctr, Liver Res Lab, Downey, CA 90242 USA. RP Bukh, J (reprint author), NIAID, Hepatitis Sect, NIH, Bethesda, MD 20892 USA. RI Chisari, Francis/A-3086-2008; OI Chisari, Francis/0000-0002-4832-1044 FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [N01-AI-52705, R01 AI020001, R01-AI20001, R21 AI052705] NR 50 TC 108 Z9 116 U1 0 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 NOV 21 PY 2000 VL 97 IS 24 BP 13318 EP 13323 DI 10.1073/pnas.230453597 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376UZ UT WOS:000165476300076 PM 11078521 ER PT J AU Kachar, B Parakkal, M Kurc, M Zhao, Y Gillespie, PG AF Kachar, B Parakkal, M Kurc, M Zhao, Y Gillespie, PG TI High-resolution structure of hair-cell tip links SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GUINEA-PIG COCHLEA; MECHANICAL TRANSDUCTION; ACTIN-FILAMENTS; CROSS-LINKS; STEREOCILIA; MEMBRANE; ADHESION; MUSCLE; EAR; ADAPTATION AB Transduction-channel gating by hair cells apparently requires a gating spring, an elastic element that transmits force to the channels. To determine whether the gating spring is the tip link, a filament interconnecting two stereocilia along the axis of mechanical sensitivity, we examined the tip link's structure at high resolution by using rapid-freeze, deep-etch electron microscopy, We found that the tip link is a right-handed, coiled double filament that usually forks into two branches before contacting a taller stereocilium; at the other end, several short filaments extend to the tip link from the shorter stereocilium. The structure of the tip link suggests that it is either a helical polymer or a braided pair of filamentous macromolecules and is thus likely to be relatively stiff and inextensible. Such behavior is incompatible with the measured elasticity of the gating spring, suggesting that the gating spring instead lies in series with the helical segment of the tip link. C1 Natl Inst Deafness & Commun Disorders, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. Otogene Inc, Seattle, WA 98103 USA. Oregon Hlth Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Vollum Inst, Portland, OR 97201 USA. RP Kachar, B (reprint author), Natl Inst Deafness & Commun Disorders, Sect Struct Cell Biol, NIH, Bldg 36,Room 5D15,MSC 4163, Bethesda, MD 20892 USA. OI Barr-Gillespie, Peter/0000-0002-9787-5860 NR 38 TC 152 Z9 159 U1 3 U2 6 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 NOV 21 PY 2000 VL 97 IS 24 BP 13336 EP 13341 DI 10.1073/pnas.97.24.13336 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376UZ UT WOS:000165476300079 PM 11087873 ER PT J AU Gretz, JE Norbury, CC Anderson, AO Proudfoot, AEI Shaw, S AF Gretz, JE Norbury, CC Anderson, AO Proudfoot, AEI Shaw, S TI Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE reticular network; mouse; rat; lymphocyte recirculation; antigen ID GENE-EXPRESSION; T-LYMPHOCYTES; CELL-ADHESION; RAT; BINDING; PERMEABILITY; ARCHITECTURE; EMIGRATION; CYTOKINES; RESPONSES AB Lymph-borne, soluble factors (e.g., chemokines and others) influence lymphocyte recirculation and endothelial phenotype at high endothelial venules (HEVs) in lymph node cortex. Yet the route lymph-borne soluble molecules travel from the subcapsular sinus to the HEVs is unclear. Therefore, we injected subcutaneously into mice and rats a wide variety of fluorophore-labeled, soluble molecules and examined their distribution in the draining lymph nodes. Rather than percolating throughout the draining lymph node, all molecules, including microbial lipopolysaccharide, were very visible in the subcapsular and medullary sinuses but were largely excluded from the cortical lymphocyte microenviroments. Exclusion prevailed even during the acute lymph node enlargement accompanying viral infection. However, low molecular mass (MW) molecules, including chemokines, did gain entry into the cortex, but in a very defined manner. Low MW, fluorophore-labeled molecules highlighted the subcapsular sinus, the reticular fibers, and the abluminal and luminal surfaces of the associated HEVs. These low MW molecules were in the fibers of the reticular network, a meshwork of collagen fibers ensheathed by fibroblastic reticular cells that connects the subcapsular sinus floor and the HEVs by intertwining with their basement membranes. Thus, low MW, lymph-borne molecules, including chemokines, traveled rapidly from the subcapsular sinus to the HEVs using the reticular network as a conduit. C1 NCI, Expt Immunol Branch, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Lab Mucosal Immunol, Ft Detrick, MD 21712 USA. Serono Pharmaceut Res Inst, CH-1228 Geneva, Switzerland. RP Shaw, S (reprint author), NCI, Expt Immunol Branch, Human Immunol Sect, NIH, Bldg 10,Rm 4B36,10 Ctr Dr,MSC 1360, Bethesda, MD 20892 USA. NR 75 TC 328 Z9 332 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 20 PY 2000 VL 192 IS 10 BP 1425 EP 1439 DI 10.1084/jem.192.10.1425 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 375ZH UT WOS:000165433000005 PM 11085745 ER PT J AU Kawamura, T Cohen, SS Borris, DL Aquilino, EA Glushakova, S Margolis, LB Orenstein, JM Offord, RE Neurath, AR Blauvelt, A AF Kawamura, T Cohen, SS Borris, DL Aquilino, EA Glushakova, S Margolis, LB Orenstein, JM Offord, RE Neurath, AR Blauvelt, A TI Candidate microbicides block HIV-1 infection of human immature Langerhans cells within epithelial tissue explants SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE AIDS; dendritic cells; cellulose acetate phthalate; aminooxypentane-RANTES; transmission ID SEXUALLY-TRANSMITTED DISEASES; SIMIAN IMMUNODEFICIENCY VIRUS; DENDRITIC CELLS; PRODUCTIVE INFECTION; T-CELLS; TRANSMISSION; EXPRESSION; AIDS; CCR5; PROGRESSION AB Initial biologic events that underlie sexual transmission of HIV-1 are poorly understood. To model these events. we exposed human immature Langerhans cells (LCs) within epithelial tissue explants to two primary and two laboratory-adapted HIV-1 isolates. We detected HIV-1(Ba-L) infection in single LCs that spontaneously emigrated from explants by flow cytometry (median of infected LCs = 0.52%, range = 0.08-4.77%). HIV-l-infected LCs downregulated surface CD4 and CD83, whereas MHC class II, CD80, and CD86 were unchanged. For all HIV-1 strains tested, emigrated LCs were critical in establishing high levels of infection (0.1-1 mug HIV-1 p24 per milliliter) in cocultured autologous or allogeneic T cells. HIV-1(Ba-L) (an R5 HIV-1 strain) more efficiently infected LC-T cell cocultures when compared with HIV-1(IIIB) (an X4 HIV-1 strain). Interestingly, pretreatment of explants with either aminooxypentane-RANTES (1-regulated upon activation, normal T cell expressed and secreted) or cellulose acetate phthalate (potential microbicides) blocked HIV-1 infection of LCs and subsequent T cell infection in a dose-dependent manner. In summary, we document HIV-1 infection in single LCs after exposure to virus within epithelial tissue, demonstrate that relatively low numbers of these cells are capable of inducing high levels of infection in cocultured T cells, and provide a useful explant model for testings of agents designed to block sexual transmission of HIV-1. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NICHHD, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA. George Washington Univ, Dept Pathol, Washington, DC 20037 USA. Univ Geneva, Dept Biochim Med, CH-1211 Geneva 4, Switzerland. New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10021 USA. RP Blauvelt, A (reprint author), Bldg 10,Rm 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. NR 50 TC 124 Z9 129 U1 2 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 20 PY 2000 VL 192 IS 10 BP 1491 EP 1500 DI 10.1084/jem.192.10.1491 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 375ZH UT WOS:000165433000010 PM 11085750 ER PT J AU Mortelmans, K Zeiger, E AF Mortelmans, K Zeiger, E TI The Ames Salmonella/microsome mutagenicity assay SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE Ames Salmonella/microsome mutagenicity assay; Salmonella strains; gene mutation ID BACTERIAL MUTATION ASSAYS; GENETIC TOXICITY TESTS; SHORT-TERM TESTS; ESCHERICHIA-COLI; MICROSOME TEST; RODENT CARCINOGENICITY; CHEMICAL CARCINOGENS; STATISTICAL-ANALYSIS; FRAMESHIFT MUTAGENS; LIVER MICROSOMES AB The Ames Salmonella/microsome mutagenicity assay (Salmonella test; Ames test) is a short-term bacterial reverse mutation assay specifically designed to detect a wide range of chemical substances that can produce genetic damage that leads to gene mutations. The test employs several histidine dependent Salmonella strains each carrying different mutations in various genes in the histidine operon. These mutations act as hot spots for mutagens that cause DNA damage via different mechanisms. When the Salmonella tester strains are grown on a minimal media agar plate containing a trace of histidine, only those bacteria that revert to histidine independence (his(+)) are able to form colonies. The number of spontaneously induced revertant colonies per plate is relatively constant. However, when a mutagen is added to the plate, the number of revertant colonies per plate is increased, usually in a dose-related manner. The Ames test is used world-wide as an initial screen to determine the mutagenic potential of new chemicals and drugs. The test is also used for submission of data to regulatory agencies for registration or acceptance of many chemicals, including drugs and biocides. International guidelines have been developed for use by corporations and testing laboratories to ensure uniformity of testing procedures. This review provides historical aspects of how the Ames was developed and detailed procedures for performing the test, including the design and interpretation of results. (C) 2000 Elsevier Science B.V. All rights reserved. C1 SRI Int, Mol & Genet Toxicol Program, Menlo Park, CA 94025 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Mortelmans, K (reprint author), SRI Int, Mol & Genet Toxicol Program, 333 Ravenswood Ave, Menlo Park, CA 94025 USA. NR 95 TC 810 Z9 849 U1 43 U2 220 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 NOV 20 PY 2000 VL 455 IS 1-2 BP 29 EP 60 DI 10.1016/S0027-5107(00)00064-6 PG 32 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 385CX UT WOS:000165985200004 PM 11113466 ER PT J AU Elkashef, AM Doudet, D Bryant, T Cohen, RM Li, SH Wyatt, RJ AF Elkashef, AM Doudet, D Bryant, T Cohen, RM Li, SH Wyatt, RJ TI 6-F-18-DOPA PET study in patients with schizophrenia SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE dopamine; F-18-DOPA; positron emission tomography; schizophrenia ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL METABOLISM; DOPAMINE-RECEPTORS; PARKINSONS-DISEASE; DECARBOXYLASE ACTIVITY; CINGULATE CORTEX; F-18 DOPA; BRAIN; NEUROTRANSMITTERS; STRIATUM AB Presynaptic dopamine metabolism was studied in a group of patients with schizophrenia and in an age- and gender-matched normal control group using 6-[F-18]fluoro-L-DOPA (F-18-DOPA) and positron emission tomography (PET). Nineteen patients, nine drug-free, 10 on neuroleptics, and 13 normal control subjects underwent PET scans using F-18-DOPA. The neuroleptic-treated patients were taking typical neuroleptics (N = 4) or the atypical neuroleptic, clozapine (N = 6). The ratio of specific/non-specific activity was calculated for eight cortical and subcortical regions of interest. Medication-free patients had a significant reduction in F-18-DOPA uptake in the ventral striatum (P = 0.04) and significantly increased uptake in the posterior cingulate (P = 0.02) compared with normal control subjects. The F-18-DOPA PET technique proved to be useful and sensitive in detecting changes in dopamine metabolism in patients with schizophrenia in vivo. The results of this study provide evidence of an aberrant dopamine system in schizophrenia. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NIDA, Clin Trials Branch, DTRD, NIH, Bethesda, MD 20892 USA. NIMH, Neuropsychiat Branch, NIH, Bethesda, MD 20892 USA. NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. RP Elkashef, AM (reprint author), NIDA, Clin Trials Branch, DTRD, NIH, 6001 Execut Blvd,Room 4123,MSC 551, Bethesda, MD 20892 USA. NR 55 TC 63 Z9 63 U1 2 U2 8 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV 20 PY 2000 VL 100 IS 1 BP 1 EP 11 DI 10.1016/S0925-4927(00)00064-0 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 379UE UT WOS:000165660200001 PM 11090720 ER PT J AU Oda, A Wakao, H Fujihara, M Ozaki, K Komatsu, N Tanaka, S Ikeda, H Miyajima, A Ikebuchi, K AF Oda, A Wakao, H Fujihara, M Ozaki, K Komatsu, N Tanaka, S Ikeda, H Miyajima, A Ikebuchi, K TI Thrombopoietin and interleukin-2 induce association of CRK with STAT5 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE platelet; signal transduction; adapter; cytokine ID FAMILY ADAPTER PROTEINS; TYROSINE PHOSPHORYLATION; HEMATOPOIETIC-CELLS; SIGNAL-TRANSDUCTION; T-LYMPHOCYTES; CYTOKINE; ACTIVATION; ERYTHROPOIETIN; TRANSCRIPTION; EXPRESSION AB Crk (Crk I and II) proteins and closely related CrkL are adapters which are commonly involved in various signaling processes in various cells, and these proteins share many ligands, Whether they have redundant or distinct physiologic roles is unclear. By coprecipitation and far Western blotting analysis, we demonstrate that Crk (I/II) binds to tyrosine phosphorylated STATE in cells stimulated by cytokines such as thrombopoietin (TPO) and interleukin-2 (IL-2), The association did not require nuclear elements and can be observed in primary cells as this was also demonstrated in TPO-stimulated platelets. Using a beta -casein promoter STATE binding site as a probe, we have also demonstrated that CrkL (a close relative of Crk) antiserum, but not Crk antiserum, supershifted the STAT5-DNA complex by an electrophoretic mobility shift assay, suggesting that CrkL, but not Crk, is the major component of the complex, Thus, Crk and CrkL may have distinct roles in the regulation of STATE. (C) 2000 Academic Press. C1 Hokkaido Red Cross Blood Ctr, Nishi Ku, Sapporo, Hokkaido 0630002, Japan. Helix Res Inst, Chiba, Japan. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Jichi Med Sch, Dept Med, Div Hematol, Minami Kawachi, Tochigi, Japan. Hokkaido Univ, Sch Med, Dept Pathol, Sapporo, Hokkaido 060, Japan. Univ Tokyo, Inst Mol & Cellular Biosci, Lab Cellular Biosynthesis, Tokyo, Japan. RP Oda, A (reprint author), Hokkaido Red Cross Blood Ctr, Nishi Ku, Yamanote 2-2, Sapporo, Hokkaido 0630002, Japan. RI Tanaka, Shinya/D-3586-2011; WAKAO, Hiroshi/A-4242-2012 NR 34 TC 16 Z9 16 U1 1 U2 3 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 NOV 19 PY 2000 VL 278 IS 2 BP 299 EP 305 DI 10.1006/bbrc.2000.3803 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 378XM UT WOS:000165610700006 PM 11097834 ER PT J AU Wilcox, AJ Dunson, D Baird, DD AF Wilcox, AJ Dunson, D Baird, DD TI The timing of the "fertile window" in the menstrual cycle: day specific estimates from a prospective study SO BRITISH MEDICAL JOURNAL LA English DT Article ID PROGESTERONE METABOLITES; URINARY ESTROGEN; OVULATION; PREGNANCY; CONCEPTION AB Objectives To provide specific estimates of the likely occurrence of the six fertile days (the "fertile window") during the menstrual cycle. Design Prospective cohort study. Participants 221 healthy women who were planning a pregnancy. Main outcome measures The timing of ovulation in 696 menstrual cycles, estimated using urinary metabolites of oestrogen and progesterone. Results The fertile window occurred during a broad range of days in the menstrual cycle. On every day between days 6 and 21, women had a minimum of 10% probability of being in their fertile window. Women cannot predict a sporadic late ovulation; 4-6% of women whose cycles had not yet resumed were potentially fertile in the fifth week of their cycle. Conclusions In only about 30% of women is the fertile window entirely within the days of the menstrual cycle identified by clinical guidelines-that is, between days 10 and 17. Most women reach their fertile window earlier and others much later. Women should be advised that the timing of the fertile window can be highly unpredictable, even if their cycles are usually regular. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Wilcox, AJ (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 18 TC 181 Z9 184 U1 1 U2 6 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD NOV 18 PY 2000 VL 321 IS 7271 BP 1259 EP 1262 DI 10.1136/bmj.321.7271.1259 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 376ET UT WOS:000165445800025 PM 11082086 ER PT J AU Munzar, P Kutkat, SW Miller, CR Goldberg, SR AF Munzar, P Kutkat, SW Miller, CR Goldberg, SR TI Failure of baclofen to modulate discriminative-stimulus effects of cocaine or methamphetamine in rats SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE baclofen; cocaine; methamphetamine; drug-discrimination; (Rat) ID VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; BEHAVIOR; MICRODIALYSIS; SUPPRESSION; INJECTION; AGONISTS; BRAIN; GABA AB The effects of baclofen, an agonist at GABAB receptors, were evaluated in rats trained to discriminate 10.0 mg/kg of cocaine or 1.0 mg/kg of methamphetamine from saline under a fixed-ratio 10 schedule of food delivery. Baclofen (0.56-5.6 mg/kg) did not attenuate the discriminative-stimulus effects of the training dose of cocaine or methamphetamine and did not produce any shift in the cocaine and methamphetamine dose-response curves. Higher baclofen doses (3.0-5.6 mg/kg), however, markedly depressed or completely eliminated food-maintained responding. This suggests that previous reports of baclofen-induced decreases in cocaine self-administration behavior are connected, in some way, with either a general suppression of appetitive behaviors or with sedation and locomotor depression, rather than with any pharmacologically specific effect, and not accompanied by changes in subjective response to cocaine, as assessed by discriminative-stimulus measures. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 30 TC 33 Z9 35 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 17 PY 2000 VL 408 IS 2 BP 169 EP 174 DI 10.1016/S0014-2999(00)00772-X PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 376PY UT WOS:000165467000009 PM 11080523 ER PT J AU Vos, MD Ellis, CA Bell, A Birrer, MJ Clark, GJ AF Vos, MD Ellis, CA Bell, A Birrer, MJ Clark, GJ TI Ras uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ONCOGENIC RAS; INCREASING COMPLEXITY; EPITHELIAL-CELLS; HUMAN CANCER; PROTEIN; GROWTH; TRANSFORMATION; KINASE; DIFFERENTIATION; REQUIREMENT AB Although activated Ras proteins are usually associated with driving growth and transformation, they may also induce senescence, apoptosis, and terminal differentiation. The subversion of these anti-neoplastic effects during Ras-dependent tumor development may be as important as the acquisition of the pro-neoplastic effects. None of the currently identified potential Ras effector proteins can satisfactorily explain the apoptotic action of Ras. Consequently, we have sought to identify novel Ras effecters that may be responsible for apoptosis induction. By examining the EST data base, we identified a potential. Ras association domain in the tumor suppressor RASSF1. We now show that RASSF1 binds Ras in a GTP-dependent manner, both in vivo and directly in vitro. Moreover, activated Ras enhances and dominant negative Ras inhibits the cell death induced by transient transfection of RASSF1 into 293-T cells. This cell death appears to be apoptotic in nature, as RASSF1-transfected 293-T cells exhibit membrane blebbing and can be rescued by the addition of a caspase inhibitor. Thus, the RASSF1 tumor suppressor may serve as a novel Ras effector that mediates the apoptotic effects of oncogenic Ras. C1 NCI, Dept Cell & Canc Biol, NIH, Rockville, MD 20850 USA. RP Clark, GJ (reprint author), NCI, Dept Cell & Canc Biol, NIH, 9610 Med Ctr Dr, Rockville, MD 20850 USA. NR 52 TC 212 Z9 231 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 NOV 17 PY 2000 VL 275 IS 46 BP 35669 EP 35672 DI 10.1074/jbc.C000463200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375CM UT WOS:000165382000004 PM 10998413 ER PT J AU Dupont, J Karas, M LeRoith, D AF Dupont, J Karas, M LeRoith, D TI The potentiation of estrogen on insulin-like growth factor I action in MCF-7 human breast cancer cells includes cell cycle components SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; IGF-BINDING-PROTEINS; PHOSPHATIDYLINOSITOL 3-KINASE; RETINOBLASTOMA PROTEIN; RECEPTOR SUBSTRATE-1; SIGNALING PATHWAYS; DEPENDENT KINASES; RIBONUCLEIC-ACID; CDK INHIBITORS; EXPRESSION AB To gain insight into the mechanisms involved in the cross-talk between IGF-1 receptor (IGF-1R) and estrogen receptor signaling pathways, we used MCF-7-derived cells (SX13), which exhibit a 50% reduction in IGF-1R expression. Growth of NEO cells (control MCF-7 cells) was stimulated by both IGF-1 and estradiol (E2), and the addition of both mitogens resulted in a synergistic response. Estrogen enhanced IGF-1R signaling in NEO cells, but this effect was markedly diminished in SX13 cells. Estrogen was also able to potentiate the IGF-1 effect on the expression of cyclin D1 and cyclin E and on the phosphorylation of retinoblastoma protein in control but not in SX13 cells. IGF-1 increased the protein level of p21 and the luciferase activity of the p21 promoter, whereas it only reduced the protein level of p27 without affecting p27 promoter activity. Estrogen did not affect the p21 inhibitor, but it decreased the protein level of p27 and the p27 promoter luciferase activity. These effects of both mitogens were also observed at the level of association of both cyclin-dependent kinase inhibitors with CDK2 suggesting that IGF-1 and E2 affect the activity of both p21 and p27. Taken together, these data suggest that in MCF-7 cells, estrogen potentiates the IGF-1 effect on IGF-1R signaling as well as on the cell cycle components. Moreover, IGF-I and E2 regulate the expression of p21 and p27 and their association with CDK2 differently. C1 NIDDK, Sect Cellular & Mol Physiol, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Sect Cellular & Mol Physiol, Clin Endocrinol Branch, NIH, Rm 8D12,Bldg 10, Bethesda, MD 20892 USA. NR 48 TC 120 Z9 124 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 NOV 17 PY 2000 VL 275 IS 46 BP 35893 EP 35901 DI 10.1074/jbc.M006741200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375CM UT WOS:000165382000037 PM 10967123 ER PT J AU Tcherkasskaya, O Bychkova, VE Uversky, VN Gronenborn, AM AF Tcherkasskaya, O Bychkova, VE Uversky, VN Gronenborn, AM TI Multisite fluorescence in proteins with multiple tryptophan residues - Apomyoglobin natural variants and site-directed mutants SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FREQUENCY-DOMAIN FLUOROMETRY; MOLTEN GLOBULE INTERMEDIATE; SPERM WHALE APOMYOGLOBINS; STRUCTURAL CHARACTERIZATION; CONFORMATIONAL PROPERTIES; FOLDING REACTIONS; ESCHERICHIA-COLI; ENERGY-TRANSFER; MYOGLOBIN; STATE AB Time-resolved fluorescence experiments were carried out on a variety of apomyoglobins with one or two tryptophan (Trp) residues located at invariant positions 7 and 14 in the primary sequence. In all cases, the Trp fluorescence kinetics were resolved adequately into two discrete lifetime domains, and decay-associated spectra (DAS) were obtained for each decay component. The DAS resolved for unfolded proteins were indistinguishable by position of the emission maxima and the spectral shapes. The folded proteins revealed noticeable differences in the DAS, which relate to the diverse local environments around the Trp residues in the individual proteins. Furthermore, the DAS of wild-type protein possessing two Trp residues were simulated well by that of one Trp mutants either in the native, molten globule, or unfolded states. Overall, employing Trp fluorescence and site-directed mutagenesis allowed us to highlight the conformational changes induced by the single amino acid replacement and generate novel structural information on equilibrium folding intermediates. Specifically, it was found that conformational fluctuations in the local cluster around the evolutionarily conserved Trp(14) are very similar in the native and molten globule states of apomyoglobins, This result indicates that residues in the E and B helices contributing to this cluster are most likely involved in the stabilization of the overall architecture of the structured molten globule intermediate. C1 NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Prot Res, Pushchino 142292, Moscow Region, Russia. Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tcherkasskaya, O (reprint author), NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RI Uversky, Vladimir/F-4515-2011 OI Uversky, Vladimir/0000-0002-4037-5857 NR 55 TC 21 Z9 22 U1 0 U2 8 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 NOV 17 PY 2000 VL 275 IS 46 BP 36285 EP 36294 DI 10.1074/jbc.M003008200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375CM UT WOS:000165382000091 PM 10948189 ER PT J AU Yamage, M Debrabant, A Dwyer, DM AF Yamage, M Debrabant, A Dwyer, DM TI Molecular characterization of a hyperinducible, surface membrane-anchored, class I nuclease of a trypanosomatid parasite SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEISHMANIA-DONOVANI PROMASTIGOTES; AMINO-ACID-SEQUENCE; 3'-NUCLEOTIDASE NUCLEASE; CRITHIDIA-LUCILIAE; PENICILLIUM-CITRINUM; ASPERGILLUS-ORYZAE; PURINE STARVATION; MESSENGER-RNAS; GENE; PROTEIN AB The 3'-nucleotidase/nuclease (5'-NT/NU) is a surface enzyme unique to trypanosomatid parasites. These organisms lack the pathway for de novo purine biosynthesis and thus are entirely dependent upon their hosts to supply this nutrient for their survival, growth, and multiplication. The 3'-NT/NU is involved in the salvage of preformed purines via the hydrolysis of either 3'-nucleotides or nucleic acids. In Crithidia luciliae, this enzyme is highly inducible. For example, in these organisms purine starvation triggers an similar to 1000-fold up-expression of 3'-NT/NU activity. In the present study, we cloned and characterized a gene encoding this intriguing enzyme from C. luciliae (Cl). Sequence analysis showed that the Cl 3'-NT/NU deduced protein possessed five regions, which we defined here as being characteristic of members of the class I nuclease family. Further, we demonstrated that the Cl 3'-NT/NU-expressed protein possessed both 3'-nucleotidase and nuclease activities. Moreover, we showed that the dramatic up-expression of 5'-NT/NU activity in response to purine starvation of C. luciliae was concomitant with the similar to 100-fold elevation in steady-state mRNA specific for this gene. Finally, results of our nuclear run-on analyses demonstrated that such up-regulation in 3'-NT/NU enzyme activity was mediated at the posttranscriptional level. C1 NIAID, Div Intramural Res, Parasit Dis Lab, Cell Biol Sect,NIH, Bethesda, MD 20892 USA. RP Dwyer, DM (reprint author), NIAID, Div Intramural Res, Parasit Dis Lab, Cell Biol Sect,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 53 TC 11 Z9 11 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 NOV 17 PY 2000 VL 275 IS 46 BP 36369 EP 36379 DI 10.1074/jbc.M004036200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375CM UT WOS:000165382000101 PM 10945983 ER PT J AU Kamhawi, S Belkaid, Y Modi, G Rowton, E Sacks, D AF Kamhawi, S Belkaid, Y Modi, G Rowton, E Sacks, D TI Protection against cutaneous Leishmaniasis resulting from bites of uninfected sand flies SO SCIENCE LA English DT Article ID EXPERIMENTAL TRANSMISSION; PARASITE TRANSMISSION; LUTZOMYIA-LONGIPALPIS; INTERFERON-GAMMA; VECTOR SALIVA; MICE; DIPTERA; CELLS; PSYCHODIDAE; IMMUNOLOGY AB Despite the fact that Leishmania are transmitted exclusively by sand flies, none of the experimental models of Leishmaniasis have established infection via sand fly bites. Here we describe a reproducible murine model of Leishmania major infection transmitted by Phlebotomus papatasi. Prior exposure of mice to bites of uninfected sand flies conferred powerful protection against Leishmania major that was associated with a strong delayed-type hypersensitivity response and with interferon-gamma production at the site of parasite delivery. These results have important implications for the epidemiology of cutaneous leishmaniasis and suggest a vaccination strategy against this and possibly other vector-borne diseases. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Entomol, Washington, DC 20307 USA. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Rowton, Edgar/A-1975-2011; Rowton, Edgar/A-4474-2012 OI Rowton, Edgar/0000-0002-1979-1485; NR 22 TC 190 Z9 197 U1 1 U2 10 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 NOV 17 PY 2000 VL 290 IS 5495 BP 1351 EP 1354 DI 10.1126/science.290.5495.1351 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 375BN UT WOS:000165379800047 PM 11082061 ER PT J AU Zeng, W Maciejewski, JP Young, NS AF Zeng, W Maciejewski, JP Young, NS TI Characterization of autoreactive T-cells in aplastic anemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 7 BP 5A EP 5A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100008 ER PT J AU Zeng, WH Young, NS Maciejewski, JP AF Zeng, WH Young, NS Maciejewski, JP TI Is there a specific effect of antithymocyte globulin on hematopoiesis? SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 11 BP 6A EP 6A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100012 ER PT J AU Moyo, VM Gangaidzo, IT Khumalo, H Rouault, T Boelaert, JR Gordeuk, VR AF Moyo, VM Gangaidzo, IT Khumalo, H Rouault, T Boelaert, JR Gordeuk, VR TI Iron stores, HIV and pulmonary tuberculosis in Southern Africa. SO BLOOD LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Zimbabwe, Sch Med, Harare, Zimbabwe. Univ Witwatersrand, Sch Med, Johannesburg, South Africa. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Algemeen Ziekenhuis Sint Jan, Unit Renal & Infect Dis, Brugge, Belgium. Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3681 BP 7B EP 7B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200021 ER PT J AU Asakura, T Lian, LR Ollinger, FK Chen, QK Li, X Iyamu, EW Abdulmalik, O Brugnara, C Evans, G AF Asakura, T Lian, LR Ollinger, FK Chen, QK Li, X Iyamu, EW Abdulmalik, O Brugnara, C Evans, G TI Screening and evaluation of antisickling agents by the NIH Sickle Cell Disease Reference Laboratory: Three new antisickling agents. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA USA. Childrens Hosp, Boston, MA 02115 USA. NIH, NHLBI, SCD Sci Res Grouparch, Bethesda, MD USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 25 BP 9A EP 9A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100026 ER PT J AU Kang, EM Areman, E Read, EJ Leitman, S Link, B Ocampo-David, V Rodgers, GP Tisdale, JF AF Kang, EM Areman, E Read, EJ Leitman, S Link, B Ocampo-David, V Rodgers, GP Tisdale, JF TI Mobilization and apheresis of sickle cell trait (SCT) donors is safe and feasible. SO BLOOD LA English DT Meeting Abstract C1 DTM, CC, NIH, Bethesda, MD USA. NIDDK, MCHB, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 46 BP 14A EP 14A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100047 ER PT J AU Foster, CB Miller, E Zhu, SX Choi, EW Chanock, SJ AF Foster, CB Miller, E Zhu, SX Choi, EW Chanock, SJ TI Single nucleotide polymorphisms (SNPs) in the phagocyte NADPH-oxidase. SO BLOOD LA English DT Meeting Abstract C1 NCI, POB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 48 BP 15A EP 15A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100049 ER PT J AU Taylor, JG Tang, D Serjeant, GR Rodgers, GP Chanock, SJ AF Taylor, JG Tang, D Serjeant, GR Rodgers, GP Chanock, SJ TI Immunoglobulin receptor polymorphisms in stroke and sickle cell disease. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, NIH, Gaithersburg, MD USA. NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. Univ W Indies, MRC Labs, Sickle Cell Unit, Kingston 7, Jamaica. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3746 BP 21B EP 21B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200086 ER PT J AU Wada, T Stewart, DM Nelson, DL Candotti, F AF Wada, T Stewart, DM Nelson, DL Candotti, F TI Functional correction of T cell lines from patients with Wiskott-Aldrich syndrome by retrovirus-mediated WASP gene transfer. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Clin Gene Therapy Branch, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 94 BP 25A EP 25A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100095 ER PT J AU Hensel, NF Boylan, A Eniafe, R Nakamura, R Barrett, AJ AF Hensel, NF Boylan, A Eniafe, R Nakamura, R Barrett, AJ TI Recovery of CMV antigen specific T cells (T-CMV) after allogeneic peripheral blood stem cell transplant (PBSCT) is biphasic and correlates with CMV antigenemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 119 BP 31A EP 31A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100120 ER PT J AU Faller, DV Lynch, E Moreland, RM Ginis, I AF Faller, DV Lynch, E Moreland, RM Ginis, I TI The hypoxia-activated ligand HAL-1/13 is identical to lupus antigen Ku80, and mediates lymphoid cell adhesion and tumor cell invasiveness in vitro. SO BLOOD LA English DT Meeting Abstract C1 Boston Univ, Canc Res Ctr, Boston, MA 02215 USA. NIDS, Stroke Branch, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 125 BP 32A EP 32A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100126 ER PT J AU Beleskin-Cokic, BB Yu, XB Cokic, VP Weksler, BB Noguchi, CT AF Beleskin-Cokic, BB Yu, XB Cokic, VP Weksler, BB Noguchi, CT TI Oxygen-dependent proliferative response of human bone marrow endothelial cells to erythropoietin. SO BLOOD LA English DT Meeting Abstract C1 NIH, Biol Chem Lab, Bethesda, MD 20892 USA. NIH, NIDDK, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 155 BP 38A EP 39A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256100156 ER PT J AU Munshi, N Ganju, RK Liang, TJ Koziel, EJ Groopman, JE AF Munshi, N Ganju, RK Liang, TJ Koziel, EJ Groopman, JE TI Mechanism of hepatitis C virus-like particle-induced apoptosis in HUVEC. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. NIDDK, Liver Dis Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 162 BP 40A EP 40A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100163 ER PT J AU Tanaka, Y Primi, D Wang, RY Umemura, T Yeo, AET Mizokami, M Shih, JWK Alter, HJ AF Tanaka, Y Primi, D Wang, RY Umemura, T Yeo, AET Mizokami, M Shih, JWK Alter, HJ TI Genomic and molecular evolutionary analysis of a novel DNA virus (SEN virus) and relationship to variants of TT virus. SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Diasorin Inc, Saluggia, Italy. Nagoya City Univ, Sch Med, Dept Med 2, Nagoya, Aichi 467, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 248 BP 59A EP 59A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100249 ER PT J AU Corten, L Wiesehahn, GP Smyers, JM Murthy, KK McClure, HM Alter, HJ AF Corten, L Wiesehahn, GP Smyers, JM Murthy, KK McClure, HM Alter, HJ TI Photochemical inactivation of hepatitis B (HBV) and hepatitis C (HCV) viruses in human plasma as assessed in a chimpanzee infectivity model. SO BLOOD LA English DT Meeting Abstract C1 Cerus Corp, Concord, CA USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 253 BP 60A EP 61A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256100254 ER PT J AU Handa, A Agbandje-Mckenna, M Brown, KE AF Handa, A Agbandje-Mckenna, M Brown, KE TI Productive replication of TT virus in hematopoietic cells: Development of an in vitro culture system and evidence that TTV requires a helper virus. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Univ Florida, Inst Brain, Gainesville, FL 32611 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 249 BP 60A EP 60A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100250 ER PT J AU Stroncek, DF Yau, YY Leitman, SF AF Stroncek, DF Yau, YY Leitman, SF TI G-CSF plus dexamethasone administration produces greater granulocyte concentrate yields while causing no more donor toxicity than G-CSF alone. SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 262 BP 62A EP 63A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256100263 ER PT J AU Radosevic, N Linnekin, D AF Radosevic, N Linnekin, D TI The nuclear fraction of Lyn is activated during the G1/S transition of stem cell factor-induced cell cycle progression and contributes to SCF-induced proliferation. SO BLOOD LA English DT Meeting Abstract C1 NCI, BRL, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 318 BP 75A EP 75A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100319 ER PT J AU Qi, Y Gabrea, A Sawyer, J Shaughnessy, JD Barlogie, B Bergsagel, PL Kuehl, WM AF Qi, Y Gabrea, A Sawyer, J Shaughnessy, JD Barlogie, B Bergsagel, PL Kuehl, WM TI The t(6;14)(p21;32) translocation causes dysregulation of cyclin D3 in multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 NCI, Med Branch, Dept Genet, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. Cornell Univ, Med Ctr, New York Hosp, Div Hematol Oncol, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 368 BP 86A EP 86A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100369 ER PT J AU Chen, L Zhang, JC Tang, DC Rodgers, GP AF Chen, L Zhang, JC Tang, DC Rodgers, GP TI Bipotentiality and reversible behavior of normal human hematopoietic stem and progenitor cells in culture. SO BLOOD LA English DT Meeting Abstract C1 NIH, NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4182 BP 115B EP 115B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200522 ER PT J AU Chute, JP Wells, M Clark, W Saini, A Stull, MK Harlan, DM Civin, C AF Chute, JP Wells, M Clark, W Saini, A Stull, MK Harlan, DM Civin, C TI Analysis of the repopulating potential of cord blood hematopoietic cells post ex-vivo expansion: CD34(+)CD38(-) phenotype does not predict function. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Navy Transplantat & Autoimmun Branch, Stem Cell Biol Lab, Bethesda, MD USA. Johns Hopkins Univ, Inst Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4185 BP 116B EP 116B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200525 ER PT J AU Mone, AP Howard, DE Molnar, I Kreitman, RJ Frankel, AE AF Mone, AP Howard, DE Molnar, I Kreitman, RJ Frankel, AE TI Resistant acute myeloid leukemia responds to a novel diphtheria toxin/GM-CSF fusion protein: Summary of an ongoing phase I trial. SO BLOOD LA English DT Meeting Abstract C1 Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. Univ Kentucky, Med Ctr, Lucille P Markey Canc Ctr, Lexington, KY 40536 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 504 BP 117A EP 117A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100505 ER PT J AU Molnar, I Hall, PD Willoghby, T Mone, A Kreitman, RJ Frankel, AE AF Molnar, I Hall, PD Willoghby, T Mone, A Kreitman, RJ Frankel, AE TI Pharmacologic and immunologic studies of a diphtheria fusion protein in patients with relapsed or refractory AML. SO BLOOD LA English DT Meeting Abstract C1 Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NIH, Mol Biol Labs, Bethesda, MD USA. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 527 BP 122A EP 123A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256100528 ER PT J AU Curtis, DJ Begley, CG Bodine, DM AF Curtis, DJ Begley, CG Bodine, DM TI Identification of a CCAAT motif essential for basal, but not leukemia inhibitory factor-stimulated, expression of the SKAP55R gene in myeloid cells. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. Western Australian Inst Med Res, Perth, WA, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4259 BP 131B EP 131B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200599 ER PT J AU Frazar, TF Anderson, SM Cline, AP Garrett, LJ Gallagher, PG Bodine, DM AF Frazar, TF Anderson, SM Cline, AP Garrett, LJ Gallagher, PG Bodine, DM TI The human Band 3 (AE 1) promoter linked to the human (A)gamma-globin gene demonstrates erythroid specific but variegated expression in transgenic mice. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. Colby Coll, Dept Biol, Waterville, ME 04901 USA. Yale Univ, Dept Pediat, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4263 BP 132B EP 132B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200603 ER PT J AU Wen, J Yu, XB Noguchi, CT AF Wen, J Yu, XB Noguchi, CT TI Selected SCL/Tal-1 binding sequences in erythroid cells resemble nuclear matrix attachment regions (MARS). SO BLOOD LA English DT Meeting Abstract C1 NIH, Lab Chem Biol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4278 BP 135B EP 135B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200618 ER PT J AU Zhao, XF Aplan, PD AF Zhao, XF Aplan, PD TI SCL binds to and modulates the trans-activation activity of p44, a subunit of basal transcription factor TFIIH. SO BLOOD LA English DT Meeting Abstract C1 SUNY Buffalo, Buffalo Gen Hosp, Dept Pathol, Buffalo, NY 14260 USA. NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4282 BP 136B EP 136B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200622 ER PT J AU Kalechman, Y Longo, DL Albeck, M Sredni, B AF Kalechman, Y Longo, DL Albeck, M Sredni, B TI Synergistic antitumorali effect of the immunomodulator AS101+paclitaxel (Taxol): Association with ras-dependent signal transduction pathways. SO BLOOD LA English DT Meeting Abstract C1 Bar Ilan Univ, Fac Life Sci, CAIR Inst, Ramat Gan, Israel. NIH, NIA, Gerontol Res Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4294 BP 139B EP 139B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200634 ER PT J AU Zapata, JM Krajewska, M Krajewski, S Kitada, S Welsh, K Monks, A McCloskey, N Gordon, J Kipps, T Gascoyne, RD Shabaik, A Reed, JC AF Zapata, JM Krajewska, M Krajewski, S Kitada, S Welsh, K Monks, A McCloskey, N Gordon, J Kipps, T Gascoyne, RD Shabaik, A Reed, JC TI TRAF-family protein expression in normal tissues and lymphoid malignancies. SO BLOOD LA English DT Meeting Abstract C1 Burnham Inst, La Jolla, CA 92037 USA. NCI, Div Canc Treatment & Diagnost, Bethesda, MD 20892 USA. Univ Birmingham, MRC, Ctr Immune Regulat, Birmingham, W Midlands, England. Univ Calif San Diego, Dept Med Hematol & Oncol, San Diego, CA 92103 USA. British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4313 BP 143B EP 143B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200653 ER PT J AU Brenner, S Theobald, N Linton, G Malech, HL AF Brenner, S Theobald, N Linton, G Malech, HL TI Relationship of ex vivo growth factors to viability and cell cycling by cultured peripheral blood CD34+progenitors. SO BLOOD LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. RI Brenner, Sebastian/D-7456-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4319 BP 144B EP 144B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200659 ER PT J AU Cokic, VP Ikonomi, P Beleslin-Cokic, BB Smith, RD Schechter, AN AF Cokic, VP Ikonomi, P Beleslin-Cokic, BB Smith, RD Schechter, AN TI Measurement of nitric oxide synthase gene expression and nitric oxide production during erythroid differentiation. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Chem Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4322 BP 144B EP 144B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200662 ER PT J AU Fonseca, R Bailey, RJ Bergsagel, PL Kuehl, WM AF Fonseca, R Bailey, RJ Bergsagel, PL Kuehl, WM TI Dysregulation of c-MAF is associated with t(14;16)(q32;q23) breakpoints that flank the Fra 16D fragile site within the WWOX gene, and can be greater than 1 Mb from c-MAF. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Cornell Univ, New York Hosp, Div Hematol & Oncol, New York, NY USA. NCI, Dept Genet, Med Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4389 BP 158B EP 158B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200729 ER PT J AU Kim, SB Baskar, S Kwak, LW AF Kim, SB Baskar, S Kwak, LW TI In vitro priming of normal donor PBMC with myeloma protein pulsed dendritic cells. SO BLOOD LA English DT Meeting Abstract C1 Univ Ulsan, Asan Med Ctr, Dept Med, Seoul, South Korea. SAIC, Frederick, MD USA. NCI, Dept Expt Transplant & Immunol, Div Clin Sci, Frederick, MD 21701 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 715 BP 166A EP 166A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100716 ER PT J AU Pavletic, SZ Lynch, JC Sannoufi, S Ketcham, MA Bishop, MR Tarantolo, S Bociek, RG Kessinger, MA AF Pavletic, SZ Lynch, JC Sannoufi, S Ketcham, MA Bishop, MR Tarantolo, S Bociek, RG Kessinger, MA TI Incidence and risks for sclerodermatous chronic graft-versus-host disease after allogeneic marrow or blood transplantation. SO BLOOD LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 833 BP 194A EP 195A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256100834 ER PT J AU Nakamura, R Bahceci, E Read, EJ Leitman, SF Childs, R Dunbar, CE Young, NS Barrett, AJ AF Nakamura, R Bahceci, E Read, EJ Leitman, SF Childs, R Dunbar, CE Young, NS Barrett, AJ TI Low transplant-related mortality from HLA-matched, T cell-depleted peripheral blood stem cell transplantation (PBSCT) followed by donor T cell add-back for hematological malignancies. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 849 BP 198A EP 198A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100850 ER PT J AU Zickler, P Schmidt, M Tisdale, JF Wu, T Dunbar, CE von Kalle, C AF Zickler, P Schmidt, M Tisdale, JF Wu, T Dunbar, CE von Kalle, C TI Tracking of long-term multi-lineage hematopoiesis in a rhesus macaque. SO BLOOD LA English DT Meeting Abstract C1 Univ Freiburg, Freiburg, Germany. NIDDK, MCHB, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 926 BP 217A EP 217A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100927 ER PT J AU Orlic, D Kajstura, J Chimenti, S Li, B Anderson, SM Jakoniuk, I Pickel, J McKay, R Bodine, DM Leri, A Anversa, P AF Orlic, D Kajstura, J Chimenti, S Li, B Anderson, SM Jakoniuk, I Pickel, J McKay, R Bodine, DM Leri, A Anversa, P TI Transplanted hematopoietic stem cells repair myocardial infarcts. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Hematopoiesis Sect, GMBB, NIH, Bethesda, MD 20892 USA. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. New York Med Coll, Dept Med, Valhalla, NY 10595 USA. NR 0 TC 7 Z9 8 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 943 BP 221A EP 221A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100944 ER PT J AU Kawabata, K Nakamaki, T Ikonomi, P Smith, RD Germain, RS Koeffler, HP AF Kawabata, K Nakamaki, T Ikonomi, P Smith, RD Germain, RS Koeffler, HP TI Expression of transferrin receptor 2 in normal and neoplastic hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 Kanazawa Med Univ, Dept Hematol Oncol, Kanazawa, Ishikawa, Japan. Showa Univ, Sch Med, Dept Hematol, Tokyo 142, Japan. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. Cedars Sinai Med Ctr, Dept Med, Div Hematol Oncol, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Sch Med, Burns & Allen Res Inst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 966 BP 226A EP 226A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100967 ER PT J AU Futaki, M Watanabe, S Tatsuguchi, A Igarashi, T Kajigaya, S Liu, JM AF Futaki, M Watanabe, S Tatsuguchi, A Igarashi, T Kajigaya, S Liu, JM TI Translocation of FANCG to endoplasmic reticulum and mitochondria after exposure to mitomycin C. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NHLBI, Sect Pathol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 978 BP 229A EP 229A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100979 ER PT J AU Liu, JM Otsuki, T Young, DB Mercurio, F AF Liu, JM Otsuki, T Young, DB Mercurio, F TI Fanconi anemia protein complex is a novel target of the IKK signalsome. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Jichi Med Sch, Dept Hematol, Minami Kawachi, Tochigi 32904, Japan. Signal Pharmaceut, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 979 BP 229A EP 229A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100980 ER PT J AU Sloand, EM Kim, S Shamburek, R Brewer, B Moss, J Kirby, M Young, NS AF Sloand, EM Kim, S Shamburek, R Brewer, B Moss, J Kirby, M Young, NS TI High density lipoproteins (HDL) may act as carriers for transfer of glycosylphosphatidylinositol (GPI)-linked proteins from blood cells to deficient cells in paroxysmal nocturnal hemoglobinuria (PNH). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NHLBI, Mol Dis Branch, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 994 BP 232A EP 233A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256100995 ER PT J AU Maciejewski, JP Follman, D Simonis, T Young, NS AF Maciejewski, JP Follman, D Simonis, T Young, NS TI Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NHLBI, Dept Biostat, Rockville, MD USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 997 BP 233A EP 233A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100998 ER PT J AU Davis, TA Grillo-Lopez, AJ McLaughlin, P Alkuzweny, B Weaver, RL White, CA AF Davis, TA Grillo-Lopez, AJ McLaughlin, P Alkuzweny, B Weaver, RL White, CA TI Repeated treatments (ReRx) with rituximab in patients (pts) with relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma (LG/F NHL) provide longer response duration (DR) compared to prior chemotherapy (CRx). SO BLOOD LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. Idec Pharmaceut Corp, San Diego, CA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4748 BP 235B EP 235B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201088 ER PT J AU Otsu, M Candotti, F AF Otsu, M Candotti, F TI Dysregulated myelopoiesis in the absence of common gamma chain/Jak3 signaling: Role of IFN-gamma producing CD4(+) T cells. SO BLOOD LA English DT Meeting Abstract C1 NIH, NHGRI, Clin Gene Therapy Branch, Bethesda, MD USA. OI Otsu, Makoto/0000-0002-9769-0217 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1019 BP 238A EP 238A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101020 ER PT J AU Francischetti, IMB Andersen, JF Ribeiro, JMC AF Francischetti, IMB Andersen, JF Ribeiro, JMC TI Rhodnius prolixus aggregation inhibitor (RPAI-1) blocks platelet aggregation by a novel mechanism: High-affinity binding to adenosine diphosphate. SO BLOOD LA English DT Meeting Abstract C1 NIH, NIAID, Parasit Dis Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1061 BP 247A EP 247A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101062 ER PT J AU Francischetti, IMB Valenzuela, JG Andersen, JF Mather, TN Ribeiro, JMC AF Francischetti, IMB Valenzuela, JG Andersen, JF Mather, TN Ribeiro, JMC TI Characterization of ixolaris, a novel recombinant tissue factor pathway inhibitor from the salivary gland of the Lyme disease vector, Ixodes scapularis. SO BLOOD LA English DT Meeting Abstract C1 NIAID, NIH, LPD, Bethesda, MD 20892 USA. Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1110 BP 258A EP 258A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101111 ER PT J AU Rivera, CE Krueger, LA Mayo, DJ Arthur, DC AF Rivera, CE Krueger, LA Mayo, DJ Arthur, DC TI Experimental treatment of transfusion dependent 5q-syndrome with leucovorin. SO BLOOD LA English DT Meeting Abstract C1 NIH, CC, DLM, Serv Hematol, Bethesda, MD USA. NIH, NCI, LP, Cytogenet Sect, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4869 BP 263B EP 263B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201209 ER PT J AU Fu, CL Horne, MK AF Fu, CL Horne, MK TI In vitro evaluation of histidine rich glycoprotein and zinc in complete neutralization of pharmacologic doses of unfractionated heparin. SO BLOOD LA English DT Meeting Abstract C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Pathol, Hematol Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1176 BP 274A EP 274A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101177 ER PT J AU Khanna-Gupta, A Zibello, T Lekstrom-Himes, J Berliner, N AF Khanna-Gupta, A Zibello, T Lekstrom-Himes, J Berliner, N TI C/EBP epsilon mediates myeloid differentiation and is regulated by the CCAAT displacement protein (CDP/cut) in 32Dc13 cells. SO BLOOD LA English DT Meeting Abstract C1 Yale Univ, Sch Med, New Haven, CT USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1212 BP 282A EP 282A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101213 ER PT J AU Kundu, M Begley, CG Liu, PP AF Kundu, M Begley, CG Liu, PP TI Mouse models for the study of the CBFB gene in hematopoiesis. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. Western Australia Inst Med Res, Perth, WA, Australia. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1216 BP 283A EP 283A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101217 ER PT J AU Nilson, DG Sabatino, DE Orkin, SH Gallagher, PG Bodine, DM AF Nilson, DG Sabatino, DE Orkin, SH Gallagher, PG Bodine, DM TI The human beta-spectrin promoter binds EKLF in vitro, but does not require EKLF for expression in transgenic mice. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Boston, MA 02115 USA. Yale Univ, Dept Pediat, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1226 BP 285A EP 285A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101227 ER PT J AU Yu, XB Brandt, SJ Noguchi, CT AF Yu, XB Brandt, SJ Noguchi, CT TI SCL/Tal-1 activates erythropoietin receptor expression and induces a mature erythroid phenotype. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1225 BP 285A EP 285A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101226 ER PT J AU Gertz, MA Lacy, MQ Dispenzieri, A Cheson, B Barlogie, B Kyle, RA Palladini, G Geyer, S Merlini, G AF Gertz, MA Lacy, MQ Dispenzieri, A Cheson, B Barlogie, B Kyle, RA Palladini, G Geyer, S Merlini, G TI A multicenter phase II trial of 4 '-iodo-4 '-deoxydoxorubicin (IDOX) in primary amyloidosis (AL). SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin, Div Hematol, Rochester, MN USA. Mayo Clin, Div Biostat, Rochester, MN USA. Arkansas Canc Res Ctr, Little Rock, AR USA. Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA. Univ Pavia, I-27100 Pavia, Italy. RI Merlini, Giampaolo/A-3817-2008; Palladini, Giovanni/G-1763-2010; Geyer, Susan/E-3112-2011 OI Merlini, Giampaolo/0000-0001-7680-3254; Palladini, Giovanni/0000-0001-5994-5138; NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4985 BP 288B EP 288B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201325 ER PT J AU Kim, SB Baskar, S Kwak, LW AF Kim, SB Baskar, S Kwak, LW TI In vitro primining of normal donor PBMC with myeloma protein pulsed dendritic cells. SO BLOOD LA English DT Meeting Abstract C1 Univ Ulsan, Asan Med Ctr, Dept Med, Seoul, South Korea. SAIC, Frederick, MD USA. NCI, Div Clin Sci, Dept Expt Transplantat & Immunol, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 4992 BP 289B EP 289B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201332 ER PT J AU Onda, M Willingham, M Wang, QC Kreitman, RJ Tsutsumi, Y Nagata, S Pastan, I AF Onda, M Willingham, M Wang, QC Kreitman, RJ Tsutsumi, Y Nagata, S Pastan, I TI Inhibition of TNF alpha produced by Kupffer cells protects against the liver toxicity of immunotoxin anti-Tac(Fv)-PE38. SO BLOOD LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 5002 BP 291B EP 291B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201342 ER PT J AU Murphy, WJ Welniak, LA Karas, M LeRoith, D AF Murphy, WJ Welniak, LA Karas, M LeRoith, D TI Disruption of IGF-I in the liver results in normal bone growth but depressed myelopoiesis in the spleens of mice. SO BLOOD LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1276 BP 296A EP 296A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101277 ER PT J AU Hou, JW Wilson, WH Kasten-Sportes, C Lietzau, J Castro, K Marchigiani, D Gress, R Fowler, DH Bishop, MR AF Hou, JW Wilson, WH Kasten-Sportes, C Lietzau, J Castro, K Marchigiani, D Gress, R Fowler, DH Bishop, MR TI An immune-depleting strategy with antitumor activity for refractory B cell malignancy prior to nonmyeloablative allogeneic stem cell transplantation. SO BLOOD LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 5039 BP 300B EP 300B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201379 ER PT J AU Feng, LS Remington-Boone, LH Huynh, V Yu, A Manns, A Baird, S Chang, HS Wachsman, W AF Feng, LS Remington-Boone, LH Huynh, V Yu, A Manns, A Baird, S Chang, HS Wachsman, W TI Analyses of the Jun-dimerization protein p21(SNFT) implicate it in HTLV pathogenesis. SO BLOOD LA English DT Meeting Abstract C1 VA San Diego Healthcare Syst, Res Serv, San Diego, CA USA. Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1296 BP 301A EP 301A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101297 ER PT J AU Kurtzberg, J Wagner, EL Cairo, MS Reese, M Chun, S Carter, SL Kernan, NA Jensen, L Fraser, JK AF Kurtzberg, J Wagner, EL Cairo, MS Reese, M Chun, S Carter, SL Kernan, NA Jensen, L Fraser, JK TI Assay method, cord blood bank, nucleated cell count, and neonatal factors influence the CD34+cell count in cord blood: The COBLT experience. SO BLOOD LA English DT Meeting Abstract C1 Duke Univ, Durham, NC 27706 USA. EMMES Corp, Potomac, MD USA. Georgetown Univ, Washington, DC 20057 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 5048 BP 302B EP 302B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201388 ER PT J AU Shami, PJ Saavedra, JE Wang, LY Buzard, G Ji, XH Bonifant, C Keefer, LK AF Shami, PJ Saavedra, JE Wang, LY Buzard, G Ji, XH Bonifant, C Keefer, LK TI Glutathione S-Transferase-sensitive nitric oxide donors of the diazeniumdiolate family. In vitro antileukemic activity. SO BLOOD LA English DT Meeting Abstract C1 Univ Utah, Vet Adm Med Ctr, Salt Lake City, UT 84132 USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1329 BP 308A EP 308A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101330 ER PT J AU Areman, EM David-Ocampo, V Kang, EM Tisdale, JF Rodgers, GP Read, EJ AF Areman, EM David-Ocampo, V Kang, EM Tisdale, JF Rodgers, GP Read, EJ TI Ammonium chloride lysis for red blood cell (RBC) depletion of peripheral blood stem cell (PBSC) products. SO BLOOD LA English DT Meeting Abstract C1 NIH, DTM, CC, Bethesda, MD 20892 USA. NIDDK, MCHB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 5151 BP 325B EP 325B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201491 ER PT J AU Mow, BM Hallgren, CG Svingen, PA Tefferi, A Sausville, EA Kaufmann, SH AF Mow, BM Hallgren, CG Svingen, PA Tefferi, A Sausville, EA Kaufmann, SH TI Comparison of the action of NSC 680410 and STI571 in chronic myelogenous leukemia cells in vitro. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin, Div Hematol, Rochester, MN USA. Mayo Clin, Div Oncol Res, Rochester, MN USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1493 BP 346A EP 346A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101494 ER PT J AU Szabolcs, P Reese, M Yancey, K Hall, RP Joanne, K AF Szabolcs, P Reese, M Yancey, K Hall, RP Joanne, K TI Combination treatment of bullous skin GVHD with anti-CD20 and anti-CD25 antibodies. SO BLOOD LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. Duke Univ, Durham, NC USA. NIH, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 5265 BP 350B EP 350B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201605 ER PT J AU Childs, RW Bradstock, KF Gottlieb, D Kefford, R Barrett, J AF Childs, RW Bradstock, KF Gottlieb, D Kefford, R Barrett, J TI Non-myeloablative allogeneic stem cell transplantation as immunotherapy for metastatic melanoma: Results of a pilot study. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Haematol Branch, Bethesda, MD 20892 USA. Westmead Hosp, Dept Haematol, Sydney, NSW, Australia. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 5277 BP 353B EP 353B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201617 ER PT J AU Kim, S Saunthararajah, Y Block, AW Barrett, J Young, NS Sloand, EM AF Kim, S Saunthararajah, Y Block, AW Barrett, J Young, NS Sloand, EM TI Appearance of monosomy 7 in cultures of bone marrow cells from patients with myelodysplasia after exposure in vitro to granulocyte-colony stimulating factor (G-CSF). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Cytogenet Lab, Buffalo, NY 14263 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1529 BP 354A EP 354A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101530 ER PT J AU Sloand, EM Kim, S Maciejewski, JP Block, AW Wang, Y Barrett, J Young, NS AF Sloand, EM Kim, S Maciejewski, JP Block, AW Wang, Y Barrett, J Young, NS TI Hematopoietic cells with trisomy 8 are more senstive to Fas-mediated apoptosis than karyotypically normal cells or cells with other cytogenetic abnormalities. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Cytogenet Lab, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1526 BP 354A EP 354A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101527 ER PT J AU Joshi, SS Pavletic, SZ Tarantolo, SR Lynch, JC Kessinger, A Bishop, MR AF Joshi, SS Pavletic, SZ Tarantolo, SR Lynch, JC Kessinger, A Bishop, MR TI Immune responses following G-CSF mobilized allogeneic blood stem cell transplantation. SO BLOOD LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 5289 BP 355B EP 355B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201629 ER PT J AU Nakamura, R Epperson, DE Saunthararajah, Y Melenhorst, JJ Barrett, AJ AF Nakamura, R Epperson, DE Saunthararajah, Y Melenhorst, JJ Barrett, AJ TI Oligoclonal T cell expansion in myelodysplastic syndrome: Evidence for an autoimmune process. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1534 BP 355A EP 355A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101535 ER PT J AU Elghetany, MT Martinez, J Patel, J Sackey, K Alter, BP AF Elghetany, MT Martinez, J Patel, J Sackey, K Alter, BP TI Granulocytic surface marker abnormalities are detected only in patients with myelodysplastic syndrome and patients with Shwachman Diamond Syndrome but not other bone marrow failure syndromes. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1540 BP 357A EP 357A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101541 ER PT J AU Widhopf, GF Marathe, CM Rassenti, LZ Byrd, JC Flinn, IW Gribben, JG Kipps, TJ AF Widhopf, GF Marathe, CM Rassenti, LZ Byrd, JC Flinn, IW Gribben, JG Kipps, TJ TI Lack of correlation between immunoglobulin somatic mutation and expression of CD38 in chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract C1 NIH, NCI, CLL Res Consortium, Bethesda, MD 20892 USA. Univ Calif San Diego, Sch Med, Div Hematol Oncol, La Jolla, CA 92093 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1586 BP 367A EP 367A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101587 ER PT J AU Rassenti, LZ Widhopf, GF Rai, KR Catovsky, D Kipps, TJ AF Rassenti, LZ Widhopf, GF Rai, KR Catovsky, D Kipps, TJ TI Chronic lymphocytic leukemia associated with acquired changes in the expressed blood T cell receptor repertoire. SO BLOOD LA English DT Meeting Abstract C1 NIH, NCI, CLL Res Consortium, Bethesda, MD 20892 USA. Univ Calif San Diego, Sch Med, Div Hematol, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Div Oncol, La Jolla, CA 92093 USA. Long Isl Jewish Med Ctr, Div Hematol, New Hyde Park, NY 11042 USA. Long Isl Jewish Med Ctr, Div Oncol, New Hyde Park, NY 11042 USA. Royal Marsden Hosp, Dept Hematol & Cytogenet, London SW3 6JJ, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1591 BP 368A EP 368A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101592 ER PT J AU Goel, A Tseng-Law, J Thornton, J Malech, HL Van Epps, D Freimark, B AF Goel, A Tseng-Law, J Thornton, J Malech, HL Van Epps, D Freimark, B TI Efficient transduction of human T cells in a closed system environment using CH-296 coated gas permeable bags. SO BLOOD LA English DT Meeting Abstract C1 Nexell Therapeut Inc, Irvine, CA USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 5392 BP 379B EP 379B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201732 ER PT J AU Mondoro, TH Lozier, JN Vostal, JG AF Mondoro, TH Lozier, JN Vostal, JG TI An adenoviral vector increases platelet leukocyte association through the upregulation of the leukocyte integrin CD11b/18. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD USA. NIH, NHGRI, Clin Gene Therapy Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 5397 BP 380B EP 380B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201737 ER PT J AU Thornton, J Goel, A Tseng-Law, J Malech, HL Van Epps, D Freimark, B AF Thornton, J Goel, A Tseng-Law, J Malech, HL Van Epps, D Freimark, B TI Increased retroviral gene transfer into human CD34(+) cells and T-cells by incorporation of a low-speed centrifugation step in a closed-system environment. SO BLOOD LA English DT Meeting Abstract C1 Nexell Therapeut Inc, Irvine, CA USA. NIH, NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 5418 BP 384B EP 384B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201758 ER PT J AU Fowler, DH Kasten-Sportes, C Wilson, WH Kwak, L Hou, JW Foley, J Leitzau, J Castro, K Marchigiani, D Hakim, F Gress, RE Bishop, MR AF Fowler, DH Kasten-Sportes, C Wilson, WH Kwak, L Hou, JW Foley, J Leitzau, J Castro, K Marchigiani, D Hakim, F Gress, RE Bishop, MR TI Immunoablative (non-myeloablative) allogeneic SCT results in rapid full donor engraftment and early anti-tumor effects independent of DLI or GVHD prophylaxis withdrawal. SO BLOOD LA English DT Meeting Abstract C1 NCI, Dept Expt Transplant & Immunol, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1760 BP 409A EP 409A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101761 ER PT J AU Brenner, S Choi, U Holmes, K Bukovsky, AA Malech, HL AF Brenner, S Choi, U Holmes, K Bukovsky, AA Malech, HL TI Use of multicolor transgenes to compare lenti- and retrovirus transduction of quiescent human CD34+cells. SO BLOOD LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. Cell Genesys Inc, Foster City, CA USA. RI Brenner, Sebastian/D-7456-2013 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1847 BP 430A EP 430A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101848 ER PT J AU Kimchi-Sarfaty, C Ben-nun-Shaul, O Goldenberg, D Rund, DG Gottesman, MM Oppenheim, A AF Kimchi-Sarfaty, C Ben-nun-Shaul, O Goldenberg, D Rund, DG Gottesman, MM Oppenheim, A TI In vitro constructed SV40 pseudovirions: Vectors for hematopoietic tissue. SO BLOOD LA English DT Meeting Abstract C1 Natl Canc Inst, Cell Biol Lab, Bethesda, MD USA. Hebrew Univ Jerusalem, Hadassah Univ Hosp, Dept Hematol, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1857 BP 432A EP 432A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101858 ER PT J AU Gallagher, PG Sabatino, DE Wong, EY Zhou, GP Wong, C Bodine, DM AF Gallagher, PG Sabatino, DE Wong, EY Zhou, GP Wong, C Bodine, DM TI 5 ' untranslated sequences are necessary for high-level, erythroid-specific expression of the alpha-spectrin gene. SO BLOOD LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT USA. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1894 BP 440A EP 440A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101895 ER PT J AU Sabatino, DE Nilson, DG Anderson, SM Garrett, LJ Basseres, DS Costa, FF Saad, ST Bodine, DM Gallagher, PG AF Sabatino, DE Nilson, DG Anderson, SM Garrett, LJ Basseres, DS Costa, FF Saad, ST Bodine, DM Gallagher, PG TI Ankyrin promoter mutations associated with hereditary spherocytosis cause significant abnormalities in ankyrin expression in vivo. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Bethesda, MD 20892 USA. UNICAMP, Campinas, Brazil. Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1893 BP 440A EP 440A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101894 ER PT J AU Nemeth, MJ Bodine, DM Lowrey, CH AF Nemeth, MJ Bodine, DM Lowrey, CH TI Remodeling of beta-globin promoter chromatin by an erythroid-specific chromatin opening element increases beta-globin expression in MEL cells and transgenic mice. SO BLOOD LA English DT Meeting Abstract C1 Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1902 BP 442A EP 442A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101903 ER PT J AU Jackson, TR Brown, FD Nie, ZZ Martin, R Foroni, L Sun, JL Miura, K Hsu, VW Donaldson, J Randazzo, PA Prentice, G AF Jackson, TR Brown, FD Nie, ZZ Martin, R Foroni, L Sun, JL Miura, K Hsu, VW Donaldson, J Randazzo, PA Prentice, G TI Centaurins beta 1 and beta 2: Arf6 GTPase activating proteins cloned from blood cells regulate cytoskeletal events in the cell periphery. SO BLOOD LA English DT Meeting Abstract C1 Royal Free & UCL Med Sch, London, England. NIH, NHLBI, Bethesda, MD 20892 USA. NIH, NCI, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1914 BP 444A EP 445A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256101915 ER PT J AU Farrell, DH Lovely, RS Moaddel, M Stafford, AR Weitz, JI AF Farrell, DH Lovely, RS Moaddel, M Stafford, AR Weitz, JI TI Fibrinogen gamma chain binds thrombin exosite II. SO BLOOD LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NIDDK, Expt Diabet Metab & Nutr Sect, Bethesda, MD USA. McMaster Univ, Hamilton Civic Hosp Res Ctr, Hamilton, ON, Canada. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1932 BP 448A EP 449A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256101933 ER PT J AU Rios, M Hue-Roye, K Miller, JL Reid, ME AF Rios, M Hue-Roye, K Miller, JL Reid, ME TI Molecular basis associated with the Dombrock null phenotype. SO BLOOD LA English DT Meeting Abstract C1 New York Blood Ctr, Immunochem Lab, New York, NY 10021 USA. NIH, NIDDK, Biol Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1945 BP 452A EP 452A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101946 ER PT J AU Mandel, D Kadereit, S Alali, A Mohammed, S Welniak, LA Murphy, WJ Bos, L Kulchycki, L Jin, W Stewart, CC Sieg, S Laughlin, MJ AF Mandel, D Kadereit, S Alali, A Mohammed, S Welniak, LA Murphy, WJ Bos, L Kulchycki, L Jin, W Stewart, CC Sieg, S Laughlin, MJ TI Generation of CD56+CD3+NKT cells from umbilical cord blood (UCB) after expansion with IL-15. SO BLOOD LA English DT Meeting Abstract C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Stanford Univ, Stanford, CA 94305 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1963 BP 456A EP 456A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101964 ER PT J AU McConnell, MJ Chevallier, N Giltnane, J Carlile, GW Staudt, LM Licht, JD AF McConnell, MJ Chevallier, N Giltnane, J Carlile, GW Staudt, LM Licht, JD TI C-MYC is a target for regulation by PLZF: Two alternate mechanisms for downregulation of gene expression. SO BLOOD LA English DT Meeting Abstract C1 CUNY Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, New York, NY 10029 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. RI Giltnane, Jennifer/D-2584-2013 NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1966 BP 457A EP 457A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101967 ER PT J AU Herblot, S Steff, AM Hugo, P Aplan, PD Hoang, T AF Herblot, S Steff, AM Hugo, P Aplan, PD Hoang, T TI Oncogene SCL collaborates with LMO1 to alter thymocyte differentiation: Inhibition of E-protein function and pre-TCR alpha chain gene expression. SO BLOOD LA English DT Meeting Abstract C1 Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada. Natl Canc Inst, Dept Genet, Med Branch, Gaithersburg, MD USA. Procrea BioSci Inc, Montreal, PQ, Canada. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1971 BP 458A EP 458A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101972 ER PT J AU Pineault, N Buske, C Faulkes, S Helgason, CD Aplan, PD Humphries, RK AF Pineault, N Buske, C Faulkes, S Helgason, CD Aplan, PD Humphries, RK TI The AML associated fusion gene NUP98-HOXD13 leads to increased myeloproliferation and decreased erythropoieisis in differentiating embryonic stem cells. SO BLOOD LA English DT Meeting Abstract C1 British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1970 BP 458A EP 458A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101971 ER PT J AU Saunthararajah, Y Wang, JX Futaki, M Igarashi, T Redner, RL Liu, JM AF Saunthararajah, Y Wang, JX Futaki, M Igarashi, T Redner, RL Liu, JM TI Targeted disruption of the interaction between AML1-ETO and the nuclear receptor co-repressor induces apoptosis of AML1-ETO leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Hematol, Tianjin, Peoples R China. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1974 BP 458A EP 459A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256101975 ER PT J AU Bartelmez, SH Iversen, PL Ruscetti, FW AF Bartelmez, SH Iversen, PL Ruscetti, FW TI Inhibition of endogenous transforming growth factor beta-1 in long term repopulating hematopoietic stem cells by morpholino antisense oligo-nucleotides (MAS) prior to transplant accelerates engraftment while reducing the number of stem cells required for long-term repopulation. SO BLOOD LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. AVI BioPharma, Corvallis, OR USA. NCI, Lab Leukocyte Biol, Frederick, MD 21701 USA. NR 0 TC 5 Z9 6 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2040 BP 474A EP 474A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102041 ER PT J AU Bishop, MR Lietzau, J Foley, J Castro, K Kasten-Sportes, C Wilson, WH Kwak, LW Hou, JW Marchigiani, D Gress, R Fowler, DH AF Bishop, MR Lietzau, J Foley, J Castro, K Kasten-Sportes, C Wilson, WH Kwak, LW Hou, JW Marchigiani, D Gress, R Fowler, DH TI High incidence of acute graft-versus-host disease and inflammatory cytokine production with complete rapid donor engraftment after non-myeloablative allogeneic stem cell transplantation. SO BLOOD LA English DT Meeting Abstract C1 NCI, Dept Expt Transplantat & Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2046 BP 475A EP 475A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102047 ER PT J AU Gladwin, MT Shelhamer, JH Ognibene, FP Pannell, LK Schechter, AN Rodgers, GP AF Gladwin, MT Shelhamer, JH Ognibene, FP Pannell, LK Schechter, AN Rodgers, GP TI Nitric oxide donor properties of hydroxyurea in patients with sickle cell disease. SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2085 BP 485A EP 485A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102086 ER PT J AU Taylor, JG Tang, D Leitman, S Heller, S Serjeant, GR Rodgers, GP Chanock, SJ AF Taylor, JG Tang, D Leitman, S Heller, S Serjeant, GR Rodgers, GP Chanock, SJ TI Identification of single nucleotide polymorphisms (SNPs) in cell adhesion molecules for a pilot study of stroke and sickle cell disease. SO BLOOD LA English DT Meeting Abstract C1 NIH, NCI, Pediat Oncol Branch, Gaithersburg, MD USA. NIH, NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD USA. MRC Labs, Sickle Cell Unit, Kingston, Jamaica. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2092 BP 486A EP 486A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102093 ER PT J AU Lozier, JN Nichols, TC Read, MS Bellinger, DA Morgan, RA AF Lozier, JN Nichols, TC Read, MS Bellinger, DA Morgan, RA TI Chapel hill canine hemophilia A is associated with a fusion transcript. SO BLOOD LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2102 BP 488A EP 489A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102103 ER PT J AU Linnekin, D Young, S Danilkovitch-Miagkova, A Ronnstrand, L Leonard, E Ferrao, P Ashman, L Chian, RJ AF Linnekin, D Young, S Danilkovitch-Miagkova, A Ronnstrand, L Leonard, E Ferrao, P Ashman, L Chian, RJ TI PI3 kinase mediates transformation of hematopoietic cells by THF V816 c-Kit mutant. SO BLOOD LA English DT Meeting Abstract C1 NCI, BRL, Frederick, MD USA. Inst Med & Vet Sci, Hanson Ctr Canc Res, Adelaide, SA, Australia. Univ Adelaide, Dept Med, Adelaide, SA 5001, Australia. NCI, LI, Frederick, MD USA. Ludwig Inst Canc Res, S-75124 Uppsala, Sweden. RI Ronnstrand, Lars/A-2429-2011; ASHMAN, LEONIE/G-7631-2013 OI ASHMAN, LEONIE/0000-0003-3559-3611 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2146 BP 498A EP 498A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102146 ER PT J AU Schmidt, M Zickler, P Wissler, M Hoffmann, G Tong, W Tisdale, J Karlsson, S Dunbar, C von Kalle, C AF Schmidt, M Zickler, P Wissler, M Hoffmann, G Tong, W Tisdale, J Karlsson, S Dunbar, C von Kalle, C TI LAM-PCR: Monitoring the clonal composition of the hematopoietic system in transplantation models in vivo. SO BLOOD LA English DT Meeting Abstract C1 Univ Freiburg, Freiburg, Germany. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, MCHB, NIH, Bethesda, MD USA. Univ Lund, Lund, Sweden. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2228 BP 518A EP 518A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102228 ER PT J AU Areman, EM David-Ocampo, V Carter, CS Read, EJ AF Areman, EM David-Ocampo, V Carter, CS Read, EJ TI Post-thaw losses of progenitor and T cells from peripheral blood stem cells (PBSC) cryopreserved in a pentastarch solution do not increase for up to 2 hours after thawing. SO BLOOD LA English DT Meeting Abstract C1 NIH, DTM, Bethesda, MD 20892 USA. NIH, CC, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2236 BP 520A EP 520A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102236 ER PT J AU Childs, RW Bahceci, E Eniafe, R Hensel, N Dunbar, CE Young, NS Barrett, AJ AF Childs, RW Bahceci, E Eniafe, R Hensel, N Dunbar, CE Young, NS Barrett, AJ TI Older patient age remains a risk factor for transplant related mortality (TRM) following nonmyeloablative allogeneic stem cell transplantation (NST). SO BLOOD LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2237 BP 520A EP 520A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102237 ER PT J AU Horwitz, ME Barrett, AJ Brown, MR Carter, CS Holland, SM Linton, GF Leitman, SF Miller, JA Read, EJ Malech, HL AF Horwitz, ME Barrett, AJ Brown, MR Carter, CS Holland, SM Linton, GF Leitman, SF Miller, JA Read, EJ Malech, HL TI Reversal of mixed hematopoietic chimerism following non-myeloablative peripheral blood stem cell transplantation (SCT) using escalating doses of donor T-lymphocytes. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. Natl Heart & Lung Inst, Hematol Branch, Bethesda, MD USA. Warren Grant Magnuson Clin Ctr, Dept Clin Pathol, Bethesda, MD USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2240 BP 521A EP 521A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102240 ER PT J AU Kelly, PF Bonifacino, AC Carrington, JA Agricola, BA Metzger, ME Kluge, KA Nienhuis, AW Donahue, RE Vanin, EF AF Kelly, PF Bonifacino, AC Carrington, JA Agricola, BA Metzger, ME Kluge, KA Nienhuis, AW Donahue, RE Vanin, EF TI Multilineage transduction of non-human primate CD34+hematopoietic cells using RD-114 pseudotyped oncoretroviruses. SO BLOOD LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NHLBI, Hematol Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2259 BP 525A EP 525A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102258 ER PT J AU Maciejewski, JP Rivera, C Dunn, DE Sloand, EM Young, NS AF Maciejewski, JP Rivera, C Dunn, DE Sloand, EM Young, NS TI Clinical features of the relationship between aplastic anemia and paroxysmal nocturnal hemoglobinuria. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2262 BP 526A EP 526A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102262 ER PT J AU Adler, RL Tong, W Boehm, M Bloom, M Dunbar, CE AF Adler, RL Tong, W Boehm, M Bloom, M Dunbar, CE TI Impact of p27Kip1 on in vivo and in vitro hematopoietic stem cell activity. SO BLOOD LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2315 BP 538A EP 539A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102315 ER PT J AU Saunthararajah, Y Nakamura, R Robyn, J Loberiza, F Brown, KE Young, NS Barrett, AJ AF Saunthararajah, Y Nakamura, R Robyn, J Loberiza, F Brown, KE Young, NS Barrett, AJ TI HLA DR15 (DR2) is over-represented in myelodysplastic syndrome (MDS) and is associated with a response to immunosuppression. SO BLOOD LA English DT Meeting Abstract C1 NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2348 BP 546A EP 547A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102348 ER PT J AU Fuzak, J Jung, US Foley, J Eckhaus, MA Fowler, DH AF Fuzak, J Jung, US Foley, J Eckhaus, MA Fowler, DH TI Allospecific Tc2 cells mediate a graft-vs.-tumor effect without inducing ongoing GVHD in a murine model of metastatic breast cancer. SO BLOOD LA English DT Meeting Abstract C1 NCI, Dept Expt Transplantat & Immunol, Bethesda, MD USA. NIH, VRP, NCRR, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2367 BP 551A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102367 ER PT J AU Shi, PA Pomper, GJ Donahue, RE Metzger, M Hoyt, R Leitman, S Dunbar, CE AF Shi, PA Pomper, GJ Donahue, RE Metzger, M Hoyt, R Leitman, S Dunbar, CE TI Peripheral blood stem cell mobilization is comparable with repeat SCF/G-CSF two weeks after an initial mobilization in murine and primate models. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIH, CC, Dept Transfus Med, Bethesda, MD USA. NHLBI, Lab Anim Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2371 BP 552A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102371 ER PT J AU Provenzano, M Bettinotti, E Bonginelli, P Marincola, FM Stroncek, DF AF Provenzano, M Bettinotti, E Bonginelli, P Marincola, FM Stroncek, DF TI A rapid method to identify new candidate CMV epitopes by direct stimulation of PBMC. SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2385 BP 555A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102385 ER PT J AU Rizzo, J Curtis, R Deeg, H Socie, G Travis, L Flowers, M Sobocinski, K Horowitz, M AF Rizzo, J Curtis, R Deeg, H Socie, G Travis, L Flowers, M Sobocinski, K Horowitz, M TI Solid cancers in survivors of allogeneic bone marrow transplantation (BMT). SO BLOOD LA English DT Meeting Abstract C1 IBMTR, Milwaukee, WI USA. NCI, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2390 BP 557A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102390 ER PT J AU Lyons, SE Lawson, ND Bennett, PJ Weinstein, BM Liu, PP AF Lyons, SE Lawson, ND Bennett, PJ Weinstein, BM Liu, PP TI Nonsense mutation in gata1 identified in the "bloodless" zebrafish vlad tepes. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2400 BP 559A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102400 ER PT J AU Tang, DC Zhu, JQ Liu, WL Sun, JF Rodgers, GP AF Tang, DC Zhu, JQ Liu, WL Sun, JF Rodgers, GP TI Identification of a hydroxyurea-inducible small GTP-binding protein associated with elevated gamma globin gene expression. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2407 BP 561A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102407 ER PT J AU Aoki, Y Tosato, G AF Aoki, Y Tosato, G TI Identification of a unique binding site for gp130 in viral interleukin-6 encoded by human herpesvirus 8. SO BLOOD LA English DT Meeting Abstract C1 NCI, Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2458 BP 572A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102458 ER PT J AU Buske, C Pineault, N Feuring-Buske, M Aplan, P Humphries, RK AF Buske, C Pineault, N Feuring-Buske, M Aplan, P Humphries, RK TI Collaboration of MEIS1 with the human leukemia-specific fusion gene NUP98-HOXD13 causes acute myeloid leukemia (AML) in mice: A model of NUP98-associated human leukemia. SO BLOOD LA English DT Meeting Abstract C1 British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2460 BP 573A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102460 ER PT J AU Cong, PJ Raffeld, M Feldstein, J Jaffe, E AF Cong, PJ Raffeld, M Feldstein, J Jaffe, E TI "In situ" follicular lymphoma: Description and analysis by laser capture microdissection. SO BLOOD LA English DT Meeting Abstract C1 NCI, Hematopathol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2470 BP 575A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102470 ER PT J AU Kreitman, RJ Wilson, WH Stetler-Stevenson, M Raggio, M Bergeron, K Margulies, I FitzGerald, DJ Pastan, I AF Kreitman, RJ Wilson, WH Stetler-Stevenson, M Raggio, M Bergeron, K Margulies, I FitzGerald, DJ Pastan, I TI High complete remission rate in chemotherapy-refractory classic or variant hairy cell leukemia induced by the anti-CD22 recombinant immunotoxin RFB4(dsFv)-PE38 (BL22). SO BLOOD LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Clin Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2477 BP 577A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102477 ER PT J AU Powell, JD Fitzhugh, CA Kang, EM Weiss, S Schwartz, RH Tisdale, JF AF Powell, JD Fitzhugh, CA Kang, EM Weiss, S Schwartz, RH Tisdale, JF TI Rapamycin induces long term bone marrow chimerism in the absence of long term immunosuppression in mismatched stem cell transplantation; Application to sickle cell mice. SO BLOOD LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2493 BP 580A EP 581A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102493 ER PT J AU Drobyski, WR Burns, WH Morse, H Sandford, G AF Drobyski, WR Burns, WH Morse, H Sandford, G TI Modulation of alloengraftment, graft-versus-host (GVH), and graft-versus-leukemia (GVL) reactivity using transgenic donor T cells expressing a thymidine kinase (TK) suicide gene: Effect of T cell dose and ganciclovir (GCV) schedule. SO BLOOD LA English DT Meeting Abstract C1 Med Coll Wisconsin, Bone Marrow Transplant Program, Milwaukee, WI 53226 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2496 BP 581A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102496 ER PT J AU Takatoku, M Sellers, S Agricola, BA Metzger, ME Kato, I Donahue, RE Dunbar, CE AF Takatoku, M Sellers, S Agricola, BA Metzger, ME Kato, I Donahue, RE Dunbar, CE TI Rested cell reinfusion improves hematopoietic stem cell retroviral gene marking in non human primates. SO BLOOD LA English DT Meeting Abstract C1 NIH, NHLBI, Hematol Branch, Bethesda, MD USA. Takara Shuzo Co Ltd, Biotechnol Res Lab, Ohtsu, Shiga, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2525 BP 588A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102525 ER PT J AU Sellers, SE Tisdale, JF Agricola, BA Kato, I Donahue, RE Dunbar, CE AF Sellers, SE Tisdale, JF Agricola, BA Kato, I Donahue, RE Dunbar, CE TI Genetically-marked rhesus peripheral blood progenitor cells (PBPC) ex vivo expanded in the presence of fibronectin 296 contribute to both short and long term engraftment. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA. Takara Shuzo Co Ltd, Biotechnol Res Labs, Otsu, Shiga 52021, Japan. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2527 BP 589A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102527 ER PT J AU Noguchi, CT Gladwin, M Diwan, B Jafri, J Buzard, G Fitzhugh, A Keefer, L Schechter, AN Mohandas, N AF Noguchi, CT Gladwin, M Diwan, B Jafri, J Buzard, G Fitzhugh, A Keefer, L Schechter, AN Mohandas, N TI Developing a useful model for sickle cell disease: Hemizygotes for the mouse beta-globin gene. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederik, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, LCC, Frederick, MD USA. Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2568 BP 598A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102568 ER PT J AU Rogers, HM Yu, XB Noguchi, CT AF Rogers, HM Yu, XB Noguchi, CT TI Low oxygen induces gamma-globin expression in erythroid progenitor cells. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2591 BP 603A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102591 ER PT J AU Chuncharunee, S Sura, T Winichagoon, P Jindadamrongwech, S Pootrakul, P Srirunkapracha, P Bunyaratavej, A Fucharoen, S Rodgers, GP AF Chuncharunee, S Sura, T Winichagoon, P Jindadamrongwech, S Pootrakul, P Srirunkapracha, P Bunyaratavej, A Fucharoen, S Rodgers, GP TI Long-term treatment of beta-thalassemia/hemoglobin E with low dose hydroxyurea. SO BLOOD LA English DT Meeting Abstract C1 Ramathibodi Hosp, Dept Med, Bangkok, Thailand. Mahidol Univ, Inst Sci & Technol, Bangkok 10700, Thailand. Mahidol Univ, Ramathibodi Hosp, Dept Pathol, Bangkok 10700, Thailand. NIH, Mol & Clin Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2598 BP 605A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102598 ER PT J AU Ikonomi, P Smith, RD Rivera, CE Riordan, M Schechter, AN AF Ikonomi, P Smith, RD Rivera, CE Riordan, M Schechter, AN TI Fetal hemoglobin induction in rythroid progenitors cultured from limited amounts of whole blood as an in vitro screen for hydroxyurea responsiveness. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NIH, Ctr Clin, Dept Clin Pathol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2599 BP 605A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102599 ER PT J AU Zhang, JC Liu, WL Tang, DC Chen, L Wang, M Pack, SD Zhuang, ZP Rogers, GP AF Zhang, JC Liu, WL Tang, DC Chen, L Wang, M Pack, SD Zhuang, ZP Rogers, GP TI hGC-1, a novel human olfactomedin-related protein, specifically expressed in myeloid lineage. SO BLOOD LA English DT Meeting Abstract C1 NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2610 BP 608A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102610 ER PT J AU Taylor, JG Leitman, SF Chanock, SJ AF Taylor, JG Leitman, SF Chanock, SJ TI Distribution of coding region single nucleotide polymorphisms (SNPs) of human beta defensin 1 (HBD1). SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, NIH, Gaithersburg, MD USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2626 BP 611A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102626 ER PT J AU Grimes, HL Doan, L Bear, SE Alexander, MA Visser, J Morse, HC Tshichlis, PN Kitay, MK AF Grimes, HL Doan, L Bear, SE Alexander, MA Visser, J Morse, HC Tshichlis, PN Kitay, MK TI Ectopic expression of Gfi-1B oncoprotein in the thymus demonstrates a unique survival-signaling requirement for CD8 T-cell fate: Support for the kinetic signaling model of thymopoiesis. SO BLOOD LA English DT Meeting Abstract C1 Univ Louisville, Inst Cellular Therapeut, Louisville, KY 40292 USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. New York Blood Ctr, New York, NY 10021 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2634 BP 613A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102634 ER PT J AU Kook, H Young, NS Maciejewski, JP AF Kook, H Young, NS Maciejewski, JP TI Increased cytotoxic T-cells with effector phenotypic in aplastic anemia (AA). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2658 BP 618A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102658 ER PT J AU Aronson, DL Moll, S Taylor, MA White, GC Krizek, DM Rick, ME AF Aronson, DL Moll, S Taylor, MA White, GC Krizek, DM Rick, ME TI Experience using a modified assay for the von Willebrand factor (vWF) protease in TTP patients. SO BLOOD LA English DT Meeting Abstract C1 NIH, Ctr Clin, Hematol Serv, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2706 BP 630A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102706 ER PT J AU Hortin, GL Murthy, JN Warshawsky, I Kohli, S Horne, M AF Hortin, GL Murthy, JN Warshawsky, I Kohli, S Horne, M TI Macromolecular chromogenic substrates for proteinases. SO BLOOD LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2742 BP 638A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102742 ER PT J AU Dittmar, K Procter, J Njoroge, J Cipolone, K Miller, J Stroncek, D AF Dittmar, K Procter, J Njoroge, J Cipolone, K Miller, J Stroncek, D TI Comparison of direct antiglobulin tests on red cells using traditional tube agglutination to gel column, affinity column and flow cytometric assays. SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, NIDDK, Biol Chem Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2824 BP 657A EP 657A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102824 ER PT J AU Griffith, LM Bolan, CD Stroncek, DF Childs, RW Barrett, AJ Leitman, SF AF Griffith, LM Bolan, CD Stroncek, DF Childs, RW Barrett, AJ Leitman, SF TI Transfusion requirements for nonmyeloablative (NMBCT) versus myeloablative (BCT) blood stem cell or marrow (BMT) transplantation. SO BLOOD LA English DT Meeting Abstract C1 NIH, NHLBI, Ctr Clin, Bethesda, MD 20892 USA. NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2834 BP 659A EP 659A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102834 ER PT J AU Schwartz, GN Vance, BA Fukazawa, M Telford, WG Levine, BM Cesar, D Hellerstein, MK Gress, RE AF Schwartz, GN Vance, BA Fukazawa, M Telford, WG Levine, BM Cesar, D Hellerstein, MK Gress, RE TI Measurements of in vivo proliferation kinetics of human marrow CD34+cells by quantitating (2)[H]-glucose incorporation into DNA of S-phase cells. SO BLOOD LA English DT Meeting Abstract C1 NCI, Med Branch, Bethesda, MD 20892 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2845 BP 662A EP 662A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102845 ER PT J AU Schurman, SH Hawley, TS Candotti, F AF Schurman, SH Hawley, TS Candotti, F TI Hematopoietic side population (SP) cells are identified by cytoplasmic Hoechst staining in a time dependent manner. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Holland Lab, Hematopoiesis Dept, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2850 BP 663A EP 663A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102850 ER PT J AU Iwama, A Osawa, M Kaneko, S Onodera, M Vinson, C Tenen, DG Nakauchi, H AF Iwama, A Osawa, M Kaneko, S Onodera, M Vinson, C Tenen, DG Nakauchi, H TI Altered myeloid differentiation with impaired function of C/EBP transcription factors. SO BLOOD LA English DT Meeting Abstract C1 Univ Tsukuba, Inst Basic Med Sci, Dept Immunol, Tsukuba, Ibaraki 305, Japan. CREST JST, Tsukuba, Ibaraki, Japan. NIH, Natl Canc Ctr, Biochem Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Harvard Inst Med, Div Hematol Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2874 BP 668A EP 668A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102874 ER PT J AU Lyons, SE Shue, BC Oates, AC Zon, LI Liu, PP AF Lyons, SE Shue, BC Oates, AC Zon, LI Liu, PP TI A novel myeloid-restricted zebrafish C/EBP with a potent transcriptional activation domain. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2877 BP 669A EP 669A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102877 ER PT J AU Slater, DJ Hilgenfeld, E Rappaport, EF Shah, NR Megonigal, MD Ried, T Felix, CA AF Slater, DJ Hilgenfeld, E Rappaport, EF Shah, NR Megonigal, MD Ried, T Felix, CA TI Identification of SEPTIN 2 as a new partner gene of MLL in infant AML with a complex translocation. SO BLOOD LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NCI, Bethesda, MD 20892 USA. Geisinger Med Ctr, Danville, PA 17822 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2976 BP 691A EP 691A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102976 ER PT J AU Jaju, RJ Fidler, C Haas, OA Strickson, AJ Watkins, F Clark, K Aplan, PD Kearney, L Boultwood, J Wainscoat, JS AF Jaju, RJ Fidler, C Haas, OA Strickson, AJ Watkins, F Clark, K Aplan, PD Kearney, L Boultwood, J Wainscoat, JS TI A novel gene is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood AML. SO BLOOD LA English DT Meeting Abstract C1 John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, LRF Mol Haematol Unit, Oxford OX3 9DU, England. John Radcliffe Hosp, Inst Mol Med, MRC, Mol Haematol Unit, Oxford OX3 9DU, England. St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria. Natl Canc Inst, Div Clin Sci, Gaithersburg, MD USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2981 BP 692A EP 692A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102981 ER PT J AU Magnusson, MK Brown, KE Krueger, LA Arthur, DC Barrett, J Dunbar, CE AF Magnusson, MK Brown, KE Krueger, LA Arthur, DC Barrett, J Dunbar, CE TI Rabaptin-5, a novel fusion partner to platelet-derived growth factor beta receptor in chronic myelomonocytic leukemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIH, NCI, Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2980 BP 692A EP 692A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102980 ER PT J AU Adya, N Chen, YD Hilgenfeld, E Khan, J Bittner, M Serve, H Berdel, WE Meltzer, P Liu, PP AF Adya, N Chen, YD Hilgenfeld, E Khan, J Bittner, M Serve, H Berdel, WE Meltzer, P Liu, PP TI Gene expression profile of the M4Eo subtype of AML with inv(16). SO BLOOD LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD USA. NIH, Natl Canc Inst, Bethesda, MD USA. Univ Munster, Dept Med, D-4400 Munster, Germany. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3016 BP 700A EP 700A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103016 ER PT J AU Lam, DH Chervinsky, DS Melman, MP Gross, KW Aplan, PD AF Lam, DH Chervinsky, DS Melman, MP Gross, KW Aplan, PD TI SCID mice are protected from the oncogenic effect of SCL and LMO1 transgenes. SO BLOOD LA English DT Meeting Abstract C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NCI, Div Clin Sci, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3022 BP 701A EP 701A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103022 ER PT J AU Kratz, CP Emerling, BM Donovan, S Laig-Webster, M Taylor, BR Thompson, P Jensen, S Banerjee, A Makalowski, W Green, ED Le Beau, MM Shannon, KM AF Kratz, CP Emerling, BM Donovan, S Laig-Webster, M Taylor, BR Thompson, P Jensen, S Banerjee, A Makalowski, W Green, ED Le Beau, MM Shannon, KM TI A physical and transcript map of a 2 Mb commonly deleted segment of 7q22 identified in myeloid malignancies. SO BLOOD LA English DT Meeting Abstract C1 Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. NHGRI, Bethesda, MD 20892 USA. Univ Chicago, Dept Med, Ctr Canc Res, Hematol Oncol Sect, Chicago, IL 60637 USA. RI Makalowski, Wojciech/I-2843-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3036 BP 704A EP 704A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103036 ER PT J AU Hilgenfeld, E Padilla-Nash, H McNeil, N Knutsen, T Montagna, C Tchinda, J Ludwig, WD Serve, H Buchner, T Berdel, WE Ried, T AF Hilgenfeld, E Padilla-Nash, H McNeil, N Knutsen, T Montagna, C Tchinda, J Ludwig, WD Serve, H Buchner, T Berdel, WE Ried, T TI SKY and FISH reveal novel chromosomal aberrations, a recurring involvement of chromosome 21, and amplification of MYC in AML-M2. SO BLOOD LA English DT Meeting Abstract C1 NCI, Dept Genet, NIH, Bethesda, MD 20892 USA. Univ Munster, Dept Human Genet, D-4400 Munster, Germany. Humboldt Univ, Robert Rossle Klin, Berlin, Germany. Univ Munster, Dept Hematol Oncol, D-4400 Munster, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3055 BP 708A EP 708A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103055 ER PT J AU Rao, VK Knutsen, T Langham, G Flynn, M Balis, F Steinberg, S Ried, T Bates, S Fojo, T AF Rao, VK Knutsen, T Langham, G Flynn, M Balis, F Steinberg, S Ried, T Bates, S Fojo, T TI Study of chemotherapy induced chromosomal aberrations in bone marrow cells. SO BLOOD LA English DT Meeting Abstract C1 NCI, DCS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3056 BP 708A EP 708A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103056 ER PT J AU Melenhorst, JJ Kirby, M Sorbara, L Hensel, NF Barrett, AJ AF Melenhorst, JJ Kirby, M Sorbara, L Hensel, NF Barrett, AJ TI Large Granular lymphocyte leukemia (LGL) originates from a clonal pool of CD57-(memory) T cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3084 BP 714A EP 714A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103084 ER PT J AU Zhang, M Yao, ZS Garmestani, K Axworthy, DB Mallett, RW Fritzberg, AR Brechbiel, MW Carrasquillo, JA Waldmann, TA AF Zhang, M Yao, ZS Garmestani, K Axworthy, DB Mallett, RW Fritzberg, AR Brechbiel, MW Carrasquillo, JA Waldmann, TA TI Pretargeting radioimmunotherapy with the alpha emitter, Bi-213, in the treatment of adult T cell leukemia (ATL). SO BLOOD LA English DT Meeting Abstract C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NEORX Corp, Seattle, WA 98119 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3117 BP 721A EP 721A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103117 ER PT J AU Szelenyi, H Ely, S Ying, Q Drexler, HG Chesi, M Kuehl, WM Bergsagel, PL AF Szelenyi, H Ely, S Ying, Q Drexler, HG Chesi, M Kuehl, WM Bergsagel, PL TI Cloning of chromosome translocations in the immunoglobulin heavy chain switch region in Hodgkin's disease. SO BLOOD LA English DT Meeting Abstract C1 Cornell Univ, Weill Med Sch, Dept Hematol, New York, NY USA. NCI, Med Branch, Dept Genet, Bethesda, MD 20892 USA. DSMZ German Collect Cell Cultures, Braunschweig, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3134 BP 725A EP 725A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103134 ER PT J AU Davis, TA Grillo-Lopez, AJ McLaughlin, P White, CA Cairelli, S Alkuzweny, B Lee, D Levy, R AF Davis, TA Grillo-Lopez, AJ McLaughlin, P White, CA Cairelli, S Alkuzweny, B Lee, D Levy, R TI Is there an optimal time for rituximab retreatment (ReRx) for patients with non-Hodgkin's lymphoma (NHL). SO BLOOD LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Idec Pharmaceut Corp, San Diego, CA USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3171 BP 733A EP 733A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103170 ER PT J AU Akin, C Longley, BJ Brockow, K Metcalfe, DD AF Akin, C Longley, BJ Brockow, K Metcalfe, DD TI Effects of the tyrosine-kinase inhibitor STI571 on mutated KIT and neoplastic mast cells. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Allerg Dis Sect, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Dermatol, New York, NY 10027 USA. Columbia Univ, Dept Pathol, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3231 BP 747A EP 747A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103230 ER PT J AU Wilson, WH Gutierrez, M Stetler-Stevenson, M Drbohlav, N Staudt, L Figg, W Sausville, E Fowler, D Bishop, M Hegde, U AF Wilson, WH Gutierrez, M Stetler-Stevenson, M Drbohlav, N Staudt, L Figg, W Sausville, E Fowler, D Bishop, M Hegde, U TI Phase I trial of 7-hydroxystaurosporine (UCN-01) and fludararbine phosphate (FAMP); In vivo evidence of UCN-01 induced apoptosis in CLL. SO BLOOD LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3268 BP 756A EP 756A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103267 ER PT J AU Murphy, WJ Koh, CY Capitini, CM Bennett, M AF Murphy, WJ Koh, CY Capitini, CM Bennett, M TI Transfer of activated NK cells with inhibitory receptor blockade results in increased donor chimerism without gvhd after allogeneic bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. Univ Texas, SW Med Ctr, Dallas, TX USA. RI Koh, Crystal/D-9986-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3335 BP 771A EP 771A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103334 ER PT J AU Wong, E Lee, S Aono, F Hines, K Lee, J Trischmann, T Chau, Q Kopp, WC Carter, C Bender, J Read, EJ AF Wong, E Lee, S Aono, F Hines, K Lee, J Trischmann, T Chau, Q Kopp, WC Carter, C Bender, J Read, EJ TI Comparison of elutriation with immunomagnetic selection to enrich monocytes for ex-vivo generation of dendritic cells. SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Nexell Therapeut Inc, Irvine, CA USA. SAIC, Frederick, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3370 BP 779A EP 779A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103369 ER PT J AU Bolan, CD Childs, R Griffith, L Procter, J Stroncek, D Barrett, AJ Leitman, SF AF Bolan, CD Childs, R Griffith, L Procter, J Stroncek, D Barrett, AJ Leitman, SF TI Pure red cell aplasia (PRCA) and delayed erythroid engraftment in non-myeloablative (NM) PBSC transplantation with major ABO incompatibility. SO BLOOD LA English DT Meeting Abstract C1 NIH, Ctr Clin, Dept Transfus Med, NHLBI, Bethesda, MD 20892 USA. NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3374 BP 780A EP 780A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103373 ER PT J AU Sloand, EM Childs, RW Greene, A Phang, S Young, NS Barrett, J AF Sloand, EM Childs, RW Greene, A Phang, S Young, NS Barrett, J TI Non-myeloablative peripheral blood stem cell transplantation for chronic myelogenous leukemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3387 BP 783A EP 783A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103386 ER PT J AU Anaissie, E Stratton, S Summerbell, R Rex, J Walsh, T AF Anaissie, E Stratton, S Summerbell, R Rex, J Walsh, T TI Opportunistic moulds in a hospital water system: A 3-year prospective study. SO BLOOD LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. Ontario Minist Hlth, Toronto, ON M5W 1R5, Canada. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3402 BP 787A EP 787A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103401 ER PT J AU Choi, UM Malech, HL AF Choi, UM Malech, HL TI Inverse PCR analysis of unique inserts found in peripheral blood neutrophils following clinical gene therapy for chronic granulomatous disease. SO BLOOD LA English DT Meeting Abstract C1 NIH, NIAID, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3478 BP 805A EP 805A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103477 ER PT J AU Yavuz, AS Lipsky, PE Metcalfe, DD Akin, C AF Yavuz, AS Lipsky, PE Metcalfe, DD Akin, C TI Evidence for a common progenitor for monocytes, B-lymphocytes and mast cells by single cell mutational analysis of cells in the peripheral blood of patients with systemic indolent mastocytosis. SO BLOOD LA English DT Meeting Abstract C1 NIH, NIAMSD, Autoimmun Branch, Bethesda, MD 20892 USA. NIH, NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3484 BP 806A EP 806A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103483 ER PT J AU Woei-A-Jin, SH Melenhorst, JJ Hensel, NF Kirby, MR Falkenburg, JHF Barrett, AJ AF Woei-A-Jin, SH Melenhorst, JJ Hensel, NF Kirby, MR Falkenburg, JHF Barrett, AJ TI Identification of memory CD8+T-cell responses against common hematopoietic proteins. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Leiden Univ, Med Ctr, Leiden, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3492 BP 808A EP 808A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103491 ER PT J AU Staunton, JE Slonim, DK Coller, HA Tamayo, P Angelo, MJ Scherf, U Weinstein, JN Mesirov, JP Lander, ES Golub, TR AF Staunton, JE Slonim, DK Coller, HA Tamayo, P Angelo, MJ Scherf, U Weinstein, JN Mesirov, JP Lander, ES Golub, TR TI Gene expression predicts chemosensitivity of cancer cell lines. SO BLOOD LA English DT Meeting Abstract C1 MIT, Ctr Genome Res, Cambridge, MA 02139 USA. NCI, Bethesda, MD 20892 USA. MIT, Dept Biol, Cambridge, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3559 BP 823A EP 823A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103558 ER PT J AU Lee, T Miller, LD Gubin, AN Makhlouf, F Wojda, U Barrett, AJ Liu, ET Miller, JL AF Lee, T Miller, LD Gubin, AN Makhlouf, F Wojda, U Barrett, AJ Liu, ET Miller, JL TI Identification of abnormal gene transcription patterns in myelodysplastic bone marrow using erythroid-focused cDNA arrays. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, Bethesda, MD USA. NCI, Div Clin Sci, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIH, CIT, Bethesda, MD 20892 USA. RI Liu, Edison/C-4141-2008; Miller, Lance/A-5633-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3599 BP 833A EP 833A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103598 ER PT J AU Hendricks, JK Buyaner, D Liu, L Lee, KM Medin, JA Murray, GJ Brady, RO Deans, R AF Hendricks, JK Buyaner, D Liu, L Lee, KM Medin, JA Murray, GJ Brady, RO Deans, R TI Use of human mesenchymal stem cells as gene delivery vehicles for the treatment of Fabry's disease. SO BLOOD LA English DT Meeting Abstract C1 Osiris Therapeut Inc, Baltimore, MD USA. Univ Illinois, Chicago, IL USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3651 BP 845A EP 845A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103650 ER PT J AU Tsai, EJ Aviles-Medoza, GJ Band, JM Anderson, SM Outsu, M Candotti, F Bodine, DM Malech, HL Puck, JM AF Tsai, EJ Aviles-Medoza, GJ Band, JM Anderson, SM Outsu, M Candotti, F Bodine, DM Malech, HL Puck, JM TI Development of XSCID gene therapy for B-cell defective post-transplant XSCID patients. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. HHMI NIH Res Scholars Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3652 BP 845A EP 845A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103651 ER PT J AU Cohen-Fix, O AF Cohen-Fix, O TI Sister chromatid separation: Falling apart at the seams SO CURRENT BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CHROMOSOME SEGREGATION; COHESIN REC8; MEIOSIS-I; ANAPHASE; YEAST; CLEAVAGE; METAPHASE; COMPLEXES; DIVISIONS C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Cohen-Fix, O (reprint author), NIDDK, Mol & Cellular Biol Lab, NIH, 8 Ctr Dr, Bethesda, MD 20892 USA. NR 24 TC 11 Z9 12 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 16 PY 2000 VL 10 IS 22 BP R816 EP R819 DI 10.1016/S0960-9822(00)00799-5 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 457NH UT WOS:000170143300006 PM 11102820 ER PT J AU Hour, MJ Huang, LJ Kuo, SC Xia, Y Bastow, K Nakanishi, Y Hamel, E Lee, KH AF Hour, MJ Huang, LJ Kuo, SC Xia, Y Bastow, K Nakanishi, Y Hamel, E Lee, KH TI 6-alkylamino- and 2,3-dihydro-3 '-methoxy-2-phenyl-4-quinazolinones and related compounds: Their synthesis, cytotoxicity, and inhibition of tubulin polymerization SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTITUMOR AGENTS; BIOLOGICAL EVALUATION; COLCHICINE; ANALOGS; 2-PHENYL-4-QUINOLONES; DERIVATIVES AB As part of our continuing search for potential anticancer candidates among 2-phenyl-4-quinolones and 2-phenyl-4-quinazolinones, two series of 6,7,2',3',4',5'-substituted 2-phenyl-4-quinazolinones and 6,2',3',4',5'-substituted 2,3-dihydro-2-phenyl-4-quinazolinones were synthesized and evaluated for cytotoxicity and as inhibitors of tubulin polymerization. In general, a good correlation was found between the two activities. Five of the 6-substituted heterocyclic 2-phenyl-4-quinozolinones (37-51) showed significant cytotoxicity against a panel of human tumor cell lines with EC50 values in the low micromolar to nanomolar concentration ranges. Compound 38 was the most potent of these compounds, as well as the most potent inhibitor of tubulin polymerization in this series. The activity of 38 was in the same range as those of the antimitotic natural products, colchicine, podophyllotoxin, and combretastatin A-4. Substituted 2-phenyl-4-quinazolinones and 2,3-dihydro-2-phenyl-4-quinazolinones also displayed highly selective cytotoxicity against the ovarian cancer 1A9 and P-gp resistant KB-VIN cell lines. C1 China Med Coll, Grad Inst Pharmaceut Chem, Taichung, Taiwan. Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Screening Technol Branch, Frederick, MD 21702 USA. RP Lee, KH (reprint author), China Med Coll, Grad Inst Pharmaceut Chem, Taichung, Taiwan. FU NCI NIH HHS [CA17625] NR 22 TC 244 Z9 253 U1 4 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 16 PY 2000 VL 43 IS 23 BP 4479 EP 4487 DI 10.1021/jm000151c PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 374HR UT WOS:000165340200016 PM 11087572 ER PT J AU Ohrui, H Kohgo, S Kitano, K Sakata, S Kodama, E Yoshimura, K Matsuoka, M Shigeta, S Mitsuya, H AF Ohrui, H Kohgo, S Kitano, K Sakata, S Kodama, E Yoshimura, K Matsuoka, M Shigeta, S Mitsuya, H TI Syntheses of 4 '-C-ethynyl-beta-D-arabino- and 4'-C-ethynyl-2'-deoxy-beta-D-ribo-pentofuranosylpyrimidines and -purines and evaluation of their anti-HIV activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PYRIMIDINE NUCLEOSIDES; BIOLOGICAL-ACTIVITIES; ANTIVIRAL AGENT; NUCLEOTIDES; POTENT; PROTEASE; ANALOGS; THERAPY AB 4'-C-Ethynyl-beta -D-arabino- and 4'-C-ethynyl-2'-deoxy-beta -D-ribo-pentofuranosylpyrine and -purine nucleosides were synthesized and evaluated for their in vitro anti-HIV activity. The key intermediate, 4-C-ethynyl- or 4-C-triethylsilylethynyl-D-ribo-pentofuranose, was prepared from D-glucose and glycosidated with various pyrimidine or purine bases. The arabino pyrimidine derivatives were prepared from the corresponding ribo derivatives via O-2,2'-anhydro nucleosides. The 2'-deoxy-ribo derivatives were synthesized by radical reduction of 2'-bromo or 2'- phenoxythiocarbonyloxy nucleosides. Among these 4'-C-ethynyl nucleosides, seven analogues proved to be potent against HIV-1 in vitro with EC50 values ranging from 0.0003 to 0.03 muM. These compounds also exerted activity against clinical and multi-dideoxy-nucleoside-resistant HIV-1 strains with comparable EC50 values. Three such 4'-C-ethynyl-2'-deoxypurine analogues including 4'-C-ethynyl-2'-deoxyadenosine and 4'-C-ethynyl-2,6-diamino-2'-deoxy-purine were less cytotoxic [selectivity indices (SIs): 975-2733] than three 4'-C-ethynyl-2-deoxycytidine analogues (SIs: 63-363). 4'-C-Ethynyl-5-fluoro-2'-deoxycytidine was least toxic (SI: >3333) and potent against all HIV strains tested. C1 Tohoku Univ, Grad Sch Agr Sci, Div Life Sci, Aoba Ku, Sendai, Miyagi 9818555, Japan. Yamasa Corp, Div Biochem, Chiba 2880056, Japan. Kyoto Univ, Inst Virus Res, AIDS Res Ctr, Lab Virus Immunol, Kyoto 6068507, Japan. Fukushima Med Univ, Dept Microbiol, Fukushima 9601295, Japan. Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 860, Japan. NCI, Div Clin Sci, Med Branch, Expt Retrovirol Sect, Bethesda, MD 20892 USA. RP Ohrui, H (reprint author), Tohoku Univ, Grad Sch Agr Sci, Div Life Sci, Aoba Ku, 1-1 Tsutsumidori Amamiyamachi, Sendai, Miyagi 9818555, Japan. RI Kodama, Eiichi /C-4032-2009 OI Kodama, Eiichi /0000-0002-6622-2752 NR 29 TC 69 Z9 73 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 16 PY 2000 VL 43 IS 23 BP 4516 EP 4525 DI 10.1021/jm000209n PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 374HR UT WOS:000165340200020 PM 11087576 ER PT J AU Knox, SS Adelman, A Ellison, RC Arnett, DK Siegmund, K Weidner, G Province, MA AF Knox, SS Adelman, A Ellison, RC Arnett, DK Siegmund, K Weidner, G Province, MA TI Hostility, social support, and carotid artery atherosclerosis in the National Heart, Lung, and Blood Institute family heart study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DISEASE; LIPIDS; RISK AB This cross-sectional study investigates the association of hostility and social support (measured by standardized instruments) to carotid artery atherosclerosis in men and women with a high familial risk for coronary heart disease (CHD) and those with low to medium risk. The hypothesis was that high hostility and low social support would have a stronger association in subjects with a familial predisposition to CHD. There were 535 low- to medium-risk women, 491 low- to medium-risk men, 1,950 high-risk women, and 1,667 high-risk men in the study. The extent of carotid artery atherosclerosis was assessed by B-mode ultrasound imaging. A lesion was defined as an intimal-medial far wall thickness of 1 mm in the common, internal, or carotid bifurcation, or identification of plaque at any site. Odds ratios and their 95% confidence intervals were calculated using generalized estimating equations (GEE) for logistic regression. Family was specified as the clustering variable, and robust SEEs were obtained that account for dependence of the data within families. After controlling for age, education, body mass index, ever having smoked, ever drinking >5 drinks a day, and metabolic index, hostility was significantly associated with increased odds of carotid lesions in only high-risk women. High-risk women showed a significantly reduced odds of carotid lesions with high social support, but the extent of this protection was reduced when age and education were included in the equation. A combination of high hostility and low social support was associated with higher odds than hostility alone in both high-risk men and women. These results suggest that women with a high familial predisposition for CHD may be more vulnerable to cardiovasculor influences from hostility and social support than high-risk men or men and women with low to medium risk. (C) 2000 by Excerpta Medica, Inc. C1 NHLBI, Rockledge Ctr 2, Bethesda, MD 20892 USA. Washington Univ, Sch Med, St Louis, MO USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. Univ So Calif, Sch Med, Los Angeles, CA USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. RP Knox, SS (reprint author), NHLBI, Rockledge Ctr 2, 6701 Rockledge Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-25104, N01-HC-25106, N01-HC-25105] NR 15 TC 37 Z9 37 U1 2 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2000 VL 86 IS 10 BP 1086 EP 1089 DI 10.1016/S0002-9149(00)01164-4 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 371NR UT WOS:000165185500006 PM 11074204 ER PT J AU Devereux, RB Roman, MJ Liu, JE Welty, TK Lee, ET Rodeheffer, R Fabsitz, RR Howard, BV AF Devereux, RB Roman, MJ Liu, JE Welty, TK Lee, ET Rodeheffer, R Fabsitz, RR Howard, BV TI Congestive heart failure despite normal left ventricular systolic function in a population-based sample: The strong heart study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PRESSURE-OVERLOAD HYPERTROPHY; AMERICAN-INDIANS; CARDIOVASCULAR-DISEASE; RISK-FACTORS; VOLUME; HYPERTENSION; PREVALENCE; MORTALITY AB In selected clinical series, greater than or equal to 50% of adults with congestive heart failure (CHF) do not have left ventricular (LV) systolic dysfunction. Little is known of the prevalence of this phenomenon in population samples. Therefore, clinical examination and echocardiography were used in the second examination of the Strong Heart Study (3,184 men and women, 47 to 81 years old) to identify 95 participants with CHF, 50 of whom had normal LV ejection fraction (EF) (>54%), 19 of whom had mildly reduced EF (40% to 54%), and 26 of whom had EF less than or equal to 40%. Compared with those with no CHF, participants with CHF and no, mild, or severe decrease in EF had higher creatinine levels (2.34 to 2.85 vs 1.01 mg/dl, p <0.001) and higher prevalences of diabetes (60% to 70% vs 50%) and hypertension (75% to 96% vs 46%, p <0.05). Compared with those with no CHF, participants with CHF and normal EF had prolonged deceleration time:(233 vs 204 ms, p <0.05) and a reduced E/A, whereas those with CHF and EF 40% had short deceleration time (158 ms, p <0.05) and high E/A (1.70, p <0.001); patients with CHF and normal EF had higher LV mass (98 vs 84 g/m(2), p <0.001) and relative wall thickness (0.37 vs 0.35, p <0.05) than those without CHF. Patients with CHF with normal EF were, compared with those without CHF or with CHF and EF less than or equal to 40%, disproportionately women (mean 84% vs 63% and 42%, p <0.001), older (mean 64 vs 60 years and 63 years, respectively, p <0.01), had higher body mass index (mean 33.1 vs 31.0 and 27.7 kg/m(2), p <0.05), and higher systolic blood pressure (mean 137 vs 130 and 128 mm Hg, both p <0.05). Thus, in a population-based sample, patients with CHF and normal LV EF were older and overweight, more often women, had renal dysfunction, impaired early diastolic LV relaxation, and concentric LV geometry, whereas patients with CHF and severe LV dysfunction were more often men, had lower body mass index, a restrictive pattern of LV filling, and eccentric LV hypertrophy. (C) 2000 by Excerpta Medica, Inc. C1 New York Presbyterian Hosp, Weill Cornell Med Ctr, Dept Med, New York, NY 10021 USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. Univ Oklahoma, Hlth Sci Ctr, Sch Publ Hlth, Oklahoma City, OK USA. Mayo Clin, Rochester, MN USA. NHLBI, Bethesda, MD 20892 USA. MedStar Res Inst, Washington, DC USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. RP Devereux, RB (reprint author), New York Presbyterian Hosp, Weill Cornell Med Ctr, Dept Med, 525 E 68th St,Box 222, New York, NY 10021 USA. FU NHLBI NIH HHS [U01-HL41642, U01-HL41652, U01-HL41654] NR 29 TC 157 Z9 164 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2000 VL 86 IS 10 BP 1090 EP 1096 DI 10.1016/S0002-9149(00)01165-6 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 371NR UT WOS:000165185500007 PM 11074205 ER PT J AU Hutter, D Chen, PL Barnes, J Liu, YS AF Hutter, D Chen, PL Barnes, J Liu, YS TI Catalytic activation of mitogen-activated protein (MAP) kinase phosphatase-1 by binding to p38 MAP kinase: critical role of the p38 C-terminal domain in its negative regulation SO BIOCHEMICAL JOURNAL LA English DT Article DE feedback control; MKP-1; protein-protein interaction; signal transduction ID DUAL-SPECIFICITY PHOSPHATASE; TYROSINE-PHOSPHATASE; HEAT-SHOCK; INFLAMMATORY CYTOKINES; OXIDATIVE STRESS; IN-VIVO; EXPRESSION; MKP-1; TRANSCRIPTION; PATHWAY AB Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) is the archetypal member of the dual-specificity protein phosphatase family, the expression of which can be rapidly induced by a variety of growth factors and cellular stress. Since MKP-1 protein localizes in the nucleus, it has been suggested to pray an important role in the feedback control of MAP kinase-regulated gene transcription. Recently it has been demonstrated that the interaction of several cytosolic MAP kinase phosphatases with MAP kinases can trigger the catalytic activation of the phosphatases. It is unclear whether such a regulatory mechanism can apply to nuclear MAP kinase phosphatases and serve as an additional apparatus for the feedback control of MAP kinase-mediated gene expression. Here we have shown that MKP-1 associates directly with p38 MAP kinase both in vitro and in vitro, and that this interaction enhances the catalytic activity of MKP-1. The point mutation Asp-316 --> Asn in the C-terminus of p38, analogous to the ERK2 (extracellular-signal-regulated kinase 2) sevenmaker mutation, dramatically decreases its binding to MKP-1 and substantially compromises its stimulatory effect on the catalytic activity of this phosphatase. Consistent with its defective interaction with MKP-1, this p38 mutant also displays greater resistance to dephosphorylation by the phosphatase. Our studies provide the first example of catalytic activation of a nuclear MAP kinase phosphatase through direct binding to a MAP kinase, suggesting that such a regulatory mechanism may play an important role in the feedback control of MAP kinase signalling in the nuclear compartment. C1 NIA, Cellular & Mol Biol Lab, Stress Signalling Unit, NIH, Baltimore, MD 21224 USA. RP Liu, YS (reprint author), NIA, Cellular & Mol Biol Lab, Stress Signalling Unit, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Liu, Yusen/E-3527-2011 NR 37 TC 87 Z9 88 U1 0 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 15 PY 2000 VL 352 BP 155 EP 163 DI 10.1042/0264-6021:3520155 PN 1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 379LH UT WOS:000165643200016 PM 11062068 ER PT J AU Klotz, LO Schieke, SM Sies, H Holbrook, NJ AF Klotz, LO Schieke, SM Sies, H Holbrook, NJ TI Peroxynitrite activates the phosphoinositide 3-kinase/Akt pathway in human skin primary fibroblasts SO BIOCHEMICAL JOURNAL LA English DT Article DE oxidative stress; signal transduction; protein kinase B ID PROTEIN-KINASE-B; NF-KAPPA-B; TYROSINE PHOSPHORYLATION; GROWTH-FACTOR; MECHANISM; STRESS; CELLS; AKT; INHIBITION; APOPTOSIS AB Peroxynitrite is a potent oxidizing and nitrating species formed in a diffusion-limited reaction between nitrogen monoxide and superoxide. It induces apoptosis through unknown mechanisms and is believed to interfere with receptor tyrosine kinase signalling through nitration of tyrosine residues. One pathway emanating from receptor tyrosine kinases is that leading to activation of the anti-apoptotic kinase Akt. In the present study we provide evidence that peroxynitrite, administered to cells using two different delivery systems, results in the dose- and time-dependent activation of Akt. Akt activation is rapid and followed by phosphorylation of glycogen synthase kinase-3, an established substrate of Akt, Akt activation is inhibited in the presence of the phosphoinositide 3-kinase (PI-3K) inhibitors wortmannin and LY294002, and by treatment with the platelet-derived growth factor (PDGF) receptor (PDGFR) inhibitor AG1295, indicating a requirement for PDGFR and PI-3K in mediating peroxynitrite-induced Akt activation. Accordingly, the PDGFR-A and PDGFR-B isoforms were shown to undergo rapid tyrosine phosphorylation on treatment with peroxynitrite. Prior exposure of cells to peroxynitrite interferes with PDGF-induced Akt phosphorylation. Our findings suggest that Akt activation occurs as an acute response to peroxynitrite treatment and could play an important role in influencing cell survival and/or alter the cellular response to other growth regulatory signals. C1 NIA, Biol Chem Lab, Cell Stress & Aging Sect, NIH, Baltimore, MD 21224 USA. Univ Dusseldorf, Inst Physiol Chem 1, D-40225 Dusseldorf, Germany. RP Holbrook, NJ (reprint author), NIA, Biol Chem Lab, Cell Stress & Aging Sect, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Sies, Helmut/B-7266-2008 NR 44 TC 108 Z9 110 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 NOV 15 PY 2000 VL 352 BP 219 EP 225 DI 10.1042/0264-6021:3520219 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 379LH UT WOS:000165643200024 PM 11062076 ER PT J AU Miyamoto, S Kimball, SR Safer, B AF Miyamoto, S Kimball, SR Safer, B TI Signal transduction pathways that contribute to increased protein synthesis during T-cell activation SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE lymphocytes; activation; signaling; translation; immunosuppressants ID GLYCOGEN-SYNTHASE KINASE-3; INITIATION-FACTOR EIF2B; CHINESE-HAMSTER OVARY; HUMAN LYMPHOCYTES-T; TRANSLATION INITIATION; PHORBOL ESTER; GENE-EXPRESSION; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; CALCIUM IONOPHORES AB Protein synthesis rates were maximally stimulated in human lymphocytes by ionomycin and the phorbol ester PMA (I+P), which promotes proliferation, whereas PMA alone, which does not promote proliferation, stimulated protein synthesis to a lesser degree. Three translation-associated activities, eIF4E phosphorylation, eIF2B activity and 4E-BP1 phosphorylation also increased with stimulation by I+P and PMA, but only 4E-BP1 phosphorylation was differentially stimulated by these conditions. Correspondingly, signaling pathways activated in T cells were probed for their connection to these activities. Immunosuppressants FK506 and rapamycin partially blocked the protein synthesis rate increases by I+P stimulation. FK506 had less of an inhibitory effect with PMA stimulation suggesting that its mechanism mostly affected ionomycin-activated signals. I+P and PMA equally stimulated phosphorylation of ERK1/2, but I+P more strongly stimulated Akt, and p70(S6K) phosphorylation. An inhibitor that blocks ERK1/2 phosphorylation only slightly reduced protein synthesis rates stimulated by I+P or PMA, but greatly reduced eIF4E phosphorylation and eIF2B activity. In contrast, inhibitors of the PI-3 kinase and mTOR pathways strongly blocked early protein synthesis rate stimulated by I+P and PMA and also blocked 4E-BP1 phosphorylation and release of eIF4E suggesting that these pathways regulate protein synthesis activities, which are important for proliferation in T cells. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NHLBI, Mol Hematol Branch, Sect Prot & RNA Biosynth, Bethesda, MD 20892 USA. Univ Calif Davis, Sch Med, Dept Biol Chem, Livermore, CA 95616 USA. Penn State Coll Med, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. RP Miyamoto, S (reprint author), NHLBI, Mol Hematol Branch, Sect Prot & RNA Biosynth, Bldg 10,Room 7D18, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK15658, DK13799]; NIGMS NIH HHS [GM22135] NR 75 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD NOV 15 PY 2000 VL 1494 IS 1-2 BP 28 EP 42 DI 10.1016/S0167-4781(00)00208-6 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 374TL UT WOS:000165360400004 PM 11072066 ER PT J AU Potratz, A Huttler, S Bierfreund, U Proia, RL Suzuki, K Sandhoff, K AF Potratz, A Huttler, S Bierfreund, U Proia, RL Suzuki, K Sandhoff, K TI Quantification of mRNAs encoding proteins of the glycosphingolipid catabolism in mouse models of GM2 gangliosidoses and sphingolipid activator protein precursor (prosaposin) deficiency SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE sphingolipidosis; mRNA quantification; real-time reverse transcription-polymerase chain reaction; lysosomal hydrolase; sphingolipid activator protein; knock-out mouse ID LIPOFUSCINOSES BATTEN-DISEASE; TAY-SACHS-DISEASE; LYSOSOMAL STORAGE; TARGETED DISRUPTION; GENE; DEGRADATION; PHENOTYPE; TISSUES; MICE; PCR AB We have investigated the mRNA amounts of six lysosomal proteins (beta -hexosaminidase alpha- and beta -subunit, sphingolipid activator protein precursor, GM2 activator protein, lysosomal sialidase, beta -glucocerebrosidase) involved in the degradation of glycosphingolipids. We analyzed extracts from brain tissues of mouse models for lysosomal storage diseases, i.e., the GM2 gangliosidoses and the deficiency of the sphingolipid activator protein precursor (prosaposin). The mRNA levels were quantified by real-time reverse transcription-polymerase chain reaction. Although storage of the respective lysosomal proteins has been reported in human and mice, no increase of their mRNA amounts could be detected here. Our results indicate that there is no transcriptional upregulation of lysosomal proteins in the examined neuronal storage disorders. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany. NIDDKD, Sect Biochem Genet, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Brain & Dev Res Ctr, Chapel Hill, NC 27599 USA. RP Sandhoff, K (reprint author), Kekule Inst Organ Chem & Biochem, Gerhard Domagk Str 1, D-53121 Bonn, Germany. RI Proia, Richard/A-7908-2012 FU NICHD NIH HHS [P30HD03110]; NINDS NIH HHS [R01NS24289] NR 27 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD NOV 15 PY 2000 VL 1502 IS 3 BP 391 EP 397 DI 10.1016/S0925-4439(00)00063-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 374RL UT WOS:000165358100007 PM 11068181 ER PT J AU George, MS Nahas, Z Molloy, M Speer, AM Oliver, NC Li, XB Arana, GW Risch, SC Ballenger, JC AF George, MS Nahas, Z Molloy, M Speer, AM Oliver, NC Li, XB Arana, GW Risch, SC Ballenger, JC TI A controlled trial of daily left prefrontal cortex TMS for treating depression SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the Society-for-Biological-Psychiatry CY MAY 13-16, 1999 CL WASHINGTON, D.C. SP Soc Biol Psychiat DE transcranial magnetic stimulation; depression; prefrontal cortex; treatments; mood; emotion; clinical trials ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; RESISTANT MAJOR DEPRESSION; RTMS IMPROVES MOOD; AFFECTIVE-DISORDERS; SLEEP-DEPRIVATION; BLOOD-FLOW; BRAIN AB Background: Transcranial magnetic stimulation (TMS) is a new technology for noninvasively stimulating the brain, Several studies have suggested that daily stimulation of the left prefrontal cortex with TMS for 2 weeks has probable antidepressant effects. We conducted a parallel-design, double-masked, sham-controlled study to address whether 2 weeks of daily TMS over the left prefrontal cortex has antidepressant activity greater than sham. Methods: Thirty medication-free adult outpatients with nonpsychotic, major depressive (n = 21) or bipolar (n = 9) (depressed phase) disorder who were in a current major depression (Hamilton Rating Scale for Depression [HRSD] 21-item score of >18) were treated each weekday for 2 weeks. Subjects were randomly assigned to receive either daily active (20 subjects) or sham (10 subjects) stimulation. Additionally, the 20 active subjects I were equally divided between slower (5 Hz) andfaster (20 Hz) frequency treatment. Antidepressant response was defined as greater than a 50% improvement in the baseline HRSD, Results: Active TMS resulted in significantly more responders (9/20) than did sham (0/10) (chi (2) = 6.42, p < .01), The number of responders did not differ significantly between the two active cells (3/10 faster and 6/10 slower). Expressed as a percent change from baseline, active TMS subjects had significantly greater improvement on the Beck Depression Inventory as well as the Hamilton Anxiety Rating Scale than did those who received sham. Conclusions: Daily left prefrontal TMS for 2 weeks significantly reduced depression symptoms greater than did sham, The two forms of active TMS treatment did not differ significantly, (C) 2000 Society of Biological Psychiatry. C1 Med Univ S Carolina, Funct Neuroimaging Div, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Hosp, Dept Psychiat, Charleston, SC USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Shangdong Med Univ, Dept Psychiat, Jinan, Peoples R China. RP George, MS (reprint author), Med Univ S Carolina, Funct Neuroimaging Div, Dept Psychiat, Brain Stimulat Lab, 171 Ashley Ave, Charleston, SC 29425 USA. NR 53 TC 232 Z9 242 U1 4 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2000 VL 48 IS 10 BP 962 EP 970 DI 10.1016/S0006-3223(00)01048-9 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 374PP UT WOS:000165353800002 PM 11082469 ER PT J AU Osuch, EA Ketter, TA Kimbrell, TA George, MS Benson, BE Willis, MW Herscovitch, P Post, RM AF Osuch, EA Ketter, TA Kimbrell, TA George, MS Benson, BE Willis, MW Herscovitch, P Post, RM TI Regional cerebral metabolism associated with anxiety symptoms in affective disorder patients SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anxiety; depression; neuroimaging; positron emission tomography; cerebral metabolism; affective disorders ID POSITRON-EMISSION-TOMOGRAPHY; PANIC DISORDER; FUNCTIONAL NEUROANATOMY; BLOOD-FLOW; DEPRESSION AB Background: We studied the relationship between regional cerebral metabolism and the severity of anxiety in mood disorder patients, controlling for depression severity. Methods: Fifty-two medication-free patients with unipolar or bipolar illness underwent positron emission tomography with [F-18]-fluorodeoxyglucose. Hamilton Depression Rating Scale and Spielberger Anxiety-Stare Scale scores were obtained for the week of the scan. Analyses were performed on globally normalized images and were corrected for multiple comparisons. Results: After covarying for depression scores, age, and gender, Spielberger Anxiety-Stare Scale scores correlated directly with regional cerebral metabolism in the right parahippocampal and left anterior cingulate regions, and inversely with metabolism in the cerebellum, left fusiform, left superior temporal, left angular gyrus, and left insula. in contrast, covarying for anxiety scores, age, and gender, Hamilton Depression Rating Scale scores correlated directly with regional cerebral metabolism in the bilateral medial frontal, right anterior cingulate, and right dorsolateral prefrontal cortices. Conclusions: Comorbid anxiety symptoms are associated with specific cerebral metabolic correlates that partially overlap with those in the primary anxiety disorders and differ from those associated with depression severity. (C) 2000 Society of Biological Psychiatry. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. N Little Rock VA Med Ctr, N Little Rock, AR USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, 10 Ctr Dr,MSC-1272,Bldg 10,Rm 3N-212, Bethesda, MD 20892 USA. RI Osuch, Elizabeth/B-5009-2015 OI Osuch, Elizabeth/0000-0001-5946-1862 NR 18 TC 107 Z9 107 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2000 VL 48 IS 10 BP 1020 EP 1023 DI 10.1016/S0006-3223(00)00920-3 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 374PP UT WOS:000165353800010 PM 11082477 ER PT J AU Barrette, S Douglas, JL Seidel, NE Bodine, DM AF Barrette, S Douglas, JL Seidel, NE Bodine, DM TI Lentivirus-based vectors transduce mouse hematopoietic stem cells with similar efficiency to Moloney murine leukemia virus-based vectors SO BLOOD LA English DT Article ID BONE-MARROW CELLS; PSEUDOTYPED RETROVIRAL VECTORS; CHRONIC GRANULOMATOUS-DISEASE; MEDIATED GENE TRANSDUCTION; HUMAN ADENOSINE-DEAMINASE; RHESUS PERIPHERAL-BLOOD; LONG-TERM ENGRAFTMENT; HIGH-TITER; IN-VIVO; REPOPULATING CELLS AB The low levels of transduction of human hematopoietic stem cells (HSCs) with Moloney murine leukemia virus (MLV) vectors have been an obstacle to gene therapy for hematopoietic diseases. It has been demonstrated that lentivirus vectors are more efficient than MLV vectors at transducing nondividing cell lines as well as human CD34(+) cells and severe combined immunodeficiency disease repopulating cells. We compared transduction of cell lines and Lin(-) bone marrow cells, using a vesicular stomatitis virus G (VSV-G)-pseudotyped lentivirus or MLV vectors carrying a green fluorescent protein marker gene. As predicted, the lentivirus vector was more efficient at transducing mouse and human growth-inhibited cell lines. The transduction of mouse HSC by lentivirus vectors was compared directly to MLV vectors in a co-transduction assay. In this assay, transduction by ecotropic MLV is a positive internal control for downstream steps in retrovirus transduction, including cell division. Both the VSV-G lentivirus and MLV vectors transduced mouse HSCs maintained in cytokine-free medium at very low frequency, as did the ecotropic control. The lentivirus vector and the MLV vector were equally efficient at transducing bone marrow HSCs cultured in interleukin 3 (IL-3), IL-6, and stem cell factor for 96 hours. In conclusion, although lentivirus vectors are able to transduce growth-inhibited cell lines, the cell cycle status of HSCs render them resistant to lentivirus-mediated transduction, and it is hypothesized that entry into cycle, not necessarily division, may be a requirement for efficient lentivirus-mediated transduction. (C) 2000 by The American Society of Hematology. C1 NHGRI, GMBB, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. Systemix, Palo Alto, CA USA. RP Bodine, DM (reprint author), NHGRI, GMBB, Hematopoiesis Sect, NIH, 49 Convent Dr,Rm 3A11, Bethesda, MD 20892 USA. NR 63 TC 38 Z9 40 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2000 VL 96 IS 10 BP 3385 EP 3391 PG 7 WC Hematology SC Hematology GA 372HA UT WOS:000165227200013 PM 11071632 ER PT J AU Rosler, ES Brandt, JE Chute, J Hoffman, R AF Rosler, ES Brandt, JE Chute, J Hoffman, R TI An in vivo competitive repopulation assay for various sources of human hematopoietic stem cells SO BLOOD LA English DT Article ID UMBILICAL-CORD BLOOD; COMBINED IMMUNODEFICIENT MICE; COLONY-STIMULATING FACTOR; IMMUNE-DEFICIENT MICE; MURINE MARROW-CELLS; HUMAN BONE-MARROW; LONG-TERM; FETAL LIVER; UNRELATED DONORS; IN-VIVO AB The marrow repopulating potential (MRP) of different sources of human hematopoietic stem cells (HSCs) was directly compared using an in vivo assay in which severe combined immunodeficient disease (SCID) mice were implanted with human fetal bones. HSCs from 2 human lymphocyte antigen (HLA)-mismatched donors were injected individually or simultaneously into the fetal bones of a 3rd distinct HLA type and donor and recipient myeloid and lymphoid cells were identified after 8 to 10 weeks. The study compared the MRP of umbilical cord blood (CB) and adult bone marrow (ABM) CD34(+) cells as well as grafts of each type expanded ex vivo. Equal numbers of CB and ABM CD34(+) cells injected individually demonstrated similar abilities to establish multilineage hematopoiesis. However, when CB and ABM cells were transplanted simultaneously, the engraftment of CB cells was markedly superior to ABM. CB and ABM CD34(+) cells were expanded ex vivo using either a porcine microvascular endothelial cell (PMVEC)based coculture system or a stroma-free expansion system. Primary CB CD34(+) cells or CD34(+) cells expanded in either culture system demonstrated a similar ability to engraft. However, the MRP of expanded grafts simultaneously injected with primary CB cells was uniformly inferior to primary CB cells. CD34(+) cell grafts expanded in the stroma-free system, furthermore, outcompeted CD34(+) cells expanded using the PMVEC coculture system. The triple HLA-mismatched SCID-hu model represents a novel in vivo stem cell assay system that permits the direct demonstration of the functional consequences of ex vivo HSC expansion and ontogeny-related differences in HSCs. (C) 2000 by The American Society of Hematology. C1 Univ Illinois, Coll Med, Hematol Oncol Sect, Chicago, IL 60607 USA. USN, NIDDK, Transplantat & Autoimmun Branch, Bethesda, MD 20084 USA. RP Hoffman, R (reprint author), Univ Illinois, Coll Med, Hematol Oncol Sect, 900 S Ashland Ave,M-C 734, Chicago, IL 60607 USA. NR 52 TC 34 Z9 36 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2000 VL 96 IS 10 BP 3414 EP 3421 PG 8 WC Hematology SC Hematology GA 372HA UT WOS:000165227200017 PM 11071636 ER PT J AU Schlienger, K Craighead, N Lee, KP Levine, BL June, CH AF Schlienger, K Craighead, N Lee, KP Levine, BL June, CH TI Efficient priming of protein antigen-specific human CD4(+) T cells by monocyte-derived dendritic cells SO BLOOD LA English DT Article ID NECROSIS-FACTOR-ALPHA; HUMAN BLOOD; IN-VITRO; GENERATION; RESPONSES; MATURE; ACTIVATION; HELP; CD40; DIFFERENTIATION AB Dendritic cells (DCs) have the unique ability to initiate an immune response in vivo by capturing antigens (Ags) in peripheral tissues and migrating to secondary lymphoid organs,where they sensitize naive CD4(+) T cells. To mimic this process in vitro, previous studies have shown that DCs directly isolated from peripheral blood can be used to elicit primary responses to neoantigens (neoAgs). In other studies, when monocyte-derived DCs have been utilized to sensitize total CD4(+) T cells in vitro, only secondary proliferation to neoAgs could be elicited, In the present study the relative abilities of CD40 ligation, protein kinase C activation, and culture in tumor necrosis factor alpha (TNF-alpha) to induce functional and phenotypic maturation of human DCs from monocyte precursors were compared. Optimal TNF-alpha -induced maturation of DCs required a prolonged 4-day culture. It was then found that loading immature DCs with the neoAgs keyhole limpet hemocyanin or human immunodeficiency virus-1 p24 gag prior to TNF-alpha -induced maturation, rather than after maturation, was crucial to sensitize CD4(+) T cells to new Ags, This primary proliferation to neoAgs was initiated from the CD4(+) CD45RA(+) naive T-cell population. Finally, it was found that monocyte-derived DCs acquired the ability to secrete interleukin-12 p70, after contact with Ag-specific T cells. The ability to prime and expand Ag-specific CD4(+) T cells ex vivo to neoAgs in serum-free conditions has potential application for cellular vaccination and adoptive immunotherapy. (C) 2000 by The American Society of Hematology. C1 Univ Penn, Dept Mol & Cellular Engn, Philadelphia, PA 19104 USA. NIDDKD, Transplantat & Autoimmun Branch, NIH, Bethesda, MD 20892 USA. Miami Univ, Sch Med, Dept Microbiol & Immunol, Miami, FL USA. RP June, CH (reprint author), Univ Penn, Dept Mol & Cellular Engn, Rm 554 Biomed Res Bldg 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. RI Levine, Bruce/D-1688-2009 NR 41 TC 54 Z9 55 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2000 VL 96 IS 10 BP 3490 EP 3498 PG 9 WC Hematology SC Hematology GA 372HA UT WOS:000165227200027 PM 11071646 ER PT J AU Hyun, T Yam, A Pece, S Xie, XZ Zhang, J Miki, T Gutkind, JS Li, WQ AF Hyun, T Yam, A Pece, S Xie, XZ Zhang, J Miki, T Gutkind, JS Li, WQ TI Loss of PTEN expression leading to high Akt activation in human multiple myelomas SO BLOOD LA English DT Article ID PROTEIN-KINASE-B; TUMOR-SUPPRESSOR PTEN; PHOSPHOINOSITIDE 3-KINASE; CELL-SURVIVAL; MURINE PLASMACYTOMAGENESIS; SIGNALING PATHWAY; V-MYC; MICE; GENE; APOPTOSIS AB Mouse plasma cell tumor (PCT) and human multiple myeloma (MM) are terminal B-cell malignancies sharing many similarities. Our recent work demonstrated that activation of the insulin-like growth factor receptor (IGF-(R)/insulin receptor substrate (IRS)/phosphatidylinositol 3' kinase (PI 3'K) pathway was evident in the tumor lines derived from both species. Although PI 3'K activity was higher in mouse tumor lines than that in human tumors, activation of AM serine/threonine kinase was markedly lower in mouse lines. This discrepancy prompted us to test the status of PTEN tumor suppressor gene, as it has been shown to be a negative regulator of PI 3'K activity. Although all the mouse lines expressed intact PTEN, 2 of the 4 human lines (Delta 47 and OPM2) possessing the highest Akt activity lost PTEN expression. Sequencing analysis demonstrated that the PTEN gene contains a deletion spacing from exon 3 to exon 5 or 6 in the Delta 47 line and from exon 3 to 7 in the OPM2 line. Restoration of PTEN expression suppressed IGF-I-induced Akt activity, suggesting that loss of PTEN is responsible for uncontrolled AM activity in these 2 lines. Despite the expression of PTEN with the concomitant low Akt activity in all mouse PCT lines, their p70S6K activities were generally higher than those in 3 human MM lines, arguing for specific negative regulation of Akt, but not p70S6K by PTEN. These results suggest that p70S6K and AM may be differentially used by the plasma cell tumors derived from mice and humans, respectively. (C) 2000 by The American Society of Hematology. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Dept Oncol, Washington, DC 20007 USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD USA. NCI, Basic Res Lab, Mol Tumor Biol Sect, Bethesda, MD 20892 USA. RP Li, WQ (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Dept Oncol, New Res Bldg,E407,3970 Reservoir Rd NW, Washington, DC 20007 USA. RI Gutkind, J. Silvio/A-1053-2009; Pece, Salvatore/B-9609-2013 OI Pece, Salvatore/0000-0003-1764-3929 NR 51 TC 87 Z9 90 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2000 VL 96 IS 10 BP 3560 EP 3568 PG 9 WC Hematology SC Hematology GA 372HA UT WOS:000165227200036 PM 11071655 ER PT J AU Singer, JH Berger, AJ AF Singer, JH Berger, AJ TI Development of inhibitory synaptic transmission to motoneurons SO BRAIN RESEARCH BULLETIN LA English DT Article DE glycine; GABA; inhibition; hypoglossal motoneuron ID RAT SPINAL-CORD; RESPIRATORY RHYTHM GENERATION; ACTIVITY-DEPENDENT DEVELOPMENT; ELECTRON-MICROSCOPIC ANALYSIS; GLYCINE RECEPTOR SUBUNIT; BRAIN-STEM MOTONEURONS; NMDA RECEPTOR; HYPOGLOSSAL MOTONEURONS; MOTOR-NEURONS; IMMUNOHISTOCHEMICAL EVIDENCE AB The inhibitory effects of the neurotransmitters glycine and gamma -aminobutyric acid (GABA) on motoneurons and their role in mediating the timing of motor output have been understood for some years. Recent work, however, has revealed that these neurotransmitters function very differently in developing motor circuits. Most strikingly, both GABA and glycine depolarize neonatal motoneurons, and, in many instances, provide excitatory drive to developing motor networks. Additionally, the relative contributions of GABA and glycine to inhibitory synaptic transmission in a circuit or, indeed, within the same synapse, change with postnatal development. Here, we review three fundamental properties of inhibitory neurotransmission that are altered postnatally and may be important in shaping the unique behaviors of these synapses early in development. (C) 2001 Elsevier Science Inc. C1 Univ Washington, Sch Med, Dept Physiol & Biophys, Seattle, WA 98195 USA. RP Singer, JH (reprint author), NINDS, NIH, 36 Convent Dr MSC-4066,Bldg 36,Room 2C09, Bethesda, MD 20892 USA. NR 96 TC 50 Z9 50 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD NOV 15 PY 2000 VL 53 IS 5 BP 553 EP 560 DI 10.1016/S0361-9230(00)00389-0 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 398QJ UT WOS:000166766900011 PM 11165791 ER PT J AU Branchereau, P Morin, D Bonnot, A Ballion, B Chapron, J Viala, D AF Branchereau, P Morin, D Bonnot, A Ballion, B Chapron, J Viala, D TI Development of lumbar rhythmic networks: From embryonic to neonate locomotor-like patterns in the mouse SO BRAIN RESEARCH BULLETIN LA English DT Article DE spinal cord; in vitro; locomotion; serotonin; excitatory; amino acids ID RAT SPINAL-CORD; METHYL-D-ASPARTATE; IN-VITRO; MOTOR PATTERNS; HINDLIMB LOCOMOTION; FICTIVE LOCOMOTION; NEWBORN RAT; NMDA; INVITRO; GENERATION AB Different aspects of spinal locomotor organization have been studied in the mouse during embryonic and neonatal development using in vitro preparations of isolated lumbosacral cords. The first consideration was the embryonic development of an alternating bilateral pattern. From embryonic day (E) 12, perfusion of serotonin could induce relatively synchronous lumbar bursts across the cord. Bilateral activity became progressively alternate at E15 due to the appearance of glycinergic inhibitory interactions (revealed by strychnine application). Strictly alternating patterns were expressed at E18 and were maintained after birth. In a second step, we investigated cellular properties involved in lumbar rhythmogenesis in postnatal day 0-2 preparations which displayed spontaneous locomotor-like activity. Perfusion of receptor antagonists showed the co-operative involvement of N-methyl-D-aspartate (NMDA)- and non-NMDA-receptors for excitatory amino acids-mediated operation of locomotor networks. In a final step we investigated the localization of locomotor networks within the lumbar cord. Data obtained from preparations exhibiting spontaneous or Mg2+-free induced bursts revealed that the networks are present throughout the lumbar cord and that rhythmogenesis is distributed throughout all segmental levels. (C) 2001 Elsevier Science Inc. C1 Univ Bordeaux 1, CNRS UMR 5816, Lab Neurobiol Reseaux, F-33405 Talence, France. NINDS, Neural Control Lab, NIH, Bethesda, MD USA. RP Branchereau, P (reprint author), Univ Bordeaux 1, CNRS UMR 5816, Lab Neurobiol Reseaux, Ave Fac, F-33405 Talence, France. RI Morin, Didier/C-6651-2014 NR 35 TC 64 Z9 65 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD NOV 15 PY 2000 VL 53 IS 5 BP 711 EP 718 DI 10.1016/S0361-9230(00)00403-2 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 398QJ UT WOS:000166766900025 PM 11165805 ER PT J AU Huang, SC Koch, CA Vortmeyer, AO Pack, SD Lichtenauer, UD Mannan, P Lubensky, IA Chrousos, GP Gagel, RF Pacak, K Zhuang, ZP AF Huang, SC Koch, CA Vortmeyer, AO Pack, SD Lichtenauer, UD Mannan, P Lubensky, IA Chrousos, GP Gagel, RF Pacak, K Zhuang, ZP TI Duplication of the mutant RET allele in trisomy 10 or loss of the wild-type allele in multiple endocrine neoplasia type 2-associated pheochromocytomas SO CANCER RESEARCH LA English DT Article ID NONRANDOM DUPLICATION; PROTOONCOGENE; DISEASE AB Inherited mutations of the RET proto-oncogene are tumorigenic in patients with multiple endocrine neoplasia type 2 (MEN 2), However, it is not understood why only few of the affected cells in the target organs develop into tumors. Genetic analysis of nine pheochromocytomas from five unrelated patients with MEN 2 showed either duplication of the mutant RET allele in trisomy 10 or loss of the wild-type RET allele, Our results suggest a "second hit" causing a dominant effect of the mutant RET allele, through either duplication of the mutant allele or loss of the wild-type allele, as a possible mechanism for pheochromocytoma tumorigenesis in patients with MEN 2. C1 NINDS, Surg Neurol Branch, Mol Pathogenesis Unit, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Zhuang, ZP (reprint author), NINDS, Surg Neurol Branch, Mol Pathogenesis Unit, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; Pack, Svetlana/C-2020-2014; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 12 TC 71 Z9 72 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2000 VL 60 IS 22 BP 6223 EP 6226 PG 4 WC Oncology SC Oncology GA 375ZD UT WOS:000165432600002 PM 11103773 ER PT J AU Ahuja, HG Hong, JM Aplan, PD Tcheurekdjian, L Forman, SJ Slovak, ML AF Ahuja, HG Hong, JM Aplan, PD Tcheurekdjian, L Forman, SJ Slovak, ML TI t(9;11)(p22;p15) in acute myeloid leukemia results in a fusion between NUP98 and the gene encoding transcriptional coactivators p52 and p75-lens epithelium-derived growth factor (LEDGF) SO CANCER RESEARCH LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; CHROMOSOME-TRANSLOCATION; NUCLEOPORIN NUP98; T(7-11)(P15-P15); INTERACTS; FUSES; HOXA9 AB A t(9;11)(p22;p15) chromosomal translocation was identified in an adult patient with de novo acute myelogenous leukemia. Fluorescence in situ hybridization and Southern blot analysis mapped the 11p15 breakpoint to the NUP98 gene. Using 3' rapid amplification of cDNA ends, we have identified a chimeric mRNA that fused the NUP98 FXFG repeats in frame to the COOH-terminal portion of the gene encoding the transcriptional coactivators p52 and p75, also known as lens epithelium-derived growth factor (LEDGF), As expected, both NUP98-p52 and NUP98-p75 (LEDGF) chimeric mRNAs were detected by reverse transcription-PCR; however, the reciprocal p52/p75 (LEDGF)-NUP98 fusion mRNA was not detected. Our results demonstrate that this is the most 5' NUP98 fusion reported and reveal a previously unrecognized genetic target, the gene encoding p52/p75 (LEDGF). C1 New York State Dept Hlth, Roswell Pk Mem Inst, Dept Med, Buffalo, NY 14263 USA. NCI, Div Clin Sci, Gaithersburg, MD 20877 USA. City Hope Natl Med Ctr, Dept Hematol & Bone Marrow Transplantat, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Dept Cytogenet, Duarte, CA 91010 USA. RP Ahuja, HG (reprint author), Univ Wisconsin, Wausau Hosp, Ctr Canc, 215 N 28th St, Wausau, WI 54401 USA. RI Aplan, Peter/K-9064-2016 FU NCI NIH HHS [CA-30206] NR 14 TC 71 Z9 73 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2000 VL 60 IS 22 BP 6227 EP 6229 PG 3 WC Oncology SC Oncology GA 375ZD UT WOS:000165432600003 PM 11103774 ER EF